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Sleep apnea treatment may not prevent sleepiness
Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.
Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.
When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.
“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.
Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.
When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.
“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
Physicians who treat obstructive sleep apnea reported that patients with OSA can experience excessive sleepiness despite being on optimized airway treatment, findings from an online surgery of clinicians show.
Jazz Pharmaceuticals and the social media network Sermo conducted an online questionnaire on topics in excessive sleepiness and obstructive sleep apnea. The study was conducted March 30-31, 2018.
When asked how often they assess their OSA patients’ sleepiness, 46% of respondents said every 3 months, 28% said every 6 months, 19% said once a month, 6% said once a year, and 0.4% (one neurologist and one pulmonologist) said never. The method of evaluation varied by specialty: 82% of pulmonologists most often use the Epworth Sleepiness Scale and 76% of psychiatrists primarily use an informal set of questions, with neurologists in between but leaning toward informal questions, Jazz reported.
“As more scientific evidence emerges around the neuronal injury occurring due to OSA and the potential neurocognitive effects of excessive sleepiness, it’s imperative that pulmonologists, neurologists and psychiatrists understand the impact ES [excessive sleepiness] can have on patients’ lives,” Richard K. Bogan, MD, of the University of South Carolina, Columbia, a paid consultant to Jazz, said in a written statement.
Customized airway stents show promise in feasibility trial
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
REPORTING FROM ATS 2018
Key clinical point: Customized, 3-D airway stents have the potential for improving tolerance and decreasing the complication rate.
Major finding: Congruence and outcomes tended to be better in stenoses involving the bronchial level (three of three, no complications).
Study details: A feasibility study of eight patients with nonmalignant, anatomically complex, and symptomatic stenosis for which conventional stents were not suitable.
Disclosures: Dr. Guibert reported having no financial disclosures.
Source: Guibert N et al. ATS 2018, Abstract 4433.
New cell-free DNA assays hold promise for lung cancer screening
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
REPORTING FROM ASCO 2018
Key clinical point: Three blood-based assays performed moderately well for identifying lung cancer in early, potentially curable stages.
Major finding: At 98% specificity, the assays had sensitivities of 38%-51% for detecting lung cancers of stage I-IIIA.
Study details: A case-control study of circulating cell-free DNA assays among 164 patients with lung cancer and 923 comparable individuals without cancer.
Disclosures: Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
Source: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
What Are Predictors of Mortality in Veterans With MS?
A retrospective study finds that 39% of patients who died during follow-up were never on a disease-modifying therapy, compared with 22% of those who were still alive.
NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.
These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.
Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.
To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.
Data From a Veterans Affairs Medical Center
The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.
Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).
Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.
The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.
Main Causes of Death
A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American.
The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.
Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.
In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.
—Erica Tricarico
A retrospective study finds that 39% of patients who died during follow-up were never on a disease-modifying therapy, compared with 22% of those who were still alive.
A retrospective study finds that 39% of patients who died during follow-up were never on a disease-modifying therapy, compared with 22% of those who were still alive.
NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.
These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.
Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.
To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.
Data From a Veterans Affairs Medical Center
The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.
Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).
Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.
The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.
Main Causes of Death
A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American.
The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.
Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.
In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.
—Erica Tricarico
NASHVILLE—Among veterans with multiple sclerosis (MS), excess MS-related mortality is mainly influenced by initial presentation with progressive MS, sensory and cerebellar complaints, and higher levels of disability. Excess mortality also may be influenced by motor complaints and low BMI, according to research presented at the 2018 CMSC Annual Meeting. Main causes of death include MS itself, infection, respiratory disease, and cancer.
These findings suggest a need to pay more attention “to preventive strategies such as yearly influenza immunization, aggressively treating MS-related complications, and comorbidities, especially vascular risk factors,” said the researchers.
Studying mortality in chronic neurologic diseases may help identify treatable risk factors, and population-based studies of English death records have found that about 64% of patients with MS have a neurologic cause of death.
To identify the predictors of mortality in veterans with MS attending outpatient clinics, Meheroz H. Rabadi, MD, Clinical Professor of Neurology at the University of Oklahoma College of Medicine and Medical Director of the Oklahoma City Veterans Affairs Medical Center MS Program, and Christopher E. Aston, PhD, Associate Research Professor of Pediatrics and a biostatistician at the University of Oklahoma Sciences Center, conducted a retrospective study.
Data From a Veterans Affairs Medical Center
The researchers conducted a retrospective electronic chart review of data from 229 veterans with MS diagnosed based on the McDonald criteria who were registered in the MS program at the Oklahoma City Veterans Affairs Medical Center between January 1, 2000, and December 31, 2014. Participants were followed up every four months in the clinic.
Data included age at initial clinic visit, gender, ethnicity and race, age at MS diagnosis, clinical MS subtype (ie, relapsing-remitting, secondary progressive, primary progressive, clinically isolated syndrome, or radiologically isolated syndrome), and initial presenting features (eg, visual complaints, motor weakness, balance disorder, and sensory complaints).
Drs. Rabadi and Aston determined an impairment index based on the presence or absence of motor and nonmotor signs on initial examination. MS severity was measured by initial Expanded Disability Status Scale and total Functional Independence Measure scores.
The researchers recorded the presence of pre-existing and new-onset comorbidities that are commonly encountered in veterans and are the most common causes of disability and death in the United States, such as hypertension, hyperlipidemia, diabetes mellitus, BMI, and history of smoking. They also recorded the presence of MS-related complications such as pressure ulcers, neurogenic bowel, and neurogenic bladder.
Main Causes of Death
A total of 226 participants were included in the analysis; 17% were female. Most participants were white (81%), 13% were black, 1% were Hispanic, and 2% were Native American.
The mortality rate at the end of the 15-year study period was 14%. Among the 33 patients who died, the main causes of death documented were MS disease itself (57% of cases), infection (43%), cancer (18%), and respiratory failure (18%). Cox regression analysis using the whole cohort found that significant predictors of mortality were progressive MS type; older age at entry into the study; the presence of sensory, cerebellar, or motor complaints on presentation; more disability on presentation; lower BMI; diabetes; not having been on disease-modifying therapy; and the presence of pressure ulcers or neurogenic bladder.
Among patients who died during follow up, 36% had primary progressive MS, compared with 17% of patients who were alive; 42% of patients who died had secondary progressive MS, compared with 21% of those who were alive.
In addition, patients who died had an average age of 56 at study entry, compared with an average age of 48 among those who were alive. BMI among those who died was 23.7, compared with 28 among patients who were alive. Thirty-nine percent of patients who died were never on a disease-modifying therapy, compared with 22% of patients who were alive. Thirty-three percent of patients who died had diabetes mellitus, compared with 16% of those who were alive. Finally, 12% of patients who died had pressure ulcers, compared with 2% of patients who were alive, and 82% of patients who died had neurogenic bladder, compared with 53% of patients who were alive.
—Erica Tricarico
Allergies linked to autism spectrum disorder in children
The prevalence of food, respiratory, and skin allergy is greater in U.S. children with autism spectrum disorder (ASD) than in U.S. children without the disorder, according to findings published June 8 in JAMA Network Open.
An analysis of data from the National Health Interview Survey found that the weighted prevalence of food, respiratory, and skin allergies was 11.25%, 18.73%, and 16.81%, respectively, in children with ASD, compared with 4.25%, 12.08%, and 9.84%, respectively, in children without ASD (P less than .001).
Survey data were collected between 1997 and 2016, and included patients aged 3-17 years. Allergic conditions were defined by the respondent, usually a parent, answering in the affirmative that the child had any kind of food, digestive, respiratory, or skin allergy in the past 12 months. ASD was defined based on an affirmative response to a question asking whether the child received an ASD diagnosis from a health professional. The question was asked as part of a 10-condition checklist from 1997 to 2013, and as a standalone item from 2014 onward, with revised wording to distinguish autism, Asperger’s disorder, pervasive developmental disorder, and ASD, wrote Guifeng Xu, MD, of the department of epidemiology at the University of Iowa, Iowa City, and her coauthors.
Of the 199,520 children included in the study, 8,734 had food allergy, 24,555 had respiratory allergy, and 19,399 had skin allergy. An ASD diagnosis was reported in 1,868 children. The weighted prevalence was 4.31% for food allergy (95% confidence interval, 4.20%-4.43%), 12.15% for respiratory allergy (95% CI, 11.92%-12.38%), and 9.91% for skin allergy (95% CI, 9.72%-10.10%), the authors said.
Children with ASD were more likely than were children without ASD to have food allergy, respiratory allergy, and skin allergy (P less than .001). After adjustment for factors including age, sex, ethnicity, and family education level, the odds ratio of ASD was more than double among children with food allergy, compared with those without food allergy (odds ratio, 2.72; 95% CI, 2.26-3.28; P less than .001).
Respiratory allergy and skin allergy also were significantly associated with ASD, but to a lesser degree, with an OR of 1.53 (95% CI, 1.32-1.78; P less than .001) for respiratory allergy and 1.80 (95% CI, 1.55-2.09; P less than .001) for skin allergy, Dr. Xu and her colleagues reported.
,” though the underlying mechanisms still need to be identified, the authors wrote.
Particularly striking were the connections found between ASD and food allergy. “Although the underlying mechanisms for the observed association between food allergy and ASD remain to be elucidated, the gut-brain-behavior axis could be one of the potential mechanisms,” Dr. Xu and her coauthors wrote. “Previous studies found higher prevalence of gastrointestinal symptoms among children with ASD.”
Limitations to the study include possible recall bias and misreporting, as well as an absence of information about onset of allergy and ASD diagnosis.
“Large prospective cohort studies starting from birth or early life are needed to confirm our findings,” the authors concluded.
No conflicts of interest were reported.
SOURCE: Guifeng X et al. JAMA Network Open. 2018 Jun 8. doi: 10.1001/jamanetworkopen.2018.0279.
The results of this study add to a “growing body of literature supporting an immune-mediated subtype of autism spectrum disorder (ASD),” Christopher J. McDougle, MD, wrote in an editorial published with the study.
Although prior studies have identified an association between ASD and respiratory and skin allergy, this study is “the first to document the association of food allergy with ASD with confidence, in part based on the large sample size they accessed,” he said (JAMA Network Open. 2018;1[2]:e180280. doi: 10.1001/jamanetworkopen.2018.0280).
Dr. McDougle is affiliated with the Lurie Center for Autism at Massachusetts General Hospital.
The results of this study add to a “growing body of literature supporting an immune-mediated subtype of autism spectrum disorder (ASD),” Christopher J. McDougle, MD, wrote in an editorial published with the study.
Although prior studies have identified an association between ASD and respiratory and skin allergy, this study is “the first to document the association of food allergy with ASD with confidence, in part based on the large sample size they accessed,” he said (JAMA Network Open. 2018;1[2]:e180280. doi: 10.1001/jamanetworkopen.2018.0280).
Dr. McDougle is affiliated with the Lurie Center for Autism at Massachusetts General Hospital.
The results of this study add to a “growing body of literature supporting an immune-mediated subtype of autism spectrum disorder (ASD),” Christopher J. McDougle, MD, wrote in an editorial published with the study.
Although prior studies have identified an association between ASD and respiratory and skin allergy, this study is “the first to document the association of food allergy with ASD with confidence, in part based on the large sample size they accessed,” he said (JAMA Network Open. 2018;1[2]:e180280. doi: 10.1001/jamanetworkopen.2018.0280).
Dr. McDougle is affiliated with the Lurie Center for Autism at Massachusetts General Hospital.
The prevalence of food, respiratory, and skin allergy is greater in U.S. children with autism spectrum disorder (ASD) than in U.S. children without the disorder, according to findings published June 8 in JAMA Network Open.
An analysis of data from the National Health Interview Survey found that the weighted prevalence of food, respiratory, and skin allergies was 11.25%, 18.73%, and 16.81%, respectively, in children with ASD, compared with 4.25%, 12.08%, and 9.84%, respectively, in children without ASD (P less than .001).
Survey data were collected between 1997 and 2016, and included patients aged 3-17 years. Allergic conditions were defined by the respondent, usually a parent, answering in the affirmative that the child had any kind of food, digestive, respiratory, or skin allergy in the past 12 months. ASD was defined based on an affirmative response to a question asking whether the child received an ASD diagnosis from a health professional. The question was asked as part of a 10-condition checklist from 1997 to 2013, and as a standalone item from 2014 onward, with revised wording to distinguish autism, Asperger’s disorder, pervasive developmental disorder, and ASD, wrote Guifeng Xu, MD, of the department of epidemiology at the University of Iowa, Iowa City, and her coauthors.
Of the 199,520 children included in the study, 8,734 had food allergy, 24,555 had respiratory allergy, and 19,399 had skin allergy. An ASD diagnosis was reported in 1,868 children. The weighted prevalence was 4.31% for food allergy (95% confidence interval, 4.20%-4.43%), 12.15% for respiratory allergy (95% CI, 11.92%-12.38%), and 9.91% for skin allergy (95% CI, 9.72%-10.10%), the authors said.
Children with ASD were more likely than were children without ASD to have food allergy, respiratory allergy, and skin allergy (P less than .001). After adjustment for factors including age, sex, ethnicity, and family education level, the odds ratio of ASD was more than double among children with food allergy, compared with those without food allergy (odds ratio, 2.72; 95% CI, 2.26-3.28; P less than .001).
Respiratory allergy and skin allergy also were significantly associated with ASD, but to a lesser degree, with an OR of 1.53 (95% CI, 1.32-1.78; P less than .001) for respiratory allergy and 1.80 (95% CI, 1.55-2.09; P less than .001) for skin allergy, Dr. Xu and her colleagues reported.
,” though the underlying mechanisms still need to be identified, the authors wrote.
Particularly striking were the connections found between ASD and food allergy. “Although the underlying mechanisms for the observed association between food allergy and ASD remain to be elucidated, the gut-brain-behavior axis could be one of the potential mechanisms,” Dr. Xu and her coauthors wrote. “Previous studies found higher prevalence of gastrointestinal symptoms among children with ASD.”
Limitations to the study include possible recall bias and misreporting, as well as an absence of information about onset of allergy and ASD diagnosis.
“Large prospective cohort studies starting from birth or early life are needed to confirm our findings,” the authors concluded.
No conflicts of interest were reported.
SOURCE: Guifeng X et al. JAMA Network Open. 2018 Jun 8. doi: 10.1001/jamanetworkopen.2018.0279.
The prevalence of food, respiratory, and skin allergy is greater in U.S. children with autism spectrum disorder (ASD) than in U.S. children without the disorder, according to findings published June 8 in JAMA Network Open.
An analysis of data from the National Health Interview Survey found that the weighted prevalence of food, respiratory, and skin allergies was 11.25%, 18.73%, and 16.81%, respectively, in children with ASD, compared with 4.25%, 12.08%, and 9.84%, respectively, in children without ASD (P less than .001).
Survey data were collected between 1997 and 2016, and included patients aged 3-17 years. Allergic conditions were defined by the respondent, usually a parent, answering in the affirmative that the child had any kind of food, digestive, respiratory, or skin allergy in the past 12 months. ASD was defined based on an affirmative response to a question asking whether the child received an ASD diagnosis from a health professional. The question was asked as part of a 10-condition checklist from 1997 to 2013, and as a standalone item from 2014 onward, with revised wording to distinguish autism, Asperger’s disorder, pervasive developmental disorder, and ASD, wrote Guifeng Xu, MD, of the department of epidemiology at the University of Iowa, Iowa City, and her coauthors.
Of the 199,520 children included in the study, 8,734 had food allergy, 24,555 had respiratory allergy, and 19,399 had skin allergy. An ASD diagnosis was reported in 1,868 children. The weighted prevalence was 4.31% for food allergy (95% confidence interval, 4.20%-4.43%), 12.15% for respiratory allergy (95% CI, 11.92%-12.38%), and 9.91% for skin allergy (95% CI, 9.72%-10.10%), the authors said.
Children with ASD were more likely than were children without ASD to have food allergy, respiratory allergy, and skin allergy (P less than .001). After adjustment for factors including age, sex, ethnicity, and family education level, the odds ratio of ASD was more than double among children with food allergy, compared with those without food allergy (odds ratio, 2.72; 95% CI, 2.26-3.28; P less than .001).
Respiratory allergy and skin allergy also were significantly associated with ASD, but to a lesser degree, with an OR of 1.53 (95% CI, 1.32-1.78; P less than .001) for respiratory allergy and 1.80 (95% CI, 1.55-2.09; P less than .001) for skin allergy, Dr. Xu and her colleagues reported.
,” though the underlying mechanisms still need to be identified, the authors wrote.
Particularly striking were the connections found between ASD and food allergy. “Although the underlying mechanisms for the observed association between food allergy and ASD remain to be elucidated, the gut-brain-behavior axis could be one of the potential mechanisms,” Dr. Xu and her coauthors wrote. “Previous studies found higher prevalence of gastrointestinal symptoms among children with ASD.”
Limitations to the study include possible recall bias and misreporting, as well as an absence of information about onset of allergy and ASD diagnosis.
“Large prospective cohort studies starting from birth or early life are needed to confirm our findings,” the authors concluded.
No conflicts of interest were reported.
SOURCE: Guifeng X et al. JAMA Network Open. 2018 Jun 8. doi: 10.1001/jamanetworkopen.2018.0279.
FROM JAMA NETWORK OPEN
Key clinical point: The prevalence of food, respiratory, and skin allergy was greater in children with autism spectrum disorder (ASD).
Major finding: The weighted prevalence of food, respiratory, and skin allergies was 11.25%, 18.73%, and 16.81%, respectively, in children with ASD, compared with 4.25%, 12.08%, and 9.84%, respectively, in children without ASD (P less than .001).
Study details: A population-based study of 199,520 children aged 3-17 years in the National Health Interview Survey.
Disclosures: No conflicts of interest were reported.
Source: Guifeng X et al. JAMA Network Open. 2018 Jun 8. doi: 10.1001/jamanetworkopen.2018.0279.
Cladribine Tablets Improve MRI Outcomes in Patients With Highly Active Relapsing-Remitting MS
The relative risk ratio for cumulative new T1 gadolinium-enhancing lesions was significantly lower in the cladribine 3.5 mg/kg group, compared with placebo.
NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.
In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.
The researchers retrospectively analyzed CLARITY participants randomized to cladribine tablets 3.5 mg/kg or placebo using the following two sets of high disease activity criteria based on relapse history, prior treatment, and MRI characteristics: 1) high relapse activity, which was defined as two or more relapses during the year before study entry whether on disease-modifying therapy or not; 2) high relapse activity plus treatment nonresponse, in which treatment nonresponse was defined as one or more relapses and one or more T1 gadolinium-enhancing lesions or nine or more T2 lesions during the year before study entry and while on therapy with other disease-modifying therapy.
For cumulative new T1 gadolinium-enhancing lesions, the relative risk ratio in the high relapse activity subgroup (0.087) was significantly lower in favor of cladribine tablets 3.5 mg/kg (n = 130) over placebo (n = 131). In the high relapse activity plus treatment nonresponse subgroup, the relative risk ratio (0.077) also significantly favored cladribine tablets 3.5 mg/kg (n = 140) versus placebo (n = 149). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097), said the researchers.
For cumulative active T2 lesions, the relative risk ratio also significantly favored cladribine tablets 3.5 mg/kg versus placebo for the high relapse activity (0.263) and the high relapse activity plus treatment nonresponse subgroups (0.254), with risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272).
The relative risk ratio for cumulative combined unique active lesions significantly favored cladribine tablets 3.5 mg/kg versus placebo for high relapse activity (0.212) and high relapse activity plus treatment nonresponse (0.203) with risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234). Comparable results were observed in the non-high-disease activity counterparts, with no significant treatment-subgroup interactions.
—Erica Tricarico
Suggested Reading
Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].
The relative risk ratio for cumulative new T1 gadolinium-enhancing lesions was significantly lower in the cladribine 3.5 mg/kg group, compared with placebo.
The relative risk ratio for cumulative new T1 gadolinium-enhancing lesions was significantly lower in the cladribine 3.5 mg/kg group, compared with placebo.
NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.
In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.
The researchers retrospectively analyzed CLARITY participants randomized to cladribine tablets 3.5 mg/kg or placebo using the following two sets of high disease activity criteria based on relapse history, prior treatment, and MRI characteristics: 1) high relapse activity, which was defined as two or more relapses during the year before study entry whether on disease-modifying therapy or not; 2) high relapse activity plus treatment nonresponse, in which treatment nonresponse was defined as one or more relapses and one or more T1 gadolinium-enhancing lesions or nine or more T2 lesions during the year before study entry and while on therapy with other disease-modifying therapy.
For cumulative new T1 gadolinium-enhancing lesions, the relative risk ratio in the high relapse activity subgroup (0.087) was significantly lower in favor of cladribine tablets 3.5 mg/kg (n = 130) over placebo (n = 131). In the high relapse activity plus treatment nonresponse subgroup, the relative risk ratio (0.077) also significantly favored cladribine tablets 3.5 mg/kg (n = 140) versus placebo (n = 149). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097), said the researchers.
For cumulative active T2 lesions, the relative risk ratio also significantly favored cladribine tablets 3.5 mg/kg versus placebo for the high relapse activity (0.263) and the high relapse activity plus treatment nonresponse subgroups (0.254), with risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272).
The relative risk ratio for cumulative combined unique active lesions significantly favored cladribine tablets 3.5 mg/kg versus placebo for high relapse activity (0.212) and high relapse activity plus treatment nonresponse (0.203) with risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234). Comparable results were observed in the non-high-disease activity counterparts, with no significant treatment-subgroup interactions.
—Erica Tricarico
Suggested Reading
Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].
NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.
In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.
The researchers retrospectively analyzed CLARITY participants randomized to cladribine tablets 3.5 mg/kg or placebo using the following two sets of high disease activity criteria based on relapse history, prior treatment, and MRI characteristics: 1) high relapse activity, which was defined as two or more relapses during the year before study entry whether on disease-modifying therapy or not; 2) high relapse activity plus treatment nonresponse, in which treatment nonresponse was defined as one or more relapses and one or more T1 gadolinium-enhancing lesions or nine or more T2 lesions during the year before study entry and while on therapy with other disease-modifying therapy.
For cumulative new T1 gadolinium-enhancing lesions, the relative risk ratio in the high relapse activity subgroup (0.087) was significantly lower in favor of cladribine tablets 3.5 mg/kg (n = 130) over placebo (n = 131). In the high relapse activity plus treatment nonresponse subgroup, the relative risk ratio (0.077) also significantly favored cladribine tablets 3.5 mg/kg (n = 140) versus placebo (n = 149). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097), said the researchers.
For cumulative active T2 lesions, the relative risk ratio also significantly favored cladribine tablets 3.5 mg/kg versus placebo for the high relapse activity (0.263) and the high relapse activity plus treatment nonresponse subgroups (0.254), with risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272).
The relative risk ratio for cumulative combined unique active lesions significantly favored cladribine tablets 3.5 mg/kg versus placebo for high relapse activity (0.212) and high relapse activity plus treatment nonresponse (0.203) with risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234). Comparable results were observed in the non-high-disease activity counterparts, with no significant treatment-subgroup interactions.
—Erica Tricarico
Suggested Reading
Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].
Caring for the offensive patient
“I only see Jewish doctors.”
The middle-aged lady across my desk repeated that several times during her visit, apparently hoping to get some response from me. I just ignored it each time.
Imagine if she’d said, “I only see white doctors,” or “I only see black doctors.” To say you came to a doctor solely because of his or her ethnicity is, to me, ignorant at best and blatant discrimination at worst.
Of course, I continued the appointment. While I found her comment offensive, I’m a doctor. Unlike a restaurant owner, I can’t refuse to serve someone because of their personal beliefs, no matter how much I disagree. I took an oath to provide equal care to all, regardless of personal differences. I try hard to measure up to that.
We live in a world that seems to be increasingly divided along tribal lines. Us against them. Me against you. Everyone for themselves.
I’m not going to play that game. For better or worse, I’ll take the high road and continue treating all people as equal. If you want to believe that religion, or color, or any other difference makes someone a better or worse physician (or person, for that matter), you’re entitled to your opinion.
I may not be able to change your mind, but that’s not going to stop me from trying to be the best doctor I can to everyone who comes to me, regardless of who they are.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I only see Jewish doctors.”
The middle-aged lady across my desk repeated that several times during her visit, apparently hoping to get some response from me. I just ignored it each time.
Imagine if she’d said, “I only see white doctors,” or “I only see black doctors.” To say you came to a doctor solely because of his or her ethnicity is, to me, ignorant at best and blatant discrimination at worst.
Of course, I continued the appointment. While I found her comment offensive, I’m a doctor. Unlike a restaurant owner, I can’t refuse to serve someone because of their personal beliefs, no matter how much I disagree. I took an oath to provide equal care to all, regardless of personal differences. I try hard to measure up to that.
We live in a world that seems to be increasingly divided along tribal lines. Us against them. Me against you. Everyone for themselves.
I’m not going to play that game. For better or worse, I’ll take the high road and continue treating all people as equal. If you want to believe that religion, or color, or any other difference makes someone a better or worse physician (or person, for that matter), you’re entitled to your opinion.
I may not be able to change your mind, but that’s not going to stop me from trying to be the best doctor I can to everyone who comes to me, regardless of who they are.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I only see Jewish doctors.”
The middle-aged lady across my desk repeated that several times during her visit, apparently hoping to get some response from me. I just ignored it each time.
Imagine if she’d said, “I only see white doctors,” or “I only see black doctors.” To say you came to a doctor solely because of his or her ethnicity is, to me, ignorant at best and blatant discrimination at worst.
Of course, I continued the appointment. While I found her comment offensive, I’m a doctor. Unlike a restaurant owner, I can’t refuse to serve someone because of their personal beliefs, no matter how much I disagree. I took an oath to provide equal care to all, regardless of personal differences. I try hard to measure up to that.
We live in a world that seems to be increasingly divided along tribal lines. Us against them. Me against you. Everyone for themselves.
I’m not going to play that game. For better or worse, I’ll take the high road and continue treating all people as equal. If you want to believe that religion, or color, or any other difference makes someone a better or worse physician (or person, for that matter), you’re entitled to your opinion.
I may not be able to change your mind, but that’s not going to stop me from trying to be the best doctor I can to everyone who comes to me, regardless of who they are.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Everolimus/exemestane improves PFS of ER+/HER2– breast cancer vs. everolimus alone
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
CHICAGO – For women with estrogen receptor–positive breast cancer resistant to endocrine therapy, the combination of everolimus and exemestane had better efficacy than did everolimus alone, but single-agent capecitabine appeared to offer benefit comparable to that of the combination therapy, results of the BOLERO-6 trial suggest.
Among 309 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of everolimus (Afinitor) and exemestane (Aromasin and generics) was associated with a 26% improvement in progression-free survival (PFS) compared with everolimus alone, reported Guy Jerusalem, MD, PhD, of Liege University, Belgium.
There was also, however, a numerical but not statistically significant difference in PFS favoring capecitabine (Xeloda and generics) “which may be attributed to various baseline characteristics favoring capecitabine, and potential informative censoring,” he said at the annual meeting of the American Society of Clinical Oncology.
“We have noted in BOLERO-6 a better-than-expected outcome in median progression-free survival of capecitabine compared with the previously reported 4.1 to 7.9 months median progression-free survival,” he said.
BOLERO-6, results of which were published online June 3 in JAMA Oncology, was a postmarketing study by the sponsors to fulfill commitments to both the Food and Drug Administration and the European Medicines Agency to estimate the treatment benefit with combined everolimus and exemestane vs. monotherapy with everolimus or capecitabine in patients with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Patients from 83 centers in 18 countries were enrolled in the open label, phase 2 study and randomly assigned to receive oral everolimus 10 mg daily with oral exemestane 25 mg daily, everolimus at the same dose alone, or oral capecitabine 1,250 mg/m2 twice daily for 2 weeks on, 1 week off.
The trial was not powered for statistical comparisons between arms, but was instead designed with the primary objective of estimated investigator-assessed PFS for the combination vs. everolimus alone.
At baseline, more patients assigned to capecitabine vs. everolimus-containing regimens were younger than 65, white, had an Eastern Cooperative Oncology Group status of 0 (fully active), and had bone-only metastases. In addition, fewer patients in the capecitabine arm had three or more metastatic sites, Dr. Jerusalem noted,
For the primary analysis, the median PFS with everolimus/exemestane was 8.4 months, compared with 6.8 months for everolimus alone. The estimated hazard ratio (HR) for PFS with everolimus/exemestane vs. everolimus alone was 0.74 (90% confidence interval [CI], 0.57-0.97)
In contrast, median PFS with capecitabine was 9.6 months, with a nonsignificant hazard ratio of 1.26 for the combination (90% CI, 0.96-1.66).
A stratified multivariate Cox regression model controlling for baseline difference and known prognostic factor yielded an HR for PFS of 1.15 (90% CI, 0.86-1.52) for the combination.
Censoring of patients was more frequent in the capecitabine arm (33% vs. 23% in the combination arm), which included 20% of patients on capecitabine who were censored for starting on a new antineoplastic therapy vs. 9% of patients on everolimus/exemestane.
The median time to treatment failure was 5.8 months with the combination, vs. 4.2 months with everolimus alone (HR, 0.66, 90% CI, 0.52-0.4), and 6.2 months with capecitabine alone (HR, 1.03, 90% CI, 0.81-1.31).
Median overall survival was 23.1 months in the combination arm, 29.3 months in the everolimus arm, and 25.6 months in the capecitabine arm. There were no statistically significant differences in overall survival among the groups.
Grade 3 or greater adverse events were more frequent in the combination vs. everolimus arms, and comparable between the combination and capecitabine arms, Dr. Jerusalem said.
Serious adverse events of any grade were more frequent in the combination arm than in the other two arms, but there were no significant differences in discontinuations due to adverse events
“The results of the present study suggest that mTOR inhibitor and endocrine therapy combinations remain important for aromatase inhibitor–refractory disease. Safety and PFS with everolimus plus exemestane in this study were consistent with BOLERO-2 and are now supported by real-world evidence,” the investigators wrote.
“The take home from the BOLERO-6 trial is that the progression-free survival for the combination of everolimus and exemestane is superior to everolimus alone, and is in line with data from the BOLERO-2 trial, and also the PrE0102 study, demonstrating the consistent activity of mTOR inhibition in combination with endocrine therapy in the aromatase inhibitor resistance setting, and this supports our use of the combination in the endocrine resistant patients,” said Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, the invited discussant.
Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
SOURCE: Jerusalem G et al. ASCO 2018 Abstract 1005
REPORTING FROM ASCO 2018
Key clinical point: The combination of everolimus and exemestane had better efficacy than did everolimus alone in women with ER+/HER2– breast cancer resistant to endocrine therapy.
Major finding: Median PFS with everolimus/exemestane was 8.4 months vs 6.8 months for everolimus.
Study details: Randomized, open label, phase 2 trial of 309 women with ER-positive, HER2-negative breast cancer that progressed during nonsteroidal aromatase inhibitor therapy.
Disclosures: Novartis funded the study. Dr Jerusalem received research funding from Novartis and Roche; honoraria from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS, and Puma Technology; and nonfinancial support from Novartis, Roche, Pfizer, Lilly, Amgen, and BMS. Dr. Ma reported consulting/advising, travel expenses, and institutional research funding from Novartis and others.
Source: Jerusalem G et al. ASCO 2018, Abstract 1005.
FDA approves rituximab for treating pemphigus vulgaris
Rituximab (Rituxan) has been approved for the treatment of adults with moderate to severe pemphigus vulgaris, the manufacturer announced on June 7.
Rituximab is the first biologic approved for treating pemphigus vulgaris, Genentech, a member of the Roche group, stated in a press release announcing the approval.
The prospective, multicenter, open-label, randomized trial, conducted in France, compared the rituximab product approved in the European Union, plus short-term corticosteroid therapy (1,000 mg rituximab administered intravenously at baseline and day 14, then 500 mg at 12 and 18 months, plus 0.5 mg/kg or 1.0 mg/kg per day of prednisone tapered over 3 or 6 months) to corticosteroid therapy alone (oral prednisone 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months), in 90 patients newly diagnosed with moderate to severe pemphigus.
At 24 months, 89% of those in the rituximab group met the primary endpoint, complete remission off therapy at 24 months, compared with 34% of those on corticosteroids (P less than .0001), the investigators reported (Lancet. 2017 May 20;389[10083]:2031-40). Severe adverse events were more commonly reported in the prednisone-only group.
First approved in 1997, rituximab, an anti-CD20 monoclonal antibody, is approved for non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukemia, and granulomatosis with polyangiitis. The prescribing information includes a boxed warning about the risks of fatal infusion reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy.
The study published in the Lancet was funded by Roche, the French Ministry of Health, and the French Society of Dermatology.
Rituximab (Rituxan) has been approved for the treatment of adults with moderate to severe pemphigus vulgaris, the manufacturer announced on June 7.
Rituximab is the first biologic approved for treating pemphigus vulgaris, Genentech, a member of the Roche group, stated in a press release announcing the approval.
The prospective, multicenter, open-label, randomized trial, conducted in France, compared the rituximab product approved in the European Union, plus short-term corticosteroid therapy (1,000 mg rituximab administered intravenously at baseline and day 14, then 500 mg at 12 and 18 months, plus 0.5 mg/kg or 1.0 mg/kg per day of prednisone tapered over 3 or 6 months) to corticosteroid therapy alone (oral prednisone 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months), in 90 patients newly diagnosed with moderate to severe pemphigus.
At 24 months, 89% of those in the rituximab group met the primary endpoint, complete remission off therapy at 24 months, compared with 34% of those on corticosteroids (P less than .0001), the investigators reported (Lancet. 2017 May 20;389[10083]:2031-40). Severe adverse events were more commonly reported in the prednisone-only group.
First approved in 1997, rituximab, an anti-CD20 monoclonal antibody, is approved for non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukemia, and granulomatosis with polyangiitis. The prescribing information includes a boxed warning about the risks of fatal infusion reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy.
The study published in the Lancet was funded by Roche, the French Ministry of Health, and the French Society of Dermatology.
Rituximab (Rituxan) has been approved for the treatment of adults with moderate to severe pemphigus vulgaris, the manufacturer announced on June 7.
Rituximab is the first biologic approved for treating pemphigus vulgaris, Genentech, a member of the Roche group, stated in a press release announcing the approval.
The prospective, multicenter, open-label, randomized trial, conducted in France, compared the rituximab product approved in the European Union, plus short-term corticosteroid therapy (1,000 mg rituximab administered intravenously at baseline and day 14, then 500 mg at 12 and 18 months, plus 0.5 mg/kg or 1.0 mg/kg per day of prednisone tapered over 3 or 6 months) to corticosteroid therapy alone (oral prednisone 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months), in 90 patients newly diagnosed with moderate to severe pemphigus.
At 24 months, 89% of those in the rituximab group met the primary endpoint, complete remission off therapy at 24 months, compared with 34% of those on corticosteroids (P less than .0001), the investigators reported (Lancet. 2017 May 20;389[10083]:2031-40). Severe adverse events were more commonly reported in the prednisone-only group.
First approved in 1997, rituximab, an anti-CD20 monoclonal antibody, is approved for non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukemia, and granulomatosis with polyangiitis. The prescribing information includes a boxed warning about the risks of fatal infusion reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy.
The study published in the Lancet was funded by Roche, the French Ministry of Health, and the French Society of Dermatology.
Multi-Modal Pain Control in Ambulatory Hand Surgery
ABSTRACT
We evaluated postoperative pain control and narcotic usage after thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of the distal radius in patients given opiates with or without other non-opiate medication using a specific dosing regimen. A prospective, randomized study of 79 patients undergoing elective CMC arthroplasty or ORIF of the distal radius evaluated postoperative pain in the first 5 postoperative days. Patients were divided into 4 groups: Group 1, oxycodone and acetaminophen PRN; Group 2, oxycodone and acetaminophen with specific dosing; Group 3, oxycodone, acetaminophen, and OxyContin with specific dosing; and Group 4, oxycodone, acetaminophen, and ketorolac with specific dosing. During the first 5 postoperative days, we recorded pain levels according to a numeric pain scale, opioid usage, and complications. Although differences in our data did not reach statistical significance, overall pain scores, opioid usage, and complication rates were less prevalent in the oxycodone, acetaminophen, and ketorolac group. Postoperative pain following ambulatory hand and wrist surgery under regional anesthesia was more effectively controlled with fewer complications using a combination of oxycodone, acetaminophen, and ketorolac with a specific dosing regimen.
Continue to: Regional anesthesia...
Regional anesthesia is a safe and effective modality of perioperative pain control in patients undergoing ambulatory hand procedures.1-10 Often, as the regional block wears off, patients experience a rebound pain effect that can be challenging to manage.
We sought to determine if an organized, multimodal approach in patients undergoing thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of distal radius fractures would provide better postoperative pain control. We hypothesized that this approach would significantly reduce postoperative pain and the need for narcotic pain medication compared with PRN dosing of oxycodone/acetaminophen alone.11-14
MATERIALS AND METHODS
Our study was approved by our Institutional Review Board. Informed consent was obtained from each patient. Patients presenting for elective thumb CMC arthroplasty or ORIF of the distal radius were screened for inclusion in a prospective, randomized study. Inclusion criteria included patients aged 18 to 65 years who could provide informed consent. Patients with chronic pain syndromes, long-term narcotic usage, chronic medical conditions precluding the use of opiates or nonsteroidal anti-inflammatory drugs (NSAIDs), and those who did not have a complete sensory and motor block postoperatively were excluded.
Patients were randomly divided into 1 of 4 study arms. Randomization was performed via sealed envelopes, which were opened in the recovery area when postoperative prescriptions were written. The group distribution was as follows: Group 1, Percocet 5 mg/325 mg alone (control); Group 2, oxycodone 5 mg, acetaminophen 325 mg administered separately; Group 3, oxycodone 5 mg, acetaminophen 325 mg, and oxycodone SR (OxyContin) 10 mg; and Group 4, oxycodone 5 mg, acetaminophen 325 mg, and ketorolac (Toradol) 10 mg (Table 1). Patients in the control group were instructed to take 1 or 2 tablets every 4 to 6 hours as needed for pain. Patients in the 3 experimental groups were given detailed instructions regarding when and how to take their medications. All patients were instructed to take 650 mg of acetaminophen every 6 hours. Patients were provided a sliding scale to assist in dosing their opioid medications according to their numeric pain score (NPS) (Table 2). Group 2 patients were given oxycodone 10 mg in the postanesthesia care unit (PACU) and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Table 1. Patient Groups
Group | Anesthesia | Pain Medications |
1 (standard treatment) | Brachial plexus block | Percocet (oxycodone and acetaminophen) 5-10 mg every 4-6 hours as needed for pain. |
2 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. |
3 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on numeric pain scale. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. OxyContin (oxycodone sustained release) 10 mg twice a day, scheduled. |
4 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. Toradol (Ketorolac) 10mg every 6 hours, scheduled. |
Table 2. Sliding Scale for Pain Control in the Experimental Groups
Pain Score | Oxycodone Dose |
0-3 | 5 mg (1 tablet) |
4-7 | 10 mg (2 tablets) |
8-10 | 15 mg (3 tablets) |
Group 3 patients were given oxycodone 10 mg in the PACU and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours and OxyContin 10 mg every 12 hours on a scheduled basis until their block wore off, then dose themselves using NPS. Group 4 patients were given oxycodone 10 mg postoperatively and ketorolac 30 mg intravenously in the PACU and instructed to take oxycodone 10 mg, acetaminophen 650 mg, and ketorolac 10 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Patients were provided with a journal and asked to record their medication usage, NPS, and any adverse effects (nausea, vomiting, and uncontrolled pain were specifically mentioned) or complications for 5 days after their procedure. We also attempted to contact patients by telephone on each of the 5 days after their procedure to remind them to complete their logs. They were asked specifically if they were having difficulty with their medications. They were also asked specifically about nausea, vomiting, and over-sedation. If patients requested additional medication to help treat their pain, they were instructed to add an over-the-counter NSAID of their choice based on the label’s suggested dosing.
Continue to: All patients received a supraclavicular...
All patients received a supraclavicular brachial plexus block using 0.75% ropivacaine under the supervision of an attending anesthesiologist experienced in regional anesthesia. Patients underwent thumb CMC arthroplasty utilizing complete resection of the trapezium followed by abductor pollicis longus suspensionplasty under the supervision of 1 of 3 fellowship-trained hand surgeons. ORIF of the distal radius was completed utilizing a volar approach and distal radius locking plate under the supervision of 1 of 3 fellowship-trained hand surgeons.
Primary outcome measures were the total number of oxycodone tablets taken daily and the average daily NPS. Secondary outcomes measured included adverse effects as noted above and the need for a trip to the emergency department for unrelieved pain.
A power analysis was completed prior to the beginning of the study. To detect a difference of at least 1 on the NPS, we determined that 18 patients per group would provide 80% power. This was based on literature utilizing the visual analog scale (VAS), a 100-mm line on which patients can place a mark to describe the intensity of their pain. The standard deviation on the VAS is approximately 15 mm. To account for potential dropout, we elected to recruit 20 patients per group. Non-paired t tests were used to compare groups.
RESULTS
One hundred and eighteen patients enrolled in the study. Of those, 79 patients completed and returned their summary logs (by group: 18 control, 20 oxycodone, 17 OxyContin, and 24 ketorolac). The remaining patients were excluded from the final analysis because they did not return their summary logs. Only 1 patient was excluded from the analysis because he did not have adequate regional anesthesia. Demographic data were analyzed and showed no significant differences between groups at the P < .05 level of significance. Surgical procedures were completed by 3 fellowship-trained hand surgeons. Distal radius fractures were performed using a volar approach. CMC arthroplasty was performed using a procedure that was standardized across surgeons. There were no between-surgeon differences in outcomes.
Average daily NPS (Figure 1) and the total number of oxycodone tablets taken (Figure 2) over the 5-day study period were recorded. Patients in the ketorolac group used fewer oxycodone tablets (19.3) than patients in the other 3 groups (24.4), P =.11, but the difference was not statistically significant. The maximum number of oxycodone tablets used was 71 in the Percocet group, 57 in the oxycodone and ketorolac groups, and 73 in the OxyContin group. The average daily NPS was lower in the ketorolac group during the period of medication use. This value only reached statistical significance on postoperative day 0 when the ketorolac group was compared with the OxyContin group (P = .01) and on postoperative day 1 when the ketorolac group was compared with the oxycodone group (P = .04). Complications (Figure 3) were greater in the non-ketorolac groups. One patient each in the oxycodone and OxyContin groups required a trip to the emergency department for pain control after their block wore off. Nausea and vomiting were present in each of the 4 groups but to a much greater degree in the Percocet and OxyContin groups; however, these results did not reach statistical significance (P = .129). Eleven of the 18 patients in the Percocet group required an additional NSAID (naproxen) and still did not achieve pain control similar to the other groups. This may explain why the average daily pain score in the Percocet group was lower than that in the oxycodone group, in which only 4 of the 20 patients supplemented with naproxen. Patients did, however, require many more oxycodone tablets to achieve pain control in the Percocet group. Over-sedation was reported in 3 patients in the oxycodone group and in 1 patient in the OxyContin group. No patients were found to have bleeding, renal, or other systemic complications.
Continue to: Discussion...
DISCUSSION
In this prospective, randomized study, we sought to determine whether a more organized approach to treating postoperative pain using a specific dosing regimen or opiates in conjunction with non-opiate medications would lead to improved pain control and a decreased need for opiates. We found that adding ketorolac to the postoperative pain regimen and outlining a more detailed set of instructions could lower narcotic usage in the first 4 postoperative days. In addition, adding ketorolac decreased other complications commonly seen with narcotic usage and was shown to be safe in our patient population.
Ketorolac has been shown to decrease narcotic pain medication usage in several surgical settings and across different surgical specialties. It is hypothesized that ketorolac potentiates the effects of narcotics.11 Ketorolac given alone has a potent analgesic effect by acting as a strong non-selective cyclooxygenase inhibitor. The major drawback to ketorolac use has been its well-known side-effect profile. Ketorolac is renally excreted, and as such, should not be used in patients with renal insufficiency. In addition, ketorolac has been shown to cause increased gastrointestinal bleeding when used for >5 days.15 Caution should be taken when combining ketorolac with thromboprophylactic medications, especially in older patients.
Many surgeons use NSAIDs along with narcotics as part of a postoperative pain regimen. While this is often adequate for some procedures, when the surgery involves manipulating fractures, internal fixation, or resection arthroplasty, the variation in individual patient pain may call for a more robust protocol. Additionally, as surgeons expand to more complex procedures performed in the outpatient setting, evaluating different combinations of analgesics taken in a more structured manner may provide for improved pain control.
A major component of patient satisfaction is postoperative pain control.3-8,12,16,17 Regional anesthesia is an important tool that allows patients to undergo a surgical procedure with a greatly reduced amount of opioid pain medications. In addition, regional anesthesia can provide significant pain control after the patient has left the ambulatory surgery center, but this relief is short-lived because the medication is designed to lose effectiveness over time. As the effects of regional anesthesia wear off, patients can experience “rebound pain” with severe levels of pain that, on occasion, cannot be controlled with oral analgesics alone. The addition of ketorolac provided improved pain control when compared with the other regimens during this transition period when the regional anesthesia was becoming ineffective. In addition, because patients taking ketorolac used less narcotic medication, they experienced less nausea, vomiting, and over-sedation.
Additionally, patients were instructed to record their medication usage and pain scores on a prospective basis, with the hope of eliminating recall bias. A potential weakness is the inability to show significance for pain relief and reduced narcotic usage with the addition of ketorolac, although there was a trend toward significance. Many of the patients who enrolled in the trial did not return their medication logs. While these patients had to be excluded from data analysis, we continued enrollment until we obtained an adequate number of patients in each group. In addition, in the OxyContin group (Group 3), we could only recruit 17 participants, instead of the 18 needed based on our power study. Although this has a potential to alter the significance of our results, we do not feel this had a substantial impact on our results.
Many patients in the non-ketorolac groups supplemented their medication regimens with NSAIDs, which may have falsely lowered pain scores and narcotic usage. While this confounds our study results, we do not believe that it invalidates the conclusion that ketorolac can be an effective adjunct pain medication for use in patients undergoing ambulatory hand surgery.
The study examined postoperative pain control for only 2 procedures, thumb basal joint arthroplasty and distal radius fracture fixation, both commonly performed in the outpatient setting under regional anesthesia and both typically requiring narcotic pain medication. Perhaps the utilization of these medication regimens with different surgical procedures would have differing results.
We conclude that ketorolac potentially provides patients with improved pain control over the use of narcotic pain medications alone in the setting of ambulatory hand surgery.
This paper will be judged for the Resident Writer’s Award.
- Boezaart AP, Davis G, Le-Wendling L. Recovery after orthopedic surgery: techniques to increase duration of pain control. Curr Opin Anaesthesiol. 2012;25(6):665-672. doi:10.1097/ACO.0b013e328359ab5a.
- Buvanendran A, Kroin JS. Useful adjuvants for postoperative pain management. Best Pract Res Clin Anaesthesiol. 2007;21(1):31-49. doi:10.1016/j.bpa.2006.12.003.
- Coluzzi F, Bragazzi L, Di Bussolo E, Pizza G, Mattia C. Determinants of patient satisfaction in postoperative pain management following hand ambulatory day-surgery. Minerva Med. 2011;102(3):177-186.
- Elvir-Lazo OL, White PF. Postoperative pain management after ambulatory surgery: role of multimodal analgesia. Anesthesiol Clin. 2010;28(2):217-224. doi: 10.1016/j.anclin.2010.02.011.
- Kopp SL, Horlocker TT. Regional anaesthesia in day-stay and short-stay surgery. Anaesthesia. 2010;65(Suppl 1):84-96. doi:10.1111/j.1365-2044.2009.06204.x.
- Rawal N. Postoperative pain treatment for ambulatory surgery. Best Pract Res Clin Anaesthesiol. 2007;21(1):129-148. doi:10.1016/j.bpa.2006.11.005.
- Schug SA, Chong C. Pain management after ambulatory surgery. Curr Opin Anaesthesiol. 2009;22(6):738-743. doi:10.1097/ACO.0b013e32833020f4.
- Sripada R, Bowens C Jr. Regional anesthesia procedures for shoulder and upper arm surgery upper extremity update--2005 to present. Int Anesthesiol Clin. 2012;50(1):26-46. doi:10.1097/AIA.0b013e31821a0284.
- Trompeter A, Camilleri G, Narang K, Hauf W, Venn R. Analgesia requirements after interscalene block for shoulder arthroscopy: the 5 days following surgery. Arch Orthop Trauma Surg. 2010;130(3):417-421. doi:10.1007/s00402-009-0959-9.
- Dufeu N, Marchand-Maillet F, Atchabahian A, et al. Efficacy and safety of ultrasound-guided distal blocks for analgesia without motor blockade after ambulatory hand surgery. J Hand Surg Am. 2014;39(4):737-743. doi:10.1016/j.jhsa.2014.01.011.
- Gutta R, Koehn CR, James LE. Does ketorolac have a preemptive analgesic effect? A randomized, double-blind, control study. J Oral Maxillofac Surg. 2013;71(12):2029-2034. doi:10.1016/j.joms.2013.06.220.
- Nossaman VE, Ramadhyani U, Kadowitz PJ, Nossaman BD. Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol. Anesthesiol Clin. 2010;28(4):647-666. doi:10.1016/j.anclin.2010.08.009.
- Warren-Stomberg M, Brattwall M, Jakobsson JG. Non-opioid analgesics for pain management following ambulatory surgery: a review. Minerva Anestesiol. 2013;79(9):1077-1087.
- Wickerts L, Warrén Stomberg M, Brattwall M, Jakobsson JJ. Coxibs: is there a benefit when compared to traditional non-selective NSAIDs in postoperative pain management? Minerva Anestesiol. 2011;77(11):1084-1098.
- Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996;275(5):376-382. doi:10.1001/jama.275.5.376.
- Hegarty M, Calder A, Davies K, et al. Does take-home analgesia improve postoperative pain after elective day case surgery? A comparison of hospital vs parent-supplied analgesia. Paediatr Anaesth. 2013;23(5):385-389. doi:10.1111/pan.12077.
- Weber SC, Jain R, Parise C. Pain scores in the management of postoperative pain in shoulder surgery. Arthroscopy. 2007;23(1):65-72. doi:10.1016/j.arthro.2006.11.002.
ABSTRACT
We evaluated postoperative pain control and narcotic usage after thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of the distal radius in patients given opiates with or without other non-opiate medication using a specific dosing regimen. A prospective, randomized study of 79 patients undergoing elective CMC arthroplasty or ORIF of the distal radius evaluated postoperative pain in the first 5 postoperative days. Patients were divided into 4 groups: Group 1, oxycodone and acetaminophen PRN; Group 2, oxycodone and acetaminophen with specific dosing; Group 3, oxycodone, acetaminophen, and OxyContin with specific dosing; and Group 4, oxycodone, acetaminophen, and ketorolac with specific dosing. During the first 5 postoperative days, we recorded pain levels according to a numeric pain scale, opioid usage, and complications. Although differences in our data did not reach statistical significance, overall pain scores, opioid usage, and complication rates were less prevalent in the oxycodone, acetaminophen, and ketorolac group. Postoperative pain following ambulatory hand and wrist surgery under regional anesthesia was more effectively controlled with fewer complications using a combination of oxycodone, acetaminophen, and ketorolac with a specific dosing regimen.
Continue to: Regional anesthesia...
Regional anesthesia is a safe and effective modality of perioperative pain control in patients undergoing ambulatory hand procedures.1-10 Often, as the regional block wears off, patients experience a rebound pain effect that can be challenging to manage.
We sought to determine if an organized, multimodal approach in patients undergoing thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of distal radius fractures would provide better postoperative pain control. We hypothesized that this approach would significantly reduce postoperative pain and the need for narcotic pain medication compared with PRN dosing of oxycodone/acetaminophen alone.11-14
MATERIALS AND METHODS
Our study was approved by our Institutional Review Board. Informed consent was obtained from each patient. Patients presenting for elective thumb CMC arthroplasty or ORIF of the distal radius were screened for inclusion in a prospective, randomized study. Inclusion criteria included patients aged 18 to 65 years who could provide informed consent. Patients with chronic pain syndromes, long-term narcotic usage, chronic medical conditions precluding the use of opiates or nonsteroidal anti-inflammatory drugs (NSAIDs), and those who did not have a complete sensory and motor block postoperatively were excluded.
Patients were randomly divided into 1 of 4 study arms. Randomization was performed via sealed envelopes, which were opened in the recovery area when postoperative prescriptions were written. The group distribution was as follows: Group 1, Percocet 5 mg/325 mg alone (control); Group 2, oxycodone 5 mg, acetaminophen 325 mg administered separately; Group 3, oxycodone 5 mg, acetaminophen 325 mg, and oxycodone SR (OxyContin) 10 mg; and Group 4, oxycodone 5 mg, acetaminophen 325 mg, and ketorolac (Toradol) 10 mg (Table 1). Patients in the control group were instructed to take 1 or 2 tablets every 4 to 6 hours as needed for pain. Patients in the 3 experimental groups were given detailed instructions regarding when and how to take their medications. All patients were instructed to take 650 mg of acetaminophen every 6 hours. Patients were provided a sliding scale to assist in dosing their opioid medications according to their numeric pain score (NPS) (Table 2). Group 2 patients were given oxycodone 10 mg in the postanesthesia care unit (PACU) and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Table 1. Patient Groups
Group | Anesthesia | Pain Medications |
1 (standard treatment) | Brachial plexus block | Percocet (oxycodone and acetaminophen) 5-10 mg every 4-6 hours as needed for pain. |
2 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. |
3 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on numeric pain scale. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. OxyContin (oxycodone sustained release) 10 mg twice a day, scheduled. |
4 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. Toradol (Ketorolac) 10mg every 6 hours, scheduled. |
Table 2. Sliding Scale for Pain Control in the Experimental Groups
Pain Score | Oxycodone Dose |
0-3 | 5 mg (1 tablet) |
4-7 | 10 mg (2 tablets) |
8-10 | 15 mg (3 tablets) |
Group 3 patients were given oxycodone 10 mg in the PACU and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours and OxyContin 10 mg every 12 hours on a scheduled basis until their block wore off, then dose themselves using NPS. Group 4 patients were given oxycodone 10 mg postoperatively and ketorolac 30 mg intravenously in the PACU and instructed to take oxycodone 10 mg, acetaminophen 650 mg, and ketorolac 10 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Patients were provided with a journal and asked to record their medication usage, NPS, and any adverse effects (nausea, vomiting, and uncontrolled pain were specifically mentioned) or complications for 5 days after their procedure. We also attempted to contact patients by telephone on each of the 5 days after their procedure to remind them to complete their logs. They were asked specifically if they were having difficulty with their medications. They were also asked specifically about nausea, vomiting, and over-sedation. If patients requested additional medication to help treat their pain, they were instructed to add an over-the-counter NSAID of their choice based on the label’s suggested dosing.
Continue to: All patients received a supraclavicular...
All patients received a supraclavicular brachial plexus block using 0.75% ropivacaine under the supervision of an attending anesthesiologist experienced in regional anesthesia. Patients underwent thumb CMC arthroplasty utilizing complete resection of the trapezium followed by abductor pollicis longus suspensionplasty under the supervision of 1 of 3 fellowship-trained hand surgeons. ORIF of the distal radius was completed utilizing a volar approach and distal radius locking plate under the supervision of 1 of 3 fellowship-trained hand surgeons.
Primary outcome measures were the total number of oxycodone tablets taken daily and the average daily NPS. Secondary outcomes measured included adverse effects as noted above and the need for a trip to the emergency department for unrelieved pain.
A power analysis was completed prior to the beginning of the study. To detect a difference of at least 1 on the NPS, we determined that 18 patients per group would provide 80% power. This was based on literature utilizing the visual analog scale (VAS), a 100-mm line on which patients can place a mark to describe the intensity of their pain. The standard deviation on the VAS is approximately 15 mm. To account for potential dropout, we elected to recruit 20 patients per group. Non-paired t tests were used to compare groups.
RESULTS
One hundred and eighteen patients enrolled in the study. Of those, 79 patients completed and returned their summary logs (by group: 18 control, 20 oxycodone, 17 OxyContin, and 24 ketorolac). The remaining patients were excluded from the final analysis because they did not return their summary logs. Only 1 patient was excluded from the analysis because he did not have adequate regional anesthesia. Demographic data were analyzed and showed no significant differences between groups at the P < .05 level of significance. Surgical procedures were completed by 3 fellowship-trained hand surgeons. Distal radius fractures were performed using a volar approach. CMC arthroplasty was performed using a procedure that was standardized across surgeons. There were no between-surgeon differences in outcomes.
Average daily NPS (Figure 1) and the total number of oxycodone tablets taken (Figure 2) over the 5-day study period were recorded. Patients in the ketorolac group used fewer oxycodone tablets (19.3) than patients in the other 3 groups (24.4), P =.11, but the difference was not statistically significant. The maximum number of oxycodone tablets used was 71 in the Percocet group, 57 in the oxycodone and ketorolac groups, and 73 in the OxyContin group. The average daily NPS was lower in the ketorolac group during the period of medication use. This value only reached statistical significance on postoperative day 0 when the ketorolac group was compared with the OxyContin group (P = .01) and on postoperative day 1 when the ketorolac group was compared with the oxycodone group (P = .04). Complications (Figure 3) were greater in the non-ketorolac groups. One patient each in the oxycodone and OxyContin groups required a trip to the emergency department for pain control after their block wore off. Nausea and vomiting were present in each of the 4 groups but to a much greater degree in the Percocet and OxyContin groups; however, these results did not reach statistical significance (P = .129). Eleven of the 18 patients in the Percocet group required an additional NSAID (naproxen) and still did not achieve pain control similar to the other groups. This may explain why the average daily pain score in the Percocet group was lower than that in the oxycodone group, in which only 4 of the 20 patients supplemented with naproxen. Patients did, however, require many more oxycodone tablets to achieve pain control in the Percocet group. Over-sedation was reported in 3 patients in the oxycodone group and in 1 patient in the OxyContin group. No patients were found to have bleeding, renal, or other systemic complications.
Continue to: Discussion...
DISCUSSION
In this prospective, randomized study, we sought to determine whether a more organized approach to treating postoperative pain using a specific dosing regimen or opiates in conjunction with non-opiate medications would lead to improved pain control and a decreased need for opiates. We found that adding ketorolac to the postoperative pain regimen and outlining a more detailed set of instructions could lower narcotic usage in the first 4 postoperative days. In addition, adding ketorolac decreased other complications commonly seen with narcotic usage and was shown to be safe in our patient population.
Ketorolac has been shown to decrease narcotic pain medication usage in several surgical settings and across different surgical specialties. It is hypothesized that ketorolac potentiates the effects of narcotics.11 Ketorolac given alone has a potent analgesic effect by acting as a strong non-selective cyclooxygenase inhibitor. The major drawback to ketorolac use has been its well-known side-effect profile. Ketorolac is renally excreted, and as such, should not be used in patients with renal insufficiency. In addition, ketorolac has been shown to cause increased gastrointestinal bleeding when used for >5 days.15 Caution should be taken when combining ketorolac with thromboprophylactic medications, especially in older patients.
Many surgeons use NSAIDs along with narcotics as part of a postoperative pain regimen. While this is often adequate for some procedures, when the surgery involves manipulating fractures, internal fixation, or resection arthroplasty, the variation in individual patient pain may call for a more robust protocol. Additionally, as surgeons expand to more complex procedures performed in the outpatient setting, evaluating different combinations of analgesics taken in a more structured manner may provide for improved pain control.
A major component of patient satisfaction is postoperative pain control.3-8,12,16,17 Regional anesthesia is an important tool that allows patients to undergo a surgical procedure with a greatly reduced amount of opioid pain medications. In addition, regional anesthesia can provide significant pain control after the patient has left the ambulatory surgery center, but this relief is short-lived because the medication is designed to lose effectiveness over time. As the effects of regional anesthesia wear off, patients can experience “rebound pain” with severe levels of pain that, on occasion, cannot be controlled with oral analgesics alone. The addition of ketorolac provided improved pain control when compared with the other regimens during this transition period when the regional anesthesia was becoming ineffective. In addition, because patients taking ketorolac used less narcotic medication, they experienced less nausea, vomiting, and over-sedation.
Additionally, patients were instructed to record their medication usage and pain scores on a prospective basis, with the hope of eliminating recall bias. A potential weakness is the inability to show significance for pain relief and reduced narcotic usage with the addition of ketorolac, although there was a trend toward significance. Many of the patients who enrolled in the trial did not return their medication logs. While these patients had to be excluded from data analysis, we continued enrollment until we obtained an adequate number of patients in each group. In addition, in the OxyContin group (Group 3), we could only recruit 17 participants, instead of the 18 needed based on our power study. Although this has a potential to alter the significance of our results, we do not feel this had a substantial impact on our results.
Many patients in the non-ketorolac groups supplemented their medication regimens with NSAIDs, which may have falsely lowered pain scores and narcotic usage. While this confounds our study results, we do not believe that it invalidates the conclusion that ketorolac can be an effective adjunct pain medication for use in patients undergoing ambulatory hand surgery.
The study examined postoperative pain control for only 2 procedures, thumb basal joint arthroplasty and distal radius fracture fixation, both commonly performed in the outpatient setting under regional anesthesia and both typically requiring narcotic pain medication. Perhaps the utilization of these medication regimens with different surgical procedures would have differing results.
We conclude that ketorolac potentially provides patients with improved pain control over the use of narcotic pain medications alone in the setting of ambulatory hand surgery.
This paper will be judged for the Resident Writer’s Award.
ABSTRACT
We evaluated postoperative pain control and narcotic usage after thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of the distal radius in patients given opiates with or without other non-opiate medication using a specific dosing regimen. A prospective, randomized study of 79 patients undergoing elective CMC arthroplasty or ORIF of the distal radius evaluated postoperative pain in the first 5 postoperative days. Patients were divided into 4 groups: Group 1, oxycodone and acetaminophen PRN; Group 2, oxycodone and acetaminophen with specific dosing; Group 3, oxycodone, acetaminophen, and OxyContin with specific dosing; and Group 4, oxycodone, acetaminophen, and ketorolac with specific dosing. During the first 5 postoperative days, we recorded pain levels according to a numeric pain scale, opioid usage, and complications. Although differences in our data did not reach statistical significance, overall pain scores, opioid usage, and complication rates were less prevalent in the oxycodone, acetaminophen, and ketorolac group. Postoperative pain following ambulatory hand and wrist surgery under regional anesthesia was more effectively controlled with fewer complications using a combination of oxycodone, acetaminophen, and ketorolac with a specific dosing regimen.
Continue to: Regional anesthesia...
Regional anesthesia is a safe and effective modality of perioperative pain control in patients undergoing ambulatory hand procedures.1-10 Often, as the regional block wears off, patients experience a rebound pain effect that can be challenging to manage.
We sought to determine if an organized, multimodal approach in patients undergoing thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of distal radius fractures would provide better postoperative pain control. We hypothesized that this approach would significantly reduce postoperative pain and the need for narcotic pain medication compared with PRN dosing of oxycodone/acetaminophen alone.11-14
MATERIALS AND METHODS
Our study was approved by our Institutional Review Board. Informed consent was obtained from each patient. Patients presenting for elective thumb CMC arthroplasty or ORIF of the distal radius were screened for inclusion in a prospective, randomized study. Inclusion criteria included patients aged 18 to 65 years who could provide informed consent. Patients with chronic pain syndromes, long-term narcotic usage, chronic medical conditions precluding the use of opiates or nonsteroidal anti-inflammatory drugs (NSAIDs), and those who did not have a complete sensory and motor block postoperatively were excluded.
Patients were randomly divided into 1 of 4 study arms. Randomization was performed via sealed envelopes, which were opened in the recovery area when postoperative prescriptions were written. The group distribution was as follows: Group 1, Percocet 5 mg/325 mg alone (control); Group 2, oxycodone 5 mg, acetaminophen 325 mg administered separately; Group 3, oxycodone 5 mg, acetaminophen 325 mg, and oxycodone SR (OxyContin) 10 mg; and Group 4, oxycodone 5 mg, acetaminophen 325 mg, and ketorolac (Toradol) 10 mg (Table 1). Patients in the control group were instructed to take 1 or 2 tablets every 4 to 6 hours as needed for pain. Patients in the 3 experimental groups were given detailed instructions regarding when and how to take their medications. All patients were instructed to take 650 mg of acetaminophen every 6 hours. Patients were provided a sliding scale to assist in dosing their opioid medications according to their numeric pain score (NPS) (Table 2). Group 2 patients were given oxycodone 10 mg in the postanesthesia care unit (PACU) and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Table 1. Patient Groups
Group | Anesthesia | Pain Medications |
1 (standard treatment) | Brachial plexus block | Percocet (oxycodone and acetaminophen) 5-10 mg every 4-6 hours as needed for pain. |
2 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. |
3 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on numeric pain scale. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. OxyContin (oxycodone sustained release) 10 mg twice a day, scheduled. |
4 | Brachial plexus block | 1. Oxycodone 0-15 mg every 4-6 hours as needed for pain based on pain scale score. 2. Tylenol (Acetaminophen) 650 mg every 6 hours, scheduled. 3. Toradol (Ketorolac) 10mg every 6 hours, scheduled. |
Table 2. Sliding Scale for Pain Control in the Experimental Groups
Pain Score | Oxycodone Dose |
0-3 | 5 mg (1 tablet) |
4-7 | 10 mg (2 tablets) |
8-10 | 15 mg (3 tablets) |
Group 3 patients were given oxycodone 10 mg in the PACU and instructed to take oxycodone 10 mg with acetaminophen 650 mg every 6 hours and OxyContin 10 mg every 12 hours on a scheduled basis until their block wore off, then dose themselves using NPS. Group 4 patients were given oxycodone 10 mg postoperatively and ketorolac 30 mg intravenously in the PACU and instructed to take oxycodone 10 mg, acetaminophen 650 mg, and ketorolac 10 mg every 6 hours on a scheduled basis until their block wore off, then dose themselves using the NPS.
Patients were provided with a journal and asked to record their medication usage, NPS, and any adverse effects (nausea, vomiting, and uncontrolled pain were specifically mentioned) or complications for 5 days after their procedure. We also attempted to contact patients by telephone on each of the 5 days after their procedure to remind them to complete their logs. They were asked specifically if they were having difficulty with their medications. They were also asked specifically about nausea, vomiting, and over-sedation. If patients requested additional medication to help treat their pain, they were instructed to add an over-the-counter NSAID of their choice based on the label’s suggested dosing.
Continue to: All patients received a supraclavicular...
All patients received a supraclavicular brachial plexus block using 0.75% ropivacaine under the supervision of an attending anesthesiologist experienced in regional anesthesia. Patients underwent thumb CMC arthroplasty utilizing complete resection of the trapezium followed by abductor pollicis longus suspensionplasty under the supervision of 1 of 3 fellowship-trained hand surgeons. ORIF of the distal radius was completed utilizing a volar approach and distal radius locking plate under the supervision of 1 of 3 fellowship-trained hand surgeons.
Primary outcome measures were the total number of oxycodone tablets taken daily and the average daily NPS. Secondary outcomes measured included adverse effects as noted above and the need for a trip to the emergency department for unrelieved pain.
A power analysis was completed prior to the beginning of the study. To detect a difference of at least 1 on the NPS, we determined that 18 patients per group would provide 80% power. This was based on literature utilizing the visual analog scale (VAS), a 100-mm line on which patients can place a mark to describe the intensity of their pain. The standard deviation on the VAS is approximately 15 mm. To account for potential dropout, we elected to recruit 20 patients per group. Non-paired t tests were used to compare groups.
RESULTS
One hundred and eighteen patients enrolled in the study. Of those, 79 patients completed and returned their summary logs (by group: 18 control, 20 oxycodone, 17 OxyContin, and 24 ketorolac). The remaining patients were excluded from the final analysis because they did not return their summary logs. Only 1 patient was excluded from the analysis because he did not have adequate regional anesthesia. Demographic data were analyzed and showed no significant differences between groups at the P < .05 level of significance. Surgical procedures were completed by 3 fellowship-trained hand surgeons. Distal radius fractures were performed using a volar approach. CMC arthroplasty was performed using a procedure that was standardized across surgeons. There were no between-surgeon differences in outcomes.
Average daily NPS (Figure 1) and the total number of oxycodone tablets taken (Figure 2) over the 5-day study period were recorded. Patients in the ketorolac group used fewer oxycodone tablets (19.3) than patients in the other 3 groups (24.4), P =.11, but the difference was not statistically significant. The maximum number of oxycodone tablets used was 71 in the Percocet group, 57 in the oxycodone and ketorolac groups, and 73 in the OxyContin group. The average daily NPS was lower in the ketorolac group during the period of medication use. This value only reached statistical significance on postoperative day 0 when the ketorolac group was compared with the OxyContin group (P = .01) and on postoperative day 1 when the ketorolac group was compared with the oxycodone group (P = .04). Complications (Figure 3) were greater in the non-ketorolac groups. One patient each in the oxycodone and OxyContin groups required a trip to the emergency department for pain control after their block wore off. Nausea and vomiting were present in each of the 4 groups but to a much greater degree in the Percocet and OxyContin groups; however, these results did not reach statistical significance (P = .129). Eleven of the 18 patients in the Percocet group required an additional NSAID (naproxen) and still did not achieve pain control similar to the other groups. This may explain why the average daily pain score in the Percocet group was lower than that in the oxycodone group, in which only 4 of the 20 patients supplemented with naproxen. Patients did, however, require many more oxycodone tablets to achieve pain control in the Percocet group. Over-sedation was reported in 3 patients in the oxycodone group and in 1 patient in the OxyContin group. No patients were found to have bleeding, renal, or other systemic complications.
Continue to: Discussion...
DISCUSSION
In this prospective, randomized study, we sought to determine whether a more organized approach to treating postoperative pain using a specific dosing regimen or opiates in conjunction with non-opiate medications would lead to improved pain control and a decreased need for opiates. We found that adding ketorolac to the postoperative pain regimen and outlining a more detailed set of instructions could lower narcotic usage in the first 4 postoperative days. In addition, adding ketorolac decreased other complications commonly seen with narcotic usage and was shown to be safe in our patient population.
Ketorolac has been shown to decrease narcotic pain medication usage in several surgical settings and across different surgical specialties. It is hypothesized that ketorolac potentiates the effects of narcotics.11 Ketorolac given alone has a potent analgesic effect by acting as a strong non-selective cyclooxygenase inhibitor. The major drawback to ketorolac use has been its well-known side-effect profile. Ketorolac is renally excreted, and as such, should not be used in patients with renal insufficiency. In addition, ketorolac has been shown to cause increased gastrointestinal bleeding when used for >5 days.15 Caution should be taken when combining ketorolac with thromboprophylactic medications, especially in older patients.
Many surgeons use NSAIDs along with narcotics as part of a postoperative pain regimen. While this is often adequate for some procedures, when the surgery involves manipulating fractures, internal fixation, or resection arthroplasty, the variation in individual patient pain may call for a more robust protocol. Additionally, as surgeons expand to more complex procedures performed in the outpatient setting, evaluating different combinations of analgesics taken in a more structured manner may provide for improved pain control.
A major component of patient satisfaction is postoperative pain control.3-8,12,16,17 Regional anesthesia is an important tool that allows patients to undergo a surgical procedure with a greatly reduced amount of opioid pain medications. In addition, regional anesthesia can provide significant pain control after the patient has left the ambulatory surgery center, but this relief is short-lived because the medication is designed to lose effectiveness over time. As the effects of regional anesthesia wear off, patients can experience “rebound pain” with severe levels of pain that, on occasion, cannot be controlled with oral analgesics alone. The addition of ketorolac provided improved pain control when compared with the other regimens during this transition period when the regional anesthesia was becoming ineffective. In addition, because patients taking ketorolac used less narcotic medication, they experienced less nausea, vomiting, and over-sedation.
Additionally, patients were instructed to record their medication usage and pain scores on a prospective basis, with the hope of eliminating recall bias. A potential weakness is the inability to show significance for pain relief and reduced narcotic usage with the addition of ketorolac, although there was a trend toward significance. Many of the patients who enrolled in the trial did not return their medication logs. While these patients had to be excluded from data analysis, we continued enrollment until we obtained an adequate number of patients in each group. In addition, in the OxyContin group (Group 3), we could only recruit 17 participants, instead of the 18 needed based on our power study. Although this has a potential to alter the significance of our results, we do not feel this had a substantial impact on our results.
Many patients in the non-ketorolac groups supplemented their medication regimens with NSAIDs, which may have falsely lowered pain scores and narcotic usage. While this confounds our study results, we do not believe that it invalidates the conclusion that ketorolac can be an effective adjunct pain medication for use in patients undergoing ambulatory hand surgery.
The study examined postoperative pain control for only 2 procedures, thumb basal joint arthroplasty and distal radius fracture fixation, both commonly performed in the outpatient setting under regional anesthesia and both typically requiring narcotic pain medication. Perhaps the utilization of these medication regimens with different surgical procedures would have differing results.
We conclude that ketorolac potentially provides patients with improved pain control over the use of narcotic pain medications alone in the setting of ambulatory hand surgery.
This paper will be judged for the Resident Writer’s Award.
- Boezaart AP, Davis G, Le-Wendling L. Recovery after orthopedic surgery: techniques to increase duration of pain control. Curr Opin Anaesthesiol. 2012;25(6):665-672. doi:10.1097/ACO.0b013e328359ab5a.
- Buvanendran A, Kroin JS. Useful adjuvants for postoperative pain management. Best Pract Res Clin Anaesthesiol. 2007;21(1):31-49. doi:10.1016/j.bpa.2006.12.003.
- Coluzzi F, Bragazzi L, Di Bussolo E, Pizza G, Mattia C. Determinants of patient satisfaction in postoperative pain management following hand ambulatory day-surgery. Minerva Med. 2011;102(3):177-186.
- Elvir-Lazo OL, White PF. Postoperative pain management after ambulatory surgery: role of multimodal analgesia. Anesthesiol Clin. 2010;28(2):217-224. doi: 10.1016/j.anclin.2010.02.011.
- Kopp SL, Horlocker TT. Regional anaesthesia in day-stay and short-stay surgery. Anaesthesia. 2010;65(Suppl 1):84-96. doi:10.1111/j.1365-2044.2009.06204.x.
- Rawal N. Postoperative pain treatment for ambulatory surgery. Best Pract Res Clin Anaesthesiol. 2007;21(1):129-148. doi:10.1016/j.bpa.2006.11.005.
- Schug SA, Chong C. Pain management after ambulatory surgery. Curr Opin Anaesthesiol. 2009;22(6):738-743. doi:10.1097/ACO.0b013e32833020f4.
- Sripada R, Bowens C Jr. Regional anesthesia procedures for shoulder and upper arm surgery upper extremity update--2005 to present. Int Anesthesiol Clin. 2012;50(1):26-46. doi:10.1097/AIA.0b013e31821a0284.
- Trompeter A, Camilleri G, Narang K, Hauf W, Venn R. Analgesia requirements after interscalene block for shoulder arthroscopy: the 5 days following surgery. Arch Orthop Trauma Surg. 2010;130(3):417-421. doi:10.1007/s00402-009-0959-9.
- Dufeu N, Marchand-Maillet F, Atchabahian A, et al. Efficacy and safety of ultrasound-guided distal blocks for analgesia without motor blockade after ambulatory hand surgery. J Hand Surg Am. 2014;39(4):737-743. doi:10.1016/j.jhsa.2014.01.011.
- Gutta R, Koehn CR, James LE. Does ketorolac have a preemptive analgesic effect? A randomized, double-blind, control study. J Oral Maxillofac Surg. 2013;71(12):2029-2034. doi:10.1016/j.joms.2013.06.220.
- Nossaman VE, Ramadhyani U, Kadowitz PJ, Nossaman BD. Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol. Anesthesiol Clin. 2010;28(4):647-666. doi:10.1016/j.anclin.2010.08.009.
- Warren-Stomberg M, Brattwall M, Jakobsson JG. Non-opioid analgesics for pain management following ambulatory surgery: a review. Minerva Anestesiol. 2013;79(9):1077-1087.
- Wickerts L, Warrén Stomberg M, Brattwall M, Jakobsson JJ. Coxibs: is there a benefit when compared to traditional non-selective NSAIDs in postoperative pain management? Minerva Anestesiol. 2011;77(11):1084-1098.
- Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996;275(5):376-382. doi:10.1001/jama.275.5.376.
- Hegarty M, Calder A, Davies K, et al. Does take-home analgesia improve postoperative pain after elective day case surgery? A comparison of hospital vs parent-supplied analgesia. Paediatr Anaesth. 2013;23(5):385-389. doi:10.1111/pan.12077.
- Weber SC, Jain R, Parise C. Pain scores in the management of postoperative pain in shoulder surgery. Arthroscopy. 2007;23(1):65-72. doi:10.1016/j.arthro.2006.11.002.
- Boezaart AP, Davis G, Le-Wendling L. Recovery after orthopedic surgery: techniques to increase duration of pain control. Curr Opin Anaesthesiol. 2012;25(6):665-672. doi:10.1097/ACO.0b013e328359ab5a.
- Buvanendran A, Kroin JS. Useful adjuvants for postoperative pain management. Best Pract Res Clin Anaesthesiol. 2007;21(1):31-49. doi:10.1016/j.bpa.2006.12.003.
- Coluzzi F, Bragazzi L, Di Bussolo E, Pizza G, Mattia C. Determinants of patient satisfaction in postoperative pain management following hand ambulatory day-surgery. Minerva Med. 2011;102(3):177-186.
- Elvir-Lazo OL, White PF. Postoperative pain management after ambulatory surgery: role of multimodal analgesia. Anesthesiol Clin. 2010;28(2):217-224. doi: 10.1016/j.anclin.2010.02.011.
- Kopp SL, Horlocker TT. Regional anaesthesia in day-stay and short-stay surgery. Anaesthesia. 2010;65(Suppl 1):84-96. doi:10.1111/j.1365-2044.2009.06204.x.
- Rawal N. Postoperative pain treatment for ambulatory surgery. Best Pract Res Clin Anaesthesiol. 2007;21(1):129-148. doi:10.1016/j.bpa.2006.11.005.
- Schug SA, Chong C. Pain management after ambulatory surgery. Curr Opin Anaesthesiol. 2009;22(6):738-743. doi:10.1097/ACO.0b013e32833020f4.
- Sripada R, Bowens C Jr. Regional anesthesia procedures for shoulder and upper arm surgery upper extremity update--2005 to present. Int Anesthesiol Clin. 2012;50(1):26-46. doi:10.1097/AIA.0b013e31821a0284.
- Trompeter A, Camilleri G, Narang K, Hauf W, Venn R. Analgesia requirements after interscalene block for shoulder arthroscopy: the 5 days following surgery. Arch Orthop Trauma Surg. 2010;130(3):417-421. doi:10.1007/s00402-009-0959-9.
- Dufeu N, Marchand-Maillet F, Atchabahian A, et al. Efficacy and safety of ultrasound-guided distal blocks for analgesia without motor blockade after ambulatory hand surgery. J Hand Surg Am. 2014;39(4):737-743. doi:10.1016/j.jhsa.2014.01.011.
- Gutta R, Koehn CR, James LE. Does ketorolac have a preemptive analgesic effect? A randomized, double-blind, control study. J Oral Maxillofac Surg. 2013;71(12):2029-2034. doi:10.1016/j.joms.2013.06.220.
- Nossaman VE, Ramadhyani U, Kadowitz PJ, Nossaman BD. Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol. Anesthesiol Clin. 2010;28(4):647-666. doi:10.1016/j.anclin.2010.08.009.
- Warren-Stomberg M, Brattwall M, Jakobsson JG. Non-opioid analgesics for pain management following ambulatory surgery: a review. Minerva Anestesiol. 2013;79(9):1077-1087.
- Wickerts L, Warrén Stomberg M, Brattwall M, Jakobsson JJ. Coxibs: is there a benefit when compared to traditional non-selective NSAIDs in postoperative pain management? Minerva Anestesiol. 2011;77(11):1084-1098.
- Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996;275(5):376-382. doi:10.1001/jama.275.5.376.
- Hegarty M, Calder A, Davies K, et al. Does take-home analgesia improve postoperative pain after elective day case surgery? A comparison of hospital vs parent-supplied analgesia. Paediatr Anaesth. 2013;23(5):385-389. doi:10.1111/pan.12077.
- Weber SC, Jain R, Parise C. Pain scores in the management of postoperative pain in shoulder surgery. Arthroscopy. 2007;23(1):65-72. doi:10.1016/j.arthro.2006.11.002.
TAKE-HOME POINTS
- While regional anesthesia is safe and effective for patients who undergo ambulatory hand surgery, patients often experience rebound pain as it wears off.
- We tested a multimodal approach for patients who underwent thumb CMC arthroplasty or ORIF of distal radius fracture.
- Patients were provided with a journal and asked to record medication usage, a NPS, and adverse effects. Seventy-nine patients completed the study.
- We found that adding ketorolac to the postoperative pain protocol, with detailed instructions, lowered narcotic usage in the first 4 postoperative days.
- Ketorolac potentially provides patients with improved pain control over the use of narcotic pain medication alone in an ambulatory hand surgery setting.