Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.

©vchal/Thinkstock

The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.

The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.

Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.

PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.

The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.

“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.

“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.

The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.

[email protected]

SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.

Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.

©vchal/Thinkstock

The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.

The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.

Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.

PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.

The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.

“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.

“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.

The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.

[email protected]

SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.

Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.

©vchal/Thinkstock

The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.

The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.

Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.

PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.

The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.

“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.

“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.

The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.

[email protected]

SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.

A group of expert robotic colorectal surgeons have published what they claim is the first European consensus on standards for total mesorectal excision (TME) and anterior resection in robotic rectal surgery in an effort to establish uniform training and education and improve outcomes for the robotic operations.

gorodenkoff/iStock/Getty Images

“The aim of this consensus study was to establish a detailed description of technical steps for robotic anterior resection and TME of the rectum as recommended by a representative group of established European expert surgeons,” wrote Danilo Miskovic, PhD, FRCS, of St. Mark’s Hospital in London, and his coauthors. The study, published in Colorectal Disease, provides a baseline for technical standards and structured training in robotic rectal surgery.

The consensus authors acted at the behest of the European Academy for Robotic Colorectal Surgery (EARCS), a nonprofit organization that provides training for robotic colorectal surgery. They cited evidence suggesting that the robotic approach to TME confers significant benefits in selected patients, compared with laparoscopic surgery (Dis Colon Rectum. 2014;57:570-7), but that the ROLARR trial found no benefit with robotic surgery (Int J Colorectal Dis. 2012;27:233-41).

“Notwithstanding the absence of evidence, robotic surgery continues to increase in popularity in many countries,” Dr. Miskovic and his coauthors wrote.

The consensus statement covers recommendations for the da Vinci Si and Xi robotic platforms in the following areas.

• Surgical setup, including patient positioning and port placement and docking.
• Colonic mobilization, including vascular pedicle dissection and splenic flexure mobilization.
• Pelvic dissection, including establishing operative planes and specimen extraction.

Dr. Miskovic and his coauthors arrived at the consensus statement by asking 24 EARCS faculty members to complete a 72-item questionnaire. The initial responses yielded an 87% agreement among the responses, but after suggested modifications, the average level of agreement for all items was 97%.

One of the limitations of the study that the investigators acknowledged is that it covers only two da Vinci robotic platforms; the recommendations may not apply to new robotic systems. Secondly, a selected group of experts provided input. “There may be other experienced surgeons who might disagree with some aspects of our recommendations,” the authors wrote. “This document should therefore be seen as a foundation for debate and modification in light of future technical developments.”

Future research should evaluate how training of technical standards within a group like EARCS impacts clinical outcomes, Dr. Miskovic and his coauthors noted.

The investigators had no financial relationships to report. Participating surgeons are members of the EARCS faculty and/or its scientific committee

SOURCE: Miskovic D et al. Colorectal Dis. 2018 Nov 29. doi: 10.1111/codi.14502.

A group of expert robotic colorectal surgeons have published what they claim is the first European consensus on standards for total mesorectal excision (TME) and anterior resection in robotic rectal surgery in an effort to establish uniform training and education and improve outcomes for the robotic operations.

gorodenkoff/iStock/Getty Images

“The aim of this consensus study was to establish a detailed description of technical steps for robotic anterior resection and TME of the rectum as recommended by a representative group of established European expert surgeons,” wrote Danilo Miskovic, PhD, FRCS, of St. Mark’s Hospital in London, and his coauthors. The study, published in Colorectal Disease, provides a baseline for technical standards and structured training in robotic rectal surgery.

The consensus authors acted at the behest of the European Academy for Robotic Colorectal Surgery (EARCS), a nonprofit organization that provides training for robotic colorectal surgery. They cited evidence suggesting that the robotic approach to TME confers significant benefits in selected patients, compared with laparoscopic surgery (Dis Colon Rectum. 2014;57:570-7), but that the ROLARR trial found no benefit with robotic surgery (Int J Colorectal Dis. 2012;27:233-41).

“Notwithstanding the absence of evidence, robotic surgery continues to increase in popularity in many countries,” Dr. Miskovic and his coauthors wrote.

The consensus statement covers recommendations for the da Vinci Si and Xi robotic platforms in the following areas.

• Surgical setup, including patient positioning and port placement and docking.
• Colonic mobilization, including vascular pedicle dissection and splenic flexure mobilization.
• Pelvic dissection, including establishing operative planes and specimen extraction.

Dr. Miskovic and his coauthors arrived at the consensus statement by asking 24 EARCS faculty members to complete a 72-item questionnaire. The initial responses yielded an 87% agreement among the responses, but after suggested modifications, the average level of agreement for all items was 97%.

One of the limitations of the study that the investigators acknowledged is that it covers only two da Vinci robotic platforms; the recommendations may not apply to new robotic systems. Secondly, a selected group of experts provided input. “There may be other experienced surgeons who might disagree with some aspects of our recommendations,” the authors wrote. “This document should therefore be seen as a foundation for debate and modification in light of future technical developments.”

Future research should evaluate how training of technical standards within a group like EARCS impacts clinical outcomes, Dr. Miskovic and his coauthors noted.

The investigators had no financial relationships to report. Participating surgeons are members of the EARCS faculty and/or its scientific committee

SOURCE: Miskovic D et al. Colorectal Dis. 2018 Nov 29. doi: 10.1111/codi.14502.

A group of expert robotic colorectal surgeons have published what they claim is the first European consensus on standards for total mesorectal excision (TME) and anterior resection in robotic rectal surgery in an effort to establish uniform training and education and improve outcomes for the robotic operations.

gorodenkoff/iStock/Getty Images

“The aim of this consensus study was to establish a detailed description of technical steps for robotic anterior resection and TME of the rectum as recommended by a representative group of established European expert surgeons,” wrote Danilo Miskovic, PhD, FRCS, of St. Mark’s Hospital in London, and his coauthors. The study, published in Colorectal Disease, provides a baseline for technical standards and structured training in robotic rectal surgery.

The consensus authors acted at the behest of the European Academy for Robotic Colorectal Surgery (EARCS), a nonprofit organization that provides training for robotic colorectal surgery. They cited evidence suggesting that the robotic approach to TME confers significant benefits in selected patients, compared with laparoscopic surgery (Dis Colon Rectum. 2014;57:570-7), but that the ROLARR trial found no benefit with robotic surgery (Int J Colorectal Dis. 2012;27:233-41).

“Notwithstanding the absence of evidence, robotic surgery continues to increase in popularity in many countries,” Dr. Miskovic and his coauthors wrote.

The consensus statement covers recommendations for the da Vinci Si and Xi robotic platforms in the following areas.

• Surgical setup, including patient positioning and port placement and docking.
• Colonic mobilization, including vascular pedicle dissection and splenic flexure mobilization.
• Pelvic dissection, including establishing operative planes and specimen extraction.

Dr. Miskovic and his coauthors arrived at the consensus statement by asking 24 EARCS faculty members to complete a 72-item questionnaire. The initial responses yielded an 87% agreement among the responses, but after suggested modifications, the average level of agreement for all items was 97%.

One of the limitations of the study that the investigators acknowledged is that it covers only two da Vinci robotic platforms; the recommendations may not apply to new robotic systems. Secondly, a selected group of experts provided input. “There may be other experienced surgeons who might disagree with some aspects of our recommendations,” the authors wrote. “This document should therefore be seen as a foundation for debate and modification in light of future technical developments.”

Future research should evaluate how training of technical standards within a group like EARCS impacts clinical outcomes, Dr. Miskovic and his coauthors noted.

The investigators had no financial relationships to report. Participating surgeons are members of the EARCS faculty and/or its scientific committee

SOURCE: Miskovic D et al. Colorectal Dis. 2018 Nov 29. doi: 10.1111/codi.14502.

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

The future of the Affordable Care Act after a ruling in Texas. Also today, baracitinib findings have immediate clinical relevance for patients with RA, a look at how often epileptic patients have treatment delayed, and the FDA issues an alert after e-cigarette liquids were found containing erectile dysfunction medication.
 

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

The future of the Affordable Care Act after a ruling in Texas. Also today, baracitinib findings have immediate clinical relevance for patients with RA, a look at how often epileptic patients have treatment delayed, and the FDA issues an alert after e-cigarette liquids were found containing erectile dysfunction medication.
 

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

The future of the Affordable Care Act after a ruling in Texas. Also today, baracitinib findings have immediate clinical relevance for patients with RA, a look at how often epileptic patients have treatment delayed, and the FDA issues an alert after e-cigarette liquids were found containing erectile dysfunction medication.
 

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo courtesy of Janssen

Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).

The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.

Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.

Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.

For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.

Trial results

Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

The ALCYONE trial was sponsored by Janssen Research & Development, LLC.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, BV+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the BV+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the BV+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the BV+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the BV+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, BV+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the BV+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the BV+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the BV+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the BV+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).

The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of a CHMP recommendation.

BV is already EC-approved to treat adults with:

• CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
• Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Relapsed or refractory systemic anaplastic large-cell lymphoma
• CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.

Phase 3 trial

The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, BV+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the BV+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the BV+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the BV+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the BV+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with BV+AVD, while pulmonary toxicity was more common with ABVD.

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.

A 3-and-a-half-year-old girl presented to a pediatrician’s office with complaints of vomiting and high fever (103.3°). She was seen by a nurse practitioner, who diagnosed gastroenteritis, prescribed fluid replacement and acetaminophen, and sent the child home.

The NP did not chart the child’s blood pressure, pulse, or respiratory rate. She did note swollen lymph nodes and absence of diarrhea. The NP performed a flu screen but did not order a rapid strep test or urinalysis.

Several hours later, the child was taken to the emergency department with shortness of breath, cough, congestion, tachycardia, hypoxia, dehydration, and lethargy. She was admitted to the pediatric ICU with diagnoses of pneumonia, acute respiratory distress, hypoxemia, neutropenia, and sepsis. She was given IV antibiotics.

Several hours later, the decision was made to transfer the patient to a regional medical center. During transfer, she suffered cardiopulmonary arrest while being placed on a ventilator for transport. Upon arrival at the hospital, she arrested again and required resuscitation for several hours until spontaneous circulation could not be restored.

An autopsy concluded the child died of sepsis and shock from Group A beta-hemolytic streptococcal infection.

It was argued that the NP failed to diagnose and treat streptococcal toxic shock syndrome at the time of the child’s presentation. In support of this contention, it was argued that the NP had failed to perform basic follow-up when the child’s flu test came back negative and that the child’s swollen lymph nodes and lack of diarrhea both mitigated against the NP’s diagnosis of gastroenteritis.

VERDICT

The parties in this case reached a $950,000 settlement.

Continue to: DISCUSSION

Every headache and fever could be an early meningitis, every vague abdominal pain an early appendicitis. So how do we handle innocuous-appearing cases with early, nonspecific symptoms of a very serious illness about to unfold?

We must start by following the Miyagi rule. In The Karate Kid, Mr. Miyagi advised that walking on the left or the right side of the road was safe, but walking in the middle would result, sooner or later, in “squish, just like grape.” Although he related this premise to karate, we can also apply it to medicine: See a patient or do not see a patient; but if you see a patient “so-so,” you will be squished—by the patient, by a plaintiff’s attorney, and/or by your state’s medical board.

A case such as this one strikes fear in the heart of anyone who has seen patients in an ambulatory setting. The initial presentation was modest: a toddler with vomiting and fever. We do not know what the other vital signs were, and we do not know whether the child appeared toxic. The lack of vital signs or recorded vital signs represent half-measures. The patient’s vitals could have been normal, and the NP’s actions could have been fully defensible. The problem is, we don’t know—and the clinician is on the hook.

All patients require vital signs. They must be done; they must be complete, and they must be recorded. At a minimum, temperature, blood pressure, respiratory rate, and (generally) O₂ saturation are required. Some specialties may have other requirements (eg, fingerstick glucose for patients with diabetes, visual acuity testing for those with eye complaints). A full list of data you should be obtaining is practice specific and beyond the scope of this article; the point is, decide on the relevant set of vitals and intake data and be sure it is recorded at every visit.

Failure to obtain and record vital signs—as seen in this case—is sloppy practice, difficult to defend, and sets up an inference of negligence. Even when the care is perfect (and without bad outcome), if the medical board reviews the record for any reason, you will be sanctioned for “failure to keep adequate and accurate medical records” and your license burdened. Here, we are told the defendant NP “did not chart the child’s blood pressure, pulse, or respiratory rate.” I am willing to bet the NP was not responsible for charting the values in the normal course of practice, but see how responsibility is parked with the clinician? If intake staff do not record vital signs, politely (yet firmly) insist they do so.

Continue to: Furthermore, the disposition of many child visits...

Furthermore, the disposition of many child visits turns on whether the patient “appeared toxic.” Any child’s condition could worsen after evaluation—and in litigation, parents, friends, and family will testify the patient was extremely ill, they “knew something was wrong,” and the clinician ignored their loved one. Thus, the jury will be invited to reconstruct how the child appeared.

When assessing children and the question of “toxic appearance” arises, don’t state a conclusion—paint a picture. Don’t merely state “child appeared nontoxic.” Use your powers of observation to record why they appear nontoxic: “Child sitting up, watching Moana on parent’s phone, smiling and laughing appropriately.” Get interactive; some pediatric providers carry a small vial of bubbles with them and record the child’s response to bubble-making (“Child appropriately reaching for bubbles, smiling, holding one on finger”). The cost is less than $1 for the bubbles, plus the documentation time. The benefit is that it paints a clear picture for the jury of a child responding appropriately. And if your observations suggest a child who is at least unwell—if the movie is poorly received or the bubbles prompt the child to scream or bury her face in her mom’s shoulder—you can consider oral antipyretics/analgesics, fluid, and re-observation.

Another way to create a strong and defensible record is to use patient quotations. These can be extremely helpful to your defense in a malpractice action; as an attorney, I have searched 8,000 pages of records in a medical malpractice case, hoping to find a clear description from a human (not a template) of how a patient looked. Make it clear by adding patient remarks to the chart—just remember that “the only thing that belongs in quotes is what comes out of the patient’s mouth.” Words from an 8-year-old boy— such as “My brother found a legendary scar [a reference to Fortnite] and almost won”—may seem silly, but this documentation itself could win your case.

With teenagers, you may have to ask more questions to glean something suitable; you could ask a 13-year-old her favorite sport and when her one-word answer is “Lacrosse,” ask why. Even if the response is “Because, I don’t know, it’s exciting. There are a lot of goals,” write that down exactly (along with any other observations, such as Teen texting on her phone). These notations tell the plaintiff’s attorney, the judge, and the jury that the patient was behaving normally and interacting with the environment. Should this teen later deteriorate with meningitis, the plaintiff will claim she was toxic in the office. The medical record, however, will show that the patient’s condition changed, and it was a departure from how she looked in your office.

Also, it never hurts to get backup. In any close call, ask the nurse to reevaluate the patient as to whether he or she is “toxic appearing” or is interacting normally with the environment. Have the nurse or medical assistant record facts, such as “patient trying to make a plane out of two tongue depressors, pretending to land it on sister’s leg.” This will create a strong and defensible record: two clinicians relaying two sets of detailed observations.

Continue to: Likewise, encourage intake staff to document...

Likewise, encourage intake staff to document what they see rather than what they conclude from it. Buzzwords (eg, listless, lethargic) should be avoided. If such characterizations find their way into the record, you must take active steps to address them. Either agree with the characterization and perform appropriate work-up, or establish why you do not agree using the methods described (detailed description, verification by another clinician).

Taking these steps will help to protect you in the event of a changing clinical course. But also be wary of those predictable circumstances that lead you into Mr. Miyagi’s middle of the road (what I call “half-visits”): a quick look at a sibling in the room during a patient’s appointment; a “curbside consult” on the medical assistant’s child; the neighborhood acquaintance who asks you to “just take a look.” Why are these dangerous? Because they remove the clinician from his or her usual routine: proper examination on a properly undressed patient, formal assessment of vital signs, and review of relevant history in the chart, among other things. (In this way, phone and email communications with patients require similar caution.) Skipping the routine leads to shortcuts, and shortcuts lead to bad medicine. And if that doesn’t worry you, remember: All these scenarios create a full legal duty and clinician/patient relationship—making them potential pathways to misdiagnosis and eventual loss of license.

IN SUMMARY

Don’t be party to a “half-visit”; insist on full vital signs and a complete visit following your usual routine. Use observational powers and patient quotations to paint a picture of how a patient looked, get backup from another clinician with similar observations. If you can’t document a reassuring record, protect the patient and make the required intervention.

A 3-and-a-half-year-old girl presented to a pediatrician’s office with complaints of vomiting and high fever (103.3°). She was seen by a nurse practitioner, who diagnosed gastroenteritis, prescribed fluid replacement and acetaminophen, and sent the child home.

The NP did not chart the child’s blood pressure, pulse, or respiratory rate. She did note swollen lymph nodes and absence of diarrhea. The NP performed a flu screen but did not order a rapid strep test or urinalysis.

Several hours later, the child was taken to the emergency department with shortness of breath, cough, congestion, tachycardia, hypoxia, dehydration, and lethargy. She was admitted to the pediatric ICU with diagnoses of pneumonia, acute respiratory distress, hypoxemia, neutropenia, and sepsis. She was given IV antibiotics.

Several hours later, the decision was made to transfer the patient to a regional medical center. During transfer, she suffered cardiopulmonary arrest while being placed on a ventilator for transport. Upon arrival at the hospital, she arrested again and required resuscitation for several hours until spontaneous circulation could not be restored.

An autopsy concluded the child died of sepsis and shock from Group A beta-hemolytic streptococcal infection.

It was argued that the NP failed to diagnose and treat streptococcal toxic shock syndrome at the time of the child’s presentation. In support of this contention, it was argued that the NP had failed to perform basic follow-up when the child’s flu test came back negative and that the child’s swollen lymph nodes and lack of diarrhea both mitigated against the NP’s diagnosis of gastroenteritis.

VERDICT

The parties in this case reached a $950,000 settlement.

Continue to: DISCUSSION

Every headache and fever could be an early meningitis, every vague abdominal pain an early appendicitis. So how do we handle innocuous-appearing cases with early, nonspecific symptoms of a very serious illness about to unfold?

We must start by following the Miyagi rule. In The Karate Kid, Mr. Miyagi advised that walking on the left or the right side of the road was safe, but walking in the middle would result, sooner or later, in “squish, just like grape.” Although he related this premise to karate, we can also apply it to medicine: See a patient or do not see a patient; but if you see a patient “so-so,” you will be squished—by the patient, by a plaintiff’s attorney, and/or by your state’s medical board.

A case such as this one strikes fear in the heart of anyone who has seen patients in an ambulatory setting. The initial presentation was modest: a toddler with vomiting and fever. We do not know what the other vital signs were, and we do not know whether the child appeared toxic. The lack of vital signs or recorded vital signs represent half-measures. The patient’s vitals could have been normal, and the NP’s actions could have been fully defensible. The problem is, we don’t know—and the clinician is on the hook.

All patients require vital signs. They must be done; they must be complete, and they must be recorded. At a minimum, temperature, blood pressure, respiratory rate, and (generally) O₂ saturation are required. Some specialties may have other requirements (eg, fingerstick glucose for patients with diabetes, visual acuity testing for those with eye complaints). A full list of data you should be obtaining is practice specific and beyond the scope of this article; the point is, decide on the relevant set of vitals and intake data and be sure it is recorded at every visit.

Failure to obtain and record vital signs—as seen in this case—is sloppy practice, difficult to defend, and sets up an inference of negligence. Even when the care is perfect (and without bad outcome), if the medical board reviews the record for any reason, you will be sanctioned for “failure to keep adequate and accurate medical records” and your license burdened. Here, we are told the defendant NP “did not chart the child’s blood pressure, pulse, or respiratory rate.” I am willing to bet the NP was not responsible for charting the values in the normal course of practice, but see how responsibility is parked with the clinician? If intake staff do not record vital signs, politely (yet firmly) insist they do so.

Continue to: Furthermore, the disposition of many child visits...

Furthermore, the disposition of many child visits turns on whether the patient “appeared toxic.” Any child’s condition could worsen after evaluation—and in litigation, parents, friends, and family will testify the patient was extremely ill, they “knew something was wrong,” and the clinician ignored their loved one. Thus, the jury will be invited to reconstruct how the child appeared.

When assessing children and the question of “toxic appearance” arises, don’t state a conclusion—paint a picture. Don’t merely state “child appeared nontoxic.” Use your powers of observation to record why they appear nontoxic: “Child sitting up, watching Moana on parent’s phone, smiling and laughing appropriately.” Get interactive; some pediatric providers carry a small vial of bubbles with them and record the child’s response to bubble-making (“Child appropriately reaching for bubbles, smiling, holding one on finger”). The cost is less than $1 for the bubbles, plus the documentation time. The benefit is that it paints a clear picture for the jury of a child responding appropriately. And if your observations suggest a child who is at least unwell—if the movie is poorly received or the bubbles prompt the child to scream or bury her face in her mom’s shoulder—you can consider oral antipyretics/analgesics, fluid, and re-observation.

Another way to create a strong and defensible record is to use patient quotations. These can be extremely helpful to your defense in a malpractice action; as an attorney, I have searched 8,000 pages of records in a medical malpractice case, hoping to find a clear description from a human (not a template) of how a patient looked. Make it clear by adding patient remarks to the chart—just remember that “the only thing that belongs in quotes is what comes out of the patient’s mouth.” Words from an 8-year-old boy— such as “My brother found a legendary scar [a reference to Fortnite] and almost won”—may seem silly, but this documentation itself could win your case.

With teenagers, you may have to ask more questions to glean something suitable; you could ask a 13-year-old her favorite sport and when her one-word answer is “Lacrosse,” ask why. Even if the response is “Because, I don’t know, it’s exciting. There are a lot of goals,” write that down exactly (along with any other observations, such as Teen texting on her phone). These notations tell the plaintiff’s attorney, the judge, and the jury that the patient was behaving normally and interacting with the environment. Should this teen later deteriorate with meningitis, the plaintiff will claim she was toxic in the office. The medical record, however, will show that the patient’s condition changed, and it was a departure from how she looked in your office.

Also, it never hurts to get backup. In any close call, ask the nurse to reevaluate the patient as to whether he or she is “toxic appearing” or is interacting normally with the environment. Have the nurse or medical assistant record facts, such as “patient trying to make a plane out of two tongue depressors, pretending to land it on sister’s leg.” This will create a strong and defensible record: two clinicians relaying two sets of detailed observations.

Continue to: Likewise, encourage intake staff to document...

Likewise, encourage intake staff to document what they see rather than what they conclude from it. Buzzwords (eg, listless, lethargic) should be avoided. If such characterizations find their way into the record, you must take active steps to address them. Either agree with the characterization and perform appropriate work-up, or establish why you do not agree using the methods described (detailed description, verification by another clinician).

Taking these steps will help to protect you in the event of a changing clinical course. But also be wary of those predictable circumstances that lead you into Mr. Miyagi’s middle of the road (what I call “half-visits”): a quick look at a sibling in the room during a patient’s appointment; a “curbside consult” on the medical assistant’s child; the neighborhood acquaintance who asks you to “just take a look.” Why are these dangerous? Because they remove the clinician from his or her usual routine: proper examination on a properly undressed patient, formal assessment of vital signs, and review of relevant history in the chart, among other things. (In this way, phone and email communications with patients require similar caution.) Skipping the routine leads to shortcuts, and shortcuts lead to bad medicine. And if that doesn’t worry you, remember: All these scenarios create a full legal duty and clinician/patient relationship—making them potential pathways to misdiagnosis and eventual loss of license.

IN SUMMARY

Don’t be party to a “half-visit”; insist on full vital signs and a complete visit following your usual routine. Use observational powers and patient quotations to paint a picture of how a patient looked, get backup from another clinician with similar observations. If you can’t document a reassuring record, protect the patient and make the required intervention.

A 3-and-a-half-year-old girl presented to a pediatrician’s office with complaints of vomiting and high fever (103.3°). She was seen by a nurse practitioner, who diagnosed gastroenteritis, prescribed fluid replacement and acetaminophen, and sent the child home.

The NP did not chart the child’s blood pressure, pulse, or respiratory rate. She did note swollen lymph nodes and absence of diarrhea. The NP performed a flu screen but did not order a rapid strep test or urinalysis.

Several hours later, the child was taken to the emergency department with shortness of breath, cough, congestion, tachycardia, hypoxia, dehydration, and lethargy. She was admitted to the pediatric ICU with diagnoses of pneumonia, acute respiratory distress, hypoxemia, neutropenia, and sepsis. She was given IV antibiotics.

Several hours later, the decision was made to transfer the patient to a regional medical center. During transfer, she suffered cardiopulmonary arrest while being placed on a ventilator for transport. Upon arrival at the hospital, she arrested again and required resuscitation for several hours until spontaneous circulation could not be restored.

An autopsy concluded the child died of sepsis and shock from Group A beta-hemolytic streptococcal infection.

It was argued that the NP failed to diagnose and treat streptococcal toxic shock syndrome at the time of the child’s presentation. In support of this contention, it was argued that the NP had failed to perform basic follow-up when the child’s flu test came back negative and that the child’s swollen lymph nodes and lack of diarrhea both mitigated against the NP’s diagnosis of gastroenteritis.

VERDICT

The parties in this case reached a $950,000 settlement.

Continue to: DISCUSSION

Every headache and fever could be an early meningitis, every vague abdominal pain an early appendicitis. So how do we handle innocuous-appearing cases with early, nonspecific symptoms of a very serious illness about to unfold?

We must start by following the Miyagi rule. In The Karate Kid, Mr. Miyagi advised that walking on the left or the right side of the road was safe, but walking in the middle would result, sooner or later, in “squish, just like grape.” Although he related this premise to karate, we can also apply it to medicine: See a patient or do not see a patient; but if you see a patient “so-so,” you will be squished—by the patient, by a plaintiff’s attorney, and/or by your state’s medical board.

A case such as this one strikes fear in the heart of anyone who has seen patients in an ambulatory setting. The initial presentation was modest: a toddler with vomiting and fever. We do not know what the other vital signs were, and we do not know whether the child appeared toxic. The lack of vital signs or recorded vital signs represent half-measures. The patient’s vitals could have been normal, and the NP’s actions could have been fully defensible. The problem is, we don’t know—and the clinician is on the hook.

All patients require vital signs. They must be done; they must be complete, and they must be recorded. At a minimum, temperature, blood pressure, respiratory rate, and (generally) O₂ saturation are required. Some specialties may have other requirements (eg, fingerstick glucose for patients with diabetes, visual acuity testing for those with eye complaints). A full list of data you should be obtaining is practice specific and beyond the scope of this article; the point is, decide on the relevant set of vitals and intake data and be sure it is recorded at every visit.

Failure to obtain and record vital signs—as seen in this case—is sloppy practice, difficult to defend, and sets up an inference of negligence. Even when the care is perfect (and without bad outcome), if the medical board reviews the record for any reason, you will be sanctioned for “failure to keep adequate and accurate medical records” and your license burdened. Here, we are told the defendant NP “did not chart the child’s blood pressure, pulse, or respiratory rate.” I am willing to bet the NP was not responsible for charting the values in the normal course of practice, but see how responsibility is parked with the clinician? If intake staff do not record vital signs, politely (yet firmly) insist they do so.

Continue to: Furthermore, the disposition of many child visits...

Furthermore, the disposition of many child visits turns on whether the patient “appeared toxic.” Any child’s condition could worsen after evaluation—and in litigation, parents, friends, and family will testify the patient was extremely ill, they “knew something was wrong,” and the clinician ignored their loved one. Thus, the jury will be invited to reconstruct how the child appeared.

When assessing children and the question of “toxic appearance” arises, don’t state a conclusion—paint a picture. Don’t merely state “child appeared nontoxic.” Use your powers of observation to record why they appear nontoxic: “Child sitting up, watching Moana on parent’s phone, smiling and laughing appropriately.” Get interactive; some pediatric providers carry a small vial of bubbles with them and record the child’s response to bubble-making (“Child appropriately reaching for bubbles, smiling, holding one on finger”). The cost is less than $1 for the bubbles, plus the documentation time. The benefit is that it paints a clear picture for the jury of a child responding appropriately. And if your observations suggest a child who is at least unwell—if the movie is poorly received or the bubbles prompt the child to scream or bury her face in her mom’s shoulder—you can consider oral antipyretics/analgesics, fluid, and re-observation.

Another way to create a strong and defensible record is to use patient quotations. These can be extremely helpful to your defense in a malpractice action; as an attorney, I have searched 8,000 pages of records in a medical malpractice case, hoping to find a clear description from a human (not a template) of how a patient looked. Make it clear by adding patient remarks to the chart—just remember that “the only thing that belongs in quotes is what comes out of the patient’s mouth.” Words from an 8-year-old boy— such as “My brother found a legendary scar [a reference to Fortnite] and almost won”—may seem silly, but this documentation itself could win your case.

With teenagers, you may have to ask more questions to glean something suitable; you could ask a 13-year-old her favorite sport and when her one-word answer is “Lacrosse,” ask why. Even if the response is “Because, I don’t know, it’s exciting. There are a lot of goals,” write that down exactly (along with any other observations, such as Teen texting on her phone). These notations tell the plaintiff’s attorney, the judge, and the jury that the patient was behaving normally and interacting with the environment. Should this teen later deteriorate with meningitis, the plaintiff will claim she was toxic in the office. The medical record, however, will show that the patient’s condition changed, and it was a departure from how she looked in your office.

Also, it never hurts to get backup. In any close call, ask the nurse to reevaluate the patient as to whether he or she is “toxic appearing” or is interacting normally with the environment. Have the nurse or medical assistant record facts, such as “patient trying to make a plane out of two tongue depressors, pretending to land it on sister’s leg.” This will create a strong and defensible record: two clinicians relaying two sets of detailed observations.

Continue to: Likewise, encourage intake staff to document...

Likewise, encourage intake staff to document what they see rather than what they conclude from it. Buzzwords (eg, listless, lethargic) should be avoided. If such characterizations find their way into the record, you must take active steps to address them. Either agree with the characterization and perform appropriate work-up, or establish why you do not agree using the methods described (detailed description, verification by another clinician).

Taking these steps will help to protect you in the event of a changing clinical course. But also be wary of those predictable circumstances that lead you into Mr. Miyagi’s middle of the road (what I call “half-visits”): a quick look at a sibling in the room during a patient’s appointment; a “curbside consult” on the medical assistant’s child; the neighborhood acquaintance who asks you to “just take a look.” Why are these dangerous? Because they remove the clinician from his or her usual routine: proper examination on a properly undressed patient, formal assessment of vital signs, and review of relevant history in the chart, among other things. (In this way, phone and email communications with patients require similar caution.) Skipping the routine leads to shortcuts, and shortcuts lead to bad medicine. And if that doesn’t worry you, remember: All these scenarios create a full legal duty and clinician/patient relationship—making them potential pathways to misdiagnosis and eventual loss of license.

IN SUMMARY

Don’t be party to a “half-visit”; insist on full vital signs and a complete visit following your usual routine. Use observational powers and patient quotations to paint a picture of how a patient looked, get backup from another clinician with similar observations. If you can’t document a reassuring record, protect the patient and make the required intervention.

Recommended Reading lists have been over the years among the most popular features in this publication. It is therefore fitting that for this last issue of ACS Surgery News, we have once again imposed upon our Editorial Advisory Board to come up with their choice of the most important studies published in 2018. They were asked to choose a few studies that they consider most significant in their subspecialties and to explain why these studies should matter to all surgeons.

Some editorial advisers for some publications fill honorary positions with no real responsibility or work involved. Not so for the Editorial Advisory Board of ACS Surgery News. Each member provided a steady stream of commentaries, recommendations, and advice. The publication and the managing editor would have been lost without their kind and willing assistance. In their busy professional lives, they somehow found the time to contribute their expertise to assist their colleagues and their profession. We all owe them a debt of gratitude for their many years of service.

We hope our readers will find the list and the comments of interest.

 

Otolaryngology

St. Laurent J et al. HPV vaccination and the effects on rates of HPV-related cancers. Curr Probl Cancer 2018; https://doi.org/10.1016/j.currproblcancer.2018.06.004

As a head and neck surgeon over the past 30+ years, I have seen the dramaticrise of one form of HPV-related cancer in the United States, namely, HPV-associated oropharyngeal cancer. This is a true epidemic. It is also a cancer that may well be preventable through vaccination. We have slowly made progress over the past 4 decades in reducing the number of tobacco- and alcohol-related cancers. Here is another cancer that truly falls within the category of a public health problem for which public health solution of vaccination is clearly the most rational approach. Everyone should be aware of these virally induced cancers and what can be done to prevent them. This article presents the “state of the art” knowledge about these cancers and what we can hopefully accomplish through worldwide public health initiatives.

Mark C. Weissler, MD, FACS

Palliative Care

Kopecky KE et al. Third-year medical students’ reactions to surgical patients in pain: Doubt, distress, and depersonalization. J Pain and Symptom Manage. 2018;56(5):719-26.

Su A et al. Beyond pain: Nurses’ assessment of patient suffering, dignity, and dying in the intensive care unit. J Pain Symptom Manage. 2018;55:1591-98.
After reading this sobering study, my reaction was, “If the gold rusts what will happen to the iron?” In this study using chart abstraction, nurses caring for 200 patients in a tertiary care cardiac ICU and a surgical ICU were interviewed about their assessment and perception of the physical and psychosocial dimensions of ICU patients’ experiences in their final week of life. The authors note that nursing symptom assessments have been previously shown to be highly reliable and end-of-life comfort and dignity have been shown to be compatible with ICU level of care. Despite this and the availability of extensive interdisciplinary support from palliative care teams, chaplains, and social workers, dying ICU patients are perceived by nurses to experience extreme indignities and suffer beyond physical pain. The study found that attention to symptoms such as dyspnea and edema might improve the quality of death in the ICU. It is small wonder that moral fatigue and burnout have become prevalent themes of ICU caring.

Balboni T et al. The spiritual event of serious illness. J Pain Symptom Manage. 2018;56(5):816-22.
An ashen-faced dear friend gently reminded me as he was hemorrhaging from an advanced gastric cancer, “Geoff, lets make this a spiritual event, not a medical one.” This paper conjured up this memory with the thoughtful, in-depth account and analysis of patients’ experiences and attitudes that shaped the authors concept of illness as a spiritual event. The idea of spirituality as a basic component of consciousness, especially as it relates to suffering, has been present from the very beginning of modern palliative care and can be traced back to the concept of “total pain” introduced by Dame Cicely Saunders in 1963. The capacity to reframe biophysical calamity as spiritual opportunity is the signature of the most skilled and adroit supportive care we can offer our patients and their families.

Geoffrey P. Dunn, MD, FACS

Colorectal Surgery

Cercek A et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. doi:10.1001/jamaoncol.2018.0071.

Brouquet A et al. Anti-TNF therapy is associated with an increased risk of postoperative morbidity after surgery for ileocolonic Crohn disease: Results of a prospective nationwide cohort. Ann Surg. 2018 Feb;267(2):221-228. doi: 10.1097/SLA.0000000000002017. 

This large prospective study of almost 600 consecutive Crohn’s disease patients with surgery at 19 French specialty centers demonstrates that anti-TNF therapy less than 3 months prior to ileocolic surgery to be an independent risk factor of the overall postoperative morbidity, preoperative hemoglobin less than10 g/dL, operative time more than180 min, and recurrent Crohn’s disease, as well as a higher risk of overall and intra-abdominal septic postoperative morbidities.

Howard R et al. Taking control of your surgery: Impact of a prehabilitation program on major abdominal surgery. J Am Coll Surg. 2018 Oct 22; https://doi.org/10.1016/j.jamcollsurg.2018.09.018

Results from the Michigan Surgical and Health Optimization Program (MSHOP) are reported in colectomy patients. This prehabilitation program engages patients in four activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. MSHOP patients were matched to emergency and elective, non-MSHOP patients. Overall, 70% of MSHOP patients complied with the program. MSHOP patients were more likely to have improved blood pressure and heart rate intraoperatively, reduction in Clavien-Dindo class 3-4 complications in the MSHOP group (30%), compared with the nonprehabilitation (38%) and emergency (48%) groups (P = .05), as well as average savings of $21,946 per patient.

Genevieve Melton-Meaux, MD, PhD, FACS

Bariatric Surgery

Kalff MC et al. Diagnostic value of computed tomography for detecting anastomotic or staple line leakage after bariatric surgery. Surg Obes Relat Dis. 2018;14(9):1310-16

Alizadeh RF et al. Risk factors for gastrointestinal leak after bariatric surgery: MBSAQIP analysis. J Am Coll Surg. 2018;227(1):135-141.

The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) 2015 database of accredited centers was the object of study. Multivariate logistic regression analysis was used to examine risk factors for GI leaks that are not typically included in similar studies. Of particular interest is finding that Roux-en-Y gastric bypass comes with a higher risk for leak, compared with a sleeve gastrectomy, but with an overall leak rate for both of 0.7% based on current results. In addition, the study found that use of an intraoperative provocative leak test and placement of a surgical drain are associated with a higher leak rate. The same is not true of a postoperative swallow contrast study, which has no effect on the incidence of leaks.

Altieri MS et al. Evaluation of VTE prophylaxis and the impact of alternate regimens on post-operative bleeding and thrombotic complications following bariatric procedures. Surg Endosc. 2018;32(12):4805-4812.

The field of venous thromboembolism prevention after bariatric surgery remains a challenging one due to the lack of consensus among surgeons. This study analyzes the Cerner Health Facts database from 2003 to 2013, particularly with ICD-9 codes, for patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy. While the authors confirm the statement that there is a lack of consistency and, therefore, there is ample variability among bariatric centers and surgeons, the use of postoperative VTE chemoprophylaxis leads to a lower incidence of VTE events, and less frequent bleeding episodes, compared with pre-operative chemoprophylaxis. Finally, mixed therapy using heparin and enoxaparin led to more bleeding complications and blood transfusion requirements.

Rodolfo J. Oviedo, MD, FACS, FASMBS
 

Cardiothoracic Surgery

Stone GW et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23; doi:10.1056/NEJMoa1806640.

Gaudino M et al. Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery. N Engl J Med. 2018;378(22):2069-77.
 

This analysis of randomized trials comparing radial artery to saphenous vein grafts for coronary artery bypass surgery is quite possibly a practice-changing publication. Routine use of the left internal thoracic (mammary) artery is commonplace among cardiac surgeons; however, the debate over conduit choice for additional bypass grafts is a “tale as old as time.” This study, part of the RADIAL project, combined patient-level data from six trials in order to achieve adequate power to identify differences in clinical outcomes. The use of radial artery grafts as opposed to saphenous vein grafts was associated with less adverse cardiac events, a lower incidence of repeat revascularization, and a higher patency rate at 5 years. Although there was no difference in all-cause mortality, the results of this study support the use of radial artery grafts when additional conduits are needed in coronary artery bypass surgery.

Irving L. Kron, MD, FACS, and Eric J. Charles, MD, PhD
 

Vascular Surgery

Anand SS. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: An international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391(10117):219-29.

These findings suggest the need for a major change in the guidelines and management for the majority of our patients with PAD. Certainly we should look to add this data point to the Vascular Quality Initiative to gather further data and confirm the findings in real world use. It is unclear whether this benefit will be unique to rivaroxaban, or whether other Direct Xa inhibitors will have similar effects. I will certainly be adding ribaroxaban to patients at low risk for bleeding based on this data. Further, rivaroxaban alone did not reduce major cardiovascular adverse events, but did reduce major adverse limb events.

Gohel MS et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14.

This multicenter study in the UK looked at over 450 patients with venous ulceration. Deep-venous reflux was also present in one-third of patients in each group. The median time to ulcer healing was decreased significantly from 82 days to 56 days. This study demonstrates the importance of early intervention for superficial reflux to enhance ulcer healing and decrease risk of recurrence. This study found that early endovenous ablation resulted in faster healing of venous ulcers, and more ulcer-free time than delayed intervention in patients treated with maximal medical therapy, including appropriate compression therapy. Previously, ablation was typically planned after ulcers healed to decrease risk of recurrence. Based on these findings, ablation should be offered to patients with nonhealing venous ulcers early in the course of therapy, in addition to standard wound care.

Linda Harris, MD, FACS

Surgical Education

Ellison EC. Ten-year reassessment of the shortage of general surgeons: Increases in graduation numbers of general surgery residents are insufficient to meet the future demand for general surgeons. Surgery. 2018 Oct;164(4):726-32.

Ellison EC et al. The impact of the aging population and incidence of cancer on future projections of general surgery workforce needs. Surgery. 2018 Mar;163(3):553-59.

Michael D. Sarap, MD, FACS
 

General Surgery

Takada T. Tokyo Guidelines 2018 (TG18). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):1-2.

Acuna SA. Operative strategies for perforated diverticulitis: A systematic review and meta-analysis. Dis Colon Rectum. 2018 Dec; 61(12):1442-53.

 This analysis of the literature considers the three predominant operations for Hinchey III and Hinchey IV perforated diverticulitis: Hartmann procedure, resection and primary anastomosis, and laparoscopic lavage. The importance of this review is that it considers the initial operation and the downstream procedures when determining overall morbidity and mortality. Laparoscopic lavage did not fare well in this review of randomized controlled trials, resulting in higher morbidity than resection in Hinchey III patients. Interestingly, none of the individual studies analyzed had shown a statistical difference, but in the meta-analysis, the number of patients was sufficient to show statistical significance. The other important conclusion was that primary resection with anastomosis (possibly with diverting ileostomy) was superior to Hartmann procedure, when the likelihood of stoma reversal and the morbidity of the second operation was taken into account.

Mark Savarise, MD, FACS
 

Foregut

Alicuben ET. Worldwide experience with erosion of the magnetic sphincter augmentation device. J Gastrointest Surg. 2018; 22(8):1442-47.

Xiong YQ. Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in Barrett’s esophagus: A meta-analysis. Clin Res Hepatol Gastroenterol. 2018 Feb;42(1):31-9.

The days of endoscopic screening and surveillance of patients at risk for the development of Barrett’s esophagus via four-quadrant biopsy every couple of centimeters are numbered. The use of confocal laser microscopy to provide accurate real-time visual data regarding the areas of interest in the esophagus is showing promise and gaining traction compared to standard biopsy techniques and narrow-band imaging.

Borbély Y. Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy. Surg Obes Relat Dis. 2018 May;14(5):611-5.
 

The development of GERD following sleeve gastrectomy is a real problem in a substantial minority of patients due to structural compromise of the lower esophageal sphincter during the procedure. Conversion to gastric bypass as a way to alleviate acid regurgitation has been the mainstay of treatment; however, many patients selected sleeve gastrectomy specifically because they did not want to undergo gastric bypass. For those patients a sleeve preserving procedure such as magnetic sphincter augmentation (currently in clinical trial), Hill procedure, or remnant gastric fundoplication are potential options. Electrical stimulation of the lower esophageal sphincter is revealing itself to be another exciting option (currently in clinical trial) which can be used in patients with as few as 30% peristaltic swallows thus expanding the treatment options for these deserving patients.

Kevin M. Reavis, MD, FACS

Trauma/Critical Care

Teixeira PGR et al. Civilian prehospital tourniquet use is associated with improved survival in patients with peripheral vascular injury . J Am Coll Surg. 2018;226(5):769-76.

Pileggi C et al. Ventilator bundle and its effects on mortality among ICU patients: A meta-analysis. Crit Care Med. 2018;46(7):1167-74.

Critically ill patients requiring mechanical ventilation are at risk for a number of complications, including ventilator-associated pneumonia (VAP) (now a subset of ventilator-associated events (VAE) which prolong ventilator and ICU time and contribute to further complication. Ventilator “bundles,” incorporating simple measures such as elevation of the head of the bed; daily “sedation holidays”; and evaluation of readiness for extubation, peptic ulcer, and DVT prophylaxis have been widely used in ICUs for nearly 20 years. Effective implementation has also emphasized multidisciplinary teamwork. Reductions in ventilator-associated pneumonia (VAP) incidence have been widely demonstrated but mortality benefits have been inconsistent. In this meta-analysis of 13 studies, 6 in Europe, 6 in the US and 1 in Brazil, an overall reduction in mortality (odds ratio, 0.9) was demonstrated. The effect was even larger when limited to studies with patients with VAP (OR, 0.71). This study both validates the effectiveness of relatively simple and inexpensive measures and emphasizes the benefits of a team approach to the care of ICU patients.

Krista L. Kaups, MD, FACS

Recommended Reading lists have been over the years among the most popular features in this publication. It is therefore fitting that for this last issue of ACS Surgery News, we have once again imposed upon our Editorial Advisory Board to come up with their choice of the most important studies published in 2018. They were asked to choose a few studies that they consider most significant in their subspecialties and to explain why these studies should matter to all surgeons.

Some editorial advisers for some publications fill honorary positions with no real responsibility or work involved. Not so for the Editorial Advisory Board of ACS Surgery News. Each member provided a steady stream of commentaries, recommendations, and advice. The publication and the managing editor would have been lost without their kind and willing assistance. In their busy professional lives, they somehow found the time to contribute their expertise to assist their colleagues and their profession. We all owe them a debt of gratitude for their many years of service.

We hope our readers will find the list and the comments of interest.

 

Otolaryngology

St. Laurent J et al. HPV vaccination and the effects on rates of HPV-related cancers. Curr Probl Cancer 2018; https://doi.org/10.1016/j.currproblcancer.2018.06.004

As a head and neck surgeon over the past 30+ years, I have seen the dramaticrise of one form of HPV-related cancer in the United States, namely, HPV-associated oropharyngeal cancer. This is a true epidemic. It is also a cancer that may well be preventable through vaccination. We have slowly made progress over the past 4 decades in reducing the number of tobacco- and alcohol-related cancers. Here is another cancer that truly falls within the category of a public health problem for which public health solution of vaccination is clearly the most rational approach. Everyone should be aware of these virally induced cancers and what can be done to prevent them. This article presents the “state of the art” knowledge about these cancers and what we can hopefully accomplish through worldwide public health initiatives.

Mark C. Weissler, MD, FACS

Palliative Care

Kopecky KE et al. Third-year medical students’ reactions to surgical patients in pain: Doubt, distress, and depersonalization. J Pain and Symptom Manage. 2018;56(5):719-26.

Su A et al. Beyond pain: Nurses’ assessment of patient suffering, dignity, and dying in the intensive care unit. J Pain Symptom Manage. 2018;55:1591-98.
After reading this sobering study, my reaction was, “If the gold rusts what will happen to the iron?” In this study using chart abstraction, nurses caring for 200 patients in a tertiary care cardiac ICU and a surgical ICU were interviewed about their assessment and perception of the physical and psychosocial dimensions of ICU patients’ experiences in their final week of life. The authors note that nursing symptom assessments have been previously shown to be highly reliable and end-of-life comfort and dignity have been shown to be compatible with ICU level of care. Despite this and the availability of extensive interdisciplinary support from palliative care teams, chaplains, and social workers, dying ICU patients are perceived by nurses to experience extreme indignities and suffer beyond physical pain. The study found that attention to symptoms such as dyspnea and edema might improve the quality of death in the ICU. It is small wonder that moral fatigue and burnout have become prevalent themes of ICU caring.

Balboni T et al. The spiritual event of serious illness. J Pain Symptom Manage. 2018;56(5):816-22.
An ashen-faced dear friend gently reminded me as he was hemorrhaging from an advanced gastric cancer, “Geoff, lets make this a spiritual event, not a medical one.” This paper conjured up this memory with the thoughtful, in-depth account and analysis of patients’ experiences and attitudes that shaped the authors concept of illness as a spiritual event. The idea of spirituality as a basic component of consciousness, especially as it relates to suffering, has been present from the very beginning of modern palliative care and can be traced back to the concept of “total pain” introduced by Dame Cicely Saunders in 1963. The capacity to reframe biophysical calamity as spiritual opportunity is the signature of the most skilled and adroit supportive care we can offer our patients and their families.

Geoffrey P. Dunn, MD, FACS

Colorectal Surgery

Cercek A et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. doi:10.1001/jamaoncol.2018.0071.

Brouquet A et al. Anti-TNF therapy is associated with an increased risk of postoperative morbidity after surgery for ileocolonic Crohn disease: Results of a prospective nationwide cohort. Ann Surg. 2018 Feb;267(2):221-228. doi: 10.1097/SLA.0000000000002017. 

This large prospective study of almost 600 consecutive Crohn’s disease patients with surgery at 19 French specialty centers demonstrates that anti-TNF therapy less than 3 months prior to ileocolic surgery to be an independent risk factor of the overall postoperative morbidity, preoperative hemoglobin less than10 g/dL, operative time more than180 min, and recurrent Crohn’s disease, as well as a higher risk of overall and intra-abdominal septic postoperative morbidities.

Howard R et al. Taking control of your surgery: Impact of a prehabilitation program on major abdominal surgery. J Am Coll Surg. 2018 Oct 22; https://doi.org/10.1016/j.jamcollsurg.2018.09.018

Results from the Michigan Surgical and Health Optimization Program (MSHOP) are reported in colectomy patients. This prehabilitation program engages patients in four activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. MSHOP patients were matched to emergency and elective, non-MSHOP patients. Overall, 70% of MSHOP patients complied with the program. MSHOP patients were more likely to have improved blood pressure and heart rate intraoperatively, reduction in Clavien-Dindo class 3-4 complications in the MSHOP group (30%), compared with the nonprehabilitation (38%) and emergency (48%) groups (P = .05), as well as average savings of $21,946 per patient.

Genevieve Melton-Meaux, MD, PhD, FACS

Bariatric Surgery

Kalff MC et al. Diagnostic value of computed tomography for detecting anastomotic or staple line leakage after bariatric surgery. Surg Obes Relat Dis. 2018;14(9):1310-16

Alizadeh RF et al. Risk factors for gastrointestinal leak after bariatric surgery: MBSAQIP analysis. J Am Coll Surg. 2018;227(1):135-141.

The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) 2015 database of accredited centers was the object of study. Multivariate logistic regression analysis was used to examine risk factors for GI leaks that are not typically included in similar studies. Of particular interest is finding that Roux-en-Y gastric bypass comes with a higher risk for leak, compared with a sleeve gastrectomy, but with an overall leak rate for both of 0.7% based on current results. In addition, the study found that use of an intraoperative provocative leak test and placement of a surgical drain are associated with a higher leak rate. The same is not true of a postoperative swallow contrast study, which has no effect on the incidence of leaks.

Altieri MS et al. Evaluation of VTE prophylaxis and the impact of alternate regimens on post-operative bleeding and thrombotic complications following bariatric procedures. Surg Endosc. 2018;32(12):4805-4812.

The field of venous thromboembolism prevention after bariatric surgery remains a challenging one due to the lack of consensus among surgeons. This study analyzes the Cerner Health Facts database from 2003 to 2013, particularly with ICD-9 codes, for patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy. While the authors confirm the statement that there is a lack of consistency and, therefore, there is ample variability among bariatric centers and surgeons, the use of postoperative VTE chemoprophylaxis leads to a lower incidence of VTE events, and less frequent bleeding episodes, compared with pre-operative chemoprophylaxis. Finally, mixed therapy using heparin and enoxaparin led to more bleeding complications and blood transfusion requirements.

Rodolfo J. Oviedo, MD, FACS, FASMBS
 

Cardiothoracic Surgery

Stone GW et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23; doi:10.1056/NEJMoa1806640.

Gaudino M et al. Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery. N Engl J Med. 2018;378(22):2069-77.
 

This analysis of randomized trials comparing radial artery to saphenous vein grafts for coronary artery bypass surgery is quite possibly a practice-changing publication. Routine use of the left internal thoracic (mammary) artery is commonplace among cardiac surgeons; however, the debate over conduit choice for additional bypass grafts is a “tale as old as time.” This study, part of the RADIAL project, combined patient-level data from six trials in order to achieve adequate power to identify differences in clinical outcomes. The use of radial artery grafts as opposed to saphenous vein grafts was associated with less adverse cardiac events, a lower incidence of repeat revascularization, and a higher patency rate at 5 years. Although there was no difference in all-cause mortality, the results of this study support the use of radial artery grafts when additional conduits are needed in coronary artery bypass surgery.

Irving L. Kron, MD, FACS, and Eric J. Charles, MD, PhD
 

Vascular Surgery

Anand SS. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: An international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391(10117):219-29.

These findings suggest the need for a major change in the guidelines and management for the majority of our patients with PAD. Certainly we should look to add this data point to the Vascular Quality Initiative to gather further data and confirm the findings in real world use. It is unclear whether this benefit will be unique to rivaroxaban, or whether other Direct Xa inhibitors will have similar effects. I will certainly be adding ribaroxaban to patients at low risk for bleeding based on this data. Further, rivaroxaban alone did not reduce major cardiovascular adverse events, but did reduce major adverse limb events.

Gohel MS et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14.

This multicenter study in the UK looked at over 450 patients with venous ulceration. Deep-venous reflux was also present in one-third of patients in each group. The median time to ulcer healing was decreased significantly from 82 days to 56 days. This study demonstrates the importance of early intervention for superficial reflux to enhance ulcer healing and decrease risk of recurrence. This study found that early endovenous ablation resulted in faster healing of venous ulcers, and more ulcer-free time than delayed intervention in patients treated with maximal medical therapy, including appropriate compression therapy. Previously, ablation was typically planned after ulcers healed to decrease risk of recurrence. Based on these findings, ablation should be offered to patients with nonhealing venous ulcers early in the course of therapy, in addition to standard wound care.

Linda Harris, MD, FACS

Surgical Education

Ellison EC. Ten-year reassessment of the shortage of general surgeons: Increases in graduation numbers of general surgery residents are insufficient to meet the future demand for general surgeons. Surgery. 2018 Oct;164(4):726-32.

Ellison EC et al. The impact of the aging population and incidence of cancer on future projections of general surgery workforce needs. Surgery. 2018 Mar;163(3):553-59.

Michael D. Sarap, MD, FACS
 

General Surgery

Takada T. Tokyo Guidelines 2018 (TG18). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):1-2.

Acuna SA. Operative strategies for perforated diverticulitis: A systematic review and meta-analysis. Dis Colon Rectum. 2018 Dec; 61(12):1442-53.

 This analysis of the literature considers the three predominant operations for Hinchey III and Hinchey IV perforated diverticulitis: Hartmann procedure, resection and primary anastomosis, and laparoscopic lavage. The importance of this review is that it considers the initial operation and the downstream procedures when determining overall morbidity and mortality. Laparoscopic lavage did not fare well in this review of randomized controlled trials, resulting in higher morbidity than resection in Hinchey III patients. Interestingly, none of the individual studies analyzed had shown a statistical difference, but in the meta-analysis, the number of patients was sufficient to show statistical significance. The other important conclusion was that primary resection with anastomosis (possibly with diverting ileostomy) was superior to Hartmann procedure, when the likelihood of stoma reversal and the morbidity of the second operation was taken into account.

Mark Savarise, MD, FACS
 

Foregut

Alicuben ET. Worldwide experience with erosion of the magnetic sphincter augmentation device. J Gastrointest Surg. 2018; 22(8):1442-47.

Xiong YQ. Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in Barrett’s esophagus: A meta-analysis. Clin Res Hepatol Gastroenterol. 2018 Feb;42(1):31-9.

The days of endoscopic screening and surveillance of patients at risk for the development of Barrett’s esophagus via four-quadrant biopsy every couple of centimeters are numbered. The use of confocal laser microscopy to provide accurate real-time visual data regarding the areas of interest in the esophagus is showing promise and gaining traction compared to standard biopsy techniques and narrow-band imaging.

Borbély Y. Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy. Surg Obes Relat Dis. 2018 May;14(5):611-5.
 

The development of GERD following sleeve gastrectomy is a real problem in a substantial minority of patients due to structural compromise of the lower esophageal sphincter during the procedure. Conversion to gastric bypass as a way to alleviate acid regurgitation has been the mainstay of treatment; however, many patients selected sleeve gastrectomy specifically because they did not want to undergo gastric bypass. For those patients a sleeve preserving procedure such as magnetic sphincter augmentation (currently in clinical trial), Hill procedure, or remnant gastric fundoplication are potential options. Electrical stimulation of the lower esophageal sphincter is revealing itself to be another exciting option (currently in clinical trial) which can be used in patients with as few as 30% peristaltic swallows thus expanding the treatment options for these deserving patients.

Kevin M. Reavis, MD, FACS

Trauma/Critical Care

Teixeira PGR et al. Civilian prehospital tourniquet use is associated with improved survival in patients with peripheral vascular injury . J Am Coll Surg. 2018;226(5):769-76.

Pileggi C et al. Ventilator bundle and its effects on mortality among ICU patients: A meta-analysis. Crit Care Med. 2018;46(7):1167-74.

Critically ill patients requiring mechanical ventilation are at risk for a number of complications, including ventilator-associated pneumonia (VAP) (now a subset of ventilator-associated events (VAE) which prolong ventilator and ICU time and contribute to further complication. Ventilator “bundles,” incorporating simple measures such as elevation of the head of the bed; daily “sedation holidays”; and evaluation of readiness for extubation, peptic ulcer, and DVT prophylaxis have been widely used in ICUs for nearly 20 years. Effective implementation has also emphasized multidisciplinary teamwork. Reductions in ventilator-associated pneumonia (VAP) incidence have been widely demonstrated but mortality benefits have been inconsistent. In this meta-analysis of 13 studies, 6 in Europe, 6 in the US and 1 in Brazil, an overall reduction in mortality (odds ratio, 0.9) was demonstrated. The effect was even larger when limited to studies with patients with VAP (OR, 0.71). This study both validates the effectiveness of relatively simple and inexpensive measures and emphasizes the benefits of a team approach to the care of ICU patients.

Krista L. Kaups, MD, FACS

Recommended Reading lists have been over the years among the most popular features in this publication. It is therefore fitting that for this last issue of ACS Surgery News, we have once again imposed upon our Editorial Advisory Board to come up with their choice of the most important studies published in 2018. They were asked to choose a few studies that they consider most significant in their subspecialties and to explain why these studies should matter to all surgeons.

Some editorial advisers for some publications fill honorary positions with no real responsibility or work involved. Not so for the Editorial Advisory Board of ACS Surgery News. Each member provided a steady stream of commentaries, recommendations, and advice. The publication and the managing editor would have been lost without their kind and willing assistance. In their busy professional lives, they somehow found the time to contribute their expertise to assist their colleagues and their profession. We all owe them a debt of gratitude for their many years of service.

We hope our readers will find the list and the comments of interest.

 

Otolaryngology

St. Laurent J et al. HPV vaccination and the effects on rates of HPV-related cancers. Curr Probl Cancer 2018; https://doi.org/10.1016/j.currproblcancer.2018.06.004

As a head and neck surgeon over the past 30+ years, I have seen the dramaticrise of one form of HPV-related cancer in the United States, namely, HPV-associated oropharyngeal cancer. This is a true epidemic. It is also a cancer that may well be preventable through vaccination. We have slowly made progress over the past 4 decades in reducing the number of tobacco- and alcohol-related cancers. Here is another cancer that truly falls within the category of a public health problem for which public health solution of vaccination is clearly the most rational approach. Everyone should be aware of these virally induced cancers and what can be done to prevent them. This article presents the “state of the art” knowledge about these cancers and what we can hopefully accomplish through worldwide public health initiatives.

Mark C. Weissler, MD, FACS

Palliative Care

Kopecky KE et al. Third-year medical students’ reactions to surgical patients in pain: Doubt, distress, and depersonalization. J Pain and Symptom Manage. 2018;56(5):719-26.

Su A et al. Beyond pain: Nurses’ assessment of patient suffering, dignity, and dying in the intensive care unit. J Pain Symptom Manage. 2018;55:1591-98.
After reading this sobering study, my reaction was, “If the gold rusts what will happen to the iron?” In this study using chart abstraction, nurses caring for 200 patients in a tertiary care cardiac ICU and a surgical ICU were interviewed about their assessment and perception of the physical and psychosocial dimensions of ICU patients’ experiences in their final week of life. The authors note that nursing symptom assessments have been previously shown to be highly reliable and end-of-life comfort and dignity have been shown to be compatible with ICU level of care. Despite this and the availability of extensive interdisciplinary support from palliative care teams, chaplains, and social workers, dying ICU patients are perceived by nurses to experience extreme indignities and suffer beyond physical pain. The study found that attention to symptoms such as dyspnea and edema might improve the quality of death in the ICU. It is small wonder that moral fatigue and burnout have become prevalent themes of ICU caring.

Balboni T et al. The spiritual event of serious illness. J Pain Symptom Manage. 2018;56(5):816-22.
An ashen-faced dear friend gently reminded me as he was hemorrhaging from an advanced gastric cancer, “Geoff, lets make this a spiritual event, not a medical one.” This paper conjured up this memory with the thoughtful, in-depth account and analysis of patients’ experiences and attitudes that shaped the authors concept of illness as a spiritual event. The idea of spirituality as a basic component of consciousness, especially as it relates to suffering, has been present from the very beginning of modern palliative care and can be traced back to the concept of “total pain” introduced by Dame Cicely Saunders in 1963. The capacity to reframe biophysical calamity as spiritual opportunity is the signature of the most skilled and adroit supportive care we can offer our patients and their families.

Geoffrey P. Dunn, MD, FACS

Colorectal Surgery

Cercek A et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. doi:10.1001/jamaoncol.2018.0071.

Brouquet A et al. Anti-TNF therapy is associated with an increased risk of postoperative morbidity after surgery for ileocolonic Crohn disease: Results of a prospective nationwide cohort. Ann Surg. 2018 Feb;267(2):221-228. doi: 10.1097/SLA.0000000000002017. 

This large prospective study of almost 600 consecutive Crohn’s disease patients with surgery at 19 French specialty centers demonstrates that anti-TNF therapy less than 3 months prior to ileocolic surgery to be an independent risk factor of the overall postoperative morbidity, preoperative hemoglobin less than10 g/dL, operative time more than180 min, and recurrent Crohn’s disease, as well as a higher risk of overall and intra-abdominal septic postoperative morbidities.

Howard R et al. Taking control of your surgery: Impact of a prehabilitation program on major abdominal surgery. J Am Coll Surg. 2018 Oct 22; https://doi.org/10.1016/j.jamcollsurg.2018.09.018

Results from the Michigan Surgical and Health Optimization Program (MSHOP) are reported in colectomy patients. This prehabilitation program engages patients in four activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. MSHOP patients were matched to emergency and elective, non-MSHOP patients. Overall, 70% of MSHOP patients complied with the program. MSHOP patients were more likely to have improved blood pressure and heart rate intraoperatively, reduction in Clavien-Dindo class 3-4 complications in the MSHOP group (30%), compared with the nonprehabilitation (38%) and emergency (48%) groups (P = .05), as well as average savings of $21,946 per patient.

Genevieve Melton-Meaux, MD, PhD, FACS

Bariatric Surgery

Kalff MC et al. Diagnostic value of computed tomography for detecting anastomotic or staple line leakage after bariatric surgery. Surg Obes Relat Dis. 2018;14(9):1310-16

Alizadeh RF et al. Risk factors for gastrointestinal leak after bariatric surgery: MBSAQIP analysis. J Am Coll Surg. 2018;227(1):135-141.

The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) 2015 database of accredited centers was the object of study. Multivariate logistic regression analysis was used to examine risk factors for GI leaks that are not typically included in similar studies. Of particular interest is finding that Roux-en-Y gastric bypass comes with a higher risk for leak, compared with a sleeve gastrectomy, but with an overall leak rate for both of 0.7% based on current results. In addition, the study found that use of an intraoperative provocative leak test and placement of a surgical drain are associated with a higher leak rate. The same is not true of a postoperative swallow contrast study, which has no effect on the incidence of leaks.

Altieri MS et al. Evaluation of VTE prophylaxis and the impact of alternate regimens on post-operative bleeding and thrombotic complications following bariatric procedures. Surg Endosc. 2018;32(12):4805-4812.

The field of venous thromboembolism prevention after bariatric surgery remains a challenging one due to the lack of consensus among surgeons. This study analyzes the Cerner Health Facts database from 2003 to 2013, particularly with ICD-9 codes, for patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy. While the authors confirm the statement that there is a lack of consistency and, therefore, there is ample variability among bariatric centers and surgeons, the use of postoperative VTE chemoprophylaxis leads to a lower incidence of VTE events, and less frequent bleeding episodes, compared with pre-operative chemoprophylaxis. Finally, mixed therapy using heparin and enoxaparin led to more bleeding complications and blood transfusion requirements.

Rodolfo J. Oviedo, MD, FACS, FASMBS
 

Cardiothoracic Surgery

Stone GW et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23; doi:10.1056/NEJMoa1806640.

Gaudino M et al. Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery. N Engl J Med. 2018;378(22):2069-77.
 

This analysis of randomized trials comparing radial artery to saphenous vein grafts for coronary artery bypass surgery is quite possibly a practice-changing publication. Routine use of the left internal thoracic (mammary) artery is commonplace among cardiac surgeons; however, the debate over conduit choice for additional bypass grafts is a “tale as old as time.” This study, part of the RADIAL project, combined patient-level data from six trials in order to achieve adequate power to identify differences in clinical outcomes. The use of radial artery grafts as opposed to saphenous vein grafts was associated with less adverse cardiac events, a lower incidence of repeat revascularization, and a higher patency rate at 5 years. Although there was no difference in all-cause mortality, the results of this study support the use of radial artery grafts when additional conduits are needed in coronary artery bypass surgery.

Irving L. Kron, MD, FACS, and Eric J. Charles, MD, PhD
 

Vascular Surgery

Anand SS. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: An international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391(10117):219-29.

These findings suggest the need for a major change in the guidelines and management for the majority of our patients with PAD. Certainly we should look to add this data point to the Vascular Quality Initiative to gather further data and confirm the findings in real world use. It is unclear whether this benefit will be unique to rivaroxaban, or whether other Direct Xa inhibitors will have similar effects. I will certainly be adding ribaroxaban to patients at low risk for bleeding based on this data. Further, rivaroxaban alone did not reduce major cardiovascular adverse events, but did reduce major adverse limb events.

Gohel MS et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14.

This multicenter study in the UK looked at over 450 patients with venous ulceration. Deep-venous reflux was also present in one-third of patients in each group. The median time to ulcer healing was decreased significantly from 82 days to 56 days. This study demonstrates the importance of early intervention for superficial reflux to enhance ulcer healing and decrease risk of recurrence. This study found that early endovenous ablation resulted in faster healing of venous ulcers, and more ulcer-free time than delayed intervention in patients treated with maximal medical therapy, including appropriate compression therapy. Previously, ablation was typically planned after ulcers healed to decrease risk of recurrence. Based on these findings, ablation should be offered to patients with nonhealing venous ulcers early in the course of therapy, in addition to standard wound care.

Linda Harris, MD, FACS

Surgical Education

Ellison EC. Ten-year reassessment of the shortage of general surgeons: Increases in graduation numbers of general surgery residents are insufficient to meet the future demand for general surgeons. Surgery. 2018 Oct;164(4):726-32.

Ellison EC et al. The impact of the aging population and incidence of cancer on future projections of general surgery workforce needs. Surgery. 2018 Mar;163(3):553-59.

Michael D. Sarap, MD, FACS
 

General Surgery

Takada T. Tokyo Guidelines 2018 (TG18). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):1-2.

Acuna SA. Operative strategies for perforated diverticulitis: A systematic review and meta-analysis. Dis Colon Rectum. 2018 Dec; 61(12):1442-53.

 This analysis of the literature considers the three predominant operations for Hinchey III and Hinchey IV perforated diverticulitis: Hartmann procedure, resection and primary anastomosis, and laparoscopic lavage. The importance of this review is that it considers the initial operation and the downstream procedures when determining overall morbidity and mortality. Laparoscopic lavage did not fare well in this review of randomized controlled trials, resulting in higher morbidity than resection in Hinchey III patients. Interestingly, none of the individual studies analyzed had shown a statistical difference, but in the meta-analysis, the number of patients was sufficient to show statistical significance. The other important conclusion was that primary resection with anastomosis (possibly with diverting ileostomy) was superior to Hartmann procedure, when the likelihood of stoma reversal and the morbidity of the second operation was taken into account.

Mark Savarise, MD, FACS
 

Foregut

Alicuben ET. Worldwide experience with erosion of the magnetic sphincter augmentation device. J Gastrointest Surg. 2018; 22(8):1442-47.

Xiong YQ. Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in Barrett’s esophagus: A meta-analysis. Clin Res Hepatol Gastroenterol. 2018 Feb;42(1):31-9.

The days of endoscopic screening and surveillance of patients at risk for the development of Barrett’s esophagus via four-quadrant biopsy every couple of centimeters are numbered. The use of confocal laser microscopy to provide accurate real-time visual data regarding the areas of interest in the esophagus is showing promise and gaining traction compared to standard biopsy techniques and narrow-band imaging.

Borbély Y. Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy. Surg Obes Relat Dis. 2018 May;14(5):611-5.
 

The development of GERD following sleeve gastrectomy is a real problem in a substantial minority of patients due to structural compromise of the lower esophageal sphincter during the procedure. Conversion to gastric bypass as a way to alleviate acid regurgitation has been the mainstay of treatment; however, many patients selected sleeve gastrectomy specifically because they did not want to undergo gastric bypass. For those patients a sleeve preserving procedure such as magnetic sphincter augmentation (currently in clinical trial), Hill procedure, or remnant gastric fundoplication are potential options. Electrical stimulation of the lower esophageal sphincter is revealing itself to be another exciting option (currently in clinical trial) which can be used in patients with as few as 30% peristaltic swallows thus expanding the treatment options for these deserving patients.

Kevin M. Reavis, MD, FACS

Trauma/Critical Care

Teixeira PGR et al. Civilian prehospital tourniquet use is associated with improved survival in patients with peripheral vascular injury . J Am Coll Surg. 2018;226(5):769-76.

Pileggi C et al. Ventilator bundle and its effects on mortality among ICU patients: A meta-analysis. Crit Care Med. 2018;46(7):1167-74.

Critically ill patients requiring mechanical ventilation are at risk for a number of complications, including ventilator-associated pneumonia (VAP) (now a subset of ventilator-associated events (VAE) which prolong ventilator and ICU time and contribute to further complication. Ventilator “bundles,” incorporating simple measures such as elevation of the head of the bed; daily “sedation holidays”; and evaluation of readiness for extubation, peptic ulcer, and DVT prophylaxis have been widely used in ICUs for nearly 20 years. Effective implementation has also emphasized multidisciplinary teamwork. Reductions in ventilator-associated pneumonia (VAP) incidence have been widely demonstrated but mortality benefits have been inconsistent. In this meta-analysis of 13 studies, 6 in Europe, 6 in the US and 1 in Brazil, an overall reduction in mortality (odds ratio, 0.9) was demonstrated. The effect was even larger when limited to studies with patients with VAP (OR, 0.71). This study both validates the effectiveness of relatively simple and inexpensive measures and emphasizes the benefits of a team approach to the care of ICU patients.

Krista L. Kaups, MD, FACS