Surgical Oncology

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

BOSTON – The day of the week a patient is discharged from the hospital may have an impact the likelihood of readmission.

Patients discharged home from the hospital on a Thursday after colorectal cancer surgery are more likely to be readmitted within 30 days than those discharged on any other day of the week, investigators found.

Neil Osterweil/Frontline Medical News

In contrast, there were no significant day-dependent differences in readmission rates among patients discharged to a skilled nursing facility or acute rehabilitation program, although patients admitted to clinical facilities had higher overall readmission rates, reported Anna Gustin and coinvestigators at the Levine Cancer Institute at the Carolinas Medical Center in Charlotte, N.C.

“For a patient discharged on a Thursday, if you’re going to get an infection, it’s going to be probably during the weekend, when it’s difficult to contact your primary physician, and when other resources are not as readily available,” said Ms. Gustin, who conducts epidemiologic research at Levine Cancer Center and is also a pre-med student and Japanese major at Wake Forest University in Winston-Salem, N.C.

In a study presented in a poster session at the annual Society of Surgical Oncology Cancer Symposium, Ms. Gustin and her coauthors looked at factors influencing readmission rates among patients undergoing surgery for primary, nonmetastatic colorectal cancer resections.

They drew on the to evaluate outcomes for 93,04 SEER-(Surveillance, Epidemiology, and End Results) Medicare database seven patients aged 66 years and older treated for primary colorectal cancer from 1998 through 2009.

They looked at potential contributing factors such as patient demographics, socioeconomic status, length of stay, days of admission and discharge, and discharge setting (home or clinical facility).

They use multivariate logistic regression models to analyze readmission rates at 14 and 30 days after initial discharge.

Focusing on home discharges, they found that as the week progressed, there was a significant likelihood that a patient discharged home would be readmitted (P less then .001 by chi-square and Cochran-Armitage tests). As noted before, the highest rate of readmission was for patients discharged on Thursday, at 12.4%, compared with 10.1% for patients discharged on Sunday, the discharge day least likely to be associated with rehospitalization.

In multivariate analysis, factors significantly associated with risk for 30-day readmission included male vs. female (hazard ratio, 1.16), black vs. other race (HR, 1.22), length of stay 5, 6-7, or 8-10 vs. 12 or more days (HR, 0.48, 0.59, 0.77, respectively), Charlson comorbidity index score 0, 1 or 3 vs. 3 (HR, 0.59, 0.73, 0.82, respectively), and home discharge vs. other (HR, 0.66; all above comparisons significant as shown by 95% confidence intervals).

The authors concluded that although home discharge itself reduces the likelihood of readmission, “improvements in preparing patients for discharge to home are needed. Additional outpatient interventions could rescue patients from readmission.”

They also suggested reexamining staffing policies and weekend availability of resources for patients, and call for addressing disparities in readmissions based on race, sex, length of stay, and comorbidities.

The study was internally supported. The authors reported having no relevant disclosures.

BOSTON – The day of the week a patient is discharged from the hospital may have an impact the likelihood of readmission.

Patients discharged home from the hospital on a Thursday after colorectal cancer surgery are more likely to be readmitted within 30 days than those discharged on any other day of the week, investigators found.

Neil Osterweil/Frontline Medical News

In contrast, there were no significant day-dependent differences in readmission rates among patients discharged to a skilled nursing facility or acute rehabilitation program, although patients admitted to clinical facilities had higher overall readmission rates, reported Anna Gustin and coinvestigators at the Levine Cancer Institute at the Carolinas Medical Center in Charlotte, N.C.

“For a patient discharged on a Thursday, if you’re going to get an infection, it’s going to be probably during the weekend, when it’s difficult to contact your primary physician, and when other resources are not as readily available,” said Ms. Gustin, who conducts epidemiologic research at Levine Cancer Center and is also a pre-med student and Japanese major at Wake Forest University in Winston-Salem, N.C.

In a study presented in a poster session at the annual Society of Surgical Oncology Cancer Symposium, Ms. Gustin and her coauthors looked at factors influencing readmission rates among patients undergoing surgery for primary, nonmetastatic colorectal cancer resections.

They drew on the to evaluate outcomes for 93,04 SEER-(Surveillance, Epidemiology, and End Results) Medicare database seven patients aged 66 years and older treated for primary colorectal cancer from 1998 through 2009.

They looked at potential contributing factors such as patient demographics, socioeconomic status, length of stay, days of admission and discharge, and discharge setting (home or clinical facility).

They use multivariate logistic regression models to analyze readmission rates at 14 and 30 days after initial discharge.

Focusing on home discharges, they found that as the week progressed, there was a significant likelihood that a patient discharged home would be readmitted (P less then .001 by chi-square and Cochran-Armitage tests). As noted before, the highest rate of readmission was for patients discharged on Thursday, at 12.4%, compared with 10.1% for patients discharged on Sunday, the discharge day least likely to be associated with rehospitalization.

In multivariate analysis, factors significantly associated with risk for 30-day readmission included male vs. female (hazard ratio, 1.16), black vs. other race (HR, 1.22), length of stay 5, 6-7, or 8-10 vs. 12 or more days (HR, 0.48, 0.59, 0.77, respectively), Charlson comorbidity index score 0, 1 or 3 vs. 3 (HR, 0.59, 0.73, 0.82, respectively), and home discharge vs. other (HR, 0.66; all above comparisons significant as shown by 95% confidence intervals).

The authors concluded that although home discharge itself reduces the likelihood of readmission, “improvements in preparing patients for discharge to home are needed. Additional outpatient interventions could rescue patients from readmission.”

They also suggested reexamining staffing policies and weekend availability of resources for patients, and call for addressing disparities in readmissions based on race, sex, length of stay, and comorbidities.

The study was internally supported. The authors reported having no relevant disclosures.

BOSTON – The day of the week a patient is discharged from the hospital may have an impact the likelihood of readmission.

Patients discharged home from the hospital on a Thursday after colorectal cancer surgery are more likely to be readmitted within 30 days than those discharged on any other day of the week, investigators found.

Neil Osterweil/Frontline Medical News

In contrast, there were no significant day-dependent differences in readmission rates among patients discharged to a skilled nursing facility or acute rehabilitation program, although patients admitted to clinical facilities had higher overall readmission rates, reported Anna Gustin and coinvestigators at the Levine Cancer Institute at the Carolinas Medical Center in Charlotte, N.C.

“For a patient discharged on a Thursday, if you’re going to get an infection, it’s going to be probably during the weekend, when it’s difficult to contact your primary physician, and when other resources are not as readily available,” said Ms. Gustin, who conducts epidemiologic research at Levine Cancer Center and is also a pre-med student and Japanese major at Wake Forest University in Winston-Salem, N.C.

In a study presented in a poster session at the annual Society of Surgical Oncology Cancer Symposium, Ms. Gustin and her coauthors looked at factors influencing readmission rates among patients undergoing surgery for primary, nonmetastatic colorectal cancer resections.

They drew on the to evaluate outcomes for 93,04 SEER-(Surveillance, Epidemiology, and End Results) Medicare database seven patients aged 66 years and older treated for primary colorectal cancer from 1998 through 2009.

They looked at potential contributing factors such as patient demographics, socioeconomic status, length of stay, days of admission and discharge, and discharge setting (home or clinical facility).

They use multivariate logistic regression models to analyze readmission rates at 14 and 30 days after initial discharge.

Focusing on home discharges, they found that as the week progressed, there was a significant likelihood that a patient discharged home would be readmitted (P less then .001 by chi-square and Cochran-Armitage tests). As noted before, the highest rate of readmission was for patients discharged on Thursday, at 12.4%, compared with 10.1% for patients discharged on Sunday, the discharge day least likely to be associated with rehospitalization.

In multivariate analysis, factors significantly associated with risk for 30-day readmission included male vs. female (hazard ratio, 1.16), black vs. other race (HR, 1.22), length of stay 5, 6-7, or 8-10 vs. 12 or more days (HR, 0.48, 0.59, 0.77, respectively), Charlson comorbidity index score 0, 1 or 3 vs. 3 (HR, 0.59, 0.73, 0.82, respectively), and home discharge vs. other (HR, 0.66; all above comparisons significant as shown by 95% confidence intervals).

The authors concluded that although home discharge itself reduces the likelihood of readmission, “improvements in preparing patients for discharge to home are needed. Additional outpatient interventions could rescue patients from readmission.”

They also suggested reexamining staffing policies and weekend availability of resources for patients, and call for addressing disparities in readmissions based on race, sex, length of stay, and comorbidities.

The study was internally supported. The authors reported having no relevant disclosures.