Federal Practitioner

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

*This article was updated 2/21/2020.

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

*This article was updated 2/21/2020.

As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.

Delpixel/Shutterstock

The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.

People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.

Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill. But fear, discrimination, and misinformation may do more damage than the virus itself.

Three key factors may help reduce the fear factor.

One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.

A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.

A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.

Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.

For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.

In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.

Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.

COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

*This article was updated 2/21/2020.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

Shorter time to metastatic development was associated with shorter time to treatment failure and shorter overall survival in an international review of over 7,000 renal cell carcinoma (RCC) patients treated with first-line tyrosine kinase inhibitors.

“Patients with synchronous disease, compared with patients with metachronous disease, have more adverse prognostic features, significantly shorter TTF [time to treatment failure], and poorer survival. This may help in patient counseling and may be taken into consideration in clinical trial designs in the future, in order to avoid an imbalance between treatment arms,” wrote investigators led by Frede Donskov, MD, a clinical professor at Aarhus (Denmark) University Hospital, in European Urology Oncology.

In the largest study to date to address the impact of timing of metastases on outcomes from tyrosine kinase inhibitor (TKI) treatment, something that’s been unclear until now, Dr. Donskov and associates turned to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare outcomes of 3,906 patients with synchronous metastases, meaning metastases within 3 months of initial RCC diagnosis, with 3,480 with metachronous disease, meaning metastases after that point.

They found that more patients with synchronous versus metachronous disease had higher T stage (T1-2, 19% vs. 34%), N1 disease (21% vs. 6%), presence of sarcomatoid differentiation (15.8% vs. 7.9%), Karnofsky performance status less than 80 (25.9% vs. 15.1%), anemia (62.5% vs. 42.3%), elevated neutrophils (18.9% vs. 10.9%), elevated platelets (21.6% vs. 11.4%), bone metastases (40.4% vs. 29.8%); and IMDC poor risk (40.6% vs.11.3%).

Synchronous versus metachronous disease by intervals of more than 3-12 months, more than 1-2 years, more than 2-7 years, and more than 7 years correlated with poor TTF (5.6 months vs. 7.3, 8.0, 10.8, and 13.3 months; P less than .0001) and poor overall survival (median, 16.7 months vs. 23.8, 30.2, 34.8, and 41.7 months; P less than .0001).

On multivariable regressions adjusting for baseline variables, metachronous disease was protective versus synchronous RCC on overall survival and TTF, with a greater protective effect the longer it took for the disease to metastasize.

“Synchronous disease may represent a distinct pathologic and molecular phenotype ... a high proportion of patients with synchronous disease have tumors with punctuated evolution, harboring aggressive disease features, consolidating in worse risk factors, requiring systemic therapy earlier, and having almost half the expected survival after the initiation of targeted therapy, compared with the latest metastatic timing, as shown in our study,” the investigators wrote.

The findings “reflect the underlying aggressive tumor biology. Whether [time to metastasis] impacts outcome to checkpoint immunotherapy is yet to be elucidated,” they added.

Patients were a median of 59 years at diagnosis, and 72.9% were men. None of the synchronous patients had a surgical nephrectomy, compared with 95.4% of metachronous patients; 67.2% of patients in both groups were treated with the TKI sunitinib (Sutent).

The work was funded by the IMDC. The lead investigator reported institutional grants from Ipsen and Pfizer, maker of sunitinib.
 

[email protected]

SOURCE: Donskov F et al. Eur Urol Oncol. 2020 Feb 6. doi: 10.1016/j.euo.2020.01.001.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.

They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.

The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.

Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10⁵ CFUs).

The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.

The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Psychiatrists do better compared with those in most specialties in finding happiness at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

About 32% of psychiatrists reported being happy at work, according to the Medscape survey, though they lagged well behind dermatologists, who were the most satisfied with their work lives. In terms of happiness outside the office, psychiatrists were in the middle of the pack with 51% reporting that they were happy.

Somewhat fewer psychiatrists reported being burned out, compared with physicians overall, at 37% versus 41%. The biggest contributing factors to psychiatrist burnout were an overabundance of bureaucratic tasks (63%), increased time devoted to EHRs (34%), and a lack of respect from colleagues in the workplace (32%).

Psychiatrists most commonly dealt with burnout by isolating themselves from others (57%), sleeping (43%), and talking with family/friends (42%). Just under half of psychiatrists took 3-4 weeks’ vacation, compared with 44% of all physicians, and 33% took less than 3 weeks’ vacation.

More than three-quarters of psychiatrists reported that they had never felt suicidal, but 17% said that they had contemplated suicide and 1% reported that they had attempted suicide. About 45% said that they were currently seeking professional help, planning to seek help, or had used help in the past to deal with burnout or depression; 48% said that they were not planning to seek help and had not done so in the past.

In an interview, Carol A. Bernstein, MD, said it is challenging to find the meaning in these survey results.

“The challenge with surveys that measure burnout is that the drivers may be somewhat different in different specialties. I am less interested in looking at ‘who has it worse’ than I am at trying to address those systemic factors that are important for all physicians, regardless of specialty,” said Dr. Bernstein of Montefiore Medical Center/Albert Einstein College of Medicine, New York.

“The survey noted some of these factors: the increased burden of regulation and bureaucratic tasks, an EHR that was designed for billing and scheduling – not for taking care of patients – and challenges of professionalism in the workplace. These are issues that we must address for the benefit of all health care providers and patients.”

Dr. Bernstein, a past president of the American Psychiatric Association, is vice chair for faculty development and well-being at Montefiore/Albert Einstein. She is a professor in the departments of psychiatry and behavioral sciences, and obstetrics/gynecology & women’s health.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

[email protected]

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

[email protected]

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

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