Liraglutide is associated with a decreased risk of cardiovascular events, compared with placebo, in individuals with type 2 diabetes, according to results from the randomized, placebo-controlled, double-blind LEADER trial.

In the 9,340 patients with type 2 diabetes in LEADER, those treated with the glucagonlike peptide–1 (GLP-1) analogue liraglutide had a 13% lower risk of a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke over a median follow-up of 3.8 years (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97; P less than .001 for noninferiority; P = .01 for superiority).

This significant reduction in the primary outcome in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) makes liraglutide (Victoza) the second antihyperglycemic drug to be shown to reduce cardiovascular outcomes since the Food and Drug Administration mandated that all such agents be tested in such a way in 2008. The first was the sodium-glucose cotransporter–2 inhibitor empagliflozin, which reduced the risk of the composite endpoint of hospitalization for heart failure or death due to cardiovascular disease by 34% in the EMPA-REG OUTCOME trial (N Engl J Med. 2015;373:2117-28).

In LEADER, the rate of death from cardiovascular causes was 22% lower in the liraglutide group than in the placebo group (95% CI, 0.66-0.93; P = .007). However, the lower incidences of nonfatal MI, stroke, and hospitalization for heart failure in the liraglutide group did not reach statistical significance.

The participants in LEADER all had a hemoglobin A_1c level of 7.0%, and were either aged over 50 with at least one cardiovascular condition such as coronary heart disease, or aged over 60 with at least one cardiovascular risk factor such as hypertension or microalbuminuria.

The participants, who were recruited from 410 sites in 32 countries, were randomized to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to equivalent placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827).

“Although glycemic control is associated with reductions in the risk of microvascular complications, the macrovascular benefits of glycemic control are less certain,” wrote Dr. Steven P. Marso of the University of Texas Southwestern Medical Center, Dallas, and his coauthors.

“Furthermore, concern has been raised about the cardiovascular safety of antihyperglycemic therapies, [and] consequently, regulatory authorities have mandated cardiovascular safety assessments of new diabetes treatments.”

The study did see a significant interaction between liraglutide and renal function. Patients who had an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m² showed more benefits from the liraglutide in terms of the primary outcomes than did those with an eGFR of at least 60 mL/min.

Individuals aged over 50 years with established cardiovascular disease also showed greater benefits in reductions in the primary outcome from liraglutide than did patients aged over 60 years with cardiovascular risk factors.

The authors commented that their findings contrast with those of the Lixisenatide in Acute Coronary Syndrome (ELIXA) trial using the shorter-acting and structurally dissimilar GLP-1 receptor agonist lixisenatide. This trial failed to show any cardiovascular benefit of the drug in patients with diabetes and a recent acute coronary syndrome, as did several other trials looking at cardiovascular outcomes in high-risk patients with type 2 diabetes treated with drugs including insulin, thiazolidinediones, and dipeptidyl peptidase–4 inhibitors.

“Our trial had greater statistical power and included patients with a higher baseline glycated hemoglobin level than did most previous studies,” the authors wrote. “However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature.

The study also examined the incidence of adverse events, finding a nonsignificantly higher overall rate of benign or malignant neoplasms with liraglutide, compared with placebo. However, there was a trend toward an increased risk of pancreatic cancer in those taking liraglutide, which approached statistical significance.

“There has been considerable interest in a potential association between the use of GLP-1 receptor agonists and pancreatitis and pancreatic cancer, although there is no consistent preclinical, pharmacovigilance, or epidemiologic evidence to date,” the authors commented.

The study was supported by Novo Nordisk and the National Institutes of Health. Several authors declared grants, consultancies and funding from the pharmaceutical industry, including from Novo Nordisk. Several authors are employees of Novo Nordisk, are on steering committees, and/or own shares in the company.

Liraglutide is associated with a decreased risk of cardiovascular events, compared with placebo, in individuals with type 2 diabetes, according to results from the randomized, placebo-controlled, double-blind LEADER trial.

In the 9,340 patients with type 2 diabetes in LEADER, those treated with the glucagonlike peptide–1 (GLP-1) analogue liraglutide had a 13% lower risk of a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke over a median follow-up of 3.8 years (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97; P less than .001 for noninferiority; P = .01 for superiority).

This significant reduction in the primary outcome in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) makes liraglutide (Victoza) the second antihyperglycemic drug to be shown to reduce cardiovascular outcomes since the Food and Drug Administration mandated that all such agents be tested in such a way in 2008. The first was the sodium-glucose cotransporter–2 inhibitor empagliflozin, which reduced the risk of the composite endpoint of hospitalization for heart failure or death due to cardiovascular disease by 34% in the EMPA-REG OUTCOME trial (N Engl J Med. 2015;373:2117-28).

In LEADER, the rate of death from cardiovascular causes was 22% lower in the liraglutide group than in the placebo group (95% CI, 0.66-0.93; P = .007). However, the lower incidences of nonfatal MI, stroke, and hospitalization for heart failure in the liraglutide group did not reach statistical significance.

The participants in LEADER all had a hemoglobin A_1c level of 7.0%, and were either aged over 50 with at least one cardiovascular condition such as coronary heart disease, or aged over 60 with at least one cardiovascular risk factor such as hypertension or microalbuminuria.

The participants, who were recruited from 410 sites in 32 countries, were randomized to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to equivalent placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827).

“Although glycemic control is associated with reductions in the risk of microvascular complications, the macrovascular benefits of glycemic control are less certain,” wrote Dr. Steven P. Marso of the University of Texas Southwestern Medical Center, Dallas, and his coauthors.

“Furthermore, concern has been raised about the cardiovascular safety of antihyperglycemic therapies, [and] consequently, regulatory authorities have mandated cardiovascular safety assessments of new diabetes treatments.”

The study did see a significant interaction between liraglutide and renal function. Patients who had an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m² showed more benefits from the liraglutide in terms of the primary outcomes than did those with an eGFR of at least 60 mL/min.

Individuals aged over 50 years with established cardiovascular disease also showed greater benefits in reductions in the primary outcome from liraglutide than did patients aged over 60 years with cardiovascular risk factors.

The authors commented that their findings contrast with those of the Lixisenatide in Acute Coronary Syndrome (ELIXA) trial using the shorter-acting and structurally dissimilar GLP-1 receptor agonist lixisenatide. This trial failed to show any cardiovascular benefit of the drug in patients with diabetes and a recent acute coronary syndrome, as did several other trials looking at cardiovascular outcomes in high-risk patients with type 2 diabetes treated with drugs including insulin, thiazolidinediones, and dipeptidyl peptidase–4 inhibitors.

“Our trial had greater statistical power and included patients with a higher baseline glycated hemoglobin level than did most previous studies,” the authors wrote. “However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature.

The study also examined the incidence of adverse events, finding a nonsignificantly higher overall rate of benign or malignant neoplasms with liraglutide, compared with placebo. However, there was a trend toward an increased risk of pancreatic cancer in those taking liraglutide, which approached statistical significance.

“There has been considerable interest in a potential association between the use of GLP-1 receptor agonists and pancreatitis and pancreatic cancer, although there is no consistent preclinical, pharmacovigilance, or epidemiologic evidence to date,” the authors commented.

The study was supported by Novo Nordisk and the National Institutes of Health. Several authors declared grants, consultancies and funding from the pharmaceutical industry, including from Novo Nordisk. Several authors are employees of Novo Nordisk, are on steering committees, and/or own shares in the company.

Liraglutide is associated with a decreased risk of cardiovascular events, compared with placebo, in individuals with type 2 diabetes, according to results from the randomized, placebo-controlled, double-blind LEADER trial.

In the 9,340 patients with type 2 diabetes in LEADER, those treated with the glucagonlike peptide–1 (GLP-1) analogue liraglutide had a 13% lower risk of a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke over a median follow-up of 3.8 years (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97; P less than .001 for noninferiority; P = .01 for superiority).

This significant reduction in the primary outcome in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) makes liraglutide (Victoza) the second antihyperglycemic drug to be shown to reduce cardiovascular outcomes since the Food and Drug Administration mandated that all such agents be tested in such a way in 2008. The first was the sodium-glucose cotransporter–2 inhibitor empagliflozin, which reduced the risk of the composite endpoint of hospitalization for heart failure or death due to cardiovascular disease by 34% in the EMPA-REG OUTCOME trial (N Engl J Med. 2015;373:2117-28).

In LEADER, the rate of death from cardiovascular causes was 22% lower in the liraglutide group than in the placebo group (95% CI, 0.66-0.93; P = .007). However, the lower incidences of nonfatal MI, stroke, and hospitalization for heart failure in the liraglutide group did not reach statistical significance.

The participants in LEADER all had a hemoglobin A_1c level of 7.0%, and were either aged over 50 with at least one cardiovascular condition such as coronary heart disease, or aged over 60 with at least one cardiovascular risk factor such as hypertension or microalbuminuria.

The participants, who were recruited from 410 sites in 32 countries, were randomized to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to equivalent placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827).

“Although glycemic control is associated with reductions in the risk of microvascular complications, the macrovascular benefits of glycemic control are less certain,” wrote Dr. Steven P. Marso of the University of Texas Southwestern Medical Center, Dallas, and his coauthors.

“Furthermore, concern has been raised about the cardiovascular safety of antihyperglycemic therapies, [and] consequently, regulatory authorities have mandated cardiovascular safety assessments of new diabetes treatments.”

The study did see a significant interaction between liraglutide and renal function. Patients who had an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m² showed more benefits from the liraglutide in terms of the primary outcomes than did those with an eGFR of at least 60 mL/min.

Individuals aged over 50 years with established cardiovascular disease also showed greater benefits in reductions in the primary outcome from liraglutide than did patients aged over 60 years with cardiovascular risk factors.

The authors commented that their findings contrast with those of the Lixisenatide in Acute Coronary Syndrome (ELIXA) trial using the shorter-acting and structurally dissimilar GLP-1 receptor agonist lixisenatide. This trial failed to show any cardiovascular benefit of the drug in patients with diabetes and a recent acute coronary syndrome, as did several other trials looking at cardiovascular outcomes in high-risk patients with type 2 diabetes treated with drugs including insulin, thiazolidinediones, and dipeptidyl peptidase–4 inhibitors.

“Our trial had greater statistical power and included patients with a higher baseline glycated hemoglobin level than did most previous studies,” the authors wrote. “However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature.

The study also examined the incidence of adverse events, finding a nonsignificantly higher overall rate of benign or malignant neoplasms with liraglutide, compared with placebo. However, there was a trend toward an increased risk of pancreatic cancer in those taking liraglutide, which approached statistical significance.

“There has been considerable interest in a potential association between the use of GLP-1 receptor agonists and pancreatitis and pancreatic cancer, although there is no consistent preclinical, pharmacovigilance, or epidemiologic evidence to date,” the authors commented.

The study was supported by Novo Nordisk and the National Institutes of Health. Several authors declared grants, consultancies and funding from the pharmaceutical industry, including from Novo Nordisk. Several authors are employees of Novo Nordisk, are on steering committees, and/or own shares in the company.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Plant-based therapies were associated with “modest reductions” in the frequency of hot flashes and vaginal dryness in menopause, but did not significantly reduce night sweats, according to a systematic review from Dr. Oscar H. Franco and his associates.

A total of 62 studies covering 6,653 women were included in the review. Phytoestrogen use decreased vaginal dryness scores by 0.31 and reduced the number of daily hot flashes by 1.31, but did not reduce the number of night sweats. Individual phytoestrogen interventions, such as dietary and supplementary soy isoflavones, decreased vaginal dryness scores by 0.26 and reduced the number of daily hot flashes by 0.79.

©Highwaystarz-Photography/Thinkstock

While evidence was limited, Chinese medicinal herbs had no association with a reduction in menopausal symptoms, while non-Chinese medicinal herbs reduced the number of daily hot flashes by 1.62 in one randomized controlled trial.

“This review underscores the lack of data on adverse effects associated with long-term use of plant-based therapies. Information on any detrimental health effects, typically available in long-term intervention studies, is essential, given their potential relevance to postmenopausal health,” Dr. Franco and his colleagues wrote.

Read the full study in JAMA (doi: 10.1001/jama.2016.8012).

[email protected]

Plant-based therapies were associated with “modest reductions” in the frequency of hot flashes and vaginal dryness in menopause, but did not significantly reduce night sweats, according to a systematic review from Dr. Oscar H. Franco and his associates.

A total of 62 studies covering 6,653 women were included in the review. Phytoestrogen use decreased vaginal dryness scores by 0.31 and reduced the number of daily hot flashes by 1.31, but did not reduce the number of night sweats. Individual phytoestrogen interventions, such as dietary and supplementary soy isoflavones, decreased vaginal dryness scores by 0.26 and reduced the number of daily hot flashes by 0.79.

©Highwaystarz-Photography/Thinkstock

While evidence was limited, Chinese medicinal herbs had no association with a reduction in menopausal symptoms, while non-Chinese medicinal herbs reduced the number of daily hot flashes by 1.62 in one randomized controlled trial.

“This review underscores the lack of data on adverse effects associated with long-term use of plant-based therapies. Information on any detrimental health effects, typically available in long-term intervention studies, is essential, given their potential relevance to postmenopausal health,” Dr. Franco and his colleagues wrote.

Read the full study in JAMA (doi: 10.1001/jama.2016.8012).

[email protected]

Plant-based therapies were associated with “modest reductions” in the frequency of hot flashes and vaginal dryness in menopause, but did not significantly reduce night sweats, according to a systematic review from Dr. Oscar H. Franco and his associates.

A total of 62 studies covering 6,653 women were included in the review. Phytoestrogen use decreased vaginal dryness scores by 0.31 and reduced the number of daily hot flashes by 1.31, but did not reduce the number of night sweats. Individual phytoestrogen interventions, such as dietary and supplementary soy isoflavones, decreased vaginal dryness scores by 0.26 and reduced the number of daily hot flashes by 0.79.

©Highwaystarz-Photography/Thinkstock

While evidence was limited, Chinese medicinal herbs had no association with a reduction in menopausal symptoms, while non-Chinese medicinal herbs reduced the number of daily hot flashes by 1.62 in one randomized controlled trial.

“This review underscores the lack of data on adverse effects associated with long-term use of plant-based therapies. Information on any detrimental health effects, typically available in long-term intervention studies, is essential, given their potential relevance to postmenopausal health,” Dr. Franco and his colleagues wrote.

Read the full study in JAMA (doi: 10.1001/jama.2016.8012).

[email protected]

I was in London for the just-concluded EULAR congress. Oh, the United Kingdom, that bastion of socialist medicine, where the National Health Service is the great equalizer. Heaven sent to some, death spiral of long wait times and old-fashioned medicine to others. While there, I chatted with people who have had experience with the NHS.

I spoke with a health care consultant, whose job is to make hospitals less wasteful. He says the U.K.’s health care expenditure as a percent of GDP [gross domestic product] is too high, compared with other Western nations. I suspect this was a line that he probably heard somewhere and blindly repeated, because when I pressed, he could not tell me what the numbers were, nor could he name the countries he was referring to.

I asked him for examples of how he thought the hospitals he’d served might save money. His biggest complaint was that many patients stay in hospital for months not out of medical necessity but because there is no system in place for lower-level care.

Another friend is the director of a home care service just outside Central London. She tells me that patients have access to an extraordinary amount of resources that allows them to stay at home: suction machines, dialysis machines, home aides. This is great for patients, but she is astounded by how many people got services that she thought were undeserved.

She also told me that, apropos of the impending Brexit, many of their home health aides come from other Eurozone countries. The British do not want to do these jobs, so should the Brexit happen, home health aides will be much harder to come by.

Of course, the most common complaint I heard was that wait times to see a physician are ridiculous. Those who can afford it, can get private insurance, which would allow them access to physicians sooner. In fact, private insurance is often an incentive for people to get promoted.

The British think their health care system is wasteful, as we do for ours. But according to the World Bank’s data from 2014, their health care spending as a percent of GDP is 9.1%, which is much better than ours at 17.1%. And although I was told by the health care consultant that their figure is higher than their neighbors, that just isn’t true. France’s figure is 11.5%, Belgium’s 10.6%, and Spain’s 9.0%. So what I took away from it was this: As different as our health care systems are, they are problematic in the same ways. People have health care that works. But hospital stays are often unnecessary, people take advantage of social safety nets, and there are jobs that mostly only immigrants are willing to perform. Wealthy people can afford to pay for private insurance. And the wait times! People will always complain about wait times, just like they do here, and elsewhere.

Dr. Chan practices rheumatology in Pawtucket, R.I.

I was in London for the just-concluded EULAR congress. Oh, the United Kingdom, that bastion of socialist medicine, where the National Health Service is the great equalizer. Heaven sent to some, death spiral of long wait times and old-fashioned medicine to others. While there, I chatted with people who have had experience with the NHS.

I spoke with a health care consultant, whose job is to make hospitals less wasteful. He says the U.K.’s health care expenditure as a percent of GDP [gross domestic product] is too high, compared with other Western nations. I suspect this was a line that he probably heard somewhere and blindly repeated, because when I pressed, he could not tell me what the numbers were, nor could he name the countries he was referring to.

I asked him for examples of how he thought the hospitals he’d served might save money. His biggest complaint was that many patients stay in hospital for months not out of medical necessity but because there is no system in place for lower-level care.

Another friend is the director of a home care service just outside Central London. She tells me that patients have access to an extraordinary amount of resources that allows them to stay at home: suction machines, dialysis machines, home aides. This is great for patients, but she is astounded by how many people got services that she thought were undeserved.

She also told me that, apropos of the impending Brexit, many of their home health aides come from other Eurozone countries. The British do not want to do these jobs, so should the Brexit happen, home health aides will be much harder to come by.

Of course, the most common complaint I heard was that wait times to see a physician are ridiculous. Those who can afford it, can get private insurance, which would allow them access to physicians sooner. In fact, private insurance is often an incentive for people to get promoted.

The British think their health care system is wasteful, as we do for ours. But according to the World Bank’s data from 2014, their health care spending as a percent of GDP is 9.1%, which is much better than ours at 17.1%. And although I was told by the health care consultant that their figure is higher than their neighbors, that just isn’t true. France’s figure is 11.5%, Belgium’s 10.6%, and Spain’s 9.0%. So what I took away from it was this: As different as our health care systems are, they are problematic in the same ways. People have health care that works. But hospital stays are often unnecessary, people take advantage of social safety nets, and there are jobs that mostly only immigrants are willing to perform. Wealthy people can afford to pay for private insurance. And the wait times! People will always complain about wait times, just like they do here, and elsewhere.

Dr. Chan practices rheumatology in Pawtucket, R.I.

I was in London for the just-concluded EULAR congress. Oh, the United Kingdom, that bastion of socialist medicine, where the National Health Service is the great equalizer. Heaven sent to some, death spiral of long wait times and old-fashioned medicine to others. While there, I chatted with people who have had experience with the NHS.

I spoke with a health care consultant, whose job is to make hospitals less wasteful. He says the U.K.’s health care expenditure as a percent of GDP [gross domestic product] is too high, compared with other Western nations. I suspect this was a line that he probably heard somewhere and blindly repeated, because when I pressed, he could not tell me what the numbers were, nor could he name the countries he was referring to.

I asked him for examples of how he thought the hospitals he’d served might save money. His biggest complaint was that many patients stay in hospital for months not out of medical necessity but because there is no system in place for lower-level care.

Another friend is the director of a home care service just outside Central London. She tells me that patients have access to an extraordinary amount of resources that allows them to stay at home: suction machines, dialysis machines, home aides. This is great for patients, but she is astounded by how many people got services that she thought were undeserved.

She also told me that, apropos of the impending Brexit, many of their home health aides come from other Eurozone countries. The British do not want to do these jobs, so should the Brexit happen, home health aides will be much harder to come by.

Of course, the most common complaint I heard was that wait times to see a physician are ridiculous. Those who can afford it, can get private insurance, which would allow them access to physicians sooner. In fact, private insurance is often an incentive for people to get promoted.

The British think their health care system is wasteful, as we do for ours. But according to the World Bank’s data from 2014, their health care spending as a percent of GDP is 9.1%, which is much better than ours at 17.1%. And although I was told by the health care consultant that their figure is higher than their neighbors, that just isn’t true. France’s figure is 11.5%, Belgium’s 10.6%, and Spain’s 9.0%. So what I took away from it was this: As different as our health care systems are, they are problematic in the same ways. People have health care that works. But hospital stays are often unnecessary, people take advantage of social safety nets, and there are jobs that mostly only immigrants are willing to perform. Wealthy people can afford to pay for private insurance. And the wait times! People will always complain about wait times, just like they do here, and elsewhere.

Dr. Chan practices rheumatology in Pawtucket, R.I.

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

[email protected]

On Twitter @ThoracicTweets

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

[email protected]

On Twitter @ThoracicTweets

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

[email protected]

On Twitter @ThoracicTweets

BALTIMORE – Approximately one in five patients is readmitted after esophagectomy, and leading risk factors for readmission are longer operative time, post-surgical ICU admission, and preoperative blood transfusions, according to a single-center study of 86 patients.

As one of the first reports on readmissions following esophagectomy with complete follow-up, this study, conducted at the Mayo Clinic in Rochester, Minn., demonstrates that even in a high volume center with specialization in esophageal and foregut surgery, readmission after esophagectomy is not uncommon, researchers reported at the annual meeting of the American Association for Thoracic Surgery.

“In the context of increasing pressures to reduce length of stay, we must also put in the effort to better understand our readmission rates and the important factors that affect them,” said study investigator Dr. Stephen Cassivi. “Reporting on ‘improved’ lengths of stay without accompanying data on readmission rates is not telling the whole story.”

According to the Mayo Clinic research team, identifying risk factors that predict readmissions might permit improved patient management and outcomes.

“Careful collection of data regarding patient outcomes, including unplanned hospital readmissions is essential to improve the quality of patient care since national databases can leave gaps in data regarding follow-up of these patients by failing to identify all readmissions after their surgery,” said Dr. Karen J. Dickinson, who presented the study at the meeting.

The study was designed such that all patients undergoing an elective esophagectomy between August 2013 and July 2014 were contacted directly to follow up on whether they had been readmitted to any medical institution within 30 days of dismissal from the Mayo Clinic. Among all patients who underwent esophagectomy during the one-year study period, 86 patients met the study inclusion criteria. Follow-up was complete in 100% of patients, according to Dr. Dickinson.

Median age of the patients at the time of surgery was 63 years, and the majority of patients were men (70 patients). The most common operative approach was transthoracic (Ivor Lewis) esophagectomy (72%); 7% of cases were performed using a minimally invasive approach. Overall 30-day mortality was 2% (2/86), and anastomotic leak occurred in 8% of the patients.

Median length of stay was 9 days, and the rate of unplanned 30-day readmission was 19% (16 patients). Of these patients, 88% were readmitted to the Mayo Clinic and 12% were readmitted to other medical institutions.

The most common reasons for readmission were due to respiratory causes such as dyspnea, pleural effusions or pneumonia and gastrointestinal causes, including bowel obstruction and anastomotic complications.

Using multivariable analysis, the researchers found that the factors significantly associated with unplanned readmission were postoperative ICU admission (13% in non-readmitted, 38% in admitted), perioperative blood transfusion (12% vs. 38%), and operative length (368 vs. 460 minutes). Importantly, initial hospital length of stay was not associated with the need for readmission. Furthermore, ASA score, sex, BMI, neoadjuvant therapy, and postoperative pain scores also were not associated with unplanned readmission.

“Identifying these risk factors in the perioperative and postoperative setting may provide opportunities for decreasing morbidity, improving readmission rates, and enhancing overall patient outcomes,” Dr. Dickinson concluded.

A video of this presentation at the AATS Annual Meeting is available online.

Dr. Dickinson and her colleagues reported having no relevant disclosures.

[email protected]

On Twitter @ThoracicTweets

BALTIMORE – Approximately one in five patients is readmitted after esophagectomy, and leading risk factors for readmission are longer operative time, post-surgical ICU admission, and preoperative blood transfusions, according to a single-center study of 86 patients.

As one of the first reports on readmissions following esophagectomy with complete follow-up, this study, conducted at the Mayo Clinic in Rochester, Minn., demonstrates that even in a high volume center with specialization in esophageal and foregut surgery, readmission after esophagectomy is not uncommon, researchers reported at the annual meeting of the American Association for Thoracic Surgery.

“In the context of increasing pressures to reduce length of stay, we must also put in the effort to better understand our readmission rates and the important factors that affect them,” said study investigator Dr. Stephen Cassivi. “Reporting on ‘improved’ lengths of stay without accompanying data on readmission rates is not telling the whole story.”

According to the Mayo Clinic research team, identifying risk factors that predict readmissions might permit improved patient management and outcomes.

“Careful collection of data regarding patient outcomes, including unplanned hospital readmissions is essential to improve the quality of patient care since national databases can leave gaps in data regarding follow-up of these patients by failing to identify all readmissions after their surgery,” said Dr. Karen J. Dickinson, who presented the study at the meeting.

The study was designed such that all patients undergoing an elective esophagectomy between August 2013 and July 2014 were contacted directly to follow up on whether they had been readmitted to any medical institution within 30 days of dismissal from the Mayo Clinic. Among all patients who underwent esophagectomy during the one-year study period, 86 patients met the study inclusion criteria. Follow-up was complete in 100% of patients, according to Dr. Dickinson.

Median age of the patients at the time of surgery was 63 years, and the majority of patients were men (70 patients). The most common operative approach was transthoracic (Ivor Lewis) esophagectomy (72%); 7% of cases were performed using a minimally invasive approach. Overall 30-day mortality was 2% (2/86), and anastomotic leak occurred in 8% of the patients.

Median length of stay was 9 days, and the rate of unplanned 30-day readmission was 19% (16 patients). Of these patients, 88% were readmitted to the Mayo Clinic and 12% were readmitted to other medical institutions.

The most common reasons for readmission were due to respiratory causes such as dyspnea, pleural effusions or pneumonia and gastrointestinal causes, including bowel obstruction and anastomotic complications.

Using multivariable analysis, the researchers found that the factors significantly associated with unplanned readmission were postoperative ICU admission (13% in non-readmitted, 38% in admitted), perioperative blood transfusion (12% vs. 38%), and operative length (368 vs. 460 minutes). Importantly, initial hospital length of stay was not associated with the need for readmission. Furthermore, ASA score, sex, BMI, neoadjuvant therapy, and postoperative pain scores also were not associated with unplanned readmission.

“Identifying these risk factors in the perioperative and postoperative setting may provide opportunities for decreasing morbidity, improving readmission rates, and enhancing overall patient outcomes,” Dr. Dickinson concluded.

A video of this presentation at the AATS Annual Meeting is available online.

Dr. Dickinson and her colleagues reported having no relevant disclosures.

[email protected]

On Twitter @ThoracicTweets

BALTIMORE – Approximately one in five patients is readmitted after esophagectomy, and leading risk factors for readmission are longer operative time, post-surgical ICU admission, and preoperative blood transfusions, according to a single-center study of 86 patients.

As one of the first reports on readmissions following esophagectomy with complete follow-up, this study, conducted at the Mayo Clinic in Rochester, Minn., demonstrates that even in a high volume center with specialization in esophageal and foregut surgery, readmission after esophagectomy is not uncommon, researchers reported at the annual meeting of the American Association for Thoracic Surgery.

“In the context of increasing pressures to reduce length of stay, we must also put in the effort to better understand our readmission rates and the important factors that affect them,” said study investigator Dr. Stephen Cassivi. “Reporting on ‘improved’ lengths of stay without accompanying data on readmission rates is not telling the whole story.”

According to the Mayo Clinic research team, identifying risk factors that predict readmissions might permit improved patient management and outcomes.

“Careful collection of data regarding patient outcomes, including unplanned hospital readmissions is essential to improve the quality of patient care since national databases can leave gaps in data regarding follow-up of these patients by failing to identify all readmissions after their surgery,” said Dr. Karen J. Dickinson, who presented the study at the meeting.

The study was designed such that all patients undergoing an elective esophagectomy between August 2013 and July 2014 were contacted directly to follow up on whether they had been readmitted to any medical institution within 30 days of dismissal from the Mayo Clinic. Among all patients who underwent esophagectomy during the one-year study period, 86 patients met the study inclusion criteria. Follow-up was complete in 100% of patients, according to Dr. Dickinson.

Median age of the patients at the time of surgery was 63 years, and the majority of patients were men (70 patients). The most common operative approach was transthoracic (Ivor Lewis) esophagectomy (72%); 7% of cases were performed using a minimally invasive approach. Overall 30-day mortality was 2% (2/86), and anastomotic leak occurred in 8% of the patients.

Median length of stay was 9 days, and the rate of unplanned 30-day readmission was 19% (16 patients). Of these patients, 88% were readmitted to the Mayo Clinic and 12% were readmitted to other medical institutions.

The most common reasons for readmission were due to respiratory causes such as dyspnea, pleural effusions or pneumonia and gastrointestinal causes, including bowel obstruction and anastomotic complications.

Using multivariable analysis, the researchers found that the factors significantly associated with unplanned readmission were postoperative ICU admission (13% in non-readmitted, 38% in admitted), perioperative blood transfusion (12% vs. 38%), and operative length (368 vs. 460 minutes). Importantly, initial hospital length of stay was not associated with the need for readmission. Furthermore, ASA score, sex, BMI, neoadjuvant therapy, and postoperative pain scores also were not associated with unplanned readmission.

“Identifying these risk factors in the perioperative and postoperative setting may provide opportunities for decreasing morbidity, improving readmission rates, and enhancing overall patient outcomes,” Dr. Dickinson concluded.

A video of this presentation at the AATS Annual Meeting is available online.

Dr. Dickinson and her colleagues reported having no relevant disclosures.

[email protected]

On Twitter @ThoracicTweets

I visited during a hot Florida summer in the mid 1990s and could readily see that the practice was great in most respects. The large multispecialty group had recruited talented hospitalists and had put in place effective operational practices. All seemed to be going well, but inappropriate overhead allocation was undermining the success of their efforts.

The multispecialty group employing the hospitalists used the same formula to allocate overhead to the hospitalists that was in place for other specialties. And compensation was essentially each doctor’s collections minus overhead, leaving the hospitalists with annual compensation much lower than they could reasonably expect. With the group deducting from hospitalist collections the same overhead expenses charged to other specialties, including a share of outpatient buildings, staff, and supplies, the hospitalists were paying a lot for services they weren’t using. This group corrected the errors but not until some talented doctors had resigned because of the compensation formula.

This was a common mistake made by multispecialty groups that employed hospitalists years ago. Today, nearly all such groups assess an appropriately smaller portion of overhead to hospitalists than office-based doctors.

Typical Hospitalist Overhead

It is still tricky to correctly assess and allocate hospitalist overhead. This meaningfully influences the apparent total cost of the program and hence the amount of support paid by the hospital or other entity. (This support is often referred to as a “subsidy,” though I don’t care for that term because of its negative connotation.)

For example, costs for billing and collections services, malpractice insurance, temporary staffing (locums), and an overhead allocation that pays for things like the salaries of medical group administrators and clerical staff may or may not be attributed to the hospitalist budget or “cost center.” This is one of several factors that make it awfully tricky to compare the total costs and/or hospital financial support between different hospitalist groups.

SHM’s State of Hospital Medicine report includes detailed instructions regarding which expenses the survey respondents should include as overhead costs, but I think it’s safe to assume that not all responses are fully compliant. I’m confident there is a meaningful amount of “noise” in these figures. Numbers like the median financial support per FTE hospitalist per year ($156,063 in the 2014 report) should only be used as a guideline and not a precise number that might apply in your setting. My reasoning is that the collections rate and compensation amount can vary tremendously from one practice to another and will typically have a far larger influence on the amount of financial support provided by the hospital than which expenses are or aren’t included as overhead. But I am confining this discussion to the latter.

APC Costs: One Factor Driving Increased Support

SHM has been surveying the financial support per physician FTE for about 15 years, and it has shown a steady increase. It was about $60,000 per FTE annually when first surveyed in the late 1990s; it has gone up every survey since. The best explanation for this seems to an increase in hospitalist compensation while production and revenue have remained relatively flat.

There likely are many other factors in play. One important one is physician assistant and nurse practitioner costs. The survey divides the total annual support provided to the whole hospitalist practice by the total number of physician FTEs. NPs and PAs are becoming more common in hospitalist groups; 65% of groups included them in 2014, up from 54% in 2012. Yet the cost of employing them, primarily salary and benefits, appears in the numerator but not the denominator of the support per physician FTE figure.

This means a group that adds NP/PA staffing, which typically requires an accompanying increase in hospital financial support, while maintaining the same number of physician FTEs will show an increase in hospital support per physician FTE. But this fails to capture that the practice’s work product (i.e., patients seen) has increased as a result of increasing its clinical staff.

This is a tricky issue to fix. SHM’s Practice Analysis Committee, which manages the survey, is aware of the issue and may make future adjustments to account for it. The best method might be to convert total staffing by physicians and NP/PAs into physician-equivalent FTEs (I described one method for doing this in my August 2009 column titled “Volume Variables”) or some other method that clearly accounts for both physician and NP/PA staffing levels. Other alternatives would be to divide the annual support by the number of billed encounters or some other measure of “work output” or to report percent of the total practice revenue that comes from hospital support versus professional fee collections and other sources.

Why Allocation of NP/PA Costs and FTEs Matter

Another way to think of this issue is that including NP/PA costs but not their work (FTEs) in the financial support per FTE figure overlooks the important work they can do for a hospitalist practice. And it can lead one to conclude hospitals’ costs per clinician FTE are rising faster than is actually the case.

This is only one of the tricky issues in accurately understanding hospitalist overhead and costs to the hospital they serve. TH

I visited during a hot Florida summer in the mid 1990s and could readily see that the practice was great in most respects. The large multispecialty group had recruited talented hospitalists and had put in place effective operational practices. All seemed to be going well, but inappropriate overhead allocation was undermining the success of their efforts.

The multispecialty group employing the hospitalists used the same formula to allocate overhead to the hospitalists that was in place for other specialties. And compensation was essentially each doctor’s collections minus overhead, leaving the hospitalists with annual compensation much lower than they could reasonably expect. With the group deducting from hospitalist collections the same overhead expenses charged to other specialties, including a share of outpatient buildings, staff, and supplies, the hospitalists were paying a lot for services they weren’t using. This group corrected the errors but not until some talented doctors had resigned because of the compensation formula.

This was a common mistake made by multispecialty groups that employed hospitalists years ago. Today, nearly all such groups assess an appropriately smaller portion of overhead to hospitalists than office-based doctors.

Typical Hospitalist Overhead

It is still tricky to correctly assess and allocate hospitalist overhead. This meaningfully influences the apparent total cost of the program and hence the amount of support paid by the hospital or other entity. (This support is often referred to as a “subsidy,” though I don’t care for that term because of its negative connotation.)

For example, costs for billing and collections services, malpractice insurance, temporary staffing (locums), and an overhead allocation that pays for things like the salaries of medical group administrators and clerical staff may or may not be attributed to the hospitalist budget or “cost center.” This is one of several factors that make it awfully tricky to compare the total costs and/or hospital financial support between different hospitalist groups.

SHM’s State of Hospital Medicine report includes detailed instructions regarding which expenses the survey respondents should include as overhead costs, but I think it’s safe to assume that not all responses are fully compliant. I’m confident there is a meaningful amount of “noise” in these figures. Numbers like the median financial support per FTE hospitalist per year ($156,063 in the 2014 report) should only be used as a guideline and not a precise number that might apply in your setting. My reasoning is that the collections rate and compensation amount can vary tremendously from one practice to another and will typically have a far larger influence on the amount of financial support provided by the hospital than which expenses are or aren’t included as overhead. But I am confining this discussion to the latter.

APC Costs: One Factor Driving Increased Support

SHM has been surveying the financial support per physician FTE for about 15 years, and it has shown a steady increase. It was about $60,000 per FTE annually when first surveyed in the late 1990s; it has gone up every survey since. The best explanation for this seems to an increase in hospitalist compensation while production and revenue have remained relatively flat.

There likely are many other factors in play. One important one is physician assistant and nurse practitioner costs. The survey divides the total annual support provided to the whole hospitalist practice by the total number of physician FTEs. NPs and PAs are becoming more common in hospitalist groups; 65% of groups included them in 2014, up from 54% in 2012. Yet the cost of employing them, primarily salary and benefits, appears in the numerator but not the denominator of the support per physician FTE figure.

This means a group that adds NP/PA staffing, which typically requires an accompanying increase in hospital financial support, while maintaining the same number of physician FTEs will show an increase in hospital support per physician FTE. But this fails to capture that the practice’s work product (i.e., patients seen) has increased as a result of increasing its clinical staff.

This is a tricky issue to fix. SHM’s Practice Analysis Committee, which manages the survey, is aware of the issue and may make future adjustments to account for it. The best method might be to convert total staffing by physicians and NP/PAs into physician-equivalent FTEs (I described one method for doing this in my August 2009 column titled “Volume Variables”) or some other method that clearly accounts for both physician and NP/PA staffing levels. Other alternatives would be to divide the annual support by the number of billed encounters or some other measure of “work output” or to report percent of the total practice revenue that comes from hospital support versus professional fee collections and other sources.

Why Allocation of NP/PA Costs and FTEs Matter

Another way to think of this issue is that including NP/PA costs but not their work (FTEs) in the financial support per FTE figure overlooks the important work they can do for a hospitalist practice. And it can lead one to conclude hospitals’ costs per clinician FTE are rising faster than is actually the case.

This is only one of the tricky issues in accurately understanding hospitalist overhead and costs to the hospital they serve. TH

I visited during a hot Florida summer in the mid 1990s and could readily see that the practice was great in most respects. The large multispecialty group had recruited talented hospitalists and had put in place effective operational practices. All seemed to be going well, but inappropriate overhead allocation was undermining the success of their efforts.

The multispecialty group employing the hospitalists used the same formula to allocate overhead to the hospitalists that was in place for other specialties. And compensation was essentially each doctor’s collections minus overhead, leaving the hospitalists with annual compensation much lower than they could reasonably expect. With the group deducting from hospitalist collections the same overhead expenses charged to other specialties, including a share of outpatient buildings, staff, and supplies, the hospitalists were paying a lot for services they weren’t using. This group corrected the errors but not until some talented doctors had resigned because of the compensation formula.

This was a common mistake made by multispecialty groups that employed hospitalists years ago. Today, nearly all such groups assess an appropriately smaller portion of overhead to hospitalists than office-based doctors.

Typical Hospitalist Overhead

It is still tricky to correctly assess and allocate hospitalist overhead. This meaningfully influences the apparent total cost of the program and hence the amount of support paid by the hospital or other entity. (This support is often referred to as a “subsidy,” though I don’t care for that term because of its negative connotation.)

For example, costs for billing and collections services, malpractice insurance, temporary staffing (locums), and an overhead allocation that pays for things like the salaries of medical group administrators and clerical staff may or may not be attributed to the hospitalist budget or “cost center.” This is one of several factors that make it awfully tricky to compare the total costs and/or hospital financial support between different hospitalist groups.

SHM’s State of Hospital Medicine report includes detailed instructions regarding which expenses the survey respondents should include as overhead costs, but I think it’s safe to assume that not all responses are fully compliant. I’m confident there is a meaningful amount of “noise” in these figures. Numbers like the median financial support per FTE hospitalist per year ($156,063 in the 2014 report) should only be used as a guideline and not a precise number that might apply in your setting. My reasoning is that the collections rate and compensation amount can vary tremendously from one practice to another and will typically have a far larger influence on the amount of financial support provided by the hospital than which expenses are or aren’t included as overhead. But I am confining this discussion to the latter.

APC Costs: One Factor Driving Increased Support

SHM has been surveying the financial support per physician FTE for about 15 years, and it has shown a steady increase. It was about $60,000 per FTE annually when first surveyed in the late 1990s; it has gone up every survey since. The best explanation for this seems to an increase in hospitalist compensation while production and revenue have remained relatively flat.

There likely are many other factors in play. One important one is physician assistant and nurse practitioner costs. The survey divides the total annual support provided to the whole hospitalist practice by the total number of physician FTEs. NPs and PAs are becoming more common in hospitalist groups; 65% of groups included them in 2014, up from 54% in 2012. Yet the cost of employing them, primarily salary and benefits, appears in the numerator but not the denominator of the support per physician FTE figure.

This means a group that adds NP/PA staffing, which typically requires an accompanying increase in hospital financial support, while maintaining the same number of physician FTEs will show an increase in hospital support per physician FTE. But this fails to capture that the practice’s work product (i.e., patients seen) has increased as a result of increasing its clinical staff.

This is a tricky issue to fix. SHM’s Practice Analysis Committee, which manages the survey, is aware of the issue and may make future adjustments to account for it. The best method might be to convert total staffing by physicians and NP/PAs into physician-equivalent FTEs (I described one method for doing this in my August 2009 column titled “Volume Variables”) or some other method that clearly accounts for both physician and NP/PA staffing levels. Other alternatives would be to divide the annual support by the number of billed encounters or some other measure of “work output” or to report percent of the total practice revenue that comes from hospital support versus professional fee collections and other sources.

Why Allocation of NP/PA Costs and FTEs Matter

Another way to think of this issue is that including NP/PA costs but not their work (FTEs) in the financial support per FTE figure overlooks the important work they can do for a hospitalist practice. And it can lead one to conclude hospitals’ costs per clinician FTE are rising faster than is actually the case.

This is only one of the tricky issues in accurately understanding hospitalist overhead and costs to the hospital they serve. TH

Donated blood

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has approved the use of a new assay to screen donated blood for the Zika virus.

The Procleix Zika Virus Assay is approved for use under an investigational new drug study protocol.

Blood banks can use the test to screen donated blood for the Zika virus in potentially endemic areas of the southern US. Testing may be extended to other areas of the US if the Zika virus continues to spread.

The Procleix Zika Virus Assay, which was co-developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology blood screening platform. The system has received regulatory approvals in countries around the world and is currently in development for the US market.

“The American Red Cross is pleased to participate in the Procleix Zika Virus Assay investigational study, which will allow us to begin blood donor testing for Zika virus early this summer in areas most likely to have local mosquito transmission of the virus,” said Susan Stramer, PhD, vice-president of scientific affairs at the American Red Cross.

The FDA previously authorized use of another test, the cobas® Zika test (developed by Roche), to screen blood donations for Zika virus. The cobas Zika test can be used under an investigational new drug study protocol for screening donated blood in areas with active, mosquito-borne transmission of the Zika virus.

Donated blood

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has approved the use of a new assay to screen donated blood for the Zika virus.

The Procleix Zika Virus Assay is approved for use under an investigational new drug study protocol.

Blood banks can use the test to screen donated blood for the Zika virus in potentially endemic areas of the southern US. Testing may be extended to other areas of the US if the Zika virus continues to spread.

The Procleix Zika Virus Assay, which was co-developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology blood screening platform. The system has received regulatory approvals in countries around the world and is currently in development for the US market.

“The American Red Cross is pleased to participate in the Procleix Zika Virus Assay investigational study, which will allow us to begin blood donor testing for Zika virus early this summer in areas most likely to have local mosquito transmission of the virus,” said Susan Stramer, PhD, vice-president of scientific affairs at the American Red Cross.

The FDA previously authorized use of another test, the cobas® Zika test (developed by Roche), to screen blood donations for Zika virus. The cobas Zika test can be used under an investigational new drug study protocol for screening donated blood in areas with active, mosquito-borne transmission of the Zika virus.

Donated blood

Photo courtesy of UAB Hospital

The US Food and Drug Administration (FDA) has approved the use of a new assay to screen donated blood for the Zika virus.

The Procleix Zika Virus Assay is approved for use under an investigational new drug study protocol.

Blood banks can use the test to screen donated blood for the Zika virus in potentially endemic areas of the southern US. Testing may be extended to other areas of the US if the Zika virus continues to spread.

The Procleix Zika Virus Assay, which was co-developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology blood screening platform. The system has received regulatory approvals in countries around the world and is currently in development for the US market.

“The American Red Cross is pleased to participate in the Procleix Zika Virus Assay investigational study, which will allow us to begin blood donor testing for Zika virus early this summer in areas most likely to have local mosquito transmission of the virus,” said Susan Stramer, PhD, vice-president of scientific affairs at the American Red Cross.

The FDA previously authorized use of another test, the cobas® Zika test (developed by Roche), to screen blood donations for Zika virus. The cobas Zika test can be used under an investigational new drug study protocol for screening donated blood in areas with active, mosquito-borne transmission of the Zika virus.

AML cells

Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.

Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.

“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.

“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”

Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.

The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.

“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.

“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”

The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.

The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.

They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.

The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.

For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.

AML cells

Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.

Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.

“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.

“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”

Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.

The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.

“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.

“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”

The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.

The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.

They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.

The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.

For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.

AML cells

Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.

Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.

“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.

“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”

Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.

The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.

“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.

“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”

The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.

The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.

They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.

The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.

For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.

A sickled red blood cell

and a normal one

Image by Betty Pace

Results of a small study suggest that long-term opioid treatment may not be the best option for pain management in adults with sickle cell disease (SCD).

The study showed that patients who received opioids long-term often fared worse in measures of pain, fatigue, and curtailed daily activities than patients who were not on long-term opioids.

Researchers reported these findings in the American Journal of Preventive Medicine.

“We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn’t effective,” said study author C. Patrick Carroll, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Too little is known about the effects of long-term opioid management of chronic pain.”

For this study, Dr Carroll and his colleagues enrolled 83 SCD patients—57 women and 26 men. All were 18 and older, and their average age was 39.

Twenty-nine of the patients had been prescribed daily, long-acting opioids to manage their pain. The remaining 54 patients weren’t on long-term opioids.

The patients filled out daily electronic pain diaries for 90 days. Self-reported levels of pain, physical activity, fatigue, and pain-related daily activity interference were recorded, along with self-reported levels of pain relief and medication satisfaction on a scale of 0 to 100.

Crises, pain, and fatigue

The proportion of days in vaso-occlusive crisis was significantly higher for patients who were on long-term opioid therapy than for those who were not—29% and 11.9%, respectively (P<0.01).

Patients on long-term opioids also reported significantly higher levels of crisis pain—60.6 and 41.0, respectively (P<0.001)—and non-crisis pain—34.5 and 10.3, respectively (P<0.001).

Patients on long-term opioid therapy had higher levels of pain-related activity interference, both on non-crisis days—24.9 and 7.4, respectively (P<0.001)—and crisis days—56.7 and 37.7, respectively (P<0.01).

And patients on long-term opioid therapy had higher levels of fatigue on non-crisis days—49.7 and 27.0, respectively (P<0.001)—and crisis days—66.1 and 53.0, respectively (P<0.05).

Central sensitization

The researchers also performed some standard measures of pain processing on the test subjects, which measured and averaged variables such as how intensely participants experienced unpleasant heat and pressure.

The team was particularly interested in the phenomenon of central sensitization, in which the central nervous system amplifies painful sensations.

Central sensitization may be one way that opioids can increase pain sensitivity, and it also may play a role in how SCD causes chronic pain, Dr Carroll said.

For example, one such measure of central sensitization uses repeated pokes from a mildly painful stimulus in succession. In people who have this hypersensitization, each poke is perceived as more intense than the last because the nervous system becomes progressively more sensitive to the pain.

Combining the data from several measures of central sensitization, the researchers used a scoring system that sets a normal measurement at 0 and rates how abnormal something is by how far the values move away from 0. They calculated a central sensitization index for patients on long-term opioids and those not taking them.

Overall, patients on long-term opioid therapy showed higher levels of central sensitization, with an index of 0.34, than those who were not on opioids, with an index of -0.10.

In patients who were not on long-term opioid therapy, the level of central sensitization correlated with the level of non-crisis pain. However, in patients who were taking long-term opioid therapy and also had higher levels of central sensitization and clinical pain, the correlation essentially vanished.

Dr Carroll said this was surprising and suggests the mechanisms of pain in SCD patients on long-term opioid therapy may be different from patients who don’t take daily opioids for pain.

Dr Carroll cautioned that this work is preliminary and should not lead to the discontinuation of long-term opioid therapy in SCD patients.

“We need to better understand how long-term opioid use affects pain sensitization and determine if certain people are more sensitive to these effects so we can prescribe the best treatment option for each individual patient,” Dr Carroll said. “We also need to learn more about how sickle cell disease may sensitize the nervous system.”

A sickled red blood cell

and a normal one

Image by Betty Pace

Results of a small study suggest that long-term opioid treatment may not be the best option for pain management in adults with sickle cell disease (SCD).

The study showed that patients who received opioids long-term often fared worse in measures of pain, fatigue, and curtailed daily activities than patients who were not on long-term opioids.

Researchers reported these findings in the American Journal of Preventive Medicine.

“We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn’t effective,” said study author C. Patrick Carroll, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Too little is known about the effects of long-term opioid management of chronic pain.”

For this study, Dr Carroll and his colleagues enrolled 83 SCD patients—57 women and 26 men. All were 18 and older, and their average age was 39.

Twenty-nine of the patients had been prescribed daily, long-acting opioids to manage their pain. The remaining 54 patients weren’t on long-term opioids.

The patients filled out daily electronic pain diaries for 90 days. Self-reported levels of pain, physical activity, fatigue, and pain-related daily activity interference were recorded, along with self-reported levels of pain relief and medication satisfaction on a scale of 0 to 100.

Crises, pain, and fatigue

The proportion of days in vaso-occlusive crisis was significantly higher for patients who were on long-term opioid therapy than for those who were not—29% and 11.9%, respectively (P<0.01).

Patients on long-term opioids also reported significantly higher levels of crisis pain—60.6 and 41.0, respectively (P<0.001)—and non-crisis pain—34.5 and 10.3, respectively (P<0.001).

Patients on long-term opioid therapy had higher levels of pain-related activity interference, both on non-crisis days—24.9 and 7.4, respectively (P<0.001)—and crisis days—56.7 and 37.7, respectively (P<0.01).

And patients on long-term opioid therapy had higher levels of fatigue on non-crisis days—49.7 and 27.0, respectively (P<0.001)—and crisis days—66.1 and 53.0, respectively (P<0.05).

Central sensitization

The researchers also performed some standard measures of pain processing on the test subjects, which measured and averaged variables such as how intensely participants experienced unpleasant heat and pressure.

The team was particularly interested in the phenomenon of central sensitization, in which the central nervous system amplifies painful sensations.

Central sensitization may be one way that opioids can increase pain sensitivity, and it also may play a role in how SCD causes chronic pain, Dr Carroll said.

For example, one such measure of central sensitization uses repeated pokes from a mildly painful stimulus in succession. In people who have this hypersensitization, each poke is perceived as more intense than the last because the nervous system becomes progressively more sensitive to the pain.

Combining the data from several measures of central sensitization, the researchers used a scoring system that sets a normal measurement at 0 and rates how abnormal something is by how far the values move away from 0. They calculated a central sensitization index for patients on long-term opioids and those not taking them.

Overall, patients on long-term opioid therapy showed higher levels of central sensitization, with an index of 0.34, than those who were not on opioids, with an index of -0.10.

In patients who were not on long-term opioid therapy, the level of central sensitization correlated with the level of non-crisis pain. However, in patients who were taking long-term opioid therapy and also had higher levels of central sensitization and clinical pain, the correlation essentially vanished.

Dr Carroll said this was surprising and suggests the mechanisms of pain in SCD patients on long-term opioid therapy may be different from patients who don’t take daily opioids for pain.

Dr Carroll cautioned that this work is preliminary and should not lead to the discontinuation of long-term opioid therapy in SCD patients.

“We need to better understand how long-term opioid use affects pain sensitization and determine if certain people are more sensitive to these effects so we can prescribe the best treatment option for each individual patient,” Dr Carroll said. “We also need to learn more about how sickle cell disease may sensitize the nervous system.”

A sickled red blood cell

and a normal one

Image by Betty Pace

Results of a small study suggest that long-term opioid treatment may not be the best option for pain management in adults with sickle cell disease (SCD).

The study showed that patients who received opioids long-term often fared worse in measures of pain, fatigue, and curtailed daily activities than patients who were not on long-term opioids.

Researchers reported these findings in the American Journal of Preventive Medicine.

“We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn’t effective,” said study author C. Patrick Carroll, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Too little is known about the effects of long-term opioid management of chronic pain.”

For this study, Dr Carroll and his colleagues enrolled 83 SCD patients—57 women and 26 men. All were 18 and older, and their average age was 39.

Twenty-nine of the patients had been prescribed daily, long-acting opioids to manage their pain. The remaining 54 patients weren’t on long-term opioids.

The patients filled out daily electronic pain diaries for 90 days. Self-reported levels of pain, physical activity, fatigue, and pain-related daily activity interference were recorded, along with self-reported levels of pain relief and medication satisfaction on a scale of 0 to 100.

Crises, pain, and fatigue

The proportion of days in vaso-occlusive crisis was significantly higher for patients who were on long-term opioid therapy than for those who were not—29% and 11.9%, respectively (P<0.01).

Patients on long-term opioids also reported significantly higher levels of crisis pain—60.6 and 41.0, respectively (P<0.001)—and non-crisis pain—34.5 and 10.3, respectively (P<0.001).

Patients on long-term opioid therapy had higher levels of pain-related activity interference, both on non-crisis days—24.9 and 7.4, respectively (P<0.001)—and crisis days—56.7 and 37.7, respectively (P<0.01).

And patients on long-term opioid therapy had higher levels of fatigue on non-crisis days—49.7 and 27.0, respectively (P<0.001)—and crisis days—66.1 and 53.0, respectively (P<0.05).

Central sensitization

The researchers also performed some standard measures of pain processing on the test subjects, which measured and averaged variables such as how intensely participants experienced unpleasant heat and pressure.

The team was particularly interested in the phenomenon of central sensitization, in which the central nervous system amplifies painful sensations.

Central sensitization may be one way that opioids can increase pain sensitivity, and it also may play a role in how SCD causes chronic pain, Dr Carroll said.

For example, one such measure of central sensitization uses repeated pokes from a mildly painful stimulus in succession. In people who have this hypersensitization, each poke is perceived as more intense than the last because the nervous system becomes progressively more sensitive to the pain.

Combining the data from several measures of central sensitization, the researchers used a scoring system that sets a normal measurement at 0 and rates how abnormal something is by how far the values move away from 0. They calculated a central sensitization index for patients on long-term opioids and those not taking them.

Overall, patients on long-term opioid therapy showed higher levels of central sensitization, with an index of 0.34, than those who were not on opioids, with an index of -0.10.

In patients who were not on long-term opioid therapy, the level of central sensitization correlated with the level of non-crisis pain. However, in patients who were taking long-term opioid therapy and also had higher levels of central sensitization and clinical pain, the correlation essentially vanished.

Dr Carroll said this was surprising and suggests the mechanisms of pain in SCD patients on long-term opioid therapy may be different from patients who don’t take daily opioids for pain.

Dr Carroll cautioned that this work is preliminary and should not lead to the discontinuation of long-term opioid therapy in SCD patients.

“We need to better understand how long-term opioid use affects pain sensitization and determine if certain people are more sensitive to these effects so we can prescribe the best treatment option for each individual patient,” Dr Carroll said. “We also need to learn more about how sickle cell disease may sensitize the nervous system.”