Pharmacology

Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.

The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.

Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.

Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.

Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.

Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.

Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.

The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.

Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.

Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.

Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.

Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.

Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.

The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.

Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.

Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.

Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.

Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.

Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.

In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.

The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).

Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.

Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.

When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.

This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.

Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.

Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.

In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.

The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).

Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.

Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.

When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.

This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.

Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.

Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.

In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.

The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).

Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.

Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.

When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.

This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.

Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.

Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.

The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A_1c; and vitamins B12, D, and folic acid levels.

The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.

The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.

Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A_1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).

The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.

Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.

Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.

Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.

Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.

The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A_1c; and vitamins B12, D, and folic acid levels.

The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.

The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.

Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A_1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).

The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.

Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.

Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.

Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.

Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.

The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A_1c; and vitamins B12, D, and folic acid levels.

The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.

The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.

Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A_1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).

The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.

Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.

Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.

Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.

Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?

Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.

However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.

Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.

The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.

Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.

Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?

Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.

However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.

Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.

The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.

Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.

Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?

Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.

However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.

Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.

The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.

Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.

Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.

Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure  (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.

The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.

The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.

At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).

However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only  –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.

Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.

The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.

However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.

Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.

Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.

Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure  (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.

The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.

The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.

At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).

However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only  –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.

Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.

The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.

However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.

Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.

Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.

Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure  (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.

The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.

The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.

At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).

However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only  –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.

Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.

The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.

However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.

Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.

Is there a link between incretin-based diabetes drugs and pancreatitis? In 2008, the FDA issued a warning, based on its review of 30 postmarketing reports of acute pancreatitis in patients taking exenatide. In 2013, the FDA updated its warning about safety risks to include a preliminary caution about a potential increase in the risk of precancerous cellular changes, although it had not yet reached any conclusions.

Because there are still concerns about safety, but evidence to support a causal relationship is weak, an international team of researchers reviewed randomized and nonrandomized studies in hopes of producing a more rigorous assessment of the risk of pancreatitis. They analyzed data from 60 studies: 55 randomized controlled trials (all industry funded), ranging from 12 to 234 weeks, and involving 33,350 patients; and 5 observational studies with 320,289 patients.

Of the randomized trials, 27 explicitly stated that no events of pancreatitis occurred during the study. Eight studies mentioned pancreatic enzymes, but none reported usable data. Overall, 37 events of pancreatitis occurred in 33,227 patients who used ≥ 1 drug. The risk did not differ by the type of incretin (GLP-1 agonists vs DPP-4 inhibitors).

Four of the 5 observational studies—3 retrospective cohort studies and 1 case-control study—found no evidence to suggest a greater risk of pancreatitis. The fifth, a case-control study of 1,269 patients, reported a greater risk of admission for acute pancreatitis for patients using sitagliptin or exenatide.

However, the risk of pancreatitis was low, the researchers conclude. In randomized trials, similar numbers of patients developed pancreatitis (0.11% in both those taking incretins and in control patients). In cohort studies, the risk of acute pancreatitis was somewhat higher (0.47%), potentially because of a higher incidence of risk factors, such as gallstones and longer follow-up, the researchers say.

These results should be interpreted cautiously, the researchers say. For one, many of the randomized trials had small sample sizes and relatively short follow-up. Moreover, the trials (mostly phase III studies) often recruited patients who had fewer comorbidities than had patients in real-world clinical practice. And finally, because pancreatitis is rare in general, the confidence intervals around relative effects are wide, the researchers say, leaving the possibility of an undetected increase in risk. They note that the trials may have failed to identify patients with subclinical, minimally symptomatic pancreatitis—the increases in pancreatic enzymes may have been signals of something they weren’t able to fully investigate for lack of complete data.

By contrast, the observational studies had larger samples but were limited, in part, because they often used the ICD-9 coding system, which meant diagnosis criteria varied.

On a further note of caution, the researchers cite the FDA adverse drug event system, which has documented 2,327 spontaneously reported cases of pancreatitis in patients taking exenatide, 888 cases in those taking liraglutide, 718 cases in those taking sitagliptin, and 125 in those taking saxagliptin. The number of cases of pancreatitis seemed larger, the researchers say, in patients taking incretins than in those taking other antidiabetic drugs.

In addition to the lack of definitive evidence to support an increased risk of pancreatitis, the researchers note that incretins are not superior to less expensive and already widely used antidiabetic drugs, such as metformin. The benefits of incretins might be outweighed by the uncertainties.

Source
Li L, Shen J, Bala MM, et al. BMJ. 2014;348:g2366.
doi: 10.1136/bmj.g2366.

Is there a link between incretin-based diabetes drugs and pancreatitis? In 2008, the FDA issued a warning, based on its review of 30 postmarketing reports of acute pancreatitis in patients taking exenatide. In 2013, the FDA updated its warning about safety risks to include a preliminary caution about a potential increase in the risk of precancerous cellular changes, although it had not yet reached any conclusions.

Because there are still concerns about safety, but evidence to support a causal relationship is weak, an international team of researchers reviewed randomized and nonrandomized studies in hopes of producing a more rigorous assessment of the risk of pancreatitis. They analyzed data from 60 studies: 55 randomized controlled trials (all industry funded), ranging from 12 to 234 weeks, and involving 33,350 patients; and 5 observational studies with 320,289 patients.

Of the randomized trials, 27 explicitly stated that no events of pancreatitis occurred during the study. Eight studies mentioned pancreatic enzymes, but none reported usable data. Overall, 37 events of pancreatitis occurred in 33,227 patients who used ≥ 1 drug. The risk did not differ by the type of incretin (GLP-1 agonists vs DPP-4 inhibitors).

Four of the 5 observational studies—3 retrospective cohort studies and 1 case-control study—found no evidence to suggest a greater risk of pancreatitis. The fifth, a case-control study of 1,269 patients, reported a greater risk of admission for acute pancreatitis for patients using sitagliptin or exenatide.

However, the risk of pancreatitis was low, the researchers conclude. In randomized trials, similar numbers of patients developed pancreatitis (0.11% in both those taking incretins and in control patients). In cohort studies, the risk of acute pancreatitis was somewhat higher (0.47%), potentially because of a higher incidence of risk factors, such as gallstones and longer follow-up, the researchers say.

These results should be interpreted cautiously, the researchers say. For one, many of the randomized trials had small sample sizes and relatively short follow-up. Moreover, the trials (mostly phase III studies) often recruited patients who had fewer comorbidities than had patients in real-world clinical practice. And finally, because pancreatitis is rare in general, the confidence intervals around relative effects are wide, the researchers say, leaving the possibility of an undetected increase in risk. They note that the trials may have failed to identify patients with subclinical, minimally symptomatic pancreatitis—the increases in pancreatic enzymes may have been signals of something they weren’t able to fully investigate for lack of complete data.

By contrast, the observational studies had larger samples but were limited, in part, because they often used the ICD-9 coding system, which meant diagnosis criteria varied.

On a further note of caution, the researchers cite the FDA adverse drug event system, which has documented 2,327 spontaneously reported cases of pancreatitis in patients taking exenatide, 888 cases in those taking liraglutide, 718 cases in those taking sitagliptin, and 125 in those taking saxagliptin. The number of cases of pancreatitis seemed larger, the researchers say, in patients taking incretins than in those taking other antidiabetic drugs.

In addition to the lack of definitive evidence to support an increased risk of pancreatitis, the researchers note that incretins are not superior to less expensive and already widely used antidiabetic drugs, such as metformin. The benefits of incretins might be outweighed by the uncertainties.

Source
Li L, Shen J, Bala MM, et al. BMJ. 2014;348:g2366.
doi: 10.1136/bmj.g2366.

Is there a link between incretin-based diabetes drugs and pancreatitis? In 2008, the FDA issued a warning, based on its review of 30 postmarketing reports of acute pancreatitis in patients taking exenatide. In 2013, the FDA updated its warning about safety risks to include a preliminary caution about a potential increase in the risk of precancerous cellular changes, although it had not yet reached any conclusions.

Because there are still concerns about safety, but evidence to support a causal relationship is weak, an international team of researchers reviewed randomized and nonrandomized studies in hopes of producing a more rigorous assessment of the risk of pancreatitis. They analyzed data from 60 studies: 55 randomized controlled trials (all industry funded), ranging from 12 to 234 weeks, and involving 33,350 patients; and 5 observational studies with 320,289 patients.

Of the randomized trials, 27 explicitly stated that no events of pancreatitis occurred during the study. Eight studies mentioned pancreatic enzymes, but none reported usable data. Overall, 37 events of pancreatitis occurred in 33,227 patients who used ≥ 1 drug. The risk did not differ by the type of incretin (GLP-1 agonists vs DPP-4 inhibitors).

Four of the 5 observational studies—3 retrospective cohort studies and 1 case-control study—found no evidence to suggest a greater risk of pancreatitis. The fifth, a case-control study of 1,269 patients, reported a greater risk of admission for acute pancreatitis for patients using sitagliptin or exenatide.

However, the risk of pancreatitis was low, the researchers conclude. In randomized trials, similar numbers of patients developed pancreatitis (0.11% in both those taking incretins and in control patients). In cohort studies, the risk of acute pancreatitis was somewhat higher (0.47%), potentially because of a higher incidence of risk factors, such as gallstones and longer follow-up, the researchers say.

These results should be interpreted cautiously, the researchers say. For one, many of the randomized trials had small sample sizes and relatively short follow-up. Moreover, the trials (mostly phase III studies) often recruited patients who had fewer comorbidities than had patients in real-world clinical practice. And finally, because pancreatitis is rare in general, the confidence intervals around relative effects are wide, the researchers say, leaving the possibility of an undetected increase in risk. They note that the trials may have failed to identify patients with subclinical, minimally symptomatic pancreatitis—the increases in pancreatic enzymes may have been signals of something they weren’t able to fully investigate for lack of complete data.

By contrast, the observational studies had larger samples but were limited, in part, because they often used the ICD-9 coding system, which meant diagnosis criteria varied.

On a further note of caution, the researchers cite the FDA adverse drug event system, which has documented 2,327 spontaneously reported cases of pancreatitis in patients taking exenatide, 888 cases in those taking liraglutide, 718 cases in those taking sitagliptin, and 125 in those taking saxagliptin. The number of cases of pancreatitis seemed larger, the researchers say, in patients taking incretins than in those taking other antidiabetic drugs.

In addition to the lack of definitive evidence to support an increased risk of pancreatitis, the researchers note that incretins are not superior to less expensive and already widely used antidiabetic drugs, such as metformin. The benefits of incretins might be outweighed by the uncertainties.

Source
Li L, Shen J, Bala MM, et al. BMJ. 2014;348:g2366.
doi: 10.1136/bmj.g2366.

Stress-induced cardiomyopathy (SIC) is usually triggered by intense emotional or physical stress, although it can also be due to invasive diagnostic procedures or surgery. Clinicians from the National Research Council Institute of Clinical Physiology and Scuola Superiore, Sant’Anna, both in Pisa; and Ospedale della Bassa val di Cecina in Cecina; all in Italy, suggest SIC could also be a delayed effect of withdrawal from long-term antidepressant use.

The authors reported on a 65-year-old woman who developed SIC 2 weeks after being weaned from a long-lasting antidepressant treatment. The SIC recurred a week later.

The patient had been admitted to an emergency department (ED) after repeated fainting episodes during and immediately after “light aerobic exercise” in a gym. In the ED, she reported weakness and mild dyspnea. She had a regular heartbeat, mild hypotension, and no sign of acute heart failure. An ECG showed normal sinus rhythm. She was postmenopausal, had never smoked, and had no history of arterial hypertension, hypercholesterolemia, diabetes, or cardiac or circulatory diseases. In fact, 3 months before the SIC episode, she was given a stress echocardiogram before starting a physical exercise program, which excluded ischemic heart disease.

She reported having severe depression for 25 years and had been treated for the past 8 years with a combination of antidepressants, both tricyclic and selective serotonin reuptake inhibitors (SSRIs), neuroleptics, anti-epileptics, and benzodiazepines. She was prescribed imipramine 25 mg bid, amitriptyline 10 mg uid, paroxuid, gabape tin 300 mg tid, trazo-done 12 mg uid, and delorazepam 0.25 mg uid.

This treatment had put her depression into remission for 2 years. Thus, her psychiatrist had admitted her to the hospital, planning to discontinue most of the drugs. The paroxetine was reduced gradually over 3 days, gabapentin was held at the same dose, and the other drugs were stopped. Diazepam and metadoxine were continuously infused intravenously during the first 3 days, then hydroxyzine 25 mg uid was started. The patient tolerated this procedure well and was discharged in good health. Two weeks later, she experienced her first SIC.

The case has several unusual features, the authors say: Both episodes were preceded by only a mild stressor; the SIC recurred, again without any apparent triggering event, in a different part of the heart; and the period between stopping the drug and the onset of the SIC was unusually long (symptoms of SSRI discontinuation usually appear within 7 days).

The authors note that acute withdrawal syndrome from alcohol or opiates has been known to trigger SIC and that rapid interruption of chronic SSRI treatment is known to induce a withdrawal syndrome, characterized by both psychological and somatic symptoms. They believe their case report provides some clues suggesting a link between SSRI withdrawal and SIC. In particular, they point to paroxetine. Due to its rapid clearance, paroxetine is the SSRI most frequently associated with withdrawal syndrome, they say. Moreover, their patient’s symptoms corresponded closely with the most frequent manifestations of SSRI withdrawal syndrome (dizziness and nausea) at the SIC onset. Her delayed reaction, though, may have been due, they say, to the extraordinarily long duration of continuous antidepressant treatment (8 years). Such long treatment may have considerable neuroplastic effects on the hippocampus—abruptly discontinuing the drugs could be a shock that induces “unpredictably delayed manifestations.”

Source
Marabotti C, Venturini E, Marobotti A, Pingitore A. Heart Lung. 2014;43(3):225-230.
doi: 10.1016/j.hrtlng.2014.03.003.

Stress-induced cardiomyopathy (SIC) is usually triggered by intense emotional or physical stress, although it can also be due to invasive diagnostic procedures or surgery. Clinicians from the National Research Council Institute of Clinical Physiology and Scuola Superiore, Sant’Anna, both in Pisa; and Ospedale della Bassa val di Cecina in Cecina; all in Italy, suggest SIC could also be a delayed effect of withdrawal from long-term antidepressant use.

The authors reported on a 65-year-old woman who developed SIC 2 weeks after being weaned from a long-lasting antidepressant treatment. The SIC recurred a week later.

The patient had been admitted to an emergency department (ED) after repeated fainting episodes during and immediately after “light aerobic exercise” in a gym. In the ED, she reported weakness and mild dyspnea. She had a regular heartbeat, mild hypotension, and no sign of acute heart failure. An ECG showed normal sinus rhythm. She was postmenopausal, had never smoked, and had no history of arterial hypertension, hypercholesterolemia, diabetes, or cardiac or circulatory diseases. In fact, 3 months before the SIC episode, she was given a stress echocardiogram before starting a physical exercise program, which excluded ischemic heart disease.

She reported having severe depression for 25 years and had been treated for the past 8 years with a combination of antidepressants, both tricyclic and selective serotonin reuptake inhibitors (SSRIs), neuroleptics, anti-epileptics, and benzodiazepines. She was prescribed imipramine 25 mg bid, amitriptyline 10 mg uid, paroxuid, gabape tin 300 mg tid, trazo-done 12 mg uid, and delorazepam 0.25 mg uid.

This treatment had put her depression into remission for 2 years. Thus, her psychiatrist had admitted her to the hospital, planning to discontinue most of the drugs. The paroxetine was reduced gradually over 3 days, gabapentin was held at the same dose, and the other drugs were stopped. Diazepam and metadoxine were continuously infused intravenously during the first 3 days, then hydroxyzine 25 mg uid was started. The patient tolerated this procedure well and was discharged in good health. Two weeks later, she experienced her first SIC.

The case has several unusual features, the authors say: Both episodes were preceded by only a mild stressor; the SIC recurred, again without any apparent triggering event, in a different part of the heart; and the period between stopping the drug and the onset of the SIC was unusually long (symptoms of SSRI discontinuation usually appear within 7 days).

The authors note that acute withdrawal syndrome from alcohol or opiates has been known to trigger SIC and that rapid interruption of chronic SSRI treatment is known to induce a withdrawal syndrome, characterized by both psychological and somatic symptoms. They believe their case report provides some clues suggesting a link between SSRI withdrawal and SIC. In particular, they point to paroxetine. Due to its rapid clearance, paroxetine is the SSRI most frequently associated with withdrawal syndrome, they say. Moreover, their patient’s symptoms corresponded closely with the most frequent manifestations of SSRI withdrawal syndrome (dizziness and nausea) at the SIC onset. Her delayed reaction, though, may have been due, they say, to the extraordinarily long duration of continuous antidepressant treatment (8 years). Such long treatment may have considerable neuroplastic effects on the hippocampus—abruptly discontinuing the drugs could be a shock that induces “unpredictably delayed manifestations.”

Source
Marabotti C, Venturini E, Marobotti A, Pingitore A. Heart Lung. 2014;43(3):225-230.
doi: 10.1016/j.hrtlng.2014.03.003.

Stress-induced cardiomyopathy (SIC) is usually triggered by intense emotional or physical stress, although it can also be due to invasive diagnostic procedures or surgery. Clinicians from the National Research Council Institute of Clinical Physiology and Scuola Superiore, Sant’Anna, both in Pisa; and Ospedale della Bassa val di Cecina in Cecina; all in Italy, suggest SIC could also be a delayed effect of withdrawal from long-term antidepressant use.

The authors reported on a 65-year-old woman who developed SIC 2 weeks after being weaned from a long-lasting antidepressant treatment. The SIC recurred a week later.

The patient had been admitted to an emergency department (ED) after repeated fainting episodes during and immediately after “light aerobic exercise” in a gym. In the ED, she reported weakness and mild dyspnea. She had a regular heartbeat, mild hypotension, and no sign of acute heart failure. An ECG showed normal sinus rhythm. She was postmenopausal, had never smoked, and had no history of arterial hypertension, hypercholesterolemia, diabetes, or cardiac or circulatory diseases. In fact, 3 months before the SIC episode, she was given a stress echocardiogram before starting a physical exercise program, which excluded ischemic heart disease.

She reported having severe depression for 25 years and had been treated for the past 8 years with a combination of antidepressants, both tricyclic and selective serotonin reuptake inhibitors (SSRIs), neuroleptics, anti-epileptics, and benzodiazepines. She was prescribed imipramine 25 mg bid, amitriptyline 10 mg uid, paroxuid, gabape tin 300 mg tid, trazo-done 12 mg uid, and delorazepam 0.25 mg uid.

This treatment had put her depression into remission for 2 years. Thus, her psychiatrist had admitted her to the hospital, planning to discontinue most of the drugs. The paroxetine was reduced gradually over 3 days, gabapentin was held at the same dose, and the other drugs were stopped. Diazepam and metadoxine were continuously infused intravenously during the first 3 days, then hydroxyzine 25 mg uid was started. The patient tolerated this procedure well and was discharged in good health. Two weeks later, she experienced her first SIC.

The case has several unusual features, the authors say: Both episodes were preceded by only a mild stressor; the SIC recurred, again without any apparent triggering event, in a different part of the heart; and the period between stopping the drug and the onset of the SIC was unusually long (symptoms of SSRI discontinuation usually appear within 7 days).

The authors note that acute withdrawal syndrome from alcohol or opiates has been known to trigger SIC and that rapid interruption of chronic SSRI treatment is known to induce a withdrawal syndrome, characterized by both psychological and somatic symptoms. They believe their case report provides some clues suggesting a link between SSRI withdrawal and SIC. In particular, they point to paroxetine. Due to its rapid clearance, paroxetine is the SSRI most frequently associated with withdrawal syndrome, they say. Moreover, their patient’s symptoms corresponded closely with the most frequent manifestations of SSRI withdrawal syndrome (dizziness and nausea) at the SIC onset. Her delayed reaction, though, may have been due, they say, to the extraordinarily long duration of continuous antidepressant treatment (8 years). Such long treatment may have considerable neuroplastic effects on the hippocampus—abruptly discontinuing the drugs could be a shock that induces “unpredictably delayed manifestations.”

Source
Marabotti C, Venturini E, Marobotti A, Pingitore A. Heart Lung. 2014;43(3):225-230.
doi: 10.1016/j.hrtlng.2014.03.003.

In a 5-month study of 973 patients with cancer, 12% of 1,299 hospital admissions were due to drug-related problems. And of those, over half were deemed preventable, say researchers from the National Cancer Centre Singapore.

The study was conducted at the 2 main oncology wards at the largest acute tertiary hospital in Singapore. Patients were screened for any drug-related problems (DRPs) that led to the hospital admission. After screening, patients were classified as DRP, non-DRP (such as cancer progression or other diseases), unclear (lacking sufficient information for definitive classification), and exclusion (eg, patients receiving trial drugs, aged < 21 years, or not diagnosed with cancer). DRP cases were classified as minor, moderate, or severe and not preventable, probably preventable, or definitely preventable.

The most common reasons for drug-related admission were myelosuppression and suspected infection (90 patients; 59.6%). Nearly all DRPs were adverse reactions, and nearly all were moderately severe.

More important, perhaps, was the fact that 51 DRPs were classified as “probably preventable” (37.2%) and 21 as “definitely preventable” (15.3%). The researchers note that, due to the complexity of cancer treatment, DRPs—particularly adverse reactions—can happen even when preventive measures are used. Moreover, they say, when an event was classified as definitely or probably preventable, “it remains uncertain whether the event could have actually been prevented even if care had been optimal.”

Length of stay was found to be correlated with direct medical costs (P < .001) and was longer for preventable drug-related admissions than for nonpreventable drug-related admissions (P = .02). The treatment cost of admissions for preventable DRPs, the researchers found, constituted almost half the total direct medical costs.

Source
Ko Y, Gwee Y-S, Huang Y-C, Chiang J, Chan A. Clin Ther. 2014;36(4):588-592.
doi: 10.1016/j.clinthera.2014.02.014.

In a 5-month study of 973 patients with cancer, 12% of 1,299 hospital admissions were due to drug-related problems. And of those, over half were deemed preventable, say researchers from the National Cancer Centre Singapore.

The study was conducted at the 2 main oncology wards at the largest acute tertiary hospital in Singapore. Patients were screened for any drug-related problems (DRPs) that led to the hospital admission. After screening, patients were classified as DRP, non-DRP (such as cancer progression or other diseases), unclear (lacking sufficient information for definitive classification), and exclusion (eg, patients receiving trial drugs, aged < 21 years, or not diagnosed with cancer). DRP cases were classified as minor, moderate, or severe and not preventable, probably preventable, or definitely preventable.

The most common reasons for drug-related admission were myelosuppression and suspected infection (90 patients; 59.6%). Nearly all DRPs were adverse reactions, and nearly all were moderately severe.

More important, perhaps, was the fact that 51 DRPs were classified as “probably preventable” (37.2%) and 21 as “definitely preventable” (15.3%). The researchers note that, due to the complexity of cancer treatment, DRPs—particularly adverse reactions—can happen even when preventive measures are used. Moreover, they say, when an event was classified as definitely or probably preventable, “it remains uncertain whether the event could have actually been prevented even if care had been optimal.”

Length of stay was found to be correlated with direct medical costs (P < .001) and was longer for preventable drug-related admissions than for nonpreventable drug-related admissions (P = .02). The treatment cost of admissions for preventable DRPs, the researchers found, constituted almost half the total direct medical costs.

Source
Ko Y, Gwee Y-S, Huang Y-C, Chiang J, Chan A. Clin Ther. 2014;36(4):588-592.
doi: 10.1016/j.clinthera.2014.02.014.

In a 5-month study of 973 patients with cancer, 12% of 1,299 hospital admissions were due to drug-related problems. And of those, over half were deemed preventable, say researchers from the National Cancer Centre Singapore.

The study was conducted at the 2 main oncology wards at the largest acute tertiary hospital in Singapore. Patients were screened for any drug-related problems (DRPs) that led to the hospital admission. After screening, patients were classified as DRP, non-DRP (such as cancer progression or other diseases), unclear (lacking sufficient information for definitive classification), and exclusion (eg, patients receiving trial drugs, aged < 21 years, or not diagnosed with cancer). DRP cases were classified as minor, moderate, or severe and not preventable, probably preventable, or definitely preventable.

The most common reasons for drug-related admission were myelosuppression and suspected infection (90 patients; 59.6%). Nearly all DRPs were adverse reactions, and nearly all were moderately severe.

More important, perhaps, was the fact that 51 DRPs were classified as “probably preventable” (37.2%) and 21 as “definitely preventable” (15.3%). The researchers note that, due to the complexity of cancer treatment, DRPs—particularly adverse reactions—can happen even when preventive measures are used. Moreover, they say, when an event was classified as definitely or probably preventable, “it remains uncertain whether the event could have actually been prevented even if care had been optimal.”

Length of stay was found to be correlated with direct medical costs (P < .001) and was longer for preventable drug-related admissions than for nonpreventable drug-related admissions (P = .02). The treatment cost of admissions for preventable DRPs, the researchers found, constituted almost half the total direct medical costs.

Source
Ko Y, Gwee Y-S, Huang Y-C, Chiang J, Chan A. Clin Ther. 2014;36(4):588-592.
doi: 10.1016/j.clinthera.2014.02.014.