Pharmacology

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.

About 1 in 3 adults in the U.S. reported using dietary supplements and prescription medications concomitantly, say researchers from the Military Nutrition Division in Natick, Massachusetts, who analyzed data from the 2005-2008 National Health and Nutrition Examination Survey.

Prevalence of concomitant use was highest among people with osteoporosis, followed by thyroid, cancer, kidney, arthritis, diabetes, heart/vascular, respiratory, and liver conditions.

Supplement-and-medicine use was significantly more common among people with a doctor-informed medical condition (DIMC) (1 in 2 adults) vs those without (1 in 6 adults). Among people with a DIMC, cardiovascular agents were the most common drugs used with supplements. Among people without DIMC, hormones were the most common.

The number of people using both supplements and medicines has risen in recent years. More than 10 years ago, 16% to 18% of prescription medication users also took supplements, the researchers note. A study published in 2008 found the prevalence (at least among adults aged 57-85 years) was up to 52%. In the current study, 69.3% of prescription medication users aged ≥ 57 years were using supplements concomitantly.

Concomitant use was widespread across all medical conditions. Thus, the researchers say, it may not be feasible to identify individuals with a specific condition who merit increased attention relative to others. Rather, they say, a broad spectrum of patients may benefit from education and guidance on the risks of interactions, particularly the potential of supplements to interfere with the metabolism and potency of prescription medications.

Multivitamins containing “other” or botanical ingredients were more commonly consumed than were standard multivitamins. The increasingly complex combinations of ingredients contained in supplements may require closer evaluation by health care and dietetics practitioners. As important as it is to ask patients about their supplement use, it may be even more important to ask them about the ingredients on the labels. 

Source
Farina EK, Austin KG, Lieberman HR. J Acad Nutr Diet. [Accepted online ahead of print January 23, 2014.]
doi: 10.1016/j.jand.2014.01.016.

About 1 in 3 adults in the U.S. reported using dietary supplements and prescription medications concomitantly, say researchers from the Military Nutrition Division in Natick, Massachusetts, who analyzed data from the 2005-2008 National Health and Nutrition Examination Survey.

Prevalence of concomitant use was highest among people with osteoporosis, followed by thyroid, cancer, kidney, arthritis, diabetes, heart/vascular, respiratory, and liver conditions.

Supplement-and-medicine use was significantly more common among people with a doctor-informed medical condition (DIMC) (1 in 2 adults) vs those without (1 in 6 adults). Among people with a DIMC, cardiovascular agents were the most common drugs used with supplements. Among people without DIMC, hormones were the most common.

The number of people using both supplements and medicines has risen in recent years. More than 10 years ago, 16% to 18% of prescription medication users also took supplements, the researchers note. A study published in 2008 found the prevalence (at least among adults aged 57-85 years) was up to 52%. In the current study, 69.3% of prescription medication users aged ≥ 57 years were using supplements concomitantly.

Concomitant use was widespread across all medical conditions. Thus, the researchers say, it may not be feasible to identify individuals with a specific condition who merit increased attention relative to others. Rather, they say, a broad spectrum of patients may benefit from education and guidance on the risks of interactions, particularly the potential of supplements to interfere with the metabolism and potency of prescription medications.

Multivitamins containing “other” or botanical ingredients were more commonly consumed than were standard multivitamins. The increasingly complex combinations of ingredients contained in supplements may require closer evaluation by health care and dietetics practitioners. As important as it is to ask patients about their supplement use, it may be even more important to ask them about the ingredients on the labels. 

Source
Farina EK, Austin KG, Lieberman HR. J Acad Nutr Diet. [Accepted online ahead of print January 23, 2014.]
doi: 10.1016/j.jand.2014.01.016.

About 1 in 3 adults in the U.S. reported using dietary supplements and prescription medications concomitantly, say researchers from the Military Nutrition Division in Natick, Massachusetts, who analyzed data from the 2005-2008 National Health and Nutrition Examination Survey.

Prevalence of concomitant use was highest among people with osteoporosis, followed by thyroid, cancer, kidney, arthritis, diabetes, heart/vascular, respiratory, and liver conditions.

Supplement-and-medicine use was significantly more common among people with a doctor-informed medical condition (DIMC) (1 in 2 adults) vs those without (1 in 6 adults). Among people with a DIMC, cardiovascular agents were the most common drugs used with supplements. Among people without DIMC, hormones were the most common.

The number of people using both supplements and medicines has risen in recent years. More than 10 years ago, 16% to 18% of prescription medication users also took supplements, the researchers note. A study published in 2008 found the prevalence (at least among adults aged 57-85 years) was up to 52%. In the current study, 69.3% of prescription medication users aged ≥ 57 years were using supplements concomitantly.

Concomitant use was widespread across all medical conditions. Thus, the researchers say, it may not be feasible to identify individuals with a specific condition who merit increased attention relative to others. Rather, they say, a broad spectrum of patients may benefit from education and guidance on the risks of interactions, particularly the potential of supplements to interfere with the metabolism and potency of prescription medications.

Multivitamins containing “other” or botanical ingredients were more commonly consumed than were standard multivitamins. The increasingly complex combinations of ingredients contained in supplements may require closer evaluation by health care and dietetics practitioners. As important as it is to ask patients about their supplement use, it may be even more important to ask them about the ingredients on the labels. 

Source
Farina EK, Austin KG, Lieberman HR. J Acad Nutr Diet. [Accepted online ahead of print January 23, 2014.]
doi: 10.1016/j.jand.2014.01.016.

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

Switching patients with atrial fibrillation (AFib) to dabigatran, instead of continuing warfarin, may increase their risk of myocardial infarction (MI) in the first 2 months of treatment, say researchers from Aalborg University in Aalborg and the Danish Health and Medicines Authority in Copenhagen, both in Denmark; and City Hospital in Birmingham, United Kingdom.

Using 3 nationwide Danish databases, the researchers identified 4,818 patients who were taking dabigatran for the first time (2,124 taking 110 mg, 2,694 taking 150 mg), and 8,133 patients taking warfarin for the first time. They also studied a second cohort of vitamin K antagonist (VKA)–experienced patients, of whom 1,554 were switched to dabigatran 110 mg and 1,825 switched to 150 mg, compared with 49,868 patients who continued on warfarin. Warfarin users were the highest-risk group in the VKA-naïve cohort, but the lowest-risk group in the VKA-experienced cohort. Mean follow-up time was 16 months.

Among the “new starters,” the analysis showed a nonsignificant trend to lower rates of MI with dabigatran for both doses, compared with warfarin. However, among the “switchers,” overall MI rates increased moderately for both dabigatran doses, and within 60 days of switching, an increased rate was “clearly significant,” the researchers say. In adjusted analyses, the early follow-up crude annual event rate was 3.19% among the 110-mg group and 2.01% among the 150-mg group, vs 0.82% among the warfarin group (110 mg hazard ratio [HR] 3.01, 95% confidence interval [CI], 1.48-6.10; 150 mg HR 2.97, 95% CI, 1.31-6.73).

In the sensitivity analysis, the 110-mg dose had a greater effect on the rate of MIs when patients with previous MIs were excluded. The researchers say this raises the possibility that dabigatran could be less protective against MI compared with warfarin, which may be explained by its weaker attenuation of thrombin generation.

In “real world” practice, the researchers note, clinicians may be more likely to switch problematic warfarin patients, such as those with poor adherence, difficulties in maintaining a high time in therapeutic range, or poor attendance at warfarin clinics, to one of the novel oral anticoagulants. (In this study, 79% of dabigatran users in the VKA-naïve cohort persisted with treatment after 3 months, compared with 89% of warfarin users. Similar numbers were seen in the VKA-experienced cohort.) Older patients with more comorbidity, the researchers add, may find it more difficult to attend for warfarin monitoring. The potential impact on MI in switchers needs to be balanced against the magnitude of benefit from stroke prevention, reduced intracranial hemorrhage, and lower vascular mortality. Still, they advise caution, especially when switching VKA-experienced patients with AFib.

Source
Larsen TB, Rasmussen LH, Gorst-Rasmussen A, et al. Am J Med. 2014;127(4):329-336.e4.
doi: 10.1016/j.amjmed.2013.12.005.

Switching patients with atrial fibrillation (AFib) to dabigatran, instead of continuing warfarin, may increase their risk of myocardial infarction (MI) in the first 2 months of treatment, say researchers from Aalborg University in Aalborg and the Danish Health and Medicines Authority in Copenhagen, both in Denmark; and City Hospital in Birmingham, United Kingdom.

Using 3 nationwide Danish databases, the researchers identified 4,818 patients who were taking dabigatran for the first time (2,124 taking 110 mg, 2,694 taking 150 mg), and 8,133 patients taking warfarin for the first time. They also studied a second cohort of vitamin K antagonist (VKA)–experienced patients, of whom 1,554 were switched to dabigatran 110 mg and 1,825 switched to 150 mg, compared with 49,868 patients who continued on warfarin. Warfarin users were the highest-risk group in the VKA-naïve cohort, but the lowest-risk group in the VKA-experienced cohort. Mean follow-up time was 16 months.

Among the “new starters,” the analysis showed a nonsignificant trend to lower rates of MI with dabigatran for both doses, compared with warfarin. However, among the “switchers,” overall MI rates increased moderately for both dabigatran doses, and within 60 days of switching, an increased rate was “clearly significant,” the researchers say. In adjusted analyses, the early follow-up crude annual event rate was 3.19% among the 110-mg group and 2.01% among the 150-mg group, vs 0.82% among the warfarin group (110 mg hazard ratio [HR] 3.01, 95% confidence interval [CI], 1.48-6.10; 150 mg HR 2.97, 95% CI, 1.31-6.73).

In the sensitivity analysis, the 110-mg dose had a greater effect on the rate of MIs when patients with previous MIs were excluded. The researchers say this raises the possibility that dabigatran could be less protective against MI compared with warfarin, which may be explained by its weaker attenuation of thrombin generation.

In “real world” practice, the researchers note, clinicians may be more likely to switch problematic warfarin patients, such as those with poor adherence, difficulties in maintaining a high time in therapeutic range, or poor attendance at warfarin clinics, to one of the novel oral anticoagulants. (In this study, 79% of dabigatran users in the VKA-naïve cohort persisted with treatment after 3 months, compared with 89% of warfarin users. Similar numbers were seen in the VKA-experienced cohort.) Older patients with more comorbidity, the researchers add, may find it more difficult to attend for warfarin monitoring. The potential impact on MI in switchers needs to be balanced against the magnitude of benefit from stroke prevention, reduced intracranial hemorrhage, and lower vascular mortality. Still, they advise caution, especially when switching VKA-experienced patients with AFib.

Source
Larsen TB, Rasmussen LH, Gorst-Rasmussen A, et al. Am J Med. 2014;127(4):329-336.e4.
doi: 10.1016/j.amjmed.2013.12.005.

Switching patients with atrial fibrillation (AFib) to dabigatran, instead of continuing warfarin, may increase their risk of myocardial infarction (MI) in the first 2 months of treatment, say researchers from Aalborg University in Aalborg and the Danish Health and Medicines Authority in Copenhagen, both in Denmark; and City Hospital in Birmingham, United Kingdom.

Using 3 nationwide Danish databases, the researchers identified 4,818 patients who were taking dabigatran for the first time (2,124 taking 110 mg, 2,694 taking 150 mg), and 8,133 patients taking warfarin for the first time. They also studied a second cohort of vitamin K antagonist (VKA)–experienced patients, of whom 1,554 were switched to dabigatran 110 mg and 1,825 switched to 150 mg, compared with 49,868 patients who continued on warfarin. Warfarin users were the highest-risk group in the VKA-naïve cohort, but the lowest-risk group in the VKA-experienced cohort. Mean follow-up time was 16 months.

Among the “new starters,” the analysis showed a nonsignificant trend to lower rates of MI with dabigatran for both doses, compared with warfarin. However, among the “switchers,” overall MI rates increased moderately for both dabigatran doses, and within 60 days of switching, an increased rate was “clearly significant,” the researchers say. In adjusted analyses, the early follow-up crude annual event rate was 3.19% among the 110-mg group and 2.01% among the 150-mg group, vs 0.82% among the warfarin group (110 mg hazard ratio [HR] 3.01, 95% confidence interval [CI], 1.48-6.10; 150 mg HR 2.97, 95% CI, 1.31-6.73).

In the sensitivity analysis, the 110-mg dose had a greater effect on the rate of MIs when patients with previous MIs were excluded. The researchers say this raises the possibility that dabigatran could be less protective against MI compared with warfarin, which may be explained by its weaker attenuation of thrombin generation.

In “real world” practice, the researchers note, clinicians may be more likely to switch problematic warfarin patients, such as those with poor adherence, difficulties in maintaining a high time in therapeutic range, or poor attendance at warfarin clinics, to one of the novel oral anticoagulants. (In this study, 79% of dabigatran users in the VKA-naïve cohort persisted with treatment after 3 months, compared with 89% of warfarin users. Similar numbers were seen in the VKA-experienced cohort.) Older patients with more comorbidity, the researchers add, may find it more difficult to attend for warfarin monitoring. The potential impact on MI in switchers needs to be balanced against the magnitude of benefit from stroke prevention, reduced intracranial hemorrhage, and lower vascular mortality. Still, they advise caution, especially when switching VKA-experienced patients with AFib.

Source
Larsen TB, Rasmussen LH, Gorst-Rasmussen A, et al. Am J Med. 2014;127(4):329-336.e4.
doi: 10.1016/j.amjmed.2013.12.005.

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.