Pharmacology

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

More than one-third of the antiarrhythmic drugs used to treat some cardiac patients aren’t being used according to guideline recommendations, say researchers from Duke Clinical Research Institute in Durham, North Carolina.

The researchers used commercial health claims to identify and categorize patients into guideline-established groups based on their most serious concurrent heart disease: heart failure (HF), coronary artery disease (CAD), hypertension (HTN), and no heart disease.

Of 78,877 patients with a prescription for ≥ 1 antiarrhythmic drug (AAD), most received 1 AAD, 12% received 2 AADs, and 2% received ≥ 3 AADs. The median time from the first inpatient or outpatient encounter for the diagnosis of atrial fibrillation (AFib) to the first prescription claim for an AAD was 29 days (range, 9-89 days).

In the patients with HF and CAD, 45% and 31% of AADs were inconsistent with first- or second-line recommendations, respectively. Only 55% of AAD use (amiodarone and dofetilide) in patients with AFib and HF conformed to recommendations. The use of sotalol, dronedarone, propafenone, and flecainide did not conform. Among patients with AFib and CAD, only 40% of AAD use (sotalol, dronedarone and dofetilide) conformed to first-line recommendations. Propafenone and flecainide, which are not recommended for patients with CAD, accounted for 31% of AAD use, the researchers found.

Among patients with AFib and HTN, all the high-use AADs were consistent with guidelines. Of the 81,891 patients with AF who did not have HF, CAD, or HTN, 19% received AADs, usually flecainide, propafenone, and sotalol, which are all acceptable according to clinical practice guidelines.

This study raises several concerns, the researchers say, such as the high use of dronedarone. As the first study to address how dronedarone, introduced in 2009, is being used in the U.S., it provides an early picture of a drug that has since been reported to have safety issues. Although dronedarone was only available for less than one-third of the study period, it accounted for 9% of all AAD use in patients with HF or CAD, 8% in patients with HTN, and 6% in patients without the selected cardiac diseases.

Although the study provides only a “snapshot” of AAD use based on claims data, the high rate of nonconformity is concerning, the researchers say. They note that much of the recent focus has been on evaluating and comparing a rate- vs rhythm-control strategy, with relatively little attention given to evaluating or comparing the specific drugs used in those strategies. The “extensive use of potentially inappropriate AADs highlights the need for more detailed analyses of AAD drug selection,” they conclude, especially for patients with concomitant HF and CAD.

Source
LaPointe NMA, Lokhnygina Y, Sanders GD, Peterson ED, Al-Khatib SM. Am Heart J. 2013;166(5):871-878.
doi: 10.1016/j.ahj.2013.08.010.

More than one-third of the antiarrhythmic drugs used to treat some cardiac patients aren’t being used according to guideline recommendations, say researchers from Duke Clinical Research Institute in Durham, North Carolina.

The researchers used commercial health claims to identify and categorize patients into guideline-established groups based on their most serious concurrent heart disease: heart failure (HF), coronary artery disease (CAD), hypertension (HTN), and no heart disease.

Of 78,877 patients with a prescription for ≥ 1 antiarrhythmic drug (AAD), most received 1 AAD, 12% received 2 AADs, and 2% received ≥ 3 AADs. The median time from the first inpatient or outpatient encounter for the diagnosis of atrial fibrillation (AFib) to the first prescription claim for an AAD was 29 days (range, 9-89 days).

In the patients with HF and CAD, 45% and 31% of AADs were inconsistent with first- or second-line recommendations, respectively. Only 55% of AAD use (amiodarone and dofetilide) in patients with AFib and HF conformed to recommendations. The use of sotalol, dronedarone, propafenone, and flecainide did not conform. Among patients with AFib and CAD, only 40% of AAD use (sotalol, dronedarone and dofetilide) conformed to first-line recommendations. Propafenone and flecainide, which are not recommended for patients with CAD, accounted for 31% of AAD use, the researchers found.

Among patients with AFib and HTN, all the high-use AADs were consistent with guidelines. Of the 81,891 patients with AF who did not have HF, CAD, or HTN, 19% received AADs, usually flecainide, propafenone, and sotalol, which are all acceptable according to clinical practice guidelines.

This study raises several concerns, the researchers say, such as the high use of dronedarone. As the first study to address how dronedarone, introduced in 2009, is being used in the U.S., it provides an early picture of a drug that has since been reported to have safety issues. Although dronedarone was only available for less than one-third of the study period, it accounted for 9% of all AAD use in patients with HF or CAD, 8% in patients with HTN, and 6% in patients without the selected cardiac diseases.

Although the study provides only a “snapshot” of AAD use based on claims data, the high rate of nonconformity is concerning, the researchers say. They note that much of the recent focus has been on evaluating and comparing a rate- vs rhythm-control strategy, with relatively little attention given to evaluating or comparing the specific drugs used in those strategies. The “extensive use of potentially inappropriate AADs highlights the need for more detailed analyses of AAD drug selection,” they conclude, especially for patients with concomitant HF and CAD.

Source
LaPointe NMA, Lokhnygina Y, Sanders GD, Peterson ED, Al-Khatib SM. Am Heart J. 2013;166(5):871-878.
doi: 10.1016/j.ahj.2013.08.010.

More than one-third of the antiarrhythmic drugs used to treat some cardiac patients aren’t being used according to guideline recommendations, say researchers from Duke Clinical Research Institute in Durham, North Carolina.

The researchers used commercial health claims to identify and categorize patients into guideline-established groups based on their most serious concurrent heart disease: heart failure (HF), coronary artery disease (CAD), hypertension (HTN), and no heart disease.

Of 78,877 patients with a prescription for ≥ 1 antiarrhythmic drug (AAD), most received 1 AAD, 12% received 2 AADs, and 2% received ≥ 3 AADs. The median time from the first inpatient or outpatient encounter for the diagnosis of atrial fibrillation (AFib) to the first prescription claim for an AAD was 29 days (range, 9-89 days).

In the patients with HF and CAD, 45% and 31% of AADs were inconsistent with first- or second-line recommendations, respectively. Only 55% of AAD use (amiodarone and dofetilide) in patients with AFib and HF conformed to recommendations. The use of sotalol, dronedarone, propafenone, and flecainide did not conform. Among patients with AFib and CAD, only 40% of AAD use (sotalol, dronedarone and dofetilide) conformed to first-line recommendations. Propafenone and flecainide, which are not recommended for patients with CAD, accounted for 31% of AAD use, the researchers found.

Among patients with AFib and HTN, all the high-use AADs were consistent with guidelines. Of the 81,891 patients with AF who did not have HF, CAD, or HTN, 19% received AADs, usually flecainide, propafenone, and sotalol, which are all acceptable according to clinical practice guidelines.

This study raises several concerns, the researchers say, such as the high use of dronedarone. As the first study to address how dronedarone, introduced in 2009, is being used in the U.S., it provides an early picture of a drug that has since been reported to have safety issues. Although dronedarone was only available for less than one-third of the study period, it accounted for 9% of all AAD use in patients with HF or CAD, 8% in patients with HTN, and 6% in patients without the selected cardiac diseases.

Although the study provides only a “snapshot” of AAD use based on claims data, the high rate of nonconformity is concerning, the researchers say. They note that much of the recent focus has been on evaluating and comparing a rate- vs rhythm-control strategy, with relatively little attention given to evaluating or comparing the specific drugs used in those strategies. The “extensive use of potentially inappropriate AADs highlights the need for more detailed analyses of AAD drug selection,” they conclude, especially for patients with concomitant HF and CAD.

Source
LaPointe NMA, Lokhnygina Y, Sanders GD, Peterson ED, Al-Khatib SM. Am Heart J. 2013;166(5):871-878.
doi: 10.1016/j.ahj.2013.08.010.