User login
Can Endocrine Therapy Adherence Be Improved?
Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.
The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.
Related: New Protocol Aims to Evaluate Medication Nonadherence
A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.
One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.
Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective
Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.
The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.
Related: Early Cancer Detection Helps Underserved Women
The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.
Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.
Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.
The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.
Related: New Protocol Aims to Evaluate Medication Nonadherence
A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.
One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.
Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective
Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.
The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.
Related: Early Cancer Detection Helps Underserved Women
The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.
Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.
Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.
The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.
Related: New Protocol Aims to Evaluate Medication Nonadherence
A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.
One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.
Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective
Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.
The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.
Related: Early Cancer Detection Helps Underserved Women
The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.
Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.
Combination Pill Approved for HCV
The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.
The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.
Related: Viral Hepatitis Awareness
The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.
Related: Is Age-Based HCV Screening a Benefit?
The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.
The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.
Related: Hepatitis C (Patient Information)
This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness.
Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.
FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.
The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.
The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.
Related: Viral Hepatitis Awareness
The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.
Related: Is Age-Based HCV Screening a Benefit?
The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.
The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.
Related: Hepatitis C (Patient Information)
This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness.
Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.
FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.
The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.
The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.
Related: Viral Hepatitis Awareness
The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.
Related: Is Age-Based HCV Screening a Benefit?
The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.
The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.
Related: Hepatitis C (Patient Information)
This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness.
Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.
FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.
Oxaliplatin-Induced Lhermitte Sign
Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.
Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m2 of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m2 of oxaliplatin every 3 weeks.
Related: The Best Times to Try Abiraterone
After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.
Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.
Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center
Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m2).
The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m2) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.
They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.
Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.
Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.
Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.
Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m2 of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m2 of oxaliplatin every 3 weeks.
Related: The Best Times to Try Abiraterone
After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.
Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.
Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center
Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m2).
The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m2) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.
They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.
Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.
Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.
Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.
Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m2 of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m2 of oxaliplatin every 3 weeks.
Related: The Best Times to Try Abiraterone
After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.
Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.
Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center
Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m2).
The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m2) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.
They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.
Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.
Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.
Antibiotic Failure: Not Only a Hospital Phenomenon
The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.
As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.
Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.
Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.
The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).
The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.
The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.
Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.
Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.
Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.
The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.
As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.
Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.
Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.
The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).
The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.
The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.
Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.
Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.
Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.
The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.
As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.
Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.
Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.
The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).
The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.
The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.
Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.
Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.
Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.
Reducing Candida-Related Shock With Empiric Treatment
The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.
The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.
Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.
The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).
The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.
Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.
The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.
The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.
Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.
The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).
The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.
Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.
The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.
The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.
Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.
The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).
The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.
Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.
Long-Acting Insulin Analogs: Effects on Diabetic Retinopathy
Long-acting insulin analogs are designed to enhance glycemic control without excessively lowering blood glucose. But structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors; in short, they can potentially raise the risk of sight-threatening diabetic retinopathy (STDR), say researchers from Taipei City Hospital and National Taiwan University, both in Taiwan.
The researchers note that some clinical trials have reported that intensification of endogenous insulin might accelerate progression of pre-existing STDR. However, they add that some studies used cancer cell lines, and insulin was administered at supraphysiologic concentrations.
The researchers conducted a retrospective study to evaluate the effects of long-acting insulin analogs (glargine and/or detemir) with neutral protamine Hagedorn (NPH) insulin on the progression of STDR in 46,739 patients with type 2 diabetesmellitus (T2DM).
They found no changed risk of STDR with the long-acting insulin analogs, between either matched or unmatched cohorts. For instance, with a median follow-up of 483 days, they found 479 events with glargine initiators in 8,947 patients. There were 541 events in a median of 541 days’ follow-up for 8,947 patients in the NPH initiators group. The detemir group, with 411 days of follow-up, had 64 events.
Despite a “relatively short” observation period, the researchers say their findings agree with those of a previous open-label randomized study of patients with T2DM, which found treatment with insulin glargine over 5 years did not increase progression of STDR, compared with NPH insulin treatment.
Source
Lin JC, Shau WY, Lai MS. Clin Ther. 2014;36(9):1255-1268.
doi: 10.1016/j.clinthera.2014.06.031.3.
Long-acting insulin analogs are designed to enhance glycemic control without excessively lowering blood glucose. But structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors; in short, they can potentially raise the risk of sight-threatening diabetic retinopathy (STDR), say researchers from Taipei City Hospital and National Taiwan University, both in Taiwan.
The researchers note that some clinical trials have reported that intensification of endogenous insulin might accelerate progression of pre-existing STDR. However, they add that some studies used cancer cell lines, and insulin was administered at supraphysiologic concentrations.
The researchers conducted a retrospective study to evaluate the effects of long-acting insulin analogs (glargine and/or detemir) with neutral protamine Hagedorn (NPH) insulin on the progression of STDR in 46,739 patients with type 2 diabetesmellitus (T2DM).
They found no changed risk of STDR with the long-acting insulin analogs, between either matched or unmatched cohorts. For instance, with a median follow-up of 483 days, they found 479 events with glargine initiators in 8,947 patients. There were 541 events in a median of 541 days’ follow-up for 8,947 patients in the NPH initiators group. The detemir group, with 411 days of follow-up, had 64 events.
Despite a “relatively short” observation period, the researchers say their findings agree with those of a previous open-label randomized study of patients with T2DM, which found treatment with insulin glargine over 5 years did not increase progression of STDR, compared with NPH insulin treatment.
Source
Lin JC, Shau WY, Lai MS. Clin Ther. 2014;36(9):1255-1268.
doi: 10.1016/j.clinthera.2014.06.031.3.
Long-acting insulin analogs are designed to enhance glycemic control without excessively lowering blood glucose. But structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors; in short, they can potentially raise the risk of sight-threatening diabetic retinopathy (STDR), say researchers from Taipei City Hospital and National Taiwan University, both in Taiwan.
The researchers note that some clinical trials have reported that intensification of endogenous insulin might accelerate progression of pre-existing STDR. However, they add that some studies used cancer cell lines, and insulin was administered at supraphysiologic concentrations.
The researchers conducted a retrospective study to evaluate the effects of long-acting insulin analogs (glargine and/or detemir) with neutral protamine Hagedorn (NPH) insulin on the progression of STDR in 46,739 patients with type 2 diabetesmellitus (T2DM).
They found no changed risk of STDR with the long-acting insulin analogs, between either matched or unmatched cohorts. For instance, with a median follow-up of 483 days, they found 479 events with glargine initiators in 8,947 patients. There were 541 events in a median of 541 days’ follow-up for 8,947 patients in the NPH initiators group. The detemir group, with 411 days of follow-up, had 64 events.
Despite a “relatively short” observation period, the researchers say their findings agree with those of a previous open-label randomized study of patients with T2DM, which found treatment with insulin glargine over 5 years did not increase progression of STDR, compared with NPH insulin treatment.
Source
Lin JC, Shau WY, Lai MS. Clin Ther. 2014;36(9):1255-1268.
doi: 10.1016/j.clinthera.2014.06.031.3.
Referring Smokers to Quitlines
Telephone-based programs to encourage and support quitting smoking—known as “quitlines”—have been established as effective both clinically and in the “real world.” However, quitlines rely on smokers calling in for them to work. Researchers from the Tobacco Cessation and Prevention Program and the Massachusetts Department of Public Health, both in Boston, say being referred to quitlines by their health care providers might help even more smokers quit.
The researchers collected data for 2,737 provider-referred and 530 self-referred smokers from the Massachusetts Smokers’ Helpline, which offers evidence-based proactive telephone counseling sessions, nicotine replacement therapy (NRT), and self-help materials. They then examined differences in demographics, service utilization, and quit outcomes. The primary outcome was quit status at the 6- to 8-month follow-up.
Twenty percent of provider-referred clients quit smoking; 26% of self-referred clients quit. Provider-referred smokers who used the quitline services had higher odds of quitting, compared with those who used methods not including a quitline. However, the provider-referral model was limited by lower enrollment, lower use, and poorer outcomes compared with self-referred services. Patients aged 18 to 34 years and those aged > 65 years had the best chances of quitting and staying smoke-free. Patients referred from private practices were more likely to quit than were those referred from a hospital.
Provider-referred smokers who read the self-help materials had 1.2 times the odds of quitting compared with those who didn’t. Using any amount of the 2-week supply of NRT doubled the odds of quitting. Clients who used a combination of counseling and NRT had the greatest success, with more than triple the chances of quitting, compared with clients who did neither.
Self-referred smokers also had good results, although not usually as quickly as provider-referred smokers, who saw significantly improved outcomes after 3 counseling sessions. It took 4 sessions for the self-referred smokers to see the same results.
Readiness to quit was an important predictor of success. Tobacco dependence also predicted quitting success. Clients in both groups who could wait > 30 minutes before smoking their first cigarette had better luck than did those who had to smoke immediately after waking.
The researchers suggest some ways to improve the provider-referred model. One is to offer more support for smokers from lower socioeconomic levels. According to other research, those smokers may need more treatment content and access to more intensive pharmacotherapy, the researchers say.
It might also help all quitline clients, they add, to minimize the wait time between referral and actual provision of service. Longer wait times can “increase the room for ambivalence for any smoker,” they note, “but may be especially detrimental for provider-referred smokers who are less ready to make a quit attempt.”
And what is the provider’s role in assessing patient readiness to quit and preparing patients for the quitline services? In reality, the researchers say, not all patients have received an evidence-based intervention or are ready to quit when they are enrolled. Moreover, many are lost in the callback process. Using 3 callback attempts, the Massachusetts quitline only reaches 40% of their potential quitters. Upping the callback rate to 5 attempts raises the reach slightly, to 50%. That shows the need, the researchers say, for better and more frequent provider training, outreach, feedback reporting, clinical champions on site, and systems support.
Source
Song G, Landau AS, Gorin TJ, Keithly L. Am J Prev Med. 2014;47(4):392-402.
doi: 10.1016/j.amepre.2014.05.043.
Telephone-based programs to encourage and support quitting smoking—known as “quitlines”—have been established as effective both clinically and in the “real world.” However, quitlines rely on smokers calling in for them to work. Researchers from the Tobacco Cessation and Prevention Program and the Massachusetts Department of Public Health, both in Boston, say being referred to quitlines by their health care providers might help even more smokers quit.
The researchers collected data for 2,737 provider-referred and 530 self-referred smokers from the Massachusetts Smokers’ Helpline, which offers evidence-based proactive telephone counseling sessions, nicotine replacement therapy (NRT), and self-help materials. They then examined differences in demographics, service utilization, and quit outcomes. The primary outcome was quit status at the 6- to 8-month follow-up.
Twenty percent of provider-referred clients quit smoking; 26% of self-referred clients quit. Provider-referred smokers who used the quitline services had higher odds of quitting, compared with those who used methods not including a quitline. However, the provider-referral model was limited by lower enrollment, lower use, and poorer outcomes compared with self-referred services. Patients aged 18 to 34 years and those aged > 65 years had the best chances of quitting and staying smoke-free. Patients referred from private practices were more likely to quit than were those referred from a hospital.
Provider-referred smokers who read the self-help materials had 1.2 times the odds of quitting compared with those who didn’t. Using any amount of the 2-week supply of NRT doubled the odds of quitting. Clients who used a combination of counseling and NRT had the greatest success, with more than triple the chances of quitting, compared with clients who did neither.
Self-referred smokers also had good results, although not usually as quickly as provider-referred smokers, who saw significantly improved outcomes after 3 counseling sessions. It took 4 sessions for the self-referred smokers to see the same results.
Readiness to quit was an important predictor of success. Tobacco dependence also predicted quitting success. Clients in both groups who could wait > 30 minutes before smoking their first cigarette had better luck than did those who had to smoke immediately after waking.
The researchers suggest some ways to improve the provider-referred model. One is to offer more support for smokers from lower socioeconomic levels. According to other research, those smokers may need more treatment content and access to more intensive pharmacotherapy, the researchers say.
It might also help all quitline clients, they add, to minimize the wait time between referral and actual provision of service. Longer wait times can “increase the room for ambivalence for any smoker,” they note, “but may be especially detrimental for provider-referred smokers who are less ready to make a quit attempt.”
And what is the provider’s role in assessing patient readiness to quit and preparing patients for the quitline services? In reality, the researchers say, not all patients have received an evidence-based intervention or are ready to quit when they are enrolled. Moreover, many are lost in the callback process. Using 3 callback attempts, the Massachusetts quitline only reaches 40% of their potential quitters. Upping the callback rate to 5 attempts raises the reach slightly, to 50%. That shows the need, the researchers say, for better and more frequent provider training, outreach, feedback reporting, clinical champions on site, and systems support.
Source
Song G, Landau AS, Gorin TJ, Keithly L. Am J Prev Med. 2014;47(4):392-402.
doi: 10.1016/j.amepre.2014.05.043.
Telephone-based programs to encourage and support quitting smoking—known as “quitlines”—have been established as effective both clinically and in the “real world.” However, quitlines rely on smokers calling in for them to work. Researchers from the Tobacco Cessation and Prevention Program and the Massachusetts Department of Public Health, both in Boston, say being referred to quitlines by their health care providers might help even more smokers quit.
The researchers collected data for 2,737 provider-referred and 530 self-referred smokers from the Massachusetts Smokers’ Helpline, which offers evidence-based proactive telephone counseling sessions, nicotine replacement therapy (NRT), and self-help materials. They then examined differences in demographics, service utilization, and quit outcomes. The primary outcome was quit status at the 6- to 8-month follow-up.
Twenty percent of provider-referred clients quit smoking; 26% of self-referred clients quit. Provider-referred smokers who used the quitline services had higher odds of quitting, compared with those who used methods not including a quitline. However, the provider-referral model was limited by lower enrollment, lower use, and poorer outcomes compared with self-referred services. Patients aged 18 to 34 years and those aged > 65 years had the best chances of quitting and staying smoke-free. Patients referred from private practices were more likely to quit than were those referred from a hospital.
Provider-referred smokers who read the self-help materials had 1.2 times the odds of quitting compared with those who didn’t. Using any amount of the 2-week supply of NRT doubled the odds of quitting. Clients who used a combination of counseling and NRT had the greatest success, with more than triple the chances of quitting, compared with clients who did neither.
Self-referred smokers also had good results, although not usually as quickly as provider-referred smokers, who saw significantly improved outcomes after 3 counseling sessions. It took 4 sessions for the self-referred smokers to see the same results.
Readiness to quit was an important predictor of success. Tobacco dependence also predicted quitting success. Clients in both groups who could wait > 30 minutes before smoking their first cigarette had better luck than did those who had to smoke immediately after waking.
The researchers suggest some ways to improve the provider-referred model. One is to offer more support for smokers from lower socioeconomic levels. According to other research, those smokers may need more treatment content and access to more intensive pharmacotherapy, the researchers say.
It might also help all quitline clients, they add, to minimize the wait time between referral and actual provision of service. Longer wait times can “increase the room for ambivalence for any smoker,” they note, “but may be especially detrimental for provider-referred smokers who are less ready to make a quit attempt.”
And what is the provider’s role in assessing patient readiness to quit and preparing patients for the quitline services? In reality, the researchers say, not all patients have received an evidence-based intervention or are ready to quit when they are enrolled. Moreover, many are lost in the callback process. Using 3 callback attempts, the Massachusetts quitline only reaches 40% of their potential quitters. Upping the callback rate to 5 attempts raises the reach slightly, to 50%. That shows the need, the researchers say, for better and more frequent provider training, outreach, feedback reporting, clinical champions on site, and systems support.
Source
Song G, Landau AS, Gorin TJ, Keithly L. Am J Prev Med. 2014;47(4):392-402.
doi: 10.1016/j.amepre.2014.05.043.
The Best Times to Try Abiraterone
Until recently, there have been few treatment options for advanced prostate cancer that is resistant to androgen-directed therapies. Newer treatments that target residual androgen production offer some hope of prolonging the interval before chemotherapy, with fewer adverse effects (AEs) and better efficacy. One of those is abiraterone, which blocks extragonadal, testicular, and tumor androgen biosynthesis.
An ongoing multinational phase 3 study is evaluating the clinical benefits of abiraterone plus prednisone vs prednisone alone in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Follow-up for the study has now exceeded 27 months, giving a good opportunity to evaluate safety and efficacy. Thus, after having reviewed outcomes so far, the independent data-monitoring committee recommended that the study be unblinded and patients be allowed to cross over from prednisone to abiraterone. The researchers reported the results of the third interim analysis, with updated analysis.
Patients were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS) and randomly assigned to receive abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone.
Patients who received abiraterone had, compared with those on prednisone, statistically significant improvement in radiographic progression-free survival (PFS), with a median time to disease progression or death of 16.5 months, vs 8.2 months (95% CI, 0.45-0.61).
Overall survival also lengthened, from a median of 35.3 months vs 30.1 months (95% CI, 0.66-0.95).
All secondary endpoints also favored abiraterone over prednisone. For instance, abiraterone treatment delayed the time to the need for opiates for cancer-related pain and the time to initiation of chemotherapy. Abiraterone also delayed the time to deterioration in ECOG-PS and prostate-specific antigen (PSA) progression. Abiraterone more than doubled the PSA response rate: 68% vs 29% with prednisone.
Patients reported more pain relief. Those receiving abiraterone had statistically significant improvement in pain interference (P = .005), although the improvement in mean pain intensity was not significant.
Adverse effects leading to dose modifications or interruption of treatment were reported in 21% of patients on abiraterone, compared with 12% of the prednisone group. Six patients (1%) in each group died of drug-related treatment-emergent AEs. The AEs of “special interest,” the researchers say, included events related to mineralocorticoid excess, such as hypertension, hypokalemia, and fluid retention—all unsurprising, given the known mechanism of action of abiraterone. Grade 3 or 4 AEs with increased alanine aminotransferase and aspartate aminotransferase were more common in the abiraterone group.
The most common subsequent therapy for patients who terminated the study was docetaxel. However, another recent study, from Johns Hopkins researchers in Baltimore, Maryland, indicates the transition warrants caution: The findings suggest a potential cross-resistance between docetaxel and abiraterone.
Their study compared outcomes in 24 men who received abiraterone before docetaxel with 95 who were abiraterone-naïve. Men who were on abiraterone were less likely to achieve a PSA response, and their cancer was more likely to progress.
The researchers concede that their study groups were small; they also say it is possible that differences in disease severity may have influenced the time to progression. However, they say the fact that PSA-PFS was significantly different between the 2 groups (P = .002) supports their initial hypothesis—that is, that abiraterone pretreatment reduces responsiveness to docetaxel.
In spite of its limitations, the researchers say their study represents the only comparative analysis of PSA-PFS and PFS after docetaxel treatment for patients who have or have not received prior abiraterone. Their report, they add, offers the “strongest available evidence to date” of a clinically meaningful cross-resistance between abiraterone and docetaxel. They conclude that their findings provide “valuable information” about which patients are likely to derive the most benefit from docetaxel.
Sources
Rathkopf DE, Smith MR, de Bono JS, et al. Eur Urol. 2014;66(5):815-825.
doi: 10.1016/j.eururo.2014.02.056.
Schewizer MT, Zhou XC, Wang H, et al. Eur Urol. 2014;66(4):646-652.
doi: 10.1016/j.eururo.2014.01.018.
Until recently, there have been few treatment options for advanced prostate cancer that is resistant to androgen-directed therapies. Newer treatments that target residual androgen production offer some hope of prolonging the interval before chemotherapy, with fewer adverse effects (AEs) and better efficacy. One of those is abiraterone, which blocks extragonadal, testicular, and tumor androgen biosynthesis.
An ongoing multinational phase 3 study is evaluating the clinical benefits of abiraterone plus prednisone vs prednisone alone in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Follow-up for the study has now exceeded 27 months, giving a good opportunity to evaluate safety and efficacy. Thus, after having reviewed outcomes so far, the independent data-monitoring committee recommended that the study be unblinded and patients be allowed to cross over from prednisone to abiraterone. The researchers reported the results of the third interim analysis, with updated analysis.
Patients were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS) and randomly assigned to receive abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone.
Patients who received abiraterone had, compared with those on prednisone, statistically significant improvement in radiographic progression-free survival (PFS), with a median time to disease progression or death of 16.5 months, vs 8.2 months (95% CI, 0.45-0.61).
Overall survival also lengthened, from a median of 35.3 months vs 30.1 months (95% CI, 0.66-0.95).
All secondary endpoints also favored abiraterone over prednisone. For instance, abiraterone treatment delayed the time to the need for opiates for cancer-related pain and the time to initiation of chemotherapy. Abiraterone also delayed the time to deterioration in ECOG-PS and prostate-specific antigen (PSA) progression. Abiraterone more than doubled the PSA response rate: 68% vs 29% with prednisone.
Patients reported more pain relief. Those receiving abiraterone had statistically significant improvement in pain interference (P = .005), although the improvement in mean pain intensity was not significant.
Adverse effects leading to dose modifications or interruption of treatment were reported in 21% of patients on abiraterone, compared with 12% of the prednisone group. Six patients (1%) in each group died of drug-related treatment-emergent AEs. The AEs of “special interest,” the researchers say, included events related to mineralocorticoid excess, such as hypertension, hypokalemia, and fluid retention—all unsurprising, given the known mechanism of action of abiraterone. Grade 3 or 4 AEs with increased alanine aminotransferase and aspartate aminotransferase were more common in the abiraterone group.
The most common subsequent therapy for patients who terminated the study was docetaxel. However, another recent study, from Johns Hopkins researchers in Baltimore, Maryland, indicates the transition warrants caution: The findings suggest a potential cross-resistance between docetaxel and abiraterone.
Their study compared outcomes in 24 men who received abiraterone before docetaxel with 95 who were abiraterone-naïve. Men who were on abiraterone were less likely to achieve a PSA response, and their cancer was more likely to progress.
The researchers concede that their study groups were small; they also say it is possible that differences in disease severity may have influenced the time to progression. However, they say the fact that PSA-PFS was significantly different between the 2 groups (P = .002) supports their initial hypothesis—that is, that abiraterone pretreatment reduces responsiveness to docetaxel.
In spite of its limitations, the researchers say their study represents the only comparative analysis of PSA-PFS and PFS after docetaxel treatment for patients who have or have not received prior abiraterone. Their report, they add, offers the “strongest available evidence to date” of a clinically meaningful cross-resistance between abiraterone and docetaxel. They conclude that their findings provide “valuable information” about which patients are likely to derive the most benefit from docetaxel.
Sources
Rathkopf DE, Smith MR, de Bono JS, et al. Eur Urol. 2014;66(5):815-825.
doi: 10.1016/j.eururo.2014.02.056.
Schewizer MT, Zhou XC, Wang H, et al. Eur Urol. 2014;66(4):646-652.
doi: 10.1016/j.eururo.2014.01.018.
Until recently, there have been few treatment options for advanced prostate cancer that is resistant to androgen-directed therapies. Newer treatments that target residual androgen production offer some hope of prolonging the interval before chemotherapy, with fewer adverse effects (AEs) and better efficacy. One of those is abiraterone, which blocks extragonadal, testicular, and tumor androgen biosynthesis.
An ongoing multinational phase 3 study is evaluating the clinical benefits of abiraterone plus prednisone vs prednisone alone in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Follow-up for the study has now exceeded 27 months, giving a good opportunity to evaluate safety and efficacy. Thus, after having reviewed outcomes so far, the independent data-monitoring committee recommended that the study be unblinded and patients be allowed to cross over from prednisone to abiraterone. The researchers reported the results of the third interim analysis, with updated analysis.
Patients were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS) and randomly assigned to receive abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone.
Patients who received abiraterone had, compared with those on prednisone, statistically significant improvement in radiographic progression-free survival (PFS), with a median time to disease progression or death of 16.5 months, vs 8.2 months (95% CI, 0.45-0.61).
Overall survival also lengthened, from a median of 35.3 months vs 30.1 months (95% CI, 0.66-0.95).
All secondary endpoints also favored abiraterone over prednisone. For instance, abiraterone treatment delayed the time to the need for opiates for cancer-related pain and the time to initiation of chemotherapy. Abiraterone also delayed the time to deterioration in ECOG-PS and prostate-specific antigen (PSA) progression. Abiraterone more than doubled the PSA response rate: 68% vs 29% with prednisone.
Patients reported more pain relief. Those receiving abiraterone had statistically significant improvement in pain interference (P = .005), although the improvement in mean pain intensity was not significant.
Adverse effects leading to dose modifications or interruption of treatment were reported in 21% of patients on abiraterone, compared with 12% of the prednisone group. Six patients (1%) in each group died of drug-related treatment-emergent AEs. The AEs of “special interest,” the researchers say, included events related to mineralocorticoid excess, such as hypertension, hypokalemia, and fluid retention—all unsurprising, given the known mechanism of action of abiraterone. Grade 3 or 4 AEs with increased alanine aminotransferase and aspartate aminotransferase were more common in the abiraterone group.
The most common subsequent therapy for patients who terminated the study was docetaxel. However, another recent study, from Johns Hopkins researchers in Baltimore, Maryland, indicates the transition warrants caution: The findings suggest a potential cross-resistance between docetaxel and abiraterone.
Their study compared outcomes in 24 men who received abiraterone before docetaxel with 95 who were abiraterone-naïve. Men who were on abiraterone were less likely to achieve a PSA response, and their cancer was more likely to progress.
The researchers concede that their study groups were small; they also say it is possible that differences in disease severity may have influenced the time to progression. However, they say the fact that PSA-PFS was significantly different between the 2 groups (P = .002) supports their initial hypothesis—that is, that abiraterone pretreatment reduces responsiveness to docetaxel.
In spite of its limitations, the researchers say their study represents the only comparative analysis of PSA-PFS and PFS after docetaxel treatment for patients who have or have not received prior abiraterone. Their report, they add, offers the “strongest available evidence to date” of a clinically meaningful cross-resistance between abiraterone and docetaxel. They conclude that their findings provide “valuable information” about which patients are likely to derive the most benefit from docetaxel.
Sources
Rathkopf DE, Smith MR, de Bono JS, et al. Eur Urol. 2014;66(5):815-825.
doi: 10.1016/j.eururo.2014.02.056.
Schewizer MT, Zhou XC, Wang H, et al. Eur Urol. 2014;66(4):646-652.
doi: 10.1016/j.eururo.2014.01.018.
NSAIDs Linked to Poor Pneumonia Outcomes
Nonsteroidal anti-inflammatory drugs (NSAIDs) given in the early stages of lower respiratory tract infection could be helping send younger adults to the intensive care unit (ICU) with serious pneumonia, say researchers from Hôpital Louis Mourier, Colombes, and Université Paris Diderot, both in France. Their concerns were triggered in part by witnessing several cases of unexpectedly severe forms of Streptococcus pneumoniae (S pneumoniae) community-acquired pneumonia (CAP) in healthy adults.
They analyzed data on 106 patients admitted with pneumococcal pneumonia or S pneumoniae and pneumonia as the discharge diagnosis. Twenty patients had received NSAIDs within 4 days prior to admission. The patients given NSAIDs were younger than those who were not prescribed NSAIDs (aged 43 years on average vs aged 62 years on average), usually working, and less likely to have comorbidities. The mean duration of NSAID treatment was 4 days. The time to the first medical consultation after pneumonia-related symptoms appeared was the same in both groups, but the patients on NSAIDs were prescribed antibiotics significantly later than those not taking NSAIDs (4.5 days vs 2 days, P = .001). They were also admitted to the ICU later.
A “noticeable and significant difference” was that more patients in the NSAID group had pleural effusion (P < .0006). New onset of pleuropulmonary complications during the ICU stay was significantly greater in the group who had received NSAIDs than in the no-NSAID group (P = .0008).
The researchers say their findings “highlight the overlooked risk of taking NSAIDs to treat physical symptoms at an early stage of CAP.” They hypothesize that patient age and comorbidity status led physicians to not diagnose CAP, and thus withhold antibiotics. NSAIDs may blunt general signs and symptoms and mask the severity of the infectious process, the researchers caution. Thus, they recommend ensuring appropriate antibiotic coverage along with NSAIDs.
In a survey of French general practitioners’ prescriptions, NSAIDs were prescribed for almost half of all patients seen for lower respiratory tract infection, “despite the fact that this prescription never appears in any national or international guideline,” the researchers say. That underscores the need to better inform general practitioners about the risks of NSAIDs, they say.
Source
Messika J, Sztrymf B, Bertrand F, et al. J Crit Care. 2014;29(5):733-738.
doi: 10.1016/j.jcrc.2014.05.021.
Nonsteroidal anti-inflammatory drugs (NSAIDs) given in the early stages of lower respiratory tract infection could be helping send younger adults to the intensive care unit (ICU) with serious pneumonia, say researchers from Hôpital Louis Mourier, Colombes, and Université Paris Diderot, both in France. Their concerns were triggered in part by witnessing several cases of unexpectedly severe forms of Streptococcus pneumoniae (S pneumoniae) community-acquired pneumonia (CAP) in healthy adults.
They analyzed data on 106 patients admitted with pneumococcal pneumonia or S pneumoniae and pneumonia as the discharge diagnosis. Twenty patients had received NSAIDs within 4 days prior to admission. The patients given NSAIDs were younger than those who were not prescribed NSAIDs (aged 43 years on average vs aged 62 years on average), usually working, and less likely to have comorbidities. The mean duration of NSAID treatment was 4 days. The time to the first medical consultation after pneumonia-related symptoms appeared was the same in both groups, but the patients on NSAIDs were prescribed antibiotics significantly later than those not taking NSAIDs (4.5 days vs 2 days, P = .001). They were also admitted to the ICU later.
A “noticeable and significant difference” was that more patients in the NSAID group had pleural effusion (P < .0006). New onset of pleuropulmonary complications during the ICU stay was significantly greater in the group who had received NSAIDs than in the no-NSAID group (P = .0008).
The researchers say their findings “highlight the overlooked risk of taking NSAIDs to treat physical symptoms at an early stage of CAP.” They hypothesize that patient age and comorbidity status led physicians to not diagnose CAP, and thus withhold antibiotics. NSAIDs may blunt general signs and symptoms and mask the severity of the infectious process, the researchers caution. Thus, they recommend ensuring appropriate antibiotic coverage along with NSAIDs.
In a survey of French general practitioners’ prescriptions, NSAIDs were prescribed for almost half of all patients seen for lower respiratory tract infection, “despite the fact that this prescription never appears in any national or international guideline,” the researchers say. That underscores the need to better inform general practitioners about the risks of NSAIDs, they say.
Source
Messika J, Sztrymf B, Bertrand F, et al. J Crit Care. 2014;29(5):733-738.
doi: 10.1016/j.jcrc.2014.05.021.
Nonsteroidal anti-inflammatory drugs (NSAIDs) given in the early stages of lower respiratory tract infection could be helping send younger adults to the intensive care unit (ICU) with serious pneumonia, say researchers from Hôpital Louis Mourier, Colombes, and Université Paris Diderot, both in France. Their concerns were triggered in part by witnessing several cases of unexpectedly severe forms of Streptococcus pneumoniae (S pneumoniae) community-acquired pneumonia (CAP) in healthy adults.
They analyzed data on 106 patients admitted with pneumococcal pneumonia or S pneumoniae and pneumonia as the discharge diagnosis. Twenty patients had received NSAIDs within 4 days prior to admission. The patients given NSAIDs were younger than those who were not prescribed NSAIDs (aged 43 years on average vs aged 62 years on average), usually working, and less likely to have comorbidities. The mean duration of NSAID treatment was 4 days. The time to the first medical consultation after pneumonia-related symptoms appeared was the same in both groups, but the patients on NSAIDs were prescribed antibiotics significantly later than those not taking NSAIDs (4.5 days vs 2 days, P = .001). They were also admitted to the ICU later.
A “noticeable and significant difference” was that more patients in the NSAID group had pleural effusion (P < .0006). New onset of pleuropulmonary complications during the ICU stay was significantly greater in the group who had received NSAIDs than in the no-NSAID group (P = .0008).
The researchers say their findings “highlight the overlooked risk of taking NSAIDs to treat physical symptoms at an early stage of CAP.” They hypothesize that patient age and comorbidity status led physicians to not diagnose CAP, and thus withhold antibiotics. NSAIDs may blunt general signs and symptoms and mask the severity of the infectious process, the researchers caution. Thus, they recommend ensuring appropriate antibiotic coverage along with NSAIDs.
In a survey of French general practitioners’ prescriptions, NSAIDs were prescribed for almost half of all patients seen for lower respiratory tract infection, “despite the fact that this prescription never appears in any national or international guideline,” the researchers say. That underscores the need to better inform general practitioners about the risks of NSAIDs, they say.
Source
Messika J, Sztrymf B, Bertrand F, et al. J Crit Care. 2014;29(5):733-738.
doi: 10.1016/j.jcrc.2014.05.021.
Do Benzodiazepines Increase Dementia Risk?
Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.
Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.
The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.
The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.
Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.
Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.
Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.
Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.
The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.
The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.
Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.
Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.
Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.
Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.
The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.
The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.
Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.
Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.