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Does use of an instant hand sanitizer reduce elementary school illness absenteeism?
BACKGROUND: Hand washing is generally considered to be beneficial in fighting the plethora of viral and bacterial pathogens in school settings. Many antimicrobial rinse-free hand-sanitizing formulas are available. The one chosen for this study (CleanHands) contains surfactants, allantoin, and benzalkonium chloride. Unlike alcohol- or triclosan-based products, this one has persistent antiviral and antimicrobial properties and does not irritate or dry the skin.
POPULATION STUDIED: All 420 students from a private elementary school were included. Their ages ranged from 5 to 12 years (all grades from kindergarten through sixth grade).
STUDY DESIGN AND VALIDITY: This was a 10-week crossover study of hand sanitizer use in conjunction with at-will soap and water hand washing. The subjects were not formally randomized; they were grouped by school class into 2 similar groups. There was no blinding. All of the students received education on the importance of hand washing before the study started. Seven classes then received instant hand sanitizer, and 7 were assigned to the control group. In addition to at-will hand washing with soap and water, children in the study group used the hand cleaner under teacher supervision immediately after entering the classroom, before eating, after sneezing or coughing, and after using the restroom. Children in the control group were only told to wash before eating and after going to the restroom but were not monitored for hand washing. The initial study group was evaluated for 4 weeks. After a 2-week washout period the 2 groups switched roles.
OUTCOMES MEASURED: The teachers recorded days absent, and parents provided the reasons for the absence, which if due to illness were then broken down into gastrointestinal (GI) illness versus respiratory illness.
RESULTS: During the study period the number of absences caused by a communicable acute illness was reduced by 33.6% (P=.001) in the first group and 55.7% (P=.001) in the second group compared with their respective control groups. Absences for all causes were reduced by 48% (P=.001) and 43% (P=.05) in the 2 groups. GI illnesses in the 2 groups were significantly reduced by 37.5% (P=.001) in the first group but not in the second group. Absences for respiratory illnesses were reduced 30.9% (P=.02) and 76% (P=.001) during the 2 time periods. During the 2-week washout period the absences were statistically similar between the 2 groups. No adverse events were reported.
This study demonstrated something mothers have always known: the benefit of clean hands. Clearly, having the teacher frequently tell children to clean their hands (and watching them do so) is more efficacious than giving them hall passes to go to the restroom unsupervised. Problems with this intervention include adding more responsibilities to teachers, adding training to institute this practice in public schools, and losing teaching time. This inexpensive, easy-to-use intervention could have an astounding impact, however, since the diverse effects of school absenteeism include effects on funding of public schools, remediation for absent students, and parents’ loss of work to stay home and care for sick children. As primary care providers, we should educate our young patients and their parents about the importance of clean hands.
BACKGROUND: Hand washing is generally considered to be beneficial in fighting the plethora of viral and bacterial pathogens in school settings. Many antimicrobial rinse-free hand-sanitizing formulas are available. The one chosen for this study (CleanHands) contains surfactants, allantoin, and benzalkonium chloride. Unlike alcohol- or triclosan-based products, this one has persistent antiviral and antimicrobial properties and does not irritate or dry the skin.
POPULATION STUDIED: All 420 students from a private elementary school were included. Their ages ranged from 5 to 12 years (all grades from kindergarten through sixth grade).
STUDY DESIGN AND VALIDITY: This was a 10-week crossover study of hand sanitizer use in conjunction with at-will soap and water hand washing. The subjects were not formally randomized; they were grouped by school class into 2 similar groups. There was no blinding. All of the students received education on the importance of hand washing before the study started. Seven classes then received instant hand sanitizer, and 7 were assigned to the control group. In addition to at-will hand washing with soap and water, children in the study group used the hand cleaner under teacher supervision immediately after entering the classroom, before eating, after sneezing or coughing, and after using the restroom. Children in the control group were only told to wash before eating and after going to the restroom but were not monitored for hand washing. The initial study group was evaluated for 4 weeks. After a 2-week washout period the 2 groups switched roles.
OUTCOMES MEASURED: The teachers recorded days absent, and parents provided the reasons for the absence, which if due to illness were then broken down into gastrointestinal (GI) illness versus respiratory illness.
RESULTS: During the study period the number of absences caused by a communicable acute illness was reduced by 33.6% (P=.001) in the first group and 55.7% (P=.001) in the second group compared with their respective control groups. Absences for all causes were reduced by 48% (P=.001) and 43% (P=.05) in the 2 groups. GI illnesses in the 2 groups were significantly reduced by 37.5% (P=.001) in the first group but not in the second group. Absences for respiratory illnesses were reduced 30.9% (P=.02) and 76% (P=.001) during the 2 time periods. During the 2-week washout period the absences were statistically similar between the 2 groups. No adverse events were reported.
This study demonstrated something mothers have always known: the benefit of clean hands. Clearly, having the teacher frequently tell children to clean their hands (and watching them do so) is more efficacious than giving them hall passes to go to the restroom unsupervised. Problems with this intervention include adding more responsibilities to teachers, adding training to institute this practice in public schools, and losing teaching time. This inexpensive, easy-to-use intervention could have an astounding impact, however, since the diverse effects of school absenteeism include effects on funding of public schools, remediation for absent students, and parents’ loss of work to stay home and care for sick children. As primary care providers, we should educate our young patients and their parents about the importance of clean hands.
BACKGROUND: Hand washing is generally considered to be beneficial in fighting the plethora of viral and bacterial pathogens in school settings. Many antimicrobial rinse-free hand-sanitizing formulas are available. The one chosen for this study (CleanHands) contains surfactants, allantoin, and benzalkonium chloride. Unlike alcohol- or triclosan-based products, this one has persistent antiviral and antimicrobial properties and does not irritate or dry the skin.
POPULATION STUDIED: All 420 students from a private elementary school were included. Their ages ranged from 5 to 12 years (all grades from kindergarten through sixth grade).
STUDY DESIGN AND VALIDITY: This was a 10-week crossover study of hand sanitizer use in conjunction with at-will soap and water hand washing. The subjects were not formally randomized; they were grouped by school class into 2 similar groups. There was no blinding. All of the students received education on the importance of hand washing before the study started. Seven classes then received instant hand sanitizer, and 7 were assigned to the control group. In addition to at-will hand washing with soap and water, children in the study group used the hand cleaner under teacher supervision immediately after entering the classroom, before eating, after sneezing or coughing, and after using the restroom. Children in the control group were only told to wash before eating and after going to the restroom but were not monitored for hand washing. The initial study group was evaluated for 4 weeks. After a 2-week washout period the 2 groups switched roles.
OUTCOMES MEASURED: The teachers recorded days absent, and parents provided the reasons for the absence, which if due to illness were then broken down into gastrointestinal (GI) illness versus respiratory illness.
RESULTS: During the study period the number of absences caused by a communicable acute illness was reduced by 33.6% (P=.001) in the first group and 55.7% (P=.001) in the second group compared with their respective control groups. Absences for all causes were reduced by 48% (P=.001) and 43% (P=.05) in the 2 groups. GI illnesses in the 2 groups were significantly reduced by 37.5% (P=.001) in the first group but not in the second group. Absences for respiratory illnesses were reduced 30.9% (P=.02) and 76% (P=.001) during the 2 time periods. During the 2-week washout period the absences were statistically similar between the 2 groups. No adverse events were reported.
This study demonstrated something mothers have always known: the benefit of clean hands. Clearly, having the teacher frequently tell children to clean their hands (and watching them do so) is more efficacious than giving them hall passes to go to the restroom unsupervised. Problems with this intervention include adding more responsibilities to teachers, adding training to institute this practice in public schools, and losing teaching time. This inexpensive, easy-to-use intervention could have an astounding impact, however, since the diverse effects of school absenteeism include effects on funding of public schools, remediation for absent students, and parents’ loss of work to stay home and care for sick children. As primary care providers, we should educate our young patients and their parents about the importance of clean hands.
Are antidepressants effective in the treatment of fibromyalgia, and is this effect independent of depression?
BACKGROUND: Common symptoms of fibromyalgia include chronic musculoskeletal pain and stiffness, fatigue, disrupted sleep, and tenderness over specific trigger points. Although commonly used for other chronic pain conditions, the efficacy of antidepressants for fibromyalgia is not well established. Also unclear is whether any benefit is independent of their effect on depression.
DATASOURCES: Forty-one articles comparing antidepressants with placebo for treating fibromyalgia were identified through a search of MEDLINE, PSYCLIT, EMBASE, FEDRIP, The Cochrane Library, and the reference list of retrieved articles. Sixteen of these were randomized placebo-controlled clinical trials reporting measurable outcomes. Two additional trials were excluded because the data were not extractable and another because it was a report of N-of-1 trials.
STUDY DESIGN AND VALIDITY: All of the potential articles were reviewed for inclusion in duplicate with strong inter-rater agreement. Each of the final 13 articles was assessed for quality by more than one person using an instrument developed by Jadad. The mean quality score was high at 5.6 (range=0-8). The authors listed the validity concerns of each article but did not exclude any of them. Since the studies were similar in terms of design, demographics, inclusion criteria, and outcomes assessment, the authors concluded quantitative pooling of the effects of antidepressants was appropriate. No effect of year of publication, study design, quality score, or drug class was found using meta-regression.
OUTCOMES MEASURED: The primary outcome was whether a patient was “improved” with therapy. Other outcomes included pain, fatigue, sleep disturbance, sense of well-being, and quantity and severity of trigger points. Additionally, the authors looked for any assessment of outcomes independent of the effect of therapy on depression.
RESULTS: From 10 trials with extractable data, the odds ratio for improvement with therapy was 4.2 (95% confidence interval [CI], 2.6-6.8). The number needed to treat (NNT) was 4 (95% CI, 2.9-6.3). The individual symptoms of pain, fatigue, sleep disturbance, and well-being showed significant improvements of moderate size, but quantity and severity of trigger points were not statistically different. The sample size was insufficient to draw meaningful conclusions regarding the relative benefit of different classes of antidepressants.
Antidepressants are effective for fibromyalgia, although it remains unclear whether this effect is independent of depression. With treatment, clinicians can expect 1 patient in 4 to improve. Antidepressants can reduce pain, fatigue, and disturbed sleep, and enhance the overall sense of well-being. However, they are not expected to diminish the severity of trigger point tenderness. Since there is more evidence for use of amitriptyline it should be considered first, but SSRIs may be just as effective. Clinicians will have to wait for additional studies to determine which class of antidepressants is most helpful and whether the benefits persist during long-term therapy for this chronic disease.
BACKGROUND: Common symptoms of fibromyalgia include chronic musculoskeletal pain and stiffness, fatigue, disrupted sleep, and tenderness over specific trigger points. Although commonly used for other chronic pain conditions, the efficacy of antidepressants for fibromyalgia is not well established. Also unclear is whether any benefit is independent of their effect on depression.
DATASOURCES: Forty-one articles comparing antidepressants with placebo for treating fibromyalgia were identified through a search of MEDLINE, PSYCLIT, EMBASE, FEDRIP, The Cochrane Library, and the reference list of retrieved articles. Sixteen of these were randomized placebo-controlled clinical trials reporting measurable outcomes. Two additional trials were excluded because the data were not extractable and another because it was a report of N-of-1 trials.
STUDY DESIGN AND VALIDITY: All of the potential articles were reviewed for inclusion in duplicate with strong inter-rater agreement. Each of the final 13 articles was assessed for quality by more than one person using an instrument developed by Jadad. The mean quality score was high at 5.6 (range=0-8). The authors listed the validity concerns of each article but did not exclude any of them. Since the studies were similar in terms of design, demographics, inclusion criteria, and outcomes assessment, the authors concluded quantitative pooling of the effects of antidepressants was appropriate. No effect of year of publication, study design, quality score, or drug class was found using meta-regression.
OUTCOMES MEASURED: The primary outcome was whether a patient was “improved” with therapy. Other outcomes included pain, fatigue, sleep disturbance, sense of well-being, and quantity and severity of trigger points. Additionally, the authors looked for any assessment of outcomes independent of the effect of therapy on depression.
RESULTS: From 10 trials with extractable data, the odds ratio for improvement with therapy was 4.2 (95% confidence interval [CI], 2.6-6.8). The number needed to treat (NNT) was 4 (95% CI, 2.9-6.3). The individual symptoms of pain, fatigue, sleep disturbance, and well-being showed significant improvements of moderate size, but quantity and severity of trigger points were not statistically different. The sample size was insufficient to draw meaningful conclusions regarding the relative benefit of different classes of antidepressants.
Antidepressants are effective for fibromyalgia, although it remains unclear whether this effect is independent of depression. With treatment, clinicians can expect 1 patient in 4 to improve. Antidepressants can reduce pain, fatigue, and disturbed sleep, and enhance the overall sense of well-being. However, they are not expected to diminish the severity of trigger point tenderness. Since there is more evidence for use of amitriptyline it should be considered first, but SSRIs may be just as effective. Clinicians will have to wait for additional studies to determine which class of antidepressants is most helpful and whether the benefits persist during long-term therapy for this chronic disease.
BACKGROUND: Common symptoms of fibromyalgia include chronic musculoskeletal pain and stiffness, fatigue, disrupted sleep, and tenderness over specific trigger points. Although commonly used for other chronic pain conditions, the efficacy of antidepressants for fibromyalgia is not well established. Also unclear is whether any benefit is independent of their effect on depression.
DATASOURCES: Forty-one articles comparing antidepressants with placebo for treating fibromyalgia were identified through a search of MEDLINE, PSYCLIT, EMBASE, FEDRIP, The Cochrane Library, and the reference list of retrieved articles. Sixteen of these were randomized placebo-controlled clinical trials reporting measurable outcomes. Two additional trials were excluded because the data were not extractable and another because it was a report of N-of-1 trials.
STUDY DESIGN AND VALIDITY: All of the potential articles were reviewed for inclusion in duplicate with strong inter-rater agreement. Each of the final 13 articles was assessed for quality by more than one person using an instrument developed by Jadad. The mean quality score was high at 5.6 (range=0-8). The authors listed the validity concerns of each article but did not exclude any of them. Since the studies were similar in terms of design, demographics, inclusion criteria, and outcomes assessment, the authors concluded quantitative pooling of the effects of antidepressants was appropriate. No effect of year of publication, study design, quality score, or drug class was found using meta-regression.
OUTCOMES MEASURED: The primary outcome was whether a patient was “improved” with therapy. Other outcomes included pain, fatigue, sleep disturbance, sense of well-being, and quantity and severity of trigger points. Additionally, the authors looked for any assessment of outcomes independent of the effect of therapy on depression.
RESULTS: From 10 trials with extractable data, the odds ratio for improvement with therapy was 4.2 (95% confidence interval [CI], 2.6-6.8). The number needed to treat (NNT) was 4 (95% CI, 2.9-6.3). The individual symptoms of pain, fatigue, sleep disturbance, and well-being showed significant improvements of moderate size, but quantity and severity of trigger points were not statistically different. The sample size was insufficient to draw meaningful conclusions regarding the relative benefit of different classes of antidepressants.
Antidepressants are effective for fibromyalgia, although it remains unclear whether this effect is independent of depression. With treatment, clinicians can expect 1 patient in 4 to improve. Antidepressants can reduce pain, fatigue, and disturbed sleep, and enhance the overall sense of well-being. However, they are not expected to diminish the severity of trigger point tenderness. Since there is more evidence for use of amitriptyline it should be considered first, but SSRIs may be just as effective. Clinicians will have to wait for additional studies to determine which class of antidepressants is most helpful and whether the benefits persist during long-term therapy for this chronic disease.
What is the most cost-effective screening regimen for colon cancer?
BACKGROUND: Expert panels recommend several different screening regimens for colorectal cancer (CRC), including annual fecal occult blood testing, sigmoidoscopy every 5 years, annual fecal occult blood testing plus flexible sigmoidoscopy every 5 years, double contrast barium enema every 5 years, and colonoscopy every 10 years. All of these tests vary considerably with respect to performance characteristics, complication rates, acceptability, and cost. Only fecal occult blood testing has been studied in a randomized controlled trial to establish effectiveness. This article compares the cost and effectiveness of CRC screening methods.
POPULATION STUDIED: The authors used a hypothetical population of men and women (white and black) aged 50 years and at average risk for colon cancer. They were placed in health categories defined by the presence or absence of a colon polyp or cancer. The categories were reassigned to simulate the natural progression of colon cancer on the basis of probabilities from studies and data from the Surveillance Epidemiology and End Results (SEER) program.
STUDY DESIGN AND VALIDITY: This study used a Markov model to simulate the evolution of normal epithelium in the colon to an adenomatous polyp and progression to malignancy. The screening mechanisms that allowed detection, removal of a polyp, and treatment of cancer were compared. Screening started at age 50 years and continued until age 85 years. Incremental analysis by rank ordering the strategies allowed methods of increasing effectiveness to dominate those methods that were more costly and less effective. Test and treatment costs were obtained from an health maintenance organization study population. Based on previous studies, an expected compliance rate of 60% was used to estimate the cost-effectiveness of screening tests. Sensitivity analysis was done to measure test performance when parameters such as test cost, sensitivity, specificity, and compliance rates were altered.
OUTCOMES MEASURED: The outcomes measured include cost-effectiveness of colorectal screening methods, life expectancy, and CRC incidence and mortality.
RESULTS: The reported results were for white men only. All CRC screening tests resulted in a reduced incidence of cancer and decreased mortality from CRC. Theoretically, the most effective test to screen for CRC is the annual rehydrated fecal occult blood test plus sigmoidoscopy every 5 years. This method has a cost-effectiveness ratio of $92,900 for each year of life saved. This compares similarly to the cost-effectiveness of screening Papanicolaou tests and mammograms. This method also resulted in a 60% reduction in the incidence of CRC and an 80% reduction in CRC mortality. Interestingly, the cost of this method became prohibitive if the model used a 100% compliance rate instead of 60%. Colonoscopy every 5 years is more effective than rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years but is cost prohibitive. If the price of colonoscopy could be reduced by 25%, colonoscopy every 10 years would be a viable option. Annual rehydrated fecal occult blood testing alone shows a 65% reduction in CRC mortality, while dry cards only show a 55% reduction. The longer life expectancy of women and the higher cancer mortality in African Americans may make CRC screening even more cost-effective in these groups.
According to this hypothetical analysis, the most effective test to screen for colorectal cancer is annual rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years (60% reduction in CRC incidence and 80% in CRC mortality). The cost-effectiveness is comparable with screening tests for other types of cancer. Annual rehydrated fecal occult blood testing alone provides a 38% decrease in CRC incidence and a 65% decrease in mortality. Future changes in the cost and availability of colonoscopy may offer an additional screening regimen with acceptable cost-effectiveness.
BACKGROUND: Expert panels recommend several different screening regimens for colorectal cancer (CRC), including annual fecal occult blood testing, sigmoidoscopy every 5 years, annual fecal occult blood testing plus flexible sigmoidoscopy every 5 years, double contrast barium enema every 5 years, and colonoscopy every 10 years. All of these tests vary considerably with respect to performance characteristics, complication rates, acceptability, and cost. Only fecal occult blood testing has been studied in a randomized controlled trial to establish effectiveness. This article compares the cost and effectiveness of CRC screening methods.
POPULATION STUDIED: The authors used a hypothetical population of men and women (white and black) aged 50 years and at average risk for colon cancer. They were placed in health categories defined by the presence or absence of a colon polyp or cancer. The categories were reassigned to simulate the natural progression of colon cancer on the basis of probabilities from studies and data from the Surveillance Epidemiology and End Results (SEER) program.
STUDY DESIGN AND VALIDITY: This study used a Markov model to simulate the evolution of normal epithelium in the colon to an adenomatous polyp and progression to malignancy. The screening mechanisms that allowed detection, removal of a polyp, and treatment of cancer were compared. Screening started at age 50 years and continued until age 85 years. Incremental analysis by rank ordering the strategies allowed methods of increasing effectiveness to dominate those methods that were more costly and less effective. Test and treatment costs were obtained from an health maintenance organization study population. Based on previous studies, an expected compliance rate of 60% was used to estimate the cost-effectiveness of screening tests. Sensitivity analysis was done to measure test performance when parameters such as test cost, sensitivity, specificity, and compliance rates were altered.
OUTCOMES MEASURED: The outcomes measured include cost-effectiveness of colorectal screening methods, life expectancy, and CRC incidence and mortality.
RESULTS: The reported results were for white men only. All CRC screening tests resulted in a reduced incidence of cancer and decreased mortality from CRC. Theoretically, the most effective test to screen for CRC is the annual rehydrated fecal occult blood test plus sigmoidoscopy every 5 years. This method has a cost-effectiveness ratio of $92,900 for each year of life saved. This compares similarly to the cost-effectiveness of screening Papanicolaou tests and mammograms. This method also resulted in a 60% reduction in the incidence of CRC and an 80% reduction in CRC mortality. Interestingly, the cost of this method became prohibitive if the model used a 100% compliance rate instead of 60%. Colonoscopy every 5 years is more effective than rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years but is cost prohibitive. If the price of colonoscopy could be reduced by 25%, colonoscopy every 10 years would be a viable option. Annual rehydrated fecal occult blood testing alone shows a 65% reduction in CRC mortality, while dry cards only show a 55% reduction. The longer life expectancy of women and the higher cancer mortality in African Americans may make CRC screening even more cost-effective in these groups.
According to this hypothetical analysis, the most effective test to screen for colorectal cancer is annual rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years (60% reduction in CRC incidence and 80% in CRC mortality). The cost-effectiveness is comparable with screening tests for other types of cancer. Annual rehydrated fecal occult blood testing alone provides a 38% decrease in CRC incidence and a 65% decrease in mortality. Future changes in the cost and availability of colonoscopy may offer an additional screening regimen with acceptable cost-effectiveness.
BACKGROUND: Expert panels recommend several different screening regimens for colorectal cancer (CRC), including annual fecal occult blood testing, sigmoidoscopy every 5 years, annual fecal occult blood testing plus flexible sigmoidoscopy every 5 years, double contrast barium enema every 5 years, and colonoscopy every 10 years. All of these tests vary considerably with respect to performance characteristics, complication rates, acceptability, and cost. Only fecal occult blood testing has been studied in a randomized controlled trial to establish effectiveness. This article compares the cost and effectiveness of CRC screening methods.
POPULATION STUDIED: The authors used a hypothetical population of men and women (white and black) aged 50 years and at average risk for colon cancer. They were placed in health categories defined by the presence or absence of a colon polyp or cancer. The categories were reassigned to simulate the natural progression of colon cancer on the basis of probabilities from studies and data from the Surveillance Epidemiology and End Results (SEER) program.
STUDY DESIGN AND VALIDITY: This study used a Markov model to simulate the evolution of normal epithelium in the colon to an adenomatous polyp and progression to malignancy. The screening mechanisms that allowed detection, removal of a polyp, and treatment of cancer were compared. Screening started at age 50 years and continued until age 85 years. Incremental analysis by rank ordering the strategies allowed methods of increasing effectiveness to dominate those methods that were more costly and less effective. Test and treatment costs were obtained from an health maintenance organization study population. Based on previous studies, an expected compliance rate of 60% was used to estimate the cost-effectiveness of screening tests. Sensitivity analysis was done to measure test performance when parameters such as test cost, sensitivity, specificity, and compliance rates were altered.
OUTCOMES MEASURED: The outcomes measured include cost-effectiveness of colorectal screening methods, life expectancy, and CRC incidence and mortality.
RESULTS: The reported results were for white men only. All CRC screening tests resulted in a reduced incidence of cancer and decreased mortality from CRC. Theoretically, the most effective test to screen for CRC is the annual rehydrated fecal occult blood test plus sigmoidoscopy every 5 years. This method has a cost-effectiveness ratio of $92,900 for each year of life saved. This compares similarly to the cost-effectiveness of screening Papanicolaou tests and mammograms. This method also resulted in a 60% reduction in the incidence of CRC and an 80% reduction in CRC mortality. Interestingly, the cost of this method became prohibitive if the model used a 100% compliance rate instead of 60%. Colonoscopy every 5 years is more effective than rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years but is cost prohibitive. If the price of colonoscopy could be reduced by 25%, colonoscopy every 10 years would be a viable option. Annual rehydrated fecal occult blood testing alone shows a 65% reduction in CRC mortality, while dry cards only show a 55% reduction. The longer life expectancy of women and the higher cancer mortality in African Americans may make CRC screening even more cost-effective in these groups.
According to this hypothetical analysis, the most effective test to screen for colorectal cancer is annual rehydrated fecal occult blood testing plus sigmoidoscopy every 5 years (60% reduction in CRC incidence and 80% in CRC mortality). The cost-effectiveness is comparable with screening tests for other types of cancer. Annual rehydrated fecal occult blood testing alone provides a 38% decrease in CRC incidence and a 65% decrease in mortality. Future changes in the cost and availability of colonoscopy may offer an additional screening regimen with acceptable cost-effectiveness.
Is the combination of ibuprofen and caffeine effective for the treatment of a tension-type headache?
BACKGROUND: Studies have shown the effectiveness of the addition of caffeine to ibuprofen for acute pain. However, this combination for use in tension-type headaches has been less well studied because of insensitive methods for evaluating this type of headache pain. The purpose of this study was to evaluate the efficacy of ibuprofen plus caffeine for the treatment of tension-type headaches and to establish a sensitive method to compare the combination versus either agent alone.
POPULATION STUDIED: This multicenter study reported on 301 evaluable patients with a history of tension-type headaches as defined by the International Headache Society.1 The mean age of the patients was 37 years. Patients were included who had 3 to 15 tension-type headaches every month for the past year and were responsive to over-the-counter analgesics at least 75% of the time. Patients who also suffered from migraines were able to participate if the type of headache pain could be differentiated by the quality of the pain or associated symptoms. Patients were excluded if they were allergic to the study drugs or had a comorbid illness that could potentially affect the pharmacokinetics of the study medication.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind parallel single-dose placebo-controlled trial comparing ibuprofen (400 mg) plus caffeine (200 mg), ibuprofen (400 mg), caffeine (200 mg), or placebo. Patients were instructed to take the study medication to treat a tension-type headache of at least moderate severity. They rated baseline pain intensity (4-point scale) and pain intensity and pain relief (5-point scale) at several time points over the next 6 hours. Patients were also given 2 stopwatches and were instructed to start both of them when the dose of medication was taken, to stop one at the onset of perceptible headache improvement, and to stop the second one after achieving meaningful headache improvement.
OUTCOMES MEASURED: Pain reduction, pain relief, and onset of relief measured as time to first perceptible relief and time to meaningful relief were the primary outcomes.
RESULTS: Pain reduction and pain relief were significantly greater for the combination of ibuprofen plus caffeine compared with placebo or either agent alone. The median time to perceptible and meaningful headache improvement was faster for patients treated with ibuprofen plus caffeine compared with ibuprofen alone or placebo (P <.05), though it was not different from caffeine alone. However, 80% of patients receiving ibuprofen plus caffeine experienced a meaningful improvement in headache compared with 67%, 61%, and 56% receiving ibuprofen alone, caffeine alone, or placebo, respectively. The percentage of patients achieving complete relief did not differ between the groups, perhaps because of the small sample size. Overall evaluations of the study medication were higher for the combination than for either agent alone or placebo (P=.007). The most common adverse effects reported were nervousness, nausea, and dizziness and occurred primarily in patients receiving either caffeine alone or ibuprofen plus caffeine.
The combination of ibuprofen and caffeine provides enhanced analgesic activity compared with ibuprofen alone. The additional analgesic effect of caffeine should be weighed against the increased risk of side effects. Caffeine is available in combination with acetaminophen or aspirin, but there are currently no products in the United States that contain ibuprofen plus caffeine.
BACKGROUND: Studies have shown the effectiveness of the addition of caffeine to ibuprofen for acute pain. However, this combination for use in tension-type headaches has been less well studied because of insensitive methods for evaluating this type of headache pain. The purpose of this study was to evaluate the efficacy of ibuprofen plus caffeine for the treatment of tension-type headaches and to establish a sensitive method to compare the combination versus either agent alone.
POPULATION STUDIED: This multicenter study reported on 301 evaluable patients with a history of tension-type headaches as defined by the International Headache Society.1 The mean age of the patients was 37 years. Patients were included who had 3 to 15 tension-type headaches every month for the past year and were responsive to over-the-counter analgesics at least 75% of the time. Patients who also suffered from migraines were able to participate if the type of headache pain could be differentiated by the quality of the pain or associated symptoms. Patients were excluded if they were allergic to the study drugs or had a comorbid illness that could potentially affect the pharmacokinetics of the study medication.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind parallel single-dose placebo-controlled trial comparing ibuprofen (400 mg) plus caffeine (200 mg), ibuprofen (400 mg), caffeine (200 mg), or placebo. Patients were instructed to take the study medication to treat a tension-type headache of at least moderate severity. They rated baseline pain intensity (4-point scale) and pain intensity and pain relief (5-point scale) at several time points over the next 6 hours. Patients were also given 2 stopwatches and were instructed to start both of them when the dose of medication was taken, to stop one at the onset of perceptible headache improvement, and to stop the second one after achieving meaningful headache improvement.
OUTCOMES MEASURED: Pain reduction, pain relief, and onset of relief measured as time to first perceptible relief and time to meaningful relief were the primary outcomes.
RESULTS: Pain reduction and pain relief were significantly greater for the combination of ibuprofen plus caffeine compared with placebo or either agent alone. The median time to perceptible and meaningful headache improvement was faster for patients treated with ibuprofen plus caffeine compared with ibuprofen alone or placebo (P <.05), though it was not different from caffeine alone. However, 80% of patients receiving ibuprofen plus caffeine experienced a meaningful improvement in headache compared with 67%, 61%, and 56% receiving ibuprofen alone, caffeine alone, or placebo, respectively. The percentage of patients achieving complete relief did not differ between the groups, perhaps because of the small sample size. Overall evaluations of the study medication were higher for the combination than for either agent alone or placebo (P=.007). The most common adverse effects reported were nervousness, nausea, and dizziness and occurred primarily in patients receiving either caffeine alone or ibuprofen plus caffeine.
The combination of ibuprofen and caffeine provides enhanced analgesic activity compared with ibuprofen alone. The additional analgesic effect of caffeine should be weighed against the increased risk of side effects. Caffeine is available in combination with acetaminophen or aspirin, but there are currently no products in the United States that contain ibuprofen plus caffeine.
BACKGROUND: Studies have shown the effectiveness of the addition of caffeine to ibuprofen for acute pain. However, this combination for use in tension-type headaches has been less well studied because of insensitive methods for evaluating this type of headache pain. The purpose of this study was to evaluate the efficacy of ibuprofen plus caffeine for the treatment of tension-type headaches and to establish a sensitive method to compare the combination versus either agent alone.
POPULATION STUDIED: This multicenter study reported on 301 evaluable patients with a history of tension-type headaches as defined by the International Headache Society.1 The mean age of the patients was 37 years. Patients were included who had 3 to 15 tension-type headaches every month for the past year and were responsive to over-the-counter analgesics at least 75% of the time. Patients who also suffered from migraines were able to participate if the type of headache pain could be differentiated by the quality of the pain or associated symptoms. Patients were excluded if they were allergic to the study drugs or had a comorbid illness that could potentially affect the pharmacokinetics of the study medication.
STUDY DESIGN AND VALIDITY: This was a randomized double-blind parallel single-dose placebo-controlled trial comparing ibuprofen (400 mg) plus caffeine (200 mg), ibuprofen (400 mg), caffeine (200 mg), or placebo. Patients were instructed to take the study medication to treat a tension-type headache of at least moderate severity. They rated baseline pain intensity (4-point scale) and pain intensity and pain relief (5-point scale) at several time points over the next 6 hours. Patients were also given 2 stopwatches and were instructed to start both of them when the dose of medication was taken, to stop one at the onset of perceptible headache improvement, and to stop the second one after achieving meaningful headache improvement.
OUTCOMES MEASURED: Pain reduction, pain relief, and onset of relief measured as time to first perceptible relief and time to meaningful relief were the primary outcomes.
RESULTS: Pain reduction and pain relief were significantly greater for the combination of ibuprofen plus caffeine compared with placebo or either agent alone. The median time to perceptible and meaningful headache improvement was faster for patients treated with ibuprofen plus caffeine compared with ibuprofen alone or placebo (P <.05), though it was not different from caffeine alone. However, 80% of patients receiving ibuprofen plus caffeine experienced a meaningful improvement in headache compared with 67%, 61%, and 56% receiving ibuprofen alone, caffeine alone, or placebo, respectively. The percentage of patients achieving complete relief did not differ between the groups, perhaps because of the small sample size. Overall evaluations of the study medication were higher for the combination than for either agent alone or placebo (P=.007). The most common adverse effects reported were nervousness, nausea, and dizziness and occurred primarily in patients receiving either caffeine alone or ibuprofen plus caffeine.
The combination of ibuprofen and caffeine provides enhanced analgesic activity compared with ibuprofen alone. The additional analgesic effect of caffeine should be weighed against the increased risk of side effects. Caffeine is available in combination with acetaminophen or aspirin, but there are currently no products in the United States that contain ibuprofen plus caffeine.
Can vaginal misoprostol be administered 1 to 3 days after mifepristone without loss of efficacy or an increase in adverse events?
BACKGROUND: The United States Food and Drug Administration (FDA) has approved the use of mifepristone (RU 486) in a protocol for early medical abortion.1 In that protocol, 600 μg of mifepristone is followed by 400 μg of oral misoprostol 48 hours later. Previous studies have shown that low-dose mifepristone (200 μg) followed 2 days later by 800 μg vaginal misoprostol has fewer side effects and is more effective than the approved protocol. Restricting administration of vaginal misoprostol to a narrow time window 2 days after the mifepristone dose may be inconvenient or unsafe.
POPULATION STUDIED: Healthy pregnant women aged 18 years and older who desired abortions were recruited from 16 sites including hospitals, abortion clinics, family practice offices, and gynecology offices. A total of 2295 women were recruited, and all underwent a transvaginal ultrasound to rule out ectopic pregnancy and to confirm fetal size consistent with a gestation of 56 days or less.
STUDY DESIGN AND VALIDITY: This is an unblinded randomized controlled trial with 3 arms. Subjects were assigned by concealed computer-generated randomization to self-administered 800 μg misoprostol vaginally either 1 (n=745), 2 (n=778), or 3 (n=772) days after a 200-μg dose of mifepristone.
OUTCOMES MEASURED: Complete medical abortion without surgical intervention was the primary outcome.
RESULTS: There was no statistically significant difference in the percentage of women who had complete medical abortions across the 3 groups. The percentages of complete medical abortions for the day 1 and day 2 groups were both 98% (95% confidence interval [CI], 97%-99%), and for the day 3 group it was 96% (95% CI, 95%-97%).
Low-dose mifepristone (200 μg) followed 1 to 3 days later by 800 μg of self-administered vaginal misoprostol is a safe and effective procedure for early medical abortion. Rigid adherence to the oral administration of misoprostol in a medical office 48 hours after mifepristone is not necessary either from a safety or efficacy perspective. Administration of misoprostol 1 or 2 days after mifepristone is preferable, since patients in the day 3 group found the wait less acceptable. Information is available on the Internet about FDA special requirements and approved protocols involving mifepristone.1
BACKGROUND: The United States Food and Drug Administration (FDA) has approved the use of mifepristone (RU 486) in a protocol for early medical abortion.1 In that protocol, 600 μg of mifepristone is followed by 400 μg of oral misoprostol 48 hours later. Previous studies have shown that low-dose mifepristone (200 μg) followed 2 days later by 800 μg vaginal misoprostol has fewer side effects and is more effective than the approved protocol. Restricting administration of vaginal misoprostol to a narrow time window 2 days after the mifepristone dose may be inconvenient or unsafe.
POPULATION STUDIED: Healthy pregnant women aged 18 years and older who desired abortions were recruited from 16 sites including hospitals, abortion clinics, family practice offices, and gynecology offices. A total of 2295 women were recruited, and all underwent a transvaginal ultrasound to rule out ectopic pregnancy and to confirm fetal size consistent with a gestation of 56 days or less.
STUDY DESIGN AND VALIDITY: This is an unblinded randomized controlled trial with 3 arms. Subjects were assigned by concealed computer-generated randomization to self-administered 800 μg misoprostol vaginally either 1 (n=745), 2 (n=778), or 3 (n=772) days after a 200-μg dose of mifepristone.
OUTCOMES MEASURED: Complete medical abortion without surgical intervention was the primary outcome.
RESULTS: There was no statistically significant difference in the percentage of women who had complete medical abortions across the 3 groups. The percentages of complete medical abortions for the day 1 and day 2 groups were both 98% (95% confidence interval [CI], 97%-99%), and for the day 3 group it was 96% (95% CI, 95%-97%).
Low-dose mifepristone (200 μg) followed 1 to 3 days later by 800 μg of self-administered vaginal misoprostol is a safe and effective procedure for early medical abortion. Rigid adherence to the oral administration of misoprostol in a medical office 48 hours after mifepristone is not necessary either from a safety or efficacy perspective. Administration of misoprostol 1 or 2 days after mifepristone is preferable, since patients in the day 3 group found the wait less acceptable. Information is available on the Internet about FDA special requirements and approved protocols involving mifepristone.1
BACKGROUND: The United States Food and Drug Administration (FDA) has approved the use of mifepristone (RU 486) in a protocol for early medical abortion.1 In that protocol, 600 μg of mifepristone is followed by 400 μg of oral misoprostol 48 hours later. Previous studies have shown that low-dose mifepristone (200 μg) followed 2 days later by 800 μg vaginal misoprostol has fewer side effects and is more effective than the approved protocol. Restricting administration of vaginal misoprostol to a narrow time window 2 days after the mifepristone dose may be inconvenient or unsafe.
POPULATION STUDIED: Healthy pregnant women aged 18 years and older who desired abortions were recruited from 16 sites including hospitals, abortion clinics, family practice offices, and gynecology offices. A total of 2295 women were recruited, and all underwent a transvaginal ultrasound to rule out ectopic pregnancy and to confirm fetal size consistent with a gestation of 56 days or less.
STUDY DESIGN AND VALIDITY: This is an unblinded randomized controlled trial with 3 arms. Subjects were assigned by concealed computer-generated randomization to self-administered 800 μg misoprostol vaginally either 1 (n=745), 2 (n=778), or 3 (n=772) days after a 200-μg dose of mifepristone.
OUTCOMES MEASURED: Complete medical abortion without surgical intervention was the primary outcome.
RESULTS: There was no statistically significant difference in the percentage of women who had complete medical abortions across the 3 groups. The percentages of complete medical abortions for the day 1 and day 2 groups were both 98% (95% confidence interval [CI], 97%-99%), and for the day 3 group it was 96% (95% CI, 95%-97%).
Low-dose mifepristone (200 μg) followed 1 to 3 days later by 800 μg of self-administered vaginal misoprostol is a safe and effective procedure for early medical abortion. Rigid adherence to the oral administration of misoprostol in a medical office 48 hours after mifepristone is not necessary either from a safety or efficacy perspective. Administration of misoprostol 1 or 2 days after mifepristone is preferable, since patients in the day 3 group found the wait less acceptable. Information is available on the Internet about FDA special requirements and approved protocols involving mifepristone.1
Are zinc acetate lozenges effective in decreasing the duration of symptoms of the common cold?
BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.
POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).
OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.
RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.
POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).
OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.
RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
BACKGROUND: Of the 10 published randomized controlled trials, only 5 reported that zinc lozenges reduced the duration of cold symptoms. The reasons for the different results among these trials include differences in doses, salts, and formulations of zinc lozenges; differences in study design; and difficulty in truly blinding study participants.
POPULATION STUDIED: Fifty ambulatory volunteers older than 18 years were recruited within 24 hours of developing cold symptoms. Potential participants were students, staff, or employees of Wayne State University who had at least 2 of 10 cold symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever. Exclusion criteria included pregnancy, immunodeficiency disorder, any chronic illness, and previous use of zinc lozenges. The treatment groups did not differ significantly in terms of age (37±11 years), however, more patients receiving placebo were smokers (35% vs 20%) and had an allergy history (15% vs 8%).
STUDY DESIGN AND VALIDITY: The appropriate study design was used for this efficacy trial. Two patients in the placebo group dropped out on day 2; all other patients completed the study and were included in the analysis. The patients, the research consultant preparing the randomization code and packages of medications, and a research assistant distributing the study medication were not aware of treatment assignment (ie, allocation was concealed).
OUTCOMES MEASURED: Both patient-oriented (cold symptoms) and disease-oriented (plasma levels of zinc and cytokines) outcomes were used to assess the patients. The primary outcome was average duration of cold symptoms.
RESULTS: Zinc-treated patients had lower overall severity scores (P <.002, test for treatment x time interaction), as well as a significantly shorter mean duration of all cold symptoms, 4.5 versus 8.1 days (3.6-day difference; 95% confidence interval, 2.6-4.6 days; P <.01). By day 4, the average severity score in the zinc group was half that in the placebo group (2.7 vs 5.4 out of a possible 30). Of the 10 measured cold symptoms, only the duration of nasal discharge and cough were significantly shorter in the zinc-treated patients. The average number of lozenges taken per day did not differ between treatment groups (6.2 for zinc and 5.8 for placebo). Patients in the zinc group had a statistically significant higher incidence of dry mouth (P=.003) and constipation (P=.02). Although it did not reach statistical significance, zinc-treated patients experienced more bad taste (52% vs 26%, P=.08).
The zinc acetate lozenge formulation used in this well-designed study was more effective than placebo in decreasing the duration and severity of cold symptoms, especially cough and nasal discharge. However, twice as many zinc-treated subjects correctly identified their lozenges at the end of the study, suggesting that blinding may not have been completely maintained. Also, the 2 groups differed with regard to potential confounders (ie, smoking status and allergy history). Despite these shortcomings, this study adds to the growing evidence that certain zinc lozenge formulations shorten the duration and decrease the severity of cold symptoms.
Are there differences by gender in response to pharmacotherapy for depression?
BACKGROUND: Depression is common in primary care, but little is known about gender differences in response to medication. This randomized trial compared men and women in response to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).
POPULATION STUDIED: A total of 235 men and 400 women between 21 and 65 years who meet Diagnostic and Statistical Manual of Mental Disorders, third edition, revised criteria for major depression with or without dysthymia were enrolled at 12 centers. The average age for men and women was 43 and 40 years, respectively. Of these, 91% were white; 64% had recurrent depression; 54% were also dysthymic; and 57% were previously treated with pharmacotherapy. Depressive symptoms were severe, averaging 25 on the Hamilton Depression (HAM-D) scale. The study population was probably similar to many patients seen by family physicians but with more severe depressive symptoms and more dysthymia. Caution should be exercised in extrapolating results to patients with mild depression, patients of color, or anyone older than 65 years.
STUDY DESIGN AND VALIDITY: This was a randomized controlled trial (allocation assignment concealed). Subjects were given imipramine or sertraline starting at 50 mg per day. Doses were increased until therapeutic results or intolerable side effects occurred, to an average of approximately 140 mg per day of sertraline and 200 mg per day for imipramine. Response to medication was measured by the HAM-D, Beck, and Clinical Global Severity and Improvement (CGI) scales. Analyses of baseline characteristics and end points were performed using the Mantel-Haenszel chi-square and analysis of variance, adjusted for site, baseline severity, and type of depression. Methodologic strengths include the randomized design, efforts to conceal allocation, and use of both intention-to-treat and efficacy-only analysis. Minor weaknesses included lack of information about treatment groups at baseline, absence of a true placebo, and the lack of control for potentially important confounding factors, such as concurrent psychotherapy, other treatments, and social support.
OUTCOMES MEASURED: Response was defined as a 50% decrease of HAM-D score, a HAM-D score of less than 15, a CGI severity score of less than or equal to 3, or a CGI improvement score of 1 or 2. Compliance, side effects, and withdrawals were also tracked. Outcomes important in primary care that were not addressed include other clinical outcomes (suicide attempts, hospitalization), the use of other modalities (additional medication, electroconvulsive therapy, therapy), functional status, patient satisfaction, and cost of care.
RESULTS: Men and women were somewhat different at baseline, although the authors did not report the characteristics of each treatment subgroup. Women were significantly more likely to have been treated for depression and to have a first-degree relative with depression, while men were more likely to be married and to have coexistent dysthymia. Follow-up was complete. Women responded better to sertraline than imipramine (57% improved vs 46%; P=.03; number needed to treat [NNT]=8), and men responded more to imipramine than to sertraline (62% vs 45%; P=.03; NNT=6). Women taking imipramine were more likely to withdraw from the study than those taking sertraline (26% vs 14%; P=.02; NNH=10), but women completing a course of imipramine still had a significantly poorer response than those taking sertraline. Men and women taking either drug showed no significant sex differences in overall frequency of treatment-emergent adverse events; however, more than 90% of all patients reported adverse effects, and adverse effects were the most common reason for withdrawal from the study. For men, imipramine caused significantly more dry mouth, dizziness, and constipation than sertralin, and a similarly high rate of sexual dysfunction and somnolence. For women, sertraline caused significantly more insomnia and diarrhea and less constipation and dry mouth than imipramine.
This study provides good evidence of gender differences in response to sertraline and imipramine for depression. Clinicians should consider using imipramine as first-line pharmacotherapy for men with depression. Like all tricyclics, imipramine carries a risk of cardiac toxicity in overdose, but clinicians should keep in mind that the risk of suicide is similar for all antidepressants. Sertraline remains a good first choice for women. Further research should address the generalizability of these results to other agents in their class, treatment in the elderly, and the role of cognitive/behavioral therapy for each sex.
BACKGROUND: Depression is common in primary care, but little is known about gender differences in response to medication. This randomized trial compared men and women in response to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).
POPULATION STUDIED: A total of 235 men and 400 women between 21 and 65 years who meet Diagnostic and Statistical Manual of Mental Disorders, third edition, revised criteria for major depression with or without dysthymia were enrolled at 12 centers. The average age for men and women was 43 and 40 years, respectively. Of these, 91% were white; 64% had recurrent depression; 54% were also dysthymic; and 57% were previously treated with pharmacotherapy. Depressive symptoms were severe, averaging 25 on the Hamilton Depression (HAM-D) scale. The study population was probably similar to many patients seen by family physicians but with more severe depressive symptoms and more dysthymia. Caution should be exercised in extrapolating results to patients with mild depression, patients of color, or anyone older than 65 years.
STUDY DESIGN AND VALIDITY: This was a randomized controlled trial (allocation assignment concealed). Subjects were given imipramine or sertraline starting at 50 mg per day. Doses were increased until therapeutic results or intolerable side effects occurred, to an average of approximately 140 mg per day of sertraline and 200 mg per day for imipramine. Response to medication was measured by the HAM-D, Beck, and Clinical Global Severity and Improvement (CGI) scales. Analyses of baseline characteristics and end points were performed using the Mantel-Haenszel chi-square and analysis of variance, adjusted for site, baseline severity, and type of depression. Methodologic strengths include the randomized design, efforts to conceal allocation, and use of both intention-to-treat and efficacy-only analysis. Minor weaknesses included lack of information about treatment groups at baseline, absence of a true placebo, and the lack of control for potentially important confounding factors, such as concurrent psychotherapy, other treatments, and social support.
OUTCOMES MEASURED: Response was defined as a 50% decrease of HAM-D score, a HAM-D score of less than 15, a CGI severity score of less than or equal to 3, or a CGI improvement score of 1 or 2. Compliance, side effects, and withdrawals were also tracked. Outcomes important in primary care that were not addressed include other clinical outcomes (suicide attempts, hospitalization), the use of other modalities (additional medication, electroconvulsive therapy, therapy), functional status, patient satisfaction, and cost of care.
RESULTS: Men and women were somewhat different at baseline, although the authors did not report the characteristics of each treatment subgroup. Women were significantly more likely to have been treated for depression and to have a first-degree relative with depression, while men were more likely to be married and to have coexistent dysthymia. Follow-up was complete. Women responded better to sertraline than imipramine (57% improved vs 46%; P=.03; number needed to treat [NNT]=8), and men responded more to imipramine than to sertraline (62% vs 45%; P=.03; NNT=6). Women taking imipramine were more likely to withdraw from the study than those taking sertraline (26% vs 14%; P=.02; NNH=10), but women completing a course of imipramine still had a significantly poorer response than those taking sertraline. Men and women taking either drug showed no significant sex differences in overall frequency of treatment-emergent adverse events; however, more than 90% of all patients reported adverse effects, and adverse effects were the most common reason for withdrawal from the study. For men, imipramine caused significantly more dry mouth, dizziness, and constipation than sertralin, and a similarly high rate of sexual dysfunction and somnolence. For women, sertraline caused significantly more insomnia and diarrhea and less constipation and dry mouth than imipramine.
This study provides good evidence of gender differences in response to sertraline and imipramine for depression. Clinicians should consider using imipramine as first-line pharmacotherapy for men with depression. Like all tricyclics, imipramine carries a risk of cardiac toxicity in overdose, but clinicians should keep in mind that the risk of suicide is similar for all antidepressants. Sertraline remains a good first choice for women. Further research should address the generalizability of these results to other agents in their class, treatment in the elderly, and the role of cognitive/behavioral therapy for each sex.
BACKGROUND: Depression is common in primary care, but little is known about gender differences in response to medication. This randomized trial compared men and women in response to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).
POPULATION STUDIED: A total of 235 men and 400 women between 21 and 65 years who meet Diagnostic and Statistical Manual of Mental Disorders, third edition, revised criteria for major depression with or without dysthymia were enrolled at 12 centers. The average age for men and women was 43 and 40 years, respectively. Of these, 91% were white; 64% had recurrent depression; 54% were also dysthymic; and 57% were previously treated with pharmacotherapy. Depressive symptoms were severe, averaging 25 on the Hamilton Depression (HAM-D) scale. The study population was probably similar to many patients seen by family physicians but with more severe depressive symptoms and more dysthymia. Caution should be exercised in extrapolating results to patients with mild depression, patients of color, or anyone older than 65 years.
STUDY DESIGN AND VALIDITY: This was a randomized controlled trial (allocation assignment concealed). Subjects were given imipramine or sertraline starting at 50 mg per day. Doses were increased until therapeutic results or intolerable side effects occurred, to an average of approximately 140 mg per day of sertraline and 200 mg per day for imipramine. Response to medication was measured by the HAM-D, Beck, and Clinical Global Severity and Improvement (CGI) scales. Analyses of baseline characteristics and end points were performed using the Mantel-Haenszel chi-square and analysis of variance, adjusted for site, baseline severity, and type of depression. Methodologic strengths include the randomized design, efforts to conceal allocation, and use of both intention-to-treat and efficacy-only analysis. Minor weaknesses included lack of information about treatment groups at baseline, absence of a true placebo, and the lack of control for potentially important confounding factors, such as concurrent psychotherapy, other treatments, and social support.
OUTCOMES MEASURED: Response was defined as a 50% decrease of HAM-D score, a HAM-D score of less than 15, a CGI severity score of less than or equal to 3, or a CGI improvement score of 1 or 2. Compliance, side effects, and withdrawals were also tracked. Outcomes important in primary care that were not addressed include other clinical outcomes (suicide attempts, hospitalization), the use of other modalities (additional medication, electroconvulsive therapy, therapy), functional status, patient satisfaction, and cost of care.
RESULTS: Men and women were somewhat different at baseline, although the authors did not report the characteristics of each treatment subgroup. Women were significantly more likely to have been treated for depression and to have a first-degree relative with depression, while men were more likely to be married and to have coexistent dysthymia. Follow-up was complete. Women responded better to sertraline than imipramine (57% improved vs 46%; P=.03; number needed to treat [NNT]=8), and men responded more to imipramine than to sertraline (62% vs 45%; P=.03; NNT=6). Women taking imipramine were more likely to withdraw from the study than those taking sertraline (26% vs 14%; P=.02; NNH=10), but women completing a course of imipramine still had a significantly poorer response than those taking sertraline. Men and women taking either drug showed no significant sex differences in overall frequency of treatment-emergent adverse events; however, more than 90% of all patients reported adverse effects, and adverse effects were the most common reason for withdrawal from the study. For men, imipramine caused significantly more dry mouth, dizziness, and constipation than sertralin, and a similarly high rate of sexual dysfunction and somnolence. For women, sertraline caused significantly more insomnia and diarrhea and less constipation and dry mouth than imipramine.
This study provides good evidence of gender differences in response to sertraline and imipramine for depression. Clinicians should consider using imipramine as first-line pharmacotherapy for men with depression. Like all tricyclics, imipramine carries a risk of cardiac toxicity in overdose, but clinicians should keep in mind that the risk of suicide is similar for all antidepressants. Sertraline remains a good first choice for women. Further research should address the generalizability of these results to other agents in their class, treatment in the elderly, and the role of cognitive/behavioral therapy for each sex.
Do women with impaired sexual function following oophorectomy benefit from transdermal testosterone at a physiologic dose?
BACKGROUND: Women who undergo bilateral oophorectomy before menopause experience a 50% drop in serum testosterone because of a lack of ovarian androgen production. Many of these women report decreased sexual desire and activity, and pleasure not improved with estrogen therapy. Previous studies of testosterone therapy have used supraphysiologic doses and were not double blinded.
POPULATION STUDIED: The investigators enrolled 75 healthy women aged 31 to 56 years from 9 clinical sites in the United States. The method of patient recruitment was not specified. Approximately two thirds of the patients were married, and two thirds were white. All had undergone bilateral salpingo-oophorectomy and hysterectomy a mean of 4.7 years ago. Other inclusion criteria were treatment with at least 0.625 mg conjugated equine estrogen daily for 2 months, history of a stable monogamous heterosexual relationship for 1 year, and a composite sexual function score (Brief Index of Sexual Functioning for Women) less than the mean value for normal women. Persons taking steroids, selective serotonin reuptake inhibitors, or tricyclic antidepressants were excluded.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled crossover study occurring over 40 consecutive weeks. It consisted of a 4-week baseline period followed by 3 12-week treatment periods. Using identical-appearing experimental patches, patients received in random order placebo, testosterone 150 mg per day, and testosterone 300 mg per day transdermally for 12 weeks each. The Brief Index of Sexual Functioning for Women was used to determine a composite sexual function score at baseline and again after each treatment period. Intention-to-treat data analysis was performed for the 65 women who completed this index at least once during treatment. Mood was assessed at similar intervals using the Psychological General Well-Being Index. A telephone-based diary was used to assess the self-reported frequency of sexual thoughts, desires, and activities. Standard laboratory tests and validated measures of hirsutism and acne were used to determine safety and tolerability. The crossover design did not include a washout period. However, analysis-of-variance models were appropriately used to rule out significant effects of treatment period, sequence, and carryover. Previously validated measurement tools were used extensively. Overall, the placebo response in this study was strong. This suggests the presence of confounding factors that could limit study usefulness. The possibilities discussed included a stimulus effect of a visible patch and a potential limitation of the crossover design, whereby patients alter their patterns of sexual activity early in the study and then maintain the new patterns throughout.
OUTCOMES MEASURED: The primary outcomes addressed were the composite sexual function score and the self-reported frequency of sexual thoughts, desires, and activities.
RESULTS: The composite sexual function score was low at baseline (52%±27% of the mean value for healthy women). Sexual function as measured by this score significantly improved with testosterone 300 mg per day (increased to 81%±37% of the mean vs 72%±38% for placebo, P=.05). The effect of testosterone 150 mg per day was not significantly different from that of placebo. Composite telephone-based diary scores did not increase significantly. Compliance with telephone reporting of sexual activity was poor and resulted in the withdrawal of 6 patients. Notable secondary outcomes were improved mood, according to the Psychological General Well-Being Index composite score (P=.04), and lack of clinically significant changes in serum lipids, hematocrit, liver function tests, and objective measures of acne and hirsutism. This study was too small to detect adverse effects on mortality.
Transdermal testosterone at 300 mg per day, when administered together with oral estrogen, provides some benefit for women who are sexually impaired following oophorectomy. The safety and efficacy of long-term treatment need to be established before widespread use. This study does not address treatment of impaired sexual function in postmenopausal women who have not had surgery. However, the results are suggestive of benefit over that of estrogen therapy in any woman lacking ovarian androgen production. Further research should answer this question as well.
BACKGROUND: Women who undergo bilateral oophorectomy before menopause experience a 50% drop in serum testosterone because of a lack of ovarian androgen production. Many of these women report decreased sexual desire and activity, and pleasure not improved with estrogen therapy. Previous studies of testosterone therapy have used supraphysiologic doses and were not double blinded.
POPULATION STUDIED: The investigators enrolled 75 healthy women aged 31 to 56 years from 9 clinical sites in the United States. The method of patient recruitment was not specified. Approximately two thirds of the patients were married, and two thirds were white. All had undergone bilateral salpingo-oophorectomy and hysterectomy a mean of 4.7 years ago. Other inclusion criteria were treatment with at least 0.625 mg conjugated equine estrogen daily for 2 months, history of a stable monogamous heterosexual relationship for 1 year, and a composite sexual function score (Brief Index of Sexual Functioning for Women) less than the mean value for normal women. Persons taking steroids, selective serotonin reuptake inhibitors, or tricyclic antidepressants were excluded.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled crossover study occurring over 40 consecutive weeks. It consisted of a 4-week baseline period followed by 3 12-week treatment periods. Using identical-appearing experimental patches, patients received in random order placebo, testosterone 150 mg per day, and testosterone 300 mg per day transdermally for 12 weeks each. The Brief Index of Sexual Functioning for Women was used to determine a composite sexual function score at baseline and again after each treatment period. Intention-to-treat data analysis was performed for the 65 women who completed this index at least once during treatment. Mood was assessed at similar intervals using the Psychological General Well-Being Index. A telephone-based diary was used to assess the self-reported frequency of sexual thoughts, desires, and activities. Standard laboratory tests and validated measures of hirsutism and acne were used to determine safety and tolerability. The crossover design did not include a washout period. However, analysis-of-variance models were appropriately used to rule out significant effects of treatment period, sequence, and carryover. Previously validated measurement tools were used extensively. Overall, the placebo response in this study was strong. This suggests the presence of confounding factors that could limit study usefulness. The possibilities discussed included a stimulus effect of a visible patch and a potential limitation of the crossover design, whereby patients alter their patterns of sexual activity early in the study and then maintain the new patterns throughout.
OUTCOMES MEASURED: The primary outcomes addressed were the composite sexual function score and the self-reported frequency of sexual thoughts, desires, and activities.
RESULTS: The composite sexual function score was low at baseline (52%±27% of the mean value for healthy women). Sexual function as measured by this score significantly improved with testosterone 300 mg per day (increased to 81%±37% of the mean vs 72%±38% for placebo, P=.05). The effect of testosterone 150 mg per day was not significantly different from that of placebo. Composite telephone-based diary scores did not increase significantly. Compliance with telephone reporting of sexual activity was poor and resulted in the withdrawal of 6 patients. Notable secondary outcomes were improved mood, according to the Psychological General Well-Being Index composite score (P=.04), and lack of clinically significant changes in serum lipids, hematocrit, liver function tests, and objective measures of acne and hirsutism. This study was too small to detect adverse effects on mortality.
Transdermal testosterone at 300 mg per day, when administered together with oral estrogen, provides some benefit for women who are sexually impaired following oophorectomy. The safety and efficacy of long-term treatment need to be established before widespread use. This study does not address treatment of impaired sexual function in postmenopausal women who have not had surgery. However, the results are suggestive of benefit over that of estrogen therapy in any woman lacking ovarian androgen production. Further research should answer this question as well.
BACKGROUND: Women who undergo bilateral oophorectomy before menopause experience a 50% drop in serum testosterone because of a lack of ovarian androgen production. Many of these women report decreased sexual desire and activity, and pleasure not improved with estrogen therapy. Previous studies of testosterone therapy have used supraphysiologic doses and were not double blinded.
POPULATION STUDIED: The investigators enrolled 75 healthy women aged 31 to 56 years from 9 clinical sites in the United States. The method of patient recruitment was not specified. Approximately two thirds of the patients were married, and two thirds were white. All had undergone bilateral salpingo-oophorectomy and hysterectomy a mean of 4.7 years ago. Other inclusion criteria were treatment with at least 0.625 mg conjugated equine estrogen daily for 2 months, history of a stable monogamous heterosexual relationship for 1 year, and a composite sexual function score (Brief Index of Sexual Functioning for Women) less than the mean value for normal women. Persons taking steroids, selective serotonin reuptake inhibitors, or tricyclic antidepressants were excluded.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled crossover study occurring over 40 consecutive weeks. It consisted of a 4-week baseline period followed by 3 12-week treatment periods. Using identical-appearing experimental patches, patients received in random order placebo, testosterone 150 mg per day, and testosterone 300 mg per day transdermally for 12 weeks each. The Brief Index of Sexual Functioning for Women was used to determine a composite sexual function score at baseline and again after each treatment period. Intention-to-treat data analysis was performed for the 65 women who completed this index at least once during treatment. Mood was assessed at similar intervals using the Psychological General Well-Being Index. A telephone-based diary was used to assess the self-reported frequency of sexual thoughts, desires, and activities. Standard laboratory tests and validated measures of hirsutism and acne were used to determine safety and tolerability. The crossover design did not include a washout period. However, analysis-of-variance models were appropriately used to rule out significant effects of treatment period, sequence, and carryover. Previously validated measurement tools were used extensively. Overall, the placebo response in this study was strong. This suggests the presence of confounding factors that could limit study usefulness. The possibilities discussed included a stimulus effect of a visible patch and a potential limitation of the crossover design, whereby patients alter their patterns of sexual activity early in the study and then maintain the new patterns throughout.
OUTCOMES MEASURED: The primary outcomes addressed were the composite sexual function score and the self-reported frequency of sexual thoughts, desires, and activities.
RESULTS: The composite sexual function score was low at baseline (52%±27% of the mean value for healthy women). Sexual function as measured by this score significantly improved with testosterone 300 mg per day (increased to 81%±37% of the mean vs 72%±38% for placebo, P=.05). The effect of testosterone 150 mg per day was not significantly different from that of placebo. Composite telephone-based diary scores did not increase significantly. Compliance with telephone reporting of sexual activity was poor and resulted in the withdrawal of 6 patients. Notable secondary outcomes were improved mood, according to the Psychological General Well-Being Index composite score (P=.04), and lack of clinically significant changes in serum lipids, hematocrit, liver function tests, and objective measures of acne and hirsutism. This study was too small to detect adverse effects on mortality.
Transdermal testosterone at 300 mg per day, when administered together with oral estrogen, provides some benefit for women who are sexually impaired following oophorectomy. The safety and efficacy of long-term treatment need to be established before widespread use. This study does not address treatment of impaired sexual function in postmenopausal women who have not had surgery. However, the results are suggestive of benefit over that of estrogen therapy in any woman lacking ovarian androgen production. Further research should answer this question as well.
Is a 5-day course of antibiotics as effective as a 10-day course for the treatment of streptococcal pharyngitis and the prevention of poststreptococcal sequelae?
BACKGROUND: Recent studies have shown that a short course of a macrolide or cephalosporin is just as effective as 10 days of penicillin. However, there has been concern that a shorter course of antibiotics would lead to an increase in poststreptococcal sequelae. This study was undertaken to determine if a shorter course of antibiotics would lead to an increased risk of acute rheumatic fever and glomerulonephritis.
POPULATION STUDIED: This study included a total of 5318 children aged 1 to 18 years from 137 pediatric practices in Germany. Inclusion criteria included temperature of at least 38°C and 1 or more of the following: exudate of the pharynx or tonsils, erythema of the pharynx or tonsils, and cervical adenopathy. They also had to have a positive rapid antigen test for Group A beta-hemolytic streptococcus (GABHS). Exclusion criteria included a negative culture for GABHS, recent antibiotic use, and a history of rheumatic fever or glomerulonephritis in the patient or a person in the same household. The racial make-up of the patients is not given, and this may limit the generalizability of this study to family physician practices in the United States.
STUDY DESIGN AND VALIDITY: This was a randomized open-label design in which patients were randomized to either 10 days of penicillin V (50,000 IU/kg/day with a maximum of 2,250,000 IU/day) or 5 days of one of the following: amoxicillin clavulanate, ceftibuten, cefuroxime axetil, loracarbef, clarithromycin, or erythromycin estolate. The patients were evaluated 2 to 4 days after the end of treatment, 7 to 9 days after the end of treatment, at 7 to 8 weeks, and at 6 and 12 months. Rheumatic fever was diagnosed on the basis of the updated Jones criteria and glomerulonephritis based on the pediatrician’s assessment. The number of patients followed up for 12 months (n=4077) was a little short of the sample size required (n=4710) to detect a difference of 3 per 1000 versus 9 per 1000 in the incidence of rheumatic fever or glomerulonephritis. Other limitations of the study include the open-label design and the failure to describe the method of allocation in more detail. Since the patients and physicians knew the group assignment, there may have been an expectation that those receiving the newer, “better” drugs would do better clinically. The study was supported by the companies making these newer drugs.
OUTCOMES MEASURED: The primary outcome was the probability of rheumatic fever or glomerulonephritis in the study groups. Secondary outcomes included clinical response as judged by the investigators, resolution of symptoms, microbiologic cure, and safety.
RESULTS: Three patients developed rheumatic fever, and 2 had glomerulonephritis during the study period (4 in the larger 5-day group). Analysis of the individual cases led the authors to conclude that none of the sequelae were related to the case of streptococcal pharyngitis treated in the study. The clinical response rates were similar at the first follow-up visit (94.5% vs 93.4%). At the 7-to 9-day visit 39.7% of the 5-day patients and 45.6% of the 10-day patients still had symptoms (P <.001). The recurrence rates between the 2 groups were 24.4% in the 10-day group and 21.9% in the 5-day group (P <.03). They also found a 6% resistance rate and 6.8% intermediate resistance rate to macrolides among the isolates in their study.
Although somewhat underpowered, this study supports the hypothesis that a 5-day course of one of the study antibiotics in children is as effective as a 10-day course of penicillin V in the treatment of GABHS pharyngitis. However, the widespread use of broad-spectrum agents for a common infection is a significant concern in an age of increasing bacterial antibiotic resistance. For patients who have documented streptococcal pharyngitis and are allergic to penicillin, the use of a 5-day course of one of the study antibiotics is reasonable.
BACKGROUND: Recent studies have shown that a short course of a macrolide or cephalosporin is just as effective as 10 days of penicillin. However, there has been concern that a shorter course of antibiotics would lead to an increase in poststreptococcal sequelae. This study was undertaken to determine if a shorter course of antibiotics would lead to an increased risk of acute rheumatic fever and glomerulonephritis.
POPULATION STUDIED: This study included a total of 5318 children aged 1 to 18 years from 137 pediatric practices in Germany. Inclusion criteria included temperature of at least 38°C and 1 or more of the following: exudate of the pharynx or tonsils, erythema of the pharynx or tonsils, and cervical adenopathy. They also had to have a positive rapid antigen test for Group A beta-hemolytic streptococcus (GABHS). Exclusion criteria included a negative culture for GABHS, recent antibiotic use, and a history of rheumatic fever or glomerulonephritis in the patient or a person in the same household. The racial make-up of the patients is not given, and this may limit the generalizability of this study to family physician practices in the United States.
STUDY DESIGN AND VALIDITY: This was a randomized open-label design in which patients were randomized to either 10 days of penicillin V (50,000 IU/kg/day with a maximum of 2,250,000 IU/day) or 5 days of one of the following: amoxicillin clavulanate, ceftibuten, cefuroxime axetil, loracarbef, clarithromycin, or erythromycin estolate. The patients were evaluated 2 to 4 days after the end of treatment, 7 to 9 days after the end of treatment, at 7 to 8 weeks, and at 6 and 12 months. Rheumatic fever was diagnosed on the basis of the updated Jones criteria and glomerulonephritis based on the pediatrician’s assessment. The number of patients followed up for 12 months (n=4077) was a little short of the sample size required (n=4710) to detect a difference of 3 per 1000 versus 9 per 1000 in the incidence of rheumatic fever or glomerulonephritis. Other limitations of the study include the open-label design and the failure to describe the method of allocation in more detail. Since the patients and physicians knew the group assignment, there may have been an expectation that those receiving the newer, “better” drugs would do better clinically. The study was supported by the companies making these newer drugs.
OUTCOMES MEASURED: The primary outcome was the probability of rheumatic fever or glomerulonephritis in the study groups. Secondary outcomes included clinical response as judged by the investigators, resolution of symptoms, microbiologic cure, and safety.
RESULTS: Three patients developed rheumatic fever, and 2 had glomerulonephritis during the study period (4 in the larger 5-day group). Analysis of the individual cases led the authors to conclude that none of the sequelae were related to the case of streptococcal pharyngitis treated in the study. The clinical response rates were similar at the first follow-up visit (94.5% vs 93.4%). At the 7-to 9-day visit 39.7% of the 5-day patients and 45.6% of the 10-day patients still had symptoms (P <.001). The recurrence rates between the 2 groups were 24.4% in the 10-day group and 21.9% in the 5-day group (P <.03). They also found a 6% resistance rate and 6.8% intermediate resistance rate to macrolides among the isolates in their study.
Although somewhat underpowered, this study supports the hypothesis that a 5-day course of one of the study antibiotics in children is as effective as a 10-day course of penicillin V in the treatment of GABHS pharyngitis. However, the widespread use of broad-spectrum agents for a common infection is a significant concern in an age of increasing bacterial antibiotic resistance. For patients who have documented streptococcal pharyngitis and are allergic to penicillin, the use of a 5-day course of one of the study antibiotics is reasonable.
BACKGROUND: Recent studies have shown that a short course of a macrolide or cephalosporin is just as effective as 10 days of penicillin. However, there has been concern that a shorter course of antibiotics would lead to an increase in poststreptococcal sequelae. This study was undertaken to determine if a shorter course of antibiotics would lead to an increased risk of acute rheumatic fever and glomerulonephritis.
POPULATION STUDIED: This study included a total of 5318 children aged 1 to 18 years from 137 pediatric practices in Germany. Inclusion criteria included temperature of at least 38°C and 1 or more of the following: exudate of the pharynx or tonsils, erythema of the pharynx or tonsils, and cervical adenopathy. They also had to have a positive rapid antigen test for Group A beta-hemolytic streptococcus (GABHS). Exclusion criteria included a negative culture for GABHS, recent antibiotic use, and a history of rheumatic fever or glomerulonephritis in the patient or a person in the same household. The racial make-up of the patients is not given, and this may limit the generalizability of this study to family physician practices in the United States.
STUDY DESIGN AND VALIDITY: This was a randomized open-label design in which patients were randomized to either 10 days of penicillin V (50,000 IU/kg/day with a maximum of 2,250,000 IU/day) or 5 days of one of the following: amoxicillin clavulanate, ceftibuten, cefuroxime axetil, loracarbef, clarithromycin, or erythromycin estolate. The patients were evaluated 2 to 4 days after the end of treatment, 7 to 9 days after the end of treatment, at 7 to 8 weeks, and at 6 and 12 months. Rheumatic fever was diagnosed on the basis of the updated Jones criteria and glomerulonephritis based on the pediatrician’s assessment. The number of patients followed up for 12 months (n=4077) was a little short of the sample size required (n=4710) to detect a difference of 3 per 1000 versus 9 per 1000 in the incidence of rheumatic fever or glomerulonephritis. Other limitations of the study include the open-label design and the failure to describe the method of allocation in more detail. Since the patients and physicians knew the group assignment, there may have been an expectation that those receiving the newer, “better” drugs would do better clinically. The study was supported by the companies making these newer drugs.
OUTCOMES MEASURED: The primary outcome was the probability of rheumatic fever or glomerulonephritis in the study groups. Secondary outcomes included clinical response as judged by the investigators, resolution of symptoms, microbiologic cure, and safety.
RESULTS: Three patients developed rheumatic fever, and 2 had glomerulonephritis during the study period (4 in the larger 5-day group). Analysis of the individual cases led the authors to conclude that none of the sequelae were related to the case of streptococcal pharyngitis treated in the study. The clinical response rates were similar at the first follow-up visit (94.5% vs 93.4%). At the 7-to 9-day visit 39.7% of the 5-day patients and 45.6% of the 10-day patients still had symptoms (P <.001). The recurrence rates between the 2 groups were 24.4% in the 10-day group and 21.9% in the 5-day group (P <.03). They also found a 6% resistance rate and 6.8% intermediate resistance rate to macrolides among the isolates in their study.
Although somewhat underpowered, this study supports the hypothesis that a 5-day course of one of the study antibiotics in children is as effective as a 10-day course of penicillin V in the treatment of GABHS pharyngitis. However, the widespread use of broad-spectrum agents for a common infection is a significant concern in an age of increasing bacterial antibiotic resistance. For patients who have documented streptococcal pharyngitis and are allergic to penicillin, the use of a 5-day course of one of the study antibiotics is reasonable.
Does mammography add any benefit to a thorough clinical breast examination (CBE)?
BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.
POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.
STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.
OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.
RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.
This study found that in women 50 to 59 years the addition of annual screening mammograms to a very thorough clinical breast examination does not reduce breast cancer mortality over a 13-year follow-up. Although cancer detection rates were slightly higher in the mammogram group, there was also a 3-fold increase in the number of biopsies. This study might be reassuring in those parts of the world where mammography is not readily accessible. However, it is unlikely that these results will change practice in the current United States health care environment. In patients who refuse mammography, a thorough CBE may be as effective.
BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.
POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.
STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.
OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.
RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.
This study found that in women 50 to 59 years the addition of annual screening mammograms to a very thorough clinical breast examination does not reduce breast cancer mortality over a 13-year follow-up. Although cancer detection rates were slightly higher in the mammogram group, there was also a 3-fold increase in the number of biopsies. This study might be reassuring in those parts of the world where mammography is not readily accessible. However, it is unlikely that these results will change practice in the current United States health care environment. In patients who refuse mammography, a thorough CBE may be as effective.
BACKGROUND: Annual screening mammography is universally accepted as the standard of care in the United States for woman 50 years and older. Although evidence supports screening as effective in reducing breast cancer mortality, it is not known whether mammography plus a clinical breast examination (CBE) is more effective at reducing cancer mortality than a thorough CBE alone.
POPULATION STUDIED: A total of 39,459 Canadian women 50 to 59 years were recruited through general publicity, mailings, and physician referral. These women had not received a mammogram in the previous year and did not have a history of breast cancer.
STUDY DESIGN AND VALIDITY: The women were randomized to receive either 5 annual CBEs with mammography or a CBE alone annually for 5 years. Well-trained nurses using a visual inspection component and palpation in a radial pattern performed most of the breast examinations. Physicians performed the others. The examinations were very thorough and took approximately 10 minutes. Patients were also taught breast self-examination. Two-view mammograms were used and independently reviewed. Patients with abnormal findings were referred to the Canadian National Breast Screening Study (CNBSS) clinic for further evaluation by a surgeon. Breast cancers were identified through the CNBSS centers and the National Cancer Registry during the 13-year follow-up. The cause of death was identified through the participant’s family members, physicians, and the Canadian Mortality Data Base. Overall the study appeared valid. The 2 randomized groups seemed equal for breast cancer risk factors and other demographics. There was excellent follow-up and good compliance within each group. Randomization was not concealed. Previous scrutiny of this study centered on a change in mammography technique during the screening. Further analysis showed high sensitivity and expected cancer detection rates despite this change. The article does not mention what types of screening the participants underwent after the initial 5-year study period. This could potentially have an effect on the mortality numbers, if women decided to stop their screening after the study period ended. This study did not address differences in quality of life, such as discomfort from mammograms and additional procedures from false-positive screenings.
OUTCOMES MEASURED: Breast cancer mortality was the primary outcome. The tumor size and number of lymph node–positive cancers were also reported.
RESULTS: Only 54 of the original participants were excluded from the analysis. At the 13-year follow-up there were 107 breast cancer deaths in the combined mammography plus CBE group and 105 deaths in the CBE-only group (rate ratio=1.02; 95% confidence interval, 0.78-1.33). A total of 622 invasive and 71 in situ cancers were found in the combined group and 610 invasive and 16 in situ cancers were identified in the CBE-only group. Mammography was able to detect a cancer 2.1 years earlier than CBE alone. However, this lead time did not appear to improve survival. Overall, the tumors identified by mammography were smaller. There was no significant difference between the 2 groups in the number of lymph node–positive cancers detected by the end of the study. As expected, there were approximately 3 times as many biopsies and more diagnostic tests performed in the mammogram group.
This study found that in women 50 to 59 years the addition of annual screening mammograms to a very thorough clinical breast examination does not reduce breast cancer mortality over a 13-year follow-up. Although cancer detection rates were slightly higher in the mammogram group, there was also a 3-fold increase in the number of biopsies. This study might be reassuring in those parts of the world where mammography is not readily accessible. However, it is unlikely that these results will change practice in the current United States health care environment. In patients who refuse mammography, a thorough CBE may be as effective.