Fact_verication/task100_ebms_answer_vertification.json

{
    "Contributors": "EBMSummariserCorpus",
    "Source": "EBMSummariserCorpus",
    "URL": "https://sourceforge.net/projects/ebmsumcorpus/",
    "Categories": [
        "Question Answering"
    ],
    "Definition": [
        "Provide a justification or evidence to support a given statement."
    ],
    "Reasoning": [],
    "Input_language": [
        "English"
    ],
    "Output_language": [
        "English"
    ],
    "Instruction_language": [
        "English"
    ],
    "Domains": [
        "Public Health",
        "Heathcare"
    ],
    "Positive Examples": [],
    "Negative Examples": [],
    "Instances": [
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "Allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "A review of placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "Studies indicate that immunotherapy is effective for several years after treatment is discontinued."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "A study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it."
        },
        {
            "input": "Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis.",
            "output": "One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen-induced rhinitis."
        },
        {
            "input": "No RCTs directly compare immunotherapy with conservative management. Treatment decisions are driven by the clinical presentation, patient and physician preferences, practice guidelines, and expert opinion.",
            "output": "A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy."
        },
        {
            "input": "False-positive reports on urine drug screens by immunoassay are rare. Nonsteroidal anti-inflammatory drugs, fluoroquinolones, and Vicks Inhaler are most frequently implicated.",
            "output": "Positive confirmation tests may occur in urine specimens from patients who legally or unknowingly ingest products that contain drugs of abuse. In these instances, the finding is a true positive but may not reflect drug abuse by the client. Many products available without prescription outside of the US contain opiates (eg, Donnagel PG from Canada)."
        },
        {
            "input": "Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen.",
            "output": "Several controlled-exposure studies have shown that as little as 1 poppy seed muffin (about 15 g of seed) can produce detectable amounts of morphine and codeine by immunoassay as well as GC-MS. In 1998, the federal government increased the threshold defining a positive screen for urine morphine and codeine from 300 to 2000 ng/mL to reduce spurious reports of opiate-positive tests from poppy seed consumption."
        },
        {
            "input": "Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen.",
            "output": "Substances that do not produce positive urine drug screens include passively inhaled crack cocaine or marijuana (unless \"extreme\"), and ingested products containing hemp or other common herbal preparations."
        },
        {
            "input": "Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen.",
            "output": "In one study, 6 volunteers in an 8x8x7-ft enclosed room were exposed to 200 mg freebase cocaine vapor; none of their urine samples exceeded the federal GC-MS threshold. In a similar study of 3 non-smokers exposed to 8 marijuana smokers (smoking 32 joints) in a 10x10x8-ft enclosed room, no samples from the nonsmokers exceeded the federal GC-MS threshold."
        },
        {
            "input": "Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen.",
            "output": "In an exposure study of 90 volunteers who ingested 8 different herbal preparations, there were no positive urine drug screens."
        },
        {
            "input": "Low-dose thiazide diuretics (eg, hydrochlorothiazide 12.5 to 25 mg/d) are the best first-line pharmacotherapy for treating uncomplicated hypertension.",
            "output": "Results from the largest antihypertensive clinical trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), were included in this meta-analysis. Although these data showed no differences between drug therapies in total and cardiovascular disease mortality, low-dose diuretics reduced certain cardiovascular endpoints (ie, heart failure, stroke, cardiovascular disease events) more than other drug therapies."
        },
        {
            "input": "Low-dose thiazide diuretics (eg, hydrochlorothiazide 12.5 to 25 mg/d) are the best first-line pharmacotherapy for treating uncomplicated hypertension.",
            "output": "Several other clinical trials have subsequently compared the effect of thiazide diuretics with that of other antihypertensive agents (beta-blockers, calcium channel blockers, and alpha-blockers) on patient-oriented outcomes. These were analyzed in a recent meta-analysis of 42 clinical trials that included 192,478 patients randomized to 7 treatment strategies including placebo."
        },
        {
            "input": "Low-dose thiazide diuretics (eg, hydrochlorothiazide 12.5 to 25 mg/d) are the best first-line pharmacotherapy for treating uncomplicated hypertension.",
            "output": "Three landmark placebo-controlled studies have established that thiazide diuretic-based treatment reduces morbidity and mortality among patients with hypertension."
        },
        {
            "input": "Alternate first-line agents include angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and calcium channel blockers",
            "output": "A long-term trial has compared an ARB to other types of drug therapy: losartan vs atenolol in the Losartan Intervention for Endpoint Reduction (LIFE) trial. In the LIFE trial, the primary composite endpoint of cardiovascular death, myocardial infarction, and stroke was less with losartan than atenolol (23.8 vs 27.9 events per 1000 patient-years, losartan and atenolol, respectively; number needed to treat=243 people-years, P=.021)."
        },
        {
            "input": "Alternate first-line agents include angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and calcium channel blockers",
            "output": "A long-term trial has compared valsartan vs amlodipine in the Valsartan Antihypertensive Long-term Use Evaluation VALUE trial. In the VALUE trial, the primary endpoint of time to cardiac event was not different between valsartan and amlodipine (25.5 vs 24.7 events per 1000 patient-years, valsartan and amlodipine, respectively; P=.49)."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "Studies combining pharmacologic intervention with Alcoholics Anonymous's 12-step program or psychological interventions showed the most significant effects on decreasing cravings and relapse rates and increasing abstinence rates."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "Fifteen studies evaluating serotonergic agents, lithium, and SSRIs (including citalopram, viqualine, fluoxetine, and others) taken for 2 to 12 weeks have shown promise for increasing abstinence rates and decreasing cravings in alcoholic patients with coexisting psychiatric conditions such as depression, anxiety, and bipolar disorder."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "When compared with placebo, disulfiram failed to significantly increase abstinence rates or decrease relapse rates or cravings."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "When compared with placebo, nalmefene taken for 3 to 24 months significantly reduced relapse without affecting abstinence rates or cravings. Acamprosate taken for 3 to 24 months significantly increased abstinence rates, but did not significantly decrease relapse or cravings as compared with placebo."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "Naltrexone reduces relapse rates by one half to two thirds."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "Naltrexone reduces relapse rates by one half to two thirds."
        },
        {
            "input": "Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs.",
            "output": "Naltrexone (50 mg qd), nalmefene (10-80 mg qd), and acamprosate (dose based on patient weight) are all superior to placebo and other agents such as the SSRIs, disulfiram, and serotonergic agents in reducing relapse rates and the phenomena of craving and in increasing abstinence rates."
        },
        {
            "input": "Patients with steatohepatitis who take HMG Co-A reductase inhibitors statins lower their elevated liver enzymes and show evidence of improvement in fatty liver on follow-up imaging.",
            "output": "Another study included patients with biopsy-confirmed fatty liver and elevated ALT levels greater than 1.5 times the upper limit of normal. In this 24-week study, 23 predominantly hypertriglyceridemic patients took omega-3 fatty acids, 5 mL 3 times daily, 28 hypercholesterolemic patients took atorvastatin 20 mg daily, and 21 dyslipidemic patients with a body mass index >27.0 took orlistat 120 mg 3 times daily. ALT levels decreased in all 3 groups during the study. Ultrasonography showed normal liver echo pattern at the end of treatment for 35% of omega-3 patients, 61% of atorvastatin patients, and 86% of orlistat patients. No serious adverse events were observed."
        },
        {
            "input": "Patients with steatohepatitis who take HMG Co-A reductase inhibitors statins lower their elevated liver enzymes and show evidence of improvement in fatty liver on follow-up imaging.",
            "output": "A 6-month unblinded study found similar results among 44 adult patients with biopsy-confirmed NASH. Twenty-seven hyperlipidemic patients (aged 50\u00b11.4 years) with an average alanine aminotransferase (ALT) of 81.8 U/L took 10 mg of atorvastatin daily. Seventeen normolipidemic patients (aged 43.7\u00b11.8 years) with an average ALT of 76.0 U/L took ursodeoxycholic acid (UDCA) 13-15 mg/kg/d for the same duration; 59% of atorvastatin-treated patients normalized liver enzyme levels compared with 23% in the UDCA group. On computed tomography scanning, both groups showed improvement in liver densities, suggesting improvement of fatty liver."
        },
        {
            "input": "Patients with steatohepatitis who take HMG Co-A reductase inhibitors statins lower their elevated liver enzymes and show evidence of improvement in fatty liver on follow-up imaging.",
            "output": "A prospective study evaluated 5 patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) who took 20 mg of pravastatin daily for 6 months. Liver enzyme levels at baseline were no more than 3 times the upper limit of normal. All 5 patients had normalized liver enzymes at the end of the study."
        },
        {
            "input": "Statins do not further increase transaminase levels for patients with pre-existing transaminase elevations.",
            "output": "A retrospective study of patients with baseline elevated transaminases who took statins showed no significant increase in transaminase levels during treatment compared with patients with elevated transaminases who did not take statins. The study reviewed electronic medical records for patients with preexisting elevated liver enzymes who initiated statin therapy (atorvastatin, simvastatin, or fluvastatin) and had follow-up labs drawn 6 months later (cohort 1, n=342). The comparison groups included patients with normal liver enzymes who initiated statins (cohort 2, n=1437) and patients with elevated baseline liver enzymes who did not take statins (cohort 3, n=2245). At follow-up, 4.7% of cohort 1 patients had mild-to-moderate elevations in liver enzymes, which did not differ significantly (P=.2) from those in cohort 3. Within cohort 2, 1.9% experienced mild-to-moderate elevations of transaminases (defined as less than 10 times the upper limit of normal)."
        },
        {
            "input": "Statins do not further increase transaminase levels for patients with pre-existing transaminase elevations.",
            "output": "A retrospective study of patients with baseline elevated transaminases who took statins showed no significant increase in transaminase levels during treatment compared with patients with elevated transaminases who did not take statins. The cohort study of patients with preexisting elevated liver enzymes found comparable results with lovastatin. Among lovastatin patients (n=135), 6.6% had mild-to-moderate elevations in transaminases during therapy vs 11% of the cohort of patients with preexisting elevated liver enzymes who did not take statins. This difference was not statistically significant (P=.2)."
        },
        {
            "input": "For patients with decompensated liver disease or advanced cirrhosis, balance the benefits of statins against the risks.",
            "output": "The National Cholesterol Education Project states that \"the incidence of clinically important transaminase elevations in the large statin trials is the same for statins as for placebo. Progression to liver failure is exceedingly rare, if it occurs.\" They further state that the use of statins for persons with decompensated liver disease or advanced cirrhosis depends on clinical judgment, but that their use in NASH is considered safe."
        },
        {
            "input": "Little evidence supports the use of the high-sensitivity C-reactive protein assay (hs-CRP) as a screening test for cardiovascular disease (CVD) in the healthy adult population. There is significant debate about its use in populations at moderate risk for cardiovascular disease, with some evidence suggesting its use if the results of the test will alter treatment recommendations.",
            "output": "Several retrospective studies have reported risk ratios for developing cardiovascular disease, ranging from 2.3 to 4.4 when comparing subjects with the highest levels of hs-CRP with those who have the lowest levels. Though systematic bias in retrospective study design limits the interpretation of these findings, the findings are of some benefit to answering this question when large, prospective, randomized studies are not available."
        },
        {
            "input": "Little evidence supports the use of the high-sensitivity C-reactive protein assay (hs-CRP) as a screening test for cardiovascular disease (CVD) in the healthy adult population. There is significant debate about its use in populations at moderate risk for cardiovascular disease, with some evidence suggesting its use if the results of the test will alter treatment recommendations.",
            "output": "Guidelines from the Institute for Clinical Systems Improvement for lipid management in adults state that, \"non-traditional risk factors C-reactive protein [CRP] and total homocysteine have been shown to have some predictive values in screening vascular disease. The value of screening for these risk factors is not yet known.\"."
        },
        {
            "input": "Little evidence supports the use of the high-sensitivity C-reactive protein assay (hs-CRP) as a screening test for cardiovascular disease (CVD) in the healthy adult population. There is significant debate about its use in populations at moderate risk for cardiovascular disease, with some evidence suggesting its use if the results of the test will alter treatment recommendations.",
            "output": "Two studies evaluating statin therapy for CVD suggest that CRP may be monitored as an independent factor for predicting CVD outcomes for patients undergoing aggressive lipid therapy. These randomized, masked trials suggest that CRP is directly predictive of recurrent events among patients with known CVD. Its usefulness may be greatest when trying to decide whether to pursue aggressive (high-dose) statin therapy for these patients."
        },
        {
            "input": "Little evidence supports the use of the high-sensitivity C-reactive protein assay (hs-CRP) as a screening test for cardiovascular disease (CVD) in the healthy adult population. There is significant debate about its use in populations at moderate risk for cardiovascular disease, with some evidence suggesting its use if the results of the test will alter treatment recommendations.",
            "output": "A large study reports adjusted odds for development of coronary artery disease of 1.45 (95% confidence interval [CI], 1.25-1.68) for subjects in the top third of hs-CRP levels compared with those in the bottom third. Odds ratios (OR) for other predictors of coronary artery disease are higher than this, in particular total cholesterol (OR=2.35; 95% CI, 2.03-2.74), cigarette smoking (OR=1.87; 95% CI, 1.62-2.22), and elevated systolic blood pressure (OR=1.50; 95% CI, 1.30-1.73). This shows that hs-CRP does not contribute as much as these factors to the established risk profile for coronary heart disease."
        },
        {
            "input": "Little evidence supports the use of the high-sensitivity C-reactive protein assay (hs-CRP) as a screening test for cardiovascular disease (CVD) in the healthy adult population. There is significant debate about its use in populations at moderate risk for cardiovascular disease, with some evidence suggesting its use if the results of the test will alter treatment recommendations.",
            "output": "C-reactive protein is a nonspecific serum marker of inflammatory response. While it is elevated in a variety of conditions, a link has been suggested between CRP and pathogenesis of clinical cardiovascular disease. A consensus statement from the American Heart Association and the Centers for Disease Control and Prevention discourages use of hs-CRP for screening in the healthy adult population. It offers support for using hs-CRP for assessment of patients at medium risk levels for whom the test will alter treatment decisions."
        },
        {
            "input": "Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3-6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency.",
            "output": "A recent Cochrane review suggests there is a clinically significant benefit for the treatment of iron-deficiency anemia; however, there is a need for further randomized controlled trials with long-term follow-up."
        },
        {
            "input": "Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3-6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency.",
            "output": "A prospective study of 1128 children identified as anemic with a screening hemoglobin level showed that subsequent testing-which included mean corpuscular volume, protoporphyrin, transferrin, and ferritin measurements-did not reliably distinguish potential responders from nonresponders to a 3-month trial of empiric iron therapy. In fact, more than half of the responders would have been missed if treatment had been restricted to infants with abnormal mean corpuscular volume or iron studies. Because of the simplicity, low cost, and relative safety of iron therapy for infants, this trial suggests that a therapeutic trial of iron be given first, reserving further work-up for the small number of infants that still have unexplained hemoglobin concentrations of <11.0 g/dL after a therapeutic trial."
        },
        {
            "input": "Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3-6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency.",
            "output": "A randomized controlled trial of iron supplementation vs placebo in 278 infants testing positive for iron-deficiency anemia demonstrated that once daily, moderate-dose ferrous sulfate (FeSO4) therapy (3 mg/kg/d of elemental iron) given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy."
        },
        {
            "input": "Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3-6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency.",
            "output": "A prospective study of 970 healthy infants identified 62 infants with a heel-stick capillary hematocrit of <33%. Of these, 31 had repeat hematocrit values of <33% as confirmed by subsequent heel-stick complete blood count measurement. Twenty of these anemic infants (65%) completed the study protocol, which included a 1-month trial of iron, a follow-up complete blood count, and hemoglobin electrophoresis for those infants with persistent microcytosis or positive sickle preparation (performed at initial screening for all African American infants). Six infants (30%) had an increase in hemoglobin concentration of 1.0 g/dL or more and were presumed to be iron-deficient; they went on to receive an additional 2 months of iron therapy. Two of these were found to have co-existing alpha-thalassemia. Of the remainder, 11 (55%) were determined to have a low-normal hematocrit (mean=31.5 \u00b1 0.9), 1 had alpha thalassemia alone, 1 had coexisting alpha-thalassemia and hemoglobin AS, and 1 had hemoglobin SC. Review of data showed that abnormal diagnoses (iron deficiency, thalassemia, and sickle cell trait or disease) were found in 9 of 11 infants with high RDW and in none of the 9 with normal RDW. The authors concluded that RDW alone appears to be predictive of identifiable causes of anemia when used to screen healthy 12-month-old babies."
        },
        {
            "input": "Further testing with a complete blood count, mean corpuscular volume, red cell distribution width (RDW), serum ferritin concentration, as well as hemoglobinopathy screening when appropriate, may be effective in determining the cause of anemia.",
            "output": "A prospective study of 1128 children identified as anemic with a screening hemoglobin level showed that subsequent testing-which included mean corpuscular volume, protoporphyrin, transferrin, and ferritin measurements-did not reliably distinguish potential responders from nonresponders to a 3-month trial of empiric iron therapy. In fact, more than half of the responders would have been missed if treatment had been restricted to infants with abnormal mean corpuscular volume or iron studies. Because of the simplicity, low cost, and relative safety of iron therapy for infants, this trial suggests that a therapeutic trial of iron be given first, reserving further work-up for the small number of infants that still have unexplained hemoglobin concentrations of <11.0 g/dL after a therapeutic trial."
        },
        {
            "input": "Further testing with a complete blood count, mean corpuscular volume, red cell distribution width (RDW), serum ferritin concentration, as well as hemoglobinopathy screening when appropriate, may be effective in determining the cause of anemia.",
            "output": "A prospective study of 970 healthy infants identified 62 infants with a heel-stick capillary hematocrit of <33%. Of these, 31 had repeat hematocrit values of <33% as confirmed by subsequent heel-stick complete blood count measurement. Twenty of these anemic infants (65%) completed the study protocol, which included a 1-month trial of iron, a follow-up complete blood count, and hemoglobin electrophoresis for those infants with persistent microcytosis or positive sickle preparation (performed at initial screening for all African American infants). Six infants (30%) had an increase in hemoglobin concentration of 1.0 g/dL or more and were presumed to be iron-deficient; they went on to receive an additional 2 months of iron therapy. Two of these were found to have co-existing alpha-thalassemia. Of the remainder, 11 (55%) were determined to have a low-normal hematocrit (mean=31.5 \u00b1 0.9), 1 had alpha thalassemia alone, 1 had coexisting alpha-thalassemia and hemoglobin AS, and 1 had hemoglobin SC. Review of data showed that abnormal diagnoses (iron deficiency, thalassemia, and sickle cell trait or disease) were found in 9 of 11 infants with high RDW and in none of the 9 with normal RDW. The authors concluded that RDW alone appears to be predictive of identifiable causes of anemia when used to screen healthy 12-month-old babies."
        },
        {
            "input": "other",
            "output": "Similar results were found in a prospective controlled treatment trial among Alaskan Native children."
        },
        {
            "input": "other",
            "output": "A study demonstrated that iron sulfate drops (40 mg elemental iron divided 3 times a day) or a single daily dose of microencapsulated ferrous fumarate sprinkles (80 mg elemental iron) plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects."
        },
        {
            "input": "other",
            "output": "Similar results were found in a trial of empiric iron therapy among infants with anemia."
        },
        {
            "input": "other",
            "output": "In a retrospective cohort study of 1358 innercity children aged 9 to 36 months who underwent screening, 343 (25%) had anemia (Hgb <11 g/dL); of these, 239 (72%) were prescribed iron and 95 (28%) were not. Responders were defined as those with a hemoglobin value of greater than 11 g/dL or an increase of 1 g/dL documented within 6 months of the initial screening visit. Follow-up rates for both groups were low (~50%), but of those prescribed iron, 107 of 150 (71%) responded to treatment compared with 27 of 48 (68%) of those who did not receive iron. Since similar response rates were seen among infants who did and infants who did not receive iron therapy, proving the benefit of routine screening followed by a trial of iron may be problematic in populations with higher rates of anemia, low follow-up rates, and high spontaneous resolution rates."
        },
        {
            "input": "Abrupt discontinuation of the offending analgesic(s), and treating rebound headaches with dihydroergotamine (DHE) as needed, results in significant improvement for most patients.",
            "output": "A case series studied 50 patients with rebound headaches for 5 or more days a week at baseline. Patients were educated regarding analgesic overuse headaches, after which their analgesics were abruptly discontinued, and they were followed up to a year. Subcutaneous DHE was used as needed for symptomatic relief of excruciating headaches. At study completion, 78% of patients had adequately stopped analgesics. The goal of greater than 6 consecutive headache-free days was achieved in 74% patients in an average of 84 days."
        },
        {
            "input": "Abrupt discontinuation of the offending analgesic(s), and treating rebound headaches with dihydroergotamine (DHE) as needed, results in significant improvement for most patients.",
            "output": "Also termed analgesic-overuse headaches, they are defined by the International Headache Society guidelines as headaches occurring more than 15 days per month, mild to moderate in intensity, developing or worsening with analgesic overuse, and resolving or reverting to the prior underlying headache pattern within 2 months of discontinuing the analgesic(s)."
        },
        {
            "input": "Abrupt discontinuation of the offending analgesic(s), and treating rebound headaches with dihydroergotamine (DHE) as needed, results in significant improvement for most patients.",
            "output": "Analgesic rebound headaches are seen in 1% of the population, mostly middle-aged women with underlying migraines."
        },
        {
            "input": "Amitriptyline does not affect the frequency or severity of rebound headaches, but it may improve quality of life.",
            "output": "A 9-week double-blind, placebo-controlled trial randomized 20 nondepressed patients with analgesic overuse headache to receive amitriptyline or active placebo (trihexyphenidyl). Patients were admitted to the hospital for 1 week and withdrawn from all analgesics. The 2 groups had similar baseline characteristics. During the hospitalization, the amitriptyline treatment group received intravenous amitriptyline escalating from 25 to 75 mg. During the following month, oral study medications were continued, and patients took low doses of aspirin or acetaminophen, as needed. There was no significant difference between the 2 groups with regard to analgesic use. At completion of this low-powered study, no difference was found between the 2 groups in headache frequency or analgesic use, although certain components of a quality-of-life scale were better in the amitriptyline group."
        },
        {
            "input": "Prednisone or naratriptan (Amerge) lessen acute withdrawal symptoms from analgesics and reduce the need for rescue medications during the first 6 days of treatment; however, they do not affect headache frequency or severity.",
            "output": "An open-label trial of patients with chronic migraine and analgesic overuse in a headache sub-specialty center abruptly withdrew 150 participants from analgesics and quasi-randomized them to 3 groups: prednisone (tapering from 60 to 20 mg over 6 days), naratriptan (Amerge) (2.5 mg twice daily for 6 days), or no prophylactic treatment. Patients given the active substances were told it would reduce withdrawal symptoms; patients given placebo were not given this advice. All patients received education about the pathophysiology of rebound headaches, kept a headache diary, and were phoned weekly to ensure compliance. In addition, they all received capsules containing gradually increasing doses of atenolol, nortriptyline, and flunarazine (a calcium channel blocker not FDA-approved.) Indo-methacin and chlorpromazine were used as needed. Results from the first 6 days showed no difference in headaches between the 3 groups; however, significantly more patients used chlorpromazine in the \"no pharmacologic treatment\" group. By the end of 5 weeks, headache frequency was significantly reduced in all groups from baseline; however, there were no differences between groups in headache frequency or intensity in this small study. Of note, there were statistically fewer withdrawal symptoms and less use of rescue medications among patients who received the initial prophylactic treatments. The indomethacin rescue use was 24%, 18%, and 14% of patients for the no prophylactic treatment, prednisone, and naratriptan groups respectively, while chlorpromazine rescue use was 14%, 0%, and 0%, respectively. The number of patients needed to treat to prevent any withdrawal symptoms (nausea, vomiting, nervousness, dizziness, etc.) was 1 for every 3.5 for naratriptan, and 6.4 for prednisone."
        },
        {
            "input": "Probably not. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT).",
            "output": "An RCT revealed a trend toward thrombus progression occurring more often in patients who were treated with bed rest compared with patients treated with ambulation and compression, though the difference didn't reach statistical significance because of small sample size. The clinical importance of these phlebographic studies isn't clear."
        },
        {
            "input": "Probably not. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT).",
            "output": "A multicenter RCT showed that thrombus progression occurred more often in patients who were treated with bed rest compared with patients treated with ambulation and compression (P<.01)."
        },
        {
            "input": "Probably not. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT).",
            "output": "A study using the RIETE registry, a Spanish registry of consecutively enrolled patients with objectively confirmed acute DVT or PE, found no significant difference in occurrence of new PE between immobilized and mobilized patients. Patients with DVT who were immobilized were generally sicker, more likely to have PaO2 <60, and more likely to have received lower doses of low-molecular-weight heparin (LMWH) compared with the group that walked (P<.005)."
        },
        {
            "input": "Probably not. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT).",
            "output": "A prospective cohort study of new PE in patients treated with ambulation and compression plus anticoagulation found that the incidence of PE was significantly lower than historical incidence rates in patients managed with bed rest."
        },
        {
            "input": "Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain.",
            "output": "RCTs have shown that ambulation with leg compression, compared with bed rest without compression, can effectively decrease leg swelling and pain."
        },
        {
            "input": "Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain.",
            "output": "The difference between ambulation with leg compression, compared with bed rest without compression, was detectable 2 years after DVT."
        },
        {
            "input": "Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain.",
            "output": "RCTs in which both ambulating and resting patients received compression therapy showed no significant difference in leg circumference at 1 or 6 months. This finding suggests that the benefit on local symptoms may result from compression rather than ambulation."
        },
        {
            "input": "Only weak data exist to suggest that early ambulation can reduce mortality.",
            "output": "A cohort study in which 691 patients were kept walking with compression therapy reported a mortality rate of 0.2%."
        },
        {
            "input": "Only weak data exist to suggest that early ambulation can reduce mortality.",
            "output": "The 0.2% mortality rate (occurred in patients older than 70 years) is lower than rates reported in the historic literature, which typically are 1% among patients treated with unfractionated heparin and bed rest."
        },
        {
            "input": "Only weak data exist to suggest that early ambulation can reduce mortality.",
            "output": "In a cohort, the mortality rate was also 0.2%, and all deaths occurred in patients older than 70 years."
        },
        {
            "input": "Only weak data exist to suggest that early ambulation can reduce mortality.",
            "output": "Data from the RIETE registry indicated that overall mortality was significantly higher in immobilized patients with a PE (3.6% vs 0.5% in mobile patients; P=.01).8 Notably, immobilized patients with a PE were more likely to be hypoxic and also tended to receive lower doses of LMWH. No differences were found in outcomes for patients with DVT."
        },
        {
            "input": "Only weak data exist to suggest that early ambulation can reduce mortality.",
            "output": "A retrospective, multicenter cohort of 1647 patients treated with unfractionated heparin and bed rest in different German hospitals reported a rate of fatal PE of 2.33%."
        },
        {
            "input": "Yes, warfarin is effective in the secondary prevention of venous thromboembolic events (VTEs) for patients positive for lupus anticoagulant or anticardiolipin antibody (also known as antiphospholipid antibodies [aPL]).",
            "output": "One study prospectively followed patients \u226515 years old recruited from 16 hospitals in Sweden, who had their first or second episode of a VTE. Patients with malignancy or a known congenital deficiency of an inhibitor of coagulation were excluded. These patients were followed for 4 years. Each received at least 6 months of warfarin therapy (INR=2.0-2.85) after initial diagnosis of a VTE. After treatment, the 4-year recurrence rate for VTEs was 29% for patients with aPL (20/68) vs 14% for patients without (47/344) (relative risk [RR]=2.1; 95% confidence interval [CI], 1.3-3.3). The risk of death for those patients with aPL was 15% (10/68) vs 6% for those without (20/324) (RR=1.8; 95% CI, 0.9-3.6). In the same study, those with an aPL and a second clot were randomized to a second 6 months of therapy vs indefinite therapy (INR=2.0-2.85). After 4 years, their risk of another recurrence was 20% (3/15) with 6 months of therapy vs 5% (1/19) with indefinite therapy. This underpowered study did not show a statistical difference under intention-to-treat analysis; however, the single failure in the treatment group had stopped the warfarin prior to the event."
        },
        {
            "input": "Patients should be treated for at least a year with warfarin.",
            "output": "Guidelines from the American College of Chest Physicians recommend at least 12 months of treatment with warfarin and suggest indefinite treatment for patients with a VTE and antiphospholipid antibodies. The guidelines also suggest a target INR of 3.0 range, 2.5-3.5 for patients with recurrent VTEs or additional risk factors, and a therapeutic INR of 2.5 range, 2.0-3.0 for patients with a VTE and lupus anticoagulant but no additional risk factors."
        },
        {
            "input": "Patients should be treated, possibly indefinitely, with warfarin.",
            "output": "A meta-analysis of these studies (done in conjunction with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups. Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated."
        },
        {
            "input": "Moderate-intensity therapy (international normalized ratio [INR] range, 2.0-3.0) appears to be the best balance between risks and benefits.",
            "output": "A meta-analysis of these studies (done in conjunction with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups. Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated."
        },
        {
            "input": "Moderate-intensity therapy (international normalized ratio [INR] range, 2.0-3.0) appears to be the best balance between risks and benefits.",
            "output": "Two recent randomized controlled trials have shown that moderate-intensity warfarin therapy (INR=2.0-3.0) is equally efficacious to high-intensity therapy (INR=3.0-4.0). In these small studies, those with aPL were randomized to moderate-intensity vs high-intensity therapy and followed for approximately 3 years."
        },
        {
            "input": "Little evidence exists regarding primary prevention for patients with an incidental finding of either aPL. For these individuals, the risks of warfarin may outweigh any benefits. Many experts recommend primary prevention with aspirin for those individuals who are aPL positive and who do not have contraindications to aspirin or another compelling reason for warfarin use (malignancy, family history, or accompanying hypercoagulable state).",
            "output": "Wahl et al constructed a decision analysis of antithrombotic therapy for patients with systemic lupus erythematosus with and without aPL. They compared observation alone with aspirin and with warfarin for the primary prevention of VTE. Using a decision analysis based on the best available efficacy rates, they recommended that the benefits of prophylactic aspirin outweigh the risks. However, due to high complication rates, warfarin's benefits are outweighed by the risks. This analysis has not been validated in an actual patient population and remains theoretical in nature, but is the best available evidence regarding primary prevention of VTE for patients with aPL."
        },
        {
            "input": "One approach is to use antidepressants alone, which reduce symptoms for patients with major depression plus symptoms of anxiety or major depression plus generalized anxiety disorder. Selective serotonin reuptake inhibitors (SSRIs), tricyclics (TCAs), bupropion, mirtazapine, nefazodone, and venlafaxine are equally effective for combined symptom relief.",
            "output": "Two open-label cohort trials (N=153) found that fluoxetine and fluvoxamine (Luvox, an older SSRI) reduced both depression and anxiety by about half."
        },
        {
            "input": "One approach is to use antidepressants alone, which reduce symptoms for patients with major depression plus symptoms of anxiety or major depression plus generalized anxiety disorder. Selective serotonin reuptake inhibitors (SSRIs), tricyclics (TCAs), bupropion, mirtazapine, nefazodone, and venlafaxine are equally effective for combined symptom relief.",
            "output": "Three trials evaluated antidepressant medication for patients who met diagnostic criteria for both major depression and generalized anxiety disorder. A manufacturer-sponsored RCT (N=90) found no differences in HAM-A or HAM-D score reduction among fluoxetine, venlafaxine, and placebo (except at 12 weeks, when venlafaxine significantly differed from placebo)."
        },
        {
            "input": "One approach is to use antidepressants alone, which reduce symptoms for patients with major depression plus symptoms of anxiety or major depression plus generalized anxiety disorder. Selective serotonin reuptake inhibitors (SSRIs), tricyclics (TCAs), bupropion, mirtazapine, nefazodone, and venlafaxine are equally effective for combined symptom relief.",
            "output": "Patients with major depression and high anxiety levels relapsed more often than those with low anxiety levels with discontinuation of fluoxetine compared with placebo in a double-blind placebo-controlled parallel trial with 596 patients."
        },
        {
            "input": "Another approach is to add a benzodiazepine to the antidepressant. This reduces anxiety symptoms (more in the short term) and decreases patient dropout, but it also has possible harms, including development of dependence and accident proneness.",
            "output": "A Cochrane systematic review (10 RCTs, N=731) compared antidepressants alone vs combinations with benzodiazepines for patients with major depression and a 35% to 85% estimated prevalence of anxiety symptoms. Three studies used standardized scales to measure anxiety symptom severity. Antidepressants in combination with benzodiazepines were more likely than antidepressants alone to reduce depression scores by 50% or more (for 50% depression improvement at 1 week, number needed to treat [NNT]=12; at 4 weeks, NNT=8). The combination group also had fewer dropouts (relative risk [RR]=0.63, 95% confidence interval [CI], 0.49-0. 81). The authors concluded that potential benefits of adding a benzodiazepine to an antidepressant must be balanced against possible harms, such as the development of dependence."
        },
        {
            "input": "Psychotherapy, particularly cognitive behavioral therapy, produces and maintains reductions in symptoms of anxiety and depression that are comparable with the reductions seen with medication.",
            "output": "A review of 13 controlled clinical trials evaluated standardized depression and anxiety score reductions for patients with generalized anxiety disorder receiving cognitive behavioral therapy compared with various control treatments (waiting list, pill placebo, or alternative therapy-such as supportive listening psychotherapy). Approximately half of the patients were also taking medication (not specified). After an average of 10 sessions, cognitive behavioral therapy reduced anxiety and depression symptom scores more than control treatments (difference in effect size were 0.71 and 0.66, respectively). At 6- to 12-month follow-up, cognitive behavioral therapy gains were maintained (difference in effect size=0.30 for anxiety scores and 0.21 for depression scores). (An effect size of 0.2 is usually considered small, 0.5 moderate, and 0.8 is large.)"
        },
        {
            "input": "Psychotherapy, particularly cognitive behavioral therapy, produces and maintains reductions in symptoms of anxiety and depression that are comparable with the reductions seen with medication.",
            "output": "Another trial assigned primary care patients (N=464) with depression or mixed depression and anxiety to 1 of 2 psychological therapy groups (cognitive behavioral therapy or non-directive counseling for 12 sessions) vs usual general practitioner care. At 4 months, both psychological therapy groups had lower Beck Depression Index scores (by 4-5 points) than the usual general practitioner care group, but by 12 months there were no significant differences among all groups."
        },
        {
            "input": "other",
            "output": "A systematic review of 28 randomized trials comparing various antidepressant medications found no significant differences in reduction of symptoms of depression and anxiety for patients who had both. Patients in these trials met DSM (Diagnostic and Statistical Manual of Mental Health) criteria for major depression, with symptom severity as measured by a standardized scale, the Hamilton Rating Scale for Depression (HAM-D). They also had moderate to severe levels of anxiety symptoms as measured by standardized scales (Hamilton Rating Scale for Anxiety [HAM-A], Covi Anxiety Rating Scale, or the anxiety/somatization factors on the HAM-D). Trials ranged from 6 to 24 weeks long, with outcomes including reductions in depression and anxiety symptom scores as measured by standardized scales. Study quality was variable; only 8 trials used a placebo control, and many were sponsored by pharmaceutical manufacturers. Although some individual studies found differences in outcomes between medications, no significant differences in efficacy were seen in combined data from each comparison group. Medication was more efficacious than placebo in most studies that used a placebo control. Side-effect profiles were not described."
        },
        {
            "input": "Testing for gonorrhea is recommended for a patient with genital chlamydia; also test for gonorrhea and chlamydia in their sexual partner because of the high prevalence of coinfection, particularly among younger patients.",
            "output": "The CDC guidelines recommend evaluation, testing and treatment of partners of persons with chlamydia. As well as testing for other STIs, the guidelines suggest Pap smear screening for women who have not been adequately screened, as they often are at high risk for later cervical cancer. All patients seeking treatment for STDs, including all patients attending STD clinics, should be screened routinely for HIV during each visit for a new complaint, regardless of whether the patient is known or suspected to have specific behavior risks for HIV infection."
        },
        {
            "input": "Testing for gonorrhea is recommended for a patient with genital chlamydia; also test for gonorrhea and chlamydia in their sexual partner because of the high prevalence of coinfection, particularly among younger patients.",
            "output": "In non-STI clinic settings, gonorrhea has been found in 9% of men and 6% of women with chlamydia."
        },
        {
            "input": "Testing for gonorrhea is recommended for a patient with genital chlamydia; also test for gonorrhea and chlamydia in their sexual partner because of the high prevalence of coinfection, particularly among younger patients.",
            "output": "A study of the prevalence rate of chlamydia, gonorrhea, and their coinfection in an adolescent population (women n=131,915 and men n=71,074) of juvenile detention centers between 1997 and 2002 found that 18% of women and 13% of males with chlamydia were coinfected with gonorrhea."
        },
        {
            "input": "Testing for gonorrhea is recommended for a patient with genital chlamydia; also test for gonorrhea and chlamydia in their sexual partner because of the high prevalence of coinfection, particularly among younger patients.",
            "output": "The high prevalence of coinfection of chlamydia and gonorrhea has been shown in several studies. One cross-sectional study of new clients to a hospital-based STI clinic with gonorrhea, chlamydia, or both infections found 39% of 1239 women and 24% of 1141 heterosexual men with gonorrhea also had chlamydia. Thirteen percent of females and 19% of heterosexual males with chlamydia also had gonorrhea. More than half of the women and a third of the men aged 15 to 19 had both gonorrhea and chlamydia. Patients with both STIs tended to be younger than those with one."
        },
        {
            "input": "Testing for gonorrhea is recommended for a patient with genital chlamydia; also test for gonorrhea and chlamydia in their sexual partner because of the high prevalence of coinfection, particularly among younger patients.",
            "output": "A pilot study evaluated the yield of testing patients for other STIs among patients with genital chlamydia diagnosed during opportunistic screening. The study screened patients of both sexes in primary health care settings, as well as men attending a genitourinary medicine clinic. All patients testing positive in the community were advised to attend the genitourinary medicine clinic for STI screening, partner notification, and testing of patients and their contacts. More than 90% of the patients testing positive for chlamydia attended the genitourinary medicine clinic for management (total numbers seen in the clinic; women n=1245 [957 screened in the community] and men n=490 [280 screened in the community]). At the clinic, further workup included evaluation and testing for chlamydia, gonorrhea, trichomonas, and bacterial vaginosis. Of the patients whose initial screening was in the genitourinary medicine clinic, 28% had an additional STI. Of the patients initially screened in the community setting, 4% had another STI. Partner testing showed that 55% of male partners of female patients had an STI and 76% of female partners of male patients had one or more STI."
        },
        {
            "input": "Testing for syphilis and HIV is also recommended for the patient and their partner.",
            "output": "The American Academy of Family Physicians AAFP strongly recommends testing for chlamydia in all sexually active women aged 25 years or younger and those at increased risk. The AAFP recommends screening all sexually active women for gonorrhea if they are at increased risk for infection; strongly recommends screening persons at increased risk for syphilis infection; and strongly recommends screening for HIV for persons seeking treatment for STIs."
        },
        {
            "input": "Testing for syphilis and HIV is also recommended for the patient and their partner.",
            "output": "All patients seeking treatment for STDs, including all patients attending STD clinics, should be screened routinely for HIV during each visit for a new complaint, regardless of whether the patient is known or suspected to have specific behavior risks for HIV infection."
        },
        {
            "input": "Testing for syphilis and HIV is also recommended for the patient and their partner.",
            "output": "The Institute for Clinical Systems Improvement recommends screening for chlamydia and gonorrhea for all sexually active women aged 25 years and younger and other asymptomatic women at risk for infection. Routine screening for HIV is also recommended to all persons at high risk, including those seeking treatment for any STI."
        },
        {
            "input": "The best way to evaluate a low-normal B12 level is to check serum methylmalonic acid and homocysteine levels.",
            "output": "Holotranscobalamin may become a first-choice assay for diagnosing early vitamin B12 deficiency. Studies have shown that it compares favorably with current combined measures (B12 levels, methylmalonic acid, homocysteine). Like current assays, holotranscobalamin is also affected by renal function. It requires further investigation to establish relevant cutoff levels before it can be recommended as a diagnostic strategy."
        },
        {
            "input": "The best way to evaluate a low-normal B12 level is to check serum methylmalonic acid and homocysteine levels.",
            "output": "Vitamin B12 is a necessary coenzyme in the metabolism of methylmalonic acid to succinyl choline, and is also a necessary coenzyme with folate in the metabolism of homocysteine to methionine. Therefore, a vitamin B12 deficiency leads to elevated levels of unmetabolized methylmalonic acid and homocysteine. At a local lab the normal range of methylmalonic acid is 0.00 to 0.40 umol/L, and homocysteine's normal range is 4.0 to 10.0 mmol/L. Normal levels might vary by laboratory. Other conditions, such as renal insufficiency, may also cause elevation of methylmalonic acid and homocysteine."
        },
        {
            "input": "The best way to evaluate a low-normal B12 level is to check serum methylmalonic acid and homocysteine levels.",
            "output": "A low-normal B12 level is 150 to 350 pg/mL. Levels less than 150 pg/mL indicate deficiency. Levels greater than 350 pg/mL indicate adequate B12 supply."
        },
        {
            "input": "Give 1 or 2 mg of oral vitamin B12 a day if levels are marginally low and either methylmalonic acid or both methylmalonic acid and homocysteine are elevated.",
            "output": "Oral vitamin B12 at doses of 1000 to 2000 mcg/d is a simple and cost-effective treatment option for any B12-deficient person, and may actually be superior to intramuscular replacement."
        },
        {
            "input": "Give 1 or 2 mg of oral vitamin B12 a day if levels are marginally low and either methylmalonic acid or both methylmalonic acid and homocysteine are elevated.",
            "output": "A Cochrane Collaboration review of oral vitamin B12 replacement found that these high doses seemed as effective as intramuscular vitamin B12 in all B12-deficient patients-even those with pernicious anemia, Crohn's disease, ileal resection, or malabsorption states. The authors of the review recommend a \"further large, pragmatic trial in a primary care setting\" to determine whether oral vitamin B12 is effective for patients with major common cases of malabsorption and to provide additional evidence for cost effectiveness."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "Using retrospective reviews, Bauer and colleagues developed a prediction rule for cases of infectious diarrhea. The \"modified 3-day rule\" recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection. When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "A systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea."
        },
        {
            "input": "Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease.",
            "output": "While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered eg, drug-induced diarrhea, inflammatory bowel disease. The Infectious Diseases Society of America's practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria including enterotoxic E coli should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days."
        },
        {
            "input": "Punch biopsy excision appears to be superior to traditional wide elliptical excision for the treatment of sebaceous cysts when intervention is necessary.",
            "output": "Minimal excision and punch biopsy techniques are purported to produce minimal bleeding, have faster healing times, and produce less scarring."
        },
        {
            "input": "Punch biopsy excision appears to be superior to traditional wide elliptical excision for the treatment of sebaceous cysts when intervention is necessary.",
            "output": "Traditional wide excision -involving dissection and removal of the cyst completely from the surrounding tissue through an elliptical incision-is considered the gold standard of treatment. This time-consuming endeavor frequently leads to significant scarring in comparison with minimal excision or punch biopsy, but has almost no recurrence when the cyst wall is entirely removed."
        },
        {
            "input": "other",
            "output": "Sebaceous cysts-more correctly referred to as epidermal inclusion cysts-are benign lesions of the skin. They rarely require intervention out of medical necessity, but are removed for cosmetic reasons. If the cysts become inflamed, secondary to internal discharge of the cysts' contents, or grow so large that they interfere with the patient's functioning, they may need to be removed."
        },
        {
            "input": "other",
            "output": "The minimal incision technique involves kneading the lesion following injection of anesthetic and expressing the cyst contents through a 2- to 3-mm incision. Following expulsion of the cyst contents, the loosened capsule is delivered through the small opening. Closure with suture is optional."
        },
        {
            "input": "other",
            "output": "Punch biopsy excision is similar to the minimal excision technique except that the incision is made using a single-use disposable dermal punch following injection of lidocaine. Expulsion of the cyst contents, with cyst wall, via lateral pressure is performed and occasionally followed by closure with one suture."
        },
        {
            "input": "other",
            "output": "The majority of authors agree that inflamed cysts should be allowed to convalesce prior to attempted removal, though one group (Kitamura et al) suggests primary resection, wound lavage, and primary suture without drainage for infected epidermal cysts."
        },
        {
            "input": "other",
            "output": "Rarely are these cysts truly infected. The inflammation is secondary to sebaceous cyst wall rupture with leakage of cyst contents, which elicits the inflammatory response."
        },
        {
            "input": "other",
            "output": "Only 1 small (n=60) randomized study compared traditional wide excision with punch biopsy. They found punch biopsy to be less time-consuming and to offer superior cosmetic results. However, cysts larger than 2 cm took longer with the punch biopsy technique. Only a single dermatologist performed all of the surgeries, which could introduce bias. There was no mention of blinding of the researcher that subsequently measured the wounds. Of the 31 patients randomized to the punch biopsy technique, there was 1 recurrence in the 16 months of follow-up compared with none in the wide excision arm. This study excluded patients with infected, inflamed, or recurrent cysts."
        },
        {
            "input": "Yes, a number of beta-blockers are effective in lowering blood pressure.",
            "output": "The European Society of Cardiology recommends beta-blockers as the first choice for antihypertensive therapy, alone or in combination, for patients with previous myocardial infarction, ischemic heart disease, arrhythmias or heart failure, asymptomatic left ventricular dysfunction, diabetes, or high risk of coronary disease, based on the efficacy of these drugs in these patient populations."
        },
        {
            "input": "Yes, a number of beta-blockers are effective in lowering blood pressure.",
            "output": "The Joint National Committee on Hypertension JNC-7 states that excellent clinical trial data demonstrate that lowering blood pressure with beta-blockers and several other drug classes will reduce the complications of hypertension."
        },
        {
            "input": "Cardioselective beta-blockers do not alter lung function studies for patients with chronic obstructive pulmonary disease (COPD) or reversible airway disease.",
            "output": "A Cochrane review on the cardioselective beta-blockers atenolol (Tenormin), bisoprolol (Zebeta), and metoprolol (Lopressor) found that single-dose and multiple-treatment studies showed no decline in lung function among patients with mild to moderate reversible airway disease or chronic obstructive pulmonary disease. The analysis was not able to identify any differential effect of these beta-blockers with or without intrinsic sympathomimetic activity for patients with lung disease."
        },
        {
            "input": "Propranolol and timolol have greater risks of causing fatigue as a side effec.",
            "output": "That said, beta-blockers do have side effects. One meta-analysis found no difference in the development of depression with beta-blocker therapy; however, first-generation beta-blockers (propranolol and timolol) had higher rates of fatigue than did the later beta-blockers. They reported that the risk of fatigue was only 18 per 1000 patients (95% confidence interval [CI], 5-30) and the risk for sexual dysfunction was 5 per 1000 patients (95% CI, 2-8) for all beta-blockers as a class. Importantly, they also stratified side-effect findings on the basis of lipophilic vs nonlipophilic and found no difference in side effect frequency."
        },
        {
            "input": "Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned.",
            "output": "A meta-analysis covered 13 randomized controlled trials (n=105,951) comparing treatment with beta-blockers with other antihypertensive drugs. Seven studies (n=27,433) were included in a comparison of beta-blockers and placebo or no treatment. The relative risk of stroke was 16% higher for beta-blockers (95% CI, 4%-30%) than for other drugs. No difference was seen for myocardial infarction. When the effect of beta-blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all beta-blockers (95% CI, 7%-29%). There was no difference for myocardial infarction or mortality."
        },
        {
            "input": "Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned.",
            "output": "A meta-analysis reviewed 4 studies that compared atenolol with placebo or no treatment, and 5 that compared atenolol with other antihypertensive drugs. They found no outcome differences between atenolol and placebo in the 4 studies, comprising 6825 patients, followed for a mean of 4.6 years. There was no difference in all-cause mortality (relative risk [RR]=1.01; 95% CI, 0.89-1.15), cardiovascular mortality (RR=0.99; 95% CI, 0.83-1.18), or myocardial infarction (RR=0.99; 95% CI, 0.83-1.19). The risk of stroke appeared to be lower in the atenolol than in the placebo group (RR=0.85; 95% CI, 0.72-1.01). When atenolol was compared with other antihypertensives, there were no major differences in blood pressure lowering between the treatment arms. The authors found a significantly higher mortality (RR=1.13; 95% CI, 1.02-1.25) with atenolol treatment than with other active treatment, in 5 studies comprising 17,671 patients who were followed up for a mean of 4.6 years. Stroke was also more frequent with atenolol in comparison with other agents."
        },
        {
            "input": "Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned.",
            "output": "Two recent meta-analyses on beta-blockers have called into question the effectiveness of these agents in preventing adverse outcomes in treating hypertension."
        },
        {
            "input": "Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned.",
            "output": "A subsequent meta-analysis found that beta-blocker therapy in younger patients (less than 60 years of age) is associated with a significant reduction in cardiovascular morbidity and mortality. Researchers used data from 145,811 participants in 21 hypertension trials, beta-blockers reduced major cardiovascular outcomes in younger patients (risk ratio=0.86; 95% CI, 0.74-0.99) but not in older patients (risk ratio=0.89; 95% CI, 0.75-1.05)."
        },
        {
            "input": "Recent meta-analyses have stirred debate on the effectiveness of the agents in preventing adverse outcomes. The level of evidence has reached the point where the practice of using beta-blockers as monotherapy should be questioned.",
            "output": "A recent systematic review found beta blockers to be inferior to calcium channel blockers and renin-angiotensin system inhibitors (ACE inhibitors or ARBs) for major endpoints of all-cause mortality, coronary heart disease, stroke, total cardiovascular events, and cardiovascular mortality. This review found beta-blockers had similar outcomes as diuretics but were less well tolerated than diuretics (RR=1.80; 95% CI, 1.33-2.42) or renin-angiotensin system inhibitors (RR=1.41; 1.29-1.54). Thirteen trials with 91,561 participants, meeting inclusion criteria, compared beta-blockers with placebo (4 trials; n=23,613), diuretics (5 trials; n=18,241), calcium-channel blockers (4 trials; n=44,825), and renin-angiotensin system inhibitors (3 trials; n=10,828). Compared with placebo, beta-blockers reduced the risk of stroke (RR=0.80; 95% CI, 0.66-0.96) with a marginal fall in total cardiovascular events (RR=0.88; 95% CI, 0.79-0.97), but did not affect all-cause mortality (RR=0.99, 0.88-1.11), coronary heart disease (RR=0.93, 0.81-1.07), or cardiovascular mortality (RR=0.93, 0.80-1.09). The effect on stroke was less than that of calcium-channel blockers (RR=1.24, 1.11-1.40) and renin-angiotensin system inhibitors (RR=1.30, 1.11-1.53). The effect on total cardiovascular events was less than that of calcium-channel blockers (RR=1.18, 1.08-1.29)."
        },
        {
            "input": "For mild comedonal acne, monotherapy with topical retinoids is the treatment of choice.",
            "output": "For mild noninflammatory (come-donal) acne, the preferred option is monotherapy with topical retinoids. Randomized controlled trials (RCTs) have proven the efficacy of tretinoin, an older retinoid for comedonal acne."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "Both 1% clindamycin and 2% erythromycin were comparable in reducing inflammatory and noninflammatory lesions for patients with moderate acne."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "In one RCT, patients were randomly assigned to 1 of 3 treatment groups, each having 33 enrollees: patients in the first group received 0.1% tazarotene gel as twice daily application; the second group received 0.1% tazarotene gel in the evening and vehicle gel in the morning; the third group received vehicle gel twice daily. By 12 weeks, the first and second groups achieved significantly greater improvement in acne than the third group, based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P=.002) and inflammatory lesions (38% and 34% vs 9%; P=.01)."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "Another 12-week RCT of 237 patients with mild to moderate acne demonstrated superior efficacy with 0.1% adapalene cream over placebo (P<.05)."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "While most studies did not compare the use of one retinoid vs another, a recent meta-analysis of placebo-controlled trials concluded that topical tazarotene is more effective in treating mild comedonal acne than adapalene or tretinoin, although it may be more likely to cause skin irritation."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "A systematic review evaluating the evidence for treatment of acne found that combining topical antibiotics with topical retinoids or benzoyl peroxide is effective for moderate noninflammatory (come-donal) and mild to moderate inflammatory (papulopustular) acne."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "Because of its antibacterial and anti-comedogenic properties, benzoyl peroxide is preferred to retinoids for inflammatory acne. Another benefit of using benzoyl peroxide with antibiotic cream is its potential to reduce antibiotic-associated resistance to Propionibacterium acnes."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "A recent narrative review of clinical trials concluded that clindamycin plus benzoyl peroxide was more effective in reducing inflammatory lesions than monotherapy with either agent alone, and was similar in efficacy to benzoyl peroxide/erythromycin combination."
        },
        {
            "input": "For moderate comedonal and mild to moderate papulopustular acne, combination therapy with either benzoyl peroxide or topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin [Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most effective.",
            "output": "Similarly, combination therapy with clindamycin and adapalene was superior to clindamycin alone in improving mild to moderate acne."
        },
        {
            "input": "other",
            "output": "Acne vulgaris is the most common cutaneous disorder, affecting about 45 million people in the United States. Five to 6 million acne-related visits are made to physicians in outpatient offices each year."
        },
        {
            "input": "Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant.",
            "output": "A randomized controlled trial, found a much lower incidence of cesarean section and operative vaginal deliveries among induced vs expectantly managed women at term."
        },
        {
            "input": "Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant.",
            "output": "A retrospective cohort study found a much lower incidence of cesarean section and operative vaginal deliveries among induced vs expectantly managed women at term."
        },
        {
            "input": "Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant.",
            "output": "A large population-based study suggests that the higher cesarean section rates in elective induction is present only among nulliparous women; in multiparous women, the rate is the same as expectant management."
        },
        {
            "input": "Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant.",
            "output": "Two large retrospective studies support the concept that cesarean section rates and admissions to neonatal intensive care units are higher with elective induction as opposed to expectant management."
        },
        {
            "input": "Women who take oral contraceptives (OCs) have an increased risk of developing new hypertension, which returns to baseline within 1 to 3 months of OC cessation.",
            "output": "A survey study of 461 women attending family planning clinics found that mean blood pressures were significantly higher for those taking OCs than for those using nonhormonal contraception. Elevated blood pressures correlated with duration of current use of OCs but returned to normal soon after stopping OCs. The mean pressures of those who had stopped OCs more than a month were similar to those of women who had never taken an OC and significantly lower than those of women who were currently taking OCs."
        },
        {
            "input": "Women who take oral contraceptives (OCs) have an increased risk of developing new hypertension, which returns to baseline within 1 to 3 months of OC cessation.",
            "output": "A systematic review of 8 case control studies (with 4907 cases and 13,443 controls) found an increased risk of stroke and MI among hypertensive women taking combined type OCs vs those not taking OCs. Women with hypertension aged 20 to 24 years had an estimated CV event risk of 312 per million woman-years while taking OCs vs 134 per million woman-years not taking OCs. Among hypertensive women aged 40 to 44 years, the estimated risks were 1213 vs 529 per million woman-years, respectively. Primary endpoints varied across the studies and statistical significance was not given."
        },
        {
            "input": "Women who take oral contraceptives (OCs) have an increased risk of developing new hypertension, which returns to baseline within 1 to 3 months of OC cessation.",
            "output": "A prospective cohort study found an increased incidence of new hypertension developing among women taking OCs. The study, conducted in the US, included 68,297 female nurses aged 25 to 42 years without a previous diagnosis of hypertension, diabetes, coronary heart disease, stroke, or cancer, who were followed for 4 years. Women were excluded from the study if they had not had a physical exam in the last 2 years or were taking antihypertensive medication at study inception. The nurses self-reported their blood pressure readings via questionnaire; medical records were sampled to validate the accuracy of self-reports. After adjusting for risk factors, current oral contraceptive use increased the risk of developing hypertension (relative risk [RR]=1.8; 95% confidence interval [CI], 1.5-2.3; corresponding to 41.5 new cases of hypertension per 10,000 person-years)."
        },
        {
            "input": "Women who take oral contraceptives (OCs) have an increased risk of developing new hypertension, which returns to baseline within 1 to 3 months of OC cessation.",
            "output": "Three studies showed that blood pressure elevations due to taking oral contraceptives returned to baseline with discontinuation of the medication. A prospective cohort study followed 13,358 women who were neither pregnant nor postpartum between the ages of 15 and 60. Women who either initiated or resumed using OCs experienced a statistically significant rise of about 4 mm Hg in the systolic pressure and 1 mm Hg in the diastolic pressure. Women who stopped using OCs experienced significant decreases in both systolic and diastolic components (about 5 mm Hg and 1.5 mm Hg, respectively."
        },
        {
            "input": "Among large populations of women with hypertension from all causes, risk of adverse cardiovascular outcomes is increased.",
            "output": "For the general population cardiovascular risk increases 30% for each 10 mm Hg rise in systolic pressure."
        },
        {
            "input": "Women with pre-existing hypertension who take OCs have an increased risk of stroke and myocardial infarction (MI) when compared with hypertensive women who do not.",
            "output": "A prospective study which followed 32 women who had taken combined OCs for 1 to 3 years and then stopped found that blood pressures returned to pretreatment levels at 3 months. Systolic pressure fell by 9.7 mm Hg and diastolic by 2.9 mm Hg compared with measurements made 1 month before stopping. No cardiovascular complications were reported among women during this study."
        },
        {
            "input": "Sulfonylureas, metformin, thiazolidinediones, and non-sulfonylurea secretagogues differ little in their ability to decrease glycosylated hemoglobin (HbA1c) levels when used as initial monotherapy for diabetes mellitus type 2.",
            "output": "Head-to-head studies are difficult to compare since hypoglycemic medications may reach peak effects at different times. An RCT compared glimepiride (Amaryl), pioglitazone (Actos), and metformin over 12 months of use by 114 patients with diabetes. There was no difference among the groups in overall HbA1c reduction. However, glimepiride decreased HbA1c rapidly over 1 month and reached a nadir at 4 months. Pioglitazone did not reduce HbA1c until 6 months and reached its nadir at 7 to 9 months. Metformin produced an intermediate response."
        },
        {
            "input": "Sulfonylureas, metformin, thiazolidinediones, and non-sulfonylurea secretagogues differ little in their ability to decrease glycosylated hemoglobin (HbA1c) levels when used as initial monotherapy for diabetes mellitus type 2.",
            "output": "A systematic review with 22 RCTs (total n=7370), ranging in length from 12 weeks to 3 years, compared 2 oral agents with a single oral agent or placebo. Combinations of oral agents produced statistically significant additional improvement in HbA1c in 21 of 22 studies. The magnitude of this effect across the studies was on the order of a 1% change in HbA1c, although the data were not subject to a formal meta-analysis."
        },
        {
            "input": "Sulfonylureas, metformin, thiazolidinediones, and non-sulfonylurea secretagogues differ little in their ability to decrease glycosylated hemoglobin (HbA1c) levels when used as initial monotherapy for diabetes mellitus type 2.",
            "output": "A systematic review with 31 placebo-controlled randomized trials (total n=12,185 patients) evaluated changes in HbA1c with monotherapy using 5 different classes of oral agents. Except for the \u0391-glucosidase inhibitor acarbose (Precose), which was less effective, all agents typically reduced HbA1c by 1% to 2%. However, in an additional 19 out of 23 randomized head-to-head studies (total n=5396) included in the same systematic review, all classes showed equal efficacy."
        },
        {
            "input": "A-glucosidase inhibitors may also be as effective.",
            "output": "A meta-analysis of head to head studies involving \u0391-glucosidase inhibitors included 8 trials comparing acarbose with sulfonylureas. In pooled results, sulfonylureas trended towards greater HbA1c reduction but did not reach significance (additional HbA1c decrease 0.4%; 95% confidence interval [CI], 0%-0.8%)."
        },
        {
            "input": "Metformin is generally indicated in obese patients because it improves all-cause mortality and diabetes related outcomes.",
            "output": "In 12 trials with 2067 patients, metformin decreased HbA1c more than sulfonylureas did (standardized mean difference [SMD] -0.14; 95% CI, -0.28 to -0.01). In 3 trials with 246 patients, metformin also produced greater HbA1c decreases than thiazolidinediones (SMD -0.28; 95% CI, -0.52 to -0.03). In the United Kingdom Prospective Diabetes Study (UKPDS), metformin improved diabetes-related outcomes and all-cause mortality in obese patients (relative risk of mortality=0.73; 95% CI, 0.55-0.97; P=.03; number needed to treat [NNT]=19)."
        },
        {
            "input": "Insulin is generally not recommended as an initial agent.",
            "output": "Inhaled insulin may expand the list of initial therapies for type 2 diabetes. A 12-week manufacturer-sponsored RCT with 134 patients (mean HbA1c=9.5) compared inhaled insulin with rosiglitazone (Avandia). More patients using inhaled insulin achieved an HbA1c <8.0 (82.7% vs 58.2%; P=.0003); however, inhaled insulin produced more adverse effects, including cough and hypoglycemia."
        },
        {
            "input": "other",
            "output": "A meta-analysis of head-to-head studies involving metformin showed equal efficacy compared with injected insulin (2 trials, 811 participants), \u0391-glucosidase inhibitors (2 trials, 223 participants), and non-sulfonylurea secretagogues (2 trials, 413 participants)."
        },
        {
            "input": "Combination therapy using insulin plus metformin (Glucophage), a sulfonylurea, or both produces glycemic control comparable with using insulin alone, but there is less weight gain when metformin is used.",
            "output": "A systematic review evaluated beginning combination therapy (adding insulin to oral medication) compared with switching to insulin alone in patients with type 2 diabetes mellitus with inadequate glycemic control on oral medication. Twenty RCTs studied a total of 1811 patients; glycemic control was the primary outcome measure. Oral medication comprised either sulfonylureas (75%), metformin (4%), or both (21%). Individual studies used different insulin dosing schedules and statistical measures. However, overall, combination therapy provided glucose control comparable with insulin alone. In only 1 small, low-quality study did insulin plus metformin reduce HbA1c more than other combination therapy regimens or insulin alone. Ten studies reported a trend toward less weight gain with combination therapy that included metformin. Fourteen studies found the same incidence of hypoglycemic episodes in combination therapy and insulin alone."
        },
        {
            "input": "Combination therapy using insulin and pioglitazone (Actos) reduces glycosylated hemoglobin (HbA1c) more than either insulin alone or adding pioglitazone to a sulfonylurea, but results in more weight gain.",
            "output": "An open-label RCT evaluated 281 patients with at least 3 months of inadequate glycemic control (HbA1c=7.4%-14.7%) on a sulfonylurea. Patients were randomized to a) switching to a combination of biphasic insulin aspart 30/70 plus pioglitazone, b) adding pioglitazone to the sulfonylurea, or c) switching to insulin alone (biphasic insulin aspart 30/70). After 18 weeks, insulin plus pioglitazone reduced HbA1c significantly more than either glyburide plus pioglitazone (P=.005) or insulin alone (P=.005). However, the insulin plus pioglitazone group had the most weight gain (mean 4 kg, similar to other pioglitazone trials). There were no major hypoglycemic events."
        },
        {
            "input": "Using insulin glargine (Lantus) in combination therapy produces fewer nocturnal hypoglycemic events than using neutral protamine Hagedorn (NPH) insulin, while producing equivalent HbA1c reduction.",
            "output": "An open-label RCT of 756 patients with inadequate glycemic control (HbA1c >7.5%, mean 8.6%) on either 1 or 2 oral agents (70% taking both metformin and a sulfonylurea) compared combination therapy using bedtime insulin glargine with combination therapy using morning NPH. Each group titrated insulin doses to achieve a target fasting glucose \u2264100. By 24 weeks, both groups had equivalently reduced HbA1c (mean HbA1c=6.96% with glargine, and 6.97% with NPH; P=NS), but fewer patients experienced nocturnal hypoglycemia with glargine than with NPH (33.2% vs 26.7%, P<.05)."
        },
        {
            "input": "When the HbA1c is high (above 9.0% to 9.5%) on 1 or 2 oral agents, beginning combination therapy is more effective than adding another oral agent.",
            "output": "Mean weight gain was similar in all 3 groups but only a minority of patients reached a target HbA1c of 6.5%. In the final study of only 16 patients, HbA1c after 6 months improved significantly and equally in both groups (baseline: 8.3%, combination therapy final: 6.8%; insulin alone final: 7.0%). However, the combination therapy group gained significantly less weight."
        },
        {
            "input": "No, it's not. No studies demonstrate that training patients to examine their skin decreases mortality from melanoma in the general population. Nor is there any evidence to suggest that teaching patients to monitor their skin for suspicious lesions results in earlier detection of melanoma, better prognosis at diagnosis, or better clinical outcomes. However, patients who have had melanoma and perform self-examination have a lower risk of death from subsequent occurrences than those who do not.",
            "output": "A case-control study compared SSE among 650 Caucasian patients newly diagnosed with melanoma and 549 age- and sex-matched controls. Fifteen percent of all patients practiced SSE. Investigators monitored a statewide registry system for 5.4 years to identify 110 participants with melanoma who had major adverse outcomes (distant metastases or death). Patients with a history of melanoma who practiced SSE had lower mortality (odds ratio [OR]=0.42; 95% confidence interval [CI], 0.21-0.85) than those who didn't. One potential weakness of the study was possible lead-time bias, which could overestimate the risk reduction from SSE. Another was the 5.4-year follow-up, because malignant melanoma can recur as long as 10 years later."
        },
        {
            "input": "Among patients who find their own melanomas, those who are more knowledgeable about melanoma and aware of their skin are less likely to delay seeking treatment or to have thick lesions upon presentation.",
            "output": "In a study, involving a cohort of 255 patients from the first study who discovered their own melanomas, researchers questioned patients about their knowledge of melanoma signs and symptoms, awareness of the appearance of their own skin, and whether they delayed seeking medical attention for >3 months after detecting the initial lesion. More knowledgeable patients were less likely to have a thick (\u22650.75 mm) tumor and a delayed diagnosis (OR=0.34; 95% CI, 0.13-0.88). Similarly, patients with greater awareness of their skin were less likely to have a thick tumor and a delayed diagnosis (OR=0.50; 95% CI, 0.28-0.89 and OR=0.30; 95% CI, 0.12-0.71, respectively). Investigators found no significant difference in mortality based on knowledge or skin awareness."
        },
        {
            "input": "Patients who detect melanomas themselves know more about the characteristic features of melanoma and are more likely to perform regular skin self-examinations than patients whose lesions are found by a physician.",
            "output": "A retrospective series of 816 consecutive cases of newly diagnosed melanoma investigated the frequency of self-detection in a Mediterranean population at intermediate risk. Subjects were statistically more likely to find melanoma themselves if they had a lesion on the lower limbs, were of younger age (49.8 vs 52.9 years of age), had fewer atypical nevi, had >8 years education, were knowledgeable about the characteristic features of melanoma, and performed regular SSE (P<.01 for all comparisons)."
        },
        {
            "input": "Depression, anxiety, and dementia, as well as older age, female gender, lower education level, and decreased physical activity, have all been associated with memory loss reported by patients or family members.",
            "output": "A prospective cohort study that followed 158 patients with no evidence of dementia showed a significant correlation between informant-reported memory problems and development of dementia at 5 years. Forty-five percent of patients with informant-reported memory problems developed dementia after 5 years compared with 25% of patients who had only self-reported memory problems (P =.02). This result suggests that subjective memory problems reported by observers (family or caregivers) may be more predictive of dementia than self-reported memory complaints."
        },
        {
            "input": "Depression, anxiety, and dementia, as well as older age, female gender, lower education level, and decreased physical activity, have all been associated with memory loss reported by patients or family members.",
            "output": "A study of 1883 patients with normal baseline short-cognitive test results found that those with subjective memory complaints had a higher incidence of dementia. At 5-year follow-up, 15% of patients with baseline subjective memory complaints had developed dementia compared to only 6% of those without such complaints (odds ratio=2.7; 95% confidence interval [CI], 1.45-4.98)."
        },
        {
            "input": "Depression, anxiety, and dementia, as well as older age, female gender, lower education level, and decreased physical activity, have all been associated with memory loss reported by patients or family members.",
            "output": "Several cross-sectional studies indicate that patients with subjective memory loss are more likely to be older, female, less physically active, in poorer health, less educated, and more depressed or anxious than unaffected patients. These studies concentrate mostly on elderly people living in the community."
        },
        {
            "input": "Memory complaints in patients with no cognitive impairment on short cognitive screening tests, such as the mini-mental status exam, may predict dementia.",
            "output": "One systematic review of 22 longitudinal cohort studies, which included more than 29,000 patients, evaluated complex patterns of mental activity in early, mid-, and late-life in relation to the incidence of dementia. Dementia was diagnosed at a significantly lower rate in patients with a higher level of cognitive exercise, such as memory-based leisure activities and social interactions, than those with less rigorous daily cognitive challenges (relative risk=0.54; 95% CI, 0.49-0.59)."
        },
        {
            "input": "No consistent evidence supports pharmacologic treatment of reported memory loss that is not corroborated by objective findings.",
            "output": "Data from trials that enrolled either asymptomatic elderly patients or patients with mild cognitive impairment don't support the use of donepezil, ginkgo biloba, NSAIDs, COX-2 inhibitors, vitamin E, vitamin B6, vitamin B12, statins, hormone replacement therapy, or omega-3 fatty acids to delay progression to dementia."
        },
        {
            "input": "Fluoxetine combined with cognitive behavioral therapy (CBT) is superior to fluoxetine alone, CBT alone, or placebo.",
            "output": "The landmark Treatment for Adolescents with Depression Study, which was included in the meta-analysis, comprised 4 treatment arms: fluoxetine alone, CBT alone, fluoxetine with CBT, and placebo. Only the combination therapy group showed a statistically significant improvement compared with placebo in the primary outcome (improved Children's Depression Rating Scale-Revised). Improvement in the Clinical Global Impressions score, a subjective measure, was statistically significant in 71% of patients receiving combination therapy and 60.6% of those treated with fluoxetine compared with placebo (34.8%) or CBT alone (43.2%)."
        },
        {
            "input": "Further research is needed to address the long-term efficacy of fluoxetine treatment.",
            "output": "A 2007 Cochrane review supports the use of SSRIs to treat major depressive disorder in adolescents, reporting efficacy as 1.28 times that of placebo (95% confidence interval, 1.17-1.41). Quality of available clinical evidence is limited. Statistical significance was demonstrated in meta-analyses only when data from smaller trials were combined. Fluoxetine was the only antidepressant studied in nonindustry-sponsored trials for major depressive disorder in adolescents. Moreover, results are not often reported separately for children (5-12 years of age) and adolescents (12-18 years of age)."
        },
        {
            "input": "Tricyclic antidepressants, citalopram, escitalopram, venlafaxine, and sertraline are minimally effective in treating depression in adolescents.",
            "output": "A post hoc subgroup analysis of 2 combined RCTs comparing extended-release venlafaxine with placebo showed modest, statistically significant improvement in depressive symptoms in adolescents, but not children."
        },
        {
            "input": "Tricyclic antidepressants, citalopram, escitalopram, venlafaxine, and sertraline are minimally effective in treating depression in adolescents.",
            "output": "Pooled results of 3 RCTs demonstrated that paroxetine was no better than placebo. Two RCTs of citalopram and 1 RCT of escitalopram showed marginally significant benefit over placebo only when pooled."
        },
        {
            "input": "Tricyclic antidepressants, citalopram, escitalopram, venlafaxine, and sertraline are minimally effective in treating depression in adolescents.",
            "output": "Two RCTs showed that sertraline was slightly, but statistically significantly, better than placebo when the 2 identically designed trials were combined."
        },
        {
            "input": "Tricyclic antidepressants, citalopram, escitalopram, venlafaxine, and sertraline are minimally effective in treating depression in adolescents.",
            "output": "A 2002 Cochrane meta-analysis reported marginal evidence to support using tricyclic antidepressants for treating adolescents. However, these drugs have significantly more side effects than placebo. No placebo-controlled RCTs of bupropion, duloxetine, mirtazapine, or St. John's wort for treating major depressive disorder in adolescents were identified."
        },
        {
            "input": "Head-to-head trials are needed to compare the efficacy of antidepressants.",
            "output": "Fifteen well-designed trials have examined the efficacy of antidepressants for treating major depressive disorder in youth. All reported the changes in total scores on standard depression scales: the Children's Depression Rating Scale-Revised, Clinical Global Impressions, Hamilton Rating Scale for Depression, or Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children."
        },
        {
            "input": "Information about the safety of tricyclic antidepressants in young people is limited because adverse effects have not been systematically reported in trials.",
            "output": "Evidence concerning the safety of tri-cyclic antidepressants in adolescents is limited because adverse effects have not been systematically reported. A 2002 Cochrane meta-analysis found a statistically significant increase in rates of vertigo, orthostatic hypotension, tremor, and dry mouth among children and adolescents taking tricyclic antidepressants compared with placebo. The drugs are modestly effective in treating depression in adolescents; concerns about side effects and safety, however, have limited their use."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "American College of Neuropsychopharmacology argues that the risk-to-benefit ratio favors drug treatment for moderate to severe adolescent depression."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "A recent study that incorporated the FDA meta-analysis analyzed data from 4582 patients. Although no completed suicides were reported in any trial, the drug-treated groups had a two-fold in-crease in suicidality compared with placebo groups (4% vs 2%; number needed to harm [NNH]=50)."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "A recent Cochrane review confirmed the increase in absolute risk (1.8; 95% confidence interval [CI], 1.19-2.72)."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "One analysis estimated the difference in risk to be 1.6-fold with a 95% CI of 1.0-2.7 (3% vs 2%; NNH=112)."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "One analysis estimated the difference in risk to be 1.6-fold with a 95% CI of 1.0-2.7 (3% vs 2%; NNH=112). The lower estimated risk results largely from a statistical reframing rather than any major difference in data analyzed. The analyses used a random-effects model instead of a fixed-effects model to calculate suicidality, assuming heterogeneity in the drugs used, trial de-signs, and outcome measures. Notably, venlafaxine had the greatest - and only statistically significant - increased risk, mostly because of suicidal ideation (7 of 9 events in 182 treated patients vs none in 179 placebo patients)."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment."
        },
        {
            "input": "Major safety concerns - prompting a US Food and Drug administration (FDA) black box label warning - have been raised about increased risk of suicidality (ideation, behavior, and attempts) among adolescents receiving antidepressant therapy. Studies indicate that SSRIs and venlafaxine increase the absolute risk of suicidality by 1% to 2% compared with placebo. However, no suicides occurred during any study. On detailed subanalysis, each SSRI was as safe as placebo, and only venlafaxine demonstrated a statistically significant increase in risk of suicidality.",
            "output": "The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment. The Society for Adolescent Medicine explicitly directs clinicians to consider the FDA black box warning in the con-text of the need to treat major depressive disorder in adolescents and endorses pharmacotherapy for appropriately selected patients."
        },
        {
            "input": "Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.",
            "output": "The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period. Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38)."
        },
        {
            "input": "Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.",
            "output": "The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0)."
        },
        {
            "input": "Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.",
            "output": "A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (\u22657 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk."
        },
        {
            "input": "There is strong evidence against suppressing PVCs with antiarrhythmics.",
            "output": "Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups."
        },
        {
            "input": "other",
            "output": "The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour."
        },
        {
            "input": "other",
            "output": "A consistent definition of frequent PVCs doesn't exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour."
        },
        {
            "input": "Three beta-blockers-carvedilol, metoprolol, and bisoprolol-reduce mortality in chronic heart failure caused by left ventricular systolic dysfunction, when used in addition to diuretics and angiotensin converting enzyme (ACE) inhibitors.",
            "output": "A study of atenolol versus placebo in subjects with ejection fraction \u226425% from various causes (N=100) was halted early when atenolol produced a 50% reduction in worsening heart failure and a 71% reduction in cardiac hospitalizations. A trend toward improved survival was noted but did not reach statistical significance."
        },
        {
            "input": "Three beta-blockers-carvedilol, metoprolol, and bisoprolol-reduce mortality in chronic heart failure caused by left ventricular systolic dysfunction, when used in addition to diuretics and angiotensin converting enzyme (ACE) inhibitors.",
            "output": "The US Carvedilol trial had several methodologic problems: it was a composite of 4 smaller studies that used exercise tolerance as the primary endpoint; median duration of data collection on subjects was only 6 months; it included many minimally symptomatic patients; the actual number of deaths was small (producing a wide confidence interval); and subjects who did not survive the run-in phase were excluded from analysis."
        },
        {
            "input": "Three beta-blockers-carvedilol, metoprolol, and bisoprolol-reduce mortality in chronic heart failure caused by left ventricular systolic dysfunction, when used in addition to diuretics and angiotensin converting enzyme (ACE) inhibitors.",
            "output": "The US Carvedilol trial demonstrated a larger reduction in mortality than that seen in other beta-blocker trials."
        },
        {
            "input": "Three beta-blockers-carvedilol, metoprolol, and bisoprolol-reduce mortality in chronic heart failure caused by left ventricular systolic dysfunction, when used in addition to diuretics and angiotensin converting enzyme (ACE) inhibitors.",
            "output": "The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), and Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) all showed similar reductions in mortality in moderately ill patients with heart failure."
        },
        {
            "input": "Three beta-blockers-carvedilol, metoprolol, and bisoprolol-reduce mortality in chronic heart failure caused by left ventricular systolic dysfunction, when used in addition to diuretics and angiotensin converting enzyme (ACE) inhibitors.",
            "output": "No large studies of older beta-blockers adequately assess mortality in heart failure. One study of propranolol (N=158) showed a 27% reduction in mortality in mild heart failure in the setting of ischemic heart disease."
        },
        {
            "input": "No differences in mortality or patient tolerance have been demonstrated in studies comparing carvedilol and metoprolol.",
            "output": "A large randomized controlled trial compared carvedilol and metoprolol head-to-head. It included 150 subjects with ejection fractions below 35% who were randomized to 1 of the 2 drugs and followed for more than 3 years. Symptom scores and quality of life assessments were similar in the 2 groups. A trend toward lower mortality in the carvedilol group did not reach statistical significance. Peak oxygen uptake during exercise was greater in the metoprolol group. The carvedilol group had a statistically greater improvement in ejection fraction (+10.9 \u00b1 11.0 vs +7.2 \u00b1 7.7 at rest)."
        },
        {
            "input": "other",
            "output": "In contrast, the Beta-Blocker Evaluation of Survival Trial (BEST) demonstrated no effect with bucindolol."
        },
        {
            "input": "other",
            "output": "The Carvedilol or Metoprolol European Trial (COMET), a larger head-to-head trial of carvedilol and metoprolol (N=3029), is ongoing."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "The UK Guidelines for the Management of Cutaneous Melanoma recommend that suspicious lesions be excised completely excisional biopsy and sent for confirmatory histopathological examination. A biopsy that transects the depth of the lesion for example, superficial shave biopsy should be avoided because histological depth of invasion is the basic criterion for staging and shave biopsy makes the staging impossible in some cases."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "Guidelines on nevocellular nevi from the American Academy of Dermatology recommend a simple excisional or incisional biopsy; they do not discuss the method of removal for benign appearing facial lesions."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "A retrospective study compared the Breslow depth determination of 4 different biopsy techniques, performed by experienced dermatologists, with the subsequent depth on definitive surgery for melanoma. This study found that superficial shave, deep shave, and punch biopsy predicted the Breslow depth 88% (95/108) of the time. As expected, excisional biopsy predicted the depth 100% (30/30) of the time. The location of the biopsy sites were not reported. The choice of biopsy was influenced by the suspicion of melanoma; thin (< 1 mm) melanomas were more likely to be superficially shaved than deep-shaved or punched."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "Atypical lesions require excisional biopsy. The depth and architecture of the lesion, if melanoma, cannot be determined by shave biopsy, and both treatment and prognosis depend on those characteristics. These guidelines derive from well-designed, nonexperimental descriptive studies."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "Researchers conducting a second retrospective study, done at least 1 year after the procedure, used a questionnaire to ask 76 patients (with a total of 83 nevi removed from the face by shave excision) about their perceptions of the scar. Patients described their lesions as: no scar (33%), white and flat (25%), depressed (19%), raised (15%), and pigmented (7%). Eighty-six percent thought their scars looked better than the nevus and 79% were \"happy with the way the scar looks now.\"."
        },
        {
            "input": "A shave biopsy with a razor blade or#15 scalpel is the best approach for a facial nevus, assuming malignancy is not suspected. the resulting scar is usually flat, smaller than the lesion, has no suture lines, and-if shaved in mid or upper dermis-has a low risk of producing a hypertrophic or hypotrophic scar.",
            "output": "One prospective study followed 55 patients after removal of nevi from the head and neck. These nevi were removed using a shave procedure with a#15 scalpel and hot cautery for bleeding. Of the 55 sites, 4 retained pigment and 30 had a visible scar with a mean diameter of 5 mm at 6- to 8-month follow-up. The mean diameter of the original lesions was 6 mm. There was no difference between the size of those lesions that scarred and those that didn't."
        },
        {
            "input": "Yes. Brushing twice daily with topical fluoride toothpaste decreases the incidence of dental caries in infants and toddlers.",
            "output": "Topical fluoride use has been associated with dental fluorosis, which causes staining or pitting of the enamel tooth surface. The incidence of significant dental fluorosis varies in children-from 5% to 7% with 1450 ppm fluoride toothpaste to 2% to 4% with 440 ppm fluoride toothpaste (number needed to harm [NNH]=20-100)."
        },
        {
            "input": "Yes. Brushing twice daily with topical fluoride toothpaste decreases the incidence of dental caries in infants and toddlers.",
            "output": "Another Cochrane review found 17 randomized controlled trials comparing different methods of topical fluoride application in children. The limited data suggested that fluoride toothpaste is as effective as mouth rinse or gel."
        },
        {
            "input": "Yes. Brushing twice daily with topical fluoride toothpaste decreases the incidence of dental caries in infants and toddlers.",
            "output": "A large Cochrane review evaluated topical fluoride therapy in the form of toothpaste, mouth rinse, varnish, or gel. Based on 133 randomized or quasi-randomized controlled trials (n=65,169), the meta-analysis indicated a 26% (95% confidence interval [CI], 24%-29%) reduction in decayed, missing, and filled tooth surfaces in children."
        },
        {
            "input": "High-concentration fluoride toothpaste delivers superior caries protection, but causes more dental fluorosis.",
            "output": "High-fluoride-concentration toothpastes (1000 ppm F) prevent 14% more caries than low-fluoride-concentration toothpastes (250 ppm F)."
        },
        {
            "input": "High-concentration fluoride toothpaste delivers superior caries protection, but causes more dental fluorosis.",
            "output": "Another randomized controlled trial, carried out in an area without fluoridated water, found the high-fluoride-concentration toothpaste (1450 ppm F) resulted in 16% fewer caries in children, while the low-fluoride-concentration toothpaste (440 ppm F) was no different than placebo."
        },
        {
            "input": "High-concentration fluoride toothpaste delivers superior caries protection, but causes more dental fluorosis.",
            "output": "A meta-analysis found that the effect of topical fluoride was independent of water fluoridation, suggesting that topical fluoride toothpaste has a beneficial effect even in communities with fluoridated water."
        },
        {
            "input": "Use of high-concentration fluoride toothpaste should be targeted towards children at highest risk of dental caries, such as those living in areas without fluoridated water.",
            "output": "Depending on the prevalence of caries in the population, between 1.6 and 3.7 children need to use a fluoride toothpaste to prevent 1 decayed, missing, or filled tooth."
        },
        {
            "input": "Yes. In children at high risk for atopy (those with a family history of allergy, asthma, or eczema in at least 1 first-degree relative), breastfeeding or giving hydrolyzed protein formula during the first 4 to 6 months reduces the risk of atopy in the first year of life, when compared with introducing cow's milk or soy formula.",
            "output": "Studies have not found a significant difference among these forms of milk for infants without a strong family history of atopic disease."
        },
        {
            "input": "Yes. In children at high risk for atopy (those with a family history of allergy, asthma, or eczema in at least 1 first-degree relative), breastfeeding or giving hydrolyzed protein formula during the first 4 to 6 months reduces the risk of atopy in the first year of life, when compared with introducing cow's milk or soy formula.",
            "output": "The relative risk for wheeze or asthma in the first year of life was 0.4 (95% confidence interval [CI] 0.19-0.85) for children fed hydrolyzed protein formulas when compared with cow's milk."
        },
        {
            "input": "Yes. In children at high risk for atopy (those with a family history of allergy, asthma, or eczema in at least 1 first-degree relative), breastfeeding or giving hydrolyzed protein formula during the first 4 to 6 months reduces the risk of atopy in the first year of life, when compared with introducing cow's milk or soy formula.",
            "output": "Breastfeeding and the use of hydrolyzed protein formulas confer the lowest risk of atopy in high-risk children when compared with cow's milk or soy-based formulas."
        },
        {
            "input": "Yes. In children at high risk for atopy (those with a family history of allergy, asthma, or eczema in at least 1 first-degree relative), breastfeeding or giving hydrolyzed protein formula during the first 4 to 6 months reduces the risk of atopy in the first year of life, when compared with introducing cow's milk or soy formula.",
            "output": "Systematic reviews analyzing the modification of early feeding practices to prevent atopic disease have all been limited by a paucity of double-blinded RCTs of sufficient duration."
        },
        {
            "input": "There is inconsistent evidence to show that early introduction of solid food increases the incidence of atopic disease.",
            "output": "There is speculation that introducing certain solid foods early increases the risk of allergies to these foods, as well as causing generalized atopic symptoms. Few studies have examined this, and no systematic reviews focus on atopic disease."
        },
        {
            "input": "There is inconsistent evidence to show that early introduction of solid food increases the incidence of atopic disease.",
            "output": "A cohort study (n=1265) comparing children who had been given 4 or more types of solid food before 4 months of age with those whose caregivers delayed solid foods showed an increased incidence of eczema by 10 years of age (relative risk=2.35; P<.05) in the early feeding group."
        },
        {
            "input": "There is inconsistent evidence to show that early introduction of solid food increases the incidence of atopic disease.",
            "output": "A prospective interventional cohort study using a retrospective cohort as a control (n=375) compared children who had strictly avoided fish and citrus products until 1 year of age with those who had an unrestricted diet. There was no difference in the frequency of allergy to these foods as quantified by history and positive challenge test, although the authors did not include a statistical analysis of their results."
        },
        {
            "input": "There is inconsistent evidence to show that early introduction of solid food increases the incidence of atopic disease.",
            "output": "A study randomized 165 high-risk children into groups with standard feeding practices or an allergy prophylaxis regimen, which included avoidance of milk protein until age 1 year, eggs until 2 years, and fish and peanuts until 3 years. Although prophylaxis decreased the prevalence of atopic disorders at 1 year, there was no difference in any atopic disease between the 2 groups at age 7."
        },
        {
            "input": "Yes. Based on current evidence, fluoxetine is the most effective selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder in adolescents. It is the only agent approved by the US Food and Drug Administration (FDA) for use in children.",
            "output": "AACAP concluded that fluoxetine is effective for the treatment of depression in children and adolescents."
        },
        {
            "input": "Yes. Based on current evidence, fluoxetine is the most effective selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder in adolescents. It is the only agent approved by the US Food and Drug Administration (FDA) for use in children.",
            "output": "A meta-analysis including both published and unpublished trials of SSRI medications found that fluoxetine was more likely than placebo to cause remission of symptoms after 7 to 8 weeks of treatment (number needed to treat [NNT]=6). Fluoxetine treatment was also associated with a reduction in symptom scores as measured with the CDRS-R (NNT=5)."
        },
        {
            "input": "Yes. Based on current evidence, fluoxetine is the most effective selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder in adolescents. It is the only agent approved by the US Food and Drug Administration (FDA) for use in children.",
            "output": "A large, multicenter, randomized controlled trial evaluated the effectiveness of fluoxetine (Prozac), cognitive behavioral therapy (CBT), or the combination of the 2. Researchers evaluated improvement with the Children's Depression Rating Scale-Revised (CDRSR). The CDRS-R uses adolescent and parent interviews to rate 17 symptom areas: impaired schoolwork, difficulty having fun, social withdrawal, appetite disturbance, sleep disturbance, excessive fatigue, physical complaints, irritability, excessive guilt, low self-esteem, depressed feelings, morbid ideas, suicidal ideas, excessive weeping, depressed facial affect, listless speech, and hypoactivity. Combination treatment with fluoxetine and CBT was statistically superior to placebo, CBT alone, or fluoxetine alone. In addition, fluoxetine alone was superior to CBT alone."
        },
        {
            "input": "All SSRI medications increase the risk of suicidal behavior in adolescents, but do not increase the risk of completing suicide.",
            "output": "In 2004, the FDA conducted a meta-analysis of the suicide related adverse events from the published and unpublished trials of SSRIs including fluoxetine, sertraline, paroxetine, fluvoxamine (Luvox), and citalopram. A team of experts reviewed the adverse events from each trial to evaluate for suicidality including suicidal ideation, preparatory acts, self-injurious behavior, or suicide attempts. They found a risk ratio of 1.66 (95% confidence interval, 1.02-2.68) for suicidality in the treatment arms compared with placebo. There were no completed suicides in any study."
        },
        {
            "input": "All SSRI medications increase the risk of suicidal behavior in adolescents, but do not increase the risk of completing suicide.",
            "output": "An ecological analysis of prescription data and US Census data found an overall decline in suicide rates as the rate of prescriptions for SSRI medications increased, suggesting a beneficial correlation of SSRI medications on suicide rates."
        },
        {
            "input": "There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control-regardless of whether it involves diet, glyburide, or insulin-leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia.",
            "output": "A meta-analysis combined 6 RCTs comparing diet alone with diet plus insulin in a total of 1281 women. Insulin was moderately superior to diet in preventing fetal macrosomia (NNT=11; 95% confidence interval, 6-36), but not in rates of hypoglycemia, hypocalcemia, hyperbilirubinemia, or congenital malformations."
        },
        {
            "input": "There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control-regardless of whether it involves diet, glyburide, or insulin-leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia.",
            "output": "Similarly, a retrospective study comparing glyburide with insulin in 584 women found little difference between the 2 approaches. Women in the glyburide group had better glycemic control, but the women in the insulin group started with higher initial blood sugars. The glyburide group had fewer NICU admissions than the insulin group (number needed to treat [NNT]=11), but higher rates of jaundice (number needed to harm [NNH]=25), pre-eclampsia (NNH=17), and maternal hypoglycemia (NNH=8). All other neonatal outcomes were similar between groups."
        },
        {
            "input": "There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control-regardless of whether it involves diet, glyburide, or insulin-leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia.",
            "output": "A high-quality randomized controlled trial comparing glyburide with insulin among 404 women found no difference in maternal hypoglycemia, neonatal mortality, or neonatal features and outcomes (including birthweight, NICU admissions, hyperbilirubinemia, and hypoglycemia; P \u2265.25). Although this was a fairly large trial, it may have been underpowered since it found small differences in such rare outcomes."
        },
        {
            "input": "There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control-regardless of whether it involves diet, glyburide, or insulin-leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia.",
            "output": "Findings from 2 studies support the notion that the treatment of gestational diabetes decreases neonatal morbidity and mortality. Both studies found a decrease in neonatal morbidity and mortality for those patients treated either with diet or insulin."
        },
        {
            "input": "There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control-regardless of whether it involves diet, glyburide, or insulin-leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia.",
            "output": "One study found a higher rate of NICU admission in the treatment group, but the authors attributed this to physician awareness of the patient having gestational diabetes."
        },
        {
            "input": "Probably not. Only 1 appetite stimulate, megestrol acetate oral suspension (Megace) at 400 mg or 800 mg daily, has been studied in this population. The data show only limited benefit, mixed outcomes, and potential harm.",
            "output": "As in all therapeutic interventions, benefit must be balanced against risk. The Megace ES package insert notes the following potential adverse effects: diarrhea, cardiomyopathy, palpitation, hepatomegaly, leukopenia, edema, paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking, thrombophlebitis, pulmonary embolism, and glucose intolerance."
        },
        {
            "input": "Probably not. Only 1 appetite stimulate, megestrol acetate oral suspension (Megace) at 400 mg or 800 mg daily, has been studied in this population. The data show only limited benefit, mixed outcomes, and potential harm.",
            "output": "In contrast, an earlier Veterans Administration (and predominantly male) study showed 13/21 of those treated with megestrol (800 mg daily for 12 weeks) noted weight gain (\u22654 lb sustained at 3 months post-treatment), compared with 5/23 of those receiving placebo (number needed to treat [NNT]=2.5).2 Of note, only 9/26 patients had sustained weight gain in the megestrol group at the 12-month endpoint post-treatment, comparable with 7/25 in the placebo group. Some small, but statistically significant, score improvements were noted during the treatment period in appetite and enjoyment of life; however, no differences were noted in scores on the more widely accepted Geriatric Depression Scale."
        },
        {
            "input": "Probably not. Only 1 appetite stimulate, megestrol acetate oral suspension (Megace) at 400 mg or 800 mg daily, has been studied in this population. The data show only limited benefit, mixed outcomes, and potential harm.",
            "output": "One placebo-controlled randomized clinical trial studied 45 malnourished patients who were recently discharged from an acute care hospital to a nursing home. The patients (predominately female, with a mean age of 83) were randomized into 4 treatment arms (placebo or megestrol 200 mg, 400 mg, or 800 mg daily) and followed for 63 days. Only those receiving megestrol (400 mg or 800 mg daily) demonstrated a statistically significant increase in patient appetite and a dose-responsive increase in prealbumin level at the 20 day interim analysis (7.5 and 9.0 mg/dL, respectfully). But at the final assessment (63 days), only the 400-mg dose maintained a statistically significant increase in prealbumin over placebo. However, there was no significant improvement in serum albumin or clinical endpoints (weight, functional status, or health-related quality of life)."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "The British Thoracic Society recommends any of the macrolides for pneumonia caused by these pathogens in children."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "The Infectious Diseases Society of America recommends a macrolide for adults with pneumonia caused by M pneumoniae or C pneumoniae, and does not promote one over another."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "A study compared antibiotics for patients with CAP aged 12 to 93 years. Subgroup analysis of those with M pneumoniae or C pneumoniae (n=27) showed similar efficacy. Pooling all 268 patients with CAP, side effects were seen in 31% of patients on clarithromycin and 59% on erythromycin (P<.001)."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "A study looked at patients aged 12 to 80 years with pneumonia due to M pneumoniae (75 cases) or Chlamydophila psittaci (formerly Chlamydia psittaci, 16 cases). All patients responded to treatment."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "Clarithromycin and erythromycin were compared in children aged 3 to 12 years with CAP. M pneumoniae or C pneumoniae was identified in 42 cases. Two of 18 patients did not respond to erythromycin; 3 of 27 patients did not respond to clarithromycin."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "In one study, side effects were noted in 10% of CAP patients on azithromycin and 20% on erythromycin (P<.05)."
        },
        {
            "input": "Erythromycin, clarithromycin, and azithromycin are equally effective in treating pneumonia caused by Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae.",
            "output": "Azithromycin and erythromycin were compared in 3 studies of children with CAP. Together, they identified 69 cases due to M pneumoniae or C pneumoniae."
        },
        {
            "input": "Tests for antibodies to Epstein-Barr viral capsid antigen (EBVCA) or Epstein-Barr nuclear antigen (EBNA) are the most sensitive, are highly specific, and are also the most expensive for diagnosing infectious mononucleosis.",
            "output": "A validating cohort study assessed the sensitivity and specificity of 6 commercial test kits for detection of Epstein-Barr virus-specific antibodies (EBVCA and EBNA). The study compared antibody levels in 139 serum specimens from patients with recent primary EBV infections (confirmed by both a positive heterophile antibody test and an EBV antibody pattern compatible with recent infection) and in 40 specimens from healthy normal controls. The average sensitivity of the antibody tests was 97% (95%-99%) and average specificity was 94% (86%-100%)."
        },
        {
            "input": "Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness.",
            "output": "A validating cohort study validating cohort studies assessed the accuracy of several commercially available test kits for the detection of heterophile antibodies (eg, \"Mono spot\" tests). The study compared 6 kits using either a latex agglutination or a solid-phase assay against a \"gold standard\" of serologic verification for 53 serum samples from primary EBV infection, 26 samples from EBV immune patients, and 21 samples from healthy donors. Serologic verification used immunoflourescence to determine: the absence of IgG but presence of IgM, the presence of IgG but absence of IgM, or the absence of both antibodies (respectively) against EBVCA."
        },
        {
            "input": "Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness.",
            "output": "The sensitivity of heterophile antibody testing is lower in children under 12 (25%-50%) and early in the illness (25% false-negative rate in first week)."
        },
        {
            "input": "The polymerase chain reaction (PCR) assay for Epstein-Barr virus DNA is more sensitive than the heterophile antibody test in children, is highly specific, but is also expensive.",
            "output": "Another validating cohort study evaluated PCR testing for EBV DNA among children (average age 9 years, 4 months), 28 with infectious mononucleosis, 25 who were EBV seronegative, and 26 who were seropositive. Children with acute infectious mononucleosis were diagnosed by symptoms, >10% atypical lymphocytes, and a positive heterophile antibody test. The PCR found a sensitivity and specificity of 75% and 98% at 1 week. Testing earlier, especially in children, is expected to decrease the sensitivity due to the lower maturity of the immune system response."
        },
        {
            "input": "The percentages of atypical lymphocytes and total lymphocytes on a complete blood count (CBC) provide another specific and moderately sensitive, yet inexpensive, test.",
            "output": "A validating cohort study compared peripheral blood samples in 181 patients aged >16 years with a clinical diagnosis of infectious mononucleosis confirmed by a positive heterophile antibody test with those from 181 similar patients with a negative test. An increased percentage of lymphocytes and atypical lymphocytes were associated with higher sensitivity and specificity for infectious mononucleosis."
        },
        {
            "input": "other",
            "output": "The second study used a similar method to test 6 more heterophile kits using blood samples from 140 patients."
        },
        {
            "input": "Cryotherapy has similar cure rates to topical salicylate (a pharmacologic therapy) for non-genital common warts.",
            "output": "Two recent reviews also found that cryotherapy is similar in efficacy to salicylic acid, and reported that other nonpharmacologic treatments lack evidence."
        },
        {
            "input": "Cryotherapy has similar cure rates to topical salicylate (a pharmacologic therapy) for non-genital common warts.",
            "output": "Longer freeze times seem to improve cryotherapy cure rates but also cause increased blistering and pain."
        },
        {
            "input": "Cryotherapy has similar cure rates to topical salicylate (a pharmacologic therapy) for non-genital common warts.",
            "output": "Seventeen studies of cryotherapy with between 30 and 400 patients show cure rates ranging from 29% to 87%, although most did not have placebo arms. Pooled data from 69 patients in 2 small studies did not show a benefit between the cryotherapy and nontreatment arms, although there were very low cure rates from cryotherapy in 1 study and high spontaneous remission rates in the other."
        },
        {
            "input": "Duct tape may be equivalent to cryotherapy.",
            "output": "One randomized controlled trial of 61 patients showed cure rates of 85% with duct tape vs 60% with cryotherapy. Duct tape therapy had the advantages of reduced cost and less pain."
        },
        {
            "input": "CO2 laser, photodynamic therapy, pulsed dye laser (PDL), and Er:Yag laser therapies may also be effective for recalcitrant warts.",
            "output": "Although pulsed dye laser has efficacy in various studies, no evidence favors it over cryotherapy or cantharidin. Treatment with CO2 laser and Er:Yag laser had an efficacy of 52% to 100%. However, many of these studies were small, poorly randomized, and had no placebo control."
        },
        {
            "input": "other",
            "output": "The potential hazard of aerosolized virus particles from these therapies has not been evaluated."
        },
        {
            "input": "other",
            "output": "Since adverse effects from treatment, such as pain and scarring, can occur, patients should be educated as to options of therapy (or no therapy)."
        },
        {
            "input": "other",
            "output": "The evaluation of treatments of nongenital warts is confounded by the propensity of simple warts to disappear spontaneously. Approximately two thirds of warts resolved without therapy over a 2-year period, according to 1 study in an institutional population."
        },
        {
            "input": "There is adequate evidence for screening neonates for hemoglobinopathies, congenital hypothyroidism, phenylketonuria.",
            "output": "The USPSTF recommendations supporting screening for hemoglobinopathies, congenital hypothyroidism, and phenylketonuria are considered standard of care."
        },
        {
            "input": "There is adequate evidence for screening neonates for cystic fibrosis.",
            "output": "A report, based on a systematic review, recommends cystic fibrosis screening in neonates based on moderate benefits and low risks of harm."
        },
        {
            "input": "Vision screening should be done for those younger than age 5 years.",
            "output": "One fair-quality controlled study (N=3490) showed a decreased prevalence of amblyopia in the screened group and evidence that treatment of amblyotic risk factors prevents amblyopia."
        },
        {
            "input": "Vision screening should be done for those younger than age 5 years.",
            "output": "A Cochrane review of this topic showed insufficient evidence for visual screening of older (school-aged) children; for amblyopia, no data sufficient for analysis was found."
        },
        {
            "input": "High-risk children should be tested for tuberculosis (TB).",
            "output": "The USPSTF recommendation to screen asymptomatic high-risk children for TB is based on the effectiveness of early intervention (14 controlled trials) and the accuracy of the Mantoux test."
        },
        {
            "input": "High-risk children should be tested for lead toxicity.",
            "output": "Although no controlled studies directly show that screening high-risk children for lead exposure improves clinical outcomes, several lesser-quality studies create a logical path to this conclusion."
        },
        {
            "input": "No patient-oriented evidence supports pneumococcal revaccination of any patient (high-risk or otherwise). Antibody levels may be augmented by revaccination; however, the clinical efficacy of revaccination, even among high-risk patients, is unknown. Revaccination is recommended by the Advisory Committee on Immunization Practices (ACIP) in certain circumstances.",
            "output": "Most recently, a Cochrane Review (updated in 2005) concluded that \"the combined results from randomized studies fail to show that the polysaccharide vaccine is effective in preventing either pneumonia or death\". However, they did recognize that the nonrandomized studies have consistently shown that the polysaccharide vaccine is effective in reducing the more specific outcome of invasive pneumococcal disease bacteremia and meningitis."
        },
        {
            "input": "No patient-oriented evidence supports pneumococcal revaccination of any patient (high-risk or otherwise). Antibody levels may be augmented by revaccination; however, the clinical efficacy of revaccination, even among high-risk patients, is unknown. Revaccination is recommended by the Advisory Committee on Immunization Practices (ACIP) in certain circumstances.",
            "output": "A study of pneumococcal strains cultured from hospitalized patients demonstrated a duration of protection against pneumococcal infection that was much longer than that predicted by the shorter duration of antibody levels. The vaccine's ability to reduce infection (due to serotypes included in the vaccine) lasted for at least 9 years and overall efficacy for preventing infection caused by the serotypes included in the vaccine was 57%."
        },
        {
            "input": "No patient-oriented evidence supports pneumococcal revaccination of any patient (high-risk or otherwise). Antibody levels may be augmented by revaccination; however, the clinical efficacy of revaccination, even among high-risk patients, is unknown. Revaccination is recommended by the Advisory Committee on Immunization Practices (ACIP) in certain circumstances.",
            "output": "Multiple studies have used measurement of antibody levels to assess the response of patients to the vaccine and for justification of the need for revaccination. However, measurement of antibody levels to pneumococcal serotypes is difficult, inexact, and is only a surrogate marker for the immune status of a patient, which also relies on the overall function of their immune system. Although pneumococcal vaccine is most highly recommended in patients with chronic disease or immunodeficiency, these patients have a poorer initial response rate and a faster decline in antibody levels than younger, immunocompetent recipients of the vaccine."
        },
        {
            "input": "Revaccination once appears to be safe, especially if provided 5 years or more after primary vaccination.",
            "output": "Revaccination is safe; particularly when performed more than 5 years after the initial vaccination. Injection site reactions are more common and more severe in revaccinated persons (rising from 3% to 15% in the immunocompetent patient)."
        },
        {
            "input": "other",
            "output": "Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and the second most common cause of bacterial meningitis in the United States. An estimated 40,000 people die annually in the US from pneumococcal infections. Even with antibiotic treatment and intensive care unit support, the mortality of patients with pneumococcal bacteremia approaches 25% to 30%."
        },
        {
            "input": "other",
            "output": "Revaccination, however, does not result in increased rates of hospitalization, and few severe reactions have been reported."
        },
        {
            "input": "other",
            "output": "Because of the importance of this pathogen, it has been the focus of several trials to demonstrate the efficacy of the primary vaccination. To date, 7 meta-analyses have been completed to assess the efficacy of pneumococcal vaccine in adults, with varying results."
        },
        {
            "input": "other",
            "output": "Among those who do respond to revaccination, antibody levels can rapidly decline to undetectable levels in a matter of months, and they may or may not retain protection against disease over time."
        },
        {
            "input": "other",
            "output": "Among those who were nonresponders to the initial vaccination, revaccination (even repeated revaccination) is not effective in stimulating any significant antibody response."
        },
        {
            "input": "A diet high in fiber (particularly fruit and vegetable fiber) and low in fat and red meat may help to decrease the risk of symptomatic diverticular disease.",
            "output": "One large, prospective study of 47,888 male health professionals gathered baseline dietary information in 1986. In 1990 and 1992, follow-up questionnaires asked the subjects if they had been diagnosed with diverticular disease in the interim, and whether they had symptoms of diverticulitis. The study showed a strong inverse relationship between fruit and vegetable fiber intake and risk of symptomatic diverticular disease. It also demonstrated a direct relationship between fat intake, particularly red meat, and symptomatic diverticular disease. For men in the highest quintile of total fat intake and lowest quintile of total fiber intake, the relative risk (RR) of diverticular disease was 2.35 (95% confidence interval [CI], 1.38-3.98) compared with men in the highest quintile of total fiber intake and lowest quintile of total fat intake. Men in the highest group of red meat intake and lowest quintile of fiber intake had a RR of 3.22 (95% CI, 1.46-7.54) compared with men with the lowest red meat intake and highest dietary fiber intake. In this study, cereal fiber did not reduce the risk of symptomatic diverticular disease."
        },
        {
            "input": "A diet high in fiber (particularly fruit and vegetable fiber) and low in fat and red meat may help to decrease the risk of symptomatic diverticular disease.",
            "output": "Approximately 60% of people living in Westernized countries who are older than 60 years will develop diverticulosis of the colon. Colonic diverticuli are thought to develop from an increase in intraluminal pressure. This pressure can be caused by colonic motility abnormalities, but a low-fiber diet can also result in a smaller stool mass and a less distended colon, thereby increasing intraluminal pressure."
        },
        {
            "input": "A diet high in fiber (particularly fruit and vegetable fiber) and low in fat and red meat may help to decrease the risk of symptomatic diverticular disease.",
            "output": "A small case series of adults treated with dietary fiber found that fiber alleviated symptoms of diverticular disease."
        },
        {
            "input": "A diet high in fiber (particularly fruit and vegetable fiber) and low in fat and red meat may help to decrease the risk of symptomatic diverticular disease.",
            "output": "Because of strong epidemiological evidence that people from cultures with high-fiber diets are far less likely to develop diverticulosis than are people who live in cultures of low-fiber diets, it has been assumed that a diet high in fiber can prevent diverticulosis. Many small, uncontrolled studies have also investigated the effect of high-fiber diets and supplements on symptoms of diverticulosis and prevention of diverticulitis episodes."
        },
        {
            "input": "For people with diverticular disease, a diet high in fiber might decrease the risk of complications.",
            "output": "A small case series of adults treated with dietary fiber found that fiber possibly reduced complications of diverticulosis."
        },
        {
            "input": "other",
            "output": "Two small randomized crossover studies evaluated the benefit of dietary fiber supplementation on symptomatic diverticular disease, with conflicting results."
        },
        {
            "input": "other",
            "output": "Another study found no significant differences between psyllium, bran, and placebo in reducing symptomatic diverticular disease."
        },
        {
            "input": "other",
            "output": "One study found that sterculia gum with an antispasmodic, a high roughage diet, and bran tablets all improved symptomatic diverticular disease, with bran tablets associated with the greatest improvement."
        },
        {
            "input": "other",
            "output": "A small randomized trial of lactulose vs dietary fiber showed both treatments to be effective in alleviating symptoms of diverticular disease."
        },
        {
            "input": "No element or combination of elements from the clinical history and physical examination are sufficiently sensitive or specific to confirm or exclude acute community-acquired pneumonia (CAP). A chest x-ray is recommended to make the diagnosis.",
            "output": "At a Veterans Administration hospital, a prospective cohort of 52 men with acute cough and change in sputum production underwent sequential blinded examination by 3 physicians. Rales and bronchial breath sounds were common, and chest x-ray confirmed pneumonia in 28 patients. Sensitivity of clinical diagnosis ranged from 47% to 69%, and specificity from 58% to 75%."
        },
        {
            "input": "No element or combination of elements from the clinical history and physical examination are sufficiently sensitive or specific to confirm or exclude acute community-acquired pneumonia (CAP). A chest x-ray is recommended to make the diagnosis.",
            "output": "Nine symptoms (cough, dyspnea, sputum production, subjective fever, chills, night sweats, myalgias, sore throat, and rhinorrhea) and 3 items in the past medical history (asthma, immunosuppression, and dementia) were associated with pneumonia. For most elements of history, both the positive and negative likelihood ratios (LR+, LR-) were in the indeterminate range of 0.5 to 2.0. No single feature was sufficient to either rule in or rule out the diagnosis. In one study, the absence of any vital sign abnormalities reduced the likelihood of pneumonia substantially (LR- = 0.18), but did not rule out the diagnosis completely. Egophony had an LR+ of 5.3. Other physical findings (rhonchi, crackles, decreased breath sounds, dullness to percussion, and bronchial breath sounds) yielded LR+s from 1.5 to 3.5, respectively. Most individual findings were insufficient to diagnose pneumonia. For example, if the baseline prevalence of pneumonia was 5%, the presence of crackles raised the probability to 10% and their absence decreased the probability to 3%."
        },
        {
            "input": "No element or combination of elements from the clinical history and physical examination are sufficiently sensitive or specific to confirm or exclude acute community-acquired pneumonia (CAP). A chest x-ray is recommended to make the diagnosis.",
            "output": "In a study, 24 physicians examined 24 patients with a variety of respiratory conditions: only 4 had pneumonia on chest x-ray. The most reliable findings (dullness to percussion and wheezing) had only fair agreement among examiners (kappa approximately 0.5)."
        },
        {
            "input": "Colposcopy is the preferred test in the work-up of patients with abnormal cervical cytology: Low-grade squamous intraepithelial lesion (LSIL): mild dysplasia. High-grade squamous intraepithelial lesion (HSIL): moderate to severe dysplasia. Atypical squamous cells of undetermined significance (ASC-US) with high-risk human papillo-mavirus (HPV) DNA. Atypical squamous cells, cannot rule out HSIL (ASC-H). Atypical glandular cells (AGC). Adenocarcinoma in situ (AIS).",
            "output": "Using histology as the gold standard, the sensitivity of colposcopy for cervical abnormalities is high 96%; 95% confidence interval [CI], 95%-97%, but the specificity is much lower 48%; 95% CI, 47%-49%. This low specificity means that more than half of women with no cervical pathology will have an abnormal colposcopy result. The corresponding positive and negative likelihood ratios are 2 and 0.1, respectively. Consequently, a normal colposcopy result can effectively rule out cervical pathology, thus supporting its role as a diagnostic rather than a screening tool."
        },
        {
            "input": "Colposcopy is also recommended for patients with symptoms suggestive of cervical cancer (abnormal appearance of the cervix, persistent and undiagnosed vaginal discharge or bleeding) regardless of cytology results, and in the follow-up of patients previously treated for cervical dysplasia.",
            "output": "Colposcopy is also indicated for patients with symptoms suggestive of cervical dysplasia or cancer abnormal appearance of the cervix, or persistent and undiagnosed vaginal discharge or bleeding, even in the setting of normal cytology."
        },
        {
            "input": "Colposcopy is also recommended for patients with symptoms suggestive of cervical cancer (abnormal appearance of the cervix, persistent and undiagnosed vaginal discharge or bleeding) regardless of cytology results, and in the follow-up of patients previously treated for cervical dysplasia.",
            "output": "One study identified 3 risk factors for recurrence of dysplasia after a loop electrocautery excision procedure LEEP: residual disease at either the endocervical or ectocervical margins, and involvement of endocervical glands. The presence of these risk factors predicted a recurrence rate of almost 70%. Because 8% of the recurrences were missed on cytology, the authors recommended colposcopy 6 months after LEEP for patients with these risk factors."
        },
        {
            "input": "Colposcopy is not recommended for routine cervical cancer screening.",
            "output": "The primary role of colposcopy is to identify cervical lesions, allowing directed biopsies to identify invasive cancer or its precursors. Although colposcopy has been studied as a primary screening technique, issues of cost, accessibility, invasiveness, and low specificity severely limit its usefulness in this role."
        },
        {
            "input": "Colposcopy is not recommended for routine cervical cancer screening.",
            "output": "While most lesions are found by abnormal cytology, the sensitivity of the Papanicolaou smear ranges from 30% to 89%."
        },
        {
            "input": "Magnetic resonance angiography (MRA) and computed tomography angiography (CTA) are the most consistently accurate, noninvasive screening methods. MRA is likely the preferred option because of its lack of radiation and reduced risk of contrast media.",
            "output": "One rare but serious concern with MRA is that contrast agents may cause nephrogenic systemic fibrosis (NSF), a debilitating and sometimes fatal diffuse disease affecting the skin, muscle, and internal organs. In 2006, 25 cases of NSF after exposure to gadolinium-based contrast agents were reported, prompting an FDA warning."
        },
        {
            "input": "Magnetic resonance angiography (MRA) and computed tomography angiography (CTA) are the most consistently accurate, noninvasive screening methods. MRA is likely the preferred option because of its lack of radiation and reduced risk of contrast media.",
            "output": "Among the primary diagnostic tests for RAS, MRA is the most consistently accurate and least operator dependent-which makes it the best choice in most situations."
        },
        {
            "input": "other",
            "output": "Significant renal artery stenosis (RAS) is defined anatomically as >50% stenosis of the lumen by renal angiography; stenosis is considered hemodynamically significant (potentially causing renovascular hypertension) if it exceeds 75%."
        },
        {
            "input": "other",
            "output": "Worsening renal function after starting an angiotensin-converting enzyme inhibitor (ACE-I)."
        },
        {
            "input": "other",
            "output": "(Worsening renal function is defined as >30% decline in estimated glomerular filtration rate or >30% increase in serum creatinine during the first 2 months of ACE-I therapy)."
        },
        {
            "input": "Routine vaccination with the meningococcal conjugate vaccine MCV4 (Menactra) is indicated for all US adolescents entering high school and for college freshmen living in dormitories.",
            "output": "Using CDC incidence data, a cost-effectiveness model compared hypothetical vaccination strategies targeting US infants (3 doses), toddlers (1 dose), or 11-year-olds (1 dose). Routine MCV4 vaccination of all 11-year-olds would prevent 270 cases and 36 deaths in this cohort over their next 22 years. For a toddler cohort, vaccination would prevent 385 cases and 33 deaths; for infants, 447 cases and 36 deaths. Conjugate meningococcal vaccines for serogroups A and C have been tested and used in children in other countries, and appear safe and effective, but are not yet available in the US. An application has been submitted for FDA approval of MCV4 for 2- to 10-year-olds."
        },
        {
            "input": "Routine vaccination with the meningococcal conjugate vaccine MCV4 (Menactra) is indicated for all US adolescents entering high school and for college freshmen living in dormitories.",
            "output": "A 1998-1999 prospective surveillance study including 50 state health departments and 231 college health centers identified 96 cases of meningococcal disease in college students (incidence 0.7/100,000). Freshmen living in dormitories had an elevated risk of meningococcal disease compared with other undergraduates or nonstudents of the same age (incidence 5.1/100,000; adjusted relative risk=3.6 [95% confidence interval [CI], 1.6-8.5). Sixty-eight percent had illness due to a vaccine-preventable serogroup."
        },
        {
            "input": "Routine vaccination with the meningococcal conjugate vaccine MCV4 (Menactra) is indicated for all US adolescents entering high school and for college freshmen living in dormitories.",
            "output": "Using active community surveillance from 1991 to 2002, Centers for Disease Control and Prevention (CDC) data found annual rates of meningococcal disease in the US of 0.5 to 1.1 per 100,000. The highest rates were found in children under age 2. Infants younger than 12 months of age were especially vulnerable (rate 9/100,000), with more than 50% of cases caused by serogroup B."
        },
        {
            "input": "Routine vaccination with the meningococcal conjugate vaccine MCV4 (Menactra) is indicated for all US adolescents entering high school and for college freshmen living in dormitories.",
            "output": "MCV4 is licensed for 11- to 55-year-olds and is the preferred vaccine in this age group, since it provides longer duration of immunity and reduces nasopharyngeal carriage."
        },
        {
            "input": "Routine vaccination of infants and toddlers with conjugate vaccine may be more cost-effective than targeting adolescents, but conjugate meningococcal vaccine for this age group is not yet available in the US.",
            "output": "Vaccinating adolescents may be particularly helpful for building herd immunity. A Norwegian study of nasopharyngeal meningococcal carriage among 943 unimmunized individuals ages 2 months to 95 years found a carriage rate of 28% among 15- to 24-year-olds, compared with 9.6% overall."
        },
        {
            "input": "Routine vaccination of infants and toddlers with conjugate vaccine may be more cost-effective than targeting adolescents, but conjugate meningococcal vaccine for this age group is not yet available in the US.",
            "output": "High hospitalization rates in US military recruits during 1964 to 1970 (25.2/100,000) led to the development of the meningococcal polysaccharide vaccine. Since 1971, all new military recruits have received polysaccharide meningococcal vaccine, and for the period 1990 to 1998 the hospitalization rate for meningococcal disease among active duty service members had decreased by 98% (to 0.51/100,000)."
        },
        {
            "input": "Routine vaccination of infants and toddlers with conjugate vaccine may be more cost-effective than targeting adolescents, but conjugate meningococcal vaccine for this age group is not yet available in the US.",
            "output": "A British study compared attack rates for meningococcal C disease in children from infancy to age 18 before and 1 to 2 years after the institution of a nationwide meningococcal serogroup C conjugate vaccination. Vaccine coverage ranged from 66% (adolescents) to 87% (schoolchildren), and vaccine efficacy was 94% to 96%. Incidence of meningococcal C disease in the unvaccinated children also decreased by 52% to 67% (from 4.08/100,000 to 1.36/100,000)."
        },
        {
            "input": "Erythromycin has a limited role in treating pediatric patients.",
            "output": "The erythromycin dose used in these studies was lower than the dosage for antibiotic purposes; no adverse effects were reported. However, cardiac arrhythmias and death have occurred when erythromycin is given to adults and children at the usual antibiotic doses."
        },
        {
            "input": "Erythromycin has a limited role in treating pediatric patients.",
            "output": "Two RCTs in neonates demonstrated that erythromycin shortened intestinal transit time and improved feeding tolerance."
        },
        {
            "input": "Erythromycin has a limited role in treating pediatric patients.",
            "output": "A small RCT of 14 children between 4 and 13 years of age showed that erythromycin improved symptoms of constipation and decreased laxative use (number needed to treat [NNT]=10)."
        },
        {
            "input": "Tegaserod is a prokinetic agent available for constipated adults, but cardiovascular risk restricts prescribing it.",
            "output": "In 2 RCTs of tegaserod for constipation, patients exhibited improved abdominal symptoms and increased spontaneous bowel movements (NNT=6 for 2 mg and 5 for 6 mg in the first study; NNT=11 for 2 mg and 7 for 6 mg in the second study)."
        },
        {
            "input": "Tegaserod is a prokinetic agent available for constipated adults, but cardiovascular risk restricts prescribing it.",
            "output": "A pooled analysis of RCTs of tegaserod revealed an increase in cardiovascular events, prompting withdrawal of the drug from the market (number needed to harm=1000)."
        },
        {
            "input": "Cisapride is a prokinetic agent available for constipated adults, but cardiovascular risk restricts prescribing it.",
            "output": "One RCT of cisapride for constipation showed that it improved symptoms."
        },
        {
            "input": "Cisapride is a prokinetic agent available for constipated adults, but cardiovascular risk restricts prescribing it.",
            "output": "Whereas another study demonstrated no significant difference between cisapride and placebo in constipation-predominant irritable bowel syndrome."
        },
        {
            "input": "other",
            "output": "Two small placebo-controlled trials demonstrated improved abdominal pain and stool consistency, but only 1 showed statistically significant results compared with placebo."
        },
        {
            "input": "other",
            "output": "Renzapride, a newer prokinetic similar to cisapride, is under investigation. It is one tenth the strength of cisapride and carries a lower potential risk of cardiac complications."
        },
        {
            "input": "No. Structured daily monitoring of fetal movement doesn't decrease the rate of all-cause antenatal death in average-risk pregnancies.",
            "output": "A prospective cohort study of 4383 births in California, using historical controls, found a drop in fetal mortality from 8.7 to 2.1 deaths/1000. The historical control rate was higher than statewide data from the same time period, however. The overall weaker design of the study and probable effect of regression to the mean significantly limit the interpretation of outcomes."
        },
        {
            "input": "No. Structured daily monitoring of fetal movement doesn't decrease the rate of all-cause antenatal death in average-risk pregnancies.",
            "output": "A recent rigorous systematic review yielded no significant outcome effect related to fetal kick counts."
        },
        {
            "input": "No. Structured daily monitoring of fetal movement doesn't decrease the rate of all-cause antenatal death in average-risk pregnancies.",
            "output": "A well-done RCT randomized 68,654 women to either usual care or structured, daily monitoring of fetal movement using the count-to-10 method-daily maternal documentation of the amount of time it takes to perceive 10 fetal movements. Usual care was comprised of a query about fetal movement at antenatal visits and instruction to perform fetal movement monitoring at the provider's discretion. Mothers were told to visit their health-care provider for evaluation if they felt no movement in 24 hours or fewer than 10 movements in 10 hours during a 48-hour period. The trial showed no benefit from monitoring in reducing the rate of antenatal death from all causes. The rate of all fetal deaths in the counting group was 2.9 per 1000 normally formed, live, singleton births; the rate in the control group was 2.67 (absolute risk reduction=0.24; 95% confidence interval [CI], -0.5 to 0.98). Women in the counting group spent an average of 160 hours counting during pregnancy and had a statistically significant increase in fetal non-stress-test (NST) monitoring (odds ratio [OR]=1.39; 95% CI, 1.31-1.49; number needed to harm [NNH]=50 to cause 1 additional NST). A statistically insignificant trend toward increased antepartum admissions was also noted in the counting group."
        },
        {
            "input": "Although maternal perception of decreased fetal movement may herald fetal death, it isn't specific for poor neonatal outcome.",
            "output": "A retrospective cohort study of 6793 patients compared pregnancy outcomes of 463 women who presented for evaluation of decreased fetal movement with outcomes among the general obstetric population. The study excluded women who reported complete cessation of fetal movement. Pregnancies evaluated for decreased fetal movement were less likely to have an Apgar score <7 at 5 minutes (relative risk [RR]=0.56; 95% CI, 0.29-0.96; P=.05) and less likely to be preterm (RR=0.68; 95% CI, 0.48-0.94; P=.02). No significant difference in cesarean section for fetal distress or admission to the neonatal intensive care unit was noted between the study and control groups. The study suggests that maternal perception of decreased fetal movement is not associated with poor fetal outcome."
        },
        {
            "input": "Monitoring fetal movement increases the frequency of non-stress-test monitoring.",
            "output": "A well-done RCT randomized 68,654 women to either usual care or structured, daily monitoring of fetal movement using the count-to-10 method-daily maternal documentation of the amount of time it takes to perceive 10 fetal movements. Usual care was comprised of a query about fetal movement at antenatal visits and instruction to perform fetal movement monitoring at the provider's discretion. Mothers were told to visit their health-care provider for evaluation if they felt no movement in 24 hours or fewer than 10 movements in 10 hours during a 48-hour period. The trial showed no benefit from monitoring in reducing the rate of antenatal death from all causes. The rate of all fetal deaths in the counting group was 2.9 per 1000 normally formed, live, singleton births; the rate in the control group was 2.67 (absolute risk reduction=0.24; 95% confidence interval [CI], -0.5 to 0.98). Women in the counting group spent an average of 160 hours counting during pregnancy and had a statistically significant increase in fetal non-stress-test (NST) monitoring (odds ratio [OR]=1.39; 95% CI, 1.31-1.49; number needed to harm [NNH]=50 to cause 1 additional NST). A statistically insignificant trend toward increased antepartum admissions was also noted in the counting group."
        },
        {
            "input": "other",
            "output": "Nearly 50% of late-pregnancy IUFDs have no associated risk factors. Fetal demise, however, may be heralded by decreased fetal movement followed by cessation of movement at least 12 hours before death."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "A retrospective review of more than 10,000 patients aged 3 to 36 months presenting to the emergency department used logistic regression to identify predictors of bacteremia. In this study, ANC (>9500/mm3) and WBC (>14,300/mm3) were of equal sensitivity (75%) and specificity (75%) in identifying serious bacterial infection."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "A review of 6579 outpatients aged 3 to 36 months presenting to the emergency department with temperatures of 39\u00baC or higher showed an ANC of >10,000/mm3 as more predictive of occult pneumococcal bacteremia than an elevated WBC count (>15,000/mm3) alone."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "To improve the diagnostic utility of the CBC, some studies have examined individual components of the white blood cell differential count. In particular, the use of the absolute neutrophil count (ANC) has been proposed as a superior marker of serious bacterial infection."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "Some studies show that the WBC alone is poorly discriminatory for identifying either bacteremia or meningitis."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "A retrospective study of 5353 infants ages 3 to 89 days presenting to the emergency department for evaluation of fever showed that 3 of 4 infants ultimately diagnosed with bacterial meningitis would have been missed if the WBC count alone were used to predict which infants need a lumbar puncture."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "Current literature does not support the premise that for acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "For acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection."
        },
        {
            "input": "No-the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections.",
            "output": "The band count alone does not accurately predict serious bacterial infection."
        },
        {
            "input": "When used in conjunction with other clinical parameters in validated decision-making algorithms, the CBC can help detect serious bacterial infections in pediatric patients with fever.",
            "output": "A lower prevalence reduces the utility of routine CBC or blood culture in the evaluation of immunized, febrile children. Parameters such as procalcitonin, interleukin-6, interleukin-8, interleukin-1 receptor antagonist and C-reactive protein show future promise as biochemical markers for identifying serious bacterial infections."
        }
    ]
}