1-1 COLLABORATIVE META-ANALYSIS OF RANDOMIZED TRIALS OF ANTIPLATELET THERAPY FOR PREVENTION OF DEATH, MYOCARDIAL INFARCTION, AND STROKE IN HIGH RISK PATIENTS
      Unless some definite contraindication exists, antiplatelet therapy (low-dose aspirin) should be considered routinely for all patients whose medical history implies a significant risk of occlusive vascular disease over the next few months or years (secondary prevention), and should generally be continued for as long as the risk remains high. Absolute benefits substantially outweigh the absolute risk of major extracranial bleeding.
      Aspirin is protective in patients with a history of ischemic stroke, unstable and stable angina, previous myocardial infarction, previous stroke or cerebral ischemia, diabetes, peripheral vascular disease, or atrial fibrillation (when warfarin is not used).
      Practical point: Primary care clinicians should prescribe aspirin more often for secondary prevention of cardiovascular events.

1-2 ASPIRIN FOR THE PRIMARY PREVENTION OF CARDIOVASCULAR EVENTS
      Five trials have examined the effects of daily or every-other-day aspirin for primary prevention over 4 to 7 years. Most subjects were men over age 50. Meta-analysis of pooled data showed that aspirin reduced the risk of coronary heart disease by 28%. No effect on total mortality or stroke.
      For patients at high risk of coronary heart disease (5% over 5 years) prophylactic aspirin would lead to avoidance of 6 to 20 CHD episodes over the 5 years.
      Primary prevention is not recommended for those with a risk of 1% per year.
      Practical point: The clinician's challenge is to judge the degree of risk and to match the patient's concerns and wishes with the risk. Many individuals will benefit from primary prevention with aspirin.

1-3 PREVALENCE OF THE METABOLIC SYNDROME AMONG US ADULTS
      About 22% of Americans have the metASDFiASDFc syndrome. (47 million) Implications for health2222 care are critical. CorrASDFASDFASDFAevention of the syndrome is a national health-care priority.
      Practical point: Correction and prevention of the syndrome in individual patients is a health-care priority.

1-4 ORAL ANTIHYPERGLYCEMIC THERAPY FOR TYPE 2 DIABETES: SCIENTIFIC REVUE
      Large trials in the UK compared metformin with placebo and intensive sulfonylurea-insulin therapy. With similar HbA1c reductions, metformin was associated with up to 40% fewer diabetic-related deaths, all cause mortality, risk of myocardial infarction, and all macrovascular endpoints.
      Metformin is the only drug associated with weight loss, or at least weight neutrality. It has become the most widely prescribed single antihyperglycemic drug. It is generally regarded as the best first-line agent, at least in the obese patient. (Most patients with DM2 are overweight.) Its virtual lack of hypoglycemia makes it an attractive option.
      There is no compelling reason in terms of antihyperglycemic effect alone, to favor one of the major class over another. However, the benefit of metformin demonstrated in the UK study (UKPDS) (which showed a lack of hypoglycemia and no weight gain) make it one of the most attractive options for obese - if not all- patients with DM2.
      Combination therapy is a logical approach, given the multiple pathophysiological lesions in DM2. Indeed, most patients after a few years will require more than one drug for good control. A second drug may provide additive effect on lowering HbA1c. There is no evidence that one specific combination is any more effective than another in lowering glucose levels.
      Only sulfonylureas and metformin have been shown to reduce microvascular complication. Metformin exhibits additional benefits on macrovascular risk. The popularity of metformin and thiazolidinediones is increasing since these agents avoid the risk of hypoglycemia and allow treatment of patients already near the euglycemic range.
      "Most patients will require combination as their disease progresses."
      Practical point: Primary care clinicians consider selecting metformin as first-choice.

1-5 EFFECT OF PREOPERATIVE SMOKING INTERVENTION ON POSTOPERATIVE COMPLICATIONS
      An effective smoking cessation program applied for at least 6 weeks prior to hip and knee surgery more than halved the frequency of postoperative complications.
      Practical point: Primary care clinicians should stress this benefit.

1-6 REDUCING ANTIBIOTIC USE FOR ACUTE BRONCHITIS IN PRIMARY CARE
      Most previously well adults who develop acute bronchitis were judged not to need antibiotics. Reassuring these patients and sharing uncertainty about the value of antibiotics in acute bronchitis is a safe strategy and reduces antibiotic use.
      Practical point: Primary care clinicians should use the "if" prescription more often.

1-7 CHRONIC FATIGUE SYNDROME; A STEP TOWARD AGREEMENT
      The Royal College of Physicians of the UK has issued a new report on the chronic fatigue syndrome (CFS) This editorial hopes it will mark a turning point in the history of the illness.
      There was agreement that the illness “is a relatively common clinical condition which can cause profound illness and disability and can have a very substantial impact on the individual and family.” It can affect both sexes, and a wide range of ages, even children. “It is no longer acceptable for clinicians to state that they do not ‘believe’ in CSF/ME. Inaction . . .due to ignorance or denial of the condition is not excusable.” A significant minority of patients who are very severely affected often receive the least attention. Patients need a positive and early diagnosis and appropriate management and advice. Patient organizations have an important role to play in this.
      Practical point: Primary care clinicians accept the fact that CFS is "real" and support the patient.

1-8 COMPARISON OF TWO DIETS FOR THE PREVENTION OF RECURRENT STONES IN IDIOPATHIC HYPERCALCIURIA
      A diet containing normal amounts of calcium and low animal protein and salt was more effective than a low calcium diet for prevention of recurrent calcium oxalate stones in men with idiopathic hypercalciuria.
      Aim to reduce concentration of oxalate in the urine, thus lowering saturation of Ca-oxalate, the chief stone former.
      Practical point: This diet should be standard therapy for recurrent calcium-oxalate stones.

1-9 RECURRENT HYPERCALCIURIC NEPHROLITHIASIS - DOES DIET HELP?
      Practical point: "Physicians should no longer prescribe a low-calcium diet to prevent recurrent nephrolithiasis in patients with idiopathic hypercalciuria."

1-11 ERADICATION OF HELICOBACTER PYLORI AND RISK OF PEPTIC ULCERS IN PATIENTS STARTING LONG-TERM TREATMENT WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS.
      Screening and treatment of H pylori infection reduced the risk of development of peptic ulcer in patients starting long-term NSAID treatment.
      Practical point: Consider screening and treatment of H pylori in select patients.

1-12 ANTIBIOTIC-ASSOCIATED DIARRHEA
      C difficile infection should be considered in all patients with unexplained diarrhea who are receiving antibiotics or who have recently received antibiotics.
      Enzyme assays to detect both toxins A and B are preferred. False negative results may occur if the only test is for toxin A.
      Many patients will respond to withdrawal of the inducing antibiotic. If the patient's condition calls for continued antibiotic therapy, use an agent that is infrequently associated with AAD. (See list in abstract.)
      If there is evidence of colitis or if discontinuation of the offending antibiotic does not result in resolution of the diarrhea, metronidazole is indicated. Lack of response to metronidazole is strong evidence against the C difficile colitis.
      If assays for C difficile toxin are negative, and symptoms persist, repeat the test, expand the diagnostic evaluation to other causes (eg, look for staph and salmonella), or treat empirically.
      Practical point: Patients who are informed of this risk may be less likely to demand antibiotics.

1-13 ALCOHOL CONSUMPTION AND RISK OF DEMENTIA: THE ROTTERDAM STUDY
      Light-to-moderate alcohol consumption was associated with a reduced risk of dementia in elderly individuals over age 65. The effect seemed to be unchanged by the type of alcohol consumed.
      Practical point: Although benefits in reducing incidence of dementia may be very modest, reports of low-dose alcohol consumption have been invariably favorable for a number of risks.

1-14 DIRECT THROMBIN INHIBITORS IN ACUTE CORONARY SYNDROMES
      Direct thrombin inhibitors were superior to heparin in preventing MI and death in patients with acute coronary syndromes including those undergoing PTCA. But the NNT to benefit one patient was large, and equaled the NNT to harm.
      The investigators recommend further development of DTIs for management of arterial thrombosis.
      Practical point: Primary care clinicians wait for further developments.

1-15 EFFICACY OF ROFECOXIB, CELECOXIB, AND ACETAMINOPHEN IN OSTEOARTHRITIS OF THE KNEE
      Rofecoxib 25 mg/d provided efficacy advantages over acetaminophen 4000 mg/d, and celecoxib 200 mg/d for symptomatic knee arthritis.
      Practical point: Despite this report, primary care clinicians will consider individual-patient response to various NSAIDs. Acetaminophen may be the best first-choice.

1-16 PLATELET GLYCOPROTEIN IIB/IIIA INHIBITORS IN ACUTE CORONARY SYNDROMES
      Glycoprotein IIb/IIIa inhibitors reduced cardiac complications in patients with acute coronary syndromes not routinely scheduled for early revascularization. Treatment might be considered early after admission in high-risk patients and continued for 2 to 4 days until a decision about revascularization is made.
      Benefit was evident only in those with a positive troponin.
      The number needed to treat to benefit one patient = 100
      Practical point: Primary care clinicians, wait for further developments.

1-17 US RELAXES SUGAR BAN FOR PEOPLE WITH DIABETES
      The American Diabetes Association has released new nutritional guidelines for diabetes control. It relaxes dietary restrictions on high sugar content foods. (Diabetes Care 2002;25:148-98, 200-12).
      Now, someone with diabetes would be able to indulge in an occasional slice of sugary pie and drink moderate amounts of alcohol without violating their diet. A moderate amount of daily alcohol intake poses no threat and may be healthy.
      Less than 10% of calorie intake should be derived from saturated fats and cholesterol intake should be no more than 300 mg/d.
      Practical point: The original may be worth accessing.

1. Serious vascular events - aspirin vs control:

   Category of trial	% odds reduction	Benefit/1000 patients	Mean months of treatment
   Previous MI	25	36	27
   Acute MI	30	38	1
   Previous stroke/TIA	22	36	29
   Acute stroke	11	9	0.7
   Other high risk	26	22	22
   All trials	22

   (NNT to benefit one person over the various time periods varied from 25 to 100.)
2. Reduction in risks in other high-risk patients:

   Vascular deaths were reduced by 15%
   All cause mortality was reduced by about 18%
   Pulmonary embolism reduced by 25%
   In patients with diabetes, serious vascular events were reduced by about 25%
   

3. Acute stroke
         Antiplatelet therapy is associated with reduction in risk of a recurrent non-fatal stroke in about 4 fewer patients per 1000 treated, and a reduction in risk of death from a vascular cause in about 5 per 1000. This was associated with 2 more major extracranial bleeds per 1000. "There is now good reason to consider starting antiplatelet therapy as soon as possible for suspected acute ischemic stroke and continuing it for some years."
4. Effects of antiplatelet drugs other than aspirin:
         Only clopidogrel (Plavix), among 7 other drugs (including dipyridamole; Persantine) showed any benefit above aspirin. (Clopidogrel blocks ADP dependent activation of platelets, acting in an entirely different manner than aspirin.) Compared with aspirin it reduced secondary occurrence of serious vascular events from 11.1% to 10.1%. Thus the NNT was low - about 100. (OnePlavix 75 mg costs over $3. In calculating the benefit/harm-cost ratio of long-term treatment, cost is an important factor, given the benefit which occurs in only 1 patient in 100. RTJ)
5. Effects of adding another antiplatelet drug to aspirin:
         Adding a drug that acts through another pathway might provide additional benefit. Adding dipyridamole (Persantine) was associated with a non-significant reduction in serious vascular events. In patients with unstable angina, clopidogrel produced additional benefit.
         Glycoprotein IIb/IIIa receptor blockers: The final common pathway of platelet aggregation is thought to be mediated by activation of platelet glycoprotein IIb/IIIa receptors. Many drugs that block this receptor have been developed. In patients with unstable angina or undergoing PTCA, short intravenous infusions (oral preparations are not effective) of a glycoprotein IIb/IIIa blocker added to aspirin produced a clinically significant reduction of 19% in serious vascular events. However, there was a 2.3% increase in major extracranial bleeds.
6. Dose of aspirin
         Within a few days of beginning 75 mg daily, cyclo-oxygenase is virtually completely inhibited in platelets. High doses (500-1500) are more gastrotoxic but are no more effective than low doses. The available evidence supports daily doses of 75-150 mg for the long term prevention of serious vascular events in high risk patients. A loading dose of 300 mg produces an immediate antithrombotic effect and can be given when an immediate effect is needed; 300 mg produces a rapid and complete inhibition of thromboxane-mediated platelet aggregation.
7. Harms of aspirin:
         Major extracranial bleeds increased. (Odds ratio = 1.6 compared with non-takers.)

Abdominal obesity -- waist circumference = 102 cm (42") in men, and = 88 cm (37") in women.
Hypertriglyceridemia -- = 150 mg/dL
Low high density cholesterol (HDL-c) , < 40 mg/dL in men; < 50 in women
High BP = 130/85
High fasting glucose = 110 mg/dL

1. A cross sectional health survey of a nationally representative sample of non-institutionalized men and women (1988-1994) analyzed data from over 8500 subjects. All were over age 20.
2. Determined prevalence of MS according to the criteria.

1. Overall prevalence was 22%. About 47 million US residents have the MS.
2. Prevalence increased from 7% of those age 20-29 to 44% in those age 60 to 69.
3. Mexican Americans (especially women) had the highest prevalence.
4. Prevalence was similar among men and women except for African American women who had a prevalence about 57% higher than African American men.

1. Up to 25% of US residents have the MS.
2. The unrelenting increase in prevalence of obesity suggests that the syndrome is likely more prevalent now.
3. Insulin resistance is thought to be an underlying feature of the MS. However, a significant proportion of patients with individual components of the MS do not have insulin resistance.
4. Some studies suggest that the association with hypertension is weak.
5. The cornerstones of treatment are management of weight and ensuring appropriate levels of physical activity.
6. Because improper nutrition and lack of physical activity are the root causes, there is an urgent need to develop comprehensive strategies directed at controlling obesity and improving physical activity.

1. Randomized trial assigned 100 daily smokers (mean age 65) to: 1) smoking intervention , or 2) control.
2. The intervention group met weekly for 6 to 8 weeks before surgery was scheduled. They received smoking counseling and nicotine replacement. They were strongly encouraged to stop smoking completely. They also had the option to reduce consumption by 50%.
3. Control group received standard care with little or no information about cessation.
4. At baseline they were consuming an average of 15 cigarettes daily with a history of 36 pack-years of smoking.
5. Registered all complications after the ensuing surgery.

1. In the intervention group, 36 stopped smoking; 14 reduced consumption; 6 continued to smoke.
2.  

   Complication rate	Intervention	Control
   Wound-related	5%	31%
   Cardiovascular	0%	10%
   Secondary surgery	4%	15%

3. Overall complication rate was 18% in the intervention group; 52% in controls.
4. Median length of stay in hospital 11 days vs 13 days: days in intensive care 2 vs 32.
5. Risks in subjects who reduced smoking, but did not stop, did not differ from those who continued to smoke.

1. Postoperative complications can be substantially reduced by smoking cessation for 6 to 8 weeks prior to surgery.
2. Pulmonary complications were unusual, probably due to the distance of the operative site from the diaphragm and early mobilization. Abdominal and gynecological surgery wold be associated with greater risk of pulmonary complications.

1. Single-blind, randomized, controlled trial entered over 250 previously well adults presenting with acute bronchitis.

   Defined as:
         Lower respiratory illness present for less than 3 weeks, cough as the main symptom; at least one other lower respiratory tract symptom - sputum production, dyspnea, wheeze, chest discomfort or pain - and no alternative explanation (not sinusitis, pharyngitis, or new presentation of asthma).

2. Forty eight (only 19%) were judged by their primary care clinician to need antibiotics. All of them were given an antibiotic prescription and encouraged to use it. Almost all did.
3. The 212 (81%) judged not to need antibiotics were also given a prescription for an antibiotic to use only if they got worse. All received verbal information of antibiotic use based on a prompt card.
4. Then randomized to: 1) receive an information leaflet, or 2) not receive the leaflet about the natural course of lower respiratory tract symptoms and the advantages and disadvantages of antibiotic use. (See copy of the prompt card and the leaflet at http://www.bmj.com/cgi/content/full/324/7329/91)
5. End point = whether the patient took the prescribed antibiotic.

1. Fewer patients who received the information leaflet took the antibiotic - 47% vs 62%.
2. Numbers seeking reconsultation were similar (11 vs 14).

1. A simple information leaflet about use of antibiotics for acute bronchitis and giving reassurance that the condition is not serious resulted in a reduction in use of the antibiotic by nearly a quarter.
2. Extrapolated to national use, many thousands of patients with acute bronchitis would avoid antibiotics.
3. The effect of verbal reassurance alone was not determined, but probably reduced antibiotic use somewhat.
4. Most episodes of acute bronchitis resolve on their own. It is not clear how to identify those who may benefit from antibiotics.
5. Rates of reconsultation were no higher in the leaflet group. No patient required referral to the hospital during follow up.
6. For the many patients (about 80%) for whom the primary care clinician believes antibiotics are not indicated, sharing the uncertainty openly and honestly is safe and effective, and lowers the number using an antibiotic.

1. A five year randomized trial compared effects of the two diets in 120 men (mean age = 45). All had recurrent calcium oxalate stones (mean = 5) with several episodes of colic in the previous year and hypercalciuria (> 300 mg/d). About 40% had family history of stones.
2. Randomized to: 1) diet with a normal amount of calcium (1200 mg/d) and with reduced amounts of animal protein (52 g/d) and salt ( 3 g NaCl); and 2) a low calcium diet ( 400 mg/d).
3. All avoided foods rich in oxalate. All increased intake of water to 2 to 3 liters per day.
4. Follow-up = 5 years.

1. Incidence of recurrent stone over 5 years: Normal Ca, low protein-low salt diet 12 of 60 men (20%) Low calcium diet 23 of 60 men (38%) [NNT 5 years = 6]
2. Recurrence was reduced by half, but this advantage was evident only after several years of follow-up.
3. During follow-up urinary calcium levels dropped significantly in both groups. But, urinary oxalate increased in men on the low calcium diet, and decreased in those on the normal calcium-low protein-salt diet. (Ie, the determining factor is a low rate urinary excretion of oxalate)

1. In men with idiopathic hypercalciuria, the normal calcium, low protein, low salt diet was more effective in reducing risk of recurrent stones than the traditional low calcium diet.
2. The difference seemed to be due to different effects of the diets on oxalate excretion. Urinary oxalate increased in the low calcium diet; decreased in the normal Ca-low salt-low protein diet. These changes appeared in one week and persisted over 5 years.
3. A low calcium diet does reduce urinary calcium excretion, but may cause an increased absorption of oxalate from the gut. This is because the low levels of calcium in the intestine reduce the amount of unabsorbable calcium-oxalate formed. This leads to less oxalate excretion in the stool, and leaves more to be absorbed and excreted in the urine where it complexes with Ca to form Ca oxalate stones.
4. Why the low animal protein? It lowers endogenous synthesis of oxalate.
5. Why the low salt? Sodium has a direct influence on calcium excretion. Low Na excretion - low Ca excretion.
6. The recommended high intake of water and the increased urine volume helped to reduce the relative oxalate saturation as did the low oxalate diet.

1. Double-blind, randomized, placebo-controlled trial followed 100 patients. None had taken NSAIDs before. All were judged to require long-term NSAID treatment.
2. All had a positive urea breath test for H pylori. All had history of dyspepsia or peptic ulcer and thus were at higher risk.
3. Randomized for one week to: 1) antibiotic eradication therapy + omeprazole (Prilosec; a proton-pump inhibitor) , or 2) omeprazole + placebo antibiotics.
4. All then received diclofenac (Generic) slow release NSAID - 100 mg daily for 6 months.
5. Endoscoped all at 6 months.

1. H pylori was eradicated in 90% of the eradication group.
2. Gastric ulcers developed in 5 of 51 in the eradication group and in 15 of 49 placebo group.
3. Six month probability of ulcer was 12% in the eradication group vs 34% in the placebo group.
4. For complicated ulcers (symptomatic or bleeding) probability was 4% vs 27%.

1. When patients who had a history of dyspepsia or ulcers and were positive for H pylori were started on long-term NSAID treatment, eradication of the infection beforehand reduced risk of developing ulcers.
2. Risk of ulcer is substantially increased during the first few months of NSAID treatment. This excess early risk is especially high in patients with H pylori infection.
3. The role of H pylori in NSAID-naďve patients seems to be different from that of those on long-term treatment. Preexisting H pylori infection contributes to an excess of ulcer development in patients starting NSAIDs. NSAIDs probably cause the majority of ulcers in long-term users irrespective of H pylori. Eradication alone is not sufficient to prevent recurrence of ulcers and ulcer bleeding in long-term users of NSAIDs
4. Even in patients treated with cyclo-oxygenase 2 inhibitors, ulcer risk is significantly higher in those with H pylori infection.
5. Screening and treatment of H pylori in patients starting on long-term NSAID treatment has the potential to reduce ulcer risk, eliminate a gastric pathogen and carcinogen, and reserve the use of expensive anti-ulcer drugs or COX-2 selective NSAIDs for patients at very high risk.
6. “Our study was designed to suit the primary care setting.”

1. A prospective population-based study entered and followed over 5000 individuals aged 55 (Mean age = 67). None had dementia at baseline. Followed to end of 1999. (Average = 6 years.)
2. Determined amount of alcohol consumed at baseline.
3. Compared risk of developing dementia between individuals who regularly consumed alcohol and those who did not.

1. During follow-up 197 individuals developed dementia (146 Alzheimer's, 29 vascular, 22 other).
2. Consumption of one to three drinks per day was significantly associated with a lower risk of any dementia (Hazard ratio = 0.58). And lower risk of vascular dementia (Hazard ratio = 0.29).
3. No relation between type of alcoholic drink and risk.

1. Individuals over age 55 who consumed up to 3 alcoholic drinks per day had a lower risk of developing dementia than abstainers.
2. Possible mechanisms for the protective value of alcohol: reduction in cardiovascular risk factors through inhibition of platelet aggregation, or alterations in lipid profile. The lower risk of vascular dementia is in agreement with this hypothesis.

1. Meta-analysis included 11 randomized trials (over 35 000 patients) comparing DTI with heparin. All received aspirin.
2. DTIs included hirudin, bivalirudin, and 3 other agents. (See text. The only one I have encountered before is hirudin. Hirudin is extracted from the salivary glands of leeches. RTJ)
3. Patients with symptoms of ACS were included if they did not have ST elevation, or were undergoing percutaneous coronary intervention.
4. Patients received up to 7 days treatment and were followed for at least 30 days.

1. At 30 days, compared to heparin, DTIs were associated with a lower risk of death or MI. (4.3% vs 5.1% - absolute risk reduction = 0.8%
2. The benefit was largely due to reduction in MI, with no apparent effect on death.
3. Benefit was also evident in patients undergoing PTCA as well as those not undergoing PTCA.
4. Compared with heparin only hirudin and bivalirudin were beneficial. (No benefit from the other 3 agents.)
5. There was increased major bleeding with hirudin, but actually a reduction in those receiving bivalirudin.
6. No excess intracranial hemorrhage.

1. The NNT to benefit one patient = 125. For every 1000 patients treated, 8 patients benefited.
2. In contrast, the recently introduced antiplatelet agents such as glycoprotein IIb/IIIa are most beneficial only when used in combination with heparin. (Glycoprotein IIb/IIIa inhibitors have only antiplatelet activity and require addition of an anticoagulant such as heparin to be fully effective.)
3. DTIs may be superior to heparin because they have effects against platelets as well as coagulation.
4. Important differences in risk of major bleeding among individual agents occurred. Hirudin was associated with almost a two-fold increased risk; bivalirudin with a 50% reduction in risk.

1. Randomized double-blind multicenter trial followed 282 patients (mean age = 63). All had OA of the knee which had been present for at least 6 months. All had used a prescription strength NSAID or high doses of acetaminophen for at least 30 days.
2. Assessed symptoms by a 100 mm visual analog scales at baseline.
3. Randomized to: 1) rofecoxib 25 mg once daily; 2) celecoxib 200 mg once daily; and 3) acetaminophen 4000 mg (1000 mg 4 times daily) daily for 6 weeks. (A 4th group assessed rofecoxib 12.5 mg. I omitted this data. RTJ)
4. Assessments at 6 weeks included pain on walking, night pain, pain at rest, and morning stiffness as well as global response to therapy among the 3 groups.

1. Mean change on 100 mm visual analogue scales from baseline to 6 weeks:

   	Acetaminophen 4000	Celecoxib 200	Rofecoxib 25
   Walking pain	-30	-36	-42
   Rest pain	-22	-23	-31
   Morning stiffness	-22	-29	-36
   Night pain	-24	-23	-32
   Global pain	-25	-29	-35

2. Discontinued - lack of efficacy : 31%; 19%; 18%
3. Good or excellent response : 46%; 56%; 60%
4. Safety profile was similar among the 3 drugs.

1. In this study, rofecoxib 25 mg/d provided greater therapeutic benefit than maximum doses of acetaminophen in patients with OA of the knee. Differences in response were noted within 6 days and persisted for 6 weeks. (Note that 39% of patients taking acetaminophen reported a good or excellent response. RTJ)
2. Celecoxib also provided greater benefits than acetaminophen.
3. Rofecoxib provided greater benefits than celecoxib.

1. Six trials enrolling over 31 000 patients (mean age = 64) were entered into the analysis of randomized trials.
2. All patients had acute coronary syndromes without persistent ST elevation. Indicators of myocardial ischemia included: ST depression, T wave inversion; creatine kinase MB elevation or evidence of coronary disease based on history and stress testing. Troponin levels were available in a minority.
3. Randomized to: 1) glycoprotein IIb/IIIa inhibitors given intravenously for up to 4 days, or 2) placebo or control therapy.
4. Glycoprotein IIb/IIIa inhibitors included tirofiban, eptifibatide, and abciximab.
5. Primary end point = composite of death and non-fatal MI.

1. Glycoprotein IIb/IIIa inhibitors at 30 days were associated with an absolute reduction of death or development of a new MI (10.8% vs 11.8%). Absolute reduction = 1%. NNT = 100. For every 1000 patients treated 10 avoided the endpoint.
2. An unexpected and significant interaction was seen between sex and allocated treatment. Overall, treatment benefited only men, not women. However women with a positive troponin also benefited.
3. Major bleeding complications were increased (2.4% vs 1.4%). Absolute difference = 1%. (NNT to harm = 100)
4. Risk reduction was evident only in subjects with a positive troponin.
5. Benefits were evident in those receiving heparin as well as those not receiving heparin.

1. Glycoprotein IIb/IIIa inhibitor treatment was associated with an absolute 1% reduction in death or MI at 30 days.
2. Glycoprotein IIb/IIIa inhibitor therapy was associated with increased bleeding, but not any increase in intracranial hemorrhage or stroke.
3. Glycoprotein IIb/IIIa inhibitor treatment was more beneficial in individuals at higher risk, especially in those with elevated troponin levels.