12-1 EFFECTS OF PRAVASTATIN IN 3260 PATIENTS WITH UNSTABLE ANGINA
      Patients who survived myocardial infarction or unstable angina had equally unfavorable prognoses. They benefited from lipid-control therapy with pravastatin started some months after the event.
      Starting statins immediately after an episode of MI or UA may be even more beneficial, and is becoming standard therapy.

12-2 HEALTH OUTCOMES ASSOCIATED WITH CALCIUM ANTAGONISTS COMPARED WITH OTHER FIRST-LINE ANTIHYPERTENSIVE THERAPIES
      "Low-dose diuretics, which have proven efficacy and low cost, should continue to be the standard therapy for hypertension." The use of long-acting calcium antagonists should be limited to patients who do not tolerate or do not respond to diuretics, beta-blockers, or ACE inhibitors.

12-3 SELECTION OF INITIAL ANTIHYPERTENSIVE DRUG THERAPY
      Diuretics and beta-blockers should be used as first-line therapy of uncomplicated hypertension. ACE inhibitors may be especially useful in patients with high risk of heart failure. Caution is needed in recommending calcium antagonists as initial therapy in populations at high risk of coronary heart disease and heart failure.

12-4 RANDOMISED CONTROLLED TRIAL OF DUAL BLOCKADE OF RENIN-ANGIOTENSIN SYSTEM IN PATIENTS WITH HYPERTENSION, MICROALBUMINURIA, AND NON-INSULIN-DEPENDENT DIABETES
      The ACE-inhibitor lisinopril and the angiotensin II blocker candesartan were equally effective in reducing BP and albumin excretion in diabetic patients with hypertension and microalbuminuria.
      When the 2 drugs were combined, BP and albuminuria were further improved.
      Combination treatment was well tolerated.

12-5 SHORT-TERM PROGNOSIS AFTER EMERGENCY DEPARTMENT DIAGNOSIS OF TIA.
      Short-term risks of patients who presented to the ED with a TIA were substantial. Five factors stratified risk and would indicate immediate intervention � age greater than 60, diabetes, symptom duration longer than 10 minutes, weakness, and speech impairment

12-6 DOES THIS PATIENT HAVE STREP THROAT?
      No single element of the history or physical examination is powerful enough to confirm the probability of strep throat. Instead, physicians should consider a combination of findings including tonsillar exudate, tender or enlarged anterior cervical nodes, absence of cough, and a history of fever.
      This clinical prediction rule can be useful and can help physicians make more informed use of rapid antigen tests and throat cultures.

12-7 BAYSEAN STATISTICAL METHODS.
      PRE-TEST PROBABILITY; SENSITIVITY, SPECIFICITY, POSITIVE LIKELIHOOD RATIO, NEGATIVE LIKELIHOOD RATIO, POST-TEST PROBABILITY.

12-8 A PROSPECTIVE, OBSERVATIONAL STUDY OF POSTMENOPAUSAL HORMONE THERAPY AND PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE.
      "In this large, observational, prospective study, the risk of major coronary events appeared to be substantially decreased among current users of hormone therapy."
      Among women taking oral conjugated estrogen (eg, Premarin) the risk reduction was similar in those taking 0.3 mg/d and 0.625 mg /d. (RR = 0.54 and 0.58 compared with never-users.)
      Primary care clinicians might be more willing to begin prescribing Premarin at the 0.3 mg dose. It would be reasonable to consider that breast and ovarian cancer may be lower in women taking this dose.

12-9 DIURNAL VARIATION IN FASTING PLASMA GLUCOSE: Implications for Diagnosis of Diabetes in Patients Examined in the Afternoon
      Fasting blood glucose concentrations are higher in the early AM than in the PM. The early AM increase in glucose and insulin requirements have been attributed to the "dawn phenomenon". Nocturnal elevations of growth hormone and early morning increases in cortisol secretion have been cited as causes of a higher blood glucose in the early AM. They also report higher serum insulin and serum C peptide levels in the morning in non-diabetic subjects.
      If current diagnostic criteria are applied to patients tested in the afternoon, many cases of undiagnosed diabetes will be missed. (Ie, FPG may be above 126 mg/dL in the early AM, and below 126 in the PM.) "Regardless of the time of day that patients are tested, physicians need to confirm the diagnosis by testing on a different day."

12-10 MANAGING DEPRESSION IN MEDICAL OUTPATIENTS
      Two simple questions can be used for case-finding:

1. During the past month, have you often been bothered by feeling down, depressed, or hopeless?
2. During the past month have you often been bothered by having little interest or pleasure in doing things?

12-11 LONGITUDINAL STUDY OF MODERATE WEIGHT CHANGE AND SLEEP-DISORDERED BREATHING
      Even modest weight loss is likely to be effective in managing SDB and reducing new occurrence of SDB.

12-12 PEGINTERFERON ALFA-2A IN PATIENTS WITH CHRONIC HEPATITIS C
      In patients with chronic HC, a regimen of peginterferon-alfa (interferon combined with polyethylene glycol) given once weekly was more effective than interferon alfa-2a given 3 times weekly.
      This compound has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferon. This maintains an antiviral effect on hepatitis C virus (HCV) and makes possible a once-weekly administration.

12-13 EFFICACY OF RIVASTIGMINE IN DEMENTIA WITH LEWY BODIES.
      Rivastigmine produced clinically significant behavioral effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.

12-14 CHOLINESTERASE INHIBITORS; EXPANDING APPLICATIONS
      The behavioral improvement achieved with rivastigmine in the study is clinically relevant. Rivastigmine has pharmacological properties that distinguish it from other cholinesterase inhibitors, so the findings may not apply to other drugs in the class.

12-15 EFFICACY AND SAFETY OF GALANTAMINE IN PATIENTS WITH MILD TO MODERATED ALZHEIMER'S DISEASE
      Compared with placebo, galantamine was effective and well tolerated in Alzheimer's disease.

12-16 EFFECT OF SIBUTRAMINE ON WEIGHT MAINTENANCE AFTER WEIGHT LOSS
      An individualized management program with sibutramine and diet achieved weight loss in 77% of obese patients, and sustained the weight loss in most patients continuing therapy with sibutramine for 2 years.

12-17 UNCOMPLICATED ACUTE BRONCHITIS
      Decreased rates of antibiotic treatment are not associated with increased utilization, return visits, or dissatisfaction with care. "The evidence is indisputable that not prescribing antibiotics to patients with uncomplicated bronchitis is safe, and does not result in excess morbidity."
      Ruling out pneumonia is the primary objective in evaluating otherwise healthy adults with acute cough illness. (Pneumonia is unlikely if heart rate is < 100, respiratory rate is < 24, and temperature < 380C [101.50F]

RECOMMENDED READING

12-20 NARRATIVE AND THE PRACTICE OF MEDICINE
12-21 ERARITJARKTJAKA
12-22 PUTTING WOMEN IN CONTROL
12-23 FROM RITES OF PASSAGE TO LAST RIGHTS
12-24 FINALE FOR 2000

REFERENCE ARTICLES

12-7 BAYSEAN STATISTICAL METHODS.
12-10 MANAGING DEPRESSION IN OUTPATIENTS
12-17 UNCOMPLICATED ACUTE BRONCHITIS
12-18 THE DIAGNOSIS AND TREATMENT OF COUGH
12-19 AGE RELATED MACULAR DEGENERATION

1. Randomized trial followed over 3000 patients with unstable angina, and over 5000 patients with acute MI. All events had occurred 3 to 36 months before randomization. Mean LDL-cholesterol = 150 mg/dL.
2. The study did not have strict criteria for diagnosis of UA, but relied on hospital discharge diagnosis.
3. Randomly assigned to: 1) 40 mg of pravastatin/d, or 2) placebo.
4. Follow-up = mean of 6 years for a range of cardiovascular events.

1. Survival of patients with UA and MI was similar in the placebo groups.
2. MI group: Relative risk reduction for mortality in the MI-pravastatin group vs placebo was 21%. Pravastatin significantly reduced the rates of all prespecified coronary end-points.
3. UA group: Relative risk reduction for mortality in the UA-pravastatin group vs placebo was 26%. Pravastatin significantly reduced coronary heart disease mortality, total mortality, myocardial infarction, need for coronary revascularization, and hospital admissions.

1. Patients who survive UA as well as those who survive MI have a similar adverse long-term prognosis.
         Over 6 years, there was a high rate of subsequent episodes of UA (25%) and MI (10%).
2. Over 6 years, pravastatin was associated with a similar improvement in prognosis in both groups.
3. In absolute terms, pravastatin therapy of 1000 patients with UA could prevent 33 deaths, 24 non-fatal MIs, and 26 coronary revascularizations.
4. The study did not include patients treated with statins immediately after the episode of MI or UA. Observational studies suggest that patients with UA or MI who start statin drugs immediately (within a few hours) after the event have a better prognosis. Starting pravastatin some time after the occurrence of UA (3 to 36 months) also improved prognosis. Starting lipid-control therapy in the hospital may lead to better adherence to the therapy.
5. There are theoretical reasons, other than lipid control, why statins may benefit: improved endothelial function, suppressed inflammatory cell activity, and decreased thrombus formation.

1. Meta-analysis of 9 trials (27 000 patients) in which hypertensive patients were randomized to calcium antagonists (intermediate-acting and long-acting) or other anti-hypertensive drugs.
2. Follow-up = at least 2 years.

1. Calcium antagonists achieved control of both systolic and diastolic BP similar to other drugs.
2. Compared with patients assigned diuretics, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. Those assigned to calcium antagonists had a significantly higher risk of acute myocardial infarction (odds ratio = 1.3), congestive heart failure (OR = 1.3), and major cardiovascular events (OR = 1.1).
3. No significant differences in risk of stroke and all-cause mortality.

1. Combined results of 9 trials showed that calcium antagonists were associated with a significantly higher risk of major complications of hypertension.
2. This was despite similar control of BP. Mechanisms not involving BP control are important in determining, at least in part, therapeutic effects.
3. Concentration on a single outcome in a hypertension trial (eg, BP control) may lead to an incomplete definition of the drug's therapeutic profile.
4. It is not evident whether calcium antagonists have a harmful effect on coronary heart disease and heart failure, or whether other drugs have special benefits. Another trial showed that the calcium antagonist nitrendipine (compared with placebo) had a lower risk of stroke. (BP control may have an especially important role in preventing stroke.)
5. Therapeutic decisions should be based on a drug's overall risks and benefits, the patient's risk profile, and the patient's preference. If, for an individual patient, prevention of stroke is the main or only concern, calcium antagonists may be equivalent of other drugs tested (But, not superior. RTJ) . However, for prevention of heart failure or combined major cardiovascular events, the findings of this study suggest that calcium antagonists are inferior to other drugs as first-line therapy.
6. The surrogate end-point, BP lowering, is not a consistent and valid marker of all the therapeutic benefits of anti-hypertensive agents.
7. The benefits of calcium antagonists as add-on therapy has not been assessed. "For a combination of antihypertensive therapies, reliance on the classes known to be superior � low-dose diuretics, beta-blockers, and ACE inhibitors � seems prudent."
8. "Low-dose diuretics, which have proven efficacy and low cost, should continue to be the standard therapy for hypertension. The use of long-acting calcium antagonists and alpha-blockers should be limited to patients who do not tolerate or do not respond to diuretics, beta-blockers, or ACE inhibitors."

1. Multicountry, randomized, parallel group, double-blind study followed almost 200 patients with type 2 diabetes and hypertension. (Mean age = 60; mean BP 163/96)
2. All had diastolic BP 90 to 110 mm Hg. and increased albumin excretion.
3. First randomization: Candesartan alone 16 mg/d, or 2) lisinopril alone 20 mg/d for 12 weeks.
4. Second randomization: Candesartan alone, or 2) lisinopril alone, or 3) both drugs combined. (Unless the patient had achieved a diastolic BP < 80 at 12 weeks.)

1. First randomization

   	Candesartan	Lisinopril
   Mean reduction in diastolic BP (mm Hg)	-9.5	-9.7
   Mean reduction in systolic BP (mm Hg)	-20	-20
   Reduction in urinary albumin:creatinine ratio	-30%	-46%

2. Second randomization.

   	Effects of candesartan + lisinopril
   Mean reduction in diastolic BP (mm Hg)	- 16.3
   Mean reduction in systolic BP (mm Hg)	- 30
   Reduction in urinary albumin:creatinine ratio	- 50%

3. Lisinopril alone and candesartan alone both reduced mean BP to 145/85. Combination therapy reduced BP to 135/80
4. Drugs were generally well tolerated. Cough in the lisinopril group occurred in less than 10% (3 patients withdrew) . 14 patients withdrew because of dizziness, weakness,

1. Both drugs reduced BP and urinary albumin excretion to an equal extent. The combination was more effective than either drug alone.
2. "We can confirm that dual blockade of the renin-angiotensin system, both at the level of ACE and at the level of the angiotensin II receptor, is associated with more effective reduction on BP than observed with a single agent." This observation extends to patients with diabetes.
3. The combination also had a beneficial effect on reducing albumin excretion.
4. The drugs were associated with an excellent safety profile.
5. Treatment of diabetic patients with hypertension should be aggressive, especially in the presence of renal disease. Dual blockade is particularly effective.

1. Multicenter cohort study followed over 1700 patients (mean age = 72) who had been identified by ED physicians as having had a TIA.
2. Determined the short-term risk of stroke and other adverse events.
3. Follow-up = 90 days.

1. Overall, stroke and other adverse events occurred in 25% of patients in the 90 day follow-up. These included cardiovascular events (2.6%); death (2.6%); and recurrent TIA (13%)
2. During follow-up, 10% returned to the ED with a stroke. About half of these strokes occurred within the first 2 days.
3. Five factors were independently associated with stroke:

   	Odds Ratio
   Age greater than 60.	1.8
   Diabetes	2.0
   Symptom duration longer than 10 minutes	2.3
   Weakness	1.9
   Speech impairment	1.5

4. Stroke-free survival varied from about 96% in those with 1 risk factor to 65% when all 5 were present.

1. TIAs carry a substantial short-term risk of stroke, hospitalization for cardiovascular events, and death. Half of the strokes occurred within 2 days of the TIA.
2. Diagnosis of TIA is problematic. Even among neurologists, there is a low inter-observer agreement.
3. Timing of presentation may be important. Since more than half the strokes occurred within 2 days, if a patient presents for evaluation after 3 days, the period of highest risk has passed.
4. Stratification of risk allows targeting expensive interventions (eg, hospitalization and urgent carotid ultrasound) to those at greatest risk.

1. Considered 9 large blinded, prospective studies each with over 300 patients presenting with sore throat. All reported history and physical examination data.
2. All used throat culture as the reference standard for diagnosis.

1. Clinical presentation.
   A. Symptoms:
   Classically, onset of strep sore throat is sudden. It is typically described as severe. Fever is moderate. Systemic symptoms are usually present.
   B. Signs:
   

   Breath: characteristically foul.
   Skin: Rash (scarlet fever) may be present. Fine erythematous papules begin on the trunk and spread to the extremities sparing the palms and soles. Rash may be accentuated in antecubital skin creases (Pastia sign). Rash blanches on pressure, and has a sandpapery feel. "Strawberry tongue" and circumoral pallor may be present. Desquamation of the skin may occur after a week or so.
   Pharynx and uvula: may be erythematous and edematous (beefy and bright red with the color ending abruptly at the soft palate). Petechiae may be present on the soft palate. Lymphoid tissue in posterior pharynx may be hypertrophied. Posterior pharynx and tonsils are covered with a gray-white membrane or exudate. [Pharyngeal vesicles and ulcers are associated with viral infections. Their presence reduces the likelihood of beta-hemolytic strep ( group A) being present.]
   Lymph nodes: anterior cervical nodes are often enlarged and tender, especially at the angle of the jaw.
   

   ( I enjoyed this review of the classical evolution of hemolytic strep infections and scarlet fever. The full blown picture must be rare now in the US. RTJ )
2. Precision: In this context, the authors mean degree of concurrence between observers assessing various symptoms and signs (present or absent). Studies have reported the concurrence is high.
3. Diagnostic accuracy of symptoms and signs:

   A. Diagnostic accuracy is measured by considering the pre-test probability of the presence of strep throat, sensitivity of diagnostic tests, specificity of diagnostic tests, the positive likelihood ratio, and the negative likelihood ratio, to arrive at a post-test probability that strep is the cause of the sore throat. (See the following article for clarification. RTJ)
   B. The diagnostic points with the highest likelihood of ruling in strep throat were: presence of tonsillar exudate (positive likelihood ratio = 3.4); pharyngeal exudate (positive likelihood ratio = 2.1); and history of exposure to strep throat within the preceding 2 weeks (positive likelihood ratio = 1.9)
   C. The diagnostic points with the highest likelihood ration of ruling out strep throat were: absence of tender anterior cervical nodes (negative likelihood ratio = 0.60); absence of tonsillar enlargement (negative likelihood ratio = 0.63); or absence of tonsillar exudate (negative likelihood ratio = 0.74)
   

4. No individual element of history or physical examination is accurate enough by itself to rule in or rule out strep throat.
5. Other validated clinical prediction rules have been described for adult populations. One of the best is a simple prediction rule developed by Centor. It considers 4 signs and symptoms:
   

   Tonsillar exudate
   Presence of swollen, tender cervical nodes
   Absence of cough
   History of fever

   Presence of 3 or 4 of these increases the likelihood that strep is the cause. Those with none of the 4 are very unlikely to have strep as the cause.
6. An algorithm on page 2917 presents a method of evaluating adults with sore throat. It assesses the likelihood of risk (low, medium, and high).

1. Previous studies of the differential diagnosis of sore throat report that viral infections are by far the most common cause.
2. The investigators used Baysean statistical methods to arrive at the probability that strep throat is present: This combines 1) pre-test probability, 2) calculation of sensitivity and specificity of the tests, 3) likelihood ratios of tests, to 4) arrive at a post-test probability that strep is the cause. (Note that a "test" may be an item in the history or examination as well as a laboratory test such as culture.)

1. The Nurses' Health Study followed over 70 000 women from 1976 to 1996.
2. Identified over 1250 major coronary events (non-fatal myocardial infarction or fatal coronary disease), and over 750 strokes.
3. Obtained data on postmenopausal HRT use.
4. Calculated relative risks between users and non-users.

1. When all cardiovascular risk factors were considered, the risk of major coronary events was lower among current users of HRT, including short-term users, compared with never-users. RR = 0.61. The reduction was similar between women taking oral conjugated estrogen alone, and those taking estrogen plus progestin.
2. Among women taking oral conjugated estrogen (eg, Premarin) the risk reduction was similar between those taking 0.3 mg/d and 0.625 mg /d. (RR = 0.54 and 0.58 compared with never-users.)
3. The risk of stroke was significantly increased among those taking 0.625 mg (RR = 1.35), and among those taking estrogen + progestin (RR = 1.45).

1. "In this large, observational, prospective study, the risk of major coronary events appeared to be substantially decreased among current users of hormone therapy."
2. Daily oral conjugated estrogen (both 0.625 mg and 0.3 mg) was associated with a reduced risk of coronary heart disease
3. Estrogen alone and estrogen combined with progestin were also associated with a reduced risk of coronary heart disease.
4. Among those taking conjugated estrogen 0.625 mg/d or more, and among those taking estrogen + progestin there was an increased risk for stroke.
5. A recent study of hormone therapy for secondary prevention1 reported an increased risk during the first year of therapy, followed by a decreased risk later. Another Nurses' Health Study (secondary prevention) also reported a higher rate of recurrent cardiovascular events with short term use.
6. This study of primary prevention observed a strong dose-response relation between estrogen and increased risk of stroke. Conjugated estrogen 0.3 mg/d may be safer than 0.625 mg/d. (And 0.3 mg/d is also strongly associated with a reduced risk of heart disease.)
7. The risk of adverse effects during the first year of primary prevention may be less than that during the first year for secondary prevention.
8. This study also found few substantial differences in lifestyle factors between women who took hormones and those who did not. All analyses were carefully adjusted for potential confounders including cigarette smoking and body mass index. "Confounding by lifestyle or health practice probably does not explain our observations." (Ie, evidence against the "healthy user" confounding effect.)

1. During the past month, have you often been bothered by feeling down, depressed, or hopeless?
2. During the past month have you often been bothered by having little interest or pleasure in doing things?

1. Population-based, prospective cohort study randomly selected about 700 employed Wisconsin residents (mean age = 46; mean BMI = 30). All were evaluated twice at a 4-year interval for SDB. (High-quality polysomnography was used.)
2. Defined moderate-to severe SDB as over 15 events per hour of sleep.
3. Outcome measures included change in the apnea-hypopnea index (AHI; apnea events + hypopnea events per hour of sleep) and relationship of change in SDB with respect to change in weight.

1. Relative to a stable weight, a 10% weight gain predicted approximately 32% increase in AHI.
2. A 10% increase in weight predicted a 6-fold increase in the odds of developing moderate-to-severe SDB. A 20% increase in weight predicted an estimated increase in AHI of 70%.
3. A 10% weight loss predicted a 26% decrease in AHI. A 20% weight loss predicted a 48% decrease.

1. In persons with SBD there was a relation between weight gain and increase in SBD severity.
2. Weight loss was associated with a reduced severity of SDB and the likelihood of developing SDB.
3. The changes were independent of many other potential confounding factors.

1. Selected over 500 patients with chronic HC infection. All had a positive test for anti-HCV antibody, HCV RNA levels over 2000 copies per mL on polymerase chain analysis, serum alanine aminotransferase above upper normal on 2 occasions in the past 6 months, and liver biopsy consistent with chronic HC.
2. Randomized to: 1) peginterferon-alfa 180 ug subcutaneously once a week for 48 weeks, or 2) interferon subcutaneously 6 million units three times weekly for 12 weeks, then 3 million units three times a week for 36 weeks.
3. Assessed at 72 weeks for a sustained virological response (an undetectable level of hepatitis C virus.)

1. At 72 weeks	Peginterferon	Interferon
   Completed follow-up	76%	58%
   Sustained virological response	39%	19%
   Sustained normal ALT	45%	25%

2. Frequency and severity of adverse events were typical of those associated with interferon and were similar between groups. Depression the most serious. Fewer than 1% in each group discontinued because of laboratory abnormalities.
3. In general, peginterferon was well tolerated. In no patient was therapy discontinued because of neutropenia. Anemia and thrombocytopenia were rare.

1. Peginterferon was associated with a significantly higher rate of sustained virologic response as compared with interferon, possibly due to the sustained anti-viral effects associated with the enhanced pharmacokinetics of the molecule.
2. The response to peginterferon was similar to that previously reported for combination therapy with interferon and ribavirin.
3. Peginterferon was not associated with long-term adverse effects on the liver.
4. Sustained virological response from peginterferon was seen in patients in whom treatment has historically been unsuccessful � some patients with HCV genotype 1, and some with bridging fibrosis or cirrhosis.

1. Randomized, placebo-controlled, double-blind, multicenter trial entered 120 patients with clinically diagnosed LBD (mild to moderate; mini-mental state examination score of 10 and above). Excluded those with severe extra-pyramidal symptoms.
2. Randomized to: 1) rivastigmine up to 12 mg daily, or 2) placebo for 20 weeks.
3. Assessed cognition and behavioral status. Follow-up = 20 weeks.

1. Only about 2/3 of patients assigned to rivastigmine completed the trial.
2. Rivastigmine patients were significantly less apathetic and anxious. Fewer had delusions and hallucinations.
3. Neuropsychological and cognitive tests showed a significantly faster and better response, particularly with the attentional component.
4. Adverse effects of cholinesterase inhibition (nausea, vomiting, anorexia) were more common in the rivastigmine group. More in the treatment group withdrew.
5. Safety and tolerability were judged acceptable. Parkinsonian symptoms did not worsen.
6. Effects were reversed rapidly on withdrawal of the drug.

1. Rivastigmine produced clinically relevant behavioral benefits in LBD. Patients were less apathetic, and less anxious, and had fewer delusions and hallucinations. In some patients improvement was substantial. 1
   
2. Improvements in attention, responsiveness, and daytime somnolence were substantial. Hallucinations and psychotic features resolved almost completely in over half of the patients receiving rivastigmine.
3. Caregivers reported patients were more alert.
4. "Our study results suggest that cholinesterase inhibitors could be a more rational choice of treatment for Lewy-body dementia patients than neuroleptics, both on an efficacy and safety basis."

1. Multicenter trial recruited over 600 obese individuals (BMI � 30 to 45). Most had repeatedly tried to lose weight in the past.
2. All entered into a 6-month period of weight loss with sibutramine (10 mg daily) and a diet calculated to be 600 kcal/d deficient based on measured resting metabolic rates.
3. The trial then entered those who had lost more than 5% of their weight during the 6 months. (N = 467).
4. Randomized to: 1) to 10 mg/d sibutramine, or 2) placebo for an additional 18 months. (Dose increased to 20 mg if weight regain occurred.)

1. Almost 50% of subjects in each group dropped out. (Another discouragement regarding long-term weight-loss therapy. RTJ)
2. Of those completing the trial: 43% of those in the sibutramine group maintained at least 80% of their original weight loss vs 16% of those in the placebo group. (Odds ratio = 4.6)
3. In the sibutramine group, substantial decreases occurred in triglyceride levels, VLDL cholesterol, insulin, and uric acid. HDL-cholesterol rose.
4. 3% of patients in the treatment group were withdrawn because of increase in BP. Mean pulse rate increased slightly.
5. Withdrawals due to adverse events: sibutramine � 14%; placebo � 5%.

1. "Almost all patients who persist with the management scheme . . . can achieve at least a 5% weight loss with sibutramine, and over half can lose more than 10% within 6 months."
2. The importance of sibutramine in maintaining a lower weight was shown by the immediate and steady increase in body weight once sibutramine was stopped.
3. Patients with hypertension were not excluded from the trial. In those taking sibutramine who achieved weight loss, BP remained unchanged.

1. Respiratory viruses appear to cause most cases of uncomplicated bronchitis.
2. Pertussis infection is present in up to 10%-20% of adults with cough illness lasting more than 2 to 3 weeks.
3. Transient bronchial hyper-responsiveness appears to be the predominant mechanism for the bothersome cough.
4. Ruling out pneumonia is the primary objective in evaluating otherwise healthy adults with acute cough illness. (Pneumonia is unlikely if heart rate is < 100, respiratory rate is < 24, and temperature < 380C [101.50F] )
5. Randomized, placebo-controlled trials do not support routine antibiotic treatment of uncomplicated bronchitis.
6. Inhaled albuterol (Proventil; Ventolin; generic) decreases the duration of the cough in adults with uncomplicated acute bronchitis. However, "Until more studies are conducted, reserving beta-agonist treatment for troublesome cough and evidence of bronchial hyper-responsiveness seems prudent."
7. Antibiotic treatment can be reduced by using a combination of patient and physician education. Decreased rates of antibiotic treatment are not associated with increased utilization, return visits, or dissatisfaction with care. "The evidence is indisputable that not prescribing antibiotics to patients with uncomplicated bronchitis is safe, and does not result in excess morbidity."
8. On an empirical basis, low-cost, low-risk actions such as elimination of environmental cough triggers (dust, dander) and using vaporized air treatments, particularly in environments with low humidity, are reasonable.