12-1 LEFT VENTRICULAR CHANGES IN ISOLATED OFFICE HYPERTENSION
      Patients with isolated office ("white coat") hypertension had LV morpho-functional characteristics which differed significantly from normotensive patients and were qualitatively similar to subjects with sustained hypertension.
      Isolated office hypertension should not be considered a benign condition.

12-2 PERSISTENT HUMAN PAPILLOMAVIRUS INFECTION AS A PREDICTOR OF CERVICAL INTRAEPITHELIAL NEOPLASIA
      The study adds to the body of evidence strongly implicating persistent HPV infections, particularly with oncogenic strains, as a cause of SIL.
      "A strong relationship exists between persistent HPV infection and SIL incidence, especially for HPV types 16 and 18."
      The study adds to the body of evidence strongly implicating persistent HPV infections, particularly with oncogenic strains, as a cause of SIL.
      The investigators support the application of repeated type-specific HPV DNA testing in screening for SIL (and by implication prevention of cervical cancer). Vaccines against oncogenic strains (especially type 16 and 18) are a potential for prevention.
      Practical point: Watch for developments. Is this the next major step in cancer prevention?

12-3 WHAT VITAMINS SHOULD I BE TAKING, DOCTOR?
      Standard advice in the past recommended that vitamin supplements were not needed for persons with an adequate diet. A sea change has occurred. Multivitamin supplements are recommended.
      The commentators cite evidence for benefits of folic acid, vitamin B6, vitamin B12, Vitamin D, and vitamin E.
      Practical point: Many primary care clinicians now recommend routine use of supplements.

12-4 SUPERIORITY OF AN INTRANASAL CORTICOSTEROID COMPARED WITH AN ORAL ANTIHISTAMINE IN THE AS-NEEDED TREATMENT OF ALLERGIC RHINITIS
      As-needed intranasal corticosteroid spray reduced allergic inflammation. It was more effective than as-needed H1 blockers in the treatment of seasonal allergic rhinitis.
      Practical point: Most patients with troublesome seasonal allergic rhinitis probably take continuing anti-histamine or intranasal steroid during the season. Choice would be personal according to trial and error comparison between the two.

12-5 COMPARISON OF CEFUROXIME WITH AND WITHOUT FLUTICASONE FOR THE TREATMENT OF RHINOSINUSITIS
      The addition of fluticasone to xylometazoline and cefuroxime improved clinical success rates and accelerated recovery of patients with a history of chronic recurrent sinusitis who presented with acute sinusitis.
      Practical point: Added fluticasone may be a possible benefit in a few patients.

12-6 EFFECT OF OMALIZUMAB ON SYMPTOMS OF SEASONAL ALLERGIC RHINITIS
      Omalizumab. an IgE blocking antibody, provided significant relief from allergic rhinitis. And reduced serum free IgE levels.
      Practical point: An entirely new development . Watch for additional reports.

12-7 TOTAL CHOLESTEROL/HDL-CHOLESTEROL RATIO VS LDL-CHOLESTEROL/HDL-CHOLESTEROL RATIO AS INDICES OF ISCHEMIC HEART RISK IN MEN
      In addition to the well-established conventional risk factors, the Total-c/HDL-c ratio may represent an important cumulative index of the presence of an atherogenic dyslipidemic profile associated with insulin resistance.
      It was a simple index of IHD risk in men in this study.
      Calculation of the LDL-c/HDL-c ratio may underestimate IHD risk in some patients since it ignores any contribution of the cholesterol in triglycerides.
      Practical point: This may be a valid alternative to risk assessment. Calculation or determination of LDL-c may be eliminated, making assessment simpler.

12-8 FREQUENCY OF EATING AND CONCENTRATIONS OF SERUM CHOLESTEROL
      In a general population, concentrations of total cholesterol and LDL cholesterol were decreased consistently by increased frequency of eating. "We need to consider not just what we eat, but how often we eat."
      Practical point: Nibbling may be healthy; gorging unhealthy. It makes sense not to stress your metabolic machinery.

12-9 INDIGESTION: WHEN IS IT FUNCTIONAL?
      Patients often complain of "indigestion". This may be defined differently by individual patients. To some it is heartburn and acid regurgitation; others may describe abdominal rumblings and belching; others, non-painful discomfort in the upper abdomen (fullness, bloating, early satiety).
      "Dyspepsia" is best restricted to mean pain or discomfort centered in the upper abdomen.
      There are many causes of dyspepsia. But, at least two thirds of patients have no structural or biochemical explanation for their symptoms.
      It has been suggested that dyspepsia can be subdivided based on clusters of symptoms. But, subgroups have not proved to be of value in identifying the underlying cause. Symptoms overlap considerably.
      Practical point: Perhaps asking patients with troublesome dyspepsia to read this article may help them.

12-10 CYCLO-OXYGENASE INHIBITORS AND THE ANTIPLATELET EFFECTS OF ASPIRIN
      Ibuprofen (Motrin; Advil) competitively inhibited the prophylactic (anti-thrombotic) effects of aspirin.
      Acetaminophen, COX-2 inhibitors, and diclofenac did not have this antagonistic effect.
      Practical point: Patients taking low-dose aspirin for primary or secondary prevention of CVD should avoid ibuprofen.

12-11 UNTANGLING VASCULAR DEMENTIA
      Questions remain about the mechanism of the interaction between cerebrovascular disease and Alzheimer's in an individual patient. Alzheimer's disease cannot be ruled out by clinical investigation. A diagnosis of vascular dementia does not rule out Alzheimer's. The part that cerebrovascular disease may play in producing symptoms of dementia is particularly difficult to understand when it is accompanied by histological features of Alzheimer's disease.
      "It is not surprising that accurate clinical diagnosis of Alzheimer's disease seems to be easier than vascular and mixed dementia. Meanwhile, it is worth noting that although 'pure' vascular dementia exists, vascular disease may be an important and potentially treatable contributor to Alzheimer's disease."
      Practical point: We await untangling the pathogenesis of Alzheimer's, and have great hope for development of specific preventive measures for the disease. In the meantime, we can do a great deal to protect the vascular system of the brain. The same prophylactic measures apply to the brain as to the coronary circulation.

12-12 ENGAGING PATIENTS IN MEDICAL DECISION MAKING
      Three questions dominate the debate about the role of the patient in making treatment decisions:

Can patients take a leading role in making decisions?
Do they want to?
What if doctors and public health professionals don't like their choices?

2-13 IDENTIFICATION AND FRACTURE OUTCOMES OF UNDIAGNOSED LOW BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN.
      About half of a large screened population of postmenopausal women had previously undetected low BMD. Determination of low BMD at peripheral sites (distal radius, heel, finger), as well as at hip and spine, was highly predictive of fracture risk.
      Given the economic and social costs of osteoporotic fractures, strategies to identify and manage osteoporosis in the primary care setting need to be established.
      Practical point: Some adverse conditions are almost inevitable as age progresses. This includes postmenopausal osteoporosis, atherosclerosis, isolated systolic BP (due to loss of arterial elasticity), and weight gain. Should we wait for confirmatory tests to determine their presence? If so, opportunities for prevention are lost. Or should we assume that preventive measures for these almost universal risks should be started at the earliest reasonable time. Much expense and better prevention would result from empirical and universal primary interventions.

12-14 HELP ARRIVES WITH THE DAWN?
      A recent investigation compared 30 minutes of bright light at 0600 hours against placebo and against dawn stimulation. Dawn stimulation consisted of exposure to white light of gradually increasing brightness which started at 0430 h while the patient was asleep. Brightness peaked at 250 lux in 90 minutes. Placebo consisted of dim red light. Dawn stimulation was associated with a significantly higher rate of remission. and a greater reduction in symptoms than either bright light or placebo. Part of the benefit may have been due to the method of delivery which helped patients adhere to a waking time of 0600 h, and thus a regular sleep schedule.
      Practical point: Interesting. watch for further reports.

12-15 SIMILAR EFFECTIVENESS OF PAROXETINE, FLUOXETINE, AND SERTRALINE IN PRIMARY CARE.
      Three SSRIs, Paroxetine (Paxil); Fluoxetine (Prozac); and Sertraline (Zoloft), were similar in effectiveness and adverse effects for depressive symptoms and domains of health-related quality of life over 9 months.
      Practical point: Individual trial and error may come up with the most effective and best tolerated.

12-16 BLOOD PRESSURE REDUCTION AND CARDIOVASCULAR RISK IN HOPE STUDY
      The investigatory concluded that ramipril confers substantial benefits in addition to those of other BP-lowering drugs. Benefit was greater than expected from the modest lowering of BP which occurred during the trial. But, is there really any benefit in reducing cardiovascular morbidity conferred by a drug in addition to its BP-lowering effect? Controversy remains.
      Practical point: The first goal in treatment of hypertension by primary care clinicians should be lowering the BP to recommended levels -- combined by treatment of all risk factors in addition to the BP. I believe that when this is accomplished, any particular drug used will have little additional benefit. RTJ

12-17 PHYSICIAN CHARTER OF PROFESSIONALISM
      A campaign to shore up physicians' special place in society has resulted in a Charter of Professionalism. The charter reminds physicians that satisfying in full the expectations of a medical professional is still within their control. Physicians may lead a full and satisfying life of medicine.
      The Physician Charter of Professionalism contains three fundamental principles:
      Primacy of patient welfare
           Patient autonomy
           Social justice

12-18 GOOD LORD, DELIVER US
      "From the inability to let well enough alone; from too much zeal for the new and contempt for what is old; for putting knowledge above wisdom, science before art, and cleverness above common sense; from treating patients as cases; and from making the cure of the disease more grievous than the endurance of the same; Good Lord, deliver us"
      Practical point: Amen

1. Enrolled:

   1)	Patients with IO hypertension (clinic BP > 140 and/or > 90 and daytime BP < 130/80);
   2)	Patients with sustained hypertension (clinic BP > 140 and/or > 90; and
   3)	Patients who were normotensive (clinic BP < 135 and/or < 85 and mean daytime BP < 130/80).

2. Forty two individuals were included in each group; mean age = 42. They were matched by age, sex, and body mass index and by mean clinic BP (IO and sustained patients) and mean daytime BP (IO and normotensives). None had been treated for hypertension.
3. Assessed left ventricular morphologic features and function with M-mode echocardiography.

1. Mean BPs:

   	Normotensive	IO hypertension	Sustained hypertension
   Clinic BP	124/73	154/93	153/93
   Daytime BP	125/74	126/74	151/97

2. Indices of systolic function were normal in all 3 groups.
3. Compared with normotensive subjects, IO hypertensives had significantly thicker LV walls, increased LV mass, reduced diastolic function, and increased prevalence of diastolic dysfunction.

1. IO may place an increased hemodynamic load on the heart. Using a cut-point of 140/90 other studies have reported that IO hypertensive patients have cardiovascular changes similar to those of patients with sustained hypertension, and significantly different from those in normotensive patients.
2. Another study also reported intima-media thickness in the carotid artery increased in like manner.

1. Longitudinal study of the natural history of HPV infections and cervical neoplasia entered over 1600 women (1993-97; mean age - 33). At baseline, none had cytological lesions. HPV status was available at the first 2 visits. (Study conducted in Sao Paulo, Brazil, an area of high endemicity.)
2. Obtained cervical specimens for Papanicolaou cytology every 4 months in the first year, and twice yearly thereafter for up to 5 years.
3. HPV status was determined by polymerase chain reaction at the first 2 visits (including the enrollment visit). Over 25 types of HPV can be detected and grouped by oncogenic potential.
   (See p 3108 for a list of 12; 16 and 18 being the most oncogenic.)
4. Main outcome -- incident cervical cancer precursor lesions (squamous intraepithelial lesions [SIL] )

1. Overall, 16% of women were HPV positive.
2. All women (except one) had initiated sexual activity by the time of their first follow-up visit, and therefore had been exposed to HPV through sexual transmission. The majority of women had only 1 to 2 partners in their lifetime.
3. Over 1600 women were free of SIL at enrollment:

   Incidence of SIL was high for those + for any oncogenic HPV at enrollment.
   Higher still for types 16 and 18 at one visit

4. Incidence of SIL:

   HPV negative at both visits 3.5%
   Positive HPV at either visit for any type 15 %
   Positive for 16 or 18 once 8%
   Positive for 16 or 18 at both visit 29%

5. Cumulative detection of SIL among those positive for 16 or 18 at both visits approached 40% over 5 years.
6. Younger women (age 18-24) had the highest rates of infection.
7. Most oncogenic strains detected at 2 visits were of the same strain. The relative risk of high grade SIL among older women with persistent HPV was higher than among the young (29% vs 5%).
8. A small group of women had HPV testing at a third visit. Some eliminated the infection by the third visit. Among these who eliminated the HPV, no persistent SIL was noted regardless of the HPV classification.

1. Persistent HPV infection (positive on two or more occasions) , particularly with known oncogenic strains, was associated with a much greater risk of incident SIL than those with HPV on only one occasion.
2. Persistent infection with "non-oncogenic" strains was also associated with increased risk of developing SIL.
3. No incidence of high grade SIL was observed among women with non-persistent (implying different types) yet with repeatedly positive HPV types.
4. "The increase in incidence of SIL in women harboring long-term oncogenic HPV infections adds to the evidence for HPV persistence as a key determinant of lesion development."
5. For women who eventually cleared their infection, no persistent SIL lesions were observed.
6. The investigators support the application of repeated type-specific HPV DNA testing in screening for SIL (and by implication prevention of cervical cancer). Vaccines against oncogenic strains (especially type 16 and 18) are a potential for prevention.

1. Randomized, open-label, parallel group study entered 88 persons with seasonal allergic rhinitis. All had a positive skin test for ragweed.
2. Randomized to: 1) as needed fluticasone nasal spray -- two 50 ug sprays per nostril (total of 4 sprays) or, 2) as needed loratidine 10 mg daily.
3. Assessed symptom and quality of life scores.

1. The median total symptom score in the fluticasone group was 4.0 vs 7.0 in the loratadine group.
2. After treatment, the number of eosinophiles was significantly smaller in the fluticasone group.

1. In this study, it was assumed that patients would elect to take the medications after the immediate reaction appeared, and before eosinophilic infiltration and changes in reactivity occurred. Thus, as the season progressed, in the fluticasone group, eosinophile infiltration and an increase in reactivity to allergen would not occur.
2. In contrast, as-needed H1 blockers does not prevent eosinophile infiltration and priming.
   Symptoms scores and quality of life would worsen as the season progressed.
3. The study does not exclude the benefits of continuous intranasal corticosteroid use which may offer additional benefits.
4. Other trials, which demonstrated efficacy, used oral antihistamines continuously. Thus, medication was in essence given prophylactically.
5. The investigators question the efficacy of intermittent use of antihistamines when taken after exposure to the allergen.
6. "Our data support the efficacy of fluticasone nasal spray in the treatment of seasonal allergic rhinitis and the superiority of its as-needed use compared with that of an as-needed H1 receptor blocker."
7. It would seem logical to use intranasal corticosteroids as first-line therapy. It could be used regularly to treat severe disease, and used as-needed for mild disease.

1. Double-blind, randomized, placebo-controlled trial followed 88 patients to completion. All had a history of recurrent or chronic rhinitis and evidence of acute infection on X-ray or nasal endoscopy. All had a history of previously diagnosed sinusitis that necessitated antibiotic therapy.
2. All had at least 2 of 5 major symptoms of sinusitis: headache; facial pain; nasal congestion; thick, colored nasal discharge; olfactory disturbance.
3. Randomized to: 1) Two puffs of fluticasone propionate (Flonase; a synthetic corticosteroid) in each nostril daily for 21 days; or 2) Placebo spray.
4. All also received inhaled xylometazoline (Nature-vent; over the counter) twice daily for 3 days, and cefuroxime (Ceftin -- a broad spectrum cefalosporin) 250 mg twice daily for 10 days.
5. Main outcome—clinical success (cure or much improved). Follow-up at 10, 21, and 56 days.

1. Those receiving fluticasone achieved a significantly higher rate of clinical success than placebo. ( 94% vs 74%)
2. Patients receiving fluticasone improved more rapidly. (6 days vs 10 days)

1. Fluticasone is a once-a-day intranasal corticosteroid indicated for management of allergic rhinitis.
2. Cefuroxime has been shown to be effective in treatment of acute bacterial sinusitis.
3. The NNT(benefit one patient - 3 weeks) = 6.
4. Xylometazoline may have aided the distribution of fluticasone in the nasal passages.

1. Randomized, double-blind, placebo-controlled trial entered over 250 patients. All had moderate to severe ragweed-induced seasonal allergic rhinitis and a positive skin test for ragweed.
2. Randomized to: 1) omalizumab 300 mg subcutaneously, or 2) placebo injection just prior to the ragweed season. Injections were repeated every 3 to 4 weeks during the season. (About 12 weeks)
3. Main outcome measures -- self-assessed symptom severity, rescue antihistamine use, and rhinitis-specific quality of life.

1. Nasal symptom severity and duration scores were significantly lower in patients receiving omalizumab. Use of rescue antihistamine was less frequent. Quality-of-life scores were consistently better.
2. Benefits did not decline during the season.
3. Serum free IgE levels declined in the omalizumab group. Patients with the lowest free IgE had the lowest symptom score.
4. Frequency of adverse events did not differ between groups.

1. Lowering free IgE with a specific blocker provided clinical benefit. Benefit continued unabated during the season as injections were repeated every 3 to 4 weeks.
2. Treatment was begun before the onset of the ragweed season. It was hypothesized that beginning before symptoms developed might prevent the priming effect. (See previous abstract.)
3. Questions remain: Will blocking IgE activity lower resistance to other infection -- eg, parasitic?

1. Entered over 2100 middle aged men (mean age = 57). None had known ischemic heart disease. Excluded men with TG over 400.
2. Measured metabolic profiles in the fasting state. LDL-c was calculated by the Friedewald equation. (LDL-c = Total-c - (HDL-c + TG/5)
3. Classified the cohort into tertiles according to the fasting TG levels.
4. Compared total-cholesterol/HDL-c ratio with LDL-c/HDL-c ratio in each tertile of TG. Determined the incidence of CHD in each tertile of TG over 5 years.

1. Overall, those who developed CHD, as expected, had a more unfavorable metabolic profile — higher TG, higher LDL-c, higher T-c, lower HDL-c and higher LDL-c/HDL-c ratio.
2. An elevated TC/HDL-c ratio in men was observed among overweight, hyperinsulinemic and hypertriglyceridemic individuals. These atherogenic metabolic alterations may not always be reflected by the variation in the LDL-c/HDL-c ratio.
3. The TC/HDL-c ratio was the strongest predictor of ischemic heart disease risk. There was a progressive increase in risk across quintiles as TC/HDL-c ratio increased. Risk of those in the first quintile (TC/HDL-c = 3.7) was considered 1.00 (referent). Odds ratio of risk of ISD increased progressively in each quintile up to quintile 5 (TC/HDL-c = 8.4) where the relative risk was 4.
4. The odds ratio of the LDL-c/HDL-c ratio did not rise as quickly. It was not until the 4th and 5th quintiles of LDL-c/HDL-c ratio that odds ratio increased to above 3.

1. High TG-low HDL-c dyslipidemia is often linked to abdominal obesity and insulin resistance.
2. LDL-c levels are usually calculated from 3 measurements — TC, HDL-c and TG. [The Friedewald equation: LDL-c = T-c - (HDL-c + Tg/5)]. There is considerable cholesterol in TGs. The higher the TG, the more the cholesterol in TG is ignored in the calculation of the cholesterol risk factor.
3. LDL-c is most often calculated rather than measured. The calculation of TG/HDL-c ratio eliminates this step. As much as 25% variation can occur in the calculated LDL-c depending on the TG level.
4. The men who developed ISD in the study had a mean TG > 177 (considered high) and low HDL-c ( < 35), They also had a higher body mass index and elevated insulin levels as compared with normolipidemic men despite identical LDL-c levels in the 2 groups.
5. The relative cholesterol content increased across TG quintiles.
6. The high TC/HDL-c ratio was also associated with an increase in small, dense LDL particles (another risk factor).

1. Cross sectional population study obtained information from a cohort of over 14 500 men and women.
2. Questionnaire determined frequency of eating. "How many times a day do you eat, including meals, snacks, biscuits with coffee breaks."
3. Divided the cohort into 5 categories of eating frequency — one or 2 times daily; three times a day; four times; five times; and six times.
4. Participants also completed a 160 item food frequency questionnaire.
5. Determined concentrations of blood lipids.

1. Mean concentrations of total cholesterol and LDL cholesterol decreased in a continuous manner as frequency of eating increased.
2. In men eating once or twice a day vs 6 times a day, mean total cholesterol was 6.11 vs 5.94 mmol/L (235 vs 228 mg/dL; 3% difference). LDL-cholesterol decreased from 4.06 to 3.86 (156 vs 148). Similar changes in women.
3. But, the HDL-cholesterol also decreased as frequency of eating increased. Thus, the ratio of LDL-cholesterol to HDL-cholesterol remained the same.
4. Increased frequency of eating was associated with higher daily intake of energy, fat, fatty acids, carbohydrate, and protein. Body mass index did not differ between the 1 to 2 meal-daily and the 6 meal-daily groups
5. Observed no consistent relation to waist/hip ratio, or BP.

1. The results might be explained by confounding factors. Frequency of eating might be a marker of a particular lifestyle such as physical activity and alcohol intake that might directly affect lipids.
2. The improvement in cholesterol was particularly striking in view of the increased energy intake in the frequent eaters and their increased consumption of fats.
3. Finding lower cholesterol levels with increased frequency of eating is consistent with observational studies and controlled interventions on metabolic wards which show a strong and independent relation between lipid concentrations and frequency of eating.
4. Gorging animals may have an adaptive mechanism—they are able to store energy from a few periodic loads of food, in contrast to nibbling animals. which feed continuously and have steady metabolism. This biological process, called "adaptive hyperlipogenesis", is characterized by higher gastrointestinal absorption of glucose, increased activity of pancreatic enzymes; increased ability to produce fat from glucose (ie, enhanced hepatic lipogenesis probably mediated by insulin action); increased hepatic synthesis of cholesterol; increased total mass of fat; and higher postprandial peaks of insulin and increased sensitivity to insulin in fat tissue. Both lipid and glucose metabolism are affected.
5. The metabolic adaptations of gorging may apply to humans, leading to an increased risk of cardiovascular disease.
6. Although the cholesterol differences were not large, the lower levels in the frequent-eater group were comparable to differences achieved by altering intake of dietary fat. A reduction of LDL-c by 5% has been reported in observational studies to be associated with a reduction in coronary heart disease by 10% to 20%.

1. To mimic clinical use, aspirin (81 mg, enteric coated) was administered once daily followed by ibuprofen (Advil; Motrin) 400 mg three times a day.
2. At 6 days, determined serum levels of thromboxane and degree of platelet aggregation as markers of of platelet cyclo-oxygenase activity.
3. Duplicated the study using, in place of ibuprofen, 1) diclofenac (another NSAID, Voltarin; delayed release, 75 mg twice daily) and 2) rofecoxib (a cyclo-oxygenase 2 inhibiting; cyclo-oxygenase-1 sparing NSAID; Vioxx 25 mg three times daily), and 3) acetaminophen (Tylenol ; 1000 mg).

1. When multiple doses of ibuprofen were given after the one daily dose of aspirin, the beneficial effects of aspirin were blocked. Aspirin's effect on inhibiting production of serum thromboxane and inhibiting platelet aggregation effectively stopped. .
2. Diclofenac, rofecoxib, and acetaminophen had no effect on aspirin's action on platelet aggregation and thromboxane production. Benefits of aspirin continued.

1. Aspirin reduces incidence of recurrent myocardial infarction and stroke. Many persons take prophylactic low-dose aspirin. Many also take NSAIDs (often over the counter) for symptomatic relief.
2. Neither NSAIDs nor selective cyclo-oxygenase-2 inhibitors would be expected to afford substantial cardioprotection. Inhibition of platelet aggregability commonly does not persist during dosing with NSAIDs.
3. Platelet cyclo-oxygenase-1 activity is unaffected by cyclo-oxygenase-2 (COX-2) inhibitors.
4. The authors suggest that indomethacin (Indocin) may also have this inhibiting effect on aspirin.

      Alzheimer's disease has traditionally been marked by insidious onset of memory loss , followed by gradual progression to dementia in the face of normal findings on neurological examination.
      Vascular dementia (or multi-infarct dementia) is characterized by stepwise cognitive decline punctuated by episodes of stroke that are accompanied by focal deficits on neurological examination and imaging abnormalities.

Can patients take a leading role in making decisions?
Do they want to?
What if doctors and public health professionals don't like their choices?

1. The National Osteoporosis Risk Assessment was a longitudinal observational study of over 200 000 ambulatory postmenopausal women. Mean age = 65. Excluded women taking a bisphosphonate (eg, Fosamax) , calcitonin (Miacalcin) , or raloxifene (Evista). Those taking current estrogen were not excluded.
2. Measured BMD by peripheral bone densitometry at heel, finger and forearm with several different machines (including ultrasound) in physician's offices. Defined low BMD by WHO criteria -- "T scores":

   T score of 0 denotes the equivalent of mean peak BMD in a population of healthy 20 to 29 year old women.
   T score of -1 represents a BMD one standard deviation below this mean.
   T score between -1 and -2.5 = BMD of 1 to 2.5 standard deviations below the mean, arbitrarily defined as "osteopenia".
   T score -2.5 and lower = BMD of 2.5 and greater standard deviations below the mean, arbitrarily defined as "osteoporosis".

3. Each standard deviation decline in T score is associated with approximately a doubling of relative risk of fracture.
4. Determined risk factors for osteoporosis by questionnaire.
5. Determined fracture rates at 12 months.

1. 39% of the women had osteopenia; 7% had osteoporosis. Eleven % had previous fracture (after age 45). Osteoporosis was associated with a 4-fold increase in fracture rate. Osteopenia with a 2-fold increase.
2. Increasing age, personal or family history of fracture, Asian of Hispanic heritage, smoking, and use of cortisone predicted increased fracture risk. The effect of advancing age was independent of all other factors. Compared with women age 50-54, odds ratios of osteoporosis increased from 1.8 for women age 55-59 to 23 for women over 80.
3. Higher body mass index, African American heritage, estrogen use, diuretic use, exercise, and use of alcohol predicted lower risk. Both former and current use of estrogen was associated with a reduction in fracture of 25% to 75% respectively. Alcohol use was protective, even use of over 14 drinks per week.
4. Odds ratio of osteoporosis in current users of estrogen was 0.27

1. The study confirms several risk factors — low BMI, history of fracture, cigarette smoking, lack of exercise, and non-use of estrogen.
2. Women found to be osteoporotic at any peripheral site were at markedly increased risk of fracture.
3. Different devices and sites yielded different estimates of low BMD. T scores are calculated by each manufacturer of measuring devices. This may lead to different T scores in the same patient when a different measuring device is used. However, women with T scores of -1 to -2.5 by any device were more likely to have fractures. "All peripheral sites measured in NORA showed similar predictive ability for overall fracture risk after accounting for age."
4. Recent studies report that only about one in 5 patients seen with minimal-trauma fractures had received osteoporosis treatment. Indeed, fracture in postmenopausal women implies osteoporosis unless proven otherwise.

1. Open label randomized trial compared 3 SSRIs in over 550 patients: Paroxetine (Paxil); Fluoxetine (Prozac); and Sertraline (Zoloft) -- starting daily dose = 20 mg; 20 mg; and 50 mg.
2. All were depressed and considered candidates for antidepression medication by their primary care clinicians. About 75% of patients had a major depression.
3. Clinicians were allowed to switch to a second or third medication if there was inadequate response to the first.
4. Judged response by a Health Survey and a Medical Component Summary score.
5. Follow up = 9 months.

1. Responses to the 3 SSRIs were comparable in all measures and at all time points.
2. Mean improvements in scores ranged from + 16 to + 17. Improvement was more rapid in the first 4 weeks of therapy.
3. Incidence of adverse effects and withdrawals were the same. About 25% discontinued or switched because of adverse effects. About 15% stopped because of lack of benefit.

1. These "results unequivocally demonstrate the lack of difference among 3 SSRIs across a broad range of outcomes over 9 months". The magnitudes and time course of benefits was similar.
2. Clinically significant adverse events were similar.
3. A fourth SSRI, citalopram (Celexa), was not compared. However, several other comparisons have not demonstrated superiority.

Post the Charter in the office.
Discuss it with individual patients, explaining the conflicts between best of care and reality of the market place.
Distribute the charter in patient's statements.
Discuss the charter in civic club meetings and letters to the editor of local press.