3-1 CLINICAL REALITY OF CORONARY PREVENTION GUIDELINES: A Comparison Of EUROASPIRE I And II In Nine Countries.
      There is a collective failure of medical practice in applying secondary prevention measures for CHD. Adverse lifestyles persist, BP remains uncontrolled, and most patients do not achieve adequate lipid control.
      Practical point: The primary care clinician must be implacable in continuing advice and supervision of secondary prevention measures for CHD.

3-2 ABCs OF SECONDARY PREVENTION OF CHD: Easier Said Than Done
      The author presents a simple A,B,C mnemonic for secondary prevention
           A Aspirin; ACE inhibitors
           B Beta-blockers
           C Cholesterol lowering drugs (especially statins)
           D Diet; Don’t smoke
           E Exercise.
      Many physicians still do not understand the benefits of secondary prevention. A systematic approach, which should be started at the time of diagnosis, is not implemented in many hospitals.
      Practical point: The burden should be on health-care providers to initiate appropriate preventive measures at the time of diagnosis. Good communication is essential.

3-3 TREATMENT OF OBESITY: Need to Focus on High Risk Abdominally Obese Patients
      Epidemiologic and metabolic studies have emphasized the notion that complications commonly found in obese persons are more closely related to where the excess fat is rather than the excess weight per se. In men, a high accumulation of intra-abdominal fat is a major risk factor for glucose intolerance, hyperinsulinism, type 2 diabetes, CHD, and related mortality. Viscerally obese persons have an atherogenic plasma lipoprotein profile.
      These individuals also tend to have hypertriglyceridemia and low concentrations of HDL-cholesterol, resulting in a high total-cholesterol/HDL-cholesterol ratio. This is a powerful predictor of CHD.
      The authors describe a triad of “new” atherogenic metabolic risk factors in these individuals.

1. Fasting hyperinsulinemia
2. Increased apolipoprotein B concentrations
3. Increased proportion of small, dense, lipoprotein particles

3-4 ABDOMINAL OBESITY AND THE "HYPERTRIGLYCERIDEMIC WAIST" PHENOTYPE
      Practical point: Measuring waist circumference in addition to BMI will enhance assessment of risk. A large waist circumference combined with an elevated triglyceride calls attention to increased risk, and can be a long-term marker of progress in improving risk.

3-5 WHAT IS THE OPTIMAL WEIGHT FOR CARDIOVASCULAR HEALTH?
      An estimated 10-year risk of CHD increased significantly in a dose-response fashion as BMI increased from <20 to >30.
      This supports previous observations of a direct linear association between BMI and CHD mortality and morbidity. Adverse metabolic consequences of adiposity may exist as a continuum. Even small increases in BMI to the lower and middle range (<25) may translate into important increases in long term risk.
      Although BMI is an imperfect surrogate for adiposity, and does not provide information about regional fat distribution, it is a simple and reliable measure of overall obesity that has been independently and consistently associated with several clinical endpoints.
      Adding waist circumference (a measure of intra-abdominal fat ) to BMI improves risk assessment.
      Practical point: It is not necessary to gain a BMI of 22 to improve health. Loss of 5 to 10 pounds will reduce risk.

3-6 AMERICANS' VIEWS ON THE USE AND REGULATION OF DIETARY SUPPLEMENTS
      Many feel so strongly about the potential benefits of some products that they would continue to take them even if scientifically conducted studies demonstrate they are ineffective.
      The majority of users believe the claims of supplement manufacturers are generally true.
      Practical point: Physicians should encourage patients to disclose their use of dietary supplements. But to do so in a non-judgmental way. Physicians should become aware of those that are indeed harmful as well as those which adversely interact with prescription drugs.

3-7 SHOULD ALL PATIENTS WITH TYPE 1 DIABETES MELLITUS AND MICROALBUMINURIA RECEIVE ANGIOTENSIN-CONVERTING ENZYME INHIBITORS?
      In normotensive patients with type 1 diabetes and microalbuminuria, ACE significantly reduced progression to macroalbuminuria, and increased chances of regression.
      Changes in BP did not explain the benefits.
      Practical point: All patients with type 1 diabetes should take ACE inhibitors.

3-8 SEVERE SEPSIS — A NEW TREATMENT WITH BOTH ANTICOAGULANT AND ANTI-INFLAMMATORY PROPERTIES.
      Recombinant human activated protein C is now available therapy This is a component of the natural anticoagulant system. It is a potent anti-thrombotic protease with substantial anti-inflammatory properties.
      A trial in this issue of NEJM reported clinically significant reductions in mortality in patients with sepsis.
      Practical point: "On the basis of this trial, activated protein C should be given to patients who meet all the inclusion criteria, including evidence of end-organ dysfunction with shock, acidosis, oliguria, or hypoxemia."

3-9 PHYSICAL ACTIVITY AND CORONARY HEART DISEASE IN WOMEN: Is "No Pain, No Gain" Passe?
      Walking need not be fast-paced for benefit. Time spent walking was more important than walking pace. Physical activity, easily within the ability of almost all women, was associated with lower CHD risk. At least one hour of purposeful walking per week, regardless of pace, was associated with lower CHD risk among relatively sedentary women.
      Practical point: A conservative approach is to endorse current guidelines recommending moderate-intensity physical activity for 30 minutes per day on most days of the week. This will reduce risk even in women who smoke, are overweight, and have elevated cholesterol levels. Duration of the walk, not the speed, is the beneficial factor.

3-10 RELATIONSHIP BETWEEN PLASMA ASCORBIC ACID AND MORTALITY IN MEN AND WOMEN IN EPIC-NORFOLK PROSPECTIVE STUDY: A Prospective Population Study.
      "Our findings suggest that an increase in dietary intake of foods rich in ascorbic acid might have benefits for cardiovascular disease and all-cause mortality in men and women and add to the large amount of evidence that lends support to the health benefits of fruit and vegetable intake. Small and feasible changes within the normal population range of intake could have a large effect."
      "Whether ascorbic acid supplements are beneficial remains to be seen."
      Practical point: Another recommendation to increase intake of fruit and vegetables.

3-11 URINARY SODIUM EXCRETION AND CARDIOVASCULAR MORTALITY IN FINLAND: A Prospective Study
      High sodium intake predicted mortality and risk of coronary heart disease independently of other risk factors, including blood pressure. "These results provide direct evidence of the harmful effects of high salt intake in the adult population."
      Practical point: Another recommendation to decrease salt intake.

3-12 ASSOCIATION BETWEEN TRANS FATTY INTAKE AND 10-YEAR RISK OF CORONARY HEART DISEASE IN THE ZUTPHEN ELDERLY STUDY : A Prospective Population-Based Study
      A high intake of TFA contributes to the risk of CHD. Over the years, a decrease in energy intake from TFA was associated with a substantial reduction in risk.
      Practical point: Trans fatty acids should be removed from the healthy diet. With due care this can be done without reducing acceptability of the diet.

3-13 IMPROVEMENT IN ATROPHIC GASTRITIS AND INTESTINAL METAPLASIA IN PATIENTS IN WHOM HELICOBACTER PYLORI WAS ERADICATED.
      In the year after successful eradication of H pylori, atrophic gastritis and intestinal metaplasia (precursors of gastric carcinoma) improved in most patients.
      Practical point: A reasonable indication to treat the infection.

3-14 PREVENTING RECURRENT UPPER GASTROINTESTINAL BLEEDING IN PATIENTS WITH HELICOBACTER PYLORI INFECTION WHO ARE TAKING LOW-DOSE ASPIRIN OR NAPROXEN
      In patients infected with H pylori, eradication of the infection greatly lowered risk of recurrent GI bleeding when low-dose aspirin was continued. Omeprazole also lowered risk.
      In patients infected with H pylori , eradication of the infection did not lower risk of recurrent GI bleeding when naproxin was continued. Omeprazole lowered risk
      Practical point: H pylori infection and low-dose aspirin may have synergistic effects to increase risk of bleeding. The protective effect of omeprazole is an important clinical point.

3-15 THERAPY FOR HELICOBACTER PYLORI IN PATIENTS WITH NONULCER DYSPEPSIA; A META-ANALYSIS OF RANDOMIZED, CONTROLLED TRIALS
      This meta-analysis provides little support for the use of H pylori eradication therapy in patients with nonulcer dyspepsia. Practical point: This does not preclude treatment. An occasional dyspeptic patient will be reassured, and may improve.

3-16 HORMONE REPLACEMENT THERAPY AND COGNITION: Systemic Review and Meta-Analysis
      In women with menopausal symptoms, HRT may have specific cognitive effects. A meta-analysis found an improvement in some aspects of cognition, and a decreased risk of dementia in HRT users, but most studies had important methodological limitations.
      Practical point: Primary care clinicians and their symptomatic menopausal patients should consider that the benefits of HRT may include some cognitive improvement, regardless of whether the benefits are specific or non-specific.

3-17 ESTROGEN REPLACEMENT THERAPY AND OVARIAN CANCER MORTALITY IN A LARGE PROSPECTIVE STUDY OF US WOMEN
      Women who used postmenopausal estrogen for 10 or more years were at increased risk of fatal ovarian cancer. Estrogen use for less than 10 years was not associated. The increased risk persisted for up to 29 years after cessation of use. These women were likely taking unopposed estrogen.
      Practical point: Would it not be prudent to now add progestin on an empirical basis in women whose ovaries remain intact after a hysterectomy?

3-18 HISTAMINE POISONING ASSOCIATED WITH EATING TUNA BURGERS.
      Histamine poisoning occurs when persons ingest fish in which bacteria have converted the amino acid histidine into histamine. (Previously termed "scombroid fish" poisoning.)
      Reported symptoms include: facial flushing, vomiting, diarrhea, dyspnea, rash, itching, tight feeling in the throat, headache, and a metallic or peppery taste in the mouth. Symptoms occur within 2 hours of ingestion.
      Practical clinical point: The syndrome should be recognized. It should be differentiated from fish and food allergy. Treatment with anti-histamines is effective.

3-19 MONOCLONAL MILESTONE
      Scientists at Cambridge University, England have found a way to use human cells to produce fully human monoclonal antibodies. (Human B cells fused to human myeloma cells as contrasted with the present monoclonal antibodies which fuse human B cells with mouse myeloma cells.)
      The technique promises a variety of clinical applications.

3-20 TREATMENT OF CIGUATERA POISONING WITH GABAPENTIN
      Ciguatera poisoning is caused by ingestion of tropical carnivorous reef fish. Ciguatoxin is a neurotoxin origination in a protozoa, and transferred up the food chain. It is not inactivated by cooking, cold or gastric juice.
      This is an anecdotal report of 2 cases treated successfully with gabapentin.
      Practical point: A possibly effective treatment for a disabling poisoning.

3-21 VACCINE AGAINST CERVICAL CANCER VIRUS PASSES PHASE 1 TRIALS
      A vaccine against HPV16, the most prevalent strain found in cervical cancer, has passed phase 1 clinical trials.
      "Women may soon be able to take a vaccine to protect themselves against cervical cancer."

1. Both studies were done in the same selected geographical areas. Identified over 6500 consecutive patients (men and women) under age 70 who had established coronary heart disease (CHD). All had undergone coronary bypass, percutaneous coronary angioplasty, or hospital admission for acute myocardial
2. infarction, or myocardial ischemia. All were interviewed in the first and second surveys to determine any changes in lifestyle or medications.
3. Most did not participate in any form of a professional cardiac rehabilitation program.

1.  

   Comparison	Survey I	Survey II
   Smoking	19%	21%
   Obesity (BMI > 30)	25%	31%
   High BP (>140/90)	55%	54%
   Cholesterol > 200 mg/dL	82%	59%
   Aspirin use	84%	84%

2. Use of beta-blockers, ACE inhibitors, and especially lipid lowering drugs increased.

1. Over the 3 to 5 years, after establishing presence of coronary heart disease, secondary prevention measures largely failed to be implemented.
2. Adverse lifestyle led to an increase in obesity and smoking.
3. There was virtually no change in the proportion of patients (55%) who maintained BP over 140/90. Indeed, in both surveys, more than a quarter patients maintained a BP over 160/95. “For so many patients with established vascular disease to have such high blood pressure in not acceptable in modern medical practice.”
4. To comply with lifelong treatments, patients must have a clear understanding of the progressive nature of atherosclerotic disease, their level of risk, and the need to take drugs for the rest of their lives.
5. In contrast with BP, and despite the rising prevalence of obesity, there was improvement in the goal of less than 200 mg/dL of total cholesterol. This was likely due to a large increase in use of statin drugs. Nevertheless, over half of the patients did not achieve this goal.
6. Prevalence of diabetes increased.
7. Use of aspirin (and in selected patients, anticoagulants), beta-blockers, and ACE inhibitors also increased. Use of calcium antagonists decreased.
8. A high prevalence of modifiable risk factors continued over 3 to 5 years after diagnosis of coronary heart disease. Adverse trends in obesity and smoking (especially in younger patients) emphasize the overarching importance of a societal approach to prevention. However, without professional support, it will be difficult for patients with CHD to resist the lifestyle trends in society.
9. Almost all patients with CHD could be prescribed an antiplatelet drug, an ACE inhibitor, and a statin.

1. Fasting hyperinsulinemia
2. Increased apolipoprotein B concentrations
3. Increased proportion of small, dense, lipoprotein particles

1. A substantial percentage of Americans reported they regularly use dietary supplements as part of their routine health regimen. Many give them to their children.
2. They do not discuss the use with their physicians because they believe that the physicians know little or nothing about these products, and may be biased against them. The medical community may not be aware of the benefits.
3. Many felt so strongly about the potential benefits of some products that they would continue to take them even if scientifically conducted clinical studies showed the products to be ineffective.
4. Nevertheless, there was broad public support for increased government regulation. The majority supported a requirement that the FDA review the safety on new dietary supplements prior to their sale; to provide increased authority to remove products shown to be unsafe; to increase government regulation to ensure that advertising claims about benefits are true.
5. The majority of users thought the claims of supplement manufacturers are generally true.

1. Obtained data from 646 patients identified in 12 trials. All were normotensive. All had microalbuminuria. (20 ug/min to 200 ug/min.)
2. All studies were randomized to ACE or placebo. Follow-up at least 2 years.
3. A variety of ACE drugs was included.

1. In patients receiving ACE, progression to macro-albuminuria (greater than 200 ug/min) was reduced. (Odds ratio = 0.38).
2. The odds ratio for regression to normoalbuminuria (less than 20 ug/min) was 3.07.
3. At 2 years, albumin excretion was 50% lower in treated patients than in placebo.
4. Benefits were lower in those at the lower end of albuminuria (@ 20 ug/min) vs those at the higher end.

1. ACE inhibitors have a clear beneficial effect on albumin excretion rate in normotensive patients with type 1 diabetes and microalbuminuria.
2. Progression to macroalbuminuria decreased to approximately 1/3 of that in the placebo group.
3. Regression to normoalbuminuria increased threefold. "ACE inhibitors may prevent or even reverse renal dysfunction."
4. Adjustment for BP levels had little effect on the albumin excretion rate, indicating that the beneficial effect must operate through other pathways.
5. Treatment effect was strongly influenced by baseline albumin excretion rates; patients with highest levels of microalbuminuria had the greatest opportunity for improvement. There was, nevertheless, some benefit on patients with the lowest levels of microalbuminuria.
6. "ACE inhibitors will benefit people with type 1 diabetes regardless of age, diabetes duration, glycemic control, or baseline blood pressure." (Note these results may apply only to adults.)
7. ACE may help reverse renal disease.

1. Cohort study enrolled over 39 000 healthy female professionals age 45 and older between 1992 and 1995.
2. Assessed physical activity by questionnaire — from inactivity to vigorous activity.
3. Follow-up for 4 to 7 years (average = 5 years) , correlating CHD incidence with recreational activity and stair climbing.

1. 244 cases of CHD occurred in follow-up.
2. Relative risk (RR) of CHD after adjusting for potential confounders:

   Less than 200 kcal/wk	1.00 (Referent)
   200-599	0.79
   600-1499	0.56
   1500 or more	0.75

3. Vigorous activity was associated with lower risk (RR = 0.63)
4. Walking (compared with no walking) without vigorous activities also predicted lower risk:

   Relative Risk
   No walking	1.0
   1 to 59 min per wk	0.86
   1.0 to 1.5 min per wk	0.49
   2 or more hours per wk	0.48

5. RR related to walking paces:

   No regular walking	1.00
   Less than 2 miles per hour	0.56
   2.0 to 3.9 mph	0.71
   3.0 mph or more	0.52

6. When analyzed simultaneously, time spent walking, but not walking pace, predicted lower risk
7. The inverse association between physical activity and CHD risk did not differ by weight or cholesterol levels.
8. Physical activity was inversely related to risk in current smokers. But not in hypertensive women.

1. "It is encouraging to observe that vigorous activities were not necessary for lower CHD rates."
2. Walking need not be fast-paced for benefit. Time spent walking was more important than walking pace.
3. Benefits of walking also occurred among those who were overweight, smokers, and women with elevated cholesterol levels.
4. This supports guidelines recommending moderate-intensity physical activity for at least 30 minutes most days of the week (generating energy expenditure of about 1000 kcal per week).
5. It is possible that even lesser degrees of activity may decrease CHD risk. A pace of walking slower than 3 miles per hour may be beneficial. Women who walked at least 1 hour per week had about half the CHD rates of women who did not walk regularly.
6. The questionnaire used probably measured purposeful walking rather than all walking (eg, walking around the home). If all walking were included, women who reported 1 hour of purposeful walking would have spent a total of about 3 hours/wk walking.
7. Among persons with little activity, institution of even light-to-moderate activity is beneficial. Among persons who are active and fit, more vigorous activity is needed for additional health benefits.

1. All of us could benefit from upping our physical activity by a notch. If you are sedentary, begin walking at least 15 minutes per day. The pace is not critical. If you already do this, up the time by 5 minutes a day. If you are already walking at a moderate time and pace, you will benefit from an increase in aerobic exercise which results in a training effect.
2. The word "purposeful" is a key.
3. Individuals with established risk factors can be informed that they will benefit from physical activity even if they do not stop smoking, do not lose weight, or do not lower their cholesterol levels. (Although physical activity may help them gain these objectives as well.) RTJ

1. Prospective study examined the relation between plasma ascorbic acid and mortality due to all-causes, cardiovascular disease, ischemic heart disease, and cancer.
2. Followed about 20 000 men and women (age 45-79 at baseline) for 4 years.
3. Participants completed a dietary, health, and lifestyle questionnaire.
4. Determined sex-specific quintiles of plasma ascorbic acid.

1. Only fruit and vegetable intake correlated consistently and more substantially with plasma ascorbic acid levels.
2. Only fruit and vegetable intake correlated with mortality due to all-causes, cardiovascular disease, and ischemic heart disease in both men and women.
3. Risk in the highest quintile of plasma ascorbic acid was about half the risk on the lowest quintile.
4. Ascorbic acid was inversely related to cancer mortality in men but not in women.
5. The relation with mortality was continuous throughout the whole distribution of ascorbic acid concentrations. A 20 umol/L rise in ascorbic acid (equivalent to about 50 g per day increase in fruit or vegetable intake) was associated with about a 20% reduction in risk, independent of many other possible confounding factors.
6. For men

   Ascorbic acid quintile	1	2	3	4	5
   Plasma ascorbic acid (umol/L)	21	38	48	57	73
   All cause mortality (per 100)	5.1	4.0	3.0	2.4	2.4
   Dietary ascorbic acid (mg/d)	51	77	83	92	109
   Fruit intake (g/d)	75	120	147	164	192
   Vegetable intake (g/d)	70	96	96	102	117

7. Women had similar outcomes, although mortality rates were less in all quintiles.
8. About 1/4 of men in the lowest quintile of ascorbic acid took supplements; about half in the highest quintile. But interestingly, the relative risk of all-cause mortality in supplement users was not associated with mortality.

1. "In this population of men and women aged between 45 and 79 years, increasing plasma ascorbic acid concentration was strongly and independently associated with reduction in risk of mortality from all causes, cardiovascular disease, and ischemic heart disease."
2. The authors admit that bias and residual confounding may be present and confound the results.
3. "Whether ascorbic acid supplements are beneficial remains to be seen. However, our findings suggest that an increase in dietary intake of foods rich in ascorbic acid might have benefits for cardiovascular disease and all-cause mortality in men and women and add to the large amount of evidence that lends support to the health benefits of fruit and vegetable intake. Small and feasible changes within the normal population range of intake could have a large effect."

1. Prospectively followed over 2500 Finish men and women age 25-64 (mean = 45) at baseline. Obtained complete data on 24-hour sodium excretion and cardiovascular risk factors.
2. The baseline mean 24 hour excretion of sodium was high in this group of Finns. In terms of NaCl, equal to about 13 g/d in men and 9 g/d in women.
3. Followed for 8 to 13 years. Obtained mortality data, and non-fatal coronary and stroke events.

1. Hazard ration associated with a 100 mmol sodium (2.3 g Na; 5.7 g NaCl) increase in urinary sodium:

   Coronary heart disease	1.5
   Cardiovascular disease	1.5
   All cause mortality	1.3

2. Frequency of acute coronary events, but not acute stroke increased significantly with increasing Na excretion.
3. There was a significant interaction between body mass index, urinary sodium, and mortality in men.

1. Coronary heart disease, cardiovascular mortality and all-cause mortality all rose significantly with increasing 24-hour sodium excretion. This was independent of other cardiac risk factors including BP, smoking, cholesterol, and body mass index.
2. A positive relation between body mass index, obesity, urinary sodium excretion, and BP has been consistently reported. Some studies have suggested that people who are overweight are more sensitive to effect of sodium on BP. Body mass index and sodium could act independently on blood pressure. A high sodium intake could have some direct effect on cardiovascular risk not mediated by blood pressure.

1. Prospectively studied 667 men age 64-84 (mean = 71) at baseline in 1985. All were free of CHD.
2. Used dietary surveys in 1985, 1990, and 1995 to establish the participants' food consumption patterns.
3. During the next 10 years (to 1995) mean energy intake of TFA fell from 4.3% to 1.9%
4. Determined incidence of CHD over 10 years. (N = 98)

1. In 1985 average TFA intake was 4.3% of energy; in 1995, 1.9%. (A remarkable population public health change.)
2. After adjustment for age, body mass index, smoking, and dietary co-variates at baseline, TFA intake was positively associated with the 10-year risk of CHD.
3. The decrease of 2% or more in mean intake of TFA over the years was associated with a substantial decrease in risk.

1. High intake of TFA at baseline was strongly associated with risk of CHD in these elderly men.
2. The TFA intake at baseline in the Netherlands was much higher than the 2% reported in the US. However, in the US, the intake has remained stable. The decrease in TFA from margarines has been counterbalanced by an increase in TFA from commercially baked products and fast foods.
3. Evidence suggests that a decrease in TFA intake has a role in lowering CHD mortality. The number of CHD deaths in the US due to TFA is thought to be considerable. In this study, the decrease of 2.4% energy intake from TFA could have contributed to about 23% fewer coronary deaths.
4. TFA content of bakery products and fast foods should be reduced. Substituting with saturated fats should be limited.

1. Prospective study entered 163 consecutive patients with dyspepsia and H pylori infection.
2. All were treated with antibiotic therapy and a proton-pump inhibitor.
3. Performed endoscopy and antral biopsy at baseline, 1, 3, and 1 year.

1. H pylori was eradicated in 115 patients (70%).
2. Inflammation and mean neutrophil activity decreased at 1 to 3 months.
3. Glandular atrophy of the corpus and intestinal metaplasia in the antrum decreased at 1 year.

   A. Glandular atrophy in the corpus improved in 89% of those with atrophy before treatment.
   B. Intestinal metaplasia improved in 61% of those who had metaplasia at baseline.

4. In the 30% of patients in whom eradication was not successful, no significant histological changes were observed.

1. "Our results suggest that eradication of H pylori is associated with modification of the natural course of atrophic gastritis and intestinal metaplasia."
2. Intestinal metaplasia may be a precursor of intestinal-type gastric carcinoma.

1. Enrolled 400 patients who had H pylori infection and a history of upper GI bleeding confirmed by endoscopy — 250 taking low-dose aspirin; 150 taking NSAIDs.
2. Their ulcers were healed by daily omeprazole for 8 weeks.
3. Then, for the next 6 months, those who had been taking aspirin were placed on 80 mg/d; those who had been taking NSAIDs were placed on naproxen 500 mg twice daily. (Naprosyn; generic)
4. The patients in each group were randomized to 1) 20 mg omeprazole [ a proton pump inhibitor] daily, or 2) eradication therapy ( bismuth subcitrate, tetracycline, and metronidazole) for one week followed by placebo for 6 months.

1. Aspirin patients
   Recurrent bleeding over 6 months

   A. H pylori eradicated 1.9%
   B. Omeprazole — H pylori not eradicated 0.9%

2. Other NSAIDs

   C. H pylori eradicated 19%
   D. Omeprazole — H pylori not eradicated 4.4%

1. In this study of secondary prevention of upper GI bleeding, in the group of patients who continued to take low-dose aspirin, eradication of H pylori was as effective as maintenance therapy with omeprazole in preventing recurrent GI bleeding. (There was no clinical important difference between recurrent bleeding in the 2 groups — 1.9% vs 0.9%).
2. In contrast, eradication of H pylori was much less beneficial compared with omeprazole in preventing recurrent bleeding for those continuing to take naproxen.
3. H pylori infection and low-dose aspirin may have synergistic effects to increase risk of bleeding.

1. Included 10 studies of patients with nonulcer dyspepsia and H pylori infection eradicated with antibiotic therapy vs control dyspeptic patients not treated with antibiotics.

1. Odds ratio for treatment success in relieving nonulcer dyspepsia with eradication therapy vs control therapy = 1.3 (not statistically significant)
2. Significant heterogeneity called into question the validity of aggregating the data in question.
3. Antibiotic therapy for H pylori did not confer significant benefit when patients in whom the infection was cured were compared with those in whom it persisted.
4. The decrease in mean symptom score with therapy was generally similar to the decrease with control therapy.

1. "Our results do not support the use of H pylori eradication therapy in the treatment of nonulcer dyspepsia."
2. Documentation of the role of H pylori in peptic ulcer disease is based on studies showing that eradication significantly reduces the recurrence rate of ulcer, rather than on studies demonstrating direct induction of ulcers by H pylori infection.
3. Mechanisms other than H pylori infection are likely to be responsible for most cases of nonulcer dyspepsia.
4. It is important to differentiate management recommendations for patients who initially present with symptoms of dyspepsia from recommendations for patients who have been evaluated and have received a diagnosis of nonulcer dyspepsia. Nonendoscopic testing for H pylori with subsequent treatment of infected patients (test and treat) is a reasonable strategy for management of patients who present with dyspepsia and no alarm symptoms. This strategy can decrease costs by decreasing the number of endoscopies performed while resulting in no change or a small improvement in symptoms. "However. after the diagnosis of nonulcer dyspepsia is established by full diagnostic evaluation, including endoscopy, our results suggest that H pylori therapy is not likely to result in benefit."
5. The benefit of "test and treat" in patients with dyspepsia is presumably caused by the cure of H pylori in the minority of patients who have ulcer disease.

With presence of H pylori, I believe treatment of the infection is reasonable to reassure the patient and to possibly lessen symptoms, at least in some individuals.
Without presence of infection, the patient may be reassured and symptomatic treatment continued.

1. Large literature search included 29 observational and randomized, controlled trials of effects of HRT on cognitive decline, and observational studies on effects on risk of dementia.

1. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions.
2. Generally, no benefits were observed in asymptomatic women.
3. A meta-analysis of observational studies suggested that HRT was associated with a decreased risk of dementia. (Odds ratio = 0.6) However, there were possible biases and potential confounders which limited interpretation.
4. Studies did not contain enough data to assess effects of progestin, various estrogen preparations, doses, or duration of use.

1. The review offers provisional conclusions:

   There were no deleterious effects of HRT on cognition.
   Estrogen does not appear to enhance asymptomatic women's performance.
   In symptomatic women, postmenopausal estrogen improved cognitive performance, especially in tests of verbal memory, vigilance, reasoning, and motor speed.
   Symptomatic women taking estrogen might perform better on cognitive testing because they have fewer hot flashes, sleep better, and have improved mood.
   Only some cognitive functions were affected by estrogen.
   

2. Previous studies suggested that HRT users have a significant decreased risk of Alzheimer's disease. However, the studies had limitations. It may be that the benefits were biased by the "healthy user effect", or variables such as education.
3. There was no evidence that estrogen improved cognitive function in women who already have dementia.
4. From a clinical prospective, the most important conclusion is that HRT improves some cognitive functions in symptomatic women. Not all functions are affected equally.

1. A prospective study (American Cancer Society's Cancer Prevention Study II) followed over 200 000 postmenopausal women from 1982 to 1996. None had history of cancer, hysterectomy, or ovarian surgery at baseline.
2. Determine incidence of ovarian cancer mortality between never-users, users at baseline, and former users as well as total years of ERT.

1. Over 14 years, 944 ovarian cancer deaths were recorded.
2. Women using ERT at baseline had higher death rates than never-users (Relative risk = 1.5)
3. Among former users RR = 1.2.
4. Duration of use was associated with increased risk among both baseline and former users. (The relative risk of cancer was higher in those using estrogen at baseline vs those who had used estrogen in the past. RR 2.2 vs 1.6.)
5. Annual age-adjusted ovarian cancer death rates for 10 or more years of use per 100 000 women = 64 for baseline users; 38 for former users; 26 for never users.
6. Risk declined with time since last reported use reported at study entry.

1. "This large prospective study supports the hypothesis that ERT increases the risk of ovarian cancer. The risk was associated with duration and recency of hormone use."
2. A possible mechanism is the negative feedback of estrogen on the pituitary. Decreased secretion of gonadotropins may significantly increase risk of ovarian cancer. Or possibly by a direct effect of estrogen on ovarian cells.
3. The majority of women in 1982 were likely taking unopposed estrogens. Therefore, the findings may or may not be relevant to hormone replacement therapy today if the addition of progesterone protects against ovarian cancer.
4. The increased risk of ovarian cancer must be considered in the context of the overall benefits of hormone replacement therapy.