8-1 CHARACTERISTICS OF PATIENTS WITH UNCONTROLLED HPERTENSION IN THE U.S.
      Most cases of uncontrolled hypertension consist of isolated systolic hypertension in older adults, most of whom have access to health care.
      Treatment of systolic hypertension does not remove the cause. (Ie, does not improve compliance of large vessels.) This risk factor remains. Nevertheless, reducing the systolic load probably slows progression of the stiffening, and lowers risk of endothelial rupture and arterial thrombosis.
      Practical point: Primary care clinicians have the opportunity and responsibility of diagnosing and treating systolic hypertension in their elderly patients. Treatment should begin low and continue slow. There is no urgency. It is most important to avoid adverse effects lest the patient become discouraged and discontinue treatment.

8-2 CONTROL OF HYPERTENSION — AN IMPORTANT NATIONAL PRIORITY
      Epidemiologic data indicate that systolic BP is more important than diastolic as a determinant of cardiovascular risk. In patients with isolated systolic BP, antihypertensive therapy has been shown to reduce mortality and the incidence of stroke, myocardial infarction, and heart failure.
      Practical point: The National Heart, Lung, and Blood Institute recommends that systolic BP become the major end point for the detection, evaluation, and treatment of hypertension. "Clearly, a shift needs to occur in clinical practice to focus more on the management of systolic rather than diastolic hypertension."

8-3 HORMONE REPLACEMENT THERAPY AND LONGITUDINAL CHANGES IN BLOOD PRESSURE IN POSTMENOPAUSAL WOMEN
      Postmenopausal women taking HRT had a smaller increase in systolic BP over time than non-users. The difference increased with age.
      Practical point: Primary care clinicians may consider this another mechanism for the protective effect of HRT. For those clinicians who believe the benefits of HRT outweigh the harms, another reason to prescribe it.

8-4 HAND HYGIENE
      Proper hand hygiene could reduce the incidence of transmission of infection. Washing with soap and water is not the only (or even the most effective) way of reducing transmission of organisms.
      The Hand Hygiene group now recommends use of a alcohol-glycerol hand rubs between patients. They are quick to use (10 to 20 seconds) and can be used while walking or talking. This overcomes the objections to soap and water washing which takes time and requires presence of sinks.
      Practical point: Clinicians — use this convenient, quick hand wash between patients

8-5 EFFICACY AND SAFETY OF TENECTEPLASE IN COMBINATION WITH ENOXAPARIN, ABCIXIMAB, OR UNFRACTIONATED HEPARIN: The ASSENT-3 Randomised Trial in Acute Myocardial Infarction
      Tenecteplase is a new genetically engineered variant of alteplase (tPA; tissue plasminogen activator). It provides a new standard of fibrinolytic therapy by virtue of its equivalent efficacy with regard to 30-day mortality, its reduced propensity for bleeding complications, and its simple administration as a bolus.
      “In view of the present data and the ease of administration, enoxaparin might be regarded an attractive alternative anticoagulant given in combination with tenecteplase.”
      Taking into account efficacy and safety, the combination of full-dose bolus tenecteplase + enoxaparin for 7 days emerged as the best treatment in this trial. Because of ease of administration and the lack of monitoring of anticoagulation, this combination should be regarded as an attractive alternative pharmacological reperfusion strategy deserving further study.
      Practical point: Primary care clinicians will soon have the opportunity and responsibility to apply immediate (bolus) out-of-hospital thrombolysis.

8-6 EFFECTS OF CLOPIDOGREL IN ADDITION TO ASPIRIN IN PATIENTS WITH ACUTE CORONARY SYNDROMES WITHOUT ST-SEGMENT ELEVATION
      The anti-platelet agent clopidogrel (Plavix) given in addition to aspirin, had significant benefits in patients with acute coronary syndromes without ST elevation. The risk of major bleeding was increased.
      Practical point: Primary care clinicians and their patients should consider the benefit/harm/cost ratio of clopidogrel. Harms are significant, costs high. but benefits may be life saving. The stakes are high.

8-7 RISK OF CARDIOVASCULAR EVENTS ASSOCIATED WITH SELECTIVE COX-2 INHIBITORS.
      The new selective COX2 inhibitors (rofecoxib Vioxx; celecoxib Celebrex) are pro-thrombotic. Meta-analyses thus far indicate an association with increased incidence of cardiovascular events compared with non-selective NSAIDs and placebo.
      Practical point: COX-2 inhibitors should be used with caution in patients with established coronary disease and those at high risk of atherosclerosis.

8-8 RISK OF MACULAR DEGENERATION IN USERS OF STATINS
      An exciting, but preliminary report of considerable lowering of risk of macular degeneration in older persons taking statin drugs.

8-9 ONE-TIME SCREENING FOR COLORECTAL CANCER WITH COMBINED FECAL OCCULT-BLOOD TESTING AND EXAMINATION OF THE DISTAL COLON
      One-time screening of asymptomatic subjects with FBOT plus sigmoidoscopy failed to identify about 1 of every 4 subjects with advanced neoplasia.
      Practical point: Primary care clinicians should advise all patients over 50 to undergo periodic colonoscopy and omit FBOT and sigmoidoscopy.

8-10 MANAGEMENT OF NODULAR THYROID DISEASE
      Although the optimum diagnostic strategy for euthyroid patients with nodular thyroid disease is still a matter of debate, there is agreement that fine needle aspiration cytology and tests of thyroid function are cornerstones of investigation.
      The challenge remains identifying which palpable nodules are malignant.
      The advice regarding investigation of nodules to detect cancer differs from the old tradition in several ways:

1. Radionuclide scanning and ultrasound may not reliably differentiate malignant from benign nodules.
2. TSH suppression with thyroxine is not indicated.
3. Differentiating single and multinodular goiters is not helpful in assessing risk of cancer.
4. Overt thyroid dysfunction effectively rules out malignancy

8-11 BONE MINERAL DENSITY RESPONSE TO ESTROGEN REPLACEMENT IN FRAIL ELDERLY WOMEN
      In physically frail women, mean age 82, 9 months of HRT significantly increased BMD.
      Traditional thought has been that the estrogen-dependent compartment of bone becomes depleted approximately 15 years after menopause. This concept has been challenged by those who believe that estrogen deficiency is also primarily responsible for the continuing decline in BMD that previously had been attributed to aging.
      It was once commonly believed that bone turnover remained elevated for only a few years after menopause and that bone loss subsequently slowed or ceased in older women. Recent studies provide evidence that bone turnover remains elevated into old age and that bone loss may accelerate rather than slow in the elderly. (Subjects in this study had high rates of bone turnover as indicated by serum and urine markers.)
      Practical point; Primary care clinicians should inform their elderly female patients of the possibility that bone sparing therapy is effective regardless of age, and allow them to make an informed choice to accept or reject.

8-12 PROGNOSTIC IMPORTANCE OF ELEVATED JUGULAR VENOUS PRESSURE AND A THIRD HEART SOUND IN PATIENTS WITH HEART FAILURE.
      Detection of elevated jugular venous pressure or a third heart sound in patients with HF was associated with adverse outcomes including progression of HF.
      Practical point: The physical examination identifies a subset of patients with a poor prognosis who would benefit from heightened therapeutic interventions.

8-13 THE JUGULAR VENOUS PULSE AND THIRD HEART SOUND IN PATIENTS WITH HEART FAILURE
      Read the description of the jugular venous pulse described by Mackenzie in 1903.

8-14 RECOGNITION AND TREATMENT OF POSTTRAUMATIC STRESS DISORDER.
      PTSD is a worldwide problem which is reaching alarming proportions. It is associated with persistent disability and comorbidity. Treatment can produce a meaningful reduction in distress. The condition must first be recognized.
      Practical point: Primary care clinicians will be seeing more patients with PTSD. Certainly they can elicit patient's experiences and feelings and listen empathetically. Compassionate understanding and treatment with selective serotonin reuptake inhibitors will benefit. There is no reason PTSD cannot be treated effectively in primary care.

8-15 SUBCLINICAL HYPERTHYROIDISM
      "Subclinical hyper-thyroidism". (SCHyperT) is defined as — the combination of an undetectable serum thyrotropin concentration (TSH), as measured by an assay with a threshold of detection that is 0.1mU per liter or less, and normal serum thyroxine and triiodothyronine concentrations (usually at the upper end of the normal range).
      For the many with endogenous SCHyperT who do not have multinodular goiter, and no complications from excess endogenous thyroxine production, treatment is not necessary. Thyroid function tests should be done every 6 months. Recognize that serum T3 may become elevated before T4.
      Treatment of patients with SCHyperT due to nodular goiter is more routinely justified given the expected progression to overt hyperthyroidism. "It would be surprising if the complications of overt hyperthyroidism were not seen, albeit at a reduced frequency, in a condition that is effectively the mildest form of thyrotoxicosis."
      Practical point: These patients should be followed for development of osteoporosis and atrial fibrillation.

1. The National Health and Nutrition Survey included over 16 000 adults at least 25 years of age.
2. From this base, estimated the prevalence of hypertension (> 140/90) and the number of those unaware of their hypertension, those untreated, those treated but uncontrolled, and those adequately controlled.

1. Estimated total number with hypertension in the US = 42 million
2. In millions:

   	Age 25-44	Age 45-64	Age >64
   Distribution by age	8	16	19
   Unaware of hypertension	3	4	6
   With hypertension known but not treated	2	3	2
   With inadequately treated hypertension	1	4	7
   Treated and controlled	2	5	4

3. About 75% of all subjects who were unaware that they had hypertension had a diastolic under 90; about 75% of those with uncontrolled, treated hypertension had a diastolic under 90; and about 60% of those with acknowledged untreated hypertension had a diastolic under 90.
4. The systolic BP elevation was mild in these 3 groups as assessed on the basis of historical standards.
5. Thus, "hypertension" in the US predominates as isolated systolic hypertension in the elderly. The pattern of an elevation of systolic and a normal diastolic was dominant in those over age 45. Only in the younger age group with hypertension was the average diastolic over 90.
6. Several factors were associated with lack of awareness of hypertension and acknowledged uncontrolled hypertension: Age > 65 (associated with the largest attributable risk for both outcomes); male sex; not having visited a physician in the past year; and black race.

1. The analysis yielded 4 important observations underlying poor control of hypertension:

   1)	Undiagnosed, as well as treated but uncontrolled hypertension, occurs largely under the watchful eye of the health care system.
   2)	Problems with lack of control are largely concentrated among older members of our society.
   3)	Lack of control is not confined to the poor, the uninsured, or minorities;
   4)	The pattern of an elevation in systolic (> 140) and a diastolic less than 90 predominates not only in the elderly, but among the middle-aged as well.

2. This dispels the stereotype that the typical patient with uncontrolled hypertension is a young man (typically black) who does not visit the physician or who will not take antihypertensive drugs regularly.
3. The increased prevalence in the elderly occurs despite that older Americans have the most frequent contact with the health system, and is the group most likely to have medical insurance.
4. There is persistent controversy about the appropriateness of the current treatment goal — a systolic under 140 in the elderly. More clinical trials are needed, particularly in view of the National High Blood Pressure Program calling for use of systolic as the chief diagnostic and management criterion. Randomized trials however, do provide evidence of the benefit of antihypertension drugs in elderly persons with systolic over 160 and a diastolic under 90. There is no such evidence regarding persons with only a mild elevation of systolic (140 - 160).

1. "The Baltimore Longitudinal Study on Aging", an observational study, followed 226 postmenopausal women (mean age 64 at baseline). All were healthy.
2. Measured lifestyle variables, BP, and traditional cardiovascular risk factors at baseline and every 2 years thereafter.
3. Determined use of HRT.

1. Of the 226, 77 continuously used estrogen/progestin; 149 used neither.
2. At baseline, systolic BP was similar in both groups. (132 mm Hg vs 134)
3. Users who were age 55 at baseline experienced a systolic BP increase of 8 mm over 10 years vs an increase of 19 mm Hg in non-users.
4. The difference was more evident in older ages. After 10 years of use, at age 65 the increase in systolic BP was 7 mm Hg in users vs 26 mm Hg in non-users.
5. Diastolic BPs did not differ.

1. Postmenopausal women have significantly higher systolic and diastolic BPs than premenopausal women.
2. The increase in systolic BP over time was significantly smaller in women taking HRT continuously.
3. The difference in systolic BP between users and non-users increased with age. These differences may not apply to older women with hypertension at baseline.
4. The investigators suggest several mechanisms: Arterial stiffness increases with aging. (Reflected by an increase in systolic BP.) Estrogen may reduce collagen accumulation, lessen loss of elastin and reduce smooth muscle proliferation in arterial walls.
5. HRT may increase production of endothelial-dependent nitric oxide (NO), with resultant vasodilation.
6. Diastolic BP is influenced primarily by peripheral vascular resistance, which represents the tone of small arteries. Although diastolic BP increases modestly up to middle age, it generally levels off and may even decrease in old age.

A recent study reported that hand rubs cause less skin irritation than soap and water. Alcohol-based hand rubs may decontaminate hands more effectively than soap and water.
Hand hygiene is effective in reducing transmission. If "hand hygiene" were a new drug it would be accepted without question.
The issue is no longer whether hand hygiene is effective, but how to produce a sustained improvement in health care worker's compliance. We should adopt a standard that alcohol hand rub is available at every bedside.

1. Followed over 6000 patients with acute ST-elevation MI. Assigned to one of 3 regimens, each of which contained the bolus fibrinolytic, tenecteplase. All were within 6 hours of onset.
2. Randomized to:

   1)	Full dose tenecteplase + enoxaparin (Lovenox — a low-molecular weight heparin) for a maximum of 7 days (enoxaparin group)
   2)	Half dose tenecteplase + 12-h infusion of abciximab (a glycoprotein IIb/IIIa platelet inhibitor) + weight-adjusted low-dose unfractionated heparin for 48 h (abciximab group)
   3)	Full dose tenecteplase + weight adjusted unfractionated heparin for 48 h (unfractionated heparin group)

3. Enoxaparin was given as an intravenous bolus followed by a subcutaneous dose every 12 h. Abciximab was given as a bolus followed by an infusion for 12 h. Tenecteplase was given as a bolus over 5 seconds, dose according to body weight, after the bolus form of the other agents was given.
4. All received aspirin in addition.
5. Primary endpoints:

   1)	Composite of 30 day mortality + in-hospital reinfarction or in-hospital refractory ischemia. (efficacy endpoint)
   2)	Above composite + in-hospital intracranial hemorrhage or in-hospital major bleeding complications (efficacy + safety endpoint)

1. Efficacy endpoint: The enoxaparin and the abciximab groups were associated with more benefit than the unfractionated heparin group. (Unfavorable outcomes = 11.4%; 11.1%; and 15.4%)
2. Efficacy + safety endpoints: Also more benefit in the enoxaparin and in the abciximab groups than in the unfractionated heparin group. (Unfavorable outcomes = 13.7%; 14.2%; and 17.0%).

1. In patients with an acute MI, treatment with full dose tenecteplase + enoxaparin, as well as half dose tenecteplase + abciximab + unfractionated heparin reduced ischemic complications of acute MI when compared with full dose tenecteplase + unfractionated heparin.
2. Benefits appeared shortly after start of treatment.
3. In the tenecteplase + enoxaparin group there was no increase in intracranial hemorrhage, no excess thrombocytopenia, and only a non-significant increase (~ 3%) in major bleeding despite the 7-day length of treatment.
4. “In view of the present data and the ease of administration, enoxaparin might be regarded an attractive alternative anticoagulant given in combination with tenecteplase.”
5. However, what role the various pharmacological combinations will ultimately have in conjunction with early coronary interventions remains to be determined.
6. “Taking into account efficacy and safety, the combination of full-dose tenecteplase + enoxaparin emerged as the best treatment in this trial.” Because of ease of administration and the lack of monitoring of anticoagulation, this combination should be regarded as an attractive alternative pharmacological reperfusion strategy deserving further study.

1. Randomized over 12 500 patients (mean age 64) with acute non-ST elevation coronary syndromes. All presented within 24 hours of onset. All had ECG changes and/or elevated cardiac enzymes at entry.
2. Randomized to: 1) clopidogrel 300 mg orally immediately followed by 75 mg once daily for up to 12 months. or 2) placebo.
3. All received daily aspirin and other drugs as indicated.
4. Follow-up = mean of 9 months

1. The first primary outcome — a composite of death from cardiovascular causes, nonfatal MI, or stroke — occurred in 9.3% of clopidogrel group vs 11.4% in placebo group. [NNT(benefit 1 patient over 9 months) = 48]
2. Second primary outcome — the first primary outcome or refractory ischemia— occurred in 16.5% of the clopidogrel group vs 18.8% of the placebo group. [NNT = 43]
3. The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization were significantly lower in the clopidogrel group. (By my calculation, the NNT varied between 100 and 143. RTJ)
4. Benefits were evident within 24 hours.
5. Adverse effects: Major bleeding occurred significantly more often in the clopidogrel group (3.7% vs 2.7%; NNT (harm one patient over 9 months) = 100). No increase in rate of hemorrhagic stroke.

1. In patients with acute coronary syndromes without ST elevation, clopidogrel was beneficial when added to aspirin and other medications (heparin, statins, ACE inhibitors, beta-blockers).The risk of MI and refractory ischemia was reduced. There was also a trend toward lower rates of ischemic stroke and death from cardiovascular causes.
2. Benefits of clopidogrel (which blocks adenosine diphosphate-induced platelet aggregation) were in addition to aspirin (which acetylates platelets).

Cyclo-oxygenase-1 (COX-1) is an enzyme present normally at all times in many cells, including the stomach and platelets. One action of COX-1 in platelets is to produce thromboxane, a platelet activator and aggregator. Thus, COX-1 is pro-thrombotic.

Cyclo-oxygense-2 (COX-2) is not present normally. It is induced by inflammation and produces prostaglandins related to pain and fever. Another action is on platelets to produce prostacyclin, a vasodilator and inhibitor of platelet aggregation. Thus, COX-2 is anti-thrombotic.

1. Followed 379 persons (age 66-75) regarding use of medications, including statins, currently and in the past 5 years.
2. Took stereoscopic photos of the fundi and graded them by the Wisconsin age-related maculopathy grading system.
3. Correlated statin use with risk of MD.

1. Of the 379, 77 (20%) had some evidence of MD.
2. Twenty seven (7%) of the 77 reported taking statins.
3. MD was less common in those taking statins:

   Of the 27 taking statins, only 1 of 27 (4%) showed signs of MD
   Of the 352 not taking statins, 79 (22%) showed signs of MD.

   (Odds ratio for MD among takers vs non-takers = 0.14) [Confidence interval = 0.02 to 0.83]
4. In a model adjusting for age, sex, smoking, and history of coronary angioplasty or bypass grafting, the odds ratio for MD among those taking statins, compared with those not taking statins, was 0.09.

1. In this study, older patients taking statins had about 1/10 the risk of age related MD compared with those not taking statins. However, the confidence intervals were wide, giving an imprecise estimate of the risk reduction.
2. The investigators suggest several mechanisms for this association:

   Statins might prevent the accumulation of the basal linear deposit in Bruch’s membrane.
         (This occurs with higher concentrations of plasma cholesterol.)
   Antioxidant properties of statins might protect the outer retina from oxidative damage.
   Simvastatin inhibits endothelial cell apoptosis and preserves ischemic vasculature. This may help to maintain a competent vascular supply to the macula.
   

1. Entered 2885 subjects age 50 to 75. (Mean = 60) All were asymptomatic.
2. All submitted cards from 3 days for rehydrated FBOT testing. (Rehydration increases sensitivity.) All underwent complete colonoscopy.
3. Defined sigmoidoscopy as examination of the rectum and sigmoid colon up to the sigmoid flexure during the colonoscopy.
4. Defined advanced neoplasia as: adenomas 10 mm or more; villous adenomas; adenoma with advanced dysplasia; or invasive cancer.

1. Of the 2885: Advanced neoplasia in the entire colon was present in 11%.
2. FBOT:

   Overall, positive in 239 (8%). False positive rate = 6%; true positive rate = 2%
   Advanced neoplasia in the entire colon was detected in 306 subjects. 182 distal; 150 proximal.
         Some were present in both.
   Of the 306, 24% had a positive FBOT.
         (Sensitivity of FBOT in detecting advanced neoplasia was low.)

3. Sigmoidoscopy:
         Detected 70% of all subjects with advanced neoplasia; missed in 30%.
4. Combined sigmoidoscopy + FBOT detected 76% of advanced neoplasia.
         (Note that when a positive FBOT test was present, or when a positive sigmoidoscopy was present, these calculations were based on the assumption that colonoscopy would be performed. Colonoscopy was considered to diagnose 100% of advanced neoplasia.)

1. FBOT is not useful in detecting small tubular adenomas.
2. FBOT identified only about 1/4 of advanced neoplasia.
3. Colonoscopy must follow a positive FBOT or a positive sigmoidoscopy to complete the screening process. Colonoscopy will include removal of most lesions.
4. In older persons, advanced neoplasia is more likely to occur in the proximal colon.
5. Sigmoidoscopy may fail to reach the splenic flexure. It would then be less sensitive in detecting advanced neoplasia than this study suggests.

More precancerous lesions will be discovered. Colonoscopy will detect precancerous lesions at an earlier stage. Most can be removed concurrently. (Ie, combined screening and treatment)

Colonoscopy will have to be done anyway:

In those with a positive sigmoidoscopy.
In those with a positive FBOT.
Over time, with yearly FBOT screens, more false positives will occur. The cumulative requirement for colonoscopy will rise.

1. Radionuclide scanning and ultrasound may not be helpful
2. TSH suppression with thyroxine is not indicated.
3. Differentiating single and multinodular goiters is not helpful in assessing risk.
4. Overt thyroid dysfunction effectively rules out malignancy

1. Randomized, double-blind placebo-controlled trial followed 67 women over age 75. (Mean age = 82) All were considered to be mild-to-moderately frail. None had been taking estrogens.
2. Randomized to: 1) conjugated estrogens (0.625 mg/d continuously) + medroxyprogesterone 5 mg/d for 13 days every 3rd month or 2) placebos.
3. All received supplemental calcium and vitamin D, adjusted to daily intake of 1200 mg and 800 U.
4. Determined 9-month change in BMD of the lumbar spine and hip.

1. Compared with placebo, HRT resulted in significantly larger increase in BMD in the lumbar spine (+4% vs +0.4%); and hip (+2% vs –0.1%).
2. Total body, femoral neck, and trochanter BMD also increased.
3. HRT also was associated with significant decreases in markers of bone turnover.
4. Adverse effects: Some intolerance developed early, but symptoms substantially decreased when dose was temporarily lowered. Only four of 45 withdrew because of adverse events — breast discomfort, bloating, vaginal bleeding, and perceived decline in well-being. Seven withdrew for other reasons.

1. In these frail elderly women over age 75, HRT resulted in significant increases in BMD.
2. The increase in lumbar spine BMD after 9 months was similar to the increases reported in younger women taking HRT.
3. Lower initial BMD and older age were associated with greater BMD response.
4. It was once commonly believed that bone turnover remained elevated for only a few years after menopause and that bone loss subsequently slowed or ceased. Recent studies provide evidence that bone turnover remains elevated into old age and that bone loss may accelerate rather than slow in the elderly. (Subjects in this study had high rates of bone turnover as indicated by serum and urine markers.)
5. Another study (Annals Internal Medicine 1999; 130: 897-904) reported a lower dose of conjugated estrogen (0.3 mg) coupled with calcium and vitamin D increased BMD in women over age 65.
6. Traditional thought has been that the estrogen-dependent compartment of bone becomes depleted approximately 15 years after menopause. This concept has been challenged by those who believe that estrogen deficiency is also responsible for the continuing decline in BMD that previously had been attributed to aging.

1. Entered a total of 2569 patients (mean age 62) with symptomatic congestive HF or a history of HF and an ejection fraction < 0.35
2. At baseline, recorded presence or absence of a 3rd heart sound and elevated jugular venous pressure. Although the physical examination was not standardized, it probably was representative of usual clinical practice.
3. Determined risks of hospitalization for HF and progression of HF, defined as death from pump failure and the composite of death + hospitalization for HF.
4. Followed a mean of 32 months to assess prognostic importance of the physical examination.

1. Elevated jugular venous pressure was present in 11%; third heart sound in 23%.
2. Elevated jugular venous pressure was associated with an increased risk of hospitalization for HF (RR = 1.3 compared with those without elevation) and death or hospitalization due to HF (RR = 1.3).
3. Presence of a third heart sound was associated with similar increased risks.

1. Finding elevated jugular venous pressure or a third heart sound on physical examination conveys important information in patients with symptomatic heart failure.
2. Elevated jugular venous pressure reflects increased right atrial pressure, which itself correlates with elevated left-sided filling pressure.
3. In one study of 50 patients with advanced HF, 96% had a third heart sound, but agreement between observers was moderate or low. Patients with HF may have a third heart sound as a result of low ventricular compliance, increased filling pressures, or increased early diastolic filling rates.

PTSD is a worldwide problem which is reaching alarming proportions.
It is associated with persistent disability and comorbidity.
Treatment can produce a meaningful reduction in distress.

      PTSD requires that clinicians give patients adequate time to disclose their stories. "Brief treatment does not mean rushed treatment." Primary care clinicians are ideally placed to provide front-line support. Education involves an explanation about the nature of PTSD and responses to stress. It involves encouraging patients to speak about their traumatic experiences in a non-pressured way.

      Selective serotonin reuptake inhibitors (SSRIs; fluoxetine (Prozac); and sertraline (Zoloft)) can have substantial benefit. SSRIs can improve quality of life and reduce disability. They can modulate affect, memories, and impulses. They often act rapidly, within weeks. One study reported that 40% of traumatized women reached clinical remission at 12 weeks. How long to continue? The long duration of PTSD is likely to require maintenance therapy -- up to 12 months. Four months of therapy may not be an adequate trial. However, if there is no improvement in 4 weeks on an adequate dose, continued treatment is unlikely to benefit.
      Since symptoms may peak within 2 weeks of the trauma, vigorous attempts to treat PTSD early on are warranted. Initial temporary use of a hypnotic agent followed within 3 weeks with a SSRI has been recommended for acute symptoms.

      In addition to drug therapy, psychosocial (cognitive-behavior) treatment is effective. (If referral to a psychotherapist is available.) Unfortunately psychosocial therapy is unlikely to be adopted in primary care unless treatment is considerably modified and simplified. One technique that might deserve further study is encouraging patients to write about their traumatic experiences. (Certainly primary care clinicians can elicit patient's experiences and feelings and listen empathetically.)

Atrial fibrillation: Risk relative to those without SCHyperT = 3.
Osteoporosis: Effects of SCHyperT on bone are less well defined than the effects of overt hyperthyroidism. Studies do indicate that in those with multinodular goiter, osteoporosis is more common. The bone loss can be reversed by treatment that restores TSH to normal.

Obviously, for patients with exogenous SCHyperT the dose of the treatment thyroxine should be reduced to return the TSH to normal.
For endogenous SCHyperT, opinions vary. The American Association of Clinical Endocrinologists concludes that endogenous SCHyperT associated with multinodular goiter should be treated.