5-1 �BUILDING� A HISTORY RATHER THAN �TAKING� ONE
      Adopting a �narrative-based medicine�(NBM) approach enables the sharing of information between patient and doctor. It incorporates the patient�s narrative into the sharing process. This article suggests a framework of skills and attitudes that can act as a foundation to improve the medical interview.
      The essence of a narrative-based approach involves the physician simultaneously attending to two narratives�one from the biomedical perspective, and one from the patient�s perspective. Listen to the patient!

5-2 WHAT DO DOCTORS FIND MEANINGFUL ABOUT THEIR WORK?
      Making a difference in someone else�s life was the most common theme in the doctors� stories. It was not making a brilliant diagnosis or an adroit technical intervention. Most of these stories took place in the context of chronic, incurable conditions, or end-of-life care. The doctors felt awed and deeply rewarded that their mere presence could be healing and comforting to patients.

5-3 USING NEW INSULIN STRATEGIES IN THE OUTPATIENT TREATMENT OF DIABETES.
      One daily injection of insulin glargine along with mealtime injections of insulin lispro significantly improves glycemic control in patients with poorly controlled type 2 DM. The combination matches each patient�s needs, simplifies adjustment of dose, and improves control while causing fewer episodes of hypoglycemia. �They are easier to use than many patients and clinicians realize.�

5-4 COMBINATION THERAPY WITH HORMONE REPLACEMENT AND ALENDRONATE FOR PREVENTION OF BONE LOSS IN ELDERLY WOMEN
      Combination therapy with HRT + alendronate was superior to either drug alone in increasing BMD.

5-5 THE SEVENTH REPORT OF THE JOINT NATIONAL COMMITTEE ON PREVENTION, DETECTION, EVALUATION, AND TREATMENT OF HIGH BLOOD PRESSURE.
      The JNC-VII provides new guidelines and key messages: Individuals with a systolic 120-139 or a diastolic 80�90 should be considered as pre-hypertensive. They require health-promoting lifestyle modifications to prevent CVD.
      The committee recognizes that the responsible physician�s judgment remains paramount.

5-6 HEALTH OUTCOMES ASSOCIATED WITH VARIOUS ANTIHYPERTENSIVE THERAPIES USED AS FIRST-LINE AGENTS
      Low-dose diuretics are the treatment of first choice for patients with uncomplicated hypertension who require drug treatment. They are the most effective drugs for preventing cardiovascular disease morbidity and mortality.

5-7 VARIATION OF SERUM PROSTATE-SPECIFIC ANTIGEN
      PSA may fluctuate over short periods of time. A single elevated PSA should be viewed with caution.
      An isolated elevation of PSA should be confirmed several weeks later before proceeding with further testing, including biopsy.

5-8 RELATIONSHIP OF CHANGES IN PHYSICAL ACTIVITY AND MORTALITY AMONG OLDER WOMEN
      Increasing and maintaining physical activity levels could lengthen life for older women.

5-9 HEART FAILURE
      This review article comments on diastolic HF and presents new staging and treatment options for systolic HF.
      The diagnosis of diastolic HF is usually made by a clinician who recognizes the typical signs and symptoms of HF and is not deterred by the finding of normal systolic function (ie, a normal ejection fraction) on echocardiography. Echocardiography may also be useful in detecting diastolic filling abnormalities. Diastolic HF is common.
      HF is largely preventable, primarily through control of risk factors. A new approach to the classification and progression of systolic HF emphasizes four stages of HF which differ from the classical NYHA functional classification.

5-10 DIETARY FIBER AND COLORECTAL ADENOMA IN COLORECTAL CANCER EARLY DETECTION PROGRAMME
      Dietary fiber from grains, cereals and fruits was associated with decreased risk of distal colon and sigmoid adenomas.

5-11 ESTROGEN PLUS PROGESTIN AND THE INCIDENCE OF DEMENTIA AND MILD COGNITIVE IMPAIRMENT IN POSTMENOPAUSAL WOMEN
      Estrogen + progestin did not reduce the risk for probable dementia in postmenopausal women age 65 and older.

5-12 PACEMAKER THERAPY FOR PREVENTION OF SYNCOPE IN PATIENTS WITH RECURRENT SEVERE VASOVAGAL SYNCOPE
      Pacing therapy did not significantly reduce the risk of recurrent syncope in patients with vasovagal syncope.

Physicians often redirect the patient to specific biomedical information early in the interview. The focus is then on narrowly constructed yes/no questions, thus losing sight of the patient�s narrative. History-building requires a conscious decision about phrasing of questions�questions that are focused, but still open-ended enough to give the patient space to discuss his narrative.

1) A profound event or emotional experience changed doctor�s perspectives about themselves, and about human nature. The experiences included the doctor�s emotional experiences with a patient, which led to sharing or reflecting on their own life experience.
      One experience concerned a doctor who home-visited a 4-year old dying of retinoblastoma. The home was ill kept. The mother was utterly isolated�abandoned by family, needed by kids. She had no resources to fall back on�no education, family, friends, spiritual framework. She watched (and smelled) her child�s head rot with creeping tumor. She helped the little body stand up to pee. Why was she not crushed? Why was she was not broken? Why am I not crushed seeing her? The doctor drew two conclusions about the world: It is a capricious, horrifying place where tragedy ultimately beats us down. It is a place where, in the face of tragedy, there can be heroic, even victorious love.
      This doctor went beyond his initial reaction to be inspired by the mother�s courage and acts of love for her son.
      Physicians often expand the boundaries of their role as scientifically detached observers.
      They recognize their patients as fellow human beings rather than objects of care. But, at times, doctors can be shocked by their own detachment.

2) The second theme was about connecting with patients in moments of intimacy.
      A doctor had followed a patient for several years. She had bowel obstruction due to carcinoid tumor, cord compression which failed treatment by radiation, and finally a urinary tract infection and terminal dehydration. �Nearing the end, I said �The end is coming soon . . . do you have anything more you need to say.� She opened her eyes and said, �Honey, I love you.� And I said �I love you too�. She cried, and I cried while I held her hand and stroked her hair. She died several hours later.
      Intimacy arose from the patient�s emotional expression, and the doctor�s willingness to respond
personally and genuinely. The language changed from technical medical jargon to personal narrative. Some doctors have been touched by a patient�s concern for the doctor�s well being�a role reversal. This doctor felt the role-reversal--the patients concern for the doctor as a person. Connections such as this may lead to discussions about life and what is really important to both patient and doctor.

3) The most common theme in the doctors� stories was making a difference in someone else�s life. This was not making a brilliant diagnoses or an adroit technical intervention. Most of these stories took place in the context of chronic, incurable conditions, or end-of-life care. The doctors felt awed and deeply rewarded that their mere presence could be healing and comforting to patients.
      One patient told her doctor �You know, whenever I see you, I feel better. My breathing is better and I feel more relaxed. She touched the doctor and said �Thanks for all you�re doing.�
      Doctors were often surprised to be thanked in the absence of cure or significant improvement. Some felt a shift from frustration because they could not eradicate a chronic symptom, to affirmation for continuing to care, and to do their best. Indeed, most stories took place in settings typically associated with medical failure�death and progressive illness.

1. Double-blind, placebo-controlled study randomized 373 community-dwelling women over age 65 (mean 72).
2. The mean BMD in the entire cohort was in the osteopenic classification; 34% had osteoporosis. This reflects patients seen in usual clinical practice.
3. Randomized to:

   1) Alendronate 10 mg daily
   2) Conjugated equine estrogen 0.626 with and without medroxyprogesterone. (About 1/3 of women had a hysterectomy and received estrogen alone. No data on this subset.)
   3) Both combined
   4) Placebo
   

4. Mean baseline dietary calcium was ~ 900 mg/day; dietary vitamin D ~ 250 IU/day. All received supplemental calcium and vitamin D. (Again reflecting the widespread deficiencies of calcium and vitamin D in the general USA population. RTJ)
5. Determined BMD at baseline and at 3 years.

1. BMD at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than in those treated with either drug alone.
2.  

   Mean annual percentage change in BMD	Placebo	HRT	Alendronate	Both
   Total hip	-0.81	+0.48	+0.97	+1.43
   Lumbar spine	-0.53	+1.30	+1.65	+2.58

3. Women treated with alendronate alone had greater increases in BMD over 3 years than those treated with HRT alone�4.2% vs 3.0%.
4. Older patients responded less often.

1. Combined therapy resulted in the greatest response at all sites.
2. Alendronate alone resulted in greater response than HRT alone.
3. The authors estimated that adding HRT to alendronate would result in an 8% reduction in fracture risk.
4. �For elderly women in whom hormone or estrogen replacement is a therapeutic alternative, combination therapy with a bisphosphonate can be considered to further improve skeletal integrity, and may be an option for women who fail to achieve an adequate response on monotherapy, or for women with more severe disease for whom monotherapy would be less desirable.�

1. In persons over age 50, systolic BP over 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP.
2. The risk of CVD, begins at 115/75 and doubles with each 20/10 increment.
3. Individuals who are normotensive at age 55 will have a 90% lifetime risk of developing hypertension. ¹
4. Individuals with a systolic 120-139 or a diastolic 80�90 should be considered as pre-hypertensive. They require health-promoting lifestyle modifications to prevent CVD.
5. Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or in combination with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of drug from other classes.
6. Most patients with hypertension will require 2 or more drugs to achieve goal BP (< 140/90), or < 130/80 for those with diabetes or chronic kidney disease.
7. If BP is more than 20/10 above goal BP, consideration should be given to initiating 2 agents, one of which usually should be a thiazide-type diuretic.
8. The best of therapy will control hypertension only if the patient is motivated.

1. Extensive systematic review identified long-term randomized controlled trials of antihypertension therapies that assessed major cardiovascular disease end points as an outcome. The authors combined previous meta-analyses, MEDLINE search, and journal reviews.
2. Included studies with both placebo-controls, and those with actively treated controls. Active drug treatments included a variety of first-line agents: diuretics, beta-blockers, alpha blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Most studies used more than one drug in the treated group. Agents were usually applied in a stepped-care approach so that the first-line therapy was clearly identified.
3. Data were combined from 42 clinical trials of over 192 000 patients randomized to 7 major treatment strategies. The authors synthesized the evidence into a single meta-analysis.
4. Since high-dose diuretics (starting with 50 mg hydrochlorothiazide or chlorthalidone and titrating upward) are no longer used or recommended, the study was limited to low-dose (12.5 to 25 mg).

1. For all outcomes, low-dose diuretics were superior to placebo. Relative risks:

   Coronary heart disease	0.79
   Congestive heart failure	0.51
   Stroke	0.71
   Cardiovascular disease mortality	0.81
   Total mortality	0.90
   (Lower RR indicates a more favorable outcome from diuretics.)

2. None of the other first-line strategies (noted above) was significantly better than low-dose diuretics for any outcome.

   1) Compared with CCBs, low-dose diuretics were associated with reduced relative risk of cardiovascular disease events (RR = 0.94) and congestive heart failure (0.74);
   2) Compared with ACE inhibitors, diuretics were associated with reduced relative risk of congestive heart failure (0.88), cardiovascular disease events (0.94), and stroke (0.86)
   3) Compared with beta-blockers, diuretics were associated with a reduced relative risk of cardiovascular disease events (0.89);
   4) Compared with alpha blockers, diuretics were associated with reduced risk of congestive heart failure (0.51) and cardiovascular disease events (0.84)

3. Blood pressure changes were similar between comparison treatments.

1. �For all outcomes, low-dose diuretics were superior to placebo.�
2. None of the other first-line treatment strategies was significantly better than low-dose diuretics for major cardiovascular disease outcome.
3. In 8 of the 30 between-drug comparisons, low-dose diuretics were significantly better than other treatments for the prevention of cardiovascular disease outcomes.
4. This provides compelling evidence that low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality.
5. Beta-blockers have long been identified as another preferred first-line treatment. In this analysis they were superior to placebo for prevention of stroke, congestive heart failure, cardiovascular disease events, and total mortality. They were inferior to low-dose diuretics for all outcomes, significantly so for cardiovascular disease events. For uncomplicated hypertension, they should be considered a second-line agent.
6. There are no long-term trials evaluating the optimal second-line therapy: Beta-blockers have been particularly effective for patients with coronary disease and heart failure. ACE inhibitors have proven to be robust therapy, effective in secondary prevention settings, including heart failure and coronary disease. They may be preferred in special populations such as those with diabetes.
7. �The most effective drug was also the least expensive.�

1. Retrospective analysis of an unscreened population of 972 men (median age = 62.) Obtained 5 blood samples over a 4-year period.
2. Determined total and free PSA levels and other markers.
3. Main outcome = abnormal PSA on repeat testing in groups with PSA higher than 4.0; higher than 2.5; higher than the age-specific cutoff; free to total PSA ratio less than 0.25; and a velocity higher than 0.75 ng/mL per year.

1. Of the entire cohort of men many met standard criteria for prostate biopsy on at least one PSA determination:

   > 4.0	21%
   >2.5	37%
   Above age-specific PSA	18%
   Free PSA ratio	20%
   PSA velocity	15%
   Any criterion	37%

   (Note the high numbers of presumably healthy men who were considered to have abnormal PSA. RTJ)
2. On repeat examination many with an initial abnormal PSA returned to normal:
   Number of participants with normal second time PSA after initial abnormal PSA:

   > 4.0	30% returned to normal
   >2.5	26%
   Age-specific PSA	37%
   Free PSA ratio	35%

3. A high percentage returned to normal at any subsequent visit-- between 65% and 83% of participants.
4. Between 65% and 83% with a previously abnormal test had normal levels on 2 consecutive repeat tests.

1. Screening for PC by PSA is widespread. This has led to a rapid increase in prostate cancer incidence, but the impact on PC mortality is not clear. PSA screening is not recommended as a screening tool by the US Preventive Services Task Force. The National Cancer Institute defines PSA testing as a strategy that is still under investigation.
2. About 10% to 15% of men will have a PSA greater than 4 ng/mL and will be recommended to undergo biopsy. (In the present study, 21% of men had a PSA over 4.0 during a 4-year period. Nearly half of these subsequently were found to have a normal PSA.
3. PSA fluctuations may result in many false positive elevations. A single elevated PSA should be viewed with caution.
4. A newly elevated PSA should be confirmed before proceeding with invasive tests.
5. Currently there is no standardized policy for the examination of an elevated PSA. Actual practice includes 3 likely scenarios:

   1) Immediate referral for biopsy. (Discounting any random fluctuations or laboratory error.)
   2) Immediate repeat of PSA. (Assumes a potential laboratory error.) If the second PSA is elevated a biopsy is recommended. If the second PSA is normal, the patient is not referred--the PSA is repeated semi-annually or annually.
   3) Wait 4 to 6 weeks before repeating the test, usually advising the patient to take antibiotics with or without an anti-inflammatory agent. (Assumes inflammation as a cause of the elevation.)

6. The present study repeated PSA once a year. There is no data on the time required for a newly elevated PSA to return to normal if it is to do so.
7. A policy of repeating PSA in 4 to 6 weeks may reduce a number of unnecessary procedures. It is not likely to alter prognosis of efficacy of treatment if cancer is present.

1. Prospective cohort study followed over 7500 community-dwelling white women age 65 and older.
2. Assessed walking and other physical activities at baseline.
3. Reassessed physical activity levels 6 years later to determine any change in physical activity over the past 6 years.
4. Determined any change in physical activity during this observation period divided into 4 groups:

   1) Those sedentary both at baseline and on follow-up.
   2) Those physically active at baseline and sedentary at follow-up
   3) Those sedentary at baseline and active at follow-up.
   4) Those physically active at both times
   

5. Followed for another 6 years to determine mortality
6. Compared rate and cause of death between groups.

1. Median walking distance at follow-up was 1.2 miles/week for those who reported being sedentary at both follow-up visits; 8.2 miles per week among those who became active after being sedentary; and 9.3 miles per week among those who were active throughout.
2. Compared with continually sedentary women, those who increased physical activity levels (group 3) had lower mortality from all cause (hazard ratio = 0.52); lower mortality from cardiovascular diseases (HR = 0.64); and lower mortality from cancer (HR = 0.49) ¹
3. The differences were independent of age, smoking, body mass index, comorbid conditions, and baseline physical activity.
4. Women who were physically active over the 12 years also had lower mortality rates than sedentary women.
5. Hazard rate ratios were lowest for women in the highest quintile for total physical activity.
6. Women who were active at baseline and became sedentary had the same mortality rates as women who remained sedentary over the entire period.

1. In this large cohort of white women over age 65 at baseline, remaining physically active and becoming active after baseline, were associated with substantially lower mortality rates. Conversely, women who remained inactive over 12 years and those who became inactive after being active did not benefit.
2. The increase in activity of those in group 3 amounted to only about 1 mile of walking per day.
3. Previously sedentary women who became active had a similar mortality rate as those who were already active.
4. Women who became sedentary after being active had the same mortality risk as those who were sedentary all along.
5. Benefits of activity were evident in those with comorbid conditions such as hypertension, diabetes, cardiovascular disease, and functional difficulties.
6. However, the benefits were less among women over age 75 and in those with poor health status.
7. The authors do remind us that observational studies such as this may mislead because of bias or confounding.

Frequently elderly as opposed to all ages in systolic HF (typically 50-70).
Frequently female
Left ventricular ejection fraction preserved, approximately 40% or higher
Left ventricular cavity size usually normal with concentric left ventricular hypertrophy
Left ventricular hypertrophy of ECG
Chest X-ray: congestion without cardiomegaly
Fourth sound gallop. (Atrial contraction sound.)
Coexisting conditions: hypertension, diabetes, obesity are especially frequent.
Atrial fibrillation frequently paroxysmal (opposed to persistent).

Patients are at high risk for developing HF, but have no apparent structural abnormality of the heart.

Patients have structural abnormalities, but have never had symptoms of HF.

Patients with HF have a structural abnormality of the heart, and current or previous symptoms of HF.

Patients have end stage symptoms of HF that are refractory to standard treatment.

1. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial compared fiber intake of over 33 000 participants (mean age 62) who were simoidoscopically negative for adenomas, with over 3500 patients with at least one histologically verified adenoma of the distal large bowel. (descending colon, sigmoid, and rectum) determined by screening.
2. Determined fiber intake by a 137-item food frequency questionnaire. Determined amount of fiber intake from grain and cereal, vegetables, legumes, and fruit.
3. Fiber intake ranged from 13 g/d to 36 g/d. (The average USA intake is 16 g/d. Intake of 30-35 g/d is recommended by current guidelines.)
4. Determined differences in incidence of adenomas related to fiber intake.

1. High intakes of fiber were associated with a lower risk of colorectal adenomas. Participants in the highest quintile of dietary fiber intake had a 27% lower risk of adenomas than those in the lowest quintile. (By my calculation from table 2 p 1493, the NNT over 7 years is about 4000 to prevent one adenoma. This could have an important effect on a population basis . RTJ )
2. The inverse association was strongest for fiber from grains, cereals and fruits. Fiber from legumes and vegetables provided no statistical benefit.
3. Risks were similar for advanced and non-advanced adenomas.
4. Risk of rectal adenomas was not associated with fiber intake.

1. Risk of adenomas in the distal colon and sigmoid was lower in subjects who consumed the greatest quantity of grain, cereal, and fruit fiber.
2. Few participants reported a fiber intake at the level reported from Africa (> 50 g/d).
3. The authors admit that confounding cannot be ruled out in observational studies such as this. (We have been seriously led astray before by observational studies. RTJ )

1. Randomized, double-blind, placebo-controlled clinical trial followed over 4500 postmenopausal women, all over age 65 at entry. (By my calculation, a median age of ~ 72. RTJ) All were free of probable dementia at baseline.
2. Randomized to:

   1) Conjugated equine estrogen 0.625 mg + medroxyprogesterone 2.5 mg daily, or
   2) Placebo

3. Structured clinical assessment (including the Mini-Mental State Examination) identified incidence of probable dementia and mild cognitive impairment.
4. Mean follow-up = 4 years

1.  

   Outcome over 4 years	Estrogen + progestin (n = 2229)	Placebo (n = 2303)
   Probable dementia	40	21
   Mild cognitive impairment	56	55

2. Twice as many women in the estrogen group developed probable dementia as in the placebo group: 45 per 10 000 person-years vs 22. (By my calculation, absolute difference = 0.23 persons per year.. [NNT(to harm one person over 1 year) = 434.] Can this be considered a clinically important adverse effect? RTJ )
3. Of the probable dementia cases, Alzheimer�s disease was diagnosed in 20 of the hormone group vs 12 in the placebo.
4. Treatment effects on mild cognitive impairment did not differ between groups.

1. Although participants assigned to active therapy were at about twice the risk for dementia, the absolute risk is low.
2. Some studies suggest that, for hormones to prevent probable dementia, women must initiate its use around the time of menopause. The study could not address that hypothesis. Women in this trial were over age 65.
3. The authors postulate that estrogen + progesterone increases progression of dementia possibly by increasing risk of stroke and undetected microinfarcts of the brain.
4. Estrogen-progestin should not be prescribed with the expectation that it will enhance cognitive performance.

1. Randomized trial entered 100 patients (mean age = 50). All had at least 3 syncopal episodes in past 2 years or 6 in lifetime. (Mean total events = 18; mean events in past year = 4.) All had a positive tilt table test.
2. Patients excluded for heart disease, EKG anomaly, any major noncardiovascular disease, or any other cause of syncope.
3. All received implantation of a dual chamber pacemaker. After implantation patients were randomized to 1) dual-chamber pacing (DDD) or 2) sensing without pacing (ODO). Both patients and their physicians remained blinded.
4. Pacemakers in patients randomized to DDD was programmed to pace if the patient�s pulse dropped 20 beats per minute, or if pulse fell below 70. The intervention rate was 100 beats per minute for 2 minutes.
5. Primary outcome was transient loss of consciousness with prompt spontaneous recovery.
6. Patients kept diaries and recorded symptoms of impending loss of consciousness that did not progress to syncope (defined as presyncope).
7. Follow-up = 6 months

1.  

   Outcome	Pacer active (n = 48)	Pacer turned off (n = 51)
   Syncope in 6 mo	16 (33%)	22 (42%) [Not significant]
   Pre syncope	46	49
   Major complications*	1	1
   Minor complications **	9	8

   (* Pericardial tamponade and infection requiring reimplantation.)
   (** Lead dislodgement, infection requiring antibiotics, vein thrombosis, wound hematoma, pain.)
2. Cumulative risk of syncope at 6 months was 31% for the DDD group and 40% for the ODO group (not significant).

1. Syncope as an outcome can have a major subjective component and is difficult to verify objectively.
2. The main finding in this trial was that a statistically significant benefit was not found for pacemaker therapy in patients with vasovagal syncope.
3. This study was designed to detect a relative risk reduction with pacing of 50%. The observed relative risk reduction was 30% with a wide 95% confidence interval. A relative risk reduction of 50% with pacing is unlikely, but still plausible. However, the large relative risk reductions in previous unblinded studies (~ 80%) are unlikely.
4. The authors believe that a relative risk reduction of 50% would be the minimum effect size to justify the cost and complications of invasive pacemaker therapy.