7-1 DIAGNOSING STREP THROAT IN THE ADULT PATIENT: DO CLINICAL CRITERIA REALLY SUFFICE?
      Recently the American College of Physicians recommended an algorithm which may be used to diagnose group A strep pharyngitis on clinical grounds alone, eschewing microbiological testing.

Tonsillar exudates
Tender anterior cervical adenopathy
Fever
Absence of cough.

7-2 ACUTE UNCOMPLICATED URINARY TRACT INFECTION IN WOMEN.
      Trimethoprim-sulfamethoxazole (TM-S) for 3 days remains the therapy of choice. Telephone consultation and treatment is safe.
      For recurrent episodes of infection and for prophylaxis, self treatment is a reasonable clinical approach.

7-3 STRUCTURAL AND SYMPTOMATIC EFFICACY OF GLUCOSAMINE AND CHONDROITIN IN KNEE OSTEOARTHRITIS
      Evidence that glucosamine benefits symptoms and slows joint deterioration.
      The purity and dose of these over-the-counter preparations are not regulated by the FDA.
      Primary care clinicians may be willing to prescribe it despite regulation by the FDA.

7-4 MORTALITY RISK REDUCTION ASSOCIATED WITH SMOKING CESSATION IN PATIENTS WITH CORONARY DISEASE.
      Smoking cessation has a greater effect on reducing the risk of mortality among patients who smoke than the effect of any other intervention. Risk of death was reduced by 36% in those who quit.
      Ask your patients who smoke to read this article.

7-5 DIRECT OBSERVATION OF REQUESTS FOR CLINICAL SERVICES IN OFFICE PRACTICE.
      Patient-requests for prescriptions are becoming more frequent as direct-to-the-public advertising by drug companies becomes more common. Patient-requests for consultations, and tests are also becoming more frequent as the public becomes more sophisticated.
      Primary care clinicians will find it necessary to negotiate with patients about these requests. Physicians’ role in educating patients about risks, benefits, and costs of new “miracle” drugs is becoming more important.
      Primary care clinicians must increasingly understand patients’ anxieties and what they really want to receive from the consultation. The patient negotiates from fear and uncertainty. The physician negotiates from a specialized knowledge. Meeting a common ground satisfactory to both requires patience and give-and-take.

7-6 THE METABOLIC SYNDROME
      The close association of type 2 diabetes with cardiovascular disease (CVD) led to the hypothesis that the two arise from a common antecedent. This concept has been codified by the WHO and others as “the metabolic syndrome”. This diagnosis might hold the promise for enhanced prevention of diabetes and CVD.
      The metabolic syndrome: Obesity (especially central obesity); Dyslipidemia (especially high triglycerides and low HDL-cholesterol); Hyperglycemia; Hypertension
      Is the risk associated with a cluster of all 4 traits likely to exceed the sum of the four traits? I believe. . . “The whole is greater than the sum of the parts”?

7-7 WOMEN NEED BETTER INFORMATION ABOUT ROUTINE MAMMOGRAPHY
      The public should be told about all the outcomes of screening in terms it can understand. Surgical and psychological morbidities are important outcomes. Unnecessary treatments arise from overdiagnosis. This includes biopsies, segmental excisions, mastectomies, and even radiotherapy. “Until tools are developed that are capable of measuring a wide variety of outcomes, we cannot weigh the evidence satisfactorily.”
      “The age at which the trade-off between benefit and harm becomes acceptable is a subjective judgment that cannot be answered on scientific grounds.” Most women who are screened have not been educated about the uncertainties.

7-8 NURSES’ EXPERIENCES WITH HOSPICE PATIENTS WHO REFUSE FOOD AND FLUIDS TO HASTEN DEATH.
      Voluntary refusal of food and fluids has been proposed as an alternative to physician-assisted suicide (PAS) for terminally ill patients who wish to hasten death. Oregon hospice nurses reported the quality of the process of dying for most of these patients was good.
      But, “We don’t know enough about it.” “We have to get this out and talk about it, because this is happening.”

7-9 CLINICAL AND ORGANIZATIONAL FACTORS ASSOCIATED WITH FEEDING TUBE USE AMONG NURSING HOME RESIDENTS WITH ADVANCED COGNITIVE IMPAIRMENT
      A growing proportion of the approximately 4 million older US adults with Alzheimer’s disease or other dementias are surviving to the advanced stages of their disease. Eating and swallowing problems typically develop during the terminal stages. Whether to initiate feeding tube use or to focus on comfort care is a challenging dilemma facing families, clinicians and institutions.
      Growing empirical data and expert opinion indicates that feeding tubes has no demonstrable health benefits in this population, and may be associated with increased risks and discomfort.
      The quality of care of cognitively impaired patients in nursing homes is inversely related to the numbers who have feeding tubes in place.
      “Comprehensive implementation of advanced care planning is likely to reduce the use of feeding tubes.”

7-10 COMPARISON OF CARVEDILOL AND METOPROLOL ON CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC HEART FAILURE
      Carvedilol extended survival compared with metoprolol.
      However, the challenge in primary care is not so much which beta-blocker to choose, but judicious use of a beta-blocker in select patients with heart failure. They are underused in primary care practice for treatment of heart failure.

7-11 EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON RISK OF ALZHEIMER’S DESEASE
      The study lends support to the hypothesis that NSAIDs may protect against the development of Alzheimer’s disease. They are too toxic to be used for this purpose in large numbers of patients.
      This is provocative study suggests that we may be on the way to developing safe preventive measures.

7-12 THE INFLUENCE OF FINASTERIDE ON DEVELOPMENT OF PROSTATE CANCER
      Finasteride prevents or delays the appearance of PC at a risk of increasing incidence of high grade cancers.
      Not yet ready for general use, but provocative. Preventive or delaying measures may be in the offing.

7-13 INTERACTION OF SPIRINOLACTONE WITH ACE INHIBITORS OR ANGIOTENSIN-RECEPTOR BLOCKERS
      Spirinolactone and ACE inhibitors act synergistically or additively to increase plasma potassium levels. Toxic and even lethal concentrations may result. Spirinolactone is established as an important additive in therapy for patients with severe heart failure. The dose should not exceed 25 mg daily, and in some patients should be less.

Tonsillar exudates
Tender anterior cervical adenopathy
Fever
Absence of cough.

Sexual activity, especially within 48 hours. (Celibate women rarely have cystitis.)
Use of spermicidal agents.
Impaired voiding and poor perineal hygiene in older women. (Neurological disease and dementia.)
Estrogen deficiency.
Diabetes.
Cystocele and incontinence.

      Pyuria on urinalysis ( about 5% false negatives; 30% false positives.)
      Dipstick testing has largely supplanted microscopy and culture. It is most accurate when the presence of nitrite or leukocyte esterase is considered a positive result. This yields a sensitivity of 75% (25% false negatives) and a specificity of 82% (18% false positives). Defined in this fashion, a positive dipstick results in a 25% higher post-test probability of infection than the pre-test probability.
      “Most patients with consistent symptoms and a positive dipstick can be treated without the need to obtain a culture.” A negative dipstick cannot rule out an infection when the pretest likelihood is high. Here it is advisable to culture.
      The accuracy of findings on a culture of a midstream “clean catch” specimen depends on how a positive culture is defined. When a positive is defined by the traditional 100 000 bacteria per milliliter, there will be few false positives, but many false negatives. (High specificity; sensitivity only about 50%.)

Acute uncomplicated LUTI:

Trimethoprim-sulfamethoxazole (TM-S--Generic; Bactrim; Septra)

A 3-day course of TM-S (double strength; 160/800 twice a day) results in bacteriological cure in about 95% of women. Longer courses are not more effective. Single-dose treatment is less effective, eradicating infection in about 87%, but is associated with a lower rate of adverse effects. Trimethoprim alone is just as effective and can be prescribed for patients allergic to sulfa. Watch for resistance to TM-S. It is becoming common in some communities. However, many women with resistant organisms are still cured by TM-S.

Fluoroquinolones (ofloxcin [Floxin]; ciprofloxacin[Cipro] )

Given for 3 days are effective, but are second-line agents because of cost and concerns about development of resistant organisms.

Nitrofurantoin (Generic; Macrodantin)

Is less active against gram negative rods other than E coli.

Beta-lactams ( ampicillin; amoxicillin )

Should be avoided because of frequent bacterial resistance and low cure rates.

Phenazopyridine (Pyridium; generic--over-the-counter) for one or two days may be helpful in women with severe dysuria.

Telephone consultations:

Acute uncomplicated LUTI treated by telephone consultation appears safe and effective.

Recurrent LUTI:

Continuous prophylaxis

Half tablet of TM-S (single strength 80/400) every night or three times weekly for 6 months, up to 5 years.

Postcoital regimen

TM-S half tablet or one tablet (80/400) once.

Intermittent self-treatment

Beginning at onset of symptoms TM-s double-strength (160/800) twice daily for 3 days.

Cranberry juice

For prevention. Contains proanthocyanidins that appear to inhibit attachment of pathogens to the uroepithelium. 200 to 750 mL daily has been reported to reduce risk of symptomatic recurrent LUTI. The amount of actual cranberry varies considerably.

Postcoital voiding:

Several studies report no benefit.

Topical estrogen

In postmenopausal women topical estriol cream may reduce episodes of recurrent LUTI
Oral estrogens are not effective.

Vaginal spermicides

Should be avoided in women who have frequent episodes of LUTI.

1. Systematic search of randomized, placebo-controlled trials up to 2002 assessed the efficacy of oral glucosamine or chondroitin.
2. Determined effects on joint space by X-ray; and joint pain, stiffness, and mobility by several different questionnaires

1. Fifteen studies met inclusion criteria. Oral glucosamine was used in 1020 patients; oral chondroitin in 755. Both were compared with placebo. Mean patient age = 62
2. Glucosamine dose was usually 1500 mg daily; chondroitin dose 800 mg to 2000 mg daily. Duration of therapy varied from one month to three years for glucosamine; 90 days to 1 year for chondroitin.
3. The quality of glucosamine trials was significantly higher than the chondroitin trials.
4. Compared with placebo, glucosamine was associated with less narrowing of the joint space. The benefit was rated as low to medium, with about 0.3 mm mean difference in the width of the space after 3 years.
   (Glucosamine has a disease-modifying effect as well as a symptom-benefiting effect. RTJ)
   No structural improvement was adequately documented in the chondroitin group.
5. Effect of symptoms for both drugs was uniformly favorable as compared with placebo. The minimal time to onset of improvement was 2 weeks. Pain, stiffness, and joint mobility were all improved.
6. The absolute difference of benefit compared to placebo was 20%. The number needed to treat to benefit one patient = 5.
7. Adverse effects were infrequent and similar to placebo. “The safety profile of glucosamine and chondroitin can be considered excellent.”

1. The inclusion criteria of this study led to selection of randomized trials representative of the pragmatic effects of the drugs (ie, the efficacy on osteoarthritis in a self-administered long-term treatment). No studies of intra-articular or intravenous administration were included. (Also no studies of the 2 drugs combined. RTJ)
2. Data suggests that glucosamine efficiently prevents the long-term progression of osteoarthritis. “The structural efficacy of glucosamine is highly significant and ranges from low to medium.”
3. All trials allowed NSAIDs as rescue medication. The favorable symptomatic effects of glucosamine and chondroitin led to lower cumulative doses of NSAIDs.
4. “In accordance with our results, it can be definitely stated that the oral administration of glucosamine or chondroitin decreases the symptoms of osteoarthritis. The tolerance of the 2 compounds is excellent.”

1. Systematic search up to April 2003 selected prospective cohorts of patients with CHD which reported all-cause mortality and had at least 2 years of follow-up.
2. Twenty studies were included which calculated the relative risk of mortality among smokers with CHD who quit with those who did not quit. Most of the studies had a follow-up between 3 and 7 years.

1. There was a 36% reduction in risk of death among those who quit compared with those who continued to smoke.
2. Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, and type of CHD.
3. Pooled risks:

   Ceased smoking			Continued smoking
   Patients	Deaths	%	Patients	Deaths	%
   5659	1044	18	6944	1884	27

   (Absolute difference = 9% Number needed to stop smoking to prevent one death = 11)
4. Non-fatal infarcts were also reduced in those who quit. (Relative risk = 0.68)

1. The reduction in risk of total mortality associated with cessation of smoking is at least as great as other secondary prevention therapies such as use of statin drugs, aspirin, beta-blockers, and ACE inhibitors.
2. The risk reduction occurs quickly after cessation, as early as 2 years.
3. Most smokers who quit do so quickly after their CHD diagnosis.

1. Observational study audiotaped over 500 patient-physician encounters.
2. All patients presented a new problem or a significant health concern.
3. Main outcome measures included prevalence of requests for physician action: requests for laboratory, imaging, or other diagnostic tests; for a new medication; for referral to a physician specialist; for all or part of a physical examination; for refill or renewal of a medication; for a therapeutic procedure or a lifestyle prescription; for referral to non-physician.

1. Twenty three percent of patients made a request for at least one diagnostic test, speciality referral, or a new prescription.
2. Requests were more common among patients experiencing greater health- related distress.
3. Requests were associated with higher likelihood of receiving specialty referrals (odds ratio = 4), and a prescription for a new medication (odds ratio = 3).
4. Physicians reported that visits during which patients requested diagnostic tests were more demanding than visits in which no requests were made.
5. Patients whose physician failed to fulfill one or more requests reported significantly less visit satisfaction.

1. Patients of primary care physicians frequently made direct requests for clinical interventions.
2. Primary care clinicians are troubled by direct-to consumer advertising which provokes patient requests.
3. This implies that primary care clinicians should develop a protocol for responding to patient’s requests.
4. Some requests by patients are veiled, not direct. The patient may suggest a candidate diagnosis, may describe symptoms characteristic of a particular diagnosis, emphasize severity of symptoms, appeal to a certain life circumstance, and share stories of previous drug efficacy.
5. Patient requests are a strong, independent predictor of referral and prescribing.
6. One implication is that programs for containing health costs must address the patient as well as the physician. “It is perhaps unrealistic to expect that physicians will refuse to provide clinical services to patients whose requests are sufficiently strident.”

Obesity (especially central obesity)
Dyslipidemia (especially high triglycerides and low HDL-cholesterol)
Hyperglycemia
Hypertension

Screening tests are meant for patients with known symptoms
Screening reduces the incidence of BC
Early detection implies reduced mortality
All breast cancers progress
Early detection is always a benefit.

1. Over 300 hospice nurses responded to questionnaires regarding terminally ill patients who voluntarily and deliberately refused all food and fluid with the primary intention of hastening death. This did not include those stopping food and fluids for other reasons such as loss of appetite or inability to eat or drink because of disease.
2. Nurses rated possible reasons why patients refused food and fluid to hasten death; patients’ overall peacefulness and suffering, and quality of the process of dying.
3. They were asked almost identical questions about patients who had died after ingestion of a prescribed lethal medication. (PAS)

1. Of the 307 nurses who responded to the questionnaire, 41% reported that in the previous 4 years, they had cared for a patient who deliberately chose to stop eating and drinking.
2. This action was taken by the patients because they were ready to die, saw continued existence as pointless, considered their quality of life poor, wished to control the manner of death, and wished to die at home.
3. Stopping drinking and eating did hasten death; 85% of the patients died within 15 days.
4. Sixteen patients subsequently resumed eating and drinking--some because families encouraged the patient to eat.
5. On a scale from 0 (very bad death) to 9 (very good death) , the median score for quality of these deaths was rated by the nurses as 8. Most nurses rated the last 2 weeks of life as peaceful, with low levels of pain and suffering. A few patients, however, had “bad” deaths with significantly higher scores of pain and suffering. As compared with patients who died by PAS, those who stopped eating and drinking were rated as suffering less and being more at peace.
6. Patients who stopped eating and drinking were older than patients who died by PAS. (74 vs 64 years).
7. Few of these patients were evaluated by a mental health professional .
8. Three nurses believed that allowing a hospice patient to hasten death deliberately in this manner was unethical. But none reported that they would actively oppose a patient’s choice.
9. A high percentage of nurses reported that most or all family members accepted the patient’s decision. The family members were more prepared for, and more accepting of, the ill person’s death than were family members of other hospice patients.

1. One third of hospice nurses in Oregon reported that at least one patient they had cared for in the previous 4 years had deliberately hastened death by stopping food and fluids.
2. Even though physician-assisted suicide is legal in Oregon, almost twice as many patients chose to stop food and fluids as died as a result of PAS.
3. Voluntary refusal of food and fluid is not common. (Only a few among 40 000 Oregon deaths.) The authors propose, however, that this choice may occur often enough to be of clinical relevance in hospice care.
4. Most deaths were peaceful, within 15 days, and with little suffering. Anorexia, which occurs in some dying patients, may facilitate the choice of stopping eating and drinking.
5. In Oregon, health care workers may suggest refusal of food and fluids as an option when patients request PAS.

      A primary complaint, dry mouth, can be treated with ice chips and swabbing.
      The process of guiding patients through this option has remained uncomfortable, and largely unknown, for most physicians. Complicity (ie, giving permission) may indeed be uncomfortable for hospice, family, and physician. “The most important thing is to insure comfort and stay involved.” In some cases, the quality of death may be poor. These patients may need comfort support with morphine. Good palliative care is essential.
      The first author of the study was worried about thoughts of thousands of depressed, elderly people going on hunger strikes, and physicians being too quick to offer this alternative. “We don’t know enough about it.” “We have to get this out and talk about it, because this is happening.”

1. Nation-wide, cross-sectional study of all residents in Medicare or Medicaid certified nursing homes who had advanced cognitive impairment. (n = over 186 000)
2. Determined the resident and nursing home factors which independently influenced feeding tube use.

1. Thirty four percent of residents with advanced cognitive impairment had feeding tubes in place.
2. Resident characteristics associated with greater likelihood of use:
   Younger age; non-white race; male sex; divorced marital status; lack of advance directives; a recent decline in functional status; no diagnosis of Alzheimer’s disease.
3. Institutional associations with increased use:
   For profit homes; homes located in urban areas; having more than 100 beds; lacking a special dementia unit; and lacking a nurse practitioner or physician on the staff.

1. “Among the most notable observations in the study is the increased likelihood of feeding tube use among residents living in for-profit nursing homes.”
2. The lay and scientific press has put forward the notion that feeding tubes are likely to be used in nursing homes as a means of cost-saving. The staff’s time required for feeding residents by hand is expensive. In addition, Medicaid reimbursement schemes in many states pay higher per diem rates for tube-fed residents. However, “While the potential for financial incentives to favor use of feeding tubes exists, this association remains to be proven.”
3. Previous studies have shown that “Do Not Resuscitate” orders strongly influence feeding tube use. “This study underscores the important role of DNR orders at the nursing home level.”
4. Facilities with a greater overall rate of DNR orders may be more proficient at engaging surrogates in discussions that lead to decisions not to use a feeding tube,
5. Nonwhites may have different cultural attitudes toward death and dying and be apprehensive about the medical system and have poor communication about advanced directives.
6. “Comprehensive implementation of advanced care planning is likely to reduce the use of feeding tubes.”

1. Randomized, double-blind trial entered over 3000 patients with chronic HF. (NYHA class II (48%); III (48%); IV (3%). Mean age = 62) All had a previous admission for a cardiac condition, an ejection less than 0.35 (mean = 0.26) , and were treated optimally with diuretics and ACE inhibitors
2. Randomized to: 1) carvedilol - target dose 25 mg twice daily, and 2) metoprolol - target dose 50 mg twice daily.
3. Primary endpoints = all-cause mortality and the composite of all-cause mortality and all-cause admission.
4. Follow-up = mean of 58 months

1. Outcomes	Carvedilol (n = 1511)	Metoprolol (n = 1518)	NNT*
   All cause mortality	512 (34%)	600 (40%)	17
   Composite endpoint	1116 (74%)	1160 (76%)	50
   Cardiovascular deaths	438 (29%)	534 (35%)	17

   (* Number of patients needed to treat for 5 years to benefit one by taking carvedilol rather than metoprolol.)
2. “Incidence of side-effects and drug withdrawals did not differ by much between the two studies groups.”
3. Resting heart rate at each visit was similar in both groups, decreasing from about 82 to 68.
4. Carvedilol extended median survival by 1.4 years as compared with metoprolol. ]

1. Metoprolol has a high specificity for the beta-1 adrenergic receptor. Carvedilol blocks beta-1, beta-2, and alpha-1 receptors.
2. Carvedilol has other effects that might be advantageous in HF, including increasing insulin sensitivity. (Metoprolol has the opposite effect).

1. Systematic review and meta-analysis of observational studies published between 1966 and 2002 examined the role of NSAID use in preventing AD.
2. Nine studies looked at NSAIDs and aspirin in adults over age 55. Six were cohort studies (over 13 000 patients); 3 were case-control (over 1400).

1. Pooled relative risks of Alzheimer’s disease users vs non-users:

   NSAIDs	0.72
   Aspirin	0.87

2. Risk related to duration of use of NSAIDs:

   Less than 24 months	0.83
   Over 24 months	0.27

1. Benefit was greater with longer use.
2. Currently no data available on COX-2 selective inhibitors.

1. Entered over 18 000 men age 55 and older. All had a normal digital rectal examination and a prostate specific antigen (PSA) of 3.0 ng/mL or lower. Of these, about 9000 were followed to the end of the study.
2. Randomized to: 1) finasteride (Proscar) 5 mg daily, or 2) placebo
3. Prostate biopsy was recommended if the annual PSA, adjusted for the effect of Finasteride ¹, exceeded 4.0 ng/mL, or if the digital examination was abnormal.
4. Follow-up = 7 years. It was estimated that 60% of participants would have PC diagnosed during the study, or would undergo a biopsy at the end of the study.
5. All men who had not been given a diagnosis of PC were offered a prostate biopsy at the end of the study.
6. Primary endpoint – prevalence of PC.

1.  

   PC was detected:	Finasteride (n=4368)	Placebo (n = 4692)	Absolute difference	NNT*
   	18.4%	24.4%	6%	17

   (* Number needed to treat over 7 years to prevent one PC.)
2. High grade tumors (Gleason 7,8,9,10) were more common in the finasteride group: Finasteride -- 6.4%; placebo -- 5.1% (Absolute increase in risk = 1.3%; one of 77 men. )
3. Finasteride has relatively little toxicity. Sexual side effects were more common in the finasteride group.² Urinary symptoms were less common. ³

1. The lifetime risk of PC in the USA is 17%. About 29 000 men are expected to die of PC in 2003.
2. The high incidence and the unpredictable biology of PC make prevention an appealing option.
3. There is evidence that PCs that develop in men with low testosterone levels have higher Gleason scores and worse outcomes. However, it is possible that finasteride selectively inhibits low-grade tumors and selects for high grade tumors. The reason is not known.
4. “For a man considering using this medication, the greater absolute reduction in the risk of prostate cancer must be weighed against the smaller absolute increase in the risk of high-grade disease. ”
5. The trade off between lower risk of prostate symptoms must also be weighed against the higher risk of sexual dysfunction. Individual preference is required.

Aldosterone is a hormone normally excreted by the adrenal. It is the “sodium-retaining, potassium-excreting” hormone.
Renin (produced by the kidney) converts
Angiotensinogen (inactive precursor produced by the liver) to
Angiotensin I (an inactive precursor protein) is converted by
Angiotensin-converting enzyme to
Angiotensin II (a highly active vasoconstrictor protein) which acts on the adrenal to produce
Aldosterone
Angiotensin-converting enzyme inhibitors (ACE inhibitors) block conversion of
Angiotensin I to
Angiotensin II, thus lowering levels of
Aldosterone, leading to
Sodium loss and potassium retention by the kidney. (As in Addison’s disease)
Angiotensin II receptor blockers (AT II RB) act directly at the cellular level to block action of
angiotensin II on the kidney, also resulting in sodium loss and potassium retention.
Spirinolactone is a direct aldosterone inhibitor. It increases excretion of sodium and impairs excretion of potassium.