2-1 LOW BACK PAIN
      This long review comments on diagnostic evaluation (physical examination and imaging), natural history, and therapy.
      For patients with non-specific low back pain, a precise pathoanatomical diagnosis is often impossible. This leads to various imprecise diagnoses (eg, sprain or strain). The natural history is favorable, and patients need this reassurance. Bed rest is not recommended for the treatment of low back pain or sciatica. A rapid return to normal activities is usually the best course.
      The use of plain radiography can be limited to patients with clinical findings suggesting underlying systemic disease. More advanced imaging can be reserved for potential candidates for surgery.
      Surgery is appropriate for a small proportion of patients. It is most successful in those with sciatica or pseudoclaudication that persists after non-surgical therapy has been tried.

2-2 ASPIRIN AND THE TREATMENT OF HEART FAILURE IN THE ELDERLY
      In elderly patients with heart failure and coronary heart disease there was a strong association between use of aspirin and lower mortality.
      Practical point: When there is likelihood that coronary atherosclerotic disease contributes to heart failure in elderly patients (as it most often does), low dose aspirin should be prescribed.

2-3 SYSTEMATIC REVIEW OF LONG TERM ANTICOAGULATION OR ANTIPLATELET TREATMENT IN PATIENTS WITH NON-RHEUMATIC ATRIAL FIBRILLATION
      "The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment."
      Practical point: Aspirin is effective preventive treatment. For the many patients for whom anticoagulation is not suitable, aspirin should be prescribed.

2-4 CARDIOVASCULAR DISEASE AND MORTALITY IN OLDER ADULTS WITH SMALL ABDOMINAL AORTIC ANEURYSMS DETECTED BY ULTRASONOGRAPHY:
      Total mortality and cardiovascular disease were higher in participants with AAA than in those without. This was independent of age, sex or other cardiovascular disease.
      We too often concentrate on the AAA itself, and not on the associated atherosclerotic disease. AAA is, by itself, evidence of prevalent atherosclerotic disease. It is a major risk factor for progression of cardiovascular disease.
      Practical point: Patients with AAA should receive utmost efforts to reduce all possible risk factors for atherosclerosis.

2-5 PREFERENCES OF PATIENTS FOR PATIENT CENTERED APPROACH TO CONSULTATION IN PRIMARY CARE: Observational Study
      Analysis suggested 3 domains of patient preferences: 1) communication; 2) partnership; and 3) health promotion.
      One in three patients did not want an examination; only a quarter wanted a prescription.

2-6 TOWARD A GLOBAL DEFINITION OF PATIENT CENTRED CARE
      Patients want care which (a) explores the patients' main reason for the visit, concerns, and need for information; (b) seeks an integrated understanding of the patients' world— that is, their whole person, emotional needs, and life issues: (c) finds common ground on what the problem is and mutually agrees on management; (d) enhances prevention and health promotion; (e) enhances the continuing relationship between the patient and the doctor. "Here, then, is the beginning of a truly international definition."
      Practical point: Long term primary care provides the greatest opportunity for patient centered care.

2-7 LONGITUDINAL ASSESSMENT OF NEUROCOGNITIVE FUNCTION AFTER CORONARY-ARTERY-BYPASS SURGERY
      Cognitive decline is common and persistent after CABG. The pattern suggests an early improvement followed by a later decline. Older age, lower educational levels and presence of a decline immediately post CABG predicted greater 5-year declines.
      This is bad news indeed for the elderly contemplating CABG. It accentuates the importance of primary prevention.
      Practical point: This would tilt some patients toward high-intensity medical treatment and toward choosing PTCA instead of CABG if they are reasonable alternatives.

2-8 EFFECT OF RISEDRONATE ON THE RISK OF HIP FRACTURE IN ELDERLY WOMEN
      The bisphosphonate, risedronate (Actonel), significantly reduced risk of hip fracture among elderly women with osteoporosis. It did not reduce risk of hip fracture among the subset of women who had increased risks for falling.
      Practical point: To prevent hip fractures, interventions to prevent falls should be added to treatment of osteoporosis.

2-9 ALENDRONATE AND NAPROXIN ARE SYNERGISTIC FOR DEVELOPMENT OF GASTRIC ULCERS
      Both alendronate and naproxin can cause gastric ulcers. The combination appears to synergistically increase risk.
      Practical point: Combined NSAIDs (including aspirin) and bisphosphonates should be used with caution.

2-10 EFFECT OF AGGRESSIVE VERSUS CONVENTIONAL LIPID LOWERING ON ATHEROSCLEROSIS PROGRESSION IN FAMILIAL HYPERCHOLESTEROLEMIA
      Aggressive LDL-cholesterol reduction was accompanied by regression of carotid intima-media thickness in patients with FHC.
      Practical point: Primary care clinicians will encounter patients with familial hypercholesterolemia. Early detection and treatment of the disease in family members will save lives.

2-11 INTERPRETATION OF THYROID FUNCTION TESTS.
      In many laboratories, the highly sensitive TSH assay (limit of detection < 0.1 mU/L) alone is used for initial screening. This is satisfactory as long as some limitations are appreciated. T3 or T4 estimation alone as initial screen will miss subclinical thyroid dysfunction and is not advised.
      In individuals with a strong clinical suspicion of thyroid diseases, all 3 tests should be done. If all 3 are normal, thyroid disease can be confidently excluded.
      The article comments on the pattern of thyroid function tests in sick patients. This is the most common abnormal pattern of interest to primary care.

2-12 ASPIRIN AND ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AMONG ELDERLY SURVIVORS OF HOSPITALIZATION FOR AN ACUTE MYOCARDIAL INFARCTION
      The benefit of ACE and aspirin in patients at discharge from hospital, either alone or combined, was associated with a reduction in mortality at 1 year.
      Practical point: The best practice appears to be to combine the two drugs.

2-13 INHALED HUMAN INSULIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
      Pulmonary delivery of insulin in type 2 diabetic patients who required insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects.
      Pulmonary administration still does not match the physiological passage of insulin through the liver.
      Practical point: This application requires much more experience.

2-14 EFFICACY OF INHALED HUMAN INSULIN IN TYPE 1 DIABETES MELLITUS: A Randomized Proof-Of-Concept Study
      The study offers proof of the concept that inhaled insulin can be effectively and safely used in type 1 diabetes. It is a well tolerated alternative to subcutaneous insulin.

2-15 ANTIBIOTIC SUSCEPTIBILITY OF STREPTOCOCCI AND RELATED GENERA CAUSING ENDOCARDITIS: Analysis of UK Reference Laboratory Referrals January 1996 To March 2000
      Gentamicin plus penicillin remains appropriate for most patients, with vancomycin plus gentamicin a universally active alternative for those who are allergic to penicillin or who have more resistant isolates.

2-16 TERMINAL SEDATION, SELF-STARVATION, AND ORCHESTRATING THE END OF LIFE.
      "Orchestrating the end of life" refers to systematically and skillfully creating conditions to help the patient enjoy and control what is left of life."
      The desire to be dead is generally not a desire to be no longer alive, but an overwhelming feeling that being dead is preferable to "living this way". When all is said and done, powerlessness, social isolation, and incapacitation are more feared than pain. If we can change the way in which patients live at the end of life (as we often can through good palliative care) the desire to die will vanish or diminish.
      Much can be done to optimize a patient's capacity for controlling his or her own wishes into consequent action. This is a central feature of "orchestrating the end of life".
      Practical point: This article convinced me that I should never suggest to a patient that he or she should discontinue food or drink to hasten the end of life. RTJ

2-17 RENAL ARTERY STENOSIS
      There seems to be a shift away from identifying patients with renovascular hypertension because of the known benefits of medical therapy and the lack of sustained cure after revascularization. Indeed, hypertension is seldom cured by revascularization, except in patients with fibromuscular dysplasia.
      There is a shift toward identifying patients with renal-artery stenosis who are at risk for excretory dysfunction. Because of this shift, medical therapy (including aspirin) and modification of risk factors to limit atherosclerosis are essential in all patients, regardless of whether they have undergone revascularization.

2-18 FOMEPIZOLE FOR THE TREATMENT OF METHANOL POISONING.
      Fomepizole, an inhibitor of alcohol dehydrogenase, appears to be safe and effective in the treatment of methanol and ethylene glycol poisoning.

2-19 LIGHT BROUGHT TO A STANDSTILL
      “Scientists in two separate laboratories at Harvard University have brought light to a complete standstill.”

1. Multicenter, retrospective cohort study of over 1000 consecutive patients hospitalized with HF associated with CAD. All were over age 65.
2. Determined prescription of aspirin at discharge.
3. Determined mortality at 1 year.

1. At discharge 41% received a prescription for aspirin.
2. Patients for whom aspirin was prescribed had a lower 1-year mortality compared with those not receiving aspirin. (Odds ratio = 0.7)
3. At one year, 27% in the non-aspirin group died; 20% in the aspirin group. [NNT(benefit-1year)= 14]

1. The current American Heart Association guidelines for patients with CAD recommend use of aspirin.
2. Despite this, the use of aspirin for patients with HF, many of whom have CAD, has been controversial. The rational was based on a potential harm resulting from inhibition of prostaglandins by aspirin.
3. This study identified a strong association between use of aspirin and lower mortality among patients with both HF and CAD.
4. There was no suggestion of significant harm from aspirin.

1. Meta-analysis of 5 randomized trials (over 3200 patients) compared outcomes of antiplatelet drugs (mainly aspirin) with anticoagulation (warfarin) in patients with chronic non-rheumatic AF.
2. Calculated odds ratios and 95% confidence intervals to estimate treatment effects.

1. Fatal vascular events: 82 in the anticoagulation; 95 in the aspirin group.
2. Individual trial sizes were small. "The pooled odds ratios . . . showed non-significant trends in favor of anticoagulation in deaths from stroke (odds ratio 0.74; 95% confidence interval = 0.39 to 1.46 and vascular death (odds ratio 0.86; confidence interval = 0.63 to 1.46)
3. Primary annual event rates varied from 1.7% to 10.6% reflecting a marked clinical heterogeneity in risk among patients included in the different trials.
4. Only one trial reported greater benefits from long term anticoagulation. "These results must be interpreted with caution because methodological quality of this trial was lower than in the other trials." (See page 323 for comments on this point.)
5. Major bleeding events were more common in the anticoagulation groups. Bleeding would probably be more common in routine clinical practice.

1. "The evidence for current clinical practice in long-term anticoagulation for patients with non-rheumatic atrial fibrillation is not strong." "For vascular deaths, anticoagulation may be up to 37% better than aspirin, or as much as 17% worse."
2. Costs of anticoagulation are much greater.
3. "Given the uncertainty over the greater efficacy of anticoagulation, its undoubted hazards, and considerations of cost effectiveness we should strongly favour antiplatelet drugs in preference to long term anticoagulation."
4. For patients who are already receiving anticoagulation and are happy and stable on this treatment, these results show that there is little to choose between the two treatments except cost. For new patients, some doctors may consider it unwise to risk the potential hazards of major bleeding with the associated higher costs and will choose an antiplatelet drug. Patient preferences also need to be taken into account.

1. Longitudinal cohort study followed over 4500 patients, all older than age 65 (mean age 75), recruited from Medicare lists.
2. Screened all for AAA by ultrasound.
3. Determined mortality and incident cardiovascular disease over 4.5 years.

1. Prevalence of AAA was 9%; 90% were 3.5 cm or less in diameter.
2. Outcome per 1000 person-years at 4.5 years

   	Total mortality	Cardiovascular mortality	Incident CVD
   AAA	65	34	47
   No AAA	33	14	31
   Relative risks	1.3	1.4	1.6

3. Outcomes were determined after adjustment for age, risk factors, and presence of other cardiovascular disease.
4. Rates of rupture and repair were low.

1. In this cohort of older persons with AAA, mortality and incident cardiovascular disease were higher than in those without AAA, independent of other risk factors.
2. Risk of rupture was small and not detectable in those with AAA of less than 4.0 cm in diameter.
3. Use of infrarenal-to-suprarenal aortic diameter ratio did not substantially increase prediction of risk.
4. Of interest — ankle/arm BP index of 0.9 occurred in 24% in AAA group vs 12% of normal aorta group.
5. "These findings reinforce the current practice of repairing aneurysms at a diameter of 5 cm."
6. The risk for mortality exceeds the risk for rupture with smaller aneurysms (those 4.0 to 5.0 cm in diameter). It will be difficult to discern a benefit of elective repair in those with diameter < 5.0 cm.
7. Patients with small AAA should be advised to modify risk factors while under surveillance for increase in the size of the AAA.

1. Exploring the experience and expectations of disease and illness: patient's ideas about the problem, their feelings, expectations for the visit, and effects on function.
   
2. Understanding the whole person" (feeling emotionally understood and the context of the illness (how the family and life has been affected).
   
3. Finding common ground regarding management (partnership): problems, priorities, goals of treatment, and roles of doctors and patient.
   
4. Health promotion: health enhancement, risk reduction, early detection of illness
   
5. Enhancing the doctor-patient relationship: sharing power; the caring and healing relationship.
   
6. And, adding a 6th domain, the realistic use of time.
   

1. Performed neurocognitive tests preoperatively (baseline) on over 250 patients (mean age 61) who underwent CABG. Repeated tests at 6 weeks, at 6 months, and at 5 years.
2. Defined a decline in cognitive function as a drop of 1 standard deviation or more in scores on tests of any one of 4 domains of cognitive function.
3. Overall neurocognitive status was assessed with a composite cognitive index score.

1. Patients with cognitive decline:

   At discharge	53%
   Six weeks	36%
   Six months	24%
   Five years	42%

2. Older age, lower level of education, and evidence of decline at discharge were significant predictors of decline at 5 years.

1. Patients whose cognitive function declined immediately after CABG were at increased risk of long-term cognitive decline.
2. The change between cognition at baseline and at 5 years was more than 2 to 3 times that demonstrated in longitudinal assessments of cognitive function of over 5500 Medicare patients followed for 5 years.
3. Adjectives such as "subtle", "transient", and subclinical" have been used to describe the cognitive decline that occurs after CABG. Such descriptions minimize the importance of these changes.
4. A downward change of 1 SD in a domain of cognition indicates a reduction of approximately 20% in cognitive function in that domain. In the Digit Symbol subtest, for which good age-related normative data exist, a 20% reduction is similar to the difference in function between 40- and 60- year-old subjects.
5. These data demonstrate a significant association between cognitive decline immediately after CABG and the incidence and the severity of cognitive decline five years later.

1. Followed over 5000 women age 70-79 with confirmed osteoporoisis (BMD at the femoral neck more than 4 standard deviations below mean peak value for young women).
2. And over 3500 women at least 80 years old who had low BMD at the hip, and at least one non-skeletal risk factor for hip fracture (eg, difficulty in standing from a sitting position, poor tandem gait, fall related injury in the previous year, low psychomotor score, poor hand-eye coordination, smoking).
3. Randomized to: risedronate 2.5 or 5 mg/d, or 2) placebo.
4. Gave the usual precautions regarding bisphosphonates — Take tablets with a cup of water on an empty stomach 30 to 60 minutes before breakfast; remain upright for 60 minutes thereafter. Women also received supplemental calcium and vitamin D.
5. Follow-up = 3 years.

1. BMD at the femoral neck and trochanter increased in the treatment groups. (Somewhat greater in the 5.0 mg group.)
2. Overall risk of hip fracture in the younger women was 3.2% in the placebo groups vs 1.9% in the treatment group. (Absolute difference = 1.3%; NNT(benefit 3 years) = 77).
3. In the older age group there was no significant difference in incidence of hip fracture. (Most of these women had non-skeletal risk factors for fracture — ie, increased risk of falling.
4. Adverse effects were reported in a high percentage of both active treatment groups and placebo group without any difference between them. Any upper GI adverse effect occurred in 22% of patients of all 3 groups. Esophagitis in 1.7 to 1.9%. (Higher in the placebo group.)

1. Risedronate was associated with a decreased incidence of hip fracture over 3 years in some women who had low BMD at the femoral neck.
2. There was no benefit in women who had non-skeletal risk factors for hip fracture.
3. "Risedronate was well tolerated. Overall, the incidence and types of adverse events were similar to those observed with use of placebo, even in women 80 years of age and older." The reasons for discontinuance associated with adverse effects were similar between groups.

1. Endoscopist-blind randomized crossover study compared: 1) Alendronate alone (10 mg), 2) Naproxin alone 500 mg twice daily, and 3) the combination.
2. Twenty six healthy volunteers age 30-50 took the drugs for 10 days in each phase of the study with a 1 to 4 week washout period between evaluations.

1. Incidence of gastric ulcers:

   Alendronate alone	Naproxin alone	Combination
   2/26	3/26	10/26

2. No esophageal injury was seen in any group.
3. Side effects were mild, and reported by 6 in the naproxin group; 14 in the alendronate group; 18 in the combined group. Abdominal pain and diarrhea were reported more often in the combined group.

1. "The evidence is now overwhelming that the use of alendronate alone can cause gastric ulcers." The study did not address the combined use of alendronate and COX-2 inhibiting— COX-1 sparing NSAIDs.
2. Alendronate combined with naproxin was more likely to produce severe gastric mucosal damage and abdominal symptoms than either drug used alone. The combination produced ulcers in more than one third of those studied.
3. These results are consistent with a follow-up study of over 800 women who filled prescriptions for alendronate. About 1/4 discontinued the drug primarily because of GI complaints.
4. "Yet, prospective studies of alendronate have not reported an increase in ulcer complications."

1. Randomized double-blind trial entered over 300 patients with FHC.
2. Randomized to: 1) atorvastatin (Lipitor) 80 mg/d, or 2) simvastatin (Zocor) 40 mg/d.
3. Measured change in IMT over 2 years.

1. Baseline IMT overall was similar between groups (0.93 mm vs 0.92 mm).
2. Mean LDL-cholesterol levels mg/dL (mmol/L):

   	Baseline	2 years	% change
   Atorvastatin	307 (8.00)	149 (3.88)	-50%
   Simvastatin	320 (8.33)	177 (4.61)	- 41%

3. After 2 years, IMT decreased in the atorvastatin group by a mean of -0.031 mm — increased in the simvastatin group by + 0.036 mm.
4. Regression of IMT occurred in 2/3 of the atorvastatin group.
5. HDL-cholesterol rose in both groups. Both drugs were well tolerated.

1. Aggressive lowering of LDL-cholesterol is warranted to modify IMT progression.
2. The most recent NCEP guidelines endorse aggressive LDL-cholesterol lowering to less than 100 mg/dL in patients with established CAD. Since LDL-cholesterol levels are higher in patients with FHC these goals are rarely met. Even if the goal is not met, atherosclerosis regression can occur.
3. IMT is increasingly used to predict future cardiovascular events. "The clinical relevance of progression of IMT as a marker for cardiovascular disease is beyond doubt."

1. Observational study evaluated the effect and interaction of aspirin and ACE on mortality in over 14 000 patients who survived MI. All over age 65.
2. At discharge from hospital, 25% received aspirin alone; 20% received ACE alone; 40% received both; 15% received neither.
3. Follow-up = 1 year

1. Compared with those who received neither drug, patients who received both aspirin and ACE had a significantly lower mortality. (Adjusted risk ratio = 0.86.)
2. Compared with those who received aspirin alone or ACE alone, risk ratio of mortality was 0.81 compared with those who received both. But the difference was not statistically significant.

1. The study found no evidence of an adverse interaction between ACE and aspirin.
2. Use of either alone or the combination was independently associated with a reduction in mortality at 1 year.
3. Benefits were consistent with previously reported studies. Aspirin alone was associated with a 15% reduction in mortality; ACE alone with a 15% reduction in mortality. The combination produced a somewhat greater benefit, but not significantly so.

1. Open label study entered 26 patients who were on a stable insulin schedule (2 or 3 injections daily).
2. During a 4-week baseline lead-in phase, patients continued their usual insulin regimen, were instructed in diet, performed home glucose monitoring, and underwent pulmonary function tests.
3. Then instructed in self-administration of inhaled insulin. Dry powder insulin was packaged in foil-blister packs containing either 1 mg or 3 mg of insulin. One mg delivers to the circulation the rough equivalent of 3 units of subcutaneous insulin. Only 10% to 30% of the insulin is absorbed.
4. Each blister was aerosolized using a specialized hand-held inhaler which delivered the insulin in a single inhalation. The median diameter of the aerosolized particles was approximately 3.5 microns, making it suitable for alveolar deposition.
5. Patients received 3 inhalations daily before meals at starting doses between the equivalent of 3 to 18 units of insulin. In addition they received a bedtime injection of ultralente insulin (Humulin-U; long-acting).
6. Dose titration was then based on preprandial glucose response targeted to 100 to 160 mg/dL
7. Follow-up = 12 weeks.

1. Inhaled insulin for 3 months significantly improved glycemic control compared with baseline: Mean HbA1c levels decreased by 0.7%. (From 8.7% to 8.0%). [Not an exemplary result. RTJ ]
2. Patients received an average of 15 mg/d of inhaled insulin, and 36 units of ultralente daily by the end of the study. This compared with 19 units/d of regular and 51 units/d of ultralente given at end of baseline.
3. An average of fewer than 1 mild to moderate hypoglycemic events occurred each month.
4. No weight change. No change in pulmonary function.

1. "Inhaled insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects."
2. Despite demonstrated benefits, tight glucose control remains a largely unmet clinical challenge. Multiple daily injections are inconvenient. Patient acceptance and adherence are poor. There is difficulty matching postprandial insulin availability to postprandial requirements.
3. Peptides, such as insulin, pass easily from the alveoli into the blood. The feasibility of pulmonary insulin delivery has been demonstrated in humans. Systemic absorption is confirmed by increased serum insulin levels.
4. Inhaled insulin appears to have an earlier onset of action than subcutaneous insulin. One mg of inhaled insulin has a peak level similar to approximately 3 units of insulin, with a similar glucose nadir.

1. Multicenter study evaluated effect of fomepizole in 11 patients with methanol poisoning. Eight had ingested windshield wiper fluid; one antifreeze — 6 in a suicidal attempt, 2 to cause inebriation, two accidentally.
2. All had serum methanol concentrations over 20 mg/dL. And 2 of 3 findings: 1) arterial pH < 7.3; 2) serum bicarbonate < 20 mmol/L; and 3) serum osmolality gap (determined by freezing point depression) of more than 10 mOsm per kilogram of water.
3. All received supportive therapy and supplemental folate. All had received ethanol before fomepizole treatment. Five patients received hemodialysis.
4. All received fomepizole iv for a mean of 30 hours.

1. Plasma formic acid concentrations fell and metabolic abnormalities resolved in all patients. Nine patients survived. The 2 who died had anoxic brain injury at the time of enrollment.
2. At entry 7 of the 9 survivors had visual abnormalities. At the end of the trial none had any detectable visual defects related to the methanol.

1. "Our findings suggest that fomepizole is a safe and effective antidote for methanol poisoning."
2. There were few adverse effects.
3. In the absence of a substantial accumulation of formic acid, as indicated by the absence of acidosis, hemodialysis is useful only to remove methanol itself. With the use of fomepizole, little methanol was metabolized. Since its elimination half-life is over 2 days, hemodialysis may be useful to remove methanol.
4. A comparison of fomepizole with ethanol could not be made. However, fomepizole is simpler to administer and with the dosing regimens used, reliable plasma concentrations can be achieved.