4-1 HOW DO YOU DEFINE DIABETES?
      The American Diabetes Society and the World Health Organization define "diabetes", "impaired fasting glucose" and "impaired glucose tolerance" differently. Primary care physicians must be aware of the sometimes modest changes in glucose metabolism which can lead to later development of diabetes and its devastating consequences. The abstract presents definitive cut points for glucose levels.
      Practical point: This is an important reference for primary care clinicians. We must be attuned to milder abnormalities of glucose concentration. Frequently this gives the best opportunity to improve lifestyles to lessen the risk of future development of harmful effects of elevated glucose concentrations.

4-2 RELATION OF IMPAIRED FASTING AND POSTLOAD GLUCOSE WITH INCIDENT TYPE 2 DIABETES IN A DUTCH POPULATION: The Hoorn Study
      The cumulative incidence of diabetes was strongly related to both impaired fasting plasma glucose and impaired glucose tolerance, and, in particular, the combined presence of both.
      Practical point: A fasting plasma glucose of 110 to 125 will predict a high risk of later progression to diabetes. An impaired glucose tolerance (post challenge glucose of 140-200 will also predict high risk. The combination of both will predict almost inevitable progression to diabetes over the years.
      Early determination of these defects in glucose metabolism permits clinicians to emphasize the importance of lifestyle changes to retard development of diabetes. The cumulative incidence of diabetes was strongly related to both impaired fasting plasma glucose and impaired glucose tolerance, and, in particular, the combined presence of both.

4-3 ADVERSE DRUG EFFECTS, COMPLIANCE, AND INITIAL DOSES OF ANTIHYPERTENSIVE DRUGS RECOMMENDED BY THE JOINT NATIONAL COMMITTEE VS THE PHYSICIANS' DESK REFERENCE
      The PDR does not reflect the lowest doses recommended for initiation of therapy for hypertension recommended by the JNC. Because avoidance of adverse drug reactions is essential in maintaining compliance, and because many ADEs are dose-related, physicians must use the very lowest, effective, least ADE-prone doses.
      Practical point: It is basically important to start therapy with the lowest reasonable dose of drugs, especially drugs for long-term use. Most adverse effects are related to dosage. Starting low and slowly titrating up will avoid many adverse effects.

4-4 RESULTS OF CURE TRIAL FOR ACUTE CORONARY SYNDROME
      Clopidogrel (Plavix- an antiplatelet drug), acts to inhibit adenosine diphosphate, an activator of platelet aggregation.
      This randomized, double-blind trial entered over 12 500 patients with acute coronary syndromes. For every 1000 persons treated for 9 months, an estimated 28 cardiovascular deaths, MIs, or strokes would be prevented.
      Practical point: The treatment of acute coronary events, including myocardial infarction, is in a state of flux. Use of thrombolysis is giving way to use of platelet inhibitors and early coronary revascularization. Primary care clinicians should be able to identify patients with acute coronary syndromes and begin treatment as early as possible. They should correlate the best current treatment with their cardiologist consultants. Watch for evolving developments.

4-5 PRIOR ALCOHOL CONSUMPTION AND MORTALITY FOLLOWING MYOCARDIAL INFARCTION
      Moderate alcohol consumption in the year prior to an acute MI was associated with reduced mortality following infarction.
      Practical point: What should we advise abstainers when discharged from the hospital following an acute MI? The number needed to treat (among those using alcohol in the year prior to the MI) to benefit one patient is comparable to other pharmacotherapeutic interventions. I believe some competent stable patients and their families should be informed of the likely (but not proven) benefits of one drink a day.
      They may then choose for themselves. Just as for any drug, a prescription for "A cocktail before dinner (1 oz spirits), or a glass of wine (4 oz) with dinner - not both" may be written. Individuals who do drink moderately and develop left ventricular dysfunction, heart failure, or other effects of CHD generally should not be told to discontinue consumption.

4-6 MODERATE ALCOHOL CONSUMPTION AND RISK OF HEART FAILURE AMONG OLDER PERSONS.
      Moderate alcohol consumption was associated with lower risk of heart failure among older persons. The observed benefits may not be entirely mediated by a reduction in risk of MI.
      Practical point: Primary care clinicians must consider the consistently substantial benefits of alcohol reported by epidemiological studies. Advice must be individualized. Stable individuals who consume small amounts of alcohol daily should not be told to stop. Abstinent individuals may be told of the risks and benefits and a prescription for "one drink daily" may be considered.

4-7 EFFECTS OF ATORVASTATIN ON EARLY RECURRENT ISCHEMIC EVENTS IN ACUTE CORONARY SYNDROMES: The MIRACL Study
      High dose atorvastatin started within 1 to 3 days after presentation for acute coronary syndromes was associated with a reduction in risk of early recurrent ischemic events, but with no other significant clinical benefit.
      Practical point: Statin drugs given immediately after onset of acute myocardial infarction or unstable angina may be associated with only small benefits over 4 months. Nevertheless, statins should be started for secondary prevention and maintained over years. Starting early in the hospital will encourage compliance.

4-8 EFFECT OF LIPID-LOWERING THERAPY ON EARLY MORTALITY AFTER ACUTE CORONARY SYNDROMES.
      Prescription of a lipid-controlling drug at hospital discharge for patients with unstable angina or MI, was independently associated with reduced short-term mortality over 1 month and 6 months.
      Practical point: There is good reason for prescribing statin drugs to patients with acute coronary syndromes (ie, established coronary disease) during their hospitalization or at discharge.

4-9 COMPARISON OF CORONARY-ARTERY BYPASS SURGERY AND STENTING FOR THE TREATMENT OF MULTIVESSEL DISEASE
      At one year, in patients with multivessel coronary disease, angioplasty with stenting and CABG offered the same protection against death, stroke, and MI. Stenting was less costly, but resulted in more revascularization procedures. The recent application of newer antiplatelet drugs (glycoprotein IIb/IIIa receptor blockers) may further tilt advantage toward stents.
      Practical point: In areas where logistic problems have been overcome, patients may be given full information about local experience and be given a choice between CABG and stenting. Many may choose stenting because of its more timely administration and less disability-time. And because of the reported cognitive declines reported in patients undergoing CABG.

4-10 RISK, CAUSES, AND PREVENTION OF ISCHAEMIC STROKE IN ELDERLY PATIENTS WITH SYMPTOMATIC INTERNAL-CAROTID STENOSIS.
      "If elderly people are denied therapy for reasons of prejudice and not of science, they may justifiably feel that they have been abandoned on the basis of age alone."
      In the secondary prevention (after TIA or non-disabling stroke) of ipsilateral stroke, patients over age 75 with 50-99% symptomatic stenosis, benefited more from endarterectomy than younger patients.
      And much more than those in the group receiving medical treatment alone.
      Practical point: Elderly patients who have experienced a TIA or non-disabling stroke are at extremely high risk of a second stroke. Since the elderly live now live longer than in the past, in patients over age 75 the benefits of surgery may outweigh the risks of surgery and of continued medical treatment. They should be informed about the local experience of endarterectomy and given the opportunity to choose for themselves.

4-11 HAEMATURIA IN ASYMPTOMATIC INDIVIDUALS
      Hematuria is often detected incidentally by "dipstick". It is common. Should hematuria in asymptomatic individuals always be investigated or should it be disregarded?
      In most cases the next step is to examine the urine by phase contrast microscopy to confirm the hematuria and to determine whether the red cells have originated from the glomerulus or elsewhere in the urinary tract. "Dysmorphic" or "glomerular" red cells are present when there is glomerulonephritis with proliferative features. "Non-glomerular" red cells appear when the bleeding comes from elsewhere in the urinary tract - usually infections, stones, or a tumor.
      Renal biopsy most often shows "thin basement membrane disease". Prognosis is excellent.
      Practical point: Primary care clinicians should be aware of this entity. It may save patients much anxiety and useless investigations

4-12 THE ANAEMIA OF CHRONIC DISEASE.
      Practical point: Is the microcytic anemia of a sick patient due to iron deficiency or to the anemia of chronic disease? Testing the soluble transferrin receptor (STR) in serum may differentiate. STR is raised in iron deficiency; normal in ACD.

4-13 THE DOCTOR'S LETTER OF CONDOLENCE
      Practical point: Reviving the old custom of writing letters of condolence to families of deceased patients may help relieve the burden of bereavement and hasten closure for physicians as well as families. ". In this medical world, shaped by technological advances, we must maintain our humanity."

4-14 ANTIBIOTICS FOR ACUTE BRONCHITIS
      No doubt - acute viral bronchitis does not respond to antibiotics. This has led to the oft repeated admonition not to prescribe antibiotics for acute bronchitis.
      The editorialist point out that in a group of patients presenting with acute bronchitis, there will be a subset who have a bacterial infection, including pneumonia. The problem is how to separate those who would benefit from antibiotics from those who will not.
      Practical point: Primary care clinicians must use clinical judgement to suspect those patients with acute bronchitis who have a bacterial infection. Patients who are aged, have physical signs of congestion, and who appear acutely ill are more likely to fit this category.

4-15 UNDERSTANDING THE EXPERIENCE OF PAIN IN TERMINALLY ILL PATIENTS
      Although half of terminally ill patients experience moderate to severe pain, only 30% of these wanted additional pain treatment. The number of patients experiencing pain remains too high, but the number is not as large as perceived.
      Many patients are willing to tolerate pain for fear of addiction; dislike of mental or physical side effects; not wanting to take more pills or injections. Physicians must communicate more effectively that addiction to opioids given for pain relief is a myth.
      Practical point: As usual, pain control as well as other aspects of treatment must be negotiated , and concordance reached, with each individual patient.

4-16 RISK OF FRACTURE IN WOMEN WITH LOW SERUM LEVELS OF THYROID-STIMULATING HORMONE
      Older women with biochemical evidence of physiological hyperthyroidism (low TSH), mainly due to too high doses of exogenous thyroxine, but also due to endogenous "subclinical hyperthyroidism", had an increased risk of hip and vertebral fracture.
      Practical point: Consider any woman with evidence of excess thyroid hormone production or administration at risk of increased severity of osteoporosis. Exogenous thyroxine dosage must be carefully monitored.

4-17 "HIGH" EAR PIERCING AND THE RISING INCIDENE OF PERICHONDRITIS OF THE PINNA
      Young persons who pierce the upper part of the ear may develop infection resulting in life-long ear deformity.
      Practical point: We should warn our young patients about this complication, and advise them to seek early medical treatment if it arises.

4-18 TAKE HOME NALOXONE AND THE PREVENTION OF DEATHS FROM OPIATE OVERDOSE
      Practical point: Naloxone, a rapidly acting opioid antagonist will save lives of the opioid abusers who overdose. It should be given routinely, on request, to all abusers.
      We cannot abandon compassionate care of those who cannot or will not care for themselves.

4-19 ANTIBIOTIC DATABASE LAUNCHED
      Johns Hopkins has a free to all peer reviewed database presenting the latest information on antibiotics and infectious diseases. (www.hopkins-abxguide.org).
      Practical point: This easily accessed website should be most helpful to primary care clinicians.

4-20 A NEW WEB SITE AND A NEW POLICY
      The NEJM's web site has been changed from www.nejm.com to www.nejm.org. An improved search system makes it possible to search the full text of all NEJM articles as far back as 1993.
      Beginning six months after publication, the full text of all original articles and special articles will be available on line free of charge.

	Fasting plasma glucose	2h post 75 g glucose
A. Normal GT	<110	<140
B. IFG and NGT	110-140	< 140
C. NFG and IGT	< 110	140-200
D. IFG and IGT	110-140	140-200
E. "Diabetes"	140 and above or	>200 or both

IFG = Impaired fasting glucose
NFG = normal fasting glucose
NGT = normal glucose tolerance
IGT = impaired glucose tolerance

1. Population-based cohort study followed over 1300 residents of Hoorn, the Netherlands. All were age 50 to 75.
2. At baseline measured fasting plasma glucose and glucose levels 2 hours after a 75 g glucose load. None had diabetes.
3. Repeated the tests after a follow-up of 4 to 9 years. (Mean = 6 years)
4. Defined diabetes by 3 different criteria: 1) ADA, 2) WHO 1999. (The study also considered the 1985 WHO concentrations. I omitted these data. RTJ )

1. Cumulative incidence of diabetes over the mean follow-up:

   By WHO 1999	9.9%
   By ADA	8.3%

2. Cumulative incidence of progression to diabetes by WHO 1999 criteria over the mean follow-up for combinations of IGF and IGT determined at baseline:

   Category	No.	Cutoff values	Cumulative incidence (%)	Odds ratio
   Normal	1125	< 110/<140	5	1.0 (referent)
   IFG and NGT	106	10-125/<140	33	10
   NFG and IGT	80	< 110/140-200	33	10
   IFG and IGT	31	110-125/140-200	65	40

   (See preceding article for definitions. RTJ )

1. The cumulative incidence of progression to diabetes (according to the WHO 1999 criteria) of individuals who had both impaired fasting plasma glucose and impaired glucose tolerance was 65% in 6 years. Of those with normal glucose at baseline (< 110), 5% developed diabetes
2. The cumulative incidence of progression to "diabetes" depends on the definition used. The WHO criteria will diagnose diabetes more often. Screening with ADA vs the WHO 1985, and the new WHO 1999 criteria diagnosed about 1.5% to 3.8% more cases of diabetes. (Ie, the WHO 1999 is the more sensitive test; the ADA is less sensitive.
3. By ADA criteria, the cumulative incidence of diabetes over 6 years was 5% for those with normal fasting plasma glucose, and 38% for those with impaired fasting plasma glucose. (Ie, if fasting plasma glucose is 110 to 125, there is one chance in 3 that you will develop diabetes within 6 years. This is an excellent opportunity to apply lifestyle changes which will modify this adverse prognosis.)
4. Almost 2/3 of participants in this study who had both impaired fasting plasma glucose and impaired postload glucose levels at baseline progressed to diabetes within 6 years.
5. Impaired fasting glucose and impaired glucose tolerance represent 2 different physiological abnormalities: 1) IFG is caused primarily by the elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia. 2) IGT is characterized by defects in both insulin secretion and insulin sensitivity.

1. Compared initial doses recommended by the PDR (1999 and 2000) with those recommended in the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI - 1997).

1. JNC VI recommends substantially lower initial doses than the PDR for over half of 40 drugs. In almost all instances, the PDR did not recommend lower doses for elderly or frail patients.
2.  

   Examples	PDR	JNC
   Hydrochlorothiazide	25 mg	12.5 mg
   Ramipril	2.5	1.25
   Losartan	50	25
   Atenolol	50	25

1. The JNC cautions against trying to bring mild to moderate hypertension under control quickly. This is to avoid the adverse effects of too great or too abrupt a reduction in BP. (Exception - when acute target organ damage is present.)
2. Initial interventions are usually aimed at life-style modifications, giving the patient an opportunity to avoid drugs if possible. Drugs may be started later.
3. Some physicians prescribe subtherapeutic doses at the start rather than the "correct" dose.
4. Treatment of hypertension in the most commonly affected group (those over age 60) can be especially challenging because of their altered pharmacokinetics and reduced liver and kidney function, and increased receptor sensitivity. The overall incidence of ADEs in the elderly is 2 to 3 times greater than in the young.
5. Treatment of hypertension requires a flexible approach, involving a low initial dose of antihypertension drugs. The dose is often lower than that recommended by the manufacturer.

1. Prospective cohort study followed over 1900 patients who survived hospitalization for acute MI.
2. Determined self-reported average weekly consumption of alcohol in the year prior to the MI.
3. Follow-up = 4 years.

1. 53% were drinkers - 36% consumed less than 7 alcoholic drinks per week; 17% consumed more than 7 drinks per week.
2. Compared with abstainers, patients who consumed < 7 drinks per week had a lower all-cause mortality (3.4 deaths per 100 person-years vs 6.3; NNT(benefit-1 year)= 34 )
3. Those who drank 7 or more drinks weekly also had a lower all-cause mortality (2.4 deaths per 100 person-years vs 6.3 for abstainers; NNT(benefit-1year)= 25 )
4. The association was similar for cardiovascular mortality among both men and women, and among different types of alcoholic beverages.

1. Adults who abstained from alcohol prior to an acute MI appeared to be at particularly high risk of long-term mortality.
2. The results of the study are consistent with the hypothesis that light to moderate alcohol use following acute MI is safe, although studies that formally assess post-MI consumption are needed to confirm this.1
3. Determination of the risks and benefits of alcohol consumption for an individual requires consideration of numerous personal, clinical, and social factors that cannot be addressed with aggregate-level observational data.

1. Prospective population-based cohort study entered over 2200 non-institutionalized elderly persons (mean age 74) in 1982. Followed to 1996.
2. All were free of HF at baseline.
3. Determined baseline consumption of alcohol in the month preceding entry. Excluded those who consumed more than 70 oz of alcohol.
4. Maximum follow-up = 14 years. Main outcome: Time to first fatal or non-fatal HF event.

1. About half of the subjects used no alcohol; 40% used 1 to 20 oz of pure alcohol in the month prior to entry: 10% used 21 to 70 oz. (1 to 20 oz is equivalent to an average of 1 to 1.5 drinks per day; 21 to 70 oz equivalent to an average of 1.5 to 4 drinks per day.)
2. Increasing alcohol consumption in the moderate range was associated with decreased rates of HF.
3. Crude HF rates per 1000 person-years of follow-up:

   No alcohol	1 to 1.5 drinks daily	1.5 to 4 drinks daily
   16	12	9

4. After multiple adjustment for possible confounders, relative risk of HF over 14 years:

   No alcohol	1 to 1.5 drinks daily	1.5 to 4 drinks daily
   1.00 (referent)	0.8	0.5

   (Four drinks daily would not be considered "moderate". However, few subjects used this amount. RTJ )

1. Compared with no alcohol consumption, increasing levels of low to moderate consumption were associated with a lower risk of HF among community based older persons. (Although the authors did not comment, the inference was that the level of alcohol use continued during the follow-up period. RTJ )
2. There was no association with different types of alcoholic beverages. This suggests that it is pure alcohol, not the type of beverage that is associated with lower risk of HF.
3. Alcohol was associated with lower HF risk even after controlling for baseline history of MI and MI during follow-up. This suggests that the reduction in risk of MI may not substantially explain the association observed.
4. Other studies have reported moderate alcohol consumption reduces risk of diabetes and also is associated with lower BP. "Even among people with heart failure, modest alcohol consumption lowers blood pressure in the short term." But, after controlling for hypertension, diabetes and pulse pressure at baseline, the inverse relationship persisted.
5. The authors speculate that alcohol may have effects on several neurotransmitters which may reduce risk of HF.

1. Multicenter, randomized, double-blind trial entered over 3000 patients with unstable angina or non-Q-wave infarction.
2. Randomized to: 1) atorvastatin 80 mg/d (a very high dose), or 2) placebo beginning within 24 to 96 hours after presentation (mean = 63 hours).
3. Follow-up = 16 weeks.

1. No significant differences in death, non-fatal MI, or cardiac arrest.
2. No significant differences in coronary revascularization, worsening heart failure, or worsening angina.
3. The only favorable outcome was a lessening of recurrent symptomatic ischemia requiring emergency rehospitalization. (6.2% vs 8.4%; NNT (benefit 1 patient- 16 weeks) = 45)

1. In this group of patients with unstable angina and non-Q-wave infarction, atorvastatin initiated within 24 to 72 hours of onset was associated with a statistically significant reduction in emergency re-hospitalization for recurrent ischemia.
2. Although death, non-fatal MI, and cardiac arrest occurred slightly less frequently in the atorvastatin group, the differences were not statistically significant.
3. The benefit did not appear to depend on baseline LDL-cholesterol levels.
4. As expected LDL-cholesterol declined - from a mean of 124 mg/dL to 72 mg/dL
5. Atorvastatin was well tolerated. Abnormal liver transaminases (> 3 times normal) occurred in 2.5% vs 0.6% in the placebo group.

1. Used data from 2 large trials 1,2. Compared all cause mortality among patients with acute coronary syndromes who were discharged from the hospital on lipid-lowering agents (LLA) vs those discharge without.
2. Over 20 000 patients were involved, including patients with acute myocardial infarction (MI). (MI with ST elevation; non-ST elevation MI; and unstable angina. )
3. Over 3500 (18%) received lipid-lowering therapy at hospital discharge. (In addition to other appropriate drugs.)
4. Follow-up = 6 months.

1.  

   Mortality	LLA	No LLA	% Difference	NNT
   At 30 days	0.5%	1%	0.5	200 (benefit 1 patient -1 month)
   At 6 months	1.7%	3.5%	1.8	55 (benefit 1 patient- 16 months)

1. In this pooled data from 2 large international randomized trials, patients discharged on lipid-controlling therapy after hospital admission for unstable angina or acute MI had a lower mortality rate than those discharged without such therapy.
2. There was no clear association between lipid-lowering and the rate of acute MI over 6 months. (The association was only for death.)
3. The reduction in mortality was evident as early as 30 days. The absolute difference was greater at 6 months.

1. Randomly assigned over 1200 patients with multivessel disease to: 1) angioplasty (PTCA) with stenting, or 2) CABG.
2. The cardiac surgeons and interventional cardiologists agreed that the same degree of revascularization could be achieved by either procedure.
3. Follow-up = 1 year.

1. At one year, no significant differences in rates of death, stroke, or myocardial infarction (MI).
2. Among those who survived without stroke or MI, a second revascularization procedure was required more often in the stent group (17% vs 4%; 13 of every 100 patients). The event-free survival favored CABG.
3. Costs were less in the stent group despite the need for repeat procedures.

1. There was no difference between groups in rates of death, stroke, or MI.
2. More revascularization procedures (PTCA or CABG) were required in the stent group
3. Angioplasty with stenting is less invasive, less costly, and was associated with faster recovery and a better quality-of-life at 1 month.
4. CABG is associated with a lower incidence of angina, less need for anti-anginal drugs, and fewer repeat interventions in the first year.
5. Stenting can be performed with less delay than CABG. The interval between randomization and treatment was about 3 times longer in the CABG group. More adverse events will occur in this time period. (In this study 8 major events in those assigned to CABG vs 1in the PTCA-stenting group- a clinically important point.)
6. The risk of stent thrombosis may be reduced by platelet glycoprotein IIbIIIa receptor blockade or by use of heparin-coated stents.

1. Reviewed data from the NASCET1 study. Compared patients over age 75 (n = 409) with those age 65-74, and those younger than 65.
2. Assessed baseline characteristics and risk of ipsilateral ischemic stroke at 2 years by degree of stenosis and treatment group.
3. All had experienced a transient ischemic attack (TIA) or non-disabling ischemic stroke within the previous 6 months. All had 50% to 99% stenosis in the ipsilateral carotid.
4. Patients were assigned to 1) the best medical care, or 2) the best medical care plus endarterectomy.

1. Outcome at 2 years: Absolute risk reduction in ipsilateral stroke following endarterectomy, compared with medical therapy alone:

   Age over 75	29%
   65-74	15%
   < 65	10%

2. Among patients with 50-69% stenosis, the absolute risk reduction was significant only in those over age 75 (17% reduction).
3. Perioperative risk of stroke and death at any degree of stenosis:

   Age over 75	5.2%
   65-74	5.5%
   < 65	7.9%

4. The number of patients aged over 75 needed to treat with endarterectomy to prevent one ipsilateral stroke within 2 years: 70-99% stenosis 3 50-69% 6
5. The 2-year risk of ipsilateral stroke in the group receiving medical treatment alone was over 35% in those over age 75 with 70-99% stenosis, considerably higher than in those under age 75. (Ie, the benefit of surgery is this age group is partly due to the high risk of stroke in those treated without surgery.)

1. There has been unease about the performance of carotid endarterectomy in elderly persons. However, the elderly patients (> age 75) in this study benefited more than younger patients.
2. The rate of perioperative stroke and death (about 5%) in the elderly group, was actually less than in the younger groups. The investigators attributed this to a greater number of vascular risk factors in the younger group (smoking, hyperlipidemia, diabetes). The elderly patients actually had less severe carotid disease, a lower frequency of intermittent claudication, and a lower prevalence of contralateral stenosis. "It is reasonable to speculate that the paucity of risk factors in elderly patients is the consequence of the early deaths of those who had many risk factors."
3. "Our study suggests that the risk reduction of ipsilateral ischemic stroke by carotid endarterectomy in the elderly subgroup is due to a decrease in large-artery stroke and to a lesser degree in lacunar stroke." (Most lacunar strokes are caused by small penetrating artery disease. At times carotid disease may cause lacunar stroke by embolic or by hemodynamic mechanisms resulting in decreased perfusion of penetrating arteries.)
4. Elderly patients in the NASCET study represent a select group with large-artery disease. They differed from most patients in the community. They had a lower frequency of associated disease, especially cardiac disease. "Therefore we recommend carotid endarterectomy only for selected elderly patients with symptomatic carotid-artery disease."
5. "These good results can only be achieved in elderly patients after scrupulous clinical evaluation to exclude disorders that could put the patients at increased risk from anesthesia or immediate cardiac complications, and with endarterectomy done by skilled surgeons."

1. Interviewed over 950 terminally ill patients. Asked whether they wanted more pain medication, or why they did not want more.

1. Half the patients reported moderate or severe pain
2. Of those treated in primary care, 30% wanted more pain therapy; 60% wanted their therapy to remain the same; 10% wanted the therapy decreased or stopped.
3. Reasons for not wanting additional therapy included: fear of addiction; dislike of mental or physical side effects; not wanting to take more pills or injections.
4. There was no association between disease and the amount of pain; no association between the disease and the desire for more treatment.
5. Black patients were more likely to seek more pain therapy, but also to fear addiction.

1. Although the extent of pain at the end of life has received much attention as a sign of poor end-of-life care, such a conclusion is questionable. The results showed that less than a third of patients with moderate to severe pain wanted additional therapy.
2. This contrasts with the perception that despite the availability of effective analgesics, pain among terminally ill patients is undertreated. The number of terminally ill patients in substantial pain is indeed too high, but the number is not as large as perceived.
3. Most patients were willing to tolerate pain. Among dying patients, other factors were often more important than pain relief. We should not focus merely on pain. The prevalence of pain might not be the best outcome measure for the assessment of the quality of end-of-life care.
4. About a third of terminally ill patients cited aversion to the side effects of opioid analgesia - constipation and confusion - as the primary reasons for not wanting to increase treatment. In many cases patients were willing to tolerate pain to avoid troublesome side effects.
5. Fear of addiction was reported in about one third of patients. "Therefore, physicians must communicate more effectively that addiction to opioids given for pain relief is a myth, and remove this belief as a barrier to adequate analgesia. Medical use of opioid analgesics is unrelated to increase in addiction or abuse."
6. Patients of ethnic minorities have more reported pain. They are more likely to receive inadequate amounts of analgesia than white persons. Barriers include poor access to medication and inadequate prescribing, as well as fear of addiction.
7. Patients with non-cancer disease experience substantial pain at the end of life. It is a prevalent misconception that pain at the end of life is greater in patients with cancer than with other diseases. In reality, pain is prevalent in those with heart disease, chronic obstructive pulmonary disease, and other illnesses. Cardiologists, pulmonologists, and other specialists should receive adequate training in pain management.

1. Prospective cohort study followed over 650 women over age 65. (Mean age = 73)
2. At baseline, measured calcaneal bone mass, performed spine radiography, and determined history of thyroid disease.
3. Measured TSH at baseline. (Low TSH, indicating increased thyroid function, considered if under 0.1 mIU/L.) (Normal = 0.5 to 5.5)
4. Follow-up = mean of 3.7 years for evidence of new fractures.

1. About 11% of patients were currently using thyroid hormones. This accounted for 86% of the low TSH levels in the cohort.
2. TSH levels were low in about 9% of those with fractures; and in about 3% of those with no fracture.
3. After adjustment for possible confounders, women with a low TSH had a three-fold increased risk of new hip fracture and a four-fold increased risk of new vertebral fracture compared with women with normal TSH.
4. A history of hyperthyroidism was independently associated with a two-fold increase in hip fracture, even after adjustment for TSH levels and bone mineral density.

1. In this cohort, most women over age 65 with a TSH of 0.1 mIU/L or less were taking thyroxine medication.
2. Those with low TSH levels had a significantly increased risk of new hip and vertebral fractures.
3. The risk for vertebral fracture was also significantly elevated among women with borderline low TSH (0.1 to 0.5).
4. Biochemical markers of bone turnover were elevated in women with low TSH. This reflects the increased skeletal remodeling caused by excessive thyroid hormone.
5. Those receiving thyroid hormone therapy whose dose is too large (as indicated by a low TSH) should have the dose reduced. Level of TSH should be carefully maintained in the normal range.
6. Use of suppressive doses of thyroid hormone for benign conditions should be reconsidered in light of the adverse skeletal consequences of low TSH.