MEDICAL SUBJECT HEADINGS
HIGHLIGHTS-INDEX
EDITORIAL COMMENTS
Statement
from the Editor/publisher
This
index is intended to be a reference document.
Each medical subject heading is linked to one or more “Highlights and Editorial Comments” of articles abstracted during the last half of
2004. It provides a means of recalling to memory, in an evening or two, what
the editor considered new and important for primary care presented in 6
flagship journals over the 6 months.
The
numbers in the brackets refer to the full abstract. For example, [10-12] indicates the 12th abstract
published in the October issue.
Each
monthly issue for the past 5 years can be found on the website
(www.practicalpointers.org). This makes possible easy and speedy access to the
full abstract and the journal reference of all articles abstracted under an
individual MeSH.
I
hope you find the publication useful and interesting.
Richard
T. James Jr. M.D.
HOW THE ARTICLES ABSTRACTED JULY-DECEMBER 2004 INFLUENCED MY PRACTICE
MEDICAL
HEADING SUBJECTS (MeSH) JULY-DECEMBER 2004
AYURVEDIC HERBAL MEDICINE
PRODUCTS
BARIATRIC SURGERY (See OBESITY)
CALCULATING THE RISK OF
DISEASE
CANCER (See also BREAST CANCER, PROSTATE CANCER)
CANCER OF THE CERVIX (See HUMAN PAPILLOMA VIRUS)
CHOLESTEROL (See STATIN DRUGS)
FATTY LIVER DISEASE (See HEPATOBILIARY
DISEASE)
FEEDING TUBE (See DEMENTIA)
GLYCEMIC
INDEX; GLYCEMIC LOAD (See also DIABETES)
HEMOGLOBIN A1C (HbA1C; See DIABETES)
HEPATOBILIARY DISEASE (See DIABETES)
HORMONE REPLACEMENT THERAPY (See MENOPAUSE)
MEDITERRANEAN DIET (See DIET)
MICROALBUMINURIA (See DIABETES)
MIGRAINE
(See HEADACHE)
MULTIPLE CONDITIONS;
MULTIPLE MEDICATIONS
NON-ALCOHOLIC FATTY LIVER DISEASE (See DIABETES [12-3]
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (See
COX2 INHIBITORS)
POSTCHALLENGE PLASMA GLUCOSE (See DIABETES)
POSTMENOPAUSAL
HORMONE THERAPY
PROSTATE SPECIFIC ANTIGEN (See PROSTATE CANCER [7-4] [7-5] [11-5])
SHARED MEDICAL DECISION
MAKING
VITAMINS (See ANTIOXIDANTS)
HIGHLIGHTS AND EDITORIAL COMMENTS JULY TO DECEMBER 2004
ALDOSTERONE
7-10 SERUM ALDOSTERONE AND THE INCIDENCE OF
HYPERTENSION IN NON-HYPERTENSIVE PATIENTS
“All known monogenic forms of hypertension in humans can
be traced to defects in renal sodium handling.”
The potential role of aldosterone in the pathogenesis
of essential hypertension is of great interest. No studies have prospectively
evaluated the effect of serum aldosterone on the incidence of hypertension.
Do
aldosterone levels within the physiological
range influence the risk of hypertension?
Higher aldosterone levels within the normal physiologic range predispose to hypertension. For
each quartile increment of serum aldosterone there was a 16% increase in the
risk of an increase of an elevation of BP category, and a 17% increase in risk
of developing hypertension.
Relative to the lowest quartile of aldosterone, the
highest quartile was associated with a 1.6-fold risk of an elevation in BP
category and a 1.6-fold risk of developing hypertension. There was a linear
increase with each quartile.
“Increasing aldosterone levels within the physiologic
range may predispose to hypertension through promotion of sodium retention,
potentiation of action of angiotensin II, and impairment of endothelial
function.”
I abstracted
this article as a matter of interest. It has no practical importance at this
time. Watch for follow-up studies. Are we beginning to take “essential” out of
essential hypertension? RTJ
10-8 ANTIOXIDANT SUPPLEMENTS OF PREVENTION OF
GASTROINTESTINAL CANCERS
“Oxidative
stress can cause cancer.” The GI tract is thought to be the major site of
antioxidant action. Many observational epidemiological studies have reported
that high intakes of fruit and vegetables (rich in antioxidants) are associated
with a lower incidence of cancer. Results of randomized trials of one or more
selected antioxidant supplements have been contradictory.
This review identified 14 randomized trials (n = 170
000 subjects) comparing antioxidants vs
placebo for
prevention of GI cancers. The quality of the trials
was generally high.
The meta-analysis did not show any significant benefits of supplementation with
beta-carotene, vitamins A, C, and E (alone or in combination) vs placebo for esophageal, gastric,
colorectal, pancreatic and liver cancer.
An analysis
of 7 high-quality trials showed that antioxidants were associated with a significantly
increased mortality. “Our result for the detrimental effect of
antioxidant supplements on mortality was unexpected.”
Four trials
(only one was high quality) reported that selenium showed significant benefit on incidence of GI cancers.
“Our systematic review contains several major
findings.” Beta-carotene, vitamin A, and vitamin E supplements given alone or
in combination do not seem to have much effect on the prevention of
gastrointestinal cancers. Further, they seem to increase overall mortality. However, 95% confidence intervals were
large in the analysis of single cancer types and could be compatible with
either beneficial or harmful effects.
Most trials have investigated the effects of antioxidant
vitamins given at substantially higher doses than those usually found in a
balanced diet, and some trials used dosages well above the recommended upper
intake levels. This might be a cause for the absence of the expected protective
effect, and for the increase in mortality associated with high-dose antioxidant
supplements.
The results should not be translated to the potential
effects of vegetables and fruits, which are rich in antioxidants. Many
substances they contain have been postulated to have anticarcinogenic
properties. Data on the effect of fruits and vegetables on cancer have been
conflicting.
Randomized
trials set up to study prevention of lung cancer showed that beta-carotene
actually increased the risk of
disease. A trial of patients at high-risk of cardiovascular disease showed no benefit after 5 years treatment with
a supplement combination. “Antioxidant supplements are not having a good
press.”
The study
found no evidence of benefit (or harm) in the combined group of 5 cancers. However,
there were 2 important exceptions: vitamin C and selenium. There was almost no
data for vitamin C used alone in cancer prevention. For selenium there was
evidence of cancer protection, although on further analysis the benefit was
confined to liver cancer.
“The
prospect that vitamin pills may not only do no good, but also may kill their
consumers is a scary speculation given the vast quantities that are used in
certain communities.” However, these results must be considered preliminary.
Nutrient
deficiency may increase risk of disease. Replacement in deficient states may
confer benefits. But for nutritionally replete individuals, excess intake may
harm.
A randomized, placebo-controlled 7-year
trial from France (Archives Int. Med. November 22, 2004) presented evidence that low-dose antioxidant
supplements reduced total cancer incidence and all-cause mortality in men but
not in women. The issue is not yet
settled. We can advise patients that as
of this date no benefit from high-dose individual vitamins has been
demonstrated for cancer prevention.
I would discourage use of high-dose
individual vitamins. I would encourage use of supplements not exceeding the
recommended daily dose.
11-4 THE SU.VI.MAX STUDY: Trial of Health
Effects of Supplementary Antioxidants.
This study tested the efficacy of nutritional doses of supplements
containing a mixture of antioxidant vitamins and minerals in reducing incidence
of cancer, CVD, and all-cause mortality in a general population.
Subjects were randomized to: 1) vitamin-mineral supplement, or 2) placebo
daily
The daily supplement contained:
Ascorbic acid 120
mg
Vitamin E 30
mg
Beta-carotene 6
mg
Selenium 100
ug
Zinc 20
mg
There was a statistically significant
protective effect in men, but not in women:
Cancer incidence in men:
Intervention 3.5%;
Placebo 4.9%. Absolute difference = 1.4% NNT 7 years = 71
Total mortality in men
Intervention 1.6%;
Placebo 2.5% Absolute difference = 0.9% NNT 7 years = 111
The authors speculate that the difference
in outcomes of men vs women might be
due to a generally lower intake and plasma concentration of antioxidants (especially
beta-carotene) in men. Indeed, baseline serum concentrations were lower in men.
The study reinforces the general recommendation of a
life-long diversified diet containing an abundance of foods rich in
antioxidants.
Is the
putative benefit of supplements clinically important? I believe it is.
How can we
apply this information to primary care in the USA?
I believe at
this time we should advise against high doses of individual vitamins and
minerals. There is no evidence of benefit and there is evidence of possible
harm.
I believe it
is likely that any benefit from supplements will be in individuals whose
nutritional status is borderline. In primary care practice, we cannot assess
the nutritional status of every individual patient.
I believe therefore that a routine recommendation for
a daily low-dose supplement for adults is reasonable. Although in adequately
nourished individuals this may not bring any benefits in protecting against
cancer or cardiovascular disese, the supplements do contain, as an added
attraction, vitamin D and folic acid which may bring benefits.
10-4 ASPARTAME AND ITS EFFECTS ON HEALTH
Aspartame (NeutraSweet; Equal; Generic) consists of
two amino acids—phenylalanine and aspartic acid. Both are contained in normal
dietary proteins. Aspartame is 200 times sweeter than sucrose. The European
population consumes about 2000 tons annually as a substitute for sugar.
Is it
harmful? The European Scientific
Committee on Food was convinced in 1988 that aspartame was safe. The committee conducted a further review
encompassing over 500 reports in 2002.
It concluded from biochemical, clinical, and behavioral research that a
daily intake of up to 40 mg/kg/day remained entirely safe—except for people
with phenyketonuria. Does aspartame
embody a healthy way of life and reduce prevalence of obesity? In most Western
countries, sugar provides about 10% of total calories (50 g daily, or about 200
kcal). If this were entirely replaced by a non-nutritive, non-caloric sweetner,
“obesity could indeed be vanquished - assuming these calories were not
replaced”. However, evidence that
aspartame prevents weight gain or obesity is generally inconclusive.
One packet of generic aspartame contains 35 mg.
An “acceptable daily intake” = up to 3500 mg, or 100 packets, much less than
usually consumed. (Persons who drink many sweetened soft drinks daily may
approach this quantity.)
One
rounded teaspoon of sucrose (5 g) contains 20 kcal. If I added a teaspoonful of
sugar to each of my 3 cups of coffee daily in place of 3 packets of aspartime
(and all other intake remained constant) my caloric intake would increase by 60
kcal each day. By my calculation, if I added this amount to my daily caloric
intake, and assuming perfect metabolism and conversion into fat tissue, I would
gain over 5 pounds a year.
I
believe sweeteners are a reasonable ingredient in the diet of persons who tend
to be overweight and obese, and especially in persons with diabetes. Primary
care clinicians should so advise them.
Use in place of sucrose will reduce postprandial blood glucose levels
and reduce a risk factor for cardiovascular disease.
12-5 ASPIRIN USE AMONG PATIENTS WITH DIABETES
Adults with diabetes, but with no clinical cardiovascular disease, may have risk of CVD events
similar to non-diabetic adults with
established CVD.
Strategies to prevent CVD events in persons with
diabetes are underused. Aspirin effectively reduces risk of first and
subsequent myocardial infarction in patients with diabetes as well as in those
without. Many adults with diabetes do not use it.
This study assessed regular aspirin use among adults
with diabetes between 1997 and 2001.
Use remained less than ideal for patients with CVD.
One quarter of diabetic patients with established heart disease or stroke did
not use aspirin. Among those with risk factors
for CVD (hypertension, dyslipidemia, smoking) 60% did not use aspirin. Almost
2/3 of those without CVD did not use aspirin.
Overall use by women was lower than by men.
Although aspirin use in patients with diabetes is
increasing, use is suboptimal, especially in women, younger patients, and in
those with major CVD risk factors.
The
benefit/harm-cost ratio of aspirin is among the highest of any drug.
Should all
patients with diabetes take aspirin? I
believe in the great majority the benefits outweigh risks. Risks of aspirin in
younger persons with no other risk factors for CVD may outweigh benefits. But
even in younger persons the duration of diabetes should be considered.
I believe at
times primary care clinicians simply forget to recommend aspirin.
7-6 PHARMACOLOGICAL MANAGEMENT TO REDUCE
EXACERBATIONS IN ADULTS WITH ASTHMA
Exacerbations are one of the most important endpoints
for clinical trials of asthma. They represent the period of greatest risk of
emergency visits, hospitalization, and death.
Corticosteroids are potent (but nonspecific)
anti-inflammatory agents. Inhaled corticosteroids (ICS) are the single most effective therapy for adult patients with
asthma who require more than an occasional inhalation of a short-acting beta
agonist. Low doses are first-line
therapy. Since airway inflammation is present even in mild disease, inhaled
corticosteroids are first-line treatments of patients who need more than an occasional
inhalation of short-acting beta agonists. Higher doses (with or without an
added long-acting beta-agonist) can be added. With long-term therapy, risk of
adverse effects increases. Proper inhaler technique, use of a spacer, and mouth
rinsing after each actuation significantly reduce systemic absorption. Patients
should be so educated.
By themselves, long-acting inhaled beta agonists have
only a modest beneficial effect in reducing exacerbations. When added to
inhaled corticosteroids, they do help to reduce exacerbations. Monotherapy is
best avoided. It its less effective than ICS.
Lifestyle management leads to the use of a minimal
amount of medication: smoking cessation, eliminating allergens, weight loss if
overweight or obese (this has been demonstrated to reduce symptoms and improve
lung function and quality-of-life in patients with asthma). If smoking
continues, oral corticosteroids do not lead to significant improvement.
Oral corticosteroids, leukotriene modifiers, and theophylline can occasionally be used
as add-on therapy.
The treatment
table on page 373 is helpful.
Smokers
should be told—“You will not get better unless you stop smoking.”
AYURVEDIC HERBAL MEDICINE PRODUCTS
12-7 HEAVY METAL CONTENT OF AYURVEDIC HERBAL
MEDICINE PRODUCTS
Ayurvedic medicine originated in India more than 2000
years ago. It relies heavily on herbal
medicine products (HMP). HMPs are
marketed as dietary supplements under the Dietary
Supplement Health and Education Act. Proof of safety and efficacy is not
required.
Ayurvedic HMPs containing heavy metals are readily
available in the USA. This study determined the prevalence and concentrations
of heavy metals in Ayurvedic HMPs.
Fourteen of 70 (20%) HMPs tested contained heavy
metals:
No. containing Median
concentration—mg/gram Range
mg/gram
Lead 13 0.040 0.005 to 37
Mercury 6 20 0.03 to 104
Arsenic 6 0.4 0.037 to 8
Taken as recommended by the manufacturer, heavy metal
intoxication may result. One in 5 Ayurvedic HMPs produced in South Asia
contains potentially harmful levels of lead, mercury, and/or arsenic. Users are
at risk.
Traditional medicines from China, Malaysia, Mexico,
Africa, and the Middle East have also been shown to contain heavy metals.
The recent
furor over unreported adverse effects of Merck’s Vioxx led me to include this
study. Can you imagine the furor which would occur if a product of Merck was
reported to contain arsenic, mercury, or lead?
Our drug oversight system is schizophrenic.
The term
Ayur-veda comes from the Sanskrit meaning Life (health) and knowledge. Google
presents over 1 million citations. The wide range of products available, which
are said to be all “natural”, include nostrums for vitality and strength;
healthy blood and skin; healthy hair growth; proper function of the immune
system, heart, joints, muscles, kidneys, adrenal, liver, lung, and reproductive
system; mental clarity; control of blood glucose; and depression.
Mammographic screening of women between ages 50-70 can
reduce mortality from BC by about 25%. The consensus is that BC screening in
this age group is effective. Although screening is frequently offered to women
under age 50 who have a genetic predisposition, efficacy is unproven.
Preliminary results of screening studies with mammography reported a low
sensitivity for detecting BC in these women.
This study compared the efficacy of magnetic resonance
imaging (MRI) with that of
mammography for screening this group of younger, high-risk women (mean age 40).
MRI detected
32 of 45 BCs (22 of these were not visible on mammography). Missed 13 of 45
(including 5 of 6 DCIS, 4 interval cancers, and 1 detected by clinical
examination.)
Mammography detected
18 of 45 BCs (10 of which were visible on MRI)’ missed 27 (including 22 visible
on MRI), but detected more DCIS (5 of 6)
With
respect to all BCs: Sensitivity Specificity
Clinical examination 18% 98%
Mammography 40% 95%
MRI 71% 90%
In younger women at high risk for BC due to a genetic
predisposition or a strong family history.
MRI
detected more BCs than mammography ( 71%.vs 40% ). The specificity of MRI was lower
(more false positives—10% vs 5%).
MRI detected 20 cancers that were not detected by
mammography or clinical examination. Tumors tended to be smaller and positive
nodes were present in only one case.
Comment:
As usual, a
test with a high sensitivity (high % of true positive tests) is associated with
a lower specificity (high % of false
positives). In this group, MRI detected
many more BCs than mammography, but the higher false positive rate led to more
follow-up examinations and biopsies. Women age 40 have more dense breast
tissue. This makes interpretation of mammography more difficult.
I wonder if
this study might reduce the frequency of prophylactic mastectomy in high risk
women. RTJ
7-3 BREAST CANCER SCREENING WITH MRI: What Are The Data For Patients At High Risk?
The average lifetime risk of BC in American women is
one in seven. This risk increases in women with a strong family history of BC,
and an inherited mutation (BRCA genes) Women with BRCA mutations make up about
5% to 10% of women with BC. Their risk of ovarian cancer is also high.
Cumulative risk of BC of women with these mutations
range from 3% at age 30, to 50% by age 50, and to 85% at age 70. These BCs
often occur at a younger age, have “pushing margins”, a high nuclear grade, and
lack estrogen receptors. Cancers in these women grow rapidly.
MRI is highly sensitive in detecting BC. Disadvantages
include cost, variations in technique and interpretation, imperfect
specificity, and variations in enhancement during the menstrual cycle (midcycle
is optimal). MRI screening will likely be refined and standardized. “Whether
the excellent results reported can be achieved in primary care practice remains
to be determined.”
Discovering
and removing a BC in these high-risk women does not end surveillance. Screening
the remaining breast tissue must continue after surgery. Considering the
lifetime need of frequent screening and the continuous anxiety associated, I
can understand that many women would grow weary and opt for bilateral
prophylactic mastectomy RTJ
CALCULATING THE RISK OF DISEASE
7-9 CALCULATING THE RISK OF DISEASE www.yourdiseaserisk.harvard.edu
A review note in BMJ July 24, 2004; 329: 237 calls
attention to an online tool for determining an individual’s risk for five of
the most important disease groups in the USA (cancer, diabetes, heart disease,
stroke, and osteoporosis). It is
presented by The Harvard Center for Cancer Prevention, part of the Harvard
School of Public Health. It is an expanded version of the center’s cancer risk
assessment website.
The site is an interactive educational tool that seeks
to encourage healthy lifestyles. It questions the inquirer’s eating habits,
drinking, and exercise, and offers personalized tips for disease prevention.
I accessed
this site on August 13, 2004 and completed the heart disease risk evaluation.
Individuals can easily and quickly complete the 21 or more questions asked. It
includes all components of the Framingham Risk Score except HDL-cholesterol.
In addition
it asks for past history of heart disease, family history, waist size,
diabetes, 7 different questions about diet and alcohol, vitamin supplements,
and exercise.
On completion
it presents a colored risk scale (low to high) and places the individual’s
estimated risk compared with average.
A useful
addition is a list of tips on how you can reduce your individual risk. I
received 5 different tips to reduce my risk. RTJ
10-8 ANTIOXIDANT SUPPLEMENTS OF PREVENTION OF
GASTROINTESTINAL CANCERS
“Oxidative stress can cause cancer.” The GI tract is thought to be the major site of antioxidant action. Many observational epidemiological studies have reported that high intakes of fruit and vegetables (rich in antioxidants) are associated with a lower incidence of cancer. Results of randomized trials of one or more selected antioxidant supplements have been contradictory.
This review identified 14 randomized trials (n = 170 000 subjects)
comparing antioxidants vs placebo for
prevention of GI cancers. The quality of the trials was generally high.
The
meta-analysis did not show any
significant benefits of supplementation with beta-carotene, vitamins A, C, and
E (alone or in combination) vs
placebo for esophageal, gastric, colorectal, pancreatic and liver cancer.
An analysis
of 7 high-quality trials showed that antioxidants were associated with a
significantly increased mortality.
“Our result for the detrimental effect of antioxidant supplements on mortality
was unexpected.”
Four trials
(only one was high quality) reported that selenium showed significant benefit on incidence of GI cancers.
“Our systematic review contains several major findings.” Beta-carotene,
vitamin A, and vitamin E supplements given alone or in combination do not seem
to have much effect on the prevention of gastrointestinal cancers. Further,
they seem to increase overall
mortality. However, 95% confidence intervals were large in the analysis of
single cancer types and could be compatible with either beneficial or harmful
effects.
Most trials have investigated the effects of antioxidant vitamins given
at substantially higher doses than those usually found in a balanced diet, and
some trials used dosages well above the recommended upper intake levels. This
might be a cause for the absence of the expected protective effect, and for the
increase in mortality associated with high-dose antioxidant supplements.
The results should not be translated to the potential effects of
vegetables and fruits, which are rich in antioxidants. Many substances they
contain have been postulated to have anticarcinogenic properties. Data on the
effect of fruits and vegetables on cancer have been conflicting.
Randomized
trials set up to study prevention of lung cancer showed that beta-carotene
actually increased the risk of
disease. A trial of patients at high-risk of cardiovascular disease showed no benefit after 5 years treatment with
a supplement combination. “Antioxidant supplements are not having a good
press.”
The study
found no evidence of benefit (or harm) in the combined group of 5 cancers.
However, there were 2 important exceptions: vitamin C and selenium. There was
almost no data for vitamin C used alone in cancer prevention. For selenium
there was evidence of cancer protection, although on further analysis the
benefit was confined to liver cancer.
“The
prospect that vitamin pills may not only do no good, but also may kill their
consumers is a scary speculation given the vast quantities that are used in
certain communities.” However, these results must be considered preliminary.
Nutrient
deficiency may increase risk of disease. Replacement in deficient states may
confer benefits. But for nutritionally replete individuals, excess intake may
harm.
A
randomized, placebo-controlled 7-year trial from France (Archives Int. Med. November
22, 2004) presented evidence that low-dose antioxidant supplements reduced
total cancer incidence and all-cause mortality in men but not in women. The issue is not yet settled. We can advise patients that as of this date
no benefit from high-dose individual vitamins has been demonstrated for cancer
prevention.
I
would discourage use of high-dose individual vitamins. I would encourage use of
supplements not exceeding the recommended daily dose.
ABCS
OF CARDIOVASCULAR DISEASE RISK MANAGEMENT
A B C
Aspirin
Beta blocker Cholesterol management
ACE
inhibitor BP control Cigarettes
D E
Diet
and weight Exercise
Diabetes
Ejection
fraction.
I believe
checklists are of value to primary care clinicians. Many effective preventive
measures are not prescribed when they are indicated.
Most of these
applications are also applicable to primary prevention.
I believe
aspirin, beta-blockers, ACE inhibitors, statins, and antihypertension drugs are
essential components of the list. Full doses may not be needed. Administration
can go low and slow. A pill cutter can drastically reduce cost.
Life-style
changes mandatory.
My wife and I
have found checklists helpful when we go on trips. We have a list of things to
do to set the apartment straight before leaving, and a list of things we should
not forget to take along. Almost every time, on going through the lists, we
note one or two items we have forgotten.
Clinical
practice has become so complex, primary care needs more check lists, RTJ
8-6 PRIMARY PREVENTION OF CARDIOVASCULAR
DISEASE WITH ATORVASTATIN IN
Current prescription rates for lipid lowering drugs in
patients with DM2 remain low, even in patients with established cardiovascular
disease (CVD).
This study assessed the effectiveness of a 10 mg dose
of atorvastatin (Lipitor) vs placebo in primary prevention of CVD in patients with DM2. None had high
concentrations of LDL-c. The trial was stopped 2 years early because of
demonstration of significant benefit.
None had documented history of CVD. All had at least
one risk factor: retinopathy, macro- or
micro-albuminuria, current smoking, or hypertension. The risk of a major
cardiovascular event in these patients was 10% over 4 years.
Incidence of major cardiovascular events was 25 per
1000 person-years at risk in the placebo group vs 15 per 1000 person-years at
risk in the atorvastatin group. Therefore, allocation of 1000 patients to
atorvastatin would avoid 37 first major events over a 4-year follow-up. 27
patients would need to be treated for 4 years to prevent one event. [NNT (for
4 years to benefit one) = 27]
“The debate about whether all patients with DM2 warrant statin therapy should now focus on
whether any patients can reliably be identified as being at sufficiently low
risk for this safe and effective treatment to be withheld.”
These data challenge the use of a particular threshold
level of LDL-c as the sole arbiter of which patients with DM2 should receive
statin therapy (as in the case of most current guidelines). Target levels of
LDL-c (100 mg/dL) could be lowered.
An editorialist comments: The conclusions of the study—“Seems too far-fetched in view of
the available clinical trials and epidemiological data”. He cites 4 large
studies of lipid control which contained many patients with DM2. Two of the
four did not report a statistically significant reduction in coronary disease.
Two did.
Clinical trials enroll carefully selected patients.
The results cannot necessarily be extrapolated to primary care practice. Many
patients may be at low risk and the benefit/ harm-cost ratio may be too low to
warrant long-term treatment. Some may be at higher risk of adverse effects from
statins. As always, individualization is required.
I believe the
majority of patients with DM2 will benefit from statin therapy for primary
prevention. Most will have one or more additional
risk factors. There would be no question regarding secondary prevention.
Authors and
publishers persist in presenting relative benefits (rather than absolute
differences). Thus, they reiterate that treatment with atorvastatin was related
to a 37% reduction in major coronary events; a 31% reduction in coronary
revascularizations; a 48% reduction in stroke; and a 27% reduction in deaths.
This can be
very misleading. I believe statements of relative benefits should be eliminated
from published reports.
9-3 ASSOCIATION OF HEMOGLOBIN A1C WITH
CARDIOVASCULAR DISEASE AND MORTALITY IN ADULTS
Diabetes raises the risk of macro-vascular disease as well as micro-vascular disease. Evidence suggests that the relation between
plasma glucose and macro-disease (cardiovascular disease; CVD) is continuous and does not have obvious thresholds.
In this study of over 10 000 subjects, the risk of
CVD, CHD and mortality increased continuously as HbA1c rose. Cardiovascular
disease events increased continuously from 6.7 per 100 men with HbA1c less than
5% to 35 per 100 men with HbA1c over 7%. The risk for CHD was significantly
increased in those with HbA1c 5.0% to 5.4% compared with those with HbA1c
concentrations less than 5%. This
included individuals without
diabetes.
Each increase of HbA1c of 1% was associated with a
relative risk of 1.26 for death from any cause. The relationship was apparent in persons without known diabetes.
(Only 193 subjects had known diabetes.)
HbA1c levels were significantly associated with
all-cause mortality and coronary and cardiovascular disease even below the
threshold commonly accepted for the diagnosis of diabetes. Each increase of
HbA1c of 1% was associated with a 20% to 30% increase in mortality and
cardiovascular events. The gradient was apparent through the population range
from less than 5% up to 6.9%.
Subjects with HbA1c over 7% made up 4% of the sample
and contributed about 25% of the excess mortality.
Reduction in HbA1c levels in persons without diabetes may lessen their risk.
The
metabolism of glucose is related to risk of cardiovascular disease. A healthful
lifestyle should include attempts to control postprandial glucose levels in
patients without diabetes as well as those with diabetes. Diets containing a low glycemic load are an
important part of healthy living. RTJ
9-4 GLYCOSYLATED HEMOGLOBIN: FINALLY READY FOR
PRIME TIME AS A CARDIOVASCULAR RISK FACTOR.
The societal burden of the diabetic epidemic is being
fueled by our current lifestyle. Diabetes is just the measured tip of a much
larger “dysglycemic iceberg”.
It is now clear that fasting and 2-h PG levels well
below the diabetes cutoffs are cardiovascular risk factors. And that a
progressive relationship between PG and CVD risks extends from normal glucose
levels right into the diabetic range, with no clear lower threshold.
Evidence is accumulating that HbA1c is a progressive
risk factor for CVD in people without
diabetes as well as people with diabetes. A HbA1c level of 6.59% in a non-diabetic person predicts a higher
CVD risk than a HbA1c of 5.5%. Even after excluding individuals with a HbA1c
level of 7% and greater, with diabetes, and with a history of heart disease,
the increase in risk for CHD, CVD, and total mortality for every 1% rise in
HbA1c was 40%, 16%, and 26% respectfully.
We can conclude that HbA1c is an independent and
progressive risk factor for incident CVD regardless of diabetes status.
“Glycosylated hemoglobin level can now be added to the list of other clearly
established indicators of CVD risk.” “The presence or absence of diabetes is
likely to become less important than the level of glycosylated hemoglobin in
the assessment of CVD risk. Reducing HbA1c in both diabetic and non-diabetic
persons may reduce cardiovascular risk.”
It will be
interesting to find out the relative risks of HbA1c and hyperinsulinemia
compared with lipids. Could it be that markers of a stressed glucose-insulin
metabolism will become clinical risk indicators as important as LDL-c and
HDL-c? This would include the 2-hour
postprandial glucose as well as the HbA1c level. Could food sugars become as
important a risk factor as saturated fats? Excess sugar intake is related to
obesity and the metabolic syndrome, and in turn to hypertension,
hyperinsulinemia, and dyslipidemia.
I believe, at
the present stage of our knowledge, we should consider aberrant glucose
metabolism an important risk factor for CVD and act on it. RTJ
10-6 COXIBS AND CARDIOVASCULAR DISEASE
Recently Vioxx (a selective COX-2 inhibitor) was
removed from the market by Merck following the results of a trial designed to
test effects on adenomatous polyp formation in the colon. The data and safety
monitoring board took action to stop the study prematurely because of a
significantly increased incidence of serious thromboembolic adverse events (vs placebo) in the group receiving 25 mg
of Vioxx daily. The incidence of
myocardial infarction and thrombotic stroke in the two groups began to diverge
after a year. FDA had approved the 3 COX-2 inhibitors on the basis of trials
that typically lasted three to six months.
In the colon polyp study, which enrolled patients
without known cardiovascular disease, 3.5% of those receiving Vioxx and 1.9% of those receiving
placebo had a myocardial infarction or stroke. (Absolute difference = 1.6%; NNT to harm one patient = 63.) This amounts to an excess of 16 extra events
per 1000 treated. And this was in a group with presumably low risk.
Considering
the tens of millions of patients who were taking rofecoxib…“We are dealing with
an enormous public health issue.” “Even a fraction of a percentage excess in
the rate of serious cardiovascular events would translate into thousands of
affected persons.”
COX-2 inhibitors blunt the production of prostaglandin
I2
(a factor which protects endothelium). They do not blunt the production of
thromboxane (a risk factor for thrombosis). A single mechanism of COX-2
inhibitors (depressing I2 while leaving thromboxane intact) might elevate BP,
accelerate atherogenesis, and predispose to thrombosis. The higher the patient’s intrinsic risk of
cardiovascular disease, the more likely the manifestation of a clinically
important adverse event.
“We now
have clear evidence of an increase in cardiovascular risk that revealed itself
in a manner consistent with a mechanistic explanation that extends to all coxibs.”
How should
clinicians respond? Selective
inhibitors of COX-2 remain a rational choice for patients at low cardiovascular
risk who have had serious gastrointestinal events, especially while taking
traditional NSAIDs. “It would appear
prudent to avoid coxibs in patients who have cardiovascular disease, or who are
at risk for it.”
This
is discouraging. Primary care clinicians are often admonished not to prescribe
a new drug until it has been in general use for 2 or 3 years (unless it has
unique benefits). Two or 3 years of general use would presumably reveal any
adverse effects not demonstrated in trials. Now we find that, after 5 or more
years of general use, Vioxx has unreported and serious adverse effects. I
suspect that more established drugs will be discovered to have unsuspected
long-term serious adverse effects. This reinforces the old adage that “The best
medicine is no medicine”.
It
has long been realized that NSAIDs increase risk of hypertension and heart
failure. It appears that the risk is
augmented in patients taking COX-2 inhibitors.
The
FDA and the drug companies manufacturing other COX-2 inhibitors now must
conduct trials to determine cardiovascular risk of their products as compared
with placebo. Meanwhile, primary care clinicians should be cautious about
prescribing any coxib.
10-5 COMPARATIVE ANALYSIS OF INDIVIDUALS WITH
AND WITHOUT CHIROPRACTIC COVERAGE.
There is
evidence supporting the efficacy of chiropractic care for back pain. A
comprehensive review reported that spinal manipulation was better, and no
trials found it significantly worse, than conventional treatment.
This
retrospective study analyzed claims data covering a 4 year period. It compared
more than 700 000 health plan members who had additional chiropractic coverage vs over 1 million members without
coverage.
Compared
with those without coverage, members with chiropractic coverage had lower annual costs (by $200). They also
had a lower average back-pain
episode-related cost.
Having
coverage was associated with a 1.6% decrease in total annual health care costs.
Back pain patients
with chiropractic coverage had lower utilization of plain radiographs and MRI;
fewer hospitalizations; less surgery and inpatient care.
Chiropractic
care sought by members with insurance coverage was more often substituted for
usual medical care. It was less often an add-on care.
Patients
treated for back pain by chiropractors tend to be more satisfied than those
treated by MDs.
The study
raises the intriguing possibility that chiropractic may in fact be the more
economic approach to the management of the complex, ill-defined, recurrent, and
often refractory symptoms of back pain.
My primary advice for a patient consulting
me for back pain would be to keep on being as active as possible. Stay out of
bed. Take acetaminophen or an NSAID temporarily. In most cases the pain will
abate spontaneously. For more protracted back pain, I would not hesitate to
refer to a chiropractor well established in the community with whom I was
personally acquainted. I would not refer for conditions other than back pain.
9-8 PHYSICAL ACTIVITY, INCLUDING WALKING, AND
COGNITIVE FUNCTION IN OLDER WOMEN
This study examined the relation of long-term regular
physical activity, including walking, to cognitive function in a large cohort
of women. Higher levels of activity were associated with better cognitive
performance. On a global score combining results of all cognitive tests, women
in the second through the fifth quintile of energy expenditures scored an
average of 0.06, 0.06, 0.09, and 0.1 standard units higher than women in the
lowest quintile.
Compared with women in the lowest physical activity
quintile, those in the highest quintile had a 20% lower risk of cognitive impairment.
“In this large prospective study of older women,
higher levels of long-term regular physical activity were strongly associated
with higher levels of cognitive function and less cognitive decline. This
benefit was similar in extent to being about 3 years younger in age.” The association was not restricted to women
engaging in vigorous activity. Walking the equivalent of at least 1.5 hours per
week at a 20 to 30 minute per mile pace was also associated with better
cognitive performance.
This is an interesting,
provocative study. It is not proof of any relationship between physical
activity and cognition. Observational studies cannot prove cause and effect.
But I believe patients should be reminded of the many benefits of physical
fitness. There is now suggestive evidence of improved cognitive function.
A companion
article in this issue of JAMA (pp 1447-52) “Walking and Dementia in Physically
Capable Elderly Men”, first author Robert D Abbott, University of Virginia
School of Medicine, Charlottesville, comes to the same conclusion. RTJ
9-2 COST-RELATED MEDICATION UNDERUSE
Patients often restrict their use of prescribed
medications because of cost. Those who have chronic conditions, and require
long-term medication are most vulnerable. Underuse has been associated with
serious health consequences, increased emergency department visits and nursing
home admissions, and decrements in self-reported health status.
This nationwide survey identified of a group of
patients with chronic illnesses who reported underuse of medication and the
reasons for underuse, mostly due to costs. About 1/3 never discussed this
problem with their doctors. Most patients were never asked about cost problems.
When patients did talk about the costs, the majority found the conversation
helpful. However, many stated their prescription was never changed to a generic
or to a less expensive alternative. They received no information about which
drug(s) might be less necessary and might be excluded. Few patients were given
other forms of assistance such as referral to a social service agency,
information about programs that help pay drug costs, or where to purchase less
expensive medication.
“Very few chronically ill patients who restrict their
medication use because of cost appeared to be receiving assistance from their
health care providers.”
“Clinicians should take a more proactive role in
identifying and assisting patients who have problems paying for prescription
drugs.”
Clinicians
consider the benefit/harm ratio of all drugs they prescribe. I believe the
ratio is better expressed as benefit/harm-cost. When a prescribed drug is
expensive it would be appropriate to mention this to even the most affluent
patient. And to routinely discuss cost considerations with those less
economically advantaged. Rapport with social services is most helpful.
This study
raises a most important consideration in these days of patient-centered
medicine. When negotiating a treatment plan with the patient, we must arrive at
a conclusion which the patient understands and is willing and able to follow.
An expert consultation is worthless if the patient cannot or will not follow
the prescription for any reason, including costs.
I believe
most doctors have little knowledge about costs of drugs and procedures they
prescribe. They should learn. The lowest cost effective and safe program should
be offered to all patients, regardless of their economic status.
I am
convinced the American public is over-charged and over-medicated.
The drug
store pages on the internet are rapidly accessible and list prices. Drugs
ordered over the internet may be less costly than at the local pharmacy. I
believe much of the cost of drugs with a large therapeutic index (eg, statins)
can be reduced by use of a pill cutter.
An 80 mg pill may cost the same as a 20 mg pill. When cut into quarters,
the cost would be reduced by 75%. It makes little difference in the
effectiveness and safety of many drugs whether the daily dose is a few
milligrams above or below the prescribed dose. This is not applicable to drugs
with a narrow dose-range for safety and effectiveness. RTJ
10-6 COXIBS AND CARDIOVASCULAR DISEASE
Recently Vioxx (a selective COX-2 inhibitor) was
removed from the market by Merck following the results of a trial designed to
test effects on adenomatous polyp formation in the colon. The data and safety
monitoring board took action to stop the study prematurely because of a
significantly increased incidence of serious thromboembolic adverse events (vs placebo) in the group receiving 25 mg
of Vioxx daily. The incidence of
myocardial infarction and thrombotic stroke in the two groups began to diverge
after a year. FDA had approved the 3 COX-2 inhibitors on the basis of trials
that typically lasted three to six months.
In the colon polyp study, which enrolled patients
without known cardiovascular disease, 3.5% of those receiving Vioxx and 1.9% of those receiving
placebo had a myocardial infarction or stroke. (Absolute difference = 1.6%; NNT to harm one patient = 63.) This amounts to an excess of 16 extra events
per 1000 treated. And this was in a group with presumably low risk.
Considering
the tens of millions of patients who were taking rofecoxib…“We are dealing with
an enormous public health issue.” “Even a fraction of a percentage excess in
the rate of serious cardiovascular events would translate into thousands of
affected persons.”
COX-2
inhibitors blunt the production of prostaglandin I2 (a factor
which protects endothelium). They do not blunt the production of thromboxane (a
risk factor for thrombosis). A single mechanism of COX-2 inhibitors (depressing
I2
while leaving thromboxane intact) might elevate BP, accelerate atherogenesis,
and predispose to thrombosis. The
higher the patient’s intrinsic risk of cardiovascular disease, the more likely
the manifestation of a clinically important adverse event.
“We now
have clear evidence of an increase in cardiovascular risk that revealed itself
in a manner consistent with a mechanistic explanation that extends to all coxibs.”
How should
clinicians respond? Selective
inhibitors of COX-2 remain a rational choice for patients at low cardiovascular
risk who have had serious gastrointestinal events, especially while taking
traditional NSAIDs. “It would appear
prudent to avoid coxibs in patients who have cardiovascular disease, or who are
at risk for it.”
This is discouraging. Primary care
clinicians are often admonished not to prescribe a new drug until it has been
in general use for 2 or 3 years (unless it has unique benefits). Two or 3 years
of general use would presumably reveal any adverse effects not demonstrated in
trials. Now we find that, after 5 or more years of general use, Vioxx has
unreported and serious adverse effects. I suspect that more established drugs
will be discovered to have unsuspected long-term serious adverse effects. This
reinforces the old adage that “The best medicine is no medicine”.
It
has long been realized that NSAIDs increase risk of hypertension and heart
failure. It appears that the risk is
augmented in patients taking COX-2 inhibitors.
The
FDA and the drug companies manufacturing other COX-2 inhibitors now must
conduct trials to determine cardiovascular risk of their products as compared
with placebo. Meanwhile, primary care clinicians should be cautious about
prescribing any coxib.
Feeding tubes are often placed in patients with
dementia who are hospitalized for an acute illness; often contrary to the
wishes of patients and families.
A growing body of research over the past decade has
questioned the utility of placing feeding tubes in patients with advanced
dementia. There is no evidence that
feeding tubes in this population prevents aspiration, prolongs life, improves
overall function, or reduces pressure sores. Feeding tubes may adversely affect
quality-of-life. Patients may require wrist restraints to prevent pulling on
the tube. They may develop cellulitis at the site, and be deprived of the
social actions and pleasure surrounding meals.
The aim of this study was to describe the effect of
efforts of an interdisciplinary team focusing on an educational program to
change the staff’s approach to use of feeding tunes. After completion of the
program, use of feeding tubes declined dramatically. This prevented patients
from receiving futile treatment.
I omitted
details of the study, and concentrated only on a reminder that feeding tubes
may be harmful and overused in primary care practice. I do believe, however,
that use is declining. RTJ
This study examined the relationships between
sugar-sweetened beverage consumption (especially soft drinks), weight gain, and
risk of diabetes in a large cohort of young and middle-aged women.
Over the entire 10 year period, women who increased their sugar-sweetened soft
drink (S-SSD) intake from low to
high had larger increases in weight compared with women who maintained a low
intake, or substantially reduced their intake.
In contrast, women who decreased their S-SSD reduced their total energy consumption by 319
kcal/d. Women who decreased their
intake during the first 5 years and maintained a low level gained less weight
than those who increased their intake (2.8 kg. vs 4.4 kg).
Participants whose consumption of diet soft drinks increased
from one drink or less per week to more than one drink per day gained
significantly less weight (1.6 kg)
than women who decreased their intake
from one or more drinks daily to 1 drink or less per week (4.2 kg). [Ie, consumption of calorie free drinks
apparently to some extent, blunts ingestion of calorie-containing foods.]
Greater S-SSD consumption was strongly associated with
progressively higher risk of type 2 diabetes.
(RR
= 1.9 in women consuming one or more drinks per day vs those consuming less than one per month.)
Sugar-sweetened fruit punch was also associated with
increased risk of diabetes. (RR = 2.0)
“Pure” fruit juice was not associated with risk of diabetes.
Over 8 years, there were positive associations between
sugar-sweetened beverage consumption and both greater weight gain and risk of
type 2 diabetes, independent of other known risk factors.
Energy provided by sugar-sweetened beverages does not
affect subsequent food and energy intake. (Ie, little or no compensation by
reduction in intake of other foods.) Weight gain and obesity result from the
positive energy balance.
Fruit juice was not
associated with diabetes risk in this study. This suggests that naturally
occurring sugars in beverages may have different metabolic effects than added
sugars
This is an
important life-style consideration.. It convinces me to ask a screening
question, especially for overweight patients and patients with type 2
diabetes—“How many Cokes and how many Diet Cokes do you drink every week?”
Grocery
stores offer a wide range of fruit flavored drinks (fruit punches). Some
contain high amounts of fructose and sucrose. Some contain an artificial
sweetener. Look at the “Nutrition Facts” label.
A 12-oz can
of Coke contains 42 gm of sugar (high fructose corn syrup or sucrose).
A 12-oz can
of Diet Coke contains zero calories.
(Aspartame).
My “pure”
orange juice contains 36 grams of sugar per 12 oz, almost as much as 12 oz of
Coke. What is the metabolic difference?
Note also that many other foods (especially breakfast
cereals) contain a high concentration of sugar. Do these foods, in contrast to
S-SSD, have a higher satiety value?
Moral: “Give your pancreas a
break”. RTJ
8-2
SUGAR-SWEETENED SOFT DRINKS, OBESITY, AND TYPE 2 DIABETES.
When individuals include liquid carbohydrate
consumption in their diet, they do not
reduce their solid food consumption. An increase in liquid carbohydrates leads,
perversely, to even greater caloric consumption of other foods.
“A better mechanism for weight gain could not have
developed than introducing a liquid carbohydrate with calories that are not
fully compensated for by increasing satiety.”
Conversely, intake of diet (non-sugar containing) sodas is associated with a lowering of risk of childhood obesity.
“Reducing sugar-sweetened beverage consumption may be
the best single opportunity to curb the obesity epidemic.”
This
convinces me to ask a routine screening question, especially for overweight
patients and patients with type 2 diabetes. How many Cokes and how many Diet
Cokes do you drink every week?” RTJ
Hemoglobin A1c is the preferred method to monitor
long-term glycemic control. Lower levels are associated with reduced risks for
both micro- and macro-vascular diabetic complications. Current recommendations
vary: a target of 7%; 6.5%; 6% and
below.
This study (of a large cohort of apparently healthy
individuals) determined the relationships between fasting plasma glucose (fasting PG), 2-hour post-challenge
plasma glucose (2-h PG), and HbA1c
levels. All had HbA1c levels under 7%.
HbA1c vs
fasting PG:
As HbA1c increased, fasting PG gradually increased.
When HBA1c reached about 6.5%, the mean fasting PG was abnormal. (110 and
over).
HbA1c vs 2-h
PG:
As the HbA1c increased, the 2-h PG increased—much more
rapidly than the fasting PG. The top 4 deciles of HbA1c were associated with an
impaired glucose tolerance. (2-h PG over 140). This included many individuals
with HbA1c levels under 6%. The 2-h PG
is a more sensitive marker of abnormal glucose metabolism than fasting PG.
HbA1c vs
diabetes:
DM2 was diagnosed in a few individuals with HbA1c
levels as low as 5%. Prevalence of DM2
was higher in individuals with HBA1c levels 5.3% to 6%. About half of those with
HbA1c over 6.33% had DM2.
Subdivided by HbA1c levels:
Impaired glucose tolerance (%) Diabetes mellitus (%)
HbA1c below 5% 16 1
HbA1c 5% to 5.4% 37 5
HbA1c 5.5% to 6.9% 53 24
Persons with fasting PG and HbA1c levels in the upper
range of “normal” may be at increased risk of cardiovascular disease due to
increased post-meal PG levels.
An appreciable number of individuals with a normal
fasting glucose will have an abnormal 2-hour PG. Their condition may be undiagnosed and untreated. As HbA1c rises, 2-h PG increases at a much
greater rate than fasting PG levels, and contributes more to the increase in
HbA1c levels. 2-h PG is a more reliable indicator of abnormal glucose metabolism
than either fasting PG or HbA1c. And a sensitive indicator of risk of
developing diabetes.
The diagnostic use of fasting PG levels, is
suboptimal. The upper limit for HbA1c, and fasting PG (at 110) is set too high.
Only 17% of subjects in this study who had impaired GT had an abnormal fasting
PG level. This supports the recommendations of the WHO that the oral glucose
tolerance test be the main diagnostic procedure.
Most individuals with HbA1c levels between 6% and 7%
have normal fasting PG levels but abnormal 2-h post challenge PG levels.
Attempts to lower HbA1c will require treatment preferentially directed at
lowering postprandial glucose levels.
This
relatively short article presented a great deal of data.
The message
is—clinicians should depend more on the 2-h PG than on either the fasting PG or
the HbA1c to determine abnormal glucose metabolism. HbA1c is not a reliable
method for diagnosing impaired glucose tolerance or DM2. Fasting PG (even at
the new standard of 100) is not as indicative of abnormal glucose metabolism as
the postprandial PG.
As a general
life-style measure, post-meal glucose levels should be maintained at low levels
by a low glycemic load diet.
I believe
primary care clinicians, when screening for DM2, can ask their patients to come
to the office about 2 hours after a meal to have their blood glucose checked. A
GTT can be requested if the post prandial PG is high.
But, beware
of formally labeling a patient as being “diabetic” or having “abnormal glucose
tolerance” if the 2-h PG levels are not unduly high. The levels may change over
time. When diagnosed by blood tests, “Once a diabetic, always a diabetic” is
not true. Levels may change according to weight loss, and diet. Labeling may
adversely affect insurance and employment and cause anxiety.
Measuring 2-h
PG levels can lead to earlier preventive therapeutic interventions than either
HbA1c or fasting PG.
Several trials have reported that persons consuming a
low glycemic index (GI) diet weigh
less than those consuming a high GI diet. However, clinical outcomes in humans
cannot be attributed solely to GI because interventions designed to modify GI
unavoidably also influence intake of fiber, and alter palatability and energy
density.
This study, in rats and mice, examined the effects of
GI on adiposity and other endpoints.
Despite maintenance of similar body weight, rats given
high GI food gained more body fat, and had less lean body mass compared with
the low-GI animals. The GI had an independent effect on body composition. Rats
in the high GI group required less food to gain the same weight. This suggests
that they had become more metabolically efficient.
The high-GI group had greater increases over time in
the areas under the curve for blood glucose and plasma insulin, a lower plasma
adiponectin, much higher plasma
triglyceride concentrations, and severe disruption of islet-cell architecture.
“We speculate that the striking chronic primary
peripheral hyperinsulinemia induced by the high-GI diet alters nutrient
partitioning in favor of fat deposition, shunting metabolic fuels from
oxidation in muscle to storage in fat.”
This study
fits in well with the preceding articles.
I rarely
abstract studies based on animal research. We cannot confidently extrapolate
the results to humans.
As these
investigators suggest, long-term studies on effects of GI and GL in humans
would be extraordinarily difficult.
If you access
“Glycemic index” on Google, you will receive much more information on
individual foods than you may wish to know. For those seeking low GI diets,
implementation is simpler than the vast tables of numerical values of
individual foods suggest: avoid “sugar”
(sucrose), use breakfast cereals based on oats, barley and bran (and without
added sugar); use grainy breads made of whole seeds; reduce the amount of
potatoes; enjoy all types of nuts, fruits, and vegetables (except potatoes),
and eat plenty of salad vegetables with an oil dressing. Most refined foods
(bread, refined cereal, potato, and glucose and sucrose) have high GI. Most
non-starchy vegetables, fruits, legumes, and nuts have low GI.
Breakfast
cereals based on refined grains and with added sugar present a “double whammy”
The food industry is gradually improving the number of available healthy foods.
Although
controversy still exists as to the clinical importance of GI and GL, it makes
common sense to me. (But, beware of “common sense”.) RTJ
8-5 PREVALENCE, CARE, AND OUTCOMES WITH
DIET-CONTROLLED DIABETES IN GENERAL PRACTICE
By tradition, a substantial number of people with type
2 diabetes (DM2) have been managed
without medication. They are usually offered dietary advice. Irrespective of
whether patients remember or follow the advice, they are referred to as being
managed by diet alone.
This study aimed to establish the proportion of
patients with DM2 in general practice treated by diet alone. And to determine
levels of complications and quality of care received as compared with patients
on medication.
Overall, about 1/3 of patients were managed with diet
alone. But, there was a great variation between practices (16% to 73%).
Diet-alone patients were much less likely to have received monitoring for
HbA1c, BP, lipids, smoking, microalbuminuria, and foot pulses.
Patients on diet alone were more likely to have high
BP, and were less likely to receive antihypertension drugs. They were 45% more
likely to have a high cholesterol, and less likely to receive lipid-controlling
drugs.
Although some individuals might be effectively managed
by diet alone, there is a case for better surveillance and for more intensive
therapy.
I believe
that in the U.S. many patients with known diabetes are not treated and followed
as carefully as they should be. And many more who have diabetes and do not know
it are not treated at all. RTJ
8-6 PRIMARY PREVENTION OF CARDIOVASCULAR
DISEASE WITH ATORVASTATIN IN TYPE 2 DIABETES
Current prescription rates for lipid lowering drugs in
patients with DM2 remain low, even in patients with established cardiovascular
disease (CVD).
This study assessed the effectiveness of a 10 mg dose
of atorvastatin (Lipitor) vs placebo in primary prevention of CVD in patients with DM2. None had high concentrations
of LDL-c. The trial was stopped 2 years early because of demonstration of
significant benefit.
None had documented history of CVD. All had at least
one risk factor: retinopathy, macro- or
micro-albuminuria, current smoking, or hypertension. The risk of a major
cardiovascular event in these patients was 10% over 4 years.
Incidence of major cardiovascular events was 25 per
1000 person-years at risk in the placebo group vs 15 per 1000 person-years at
risk in the atorvastatin group. Therefore, allocation of 1000 patients to
atorvastatin would avoid 37 first major events over a 4-year follow-up. 27
patients would need to be treated for 4 years to prevent one event. [NNT (for
4 years to benefit one) = 27]
“The debate about whether all patients with DM2 warrant statin therapy should now focus on
whether any patients can reliably be identified as being at sufficiently low
risk for this safe and effective treatment to be withheld.”
These data challenge the use of a particular threshold
level of LDL-c as the sole arbiter of which patients with DM2 should receive
statin therapy (as in the case of most current guidelines). Target levels of
LDL-c (100 mg/dL) could be lowered.
An editorialist comments: The conclusions of the study—“Seems too far-fetched in view of
the available clinical trials and epidemiological data”. He cites 4 large
studies of lipid control which contained many patients with DM2. Two of the
four did not report a statistically significant reduction in coronary disease.
Two did.
Clinical trials enroll carefully selected patients.
The results cannot necessarily be extrapolated to primary care practice. Many
patients may be at low risk and the benefit/ harm-cost ratio may be too low to
warrant long-term treatment. Some may be at higher risk of adverse effects from
statins. As always, individualization is required.
I believe the
majority of patients with DM2 will benefit from statin therapy for primary
prevention. Most will have one or more
additional risk factors. There would be no question regarding secondary
prevention.
Authors and
publishers persist in presenting relative benefits (rather than absolute
differences). Thus, they reiterate that treatment with atorvastatin was related
to a 37% reduction in major coronary events; a 31% reduction in coronary
revascularizations; a 48% reduction in stroke; and a 27% reduction in deaths.
This can be
very misleading. I believe statements of relative benefits should be eliminated
from published reports.
9-3 ASSOCIATION OF HEMOGLOBIN A1C WITH
CARDIOVASCULAR DISEASE AND MORTALITY IN ADULTS
Diabetes raises the risk of macro-vascular disease as well as micro-vascular disease. Evidence suggests that the relation between
plasma glucose and macro-disease (cardiovascular disease; CVD) is continuous and does not have obvious thresholds.
In this study of over 10 000 subjects, the risk of
CVD, CHD and mortality increased continuously as HbA1c rose. Cardiovascular
disease events increased continuously from 6.7 per 100 men with HbA1c less than
5% to 35 per 100 men with HbA1c over 7%. The risk for CHD was significantly
increased in those with HbA1c 5.0% to 5.4% compared with those with HbA1c
concentrations less than 5%. This
included individuals without
diabetes.
Each increase of HbA1c of 1% was associated with a
relative risk of 1.26 for death from any cause. The relationship was apparent in persons without known diabetes.
(Only 193 subjects had known diabetes.)
HbA1c levels were significantly associated with
all-cause mortality and coronary and cardiovascular disease even below the
threshold commonly accepted for the diagnosis of diabetes. Each increase of
HbA1c of 1% was associated with a 20% to 30% increase in mortality and
cardiovascular events. The gradient was apparent through the population range
from less than 5% up to 6.9%.
Subjects with HbA1c over 7% made up 4% of the sample
and contributed about 25% of the excess mortality.
Reduction in HbA1c levels in persons without diabetes may lessen their risk.
The
metabolism of glucose is related to risk of cardiovascular disease. A healthful
lifestyle should include attempts to control postprandial glucose levels in
patients without diabetes as well as those with diabetes. Diets containing a low glycemic load are an
important part of healthy living. RTJ
9-4 GLYCOSYLATED HEMOGLOBIN: FINALLY READY FOR
PRIME TIME AS A CARDIOVASCULAR RISK FACTOR.
The societal burden of the diabetic epidemic is being
fueled by our current lifestyle. Diabetes is just the measured tip of a much
larger “dysglycemic iceberg”.
It is now clear that fasting and 2-h PG levels well
below the diabetes cutoffs are cardiovascular risk factors. And that a
progressive relationship between PG and CVD risks extends from normal glucose
levels right into the diabetic range, with no clear lower threshold.
Evidence is accumulating that HbA1c is a progressive
risk factor for CVD in people without
diabetes as well as people with diabetes. A HbA1c level of 6.59% in a non-diabetic person predicts a higher
CVD risk than a HbA1c of 5.5%. Even after excluding individuals with a HbA1c
level of 7% and greater, with diabetes, and with a history of heart disease,
the increase in risk for CHD, CVD, and total mortality for every 1% rise in
HbA1c was 40%, 16%, and 26% respectfully.
We can conclude that HbA1c is an independent and
progressive risk factor for incident CVD regardless of diabetes status. “Glycosylated
hemoglobin level can now be added to the list of other clearly established
indicators of CVD risk.” “The presence or absence of diabetes is likely to
become less important than the level of glycosylated hemoglobin in the
assessment of CVD risk. Reducing HbA1c in both diabetic and non-diabetic
persons may reduce cardiovascular risk.”
It will be
interesting to find out the relative risks of HbA1c and hyperinsulinemia
compared with lipids. Could it be that markers of a stressed glucose-insulin
metabolism will become clinical risk indicators as important as LDL-c and
HDL-c? This would include the 2-hour
postprandial glucose as well as the HbA1c level. Could food sugars become as
important a risk factor as saturated fats? Excess sugar intake is related to
obesity and the metabolic syndrome, and in turn to hypertension,
hyperinsulinemia, and dyslipidemia.
I believe, at
the present stage of our knowledge, we should consider aberrant glucose
metabolism an important risk factor for CVD and act on it. RTJ
10-3 POSTPRANDIAL GLUCOSE REGULATION AND
DIABETIC COMPLICATIONS.
There is
increasing evidence that postprandial hyperglycemia is implicated in the
development of cardiovascular disease. Postprandial hyperglycemia may be
directly involved in the pathogenesis of diabetes complications through its
harmful effects on the vasculature.
Several
studies have demonstrated a striking relationship between postprandial glucose
levels and cardiovascular complications. Some have reported that 2-hour glucose
is a better predictor of complications and mortality than HbA1c or the fasting
blood glucose. The risk of death in subjects with postchallenge hyperglycemia
was reported to be almost as high as in patients with previously diagnosed type
2 diabetes.
A number of
trials have demonstrated that specific pharmacological approaches can reduce
the impact of post-prandial glycemic excursions on overall glycemic control.
The disaccharidase inhibitor acarbose (Precose)
delays the digestion of complex carbohydrates in the small bowel, and blunts
postprandial hyperglycemia. Repaglinide (Prandin),
administered immediately before meals, has pharmacological actions that make it
more attractive than sulfonylureas as an acute insulin secretogogue. It
provides a more potent effect in reducing postprandial glycemic excursions.
To achieve
normal or near-normal blood glucose levels, measurement of postprandial
hyperglycemia is essential because it not only reflects glycemic exposure
during the longest period of the day, but it may also be a required target of
diabetes management to prevent the noxious effects of hyperglycemia on the
vascular wall. Controlling postprandial glucose levels can help to optimize metabolic
control and may be particularly important for prevention of vascular
complications.
This is an important sea-change in
approach to diabetes control. It goes beyond believing that “normal” fasting
glucose and HbA1c within an “acceptable” range predict adequate diabetes
control. They do not.
It
does emphasize the importance of postprandial levels of glucose. Indeed, I
believe that a 2-hour postprandial glucose at the high range of “normal” (eg.
130) will lead to greater risk of cardiovascular disease than a postprandial
glucose of 100. I suspect there is a linear relationship between post-prandial
glucose levels and vascular disease. This would lead incorporation of a low
glycemic load diet for all persons as part of a healthy lifestyle.
This
presents a practical application—routinely checking postprandial blood glucose
in the office, noting the time after the last meal. This would be much more
convenient, and more meaningful, than requiring the patient to come to the
office fasting.
See
Practical Pointers September 2004 9-3 and 9-4 for articles on relationship
between glucose control and cardiovascular disease.
11-8 PREVENTING MICROALBUMINURIA IN TYPE 2
DIABETES.
This study was designed to assess whether an
angiotensin-converting-enzyme inhibitor or a non-dihydropyridine
calcium-channel blocker, or the combination, would prevent microalbuminuria in patients with DM2 who had hypertension
and normal urinary albumin excretion.
Mean trough BP attained: Development of microalbuminuria
(%):
Trandolapril alone 139/81 Trandolapril
alone 6
Verapamil alone 141/82 Verapamil alone 11.9
Both 139/80 Both 5.7
Placebo 142/83 Placebo 10
Trandolapril alone significantly reduced the incidence
of microalbuminuria in patients with DM2.
(NNT 4 years = 25)
In subjects with DM2 and hypertension,
normoalbuminuria, and normal renal function, ACE-inhibitor therapy with
trandolapril prevented the onset of microalbuminuria. A calcium blocker did
not.
Should all
patients with DM2 receive an ACE inhibitor regardless of BP or
microalbuminuria? This study would tilt toward this application. Patients with
DM2 who have hypertension (systolic > 130) will likely develop
microalbuminuria eventually.
COST: Drug
store.com quotes telmisartan (Mavix 2 mg) about $1 per day
Enalapril
(Generic 20 mg) about 20 cents.
Note that the
target BP was not reached. ACE inhibitors have effects on the vasculature of
the kidney and other endothelium exceeding their effect on BP.
What about
angiotensin II blockers? A companion study in this issue of NEJM (pp 1952-61),
first author Anthony H Barnett, University of Birmingham, Alabama, reports
that the angiotensin II blocker
telmisartan was as effective (but not more effective) than the ACE inhibitor enalapril (Generic) in providing long-term
renoprotection in DM2. At present, ACE inhibitors are first-line therapy.
Angiotensin II inhibitors are reserved for those who cannot tolerate ACE.
12-3 HEPATOBILIARY DISEASE IN TYPE 2
DIABETES: A Narrative Review
This article discusses the spectrum of liver disease in DM2: non-alcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis C, acute liver failure, and cholelithiasis.
The insulin resistance and relative insulin deficiency in patients with DM2 affects lipid as well as carbohydrate metabolism. Insulin resistance decreases glucose uptake in the skeletal muscle and increases lipolysis from adipocytes. Lipolysis increases circulating free fatty acids. This in turn may lead to more insulin resistance and more lipolysis. Thus a vicious cycle is started. The net effect is increased storage of fat in the liver.
“Non-alcoholic fatty liver disease is the most prevalent liver disease in the USA.” NAFLD is a broad spectrum. It ranges from steatosis (bland fatty infiltration of hepatocytes), to non-alcoholic steatohepatitis (steatosis plus inflammation, necrosis, and fibrosis) and, in some patients, to end-stage liver disease and hepatocellular carcinoma. Prevalence of NAFLD is as high as 50% in patients with DM2 and obesity. (Of these, up to 50% have steatohepatitis; 19% cirrhosis).
The diagnosis is suspected in persons who do not use alcohol and have mildly elevated aminotransferase levels (AST and ALT; AST/ALT ratio greater than 1). Clinical features are non-descript. Some patients report malaise and a sense of fullness. Hepatomegaly may be present.
Imaging studies reveal a diffuse increase in echogenicity (“bright liver”). But only liver biopsy can assess the severity of damage and prognosis.
Treatment: Good metabolic control; caloric restriction (low glycemic index foods may be especially important); weight loss; exercise. Alcohol should be avoided. It is recommended that drug therapy begin with a secretogogue (a sulfonylurea) with rapid advancement to insulin therapy if control is not established. Insulin-sensitizing agents such as pioglitazone and rosiglitazone may be especially useful. The alpha-glucosidase inhibitors are also useful.
Cirrhosis, hepatocellular carcinoma, hepatitis C, acute liver failure, and cholelithiasis are also more common in patients with diabetes.
I was not aware of the frequency of NAFLD
associated with DM2
Biochemical profiles sometimes unexpectedly
report mildly increased liver enzymes. In the past, if I did not know of any
clinical indication for the elevations, I would ignore the report. This article
changes my approach. They may be indicating a significant illness which can be
treated. Glucose tolerance should be checked in these patients.
12-5 ASPIRIN USE AMONG PATIENTS WITH DIABETES
Adults with diabetes, but with no clinical cardiovascular disease, may have risk of CVD events similar to non-diabetic adults with established CVD.
Strategies to prevent CVD events in persons with diabetes are underused. Aspirin effectively reduces risk of first and subsequent myocardial infarction in patients with diabetes as well as in those without. Many adults with diabetes do not use it.
This study assessed regular aspirin use among adults with diabetes between 1997 and 2001.
Use remained less than ideal for patients with CVD. One quarter of diabetic patients with established heart disease or stroke did not use aspirin. Among those with risk factors for CVD (hypertension, dyslipidemia, smoking) 60% did not use aspirin. Almost 2/3 of those without CVD did not use aspirin.
Overall use by women was lower than by men.
Although aspirin use in patients with diabetes is increasing, use is suboptimal, especially in women, younger patients, and in those with major CVD risk factors.
The benefit/harm-cost ratio of aspirin is
among the highest of any drug.
Should all patients with diabetes take
aspirin? I believe in the great
majority the benefits outweigh risks. Risks of aspirin in younger persons with
no other risk factors for CVD may outweigh benefits. But even in younger
persons the duration of diabetes should be considered.
I believe at times primary care clinicians
simply forget to recommend aspirin.
9-5 MEDITERRANEAN DIET, LIFESTYLE FACTORS, AND
10-YEAR MORTALITY IN ELDERLY EUROPEAN MEN AND WOMEN
Because of the cumulative effect of adverse factors
throughout life, it is particularly important for older persons to adopt diet
and lifestyle practices that minimize their risk of death and morbidity and
maximize their prospects for healthful aging.
This study investigated the association of dietary
patterns and lifestyle factors with mortality in elderly men and women in 11
European countries.
Followed a cohort of over 1500 apparently healthy men
and over 800 apparently healthy women age 70-90 (mean = 75) at baseline.
Investigated the single and combined effect of 4
factors (Mediterranean diet, being physically active, moderate alcohol use, and
non-smoking) on mortality.
Each of the 4 factors was individually associated with
lower mortality rates from CHD, CVD, cancer, and all causes.
Individuals with 2, 3, or 4 low-risk factors had a
significantly and progressively lower mortality compared with individuals with
0 or 1 low-risk factors.
Among individuals age 70 to 90, adherence to a MD and
healthful lifestyles was associated with a more than 50% lower risk of
mortality over 10 years.
There was no
indication of the life-style habits in these persons during their earlier life.
I suspect the habits were the same when they were young as when they aged.
Have we
finally found the Fountain of Youth, or at least taken a sip from it? RTJ
10-10 EFFECTIVENESS OF PRIMARY CARE-BASED
VESTIBULAR REHABILITATION FOR CHRONIC DIZZINESS
The central
element of vestibular rehabilitation (VR)
is a program of graded exercises that consists of eye, head, and body movements
designed to stimulate the vestibular systems. The simulation promotes central
compensation—neurologic adaptation to the altered input from the damaged
labyrinth. The exercises also help patients overcome fear, and to regain skill
and confidence in balance. Vestibular rehabilitation may be an effective
treatment for dizziness resulting from many causes. It is a simple therapy with no requirement for equipment. It is
highly suitable for primary care.
It is
applicable only to patients with dizziness associated with head movement.
The study
reported that, at 3 months, improvement occurred in all 5 primary outcome
measures in the VR group. Of 83 treated patients, 67% reported clinically
significant improvement compared with 38% of the usual care group; (NNT = 3). Improvement was maintained at 6 months.
The success
of VR relies on the willingness of patients to practice daily movements that
may make their symptoms worse initially. Patients should be informed of this
and that recovery may be partial. Only those who are committed should be
accepted into treatment.
“Our study
provides substantive demonstration that it is feasible to offer an effective,
inexpensive treatment to patients with dizziness in primary care.” A single
brief session with a nurse was sufficient.
This application requires an enthusiastic
mentor and a willing patient. But, this is not a reason to refrain from
recommending the procedure. RTJ
10-11 VESTIBULAR EXERCISES FOR BALANCE CONTROL: Easy,
Inexpensive, and Effective
Movement-provoked
dizziness is a typical sign of vestibular origin and therefore should respond
to vestibular rehabilitation. The response mechanism seems to be central
nervous system plasticity, a specific sensorio-motor rearrangement which can
compensate for peripheral and central neurological defects.
To
facilitate control capacities, we should expose patients to increasingly
unstable body positions. Exercise rehabilitation should begin as early as
possible, ideally immediately after symptom onset.
“This
important study strikingly demonstrates that daily vestibular exercises in the
aging population reduce symptoms, postural instability, handicaps, and falls
due to dizziness.” “These findings place the onus on primary care physicians to
put into practice such an inexpensive, simple-to-perform treatment.”
I believe other balance exercises may
benefit: e.g. standing still on one foot; walking in tandem heel to toe.
The objective is to fatigue an old symptom
and train a new one.
See
the preceding abstract for description of the exercises. RTJ
11-2 THE FAMILY HISTORY—More Important Than Ever
“Today, with medicine poised at the dawn of the
genomic era, it is seductive to believe that such high-tech options have
already become the most important genomic tools in health care.” However, as so often happens in medicine, new
developments do not eclipse the tried-and-true method; instead, they give it
new meaning and power.
Most diseases are the result of the interactions of
multiple genes and environmental factors.
Almost every patient today has access to a free,
well-proven, personalized genomic tool that captures many of these interactions
and can serve as the cornerstone for individualized disease prevention. This
valuable tool is the family history (FH).
It will remain highly relevant for years to come.
Government agencies are now spearheading a national
campaign to encourage families to record their health histories. Thanksgiving
Day, when families traditionally gather, has been designated as the National Family History Day. This will
serve to remind us about the value of the FH.
The government has launched a web site which allows
families to collect, organize, and maintain the family history.
The article
cites several web sites. One: www.hhs.gov/familyhistory
Most elderly
patients will not have detailed information about their forebears. Individuals
now age 70 and above may not have accurate information about their
grandparents, but they can accurately add their own accounts and that of their
cousins to the FH.
11-12 MANAGEMENT OF FIBROMYALGIA SYNDROME
The diagnosis of the fibromyalgia syndrome (FMS) is based on a history of
widespread chronic, bilateral upper body, lower body, and spine pain, and the presence
of excessive tenderness on applying pressure to 11 or more of 18 specific
muscle-tendon sites. FMS has not been traced to any specific structural or
inflammatory cause.
FMS is the second most common disorder observed by
rheumatologists (after osteoarthritis). It has a prevalence of 2% in the US. It
is much more common in women. Chronic pain syndromes such as FMS are defined by
subjective symptoms. No discrete boundary separates FMS from chronic fatigue
syndrome, irritable bowel syndrome, and chronic muscular headache. Mood
disturbances are comorbid with all.
This article summarizes the findings of a report
(based on a detailed literature search) commissioned by the American Pain
Society to provide evidence-based guidelines for the optimal management of FMS.
There are major limitations to the literature. Many treatment trials are of
short duration and lack masking. No
medical therapies have been specifically approved by the FDA.
Despite the chronicity and complexity of FMS, there
are interventions that may have clinical benefit
in
primary care practice. Several drugs and non-medical therapies are suggested.
12-8 BALANCING THE RISKS AND BENEFITS OF FISH CONSUMPTION
Studies from the past 2 decades have repeatedly linked
consumption of fish—especially fish high in omega-3 fatty acids—with healthier
hearts in the aging population. A reduced risk of stroke, dementia, kidney
disease, asthma, and diabetes has also been reported.
There are risks stemming from 2 toxins—mercury and
polychlorinatedbiphenyls (PCBs)
which are found in fish living in polluted waters and in some farmed fish.
Mercury exposure and the role of the
internist:
The only important source of organic mercury
(methylmercury) is contaminated fish. Methylmercury reaches its highest levels
in large predatory species such as shark, tilefish, swordfish king mackerel,
and tuna; and in bottom feeders such as crab. A single serving of highly
contaminated fish can contain more than 200 ug of mercury. Five of the most
commonly eaten fish that are low in mercury are shrimp, canned light tuna,
salmon, pollock, and catfish.
Fish sticks and “fast food” sandwiches are commonly
made from fish low in mercury.
PCB exposure and the role of the
internist:
PolyChlorinated Biphenyls (eg, dioxin) are a mixture
of individual chemicals which are no longer produced in the USA. Prior to 1979
their use was widespread in industry. There are no known natural sources of
PCBs. They do not break down in the environment, and may remain there for very
long periods.
Fish are the main sources of concentrated PCB
exposure. The highest levels have been found in farmed salmon. (90% of salmon
consumed in the USA are farmed.) In the
past they were fed PCB-contaminated ground-up fish. The fishing industry has
started to change the way it feeds farmed fish. Contamination levels in salmon
have declined by 90%. As of March 2004, the FDA maintained that the level of
PCBs in farm-raised salmon is well below the safety standard.
The FDA emphasizes that the benefits of eating salmon
on cardiovascular health outweigh the risk from PCBs, especially for those at
highest risk.
I consider
this a legitimate point for primary care clinicians to address. Patients may be
asking about it.
I have
wondered about the omega-3 content of fish, especially farm-fed fish. The
natural content of omega-3 in fish comes up in the food chain beginning with
plankton. How much omega-3 is contained in the food fed to farmed fish?
The relation
between PCBs and cancer is very tenuous. The article cites a risk of one
additional case of cancer in 100 000 people over a 70-year lifetime.
It is
impossible for individual consumers to know the mercury and PCB content of the
fish they consume.
I believe it
reasonable for primary care clinicians to advise pregnant women and children
against eating large predatory fish. For elders, the benefits of any fish far
outweigh any risk. The good news is that older adults are the most likely to
benefit from fish consumption. I will continue to eat fish at least twice a
week,
The recent
furor over the outrageous dioxin poisoning of the now President of Ukraine will
allow us to follow the adverse effects of mega-doses in one individual.
The Internet
is packed with information about contamination of fish. Go to Google and access
salmon and mercury; and polychlorinatedbiphenyls. I included a few points from
the Internet in the abstract.
9-6 FRAILTY—AND ITS DANGEROUS EFFECTS—MIGHT BE
PREVENTABLE.
The differences between a 70-year-old who is robust
and one who is frail are easily detectable Frail old people are more
vulnerable, withdrawn, unsteady, and weak.
“In short, doctors know frailty when they see it.” The newer view moves away from the common
view that frailty is an inevitable part of old age toward a new view of frailty
as an avoidable condition. Some experts believe that frailty may some day be an
official coded disease, replete with FDA-approved treatments. It is likely that
the diagnosis will be based on both laboratory tests and physical findings.
A recent study defined frailty as having at least 3 of
5 attributes: unintentional weight
loss; muscle weakness; slow walking
speed; exhaustion; and low physical activity. These findings persist in some old persons
despite exclusion of the most common chronic illnesses. About 7% of persons
older than 65, and 20% of those over age 80 may fit the definition of frailty.
A screening tool for frailty has been described—gait speed, chair stands, and
tandem balance.
“There is a biology of frailty that may be independent
of age and specific disease states.”
I enjoyed
abstracting this article. Although somewhat “far out”, it focused on a concept
I had not thought about beforehand. We continue to search for the Fountain of
Youth.
Can we die of
“old age”? Do we require a more
definitive cause of death on the death certificate?
I believe
that, despite identical beneficial life-styles, some individuals become frailer
at a younger age than others. There is something different between them. This
is especially evident to residents of retirement communities and nursing homes.
As many studies
have demonstrated, healthful lifestyles can delay the onset of frailty and
prolong a productive and enjoyable life span. RTJ
10-9 THE EFFECT OF LONG-TERM INTAKE OF CIS
UNSATURATED FATS ON THE RISK OF GALLSTONE DISEASE IN MEN
Cholesterol
gallstones have many causes. One of the most important is hypersecretion of
cholesterol into the biliary tract. Studies report that diets high in
poly-unsaturated and mono-unsaturated fatty acids (both cis unsaturated fats)
can inhibit cholesterol excretion in the bile, and may protect against
cholesterol gallstone disease.
This study
examined long-term dietary intakes of cis unsaturated fatty acids in relation
to occurrence of gallstone disease.
After
adjustment for age and other potential confounding risk factors, the relative
risk (RR) of gallstone disease among men in the highest quintile of cis
unsaturated fats compared with the lowest quintile was 0.82.
Median
intake: Poly-unsaturated Mono-unsaturated
Lowest
quintile Highest quintile Lowest quintile Highest quintile
Grams per
day 9.0 18 19 36
“In this
large prospective study, a high intake
of cis unsaturated fats was associated with a lower risk of gallstone disease
in men. ” The inverse relationship was evident for both mono-and
poly-unsaturated fat.
Cis fatty acids have a protective effect
on risk of atherosclerotic disease. Reduction in gallstone formation may be an
added attraction.
A US population study reports 800 000
hospitalizations / year due to gallstone disease. A 20% reduction would be a
major public health advance.
GLYCEMIC INDEX; GLYCEMIC LOAD (See also DIABETES)
This study determined whether dietary composition can
influence the physiological adaptations of a weight-reducing diet as assessed
by resting energy expenditure. It also
determined if cardiovascular risk factors would be reduced on a low GL diet.
Randomized 39 overweight and obese adults (BMI at
least 27; age 18 to 40) to low calorie diets. All subjects were in generally
good health. Follow-up on diet = about 10 weeks.
The higher GL diet (lower-fat) was generally
consistent with National Cholesterol Education Program guidelines for a
heart-healthy diet.
Composition of the diets: Run-in diet Low-GL diet (higher fat)
Higher GL diet (lower fat)
% of energy needs 100 60 60
Kcal/d 2600 1500 1500
Glycemic load 287 82 205
Carbohydrate % of total kcal 49 43 65
Fat % total kcal 37 30 18
Outcomes at 10 weeks Low
GL diet Higher GL diet
A. Resting energy expenditure -96 kcal/d
(- 6%) -176 kcal/d (-11%)
(Although absolute resting energy expenditure
decreased in both groups, subjects on the low GL diet continued to burn more
calories per day than those on the higher GL diet. This would lead to more
efficient and continuing weight loss, estimated to be in the range of several
pounds per year.)
B. Perception of hunger was less in the low GL diet
subjects.
C. Insulin resistance, triglycerides, C-reactive protein, and BP improved more in the low GL diet group than in the higher GL diet.
“Incorporation of glycemic load principles into
current dietary guidelines may aid in the treatment of obesity and prevention
of cardiovascular disease and diabetes.”
This
represents a continuing sea change in our thinking about benefits and risks of
diets. What is the most beneficial
diet? Are foods with a high glycemic load,
which lead to continuing elevations in blood glucose, just as harmful as foods
containing a high load of unsaturated fats?
Our US diets
are high in sugar. I believe that a healthy diet should contain smaller amounts
of sugar. This would suggest diets similar to the Mediterranean diet which is
established as beneficial.
In the
future, food manufacturers may be inclined to list the glycemic load of their
products (especially if they are low).
“Sinus” headache may constitute one of the most common
and misdiagnosed clinical presentations of migraine. Symptoms referable to the
sinus areas are frequently reported during migraine attacks. They are not
recognized as diagnostic criteria for migraine.
This study determined the presence of migraine-type
headache (defined by the International Headache Society (IHS) classification of migraine) in patients with “sinus”
headaches. The IHS states that chronic sinusitis is not validated as a cause of HA or facial pain unless it relapses
into an acute phase.
The great majority of patients with a history of
“sinus” HA were determined to have migraine-type HA. The referral of pain to
the sinus-area may be a part of the migraine process. Overdiagnosis of “sinus”
HA contributes to under-recognition of migraine. And undertreatment.
Certainly a
clinical point worth considering. RTJ
11-9 COMBINATION OF ISOSORBIDE AND HYDRALAZINE
IN BLACKS WITH HEART FAILURE
Endothelial dysfunction, impaired bioavailability of
nitric oxide, and increased oxidant stress occur in HF. Augmentation of nitric
oxide (by the nitric oxide donor, isosorbide) may be an alternative or
supplemental approach to treatment of HF. Hydralazine may confer protection against
degradation of nitric oxide induced by
oxidative stress.
Studies have suggested that persons who identify
themselves as black may have a less active renin-angiotensin system, and lower
bioavailability of nitric oxide than those self-identified as white.
This study examined whether a fixed dose of
isosorbide/hydralazine would provide additional benefits in blacks with
advanced HF.
Black patients with grade III & IV HF were randomized to: 1) A fixed dose of isosorbide/hydralazine given
by mouth daily, or 2) Placebo. Dose =
37.5 mg hydralazine + 20 mg isosorbide dinitrate three times daily. Dose could
be increased to a total of 225/120 mg
daily depending on absence of drug-induced side effects.
The study was terminated early owing to a
significantly higher mortality in the placebo group.
(10%
vs 6%; absolute difference = 4%; NNT for 10 months = 25)
There was an absolute reduction in first
hospitalization for HF of 10%; and improvement in the quality-of-life score vs placebo of 2 points in a scale of 0
to 105.
Would not
white persons also benefit?
This
remarkable study was facilitated by the Association of Black Cardiologists. It
included patients from 161 centers. It needs independent confirmation. The
study was supported by NitroMed. I wondered why a drug company would sponsor a
study of drugs which can be readily obtained in generic form.
There is a
substantial problem in classifying individuals in the USA as “black”, and
lumping them together as African-American. See the following commentary.
“Persistent infection with high-risk HPV types is the
necessary cause of cervical cancer.” HPV-18 and HPV-16 are the most prevalent
types.
This study determined if vaccination against the
common oncogenic types of HPV (16 and 18) could prevent development of cervical
infection.
Double-blind trial randomized over 1100 healthy women
between ages 15 and 25. All were initially cytologically negative and
seronegative for 16 and 18, and negative for HPV-DNA by PCR.
Randomized to:
Three injections of: 1) HPV 16/18 vaccine formulated with an adjuvant,
or 2) Placebo injections at months 0, 1, and 6.
Vaccine efficacy against incident infection with 16/18
was 92%. Efficacy against persistent infection was 100%. It was 93% effective
against cytological abnormalities associated with 16/18. Three episodes of
atypical squamous cells of undetermined significance occurred in the vaccinated
group; 33 in the placebo group.
The vaccine was generally safe, well tolerated, and
highly immunogenic.
Other HPV
types also cause cervical cancer. The final composition of the vaccine remains
to be determined.
The long-term protective effect is still not clear.
This is very
exciting—likely to be the first vaccine to prevent cancer, and the first
licensed vaccine to prevent a sexually transmitted disease.
World-wide
implementation might be an impossible task.
7-10 SERUM ALDOSTERONE AND THE INCIDENCE OF
HYPERTENSION IN NON-HYPERTENSIVE PATIENTS
“All known monogenic forms of hypertension in humans
can be traced to defects in renal sodium handling.” The potential role of aldosterone in the pathogenesis of
essential hypertension is of great interest. No studies have prospectively
evaluated the effect of serum aldosterone on the incidence of hypertension.
Do aldosterone levels within the physiological range influence the risk of hypertension?
Higher aldosterone levels within the normal physiologic range predispose to hypertension. For
each quartile increment of serum aldosterone there was a 16% increase in the
risk of an increase of an elevation of BP category, and a 17% increase in risk
of developing hypertension.
Relative to the lowest quartile of aldosterone, the highest
quartile was associated with a 1.6-fold risk of an elevation in BP category and
a 1.6-fold risk of developing hypertension. There was a linear increase with
each quartile.
“Increasing aldosterone levels within the physiologic
range may predispose to hypertension through promotion of sodium retention,
potentiation of action of angiotensin II, and impairment of endothelial
function.”
I abstracted
this article as a matter of interest. It has no practical importance at this
time. Watch for follow-up studies. Are we beginning to take “essential” out of
essential hypertension? RTJ
9-1 SYSTOLIC HYPERTENSION IN OLDER PERSONS
Systolic hypertension (SH, or preferably isolated systolic hypertension ISH) is defined as a
systolic BP of 140 and above and a diastolic BP less than 90. Stage one ISH is
defined as systolic 140-159, and diastolic less than 90.
It is the most common form of hypertension in elderly
persons. It is a major public health issue. In persons over age 60, SH is a
much more important cardiovascular risk factor than diastolic hypertension.
Guidance for treatment comes primarily from
observational data which document increased risks in patients with ISH. The Framingham study reported a greater risk
of development of cardiovascular disease; coronary heart disease; stroke; and
heart failure in patients with stage one ISH (RRs = 1.47; 1.40; 1.42; and 1.60)
compared with normotensive patients. (Would
it then be reasonable to assume that lowering BP would reduce risks? But the
study did not consider effect of treatment. RTJ)
In one trial, the benefit of active treatment compared
with placebo reached its maximum at age 80. The RR for stroke in the oldest age
group was 0.53 vs 0.74 in age 60-69.
“Evidence suggests that older patients do benefit from treatment.”
While there is strong evidence of benefit to guide
treatment of ISH at a systolic BP of 160 and above, the evidence for treating
BP between 140 and 159 is less strong.
JNC 7 states that a BP higher than 140/90 warrants drug therapy,
irrespective of age. But— “ No randomized clinical trial evidence is available
to demonstrate that reducing a BP of 140 to 159 in older persons (to under 140)
reduces morbidity or mortality.” Although
JNC 7 states that patients should be treated to targets of less than 140 in
most cases, and less than 130 for diabetes or chronic renal disease, there are
no clinical trial data to support this recommendation.a
However, treatment should not be withheld solely
according to advanced age. This group has especially high cardiovascular risk.
Therapy should be determined by balancing potential benefits of treatment with
individual patient preference and tolerance to therapy.
a This does not suggest that there is evidence that
reducing systolic BP below 140 does not reduce risk of cardiovascular
complications. I believe there is a linear relationship between BP and risk,
extending to the lower systolic levels. The problem is to judge how vigorously
and rapidly drug treatment should be applied.
This is an
important clinical consideration for primary care. I believe many elders with
ISH are overtreated. Some articles suggest that clinicians are not doing a good
job of controlling hypertension if target levels are not reached.
Caution in
using drastic BP-reduction in elderly patients! Go slow and go low. They are sensitive to adverse effects of
drugs as well as to rapid reduction of BP. I believe many patients with ISH
(especially the very elderly) are over-treated. A home BP monitoring device
would be helpful in guiding treatment. Home BP may be lower than office BP and
allow reduction in dose of drugs. I believe slight differences in the BP
response reported between different dugs are not as meaningful as adverse
effects. I would choose the lowest dose(s) of the least expensive drug and very
gradually adjust as tolerated. I would try to get the systolic below 160, and
would be content at this level if pushing the dose higher were not well
tolerated.
The cause of elevation of systolic BP in
older persons is increased stiffness and lack of compliance of their arterial
system. Reducing the systolic BP does not remove the cause. It may reduce
incidence of CVD by lessening stress and shear forces on the arteries. RTJ
12-2 ASSOCIATION BETWEEN CARDIOVASCULAR OUTCOMES
AND ANTIHYPERTENSIVE DRUG TREATMENT IN OLDER WOMEN
This study, limited to postmenopausal women with hypertension, asked—1) What single drug is most effective in lowering risk of cardiovascular events? 2) What 2-drug combination is most effective?
Over a 6-year follow-up determined relationship between incidence of CVD and baseline use of 1) Diuretics, 2) ACE inhibitors, 3) Beta-blockers, 4) Calcium channel blockers, as monotherapy; and 5) dual therapy (combinations of two).
Used as monotherapy, the hazard ratio of CVD death calcium blocker vs diuretic = 1.55 (Ie, calcium blocker was more hazardous than diuretic, a statistically significant difference.) Neither of the other two drugs had statistically significant differences in risk as compared with diuretics.
In the subset of patients receiving dual therapy at baseline, those taking a calcium blocker + diuretic had an 85% greater risk of CVD death as compared with beta-blocker + diuretic.
There were no statistically significant differences between other combinations and risk of CVD.
In prevention of CVD in women with hypertension (and no history of cardiovascular disease) monotherapy with diuretics was equal or superior to monotherapy beta-blockers, ACE inhibitors or calcium blockers in preventing CVD complications.
Dual combination therapy with a calcium blocker + a diuretic was associated with higher CVD mortality than ACE inhibitors + diuretics and beta-blocker + diuretics.
The practical point for primary care
clinicians: The less expensive
diuretics and beta-blockers, and the combination, are in no way inferior to any
other antihypertension drugs. Unless there is a strong indication for ACE
inhibitors or calcium blockers, or unless there is intolerance to diuretics or
beta-blockers, a diuretic or a beta-blocker or the combination should be
first-line therapy.
I would use relatively low-dose of thiazide
(not over 25 mg hydrochlorothiazide), and then add a beta-blocker.
11-3 DOSE SPARING WITH INTRADERMAL INJECTION OF INFLUENZA
VACCINE
This randomized trial compared the immunogenicity and
safety of intradermal vs standard
intramuscular vaccine.
Healthy young adults were randomized to a single dose
of: 1) Intramuscular injection of the standard 0.5 mL of trivalent vaccine
containing at least 15 ug of hemagglutinin per strain, or 2) Intradermal
injection of 0.1 mL containing at least 3 ug of hemagglutinin per strain. Injections were made in the deltoid region.
Subjects who received the intradermal injections (1/5
the standard dose) had increases in hemagglutination-inhibition antibody (HAI)
titers by a factor of 12 to 19 for the three strains. This was similar to the
intramuscular response (factors of 7 to 15).
On day 21, seroconversion and seroprotection rates
were similar between groups.
The data clearly show that intradermal injection of 1/5 the dose the standard dose of
commercial vaccine elicits immune responses that are similar or superior to
those elicited by a full dose of vaccine given intramuscularly to healthy young
adults. It is generally accepted that the HAI response represents a fair
surrogate marker for protection.
In times of
vaccine shortage, we must decide whether to vaccinate a relatively few
intramuscularly and induce a known response, or vaccinate many more
intradermally with the hope of inducing a protective response in the majority.
At present, I would be inclined to use the full intramuscular dose in elderly
infirm persons, nursing home residents, and in those with impaired immunity and
chronic diseases such as asthma, heart and lung disease. If the supply were
greatly impaired, and I had no other choice, I would give the ID dose. Combined
half-dose IM and ID doses would save some vaccine.(And perhaps lead to greater
immunity.)
The
possibility of a pandemic of flu (predicted by many authorities as inevitable)
would make ID vaccination more applicable.
Obviously the
ID dose is preferable to no dose. I believe smaller doses, both IM and ID, will
produce an adequate response in many persons.
Make sure the
injection is not made into fat tissue. Immune response will be inadequate. In
very obese persons, an intradermal injection may be preferable. The standard needle might not reach muscle.
I remember a
vaccine shortage in the late 1950s or early 60s. We opted to give (on an
empirical basis) intradermal vaccine to many more recipients than would have
received it if the vaccine were given IM at full dose. We had no data on the
response. Now it seems this was not such a bad idea.
Patients with IBS have a health-related quality of
life (HRQOL) that may be significantly
worse than some other chronic diseases such as diabetes and end-stage kidney
disease.
This study identified a concise set of mental and
physical factors in patients with IBS that might lead to physician’s gaining
better insight into these patients.
Seven factors independently predicted physical HRQOL: 1) more than 5 physician visits per year; 2)
tiring easily; 3) low in energy; 4) severe symptoms; 5) predominantly pain
symptoms; 6) feeling that there is something seriously wrong with body; 7) symptom
flares longer than 24 hours.
Other factors independently predicted mental HRQOL: 1) feeling tense; 2)
feeling nervous; 3) feeling hopeless; 4) difficulty sleeping; 5) tiring easily;
6) low sexual interest; 7) IBS symptoms interfere with sexual interest.
HRQOL in patients with IBS is primarily lowered by extraintestinal symptoms rather than
traditional gastrointestinal symptoms.
By screening for predictors
of HRQOL, physicians may be in a position to initiate effective, timely, and
self-empowering therapy. Addressing HRQOL allows clinicians to better
understand patient’s needs and modify care-seeking patterns.
Instead of focusing on physiological epiphenomena
(stool frequency, stool characteristics, and subtype of IBS) physicians might
better serve the patient by gauging global
symptom severity, addressing anxiety, and identifying and helping the patient
to eliminate factors contributing to chronic stress.
This begs the
question – Exactly how should the busy primary care clinician respond to these
suggestions?
A basic
function of primary care is to get to know the patient as a person. Merely
allowing the patient to recognize and ventilate these HRQOL problems and
validating them may in itself be therapeutic. It does not follow necessarily
that improving the patient’s HRQOL will reduce symptoms of IBS. Improving HRQOL
in itself is beneficial.
While we
continue to seek a pathophysiogical basis for IBS and assess various new drug
treatments, we already have a meaningful therapeutic approach. RTJ
11-11 LEFT VENTRICULAR HYPERTROPHY: The Next Silent Killer?
Even mild increases in BP are associated with
increased left ventricular mass (LV
mass).
Left ventricular hypertrophy (LVH) is a risk factor for premature death and cardiovascular
events. The Framingham study has reported that LVH, as confirmed by ECG, is
associated with a mortality rate as high as that associated with a Q-wave
myocardial infarction.
LVH associated with hypertension appears to be
reversible. A long-term reduction in BP is associated with reductions LV mass.
Two articles in this issue of JAMA report that
reductions in left ventricular mass in the setting of treatment for hypertension
correlate with long-term cardiovascular outcomes. The first trial of
hypertensive patients with LVH documented by ECG criteria, reported the greater
the treatment-decrease in ECG markers of LVH, the greater the reduction in
cardiovascular events. The second trial
reported data obtained by echocardiography. Over time, reductions in LV mass
with treatment of hypertension were associated with reduced risk of
cardiovascular events.
“Active efforts to reduce left ventricular mass may
have important clinical benefits.”
Treatment to reduce LV mass may follow a course similar to reductions in
cholesterol and BP.
I believe
this is a clinically important point. Many primary care clinicians will have
ECG available. If LVH is present, extra efforts should be taken to treat
hypertension. A more careful follow-up
is warranted.
12-9 PEGAPTANIB FOR NEOVASCULAR AGE-RELATED
MACULAR DEGENERATION
Extensive evidence has suggested a causal role of vascular endothelial growth factor (VEGF) in diseases of the eye in which
neovascularization and increased vascular permeability occur.
Neovascularization in ARMD is dependent on VEGF. It is
characterized by choroidal neovascularization that involves the subretinal
space, often leading to exudation and hemorrhage, followed by a fibrovascular
scar. Loss of central vision results.
Now a specific antagonist to VEGF (Peg-aptanib) is
being tested in the treatment of neovascular ARMD. Peg-aptanib binds to and
blocks activity of extracellular VEGF.
Results favored peg-aptanib. Fewer patients lost more
than 15 letters. Fewer patients had severe visual loss. Some maintained or
gained visual acuity.
This, of
course, is not a practical point at this time.
I considered the ray of hope to be interesting enough to include.
8-7 SHORT-TERM MENOPAUSAL HORMONE THERAPY FOR
SYMPTOM RELIEF
Hormone therapy (HT)
provides the most effective relief of menopausal symptoms. Recently caution has
been recommended because of an associated increase in risks of coronary heart
disease (CHD), stroke, breast cancer
(BC), and pulmonary embolism (PE). However, the average risk is very
low—7 additional cases of CHD events, 8 more strokes, 8 more PEs, and 8 more
BCs per 10 000 women each year. (3
chances per 1000/year.)
HT is associated with small losses in life expectancy.
It is inappropriate for primary
prevention of chronic disease. There is no place for its use in
asymptomatic women.
This study identified women who would benefit from
short-term HT by exploring the trade-off between relief of menopausal symptoms
and risks of inducing disease.
Among women at low risk for CHD (no risk factors) , HT
extended quality-adjusted life expectancy (QALE) even if menopausal symptoms were mild
(reducing quality of life by as little as 4%). Among women at high CHD risk (3
risk factors), HT extended QALE if symptoms lowered quality of life by 12% or
more.
“Whether short-term is beneficial or harmful depends
primarily on a woman’s treatment goals, the severity of her estrogen-responsive
symptoms, and her cardiovascular disease risk.” Each woman’s values must be
incorporated into the HT decision. Is she willing to accept a very small risk
of breast cancer; coronary events; stroke; in order to be free of menopausal
symptoms?
If the goal is to maximize QALE, HT can be beneficial,
especially among women at low CVD risk, even when menopausal symptoms are mild.
The decision to use HT depends on its efficacy in
alleviating symptoms. Not all symptoms during perimenopause are due to
declining estrogen levels. Not all respond to HT. There is a large placebo
effect. Clinical trials examining the impact of HT on symptoms suggest that a
1-month trial is sufficient to determine response. If response is not
satisfactory, HT may be withdrawn.
I have found
results of simulating “models” unhelpful in primary care practice. They cannot
readily be applied to individuals. However, they may tilt clinicians toward or
against using certain interventions, especially if there are other studies
indicating a balance of benefit to harm.
A 12%
reduction in quality of life seems to me to be a relatively small reduction. I believe
if HT improved symptoms and QOL in
women with such a moderate reduction of QOL, it would be much more
strongly indicated in women with severe symptoms (eg, a 50% reduction in QOL.)
Treatment-associated
risks increase with duration of HT.
American College of Obstetricians and Gynecologists is considering
advising short-term HT (less than 5 years) for control of menopausal symptoms.
Estrogen-alone
therapy (in hysterectomized women) is much safer than combined
estrogen/progestin.
I believe
most primary care clinicians are generous in prescribing HT. The dose of HT
should be kept as low as possible to relieve symptoms, and continued for as
short a time as is necessary.
I would be
more hesitant to prescribe HT for a woman who smokes, has high BP, diabetes or
glucose intolerance, uncontrolled lipids, a strong family history of BC, is a
carrier of the breast cancer gene, or has a past history of BC or CVD. RTJ
MULTIPLE CONDITIONS;
MULTIPLE MEDICATIONS
12-1 POTENTIAL PITFALLS OF DISEASE-SPECIFIC
GUIDELINES FOR PATIENTS WITH MULTIPLE CONDITIONS
Primary care clinicians are encouraged to adhere to
evidence-based guidelines for the management of specific diseases. The goal is
to maximize benefits, including prevention of disease-specific outcomes,
deaths, and hospitalizations.
For patients with several coexisting health
conditions, the long-term net benefits and harms of the combination of all
medications taken in adherence to disease-specific guidelines is less clear.
Twenty percent of Medicare beneficiaries have 5 or more chronic conditions, and
50% are receiving 5 or more drugs. Take, for instance, a 70-year old woman who
has hypertension, a past myocardial infarction, depression, diabetes, and
osteoporosis. According to guidelines she should be receiving aspirin, a
beta-blocker, and ACE inhibitor, a bisphosphonate, calcium, a diuretic, a SSRI,
a statin, a sulfonylurea, and perhaps a thiazolidinedione and vitamin D.
What added benefit (and added harm) does the 7th,
8th, or 9th medication provide over the 2nd or
3rd? The risk of adverse effects increases as the number of
medications (and the length of time they
are taken) increases.
The prevalence of problems associated with multiple
medications is probably underestimated. The broader physical, cognitive,
psychological, and other effects remain unknown and unexplored. Patients,
especially the elderly, and those with multiple complaints, vary in regard to
the importance they place on health outcomes such as longer survival, the
prevention of specific disease events, physical and cognitive functioning, and
the amount of inconvenience and risk of adverse effects (and costs) they are willing to tolerate.
Elderly
patients with multiple health problems who are receiving long-term,
multiple-drug therapy present an important clinical problem. I believe older
patients take too much medicine.
We have no
way of knowing the benefits or adverse effects of multiple-drug combinations.
No randomized trial has considered (or can consider) effects of a particular
combination of 10 drugs with another 10 drugs, or with placebo. For example, an
elderly patient takes 10 different drugs. [1, 2, 3, 4, 5, 6, 7, 8, 9,10]. Does drug 4 (even though medically indicated)
add to her quality and length of life? We have no way of determining this. No
conclusive randomized trial will, or can, be conducted comparing: 1) a group
taking 9 drugs (omitting drug 4) with 2) a group taking all 10 drugs. I believe
the benefit obtained from each of the 10 drugs would be much less for a patient
taking 10 drugs than for a patient taking only one drug for one indication. I
also believe that taking all 10 would be associated with more adverse effects
than taking 9.
Clinicians
(including myself), when presented with a new complaint by an elderly patient
often automatically prescribe a drug for which the basis of benefit is
established when prescribed for a lone condition. Multiple conditions and
multiple drugs confuse the clinical picture. We should think twice.
Will adding a
new drug really increase length and quality of life? Will it provide additional
comfort? By how much? At what
cost? Certainly many drugs given to
younger patients for a specific condition do effectively prolong quality and
length of life. But for elderly patients receiving multiple drugs little may be
gained and much lost. Consider an elderly patient with limited life expectancy
who is receiving multiple drugs, all with established benefits when used as
lone therapy for a younger person. Will lowering her LDL-cholesterol from 130
to 100 enhance her length and quality of life? Will lowering his systolic BP
from 170 to 140? Will increasing her
bone density by 3%? Will lowering her HbA1c from 8% to 7%?
Periodically,
I read in the newspaper of an elderly, economically disadvantaged, couple who
must choose between paying for their medications or paying the rent. I feel
compassion. I also think—How necessary
are the drugs they are struggling to pay for? Do all of them add length and
quality to their lives?
How should
clinicians respond to this problem?
There is no “scientific” answer. It depends on “clinical judgment” by
the clinician and the informed preference of the patient. Patients should be
able to judge for themselves the risks vs costs and harms. (Although at the
practical clinical level this maybe impossible.) I believe short-term
symptom-relieving drugs are more likely to improve quality-of-life in an elder
than long-term risk-reducing medication. Regarding the illustrative patient,
the SSRI may be the most important drug she receives.
When
consulting with an elderly patient with multiple complaints who is receiving
multiple medications ask--How do you feel?
If “poorly”, perhaps it might best to remove a drug instead of adding
one.
What is the
primary care clinician to do when consulting with 80-year-old Mrs. Jones who is
already receiving multiple medications and presents with a new complaint which
may lead to her receiving yet another long-term drug? “Mrs. Jones, I can prescribe a drug for your condition, but I do
not know if, when added to the other drugs your are taking, you will be
benefited or harmed. If you do wish to take an added drug, it is very important
that you let me know soon whether it really makes you feel better.”
This study examined the relationships between
sugar-sweetened beverage consumption (especially soft drinks), weight gain, and
risk of diabetes in a large cohort of young and middle-aged women.
Over the entire 10 year period, women who increased their sugar-sweetened soft
drink (S-SSD) intake from low to
high had larger increases in weight compared with women who maintained a low
intake, or substantially reduced their intake.
In contrast, women who decreased their S-SSD reduced their total energy consumption by 319
kcal/d. Women who decreased their
intake during the first 5 years and maintained a low level gained less weight
than those who increased their intake (2.8 kg. vs 4.4 kg).
Participants whose consumption of diet soft drinks increased
from one drink or less per week to more than one drink per day gained
significantly less weight (1.6 kg)
than women who decreased their intake
from one or more drinks daily to 1 drink or less per week (4.2 kg). [Ie, consumption of calorie free drinks
apparently to some extent, blunts ingestion of calorie-containing foods.]
Greater S-SSD consumption was strongly associated with
progressively higher risk of type 2 diabetes.
(RR
= 1.9 in women consuming one or more drinks per day vs those consuming less than one per month.)
Sugar-sweetened fruit punch was also associated with
increased risk of diabetes. (RR = 2.0)
“Pure” fruit juice was not associated with risk of diabetes.
Over 8 years, there were positive associations between
sugar-sweetened beverage consumption and both greater weight gain and risk of
type 2 diabetes, independent of other known risk factors.
Energy provided by sugar-sweetened beverages does not
affect subsequent food and energy intake. (Ie, little or no compensation by
reduction in intake of other foods.) Weight gain and obesity result from the
positive energy balance.
Fruit juice was not
associated with diabetes risk in this study. This suggests that naturally
occurring sugars in beverages may have different metabolic effects than added
sugars.
This is an
important life-style consideration.. It convinces me to ask a screening
question, especially for overweight patients and patients with type 2
diabetes—“How many Cokes and how many Diet Cokes do you drink every week?”
Grocery
stores offer a wide range of fruit flavored drinks (fruit punches). Some
contain high amounts of fructose and sucrose. Some contain an artificial
sweetener. Look at the “Nutrition Facts” label.
A 12-oz can
of Coke contains 42 gm of sugar (high fructose corn syrup or sucrose).
A 12-oz can
of Diet Coke contains zero calories.
(Aspartame).
My “pure”
orange juice contains 36 grams of sugar per 12 oz, almost as much as 12 oz of
Coke. What is the metabolic difference?
Note also
that many other foods (especially breakfast cereals) contain a high
concentration of sugar. Do these foods, in contrast to S-SSD, have a higher
satiety value? Moral: “Give your pancreas a break”. RTJ
8-2 SUGAR-SWEETENED SOFT DRINKS, OBESITY, AND
TYPE 2 DIABETES.
When individuals include liquid carbohydrate
consumption in their diet, they do not
reduce their solid food consumption. An increase in liquid carbohydrates leads,
perversely, to even greater caloric consumption of other foods.
“A better mechanism for weight gain could not have
developed than introducing a liquid carbohydrate with calories that are not
fully compensated for by increasing satiety.”
Conversely, intake of diet (non-sugar containing) sodas is associated with a lowering of risk of childhood obesity.
“Reducing sugar-sweetened beverage consumption may be
the best single opportunity to curb the obesity epidemic.”
This
convinces me to ask a routine screening question, especially for overweight
patients and patients with type 2 diabetes. How many Cokes and how many Diet
Cokes do you drink every week?” RTJ
10-7
BARIATRIC SURGERY: A Systematic Review and Meta-Analysis
This
systematic review determined the impact of bariatric surgery on weight loss,
the effect on co-morbidities of obesity, and operative mortality.
Mean
absolute weight loss = 40 kg; mean BMI
decrease = 14. Mean percentage of excess-weight loss was 61%. In most cases,
the degree of weight loss remained the same 2 years after surgery as before.
Operative
mortality depended on the complexity of the procedure, from 0.1% for gastric
binding to 1% for bilio-pancreatic diversion and duodenal switch.
“Bariatric surgery in morbidly obese
individuals reverses, eliminates, or significantly ameliorates diabetes,
hyperlipidemia, hypertension, and obstructive sleep apnea.” It benefits the
majority of patients.
I have read that there are now more obese
individuals in the world than malnourished.
Certainly
the approach to this universal problem is not surgery. How could 8 million
persons in the USA undergo surgery? The USA needs concerted efforts to reduce
obesity, This requires co-operation between educators, food manufacturers,
public health officials, and primary care clinicians. I believe we are making
some progress. It is slow.
The mean life-expectancy had increased dramatically in the USA over the past 80 years. What an even more remarkable change would have occurred if the obesity epidemic had been prevented! RTJ
Traditional health promotion efforts have focused on the individual, relying on education, skills training, and building social support to help people change behavior. In the case of obesity, these approaches are failing. Public health officials are wondering—Why do people not listen?
This essay suggests that economics plays a large part in the obesity epidemic. Food, especially foods high in fat and sugar, have become cheaper as obesity rates have risen. Obesity rates among the poor are substantially higher than among those in higher income groups. The poor are more likely to depend on high fat, high sugar, less expensive foods As income drops, choice of foods contracts. From economists’ perspective, people are rational beings who try to attain the maximum happiness within the constraints of their circumstances such as their income, available time, and other resources. The economic situation of low-income people forces them to adopt “obesogenic” diets. Economists say if you want to change behavior, change costs.
Obesity is a low-income problem, yet we offer middle-class solutions. “We say you need to eat more fresh fruits and vegetables and to exercise more. Well, if you live in the inner city you aren’t going to suddenly start eating mangos and playing tennis.”
Another important factor affecting diet is time. In order to prepare so called “thrifty” diets you need 20 hours a week for food preparation. The typical working mother spends 5 hours a week on this task. The poor often work long hours and have long commutes. They are “time poor” as well as cash poor.
Ultimately the solution to the problem of obesity is to improve the socioeconomic situation of the poor by providing better jobs, wages, and social services. “Obesity is, profoundly, a socioeconomic issue, and medical approaches will not work.”
I enjoyed this perspective. I believe it
contains much truth. But it is certainly not the whole truth. Many economically
advantaged persons are obese. Observe in any upscale mall. (I wonder what the poor/rich ratio is
regarding obesity.)
The article will make me more compassionate
and less critical when discussing the “overweight problem” of the majority of
my patients. Some have great limitations regarding their choices of foods,
convenience of shopping, and time to prepare. For many, eating fat and sweets
is one of the pleasures of their lives. They do not want to give it up.
Cultural influences remain strong.
Disadvantaged persons are also greatly
limited in their choices of exercise. Walking through the neighborhood may be
unsafe, unpleasant, and stressful. Sidewalks may be broken and uneven. Walkers
may be harassed.
The just-published changes in the food
pyramid call for more of the same expensive foods and for more exercise. Costs,
time, and opportunity have become more limiting. Three daily glasses of skim
milk are recommended. A gallon of milk now costs me over $3. For a family of 4 or 5, this adds up.
Obviously the root causes of the obesity
epidemic have not been addressed.
A note about children: There is an effective
means of limiting fat and sweets from their diet through changes in the school
meal programs. I believe we are making headway in this regard.
8-8 APPROPRIATE USE OF OPIOIDS FOR PERSISTENT
NON-CANCER PAIN
Primary care clinicians have been torn between
opposing perspectives on use of opioids for severe non-cancer pain. Risks and
benefits continue to be debated.
Beginning in the mid-1980s, the consensus view of pain
specialists rapidly shifted toward less restrictive use. By 1997, opioid therapy for chronic pain was
described as an “extension of the basic principles of good medical practice”.
Data highlighted the variability of the population with chronic pain and showed
highly favorable outcomes in some patients who received opioid therapy. Many
patients with chronic pain who were treated with opioids for months or years
had constant pain relief, no significant toxicity, and stable or improved
function. Data confirmed that patients could handle these drugs responsibly,
without the problematic behaviors of abuse and addiction.
Unfortunately, increased medical use was associated
with heightened abuse. The burgeoning non-medical use of oxycodone and other
drugs, combined with media stories of abuse-related tragedies, seemed to
threaten medical practice with a regulatory backlash. Pain specialists
perceived that championing this therapy could not continue without a clear
focus on the risks of abuse, addiction in predisposed persons, and diversion to
an illicit market. This evolution
brought the concept of balance to the level of the individual practitioner.
Safe and effective prescribing requires skills in pharmacotherapy and in risk
assessment and management.
Current recommendations for appropriate use for
persistent non-cancer pain aim for a balance. The primary goal is comfort.
Opioid therapy is just one tool among many to manage pain.
I believe
most primary care clinicians would refer these patients to a pain center, if
available. Occasionally the burden of prescription will fall on the generalist.
I would suggest that the single main consideration for long-term opioid use
would be—“Know the patient well”. Know his personal history as well as his
medical history.
If the
sufferer lives in the community and he and his family have been known to you
for years, the risk of abuse would be minimized. RTJ
See the
abstract for web sites. RTJ
PERIPHERAL ARTERIAL DISEASE
7-7 FUNCTIONAL DECLINE IN PERIPHERAL ARTERIAL
DISEASE
Currently, many medical textbooks and review articles
report that most persons with peripheral arterial disease (PAD) and intermittent claudication experience stabilization or
improvement in their symptoms over time. However, symptoms may not correlate
with objective measurement of functional decline. It is possible that patients
with PAD reduce their activity to keep leg symptoms in check. Patient-reported
improvement or stabilization of leg symptoms may mask PAD-associated functional
decline.
This study assessed whether PAD, ankle-brachial index (ABI), and specific leg symptoms
predict functional decline over 2 years.
Lower baseline ABI values were associated with greater
mean annual decline in 6-minute walk
performance:
Patients with asymptomatic
PAD at baseline (compared with patients without PAD), had a greater mean annual
decline in 6-minute walk performance, and an increased odds ratio for becoming
unable to walk continuously for 6 minutes.
Patients with PAD who experienced leg pain at baseline
(compared to patients without PAD) had a greater decline in 6-minute walk, and
a decrease in usual-pace 4-meter walking velocity.
This challenges standard thinking about the natural
history of leg functioning in patients with PAD. In previous studies, most
patients with intermittent claudication reported improvement or stabilization
of leg symptoms over 5 years, implying a benign course. However, stabilization
or improvement of symptoms does not necessarily indicate stabilization or
improvement of leg performance.
Clinicians should consider patients with PAD to be at
increased risk of functional decline.
The prevalence of PAD among older persons is high and
often unrecognized.
PAD is a
serious, progressive, and deadly disease. It requires the same primary and
secondary prevention measures as for coronary disease.. Smokers may be told
“You will not get better until you stop smoking”.
9-8 PHYSICAL ACTIVITY, INCLUDING WALKING, AND
COGNITIVE FUNCTION IN OLDER WOMEN
This study examined the relation of long-term regular
physical activity, including walking, to cognitive function in a large cohort
of women. Higher levels of activity were associated with better cognitive performance.
On a global score combining results of all cognitive tests, women in the second
through the fifth quintile of energy expenditures scored an average of 0.06,
0.06, 0.09, and 0.1 standard units higher than women in the lowest quintile
Compared with women in the lowest physical activity
quintile, those in the highest quintile had a 20% lower risk of cognitive
impairment.
“In this large prospective study of older women,
higher levels of long-term regular physical activity were strongly associated
with higher levels of cognitive function and less cognitive decline. This
benefit was similar in extent to being about 3 years younger in age.” The association was not restricted to women
engaging in vigorous activity. Walking the equivalent of at least 1.5 hours per
week at a 20 to 30 minute per mile pace was also associated with better
cognitive performance.
This is an
interesting, provocative study. It is not proof of any relationship between
physical activity and cognition. Observational studies cannot prove cause and
effect. But I believe patients should be reminded of the many benefits of
physical fitness. There is now suggestive evidence of improved cognitive
function.
A companion
article in this issue of JAMA (pp 1447-52) “Walking and Dementia in Physically
Capable Elderly Men”, first author Robert D Abbott, University of Virginia
School of Medicine, Charlottesville, comes to the same conclusion. RTJ
10-2 QUESTIONNAIRE SURVEY ON USE OF PLACEBO
One might
surmise that clinical use of placebos is rare. The deception involved in
administering a placebo raises ethical questions. There is a dearth of
discussion about placebos in the medical literature. Almost all citations in
Medline refer to a research context. Informal discussions with clinicians
indicate that use still occurs.
This study
from Israel concerned the frequency and circumstances of use of placebo in
clinical practice, and attitudes towards its use among those who administer it.
Placebos were given in the form of saline infusions, intramuscular injections,
or vitamin C tablets. They were used for anxiety, pain, agitation, vertigo,
sleep problems, asthma, contractions in labor, withdrawal from recreational drugs.
The
majority of health care workers used placebos, some as often as once a
month. Most found them to be generally
or occasionally effective.
Ethical issues: Only 5% thought
use should be categorically prohibited. Most others considered use conditional
on circumstances such as prior experience with use, notifying the patient that
a placebo was given, or evidence from research that the placebo was effective.
“Used wisely, placebos might have a legitimate place in therapeutics.”
Placebos are fascinating. Over the ages,
myriads of humankind have received interventions which possess no possible
pharmacological benefits.
Placebos
do not cure anything. Although, by definition, a placebo pill has no more
pharmacological action than a teaspoon of water, it may have profound
psychological effects in relieving distress. I believe relief of symptoms and
lessening of anxiety in some patients may lead to faster resolution of the
illness.
We
do not use placebos to treat anemia, hypertension, or diabetes or any specific
disease for which there is established treatment. We may use them in hope of
providing relief of symptoms. Indeed, a simple (placebo) statement from the
doctor may relieve considerable anxiety and bring peace. “You will be fine, Mr.
Jones.” Response depends on the culture
in which it is presented and the enthusiasm and beliefs of the practitioner, as
well as the confidence of the recipient that it will help.
Are placebos ethical? Is their use deceptive?
Does the end justify the means? This depends on whether the practitioner
believes that there truly are benefits. It is true that placebos have no
pharmacological action. But, they may relieve symptoms even though we do not
know the mechanism. I believe placebos are a legitimate intervention in special
circumstances. They may act by providing relief and comfort while the patient
recovers naturally.
Should
clinicians disclose that they are prescribing a placebo? Would this negate
benefit? We do not explain to patients
how penicillin works. Indeed, clinicians may not know the mechanism of action
of many drugs they prescribe, and certainly do not so inform the patient. For
some beneficial drugs, an exact mechanism of action may not be established. Use
may depend solely on an empirical basis. Their use is nevertheless ethical.
I
do not believe clinicians should routinely inform the patient. If she asks,
however, I would not hesitate to disclose. I believe fully informing the
patient about possible benefits will be an adequate defense. Indeed there is
evidence that placebos initiate release of endorphins.
Should
clinicians charge for placebos? This may be a more difficult decision. I
believe most clinicians would be able to include a placebo without increasing
the charge for a consultation.
Although
extent of use may vary between individual clinicians, I believe use of placebos
is much more prevalent than acknowledged. We use the placebo effect every day
of practice. We use vast quantities of drugs for which there is no possible benefit.
This may be the most common use of placebos in modern clinical practice.
Consider the widespread use of antibiotics prescribed for viral infections.
Would not this be considered a placebo intervention? The prescription is given
to console the patient. Such use of drugs is becoming much more common now that
advertising is directed specifically to patients.
Should
placebos be used as a diagnostic tool? This could lead to erroneous and harmful
conclusions. If the patient obtains relief, some would say that their symptoms
are not due to organic disease. This is not true.
Do
you believe the “nocebo” effect? Ie,
are some interventions which have no possible pharmacological effects
associated with onset and worsening of symptoms? (“That flu shot gave me the
flu.”) If you believe the nocebo effect, you must believe in the placebo
effect.
10-12 RISK OF COMMUNITY-ACQUIRED PNEUMONIA AND
USE OF GASTRIC ACID-SUPPRESSIVE DRUGS.
Intragastric
acid constitutes a major non-specific defense mechanism against ingested
pathogens. When the pH is under 4.0, most pathogens are promptly killed. They survive in hypochlorhydric or
achlorhydric states.
The
bacteria and viruses in a contaminated stomach in persons receiving
acid-suppressing drugs (ASD) have been identified as species from the oral
cavity. This is likely due to reduction of gastric acid leading to increased
prevalence of microbial colonization of the stomach. Microbes then backflow
from the stomach to the oral cavity, and then infect the lungs.
This study
examined the association between use of ASD and community-acquired pneumonia.
Rates of
incident pneumonia: 1) no ASD use = 0.6
per 100 person-years; 2) ASD use = 2.45 per 100 person-years. About 0.5% of
patients not taking ASDs developed pneumonia over one year vs about 2.4% of those taking ASDs for a year. Absolute difference = about 2% per year of
administration. NNT (harm one person each
year) = 50
Acid-suppressive
drugs were associated with an increased risk of community-acquired pneumonia.
This is likely a real biological effect.
I believe this is an important clinical
point especially for elderly patients, considering the large numbers of
patients taking ASDs. Primary care clinicians should be attuned to early
suspicion of pneumonia in patients taking ASDs
who develop lower respiratory symptoms.
The concept of the Polypill was introduced in
2003. It was based on the premise
that everyone in Western societies is at risk for cardiovascular disease. The investigators suggested it would
immeasurably benefit if it were taken by everyone over age 50. The pill contained 6 individual drugs: a statin drug; 2) folic acid 800 micrograms;
3) aspirin 75 mg; 4), 5), 6) three antihypertension drugs at half dose (choose
from a thiazide, beta-blocker, ACE inhibitor or angiotensin II blocker, and a
calcium blocker).
The objective of the present study was to define a
safer non-pharmacological and tastier alternative to the Polypill (a Polymeal)
for use by the general population. The foods to be ingested daily: Wine, fish, dark chocolate, fruit and
vegetables, garlic, and almonds.
Combining all ingredients of the Polymeal was
calculated to reduce CVD in men by 76% and increase life expectancy free of
cardiovascular disease by 9 years. In
patients with CVD, life would be extended by 2.4 years.
The FDA would
not approve any combination of drugs to be given to the general population
without determination of individual risk. The Polymeal, although somewhat
fanciful, is much more acceptable. Indeed, it has merit in reminding us of the
benefits of diet in reducing risk of CVD. Except for garlic and dark chocolate,
I believe the ingredients would be acceptable to many persons on a daily basis.
Note that
wine is the most beneficial component of the diet. Some epidemiologists are so
convinced of its benefits that they consider abstinence to be a risk factor.
10-1 PREVALENCE OF HEART DISEASE AND STROKE RISK
FACTORS IN PERSONS WITH PRE-HYPERTENSION
Pre-hypertension
is defined as a BP of 120-139/80-89. This is considered to be above-optimal BP.
Optimal or “normal” BP is defined as under 120/80. Persons
with prehypertension have a greater risk of developing hypertension later in
life than those with lower BP.
Are persons
with prehypertension more likely to have other risk factors for stroke and
heart disease?
Compared to patients with “normal” BP, those with
prehypertension were more likely to have an elevated cholesterol, to be
overweight, and have diabetes. They were 1.7 times more likely to have at least
one other risk factor compared with normotensives. Only about ¼ of adults with
prehypertension had none of the major
risk factors.
The
relation between BP and cardiovascular disease risk is graded and continuous.
Appropriate prevention efforts can be initiated in persons at any level of BP
to avert development of risk factors. This extends to persons with
prehypertension.
The greater prevalence of cardiovascular risk factors
in persons with prehypertension vs
normotension suggests the need for early clinical detection and intervention.
It calls for comprehensive preventive and public health efforts.
This is an important clinical point for
primary care. It presents an
opportunity for earlier intervention and application of the most effective
preventive measures (especially lifestyle).
Primary
care clinicians should check patients with prehypertension for other risk
factors: overweight/obesity,
dyslipidemia, glucose intolerance and diabetes. It is evident that attaining
“normal” BP, weight, and LDL-cholesterol does not assure the most favorable reductions
in risk. Risk is graded and continuous for all these factors. Risk may be lowered by achieving levels
below the usually quoted “normal” levels. What are the most favorable low
levels? Still to be determined.
A
host of persons in the USA who have hypertension are not aware of it. This lack
of awareness must be much higher in those with prehypertension.
PROSTATE CANCER
7-4 PREOPERATIVE PSA VELOCITY AND RISK OF DEATH
FROM PROSTATE CANCER AFTER RADICAL PROSTATECTOMY
This study assessed whether the PSA velocity during
the year before the diagnosis of PC could identify those at higher risk for
death from PC after radical prostatectomy.
Men whose PSA increased by more than 2.0 ng per mL (vs an increase of less than 2.0) during
the year preceding the diagnosis of PC had a higher relative risk of dying from
PC despite undergoing radical prostatectomy. (RR = 25)
An annual velocity over 2.0 was significantly
associated with advanced pathological stage, and high-grade disease. Five % of
men with an annual velocity over 2.0 had positive lymph nodes, as compared with
0.7% in men with velocity 2.0 or less.
“Watchful waiting may not be the best option” in men
with higher velocities. However,
whether these men would have a higher and faster rate of death from PC if they
were treated with watchful waiting rather than with radical prostatectomy is
not known. This awaits a randomized trial.
The initial Gleason score, clinical tumor stage, and
PSA level at diagnosis also are important determinants of risk of death from
PC.
PSA may
fluctuate over time. This may be due to a “natural” variation, or to
differences in and between laboratories. We must be assured that the laboratory
produces reliable and reproducible results. It would be well to repeat an
outlying PSA.
How can we
apply the information from this essentially retrospective study to
practicalities of primary care? This is not easy. Primary care patients are
rarely followed by PSA determinations made every 6 months. The “length time”
between determinations is usually much longer. Still, I believe, it would be
well to consider a possible developing PC in a man whose PSA is rapidly rising.
The cut point of 2.0 ng per mL/year is arbitrary.
A high
initial PSA (confirmed) would also lead to consideration for biopsy. (The cut
points are also debatable.) The usually
stated cut point of 4.0 ng/mL is not reassuring. A cut point of 2.5 has been
recommended for younger men. The Mayo Clinic cites an increase in “normal”
range as age progresses. See the internet connection cited below.
“Few issues
are as controversial” as screening for PC. All men considered for screening
should be fully informed about risks as well as benefits of screening and then asked
to make up their own minds. It is a mistake for primary care clinicians to add
a PSA determination to the routine battery of screening chemical tests without
informing the patient.
The U.S.
Preventive Services Task Force concludes:
The evidence
is insufficient to recommend for or against routine PSA screening. There is
good evidence that PSA can detect early-stage PC. There is mixed and
inconclusive evidence that early detection improves health outcomes Screening
is associated with important harms.
I believe
older men and men with co-morbidity which would limit life span to 10 years or
less should not be screened.
Many younger
men do opt for screening. The object is to detect localized PC at a time when
cure is possible. In younger men who have no nodules and who are screened
periodically, an increased PSA velocity (or doubling time) as well as a high
(and confirmed) initial PSA level would be a consideration for biopsy. There is
still no precise answer to the implied question—“When both the patient and the
physician agree that the potential adverse effects of treatment exceed the
benefits, watchful waiting is an option for managing localized prostate
cancer.” The track record of the
consultant surgeon who will do the radical prostatectomy is an important
consideration. RTJ
7-5 PROGRESS TOWARD IDENTIFYING AGGRESSIVE
PROSTATE CANCER
A substantial proportion of men in the age group most
affected by PC die of other causes. Yet the rate of death from PC remains high.
(In the USA, 82 men die of PC every day.) Evidence of tumor outside the gland
and biochemical relapse may be indicative of incurable disease, but are not necessarily predictors of death from
PC.
A considerable proportion of cancers diagnosed by
screening are indolent and non-lethal, and otherwise would not have been
detected during the patient’s lifetime. In such men, treatment-related
complications could exceed disease-related complications.
The rapidly growing body of information regarding the
predictive value of PSA velocity (and PSA doubling time) suggests that this
approach will become critical in predicting PC-specific survival. In the
editorialist’s experience, patients with biochemical relapse after prostatectomy,
the Gleason score, the time to relapse, and the PSA doubling time all
independently predict the probability of distant metastases, and might be an
indication for early adjunctive treatment.
The PSA doubling time overrides the other variables. The 10-year cancer-specific survival was 93%
among patients with a PSA doubling time of more than 10 months, and 58% among
those with a doubling time of less than 10 months.
I have tried
to think through some guidelines for PSA screening applicable to primary care.
This is a personal appraisal. Urologists and other experts may have a different
approach.
I believe
clinicians may legitimately ask suitable patients if they wish to be screened,
while deterring others who might seek a PSA screening, and not even mentioning
screening to others.
A. Who should we not screen with PSA
Men who are
not beforehand fully informed about ultimate risks as well as possible
benefits. (PSA should not routinely be included in the biochemical screen in
men who come for a “check up”.)
Older men and
men with co-morbidity whose life expectancy is less than 10 years.
Men who would
not be willing to undergo radical prostatectomy or radiation if indicated.
B. Who should we screen with PSA?
Only men who
are fully informed about ultimate risks as well as benefits of screening
Only men with
a quality life expectancy over 10 years.
(This would tilt screening toward younger,
healthier men.)
Only men who
would be willing to undergo a radical prostatectomy or radiation if indicated.
C. How often should we screen?
This depends
on the patient’s degree of concern, and the doctor’s willingness to comply with
the concerns.
Once a year
could be considered reasonable unless an upward trend is suspicious.
D. When should we advise prostate biopsy?
When initial
PSA is high for patient’s age.
When the PSA
velocity over time is increasing rapidly.
When a
suspicious nodule is discovered on DRE. (This now becomes a diagnostic
procedure, not a screen.)
E. If cancer cells are found, when should radical
prostatectomy be advised?
Gleason score
6 and over.
High initial
PSA level.
High PSA
velocity or short-time doubling
Nodule
present
For younger
men. In younger men, I believe definitive therapy is almost always indicated.
They are more
at risk because they have more time to develop extension of PC. And a greater
risk of developing a more aggressive tumor later in life.
F. If cancer cells are found, when should
prostatectomy not be advised? (In favor of “watchful waiting”a.)
In older men:
With
significant co-morbidity and a limited life expectancy
With a
Gleason score under 6
With a low
PSA
No nodule
present
Slow PSA
velocity
(a I am not sure what “watchful waiting”
means. Watch for what? Perhaps advising
early adjuvant therapy if extension occurs.)
I believe the
opening statement of the preceding study is a key determinant. “When both the patient and the physician
agree that the potential adverse effects of treatment exceed the benefits,
watchful waiting is an option for managing localized prostate cancer.” This is a judgment call by both. Patient
preference is important.
The purpose
is to detect and treat while cure is possible and to extend quality life. RTJ
11-5 IS PSA TESTING STILL USEFUL?
Dr. Thomas A. Stamey (Stanford University School of
Medicine), who is considered to be the “father” of PSA testing, says it is no
longer a useful tool for screening for PC. In fact, it may be causing
unwarranted treatment for a typically slow-growing tumor. Dr. Stamey drew his
conclusions after studying over 1300 consecutive radical prostatectomies. Over
time, there was a linear decrease in most parameters associated with PC. During
the first 5 years of screening, 91% of cancers were palpable, the mean PSA was
25 ng/mL, the mean age was 64, and cancer volume was over 5 cm3. During the last 5-years of screening, 17%
were palpable, the mean PSA was 8 ug/mL, the mean age was 59, and the cancer
volume was 2.4 cm3. When PSA screening
was first introduced, high levels were associated with a 50% chance of having a
large PC for which treatment was warranted. Over the past 5 years, the chance
of having a large PC has fallen to 2%, presumably due to over screening. “Most
prostate cancers we (now) remove need
not be removed.”
An estimated 230 000 men in the USA will be diagnosed
as having PC this year; 30 000 are expected to die of PC. Dr. Stamey says the fear of dying of PC may
be disproportionate to the odds of death. One study reported that the
prevalence of PC was 8% in men in their 20s, and the percentage grew linearly
to 80% in men over 70. “It’s a cancer we all get if we live long enough.”
There is ambivalence in the prostate-treatment
community regarding screening. Some researchers remain convinced that screening
effectively detects clinically significant PC and leads to a reduced mortality.
“Physicians continue to be concerned about diagnosing
prostate cancer at the earliest stage when it is most treatable, while at the
same time avoiding unneeded biopsies and treatment for prostate cancers that
might not become clinically meaningful.”
The mortality rate from the disease is low. But the
reality is that some patients may benefit from early detection. Thus, PSA has
lost some value, but it still may have some clinical relevance.
Patients at risk of overtreatment have a low, stable
PSA with low-grade, low-volume cancers. We are detecting many low volume
cancers that may not require treatment.
No doubt many
men are now undergoing unnecessary treatments for PC. Undoubtedly some lives
are saved. Where to draw the line?
I believe PSA
should not be considered a “routine” screen (as is BP, blood glucose, and
cholesterol). Patients should be fully informed about risks and benefits beforehand.
I believe primary care clinicians should not even broach the subject when
consulting with elderly men. Digital rectal examination is a more reasonable
screen.
There are
some guidelines when results of PSA are obtained in younger men. If the PSA is
high, and if the rate of increase is rapid (eg, doubling time, or an increase
of over 2.0 ug/year), biopsy is warranted. Surgery then depends on the grade of
PC determined by biopsy.
When I was a
child, almost all children and many adults underwent tonsillectomy. It seemed
to be the mode. When we would consult with our European colleagues, they would
admonish—“Hold onto your tonsils”. I
believe many man in the USA should “Hold onto your prostate”.
11-10 A RATIONAL BASIS FOR RACE
Humans are not divided along clear color-based lines
which are traditionally used in anthropological records. Some ask—Does race
exist at all?
The problem occurs when society and the medical community
generalizes findings to an entire group. Prostate cancer has a higher
prevalence among African-American men. This does not mean that all
African-American men have similar risks for prostate cancer.
The connection between self-identified race and genetic
variation is very blurry. Culture, lifestyle, and social stress may play a
greater role in disparity.
Black
“African Americans” are an extremely diverse group.
We often
choose subsets of individuals for screening—race may be one. I believe
divisions according to ‘race” still has some clinical validity. The disparity
between races in the USA is gradually disappearing.
7-9 CALCULATING THE RISK OF DISEASE www.yourdiseaserisk.harvard.edu
A review note in BMJ July 24, 2004; 329: 237 calls
attention to an online tool for determining an individual’s risk for five of
the most important disease groups in the USA (cancer, diabetes, heart disease,
stroke, and osteoporosis). It is
presented by The Harvard Center for Cancer Prevention, part of the Harvard
School of Public Health. It is an expanded version of the center’s cancer risk
assessment website.
The site is an interactive educational tool that seeks
to encourage healthy lifestyles. It questions the inquirer’s eating habits,
drinking, and exercise, and offers personalized tips for disease prevention.
I accessed
this site on August 13, 2004 and completed the heart disease risk evaluation.
Individuals can easily and quickly complete the 21 or more questions asked. It
includes all components of the Framingham Risk Score except HDL-cholesterol.
In addition
it asks for past history of heart disease, family history, waist size,
diabetes, 7 different questions about diet and alcohol, vitamin supplements,
and exercise.
On completion
it presents a colored risk scale (low to high) and places the individual’s
estimated risk compared with average.
A useful
addition is a list of tips on how you can reduce your individual risk. I received
5 different tips to reduce my risk. RTJ
SHARED MEDICAL DECISION MAKING
11-6 SHARED MEDICAL DECISION MAKING: Problems,
Process, Progress
“Sharing with a patient who faces tough choices when he or she is ill is one of the true gifts of
being in the medical profession.” The
patient-physician relationship is the sacrosanct epitome of professionalism
with the goals of ensuring that patients receive the treatment best for them
(science) and that the best treatment is carried out in the most efficient and
compassionate manner (quality and safety).
“Physicians should never make a choice for a
patient—even if the patient wants the physician to do so .” Instead, physicians should ensure that the
information used in the patient’s decision-making is reasonable for the
individual patient and that the patient understands the ramifications of
choice. “The physician should be a navigator, not a pilot.”
The consequences of a patient’s choice cannot be
shared with anyone else. Only the patient will suffer or enjoy the
probabilistic outcomes associated with choosing one option over another. Only
the patient will know how he or she feels about experiencing an adverse effect
of a treatment or a reduced chance of an adverse outcome that a treatment is
designed to alter. Patients must have time to reflect.
A decision that appropriately involves a patient requires
viable options, and choosing one option over another must engender some element
of risk. There has to be a definable trade-off of harm and benefit.
Some actions, however, are not really decisions to be
made by the patient and do not require a patient’s input. Patients need not
decide if antibiotics are required for bacterial pneumonia. Sick patients
should not be allowed to make decisions about treatments that are of clear
value and that do not create significant levels of harm. If the significance of
an adverse effect or harm is so minor compared with the benefit, no decision is
required.
The conceptional framework for making a choice is
understandable as a balance between harms and benefits weighed by the patient’s
values for gains and losses. Only the patient can do it. “Physicians cannot
deny patients the opportunity and means to make their own choices.”
I enjoyed
this thought-provoking commentary.
The demise of
physician’s paternalism and authoritarianism has transferred some
decision-making to the patient. In some circumstances, the physician’s
responsibility must be to fully inform patients of the best evidence about
harms as well as benefits of treatment. This enables patients to choose based
on their individual circumstances. How strictly should primary care
clinicians apply this principle?
Shared
decision-making is applicable when the choices are “tough”. I believe the process needs to be applied to
relatively few patients seen in daily primary care practice. If this process
were applied to every patient, practice would grind to a halt. The process
would be more applicable to patients seen in specialty care (eg, oncology,
surgery).
The comment
about no need for patient- decision making in clear cut situations such as
antibiotics for pneumonia may not be so simple for an elderly, infirm patient
who does not wish to receive therapy.
If the patients is competent and wishes to avoid therapy, this is his
decision.
There are
many obstacles to application of “shared decision” in the real world of primary
care:
The patient
may be incompetent.
What about
decisions for children?
Patients are
often medically illiterate.
There may be
cultural and language barriers. In some cultures, patients may rely on family
and will refuse to make their own choice.
Some patients may defer to the physician asking “What would you do?” and
may refuse to choose.
Estimates of benefit/harm may not apply to individual “real world” patients. The true benefit/harm ratio may not be well established. It may be subject to change as more information becomes available.
The patient’s best choice is often not available The patient may not be able to pay for the choice he makes. Insurance may not cover the costs.
How should
the clinician respond when the patient chooses a course the physician considers
futile?
I believe
medical paternalism and authoritarianism is not dead yet.
7-12 ARE OTC STATINS READY FOR PRIME TIME?
This month, the 10 mg dose of simvastatin (Zocor) is expected to become available
to the general public in the UK without a prescription. The UK government hopes
this will make it easier for individuals to acquire a low-cost statin, and will
increase use and reduce cardiovascular morbidity and mortality
There are opponents and proponents, both with good
reasons.
Four years ago, a similar attempt in the USA failed to
achieve OTC status. The FDA did not
believe evidence was sufficient that a 10 mg statin could be used safely. However,
the FDA is considering reversing this course. The National Lipid Association
has received a grant from Johnson and Johnson-Merck to explore the pros and
cons of OTC statin availability in the USA.
I wonder if a
compromise would be feasible. The doctor writes a note (not a prescription)
informing the pharmacy staff that Mr X is a candidate for OTC statin. This
would give the clinician and the pharmacist an opportunity to educate the
patient about risks as well as benefits. And also to give the clinician the
opportunity to check on adverse effects and effectiveness at future
consultations.
The note
could be presented at time of each purchase. The statin is not displayed on the
shelf. It is available and paid for at the pharmacy check-out, not at the check-out
for general purchases and other OTC drugs.
I believe a
good argument could be made that statins are safer than some drugs now freely
available OTC—eg, NSAIDS, aspirin, and all
sorts and conditions of “natural” and “alternative” nostrums. RTJ
I would vote
in favor of OTC status. RTJ
8-6 PRIMARY PREVENTION OF CARDIOVASCULAR
DISEASE WITH ATORVASTATIN IN TYPE 2 DIABETES
Current prescription rates for lipid lowering drugs in
patients with DM2 remain low, even in patients with established cardiovascular
disease (CVD).
This study assessed the effectiveness of a 10 mg dose
of atorvastatin (Lipitor) vs placebo in primary prevention of CVD in patients with DM2. None had high concentrations
of LDL-c. The trial was stopped 2 years early because of demonstration of
significant benefit.
None had documented history of CVD. All had at least
one risk factor: retinopathy, macro- or
micro-albuminuria, current smoking, or hypertension. The risk of a major
cardiovascular event in these patients was 10% over 4 years.
Incidence of major cardiovascular events was 25 per
1000 person-years at risk in the placebo group vs 15 per 1000 person-years at
risk in the atorvastatin group. Therefore, allocation of 1000 patients to
atorvastatin would avoid 37 first major events over a 4-year follow-up. 27
patients would need to be treated for 4 years to prevent one event. [NNT (for
4 years to benefit one) = 27]
“The debate about whether all patients with DM2 warrant statin therapy should now focus on
whether any patients can reliably be identified as being at sufficiently low
risk for this safe and effective treatment to be withheld.”
These data challenge the use of a particular threshold
level of LDL-c as the sole arbiter of which patients with DM2 should receive
statin therapy (as in the case of most current guidelines). Target levels of
LDL-c (100 mg/dL) could be lowered.
An editorialist comments: The conclusions of the study—“Seems too far-fetched in view of
the available clinical trials and epidemiological data”. He cites 4 large
studies of lipid control which contained many patients with DM2. Two of the
four did not report a statistically significant reduction in coronary disease.
Two did.
Clinical trials enroll carefully selected patients.
The results cannot necessarily be extrapolated to primary care practice. Many
patients may be at low risk and the benefit/ harm-cost ratio may be too low to warrant long-term
treatment. Some may be at higher risk of adverse effects from statins. As
always, individualization is required.
I believe the
majority of patients with DM2 will benefit from statin therapy for primary
prevention.. Most will have one or more additional risk factors. There would be
no question regarding secondary prevention.
Authors and
publishers persist in presenting relative benefits (rather than absolute
differences). Thus, they reiterate that treatment with atorvastatin was related
to a 37% reduction in major coronary events; a 31% reduction in coronary
revascularizations; a 48% reduction in stroke; and a 27% reduction in deaths.
This can be
very misleading. I believe statements of relative benefits should be eliminated
from published reports.
This study examined the relationships between
sugar-sweetened beverage consumption (especially soft drinks), weight gain, and
risk of diabetes in a large cohort of young and middle-aged women.
Over the entire 10 year period, women who increased their sugar-sweetened soft
drink (S-SSD) intake from low to
high had larger increases in weight compared with women who maintained a low
intake, or substantially reduced their intake.
In contrast, women who decreased their S-SSD reduced their total energy consumption by 319
kcal/d. Women who decreased their
intake during the first 5 years and maintained a low level gained less weight
than those who increased their intake (2.8 kg. vs 4.4 kg).
Participants whose consumption of diet soft drinks increased
from one drink or less per week to more than one drink per day gained
significantly less weight (1.6 kg) than
women who decreased their intake from
one or more drinks daily to 1 drink or less per week (4.2 kg). [Ie, consumption of calorie free drinks
apparently to some extent, blunts ingestion of calorie-containing foods.]
Greater S-SSD consumption was strongly associated with
progressively higher risk of type 2 diabetes.
(RR = 1.9 in women consuming one or more drinks per day vs those consuming less than one per
month.)
Sugar-sweetened fruit punch was also associated with
increased risk of diabetes. (RR = 2.0)
“Pure” fruit juice was not associated with risk of diabetes.
Over 8 years, there were positive associations between
sugar-sweetened beverage consumption and both greater weight gain and risk of
type 2 diabetes, independent of other known risk factors.
Energy provided by sugar-sweetened beverages does not
affect subsequent food and energy intake. (Ie, little or no compensation by
reduction in intake of other foods.) Weight gain and obesity result from the
positive energy balance.
Fruit juice was not
associated with diabetes risk in this study. This suggests that naturally
occurring sugars in beverages may have different metabolic effects than added
sugars.
This is an
important life-style consideration.. It convinces me to ask a screening question,
especially for overweight patients and patients with type 2 diabetes—“How many
Cokes and how many Diet Cokes do you drink every week?”
Grocery
stores offer a wide range of fruit flavored drinks (fruit punches). Some
contain high amounts of fructose and sucrose. Some contain an artificial
sweetener. Look at the “Nutrition Facts” label.
A 12-oz can
of Coke contains 42 gm of sugar (high fructose corn syrup or sucrose).
A 12-oz can
of Diet Coke contains zero calories.
(Aspartame).
My “pure”
orange juice contains 36 grams of sugar per 12 oz, almost as much as 12 oz of
Coke. What is the metabolic difference?
Note also that many other foods (especially breakfast
cereals) contain a high concentration of sugar. Do these foods, in contrast to
S-SSD, have a higher satiety value?
Moral: “Give your pancreas a
break”. RTJ
8-2 SUGAR-SWEETENED SOFT DRINKS, OBESITY, AND
TYPE 2 DIABETES.
When individuals include liquid carbohydrate consumption
in their diet, they do not reduce
their solid food consumption. An increase in liquid carbohydrates leads,
perversely, to even greater caloric consumption of other foods.
“A better mechanism for weight gain could not have
developed than introducing a liquid carbohydrate with calories that are not
fully compensated for by increasing satiety.”
Conversely, intake of diet (non-sugar containing) sodas is associated with a lowering of risk of childhood obesity.
“Reducing sugar-sweetened beverage consumption may be
the best single opportunity to curb the obesity epidemic.”
This
convinces me to ask a routine screening question, especially for overweight
patients and patients with type 2 diabetes. How many Cokes and how many Diet
Cokes do you drink every week?” RTJ
7-1 ASSOCIATION BETWEEN CHILD AND ADOLESCENT
TELEVISION VIEWING AND ADULT HEALTH.
Watching TV in childhood and adolescence has been
linked to adverse health outcomes.
This study explored the long-term health effects of
childhood TV viewing.
Mean weekday viewing hours varied between 1.9 hours at
age 5 to 3.9 hours at age 13. Ages 5-15
61% of subjects averaged more than 2 hours of TV on
weekdays.
Adolescent TV watching correlated with lower childhood
socio-economic status, increased parental smoking, higher maternal and paternal
BMI, and higher BMI at age 5.
Childhood and adolescent TV viewing predicted (at age
26) a higher BMI, lower VO2 max, higher cholesterol, and increased smoking:
Several childhood behaviors could explain the relation
between TV viewing and health. The most obvious are physical activity and diet.
Watching TV could affect fitness and obesity by displacing time which would be
spent on more active pursuits. TV viewing may influence cigarette smoking.
Viewing habits established in childhood may persist
into early adulthood.
“We believe that reducing television viewing should
become a population health problem.”
Excessive viewing might have long-lasting adverse
effects on health.
What else can
I say? RTJ
8-9 TERMINAL SEDATION: An Acceptable Exit
Strategy?
Terminal sedation is used by the physician to sedate a
terminally ill patient until coma develops in order to alleviate intolerable
suffering refractory to conventional palliative measures. It is controversial.
It is illegal except in Oregon.
It has been condemned by some as euthanasia in
disguise. Others, such as the U.S.
Supreme Court Justice O’Connor, have endorsed the practice arguing that “a
patient who is suffering from a terminal illness and who is experiencing great
pain has no legal barrier to obtaining medication from qualified physicians to
alleviate that suffering, even to the point of causing unconsciousness and
hastening death”.
One of the major objections to terminal sedation is
that its intent may be to kill the patient in order to alleviate suffering. The
intent of palliative care, by contrast, is to relieve suffering, even if the
treatment, such as opioids, shortens life. “Intent matters”—in law and in
ethics. The rule of “double effect” states that foreseeable adverse
consequences of treatment (ie,
side-effects) are acceptable only if they are not intended. A second
objection is that terminal sedation could take place without the patient’s
consent, a process indistinguishable from involuntary euthanasia.
In America, we worry that patients who lack access to
care, or whose values differ from those of their physicians, might be
euthananized without their consent. And that the rate of terminal sedation
might be high in the U.S. because physician-assisted suicide is largely
unavailable.
“We need to control the use of terminal sedation by
developing and implementing practice guidelines.” We must confirm the diagnosis, consider alternative approaches,
and obtain informed consent.
Is the
patient conscious and competent to make his own decisions when nearing death?
Then possible approaches to end-of-life care would include:
1) Request
palliative, comfort care until death.
2) Request
withdrawal of life-sustaining treatment.
3) Decide to
cease intake of food and fluids
4) Request
administration of a state of coma, or near coma, to be sustained until death.
5) Request a
prescription of barbiturates to have on hand if the patient wishes at some time
to take them.
(Although
this is not legal in almost all states, I believe physicians invoke the
practice in many cases by subterfuge.)
If the
patient is not competent to make his own decisions, or if his directions before
loss of competency were not clearly stated, the problem becomes more difficult.
A surrogate must then decide what is in the best interest of the patient.
Options would include only 1), 2) and 3). RTJ
7-11 METHYLPREDNISOLONE, VALACYCLOVIR, OR THE
COMBINATION FOR VESTIBULAR NEURITIS
This study was performed to determine if anti-viral
therapy with valacyclovir (Valtrex
which is rapidly converted to acyclovir) and/or corticosteroids would benefit.
Methylprednisolone alone significantly improved the
long-term outcome of peripheral vestibular function. Antiviral therapy did not benefit any more than placebo.
There is good evidence that the major damage in VN is
caused by swelling and mechanical compression of the vestibular nerve within
the temporal bone. (As is assumed with the facial nerve in Bell’s palsy.)
A reduction in swelling due to the anti-inflammatory
effect of corticosteroid may explain why these drugs result in improvement.
Some patients
(placebo group) apparently improved spontaneously, and about 4 out of 10 treated
with methylprednisolone did not improve. Residual symptoms of VN may persist
for years.
During their
careers, primary care clinicians will likely encounter at least one case of VN.
Incidence is about one case per 30 000 population.
Benign
paroxysmal positional vertigo is common. Although the pathogenesis is vastly
different. I wonder if a trial of
short-term corticosteroids might help. RTJ