HHAL MEDICAL NEWS FEBRUARY 2011
Zinc Ameliorates Cold Symptoms, Meta-Analysis Finds
Sniffling people will likely ask about a Cochrane
Library meta-analysis that finds zinc to be effective in shortening the duration of the common cold.
In
an update of a 1999 Cochrane review, the authors examined zinc's efficacy both in shortening the duration of colds and in preventing
them. They considered the results of 15 randomized trials, totaling over 1300 participants.
Zinc supplements significantly
reduced the severity of cold symptoms as well as the length of illness. Among people taking zinc within 24 hours of the start
of symptoms, the risk for still having symptoms at the 7-day mark was about half that of
those not taking zinc. In preventing colds, zinc supplements taken for at least 5 months conferred a risk for catching a cold
that was only two thirds that of controls.
Zinc's side effects included a bad
taste and nausea.
Cochrane
Library abstract
A
New Treatment for Insomnia?
A
combination of melatonin, zinc, and magnesium was safe and effective, but the results are preliminary.
Rondanelli M et al. J Am Geriatr Soc 2011 Jan 59:82
Dietary Fiber Intake and Mortality in the NIH-AARP Diet and Health Study
Yikyung Park, ScD; Amy F. Subar, PhD; Albert Hollenbeck, PhD; Arthur Schatzkin,
MD
Arch Intern Med. Published online February
14, 2011. doi:10.1001/archinternmed.2011.18
Background Dietary fiber has been
hypothesized to lower the risk of coronary heart disease, diabetes, and some cancers. However,
little is known of the effect of dietary fiber intake on total death and cause-specific deaths.
Methods We examined dietary fiber intake in relation to total mortality and death
from specific causes in the NIH (National Institutes of Health)-AARP Diet and Health Study, a prospective cohort
study. Diet was assessed using a food-frequency questionnaire at baseline. Cause of death was identified using
the National Death Index Plus. Cox proportional hazard models were used to estimate relative
risks and 2-sided 95% confidence intervals (CIs).
Results During an average of 9 years of follow-up, we identified 20 126
deaths in men and 11 330 deaths in women. Dietary fiber intake was associated with a significantly lowered
risk of total death in both men and women (multivariaterelative risk comparing the highest with the lowest quintile, 0.78
[95% CI, 0.73-0.82; P for trend, <.001] in men and 0.78 [95% CI, 0.73-0.85; P for
trend, <.001] in women). Dietary fiber intake also lowered the risk of death from cardiovascular, infectious,
and respiratory diseases by 24% to 56% in men and by 34% to 59% in women. Inverse association between dietary fiber
intake and cancer death was observed in men but not in women. Dietary fiber from grains, but not from other
sources, was significantly inversely related to total and cause-specific death in both men
and women.
Conclusions Dietary fiber
may reduce the risk of death from cardiovascular, infectious, and respiratory diseases. Making fiber-rich
food choices more often may provide significant health benefits.
FDA Approves Edarbi for Hypertension
The
FDA has approved the angiotensin II receptor blocker azilsartan medoxomil
to treat hypertension in adults.
The drug, marketed as Edarbi,
was shown to be more effective in lowering 24-hour blood pressure than valsartan or
olmesartan. The agency says the drug will be available in two doses, 40 and 80 mg, with
the lower dose intended for patients on high-dose diuretics.
A boxed warning cautions
against use during pregnancy,
because the drug can harm the fetus.
FDA announcement (Free)
Covering
All the Bases
In a randomized trial,
initiating treatment with a combination of aliskiren and amlodipine resulted in earlier blood pressure control than
either agent alone.
Brown MJ et al. Lancet 2011 Jan 22; 377:312
CPAP
Treatment Lowers BP in Hypertensive Patients with Sleep Apnea
Blood pressure benefits
of continuous positive airway pressure treatment were significant but small.
Durán-Cantolla
J et al. BMJ 2010 Nov 24; 341:c5991
A better way to reduce peripheral edema
In patients with hypertension, the
calcium channel blocker/renin-angiotensin system blocker combination reduces the risk of calcium channel blocker-associated
peripheral edema when compared with calcium channel blocker monotherapy. The ACE inhibitor seems to be more efficacious
than ARB in reducing calcium channel blocker-associated peripheral edema, but head-to-head comparison studies are needed to
prove this. The American Journal of Medicine
Vitamin
D and Frailty — A Not-So-Simple Relation
Both low and high vitamin D levels were associated with frailty
in older women.
Ensrud KE et al. J Clin Endocrinol Metab 2010 Dec 95:5266
Vitamin
D levels don't affect women's diabetes risk, study says
A study in the journal Diabetes Care found that
6% of 5,140 women without Type 2 diabetes at the outset of the study developed the disease during a seven-year period. When
researchers accounted for diabetes risk factors such as
body weight, exercise and diet, they found vitamin D levels in women's blood did not affect their risk for the disease. Reuters
Vitamin D may reduce colorectal cancer risk, data find
A report in the International Journal of Cancer found that high
blood levels of vitamin D may reduce the risk of colorectal cancer. A team led by the International Prevention Research Institute
in France analyzed data from nine studies and found that for every 10-nanograms-per-milliliter increase in levels of vitamin
D, the risk of colorectal cancer decreased by 15%.NutraIngredients
High Prostate-Specific Antigen "Velocity" Not a Reason for Biopsy
Patients may ask about a study that finds a high rate of change in prostate-specific
antigen values — called PSA velocity — is not sufficient grounds for biopsy. The study appears in theJournal
of the National Cancer Institute.
As part of a randomized trial of finasteride versus placebo in healthy men, researchers evaluated some 5500 men in the placebo arm. The men were
aged 55 and older with initial PSA levels of 3.0 or less and normal digital rectal
exams. They received yearly PSA tests and underwent biopsy after 7 years of
placebo treatment.
The authors found that doing biopsy on the basis of a PSA velocity of greater
than 0.35 ng/mL/yr — as some current guidelines suggest — would lead to only a "very small increase"
in predictive accuracy and recommend against use of the measure in clinical guidelines. They argue that use of the velocity
measure alone as an indication for biopsy would lead to large numbers of additional, unnecessary procedures.
Editorialists
write that the results "remind us that the use of PSA as a screening tool still leaves much to be desired."
JNCI study (Free abstract)
Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and
Vascular Dementia
Minna Rusanen, MD; Miia
Kivipelto, MD, PhD; Charles P. Quesenberry Jr, PhD; Jufen Zhou, MS; Rachel A. Whitmer, PhD
Arch Intern Med. 2011;171(4):333-339. doi:10.1001/archinternmed.2010.393
Background Smoking is a risk factor for several life-threatening diseases, but its
long-term association with dementia is controversial and somewhat understudied. Our objective was to investigate the
long-term association of amount of smoking in middle age on the risk of dementia, Alzheimer disease (AD),
and vascular dementia (VaD) several decades later in a large, diverse population.
Methods We analyzed prospective data from a multiethnic population-based cohort
of 21 123 members of a health caresystem who participated in a survey between 1978 and 1985. Diagnoses of
dementia, AD, and VaD made in internal medicine, neurology, and neuropsychology were collected from January
1, 1994, to July 31, 2008. Multivariate Cox proportional hazards models were used to investigate
the association between midlife smoking and risk of dementia, AD, and VaD.
Results A total of 5367 people (25.4%) were diagnosed as having dementia (including
1136 cases of AD and 416 casesof VaD) during a mean follow-up period of 23 years. Results were adjusted for
age, sex, education, race, marital status,hypertension, hyperlipidemia, body mass index, diabetes, heart disease,
stroke, and alcohol use. Compared with nonsmokers, those smoking more than 2 packs a day had an elevated risk
of dementia (adjusted hazard ratio [HR], 2.14; 95% CI, 1.65-2.78), AD (adjusted HR, 2.57;
95% CI, 1.63-4.03), and VaD (adjusted HR, 2.72; 95% CI, 1.20-6.18).
Conclusions In this large cohort, heavy smoking in midlife was
associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest
that the brain is not immune to long-term consequences of heavy smoking.
Frequent Hypoglycemia Among Elderly Patients With Poor Glycemic Control
Medha N. Munshi, MD; Alissa R. Segal, PharmD; Emmy Suhl, RD; Elizabeth Staum,
RD; Laura Desrochers, BS;Adrianne Sternthal, BS; Judy Giusti, RD; Richard McCartney, BA; Yishan Lee, MS; Patricia
Bonsignore, MS;Katie Weinger, EdD
Arch Intern Med. 2011;171(4):362-364. doi:10.1001/archinternmed.2010.539
Background Episodes of hypoglycemia are particularly
dangerous in the older population. To reduce the risk of hypoglycemia, relaxation of the standard
hemoglobin A1c (HbA1c) goals has been proposed for frail elderly patients. However, the risk of
hypoglycemia in this population with higher HbA1c levels is unknown.
Methods Patients 69 years or older with HbA1C values of 8% or
greater were evaluated with blinded continuous glucose monitoring for 3 days.
Results Forty adults (mean [SD] age, 75 [5] years; HbA1C value, 9.3%
[1.3%]; diabetes duration, 22 [14] years; 28 patients [70%] with type 2 diabetes mellitus; and 37 [93%] using
insulin) were evaluated. Twenty-six patients (65%) experienced 1 or more episodes of hypoglycemia
(glucose level <70 mg/dL). Among these, 12 (46%) experienced a glucose level below 50 mg/dL and 19
(73%), a level below 60 mg/dL. The average number of episodes was 4; average duration, 46 minutes. Eighteen
patients (69%) had at least 1 nocturnal episode (10 PM to 6 AM). Of the total of
102 hypoglycemic episodes, 95 (93%) were unrecognized by finger-stick glucose measurements performed 4 times
a day orby symptoms.
Conclusions Hypoglycemic episodes
are common in older adults with poor glycemic control. Raising HbA1C goals may not be
adequate to prevent hypoglycemia in this population.
Oral Steroids plus Intranasal Steroids Effective for Chronic Rhinosinusitis and Nasal Polyps
In
rhinosinusitis with nasal polyposis, initial treatment with oral steroids followed by intranasal steroids works better than
intranasal steroids alone. The advantage lasts about 6 months, according to an Annals of Internal Medicine study.
Researchers
studied 60 adult patients who'd been referred because of moderate or large nasal polyps. The patients were randomized
to an initial 2-week treatment with either oral prednisolone or placebo; thereafter, all received 8 weeks of fluticasone nasal
drops followed by 18 weeks of fluticasone spray. Group-mean measures of polyp sizes dropped significantly more among the prednisolone
recipients; in addition, the treatment group also had greater improvement in olfaction
scores. By the 28-week mark, however, the differences were no longer statistically significant.
Prednisolone
recipients experienced suppressed adrenal function and increased bone turnover, which returned to baseline by 28 weeks.
Editorialists
caution against overenthusiasm for the oral regimen, given its potential adverse effects.
Annals
of Internal Medicine article (Free abstract)
Cannabis Use Associated with Psychotic Symptoms
in Young Adults
Cannabis use is associated with the development of psychosis in young adults, according to aBMJ study.
Researchers followed some 1900 German participants, aged 14 to 24 at baseline,
to assess their use of cannabis and incidence of psychotic experiences. When participants with prior cannabis use and previous
psychotic experiences at baseline were excluded, those who started using cannabis during the first 3.5-year period of follow-up
were nearly twice as likely to experience psychotic symptoms within the subsequent 5-year period, compared with those who
didn't use cannabis (odds ratio, 1.9). And continuing use in the 5-year period was, similarly,
associated with a doubling in risk relative to nonusers.
Editorialists write, "The
results cast doubt on the argument that uncontrolled confounding explains the association between cannabis and psychosis."
BMJ article (Free)
Cardiovascular Risk Assessment in Asymptomatic
Adults)
New
guidelines reflect a conservative approach.
Key Points:
1. A global risk score (e.g., Framingham Risk Score, including results
of blood-pressure and cholesterol tests, should be obtained in all asymptomatic adults (Class I recommendation). The guideline
authors deem it "reasonable" to begin acquiring global risk scores at a somewhat arbitrary age of 20 years and
then every 5 years thereafter.
2. In patients at intermediate risk according
to a global risk score, the authors found no benefit of genetic testing, advanced lipid testing, natriuretic-peptide testing,
coronary computed tomography angiography, magnetic resonance imaging for the detection of vulnerable plaques, or stress echocardiography.
3. Measuring high-sensitivity C-reactive protein (hsCRP) is recommended in men aged 50 or women aged 60 to determine if they might benefit from statin therapy for
primary prevention (Class IIa). Measuring hsCRP in men aged <50 or women aged <60 may be reasonable in those at intermediate
risk (Class IIb).
4. Consistent with other guidelines, hsCRP testing is not recommended for high- or low-risk individuals (Class III).
5. The use of ultrasound measurement of carotid intima–media thickness (CIMT) is reserved for intermediate-risk
individuals at well-equipped sites by highly trained operators (Class IIa). Serial measurement of CIMT is not advised, given
the lack of a clear process–outcome link.
6. Similarly, the measurement of coronary
artery calcium is reserved for intermediate-risk individuals and those aged 40 with diabetes
(Class IIa). Again, serial testing
is not advised, given the lack of a clear process–outcome link.
Journal Watch Cardiology February 9, 2011
· Medline abstract (Free)
Updated Guidelines Issued for Women's Cardiovascular Disease Prevention
The American Heart Association has released updated guidelines for preventing cardiovascular
disease in women.
Published in Circulation, the changes
since the 2007 update include the following:
· There's been a title change
from "Evidence-Based" to "Effectiveness-Based."
· The guidelines define "high
risk" in women as being at a 10% or greater 10-year risk for all cardiovascular disease, not just coronary heart
disease.
· Clinicians should consider the importance of racial, ethnic,
and socioeconomic factors and be sensitive to how those factors affect cardiovascular risk.
·
Women with existing cardiovascular disease should be screened for depression, since the condition may affect whether
patients adhere to treatment regimens.
· Women with systemic lupus
erythematosus and rheumatoid arthritis should be considered at risk for cardiovascular disease and be screened
for other risk factors.
· Similarly, women who have experienced
pregnancy complications, such as preeclampsia,gestational diabetes, or preterm birth, should have those factors taken
into account when their risks are evaluated later in their lives.
Circulation article (Free
PDF)
Prevention of Cardiovascular Disease in Women
Revised
guidelines redefine risk for cardiovascular disease and its management in women.
Sponsoring Organization: American Heart
Association
Background and
Purpose: In reviewing evidence for this update to the 2007 guidelines, the authors widened their focus to include
data on effectiveness (observed clinical benefits and risks) as well as on efficacy (results of controlled trials). Consequently,
the revision incorporates several new strategies for the prevention of cardiovascular events in women.
Key
Points:
1. The classification scheme for assessing cardiovascular risk now stratifies women into "high risk," "at
risk," and "ideal cardiovascular health" categories.
2. Women with a 10-year predicted risk for cardiovascular disease of 10% (as opposed to a 10-year risk for coronary heart disease of 20%)
are now considered at high risk.
3. In the at-risk category, hypertension and hypercholesterolemia are
specifically defined, and evidence of subclinical atherosclerosis now includes carotid plaque and thickened carotid intima–media
thickness as well as coronary calcification. In addition, systemic autoimmune collagen-vascular disease and history
of preeclampsia, gestational diabetes, or pregnancy-induced
hypertension are included as risk factors in this category.
4. Ideal cardiovascular health is defined as meeting all of the following criteria:
·
Non-HDL level <130 mg/dL (untreated)
·
Blood pressure <120/80
mm Hg (untreated)
· Fasting
blood glucose level <100
mg/dL (untreated)
· Body-mass
index <25 kg/m2
· Abstinence
from smoking
· Physical
activity at goal for adults aged >20
· A diet similar
to Dietary Approaches to Stop Hypertension (DASH)
5. A variety of 10-year risk equations other
than the Framingham risk score are now accepted for the prediction of 10-year global cardiovascular risk. Alternatives include
the Reynolds risk score for women, which incorporates high-sensitivity C-reactive protein(CRP) level, although the authors do not endorse routine CRP testing.
6. Lifestyle interventions include stronger recommendations for increased exercise. Providers are advised
to consistently encourage women to accumulate at least 150 minutes of moderate or 75 minutes of vigorous exercise per week
(for additional benefit, 300 minutes of moderate or 150 minutes of vigorous exercise per week are recommended), and to sustain
aerobic activities for at least 10 minutes per episode. In addition, women should be encouraged to perform strengthening exercises involving all major muscle groups at least 2 days per
week.
7. Diet recommendations are more stringent
and prescriptive than in previous guidelines:
· Fruits
and vegetables, 4.5 cups per day
·
Fiber, 30 g per day (1.1 g fiber/10.0 g carbohydrate)
· Whole
grains, 3 servings per day
· Sugar,
5 servings (1 tablespoon) per week
· Nuts,
4 servings per week
· Saturated fat, <7% of total energy intake
·
Cholesterol, <150 mg per day
· Sodium, <1500 mg (1 teaspoon)
per day
8. Consumption of omega-3 fatty acids in fish or in capsule form (e.g., 1800 mg/day of eicosapentaenoic
acid) may be considered for primary or secondary prevention of cardiovascular events in women with hypercholesterolemia, hypertriglyceridemia,
or both.
9. The algorithm for preventive care now
includes specific recommendations for stroke prevention in women with atrial fibrillation.
10. Finally, the guidelines continue to emphasize
avoidance of therapies without demonstrated benefit or with risks that outweigh their benefits (Class III interventions):
·
Noncontraceptive hormone therapy outside of indications for menopausal symptoms
· Antioxidant vitamin supplements
· Folic acid supplements, except during childbearing years to prevent neural tube defects in offspring
·
Routine use of aspirin in healthy women aged <65
Impaired
Balance After Taking Zolpidem
The effect was particularly
striking among older adults.
Frey DJ et al. J Am Geriatr Soc 2011 Jan 59:73
Recurrent
Shingles Is More Common Than You Might Think
Shingles recurred in 6% of patients during
8 years of follow-up.
Yawn BP et al. Mayo Clin Proc 2011 Feb 86:88
Association
Between Enterovirus Infection and Type 1 Diabetes
The clinically significant
link probably involves viruses, pancreatic islet cells, and patients' immune systems and genotypes.
Yeung
W-CG et al. BMJ 2011 Feb 3; 342:d35
Hober D and Sane F. BMJ 2011 Feb 3; 342:c7072
Plasma
Amyloid-Beta Levels and Cognitive Decline
Among community-dwelling elders without dementia, lower plasma
amyloid-beta 42/40 levels were associated with greater cognitive decline, and "cognitive reserve" modified the association.
Yaffe
K et al. JAMA 2011 Jan 19; 305:261
Validating PET Amyloid Imaging with Autopsy
Florbetapir positron emission tomography imaging of amyloid-beta showed
strong correlations with autopsy measures of amyloid plaque pathology obtained within 1 year after imaging.
A hallmark pathology of Alzheimer disease (AD) is the amyloid-beta (Aβ) plaque, which
could not be detected during life until recently. Advances have permitted its detection in cerebrospinal fluid and with positron
emission tomography (PET) scanning using the [11C]Pittsburgh compound B. However, this compound's short half-life
requires local cyclotron production, so it is not clinically useful. Several companies are developing PET amyloid imaging
agents labeled with [18F] that could be transported long distances to hospitals and clinics.
For this partially manufacturer-funded study, investigators recruited patients with terminal
diseases. Patients were scanned using the PET amyloid imaging agent [18F]florbetapir within 1 year of death; 74
younger, healthy controls were also scanned. Blinded investigators evaluated the images both quantitatively and with visual
ratings. Autopsies, performed on 35 of the case patients, included both Aβ measurement with quantitative immunohistochemistry
and rating of tissue slides for neuritic plaques.
Regardless of the method used
for analysis of the PET and postmortem data, PET image findings obtained during life correlated strongly with the degree of
pathology seen at autopsy.
Journal Watch Neurology February 22, 2011
·
Medline abstract (Free)
Topical Botulinum Toxin for Wrinkles
No need to frown if you don't like needles.
Botulinum toxin A (BTX-A) injection is the most popular cosmetic procedure
in the U.S. The main medical limitations of BTX-A treatment include the need for injection and the resultant bruising. In
this randomized, double-blind, repeat-dose, placebo-controlled, manufacturer-sponsored study, a
topical BTX-A preparation (RT001) was applied under occlusion for 30 minutes to the crow's feet of 19 subjects,
and placebo ointment was applied to the crow's feet of another 17 subjects. The treatments were repeated at 4 weeks. The
degree of improvement was assessed in patients at rest on a 5-point wrinkle scale at 4 and 8 weeks after the first treatment.
At
4 and 8 weeks, 95% of RT001 subjects had at least a 1-point improvement in their wrinkle
score, compared with only 15% of placebo subjects. Improvement of at least 2 points was noted in 29% of RT001 recipients
at 4 weeks and in 50% of RT001 recipients at 8 weeks, compared with none of the placebo recipients. On self-ratings at 8 weeks,
84% of the RT001-treated subjects and 41% of the placebo-treated subjects rated their crow's feet to be improved. All
comparisons were statistically significant. There were no treatment-related adverse events.
Journal Watch Dermatology February 11, 2011
Early balding seen doubling
prostate cancer risk
Men with prostate
cancer are twice as likely to have had male pattern baldness starting at age 20, according to results of a study that found
no increased risk among men who began balding in their 30s or 40s.
The findings, published Feb.
16 in Annals of Oncology (doi:10.1093/annonc/mdq695), suggest that men with early baldness may benefit from routine prostate
cancer screening or preventive measures that could include the systematic use of 5-alpha reductase inhibitors.
Obesity? Expect more and more atrial fibrillation
This study concluded that obesity is associated with a higher incidence of recurrence of atrial fibrillation and greater atrial fibrillation burden. The American Journal of
Cardiology
Obesity alone increases coronary
heart disease death risk
Being obese may significantly increase the risk of having a
fatal coronary heart disease event independent of known obesity-affiliated cardiovascular risk factors such as high blood
pressure and high cholesterol, investigators in Scotland have found.
By contrast, obesity alone was
not seen as significantly increasing the risk of nonfatal CHD events.
The findings, derived from the
long-term follow-up of a large pharmaceutical trial, and published Feb. 15 in the journal Heart
Obesity on its own raises heart attack risk, study says
A study of 6,000 middle-age men found that those who were obese had a 60% higher risk of death
from a heart attack independent of other factors, according to a report in the journal Heart. Researchers at the University
of Glasgow in Scotland suggested the reason may be tied to chronic inflammation that often accompanies significant weight
gain. HealthDay News
Bariatric surgery may improve heart health for obese patients
Severely obese patients had reductions in their left ventricular mass and right ventricular
cavity volume -- changes that indicate more normal shape and less stress on the heart -- after undergoing bariatric surgery,
researchers reported in the Journal of the American College of Cardiology. The study also
found that obese patients who had the procedure lost an average of nearly 100 pounds and had healthier blood pressure and
cholesterol levels compared with a control group. USA TODAY/HealthDay News
Help for cancer patients with vertebral body compression fractures
For painful VCFs in patients with cancer, kyphoplasty
is an effective and safe treatment that rapidly reduces pain and improves function. The Lancet Oncology
Adolescent hearing loss on the rise
Among low-socioeconomic status adolescent girls, the rate of high-frequency hearing loss has doubled over the past two decades. Much of this increase appears to be related to a huge increase in the
use of personal listening devices. (Full-text access is time-limited.) Journal of Adolescent Health
Study ties hearing loss to dementia risk
Elderly people with mild hearing loss were about twice as likely to suffer dementia as those
without hearing impairment, researchers reported in the Archives of Neurology. The study also found older people with severe
hearing loss had about a five times increased risk of dementia.CNN
High bilirubin levels are tied to lower risk of death
A study of 504,206 people in the U.K. found that every 0.1 milligram per deciliter increase
in bilirubin -- a protein product of hemoglobin breakdown -- led to an 8% lower risk of lung cancer among men and an 11% lower
risk among women. The study in the Journal of the American Medical Association also linked each additional 0.1 milligram per
deciliter of bilirubin to a 6% decreased risk of chronic obstructive pulmonary disease and 3% lower mortality risk among both
men and women. Bloomberg Businessweek/HealthDay News
When and why aspirin fails
Results of this study suggest that aspirin failure is merely
a marker of higher risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy. The American Journal of Cardiology
Long-Term Bisphosphonate Use
Linked to Subtrochanteric and Femoral Shaft Fractures in Older Women
Long-term oral bisphosphonate use is associated with an increased risk for subtrochanteric
or femoral shaft fractures, but the absolute risk remains low, according to a JAMA study.
Researchers
examined Canadian provincial databases to identify some 700 Ontario women over age 68 taking oral bisphosphonates who were
hospitalized for a subtrochanteric or femoral shaft fracture. Cases were age-matched to 3500 controls — also taking
bisphosphonates — without such fractures.
Women who took bisphosphonates for
at least 5 years had an increased risk for subtrochanteric or femoral shaft fractures (adjusted odds ratio, 2.74), compared with women who used bisphosphonates for fewer than 100 days. Among women treated at
least 5 years, the absolute risk of developing one of these fractures was low (0.13% within the following year, 0.22% within
2 years).
The authors note that clinicians should continue prescribing bisphosphonates
for appropriate patients. However, "long-term use of these drugs may warrant reconsideration, especially in patients
at relatively low risk of fracture. It may be appropriate to consider a drug holiday for selected patients."
JAMA article
In-Clinic Tests Can Help Determine
Who Is Fit to Drive After a Stroke
Three office-based tests may
help identify which stroke survivors are at risk for failing a driving test, according to a meta-analysis in Neurology.
Researchers analyzed 27 studies comprising some 1700 stroke survivors, over half of whom were
declared fit to drive after they passed an on-road test. Patients had a higher likelihood of passing if they had undergone
on-road or simulator-based driving training before their test.
The following office-based tests predicted who was at risk for failing the on-road test:
·
Road Sign Recognition test — Measures traffic knowledge and visual comprehension (sensitivity, 84%; specificity,
54%);
·
Compass test — Assesses cognitive speed and visual-perceptual and visual-spatial abilities (sensitivity, 85%;
specificity, 54%);
· Trail Making Test Part B — Looks at visual-motor
tracking and visual scanning (sensitivity, 80%; specificity, 62%).
Three of four studies found no increased crash risk among stroke survivors who passed the on-road test, but
the authors write that there were too few studies to enable a firm conclusion on that point.
Neurology article
Trail Making Test (Free PDF)
New-onset diabetes may help
guide pancreatic cancer screening
A
new diagnosis of diabetes may help identify older adults who will develop pancreatic cancer while there is still time for
screening and early detection, researchers reported at a meeting on gastrointestinal cancers sponsored by the American
Society of Clinical Oncology.
In an observational study of more than 20,000 older
adults with pancreatic cancer, 10 antecedent diagnoses were found to be significantly associated with the cancer diagnosis.
PPIs and H2-Blockers — Not So Benign
Acid suppression with proton-pump inhibitors or histamine-2
blockers heightens risk for pneumonia in hospitalized patients.
Effects of intensive blood-pressure control in type 2 diabetes mellitus.
CONCLUSIONS: In
patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120
mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular
events.
ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG,Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F.
Abstract
BACKGROUND: There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to
140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e.,
<120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.
METHODS: A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting
a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The
primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean
follow-up was 4.7 years.
RESULTS: After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the
standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy
group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of
death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55).
The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard
ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77
of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group
(1.3%) (P<0.001).
Effect of intensive treatment of hyperglycaemia on microvascular
outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.
INTERPRETATION: Microvascular benefits
of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased
weight gain, and high risk for severe hypoglycaemia.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr,Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian A, O'Connor P, Pop-Busui R, Schubart U, Simmons D, Taylor H,Thomas A, Weiss D, Hramiak I; ACCORD trial group.
Abstract
BACKGROUND: Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We
investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people
with type 2 diabetes.
METHODS: ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high
HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned
by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy.
In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7
micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first
composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function
were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients
who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or
compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.
FINDINGS: 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard
group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned
to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group
versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in
1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556
of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01,
p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset
of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive
therapy (p<0.05).
INTERPRETATION: Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related
mortality, increased weight gain, and high risk for severe hypoglycaemia.
Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type
2 diabetes: a randomized controlled trial.
CONCLUSIONS: Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared
with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone.
Abstract
CONTEXT: Exercise guidelines for individuals with diabetes include both aerobic and resistance training although
few studies have directly examined this exercise combination.
OBJECTIVE: To examine the benefits of aerobic training alone, resistance training alone, and a combination of both
on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes.
DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial in which 262 sedentary
men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise
program between April 2007 and August 2009.
INTERVENTION: Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72
to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which
they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary
outcomes included measures of anthropometry and fitness.
RESULTS: The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with
a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination
training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c)
were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic
(-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved
maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise
groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost
a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3
to -1.1 kg; P < .05) compared with the control group.
CONCLUSIONS: Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise
control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone.
Combining paracetamol (acetaminophen)
with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.
CONCLUSION: Current evidence suggests that a combination of paracetamol and an NSAID may offer
superior analgesia compared with either drug alone.
Abstract
BACKGROUND: There has been a trend over recent years
for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However,
therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated
the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models.
METHODS: A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature,
and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans
that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified
studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity
scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality
using a validated scale.
RESULTS: Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac
(n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination
of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively.
The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive
studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the
positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found
between experimental groups.
CONCLUSION: Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with
either drug alone.
Effects of Combination Lipid Therapy in
Type 2 Diabetes Mellitus
Conclusions
The combination of fenofibrate and simvastatin did not reduce the
rate of fatal
cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone.
These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular
risk in
the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov
number
Background
We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would
reduce the risk of cardiovascular disease in
patients with type 2 diabetes
mellitus who were at high risk for cardiovascular
disease.
Methods
We randomly assigned 5518 patients with type
2 diabetes who were being treated
with open-label simvastatin to receive either
masked fenofibrate or placebo. The primary outcome was the f irst occurrence of nonfatal myocardial infarction, nonfatal
stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
Results
The annual rate of the primary outcome was
2.2% in the fenofibrate group and
2.4% in the placebo group (hazard ratio in
the fenof ibrate group, 0.92; 95% conf idence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences
bet ween t he t wo st udy groups wit h respect t o any secondar
y out come. Annual rat es
of death were 1.5% in the fenofibrate group
and 1.6% in the placebo group (hazard
ratio, 0.91; 95% CI, 0.75
to 1.10; P=0.33). Prespecified subgroup analyses suggested
heterogeneit y in treatment
effect according to sex, with a benef it for men and possible harm for women (P=0.01 for interaction), and a possible interaction
according
to lipid subgroup, with a possible benefit for patients with both
a high baseline
triglyceride level and a low baseline level of high-density
lipoprotein cholesterol
(P=0.057 for interaction).
Conclusions
The combination of fenofibrate and simvastatin
did not reduce the rate of fatal
cardiovascular events, nonfatal myocardial
infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination
therapy with fenofibrate and simvastatin to reduce cardiovascular risk in
the majority of high-risk patients with type 2 diabetes.
Major lipids, apolipoproteins,
and risk of vascular disease.
CONCLUSION: Lipid assessment in vascular disease can be simplified by measurement of either total
and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.
Abstract
CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified.
OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk.
DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people
without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million
person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534
ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes.
MAIN OUTCOME MEASURES: Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values:
0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein
AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression
analyses were adjusted for within-person variation and combined using meta-analysis.
RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions,
respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for
CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with
non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was
0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins
or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with
the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C.
Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and
1.12 (95% CI, 1.04-1.20) with non-HDL-C.
CONCLUSION: Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or
apolipoproteins without the need to fast and without regard to triglyceride.
http://jama.ama-assn.org/content/302/18/1993.full.pdf+html
Restricted Diet May Improve ADHD Symptoms, but Not Based on IgG Testing
A restricted diet may help reduce symptoms of attention-deficit
hyperactivity disorder in children, according to a study in the Lancet.
Hypothesizing that ADHD might be a hypersensitivity disorder,
researchers randomized 100 children aged 4 to 8 years with ADHD to a diet or control group. The intervention group ate an
individually designed restricted diet consisting of rice, meat, vegetables, pears, water,
potatoes, fruits, and wheat. After 5 weeks, 64% of children in the restricted diet group showed a clinical improvement
of at least 40% on ADHD scores.
The 30 children with clinical improvement moved on to the
challenge phase — having either three high-IgG or three low-IgG foods (based on individual blood tests) reintroduced
into their diet for 2 weeks before switching to the other IgG group. Most children (63%) experienced a relapse of ADHD behavior
during this phase, regardless of whether they were receiving high- or low-IgG food components.
A
commentator says that the results provide "evidence against the benefit of using IgG blood levels (a common practice
in complementary medicine) to determine which foods are triggering ADHD symptoms." She says that children with ADHD may
go on a restricted diet for 2 to 5 weeks, and then reintroduce one food per week.
Lancet article
