HHAL MEDICAL NEWS SEPTEMBER 2010
Higher magnesium intake is linked to lower
diabetes risk
A study in Diabetes Care of about 4,500 people found that those who had the highest consumption of magnesium from
foods and supplements had a 47% lower risk of developing diabetes than those with the lowest
intake. The researchers also found high magnesium intake can help improve insulin sensitivity and reduce inflammation.
http://www.reuters.com/assets/print?aid=USTRE68N4ZA20100924
High Intake of Green Leafy Vegetables Is
Associated with Lower Risk for Type 2 Diabetes
Eat your spinach.
Actos (pioglitazone): Ongoing Safety Review - Potential Increased
Risk of Bladder
Cancer
ISSUE: FDA notified healthcare professionals
and patients that the Agency is reviewing data from an ongoing, ten-year epidemiological study designed to evaluate whether
Actos (pioglitazone) is associated with an increased risk of bladder cancer. Findings from studies in animals and humans suggest
this is a potential safety risk that needs further study. At this time, FDA has not concluded that Actos increases the risk
of bladder cancer. Its review is ongoing, and the Agency will update the public when it has additional information.
BACKGROUND: The drug manufacturer, Takeda, conducted a planned analysis of the study data at the five-year
mark, and submitted their results to FDA. Overall, there was no statistically significant association between Actos exposure
and bladder cancer risk. However, further analyses were also performed looking at how long
patients were on Actos and the total amount of the drug they received during that time. An increased risk of bladder cancer
was observed among patients with the longest exposure to Actos, as well as in those exposed to the highest cumulative dose
of Actos.
RECOMMENDATIONS: Healthcare professionals should continue to follow the recommendations
in the drug label when prescribing Actos. Patients should continue taking Actos unless told otherwise by their healthcare
professional. Patients who are concerned about the possible risks associated with using Actos should talk to their healthcare
professional.
http://www.fda.gov/Drugs/DrugSafety/ucm226214.htm#ds
Even Low-Dose Aspirin Might Lower Risk for Colorectal
Cancer
Even the lowest daily dose of aspirin is associated with reduced risk for colorectal cancer, according
to a case-control study in Gut.
Using questionnaires, Scottish researchers examined use of NSAIDs,
including aspirin, in some 2300 adults with colorectal cancer and 2900 controls. As noted in previous studies, they found
a lower likelihood of cancer with use of any NSAID (odds ratio, 0.73). In addition, they found
that even the lowest daily dose of aspirin (75 mg) was associated with lower risk (0.78) — an effect that was apparent
after 1 year of consistent use and became significant after 5 years.
NSAID use, however, was not associated
with improved colorectal cancer survival during about 4.5 years' follow-up.
The authors say their
study is the first to show reduced colorectal cancer risk with such a low dose of aspirin.
http://gut.bmj.com/content/early/2010/08/12/gut.2009.203000.abstract
New Study Links Oral Bisphosphonates to Esophageal Cancer
A case-control study
in BMJ finds that oral bisphosphonates are associated with increased risk for esophageal
cancer, thus contradicting a recent JAMA study finding no such link.
In the current study, British researchers
used a national database to identify nearly 16,000 adults diagnosed with esophageal, stomach, or colorectal cancer over a
10-year period, and matched them with some 78,000 controls without cancer. Prescriptions for bisphosphonates were then assessed
for the 7.5 years before diagnosis.
Bisphosphonate prescriptions were associated with a 30% increase in risk for esophageal cancer, with the elevated risk
largely limited to patients with 10 or more prescriptions. The drugs did not appear to increase risk for stomach or colorectal
cancer.
The researchers, noting that the contradictory JAMA study used the same database, say the
disparate result may be due, in part, to the longer follow-up and greater number of controls in the current study.
http://www.bmj.com/content/341/bmj.c4444.full
Meat-Based Low-Carb Diet Linked
to Higher Mortality Risk
A low-carbohydrate diet heavy on animal
protein and fat is associated with greater long-term mortality, while a plant-based low-carbohydrate diet is linked to lower
mortality, according to an Annals of Internal Medicine study.
Researchers analyzed
food frequency questionnaires from 85,000 women from the Nurses' Health Study and 45,000
men from the Health Professionals' Follow-Up Study. Among the findings over roughly 20 years' follow-up:
- People who had the highest scores for an animal-based low-carbohydrate diet were at increased risk
for all-cause and cardiovascular mortality.
- Those with the highest
plant-based low-carbohydrate diet scores had a reduced risk for all-cause and cardiovascular mortality.
- Men who more closely followed any low-carbohydrate diet had a higher cancer mortality risk.
Editorialists see
flaws in the study and observe that "no one can legitimately claim that a low-carbohydrate diet is either harmful or
safe with any degree of certainty" in the absence of a large-scale randomized study.
Studies
Make Case for Less Routine Use of PSA Testing For Screening
for prostate cancer: systematic review and meta-analysis of randomised controlled trials
BMJ has published two studies suggesting that less routine use of prostate-specific antigen (PSA) testing
for cancer screening may be beneficial.
One study — a meta-analysis of six randomized
controlled trials comprising almost 400,000 participants — finds no mortality benefit from PSA testing, with
or without digital rectal exam.
The other study, using blood samples from nearly 1200 Swedish men at age
60 in 1981, finds that PSA levels at age 60 correlate very closely with the risk for metastatic
cancer or death from prostate cancer by age 85. In fact, levels under 1 ng/mL were associated
with a low likelihood of suffering prostate cancer metastases (0.5%).
An editorialist says
that "elderly men and those with low risk of disease could be tested less often, if at all."
http://www.bmj.com/content/341/bmj.c4543.full
Screening Mammography Contributes Only a Modest Reduction in Breast Cancer Mortality
Breast cancer mortality
in Norway has dropped since a national screening program was implemented, but only a small proportion is attributable to screening
alone, according to a New England Journal of Medicine study.
Researchers compared mortality rates
among four groups comprising some 40,000 women diagnosed with breast cancer as follows:
- The screened group was diagnosed after a national screening program was implemented (between 1996 and
2005) and lived in counties that had begun screening.
- The unscreened
group was also diagnosed in this period but lived where screening was unavailable.
- Two historical control groups comprised women diagnosed before the screening program was implemented (1986–1995).
The researchers found
that breast cancer mortality fell by 7.2 deaths per 100,000 person-years between the screened group and historical controls.
However, it also dropped, by 4.8 deaths per 100,000 person-years, in the unscreened group compared with historical
controls. Thus, only a drop of 2.4 deaths per 100,000 person-years could be attributed to screening alone. Improvements in
care may have accounted for some of the remaining benefit.
http://www.nejm.org/doi/full/10.1056/NEJMoa1000727
Glucosamine and Chondroitin Are of No Help in Osteoarthritis, Researchers Find
Glucosamine and chondroitin, either alone or in combination, have no clinically relevant effect on joint
pain in osteoarthritis, according to a BMJ meta-analysis.
The authors analyzed
results from 10 randomized trials encompassing some 3800 patients allocated to glucosamine,
chondroitin, both, or placebo. Reductions in pain scores in some trials, although occasionally attaining statistical
significance at certain time points, did not reach clinical relevance.
The authors conclude: "We are confident
that neither of the preparations is dangerous. Therefore, we see no harm in having patients continue these preparations as
long as they perceive a benefit and cover the costs of treatment themselves."
http://www.bmj.com/content/341/bmj.c4675
Compression
Stockings: Thigh-Length Outperforms Below-Knee Variety After Stroke
In patients immobilized by stroke, use of thigh-length compression stockings is
associated with a lower rate of deep venous thrombosis than the below-knee variety, according
to an Annals of Internal Medicine study.
Investigators in the CLOTS-2 trial randomized some 3100 immobile
patients hospitalized for stroke to usual care plus either thigh-length or below-knee stockings. Patients underwent ultrasonography
at roughly 7 and 30 days. The primary outcome, thrombosis in the femoral or popliteal veins,
occurred more often in the below-knee group (8.8%) than in the thigh-length group (6.3%).
Editorialists point
out that the 2009 CLOTS-1 trial found no advantage to thigh-length stockings over no stockings
— and an added risk for skin breaks. They conclude: "Clinicians need to realize that despite the ubiquity of graduated compression stockings in many settings, the net benefits and risks of this seemingly innocuous
intervention remain uncertain."
http://www.annals.org/content/early/2010/09/20/0003-4819-153-9-201011020-00280.full
USPSTF
Reaffirms 2004 Guideline on Testicular Cancer Screening
Physicians
need not regularly screen asymptomatic men for testicular cancer, the U.S. Preventive Services Task Force reaffirms in the Annals of Internal Medicine.
Since issuing its
last guideline in 2004, the USPSTF has not found any new evidence on the benefits or harms of screening, so the guideline
remains unchanged.
The USPSTF is accepting public comments on this recommendation on its website
http://www.annals.org/content/153/6/396.abstract
Tiotropium Bromide Step-Up Therapy for Adults with Uncontrolled Asthma
Conclusions
When added to an inhaled glucocorticoid, tiotropium
improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent
to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov
number, NCT00565266.)
http://www.nejm.org/doi/full/10.1056/NEJMoa1008770?query=OF
Fat-free milk for constipation?
A new benefit may have been found for drinking fat-free milk. In a study of individuals
with chronic constipation, supplementation with fat-free milk significantly increased intestinal motility (as measured by
levels of motilin and ghrelin) in all groups, including the control subjects. Whole milk, in the control group, had the opposite
effect.
Working long hours may up heart disease risk in unfit men
Unfit men who worked 41 to 45 hours a week had a 59% higher risk
for cardiovascular disease compared to those who worked fewer hours, a Danish study published
in the journal Heart showed. Researchers also found that men who were physically fit were 45% less likely to die of heart
disease and 38% less likely to die of other causes than colleagues who were unfit.
http://www.bloomberg.com/news/2010-09-06/fitness-protects-men-working-long-hours-from-early-death-study-shows.html
Vitamin D: Nobody has enough and the results
are bad
This study confirms a
high prevalence of vitamin D deficiency in the general health care population and an association between vitamin D levels and prevalent and incident cardiovascular risk factors
and outcomes.
http://www.ajconline.org/article/S0002-9149(10)01131-8/fulltext
Study links metabolic syndrome to heart events, stroke
A review of 87 studies showed that patients with metabolic syndrome had a twofold or
greater risk of heart complications, heart attack or stroke and a 50% increased risk of dying from any cause. The study in
the Journal of the American College of Cardiology also showed the detrimental health effects of metabolic syndrome were stronger
in women than men, but researchers said they were unsure of why.
http://www.reuters.com/assets/print?aid=USTRE68K2D320100921
Nearly
10% of U.S. Adults Are Depressed
Nearly 1 in 10 U.S. adults is depressed, according to an MMWR
report.
CDC researchers examined data from the 2006
and 2008 Behavioral Risk Factor Surveillance System surveys, which included the Patient Health
Questionnaire 8 (a depression screening tool). Some 235,000 U.S. adults were included in the analysis.
Among the other findings:
- Current depression was most common in the Southeast, with Mississippi having the highest prevalence
(14.8%); prevalence was lowest in North Dakota (4.8%).
- Depression
was more common among women than men; among blacks and Hispanics than whites; and among middle-aged adults than among younger
and older adults.
- Those without health insurance were significantly
more likely to be depressed than those with coverage.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5938a2.htm?s_cid=mm5938a2_x
Glomerular Filtration Rate May Be an Indicator of Future Vascular Risk
The earliest stages
of chronic kidney disease seem to portend a higher risk for incident vascular disease,
according to a meta-analysis and a prospective study in BMJ.
The meta-analysis
— encompassing 33 prospective studies and over 275,000 subjects — set out to explore
the link between estimated glomerular filtration rate (eGFR) and risk for incident stroke. It found a 43% higher risk among those with eGFRs under 60
mL/min at baseline. The risk was even higher among Asians.
The prospective study, undertaken in
Iceland, involved some 17,000 people without apparent vascular disease at entry. During a median follow-up of 24 years, those
with eGFRs under 60 at baseline were more likely to suffer coronary disease. The added contribution of eGFR in estimating
risk was only modest, however — less important than smoking status or diabetes.
Editorialists write
that "chronic kidney disease ... should act as a 'red flag' that triggers cardiovascular risk assessment and implementation of appropriate preventive strategies."
http://www.bmj.com/content/341/bmj.c4249.full
Monoarticular Arthritis: Which Patients
to Treat for Gout?
A new clinical score supports
decision making.
Researchers at an academic
rheumatology department in the Netherlands prospectively developed a diagnostic rule for gout using data from 381 consecutive
patients with monoarticular arthritis who were referred by family physicians. Within 24 hours of visits to family practitioners,
patients underwent joint aspiration, examination of synovial fluid for monosodium urate (MSU) crystals, physical examination,
and laboratory testing. Researchers, who were blinded to the family practitioners' diagnoses of gout or nongouty arthritis,
analyzed predefined potentially diagnostic variables in logistic regression models; variables that were significantly associated
with presence of MSU crystals were weighted and used to develop a clinical prediction model. The best-fit model included seven
clinical variables, with a maximum clinical score of 13 (see the table).
MSU
crystals were identified in 216 patients (57%). The prevalence of gout was 2.8% among patients with scores 4 and 80.4% among those with scores 8. The authors
recommend that patients with scores 8 should receive therapy for gout and
that those with scores between 4 and 8 should undergo joint aspiration and examination for MSU crystals, as well as examination
for the remote prospect of infection, depending on history and clinical presentation
http://www.umcn.nl/Research/Departments/eerstelijnsgeneeskunde/Pages/Jichtcalculator.aspx
Reducing 10-year stroke risk through surgery
Successful carotid endarterectomy (CEA) for asymptomatic patients younger than 75 years of age reduces 10-year
stroke risks. Half this reduction is in disabling or fatal strokes. Net benefit in future patients will depend on their risks
from unoperated carotid lesions (which will be reduced by medication), on future surgical risks (which might differ from those
in trials), and on whether life expectancy exceeds 10 years.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61197-X/abstract
Report: U.S. cancer rates are on the decline
The number of new cancer diagnoses in the U.S. fell by about 1% annually between 1999 and 2006, while deaths from
all cancer types also declined by 1.6% annually from 2001 to 2006, according to an report by the CDC
and several cancer groups. Experts said the results could be attributed to advances in medical screening technology and treatment
and a deeper understanding of cancer and its sources.
http://www.businessweek.com/lifestyle/content/healthday/636217.html
Flu shots may help curb heart attack risk, study finds
U.K. researchers found that older patients who received flu shots were 19% less likely than those who did not get
vaccinated to have a heart attack in the following year. The study in the Canadian Medical Association Journal also showed
early vaccination was associated with a 21% reduced risk of heart attack compared with vaccination later in the flu season,
which had a 12% reduced risk.
http://www.reuters.com/article/idUSTRE68J3RU20100920
Hiding the results? Obesity and prostate cancer
Obesity was associated
with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate
cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.
http://www.amjmed.com/article/S0002-9343(10)00461-4/fulltext
What can fenofibrate do for the high-risk patient?
In this study the fenofibrate/pravastatin
160/40 mg fixed-dose combination therapy significantly improved the global atherogenic lipid profile in high-risk patients
with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.
http://www.ajconline.org/article/S0002-9149(10)01041-6/fulltext
Better than aspirin in secondary stroke prevention
Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after
an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol
could be used for prevention of stroke in patients with non-cardioembolic stroke.(
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70198-8/abstract
What can 7-day Holter monitoring detect? And not?
According to these authors,
7-day Holter monitoring clearly improves detection and allows a better characterization of
ventricular arrhythmic episodes but seems to be less useful for supraventricular events.
http://www.ajconline.org/article/S0002-9149(10)00963-X/fulltext
Long-term Effects of a Lifestyle Intervention
on Weight and Cardiovascular Risk Factors in Individuals With Type 2 Diabetes Mellitus
Four-Year Results of the Look AHEAD Trial
The
Look AHEAD Research Group
Arch Intern Med. 2010;170(17):1566-1575.
doi:10.1001/archinternmed.2010.334
Background Lifestyle interventions produce short-term improvements in glycemia and cardiovascular disease (CVD) risk
factors in individuals with type 2 diabetes mellitus, but no long-term data are available. We examined the
effects of lifestyle intervention on changes in weight, fitness, and CVD risk factors during a 4-year
study.
Methods
The Look AHEAD (Action for Health in Diabetes) trial is a multicenter randomized clinical trial comparing the
effects of an intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control
group) on the incidence of major CVD events in 5145 overweight or obese individuals (59.5% female; mean
age, 58.7 years) with type 2 diabetes mellitus. More than 93% of participants provided outcomes data at each
annual assessment.
Results Averaged across 4 years, ILI participants had a greater percentage of weight loss than DSE participants
(–6.15% vs –0.88%; P < .001) and greater improvements in treadmill
fitness (12.74% vs 1.96%; P < .001), hemoglobin A1c level (–0.36% vs –0.09%;
P < .001), systolic (–5.33 vs –2.97 mm Hg; P < .001)
and diastolic (–2.92 vs –2.48 mm Hg; P = .01) blood pressure, and levels of
high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P < .001) and triglycerides
(–25.56 vs –19.75 mg/dL; P < .001). Reductions in low-density lipoprotein
cholesterol levels were greater in DSE than ILI participants (–11.27 vs –12.84 mg/dL; P = .009)
owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI participants maintained
greater improvements than DSE participants in weight, fitness, hemoglobin A1c levels, systolic blood
pressure, and high-density lipoprotein cholesterol levels.
Conclusions Intensive lifestyle intervention
can produce sustained weight loss and improvements in fitness, glycemic control, and CVD risk factors
in individuals with type 2 diabetes. Whether these differences in risk factors translate to reduction in
CVD events will ultimately be addressed by the Look AHEAD trial.
Impaired Physical Capability in Elders Associated with Increased
Mortality Risk
Community-dwelling older adults who have difficulty performing everyday physical tasks face increased
mortality risk, according to a meta-analysis in BMJ.
Researchers evaluated 28 studies that examined associations
between at least one measure of physical capability — grip strength, walking speed, chair rises, or standing balance
— and all-cause mortality. They found that weaker grip strength, slower walking speed, and slower chair rise time were
all significantly associated with elevated mortality, even after adjustment for age, sex, and body-mass index. Data on standing
balance were limited, but there was a trend toward higher mortality with poorer balance.
The authors conclude:
"Such measures may therefore provide useful tools for identifying older people at higher risk of death."
http://www.bmj.com/content/341/bmj.c4467.full
Avoid Stenting for Carotid Stenosis in Those 70 and Older, Meta-Analysis Suggests
Stenting in patients
with symptomatic carotid stenosis should be avoided in those aged 70 and older, according
to a Lancet meta-analysis.
Investigators from three randomized trials,
seeking to reconcile disparate findings on the risks of treatment with endarterectomy versus stenting, undertook a preplanned
meta-analysis of their data. Their trials comprised some 3400 patients with symptomatic stenosis who were judged to be at
standard surgical risk.
In both the intention-to-treat group (analyzed at 120 days) and per-protocol group (analyzed
at 30 days), patients under age 70 showed no difference in risk for the primary outcome (the combination of any stroke or
death), regardless of the therapy. In those 70 and older, however, stenting was associated with a doubling of risk.
The authors conclude
their findings provide "strong evidence that, in the short term, the harm of stenting compared with endarterectomy decreases
with younger age
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61009-4/abstract
Does Intensive Blood Pressure
Control Delay Progression of Hypertension-Related Kidney Disease?
Maybe, in patients with proteinuria.
In the previously published African-American Study of Kidney Disease and Hypertension
(AASK), 1094 nondiabetic black patients with hypertension-related chronic kidney disease were
randomized to intensive or standard blood pressure (BP) control. Despite significantly lower average BP with intensive treatment
(130/78 mm Hg vs. 141/86 mm Hg), a composite outcome (50% reduction in glomerular filtration rate,
end-stage renal disease, or death) was similar in the two groups at 4 years (JW Gen Med Dec 17 2002). In the AASK trial, researchers also compared ramipril, metoprolol, and amlodipine
as initial therapies; outcomes were best with ramipril.
After the randomized phase, patients were followed for about 6 more years in a "cohort phase," during
which the target BP was <130/80 mm Hg, and all patients received ramipril (plus other drugs if necessary). During this
phase, BP remained slightly lower in the initial intensive-treatment group (by an average of 3 mm Hg systolic) than in the
standard-control group. The researchers now report final 10-year outcomes.
The rate of a composite endpoint (doubling of serum creatinine, end-stage renal
disease, or death) remained similar in the two groups — about 7 events per 100 person-years. However, in patients
whose baseline protein-to-creatinine ratio exceeded 0.22 (roughly equivalent to 300 mg proteinuria daily), intensive BP control
was associated with a significantly lower incidence of the endpoint, compared with standard control (hazard
ratio [HR], 0.73). In contrast, among patients with protein-to-creatinine ratios 0.22, intensive BP control was associated with a nonsignificantly higher incidence of the endpoint, compared
with standard control (HR, 1.18).
Comment:
Overall, the AASK trial does not a support the idea that a target BP of 130/80 mm Hg prevents progression of hypertensive
renal disease. However, the subgroup of patients with substantial proteinuria appeared to benefit from lowering BP to this
target, and additional research should focus on that subgroup. According to the authors, the mechanism for the observed proteinuria-related
differential effect is unclear
Appel LJ et
al. N Engl J Med 2010 Sep 2; 363:918
