viernes, 17 de octubre de 2014

Questioning Medicine: Prostate Cancer Screening

Andrew Buelt, DO, and Joe Weatherly, DO, are family medicine residents in St. Petersburg, Fla. Together, they co-produce the podcast Questioning Medicine, where they deconstruct issues confronting today's clinicians. In this guest blog, Buelt gives his take on the overuse of prostate cancer screenings
Let the Prostate Be
As prostate cancer awareness month just ended, prostate cancer screening seemed a fitting subject for this week's blog.
Those who know the evidence might think this argument pits European practices against our own domestic actions. Almost like a Ryder Cup for prostate screening. However, I recently saw that almost 50% of patients admit to undergoing lubed finger insertions and blood tests, which we know to be fairly inaccurate, in the last 12 months.
In a Research Letter in JAMA Internal Medicine by Sammon et al., the fact that so many physicians are still screening for prostate cancer makes my evidence-based medicine soul cringe. In a 2012 survey, the authors found that among 114,544 respondents, 37% had undergone screening. Higher socioeconomic status nearly doubled a man's odds of being screened (odds ratio 1.91, 95% CI 2.69-3.34).
Prostate cancer screening has been placed in the no-go category by the U.S. Preventive Services Task Force and the Choosing Wisely campaign, as well as by many other major medical associations.
Even the American Urological Association, which stands to lose the most money from reduced screening, states, "Men ages 55 to 69 ... should talk with their doctors about the benefits and harms of testing ...." In my opinion, they deserve a standing ovation for speaking to the evidence and not to the money, as the American College of Obstetrics and Gynecologists has with pelvic exams.
I suppose some physicians will try to argue that rectal exams are not unpleasant or uncomfortable for the patient, as many did in the comments section of my pelvic exam post. However, if you really believe that, it's probably been a while since your last rectal exam.
The Screening Process
There are two parts to prostate screening: the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Guided by evidence, here's a look at harms and benefits.
First, is the index finger so sensitive and accurate that it can really detect cancer with the DRE? A little common sense would tell us "no chance," and the evidence seems to support that.
In a study published in the Annals of Surgical Oncology by Richie et al., among 644 asymptomatic men, 241 had an abnormal DRE or elevated PSA. And of the 163 who underwent further ultrasound or biopsy, 77% were found to have normal results.
A retrospective analysis of 14 studies by Hoogendam et al. suggested that the positive predictive value of the DRE was only 28% (95% CI 0.20-0.36), meaning that out of 100 men who were diagnosed by their physician's finger, 72 did not actually have cancer. Plus, according to an analysis by Collins et al., 25% of the time when cancer was found after DRE, the biopsy located it in a different part of the prostate!
So unless your patient has a fecal impaction there is probably very little reason to perform a DRE.
What about the PSA blood test? Its accuracy is also riddled with way too many false positives and false negatives. This is one of those tests that has led to serious rates of overdiagnosis.
Only about 24% of those who undergo prostate biopsy because of elevated PSA actually have prostate cancer (Studer and Collette). The study included 162,243 men, and about 76% of those with a PSA over 3 ng/mL were false positives.
In a study published in the Journal of the National Cancer Institute, which reported the results of The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Andriole et al. found barely any benefit with PSA screening and DRE. The cumulative mortality rates in the intervention arm were 3.7 compared to 3.4 per 10,000 person-years in the control arm.
Authors of the European Randomized Study of Screening for Prostate Cancer (ERSPC) found a 20% reduction in prostate cancer deaths with PSA. Yet, when you look at actual numbers, it paints a much different picture. The ERSPC study estimated that 1,410 men would need to undergo screening, and 48 more cases of prostate cancer would need to be treated, for one life to be saved. Meaning 48 men will possibly endure erectile dysfunction or urinary incontinence for life, for every one life saved.
When the USPSTF looked at the evidence, they found for every 1,000 men screened for 10 years, roughly 220 had a positive result. About 110 subsequently get a true diagnosis of prostate cancer, 50 get a complication from treatment, and at most one life is saved.
I'll repeat the most important part of that rant: one out of a thousand is saved! At least 50 men will have a serious complication and about 100 will have to undergo anxiety and sleepless nights for a disease they don't even have.
Better Left Unchecked
Finally, in an estimate by Draisma et al., almost 50% of those diagnosed with prostate cancer would have never developed any symptoms of disease had they been left unchecked. Too often people will argue a 10 to 12 years' increase in survival with those screened for prostate cancer.
The problem is the very small or almost nonsignificant increase in mortality. I do not care if my patient survives longer with a disease, as long as the age of mortality remains the same.
After all, the reason we treat hypertension, high cholesterol, or screen for cancer is to have people live longer; not to die at the same age.
Of course, there are physicians out there with anecdotal evidence of catching life-threatening prostate cancer in early stages during a routine DRE or PSA, and will therefore insist they are great tests, just like the pelvic exam.
What shouldn't be forgotten is all of the men who now wear a diaper, can't get an erection, or can't sleep from high anxiety.
So why even have the test available? Possibly if the patient has a positive family history. It seems to increase the patient's risk two or three times above the standard rate of incidence, according to Whittemore et al.
Thus, instead of one out of 1,000, it is 2.5 out of 1,000. At that point, it might be worth at least a conversation. It is also decent to trend the success of prostate cancer treatment. However, as a screening tool it's like swimming with a shark: rarely will it kill you, but it will likely to leave you mentally or physically scarred, feeling vulnerable, and with high anxiety.
Tomado de:  By Andrew Buelt, DO

jueves, 9 de octubre de 2014



sábado, 4 de octubre de 2014

New study challenges claims that low vitamin D causes type 2 diabetes

A new study from the University of Cambridge in the UK challenges findings of earlier research that concludes having higher levels of circulating vitamin D might prevent type 2 diabetes.
These earlier observational studies raised suggestions that low vitamin D contributes to the development of type 2diabetes. But because they were not designed to investigate cause and effect, they could not prove it: they could only establish a link.
Now a large genetic study published in The Lancet Diabetes and Endocrinology journal, concludes there is no evidence that a person's low level of vitamin D leads them to develop type 2 diabetes.
Senior author Dr. Nita Forouhi, leader of the Nutritional Epidemiology program at Cambridge's Medical Research Council (MRC) Epidemiology Unit, says:
"Observational studies that show a strong and consistent higher risk of type 2 diabetes with lower levels of vitamin D may do so because they have thus far not been able to adequately control for distorting or confounding factors, such as physical activity levels, that may be related both to vitamin D levels and to the risk of type 2 diabetes."
Using data from several studies covering thousands of people of European descent, Dr. Forouhi and colleagues investigated the link between levels of vitamin D and risk of developing diabetes by examining the genes that control blood levels of vitamin D.
The authors also used circulating 25-hydroxyvitamin D levels - considered the best indicator of vitamin D status - as the measure for vitamin D. Insufficiency was defined as having blood levels of 25-hydroxyvitamin D under 50 nmol/L.

No evidence that low vitamin D causes type 2 diabetes

The researchers found no evidence of a link between the risk of developing type 2 diabetes and the different gene variants that control blood levels of vitamin D.
They also found no links between varying levels of vitamin D and several features of type 2 diabetes, such as glucose and glycated hemoglobin, and neither did they find evidence that low vitamin D causes the disease.
Dr. Forouhi says their results echo those of randomized controlled trials - the classic way to test cause and effect links - which have generally concluded taking vitamin D supplements does not stop people developing type 2 diabetes.
"Our findings suggest that interventions to reduce the risk of type 2 diabetes by increasing concentrations of vitamin D are not currently justified," she notes.

Research must continue, especially with longer-term trials say experts

However, "we are far from done with this topic," says Dr. Forouhi who calls for better clinical trials and observational studies to measure more precisely the factors that might link vitamin D to disease.
"Until then, we need to be cautious about vitamin D's potential role in the prevention of type 2 diabetes and stick to things that are proven to work - diet and exercise," she urges.
One of the reasons to persist with research on the link between vitamin D and diabetes is that there appears to be a plausible biological explanation. The active form of the vitamin interacts with proteins in the insulin-producing beta cells in the pancreas. Also, people with diabetes tend to have low blood levels of vitamin D.
Another expert commenting in a linked article says the new findings need to be interpreted carefully. He also makes the point that despite the fact results of short-term studies do not appear to offer much hope, we need to await the results of longer-term trials before drawing final conclusions. However:
"The sky is becoming rather clouded for vitamin D in the context of preventing type 2 diabetes," says Dr. Brian Buijsse, of the German Institute of Human Nutrition in Potsdam-Rehbruecke in Germany.
This news follows reports of another UK study that found contrary to some previous claims, taking vitamin D supplements does not prevent heart attack or stroke.
Tomado: Medical News Today  Written by Catharine Paddock PhD.    Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study, Zheng Ye, et al., Lancet Diabetes Endocrinol, DOI: 10.1016/S2213-8587(14)70184-6, abstract.

miércoles, 1 de octubre de 2014

Gene Study Finds No Proof Vitamin D Guards Against Type 2 Diabetes

There's no genetic evidence that high levels of vitamin D can prevent type 2 diabetes, a new study says.
Some previous research had suggested that elevated levels of vitamin D might protect people against type 2 diabetes, raising the possibility of a link between vitamin D deficiency and the blood sugar disease.
In this study, British researchers investigated the association between diabetes risk and vitamin D by focusing on genes that control blood levels of vitamin D. They found no connection between different variants of these genes and the risk of developing type 2 diabetes.
The results were published Sept. 30 in The Lancet Diabetes & Endocrinology.
"Our findings suggest that interventions to reduce the risk of type 2 diabetes by increasing concentrations of vitamin D are not currently justified. Observational studies that show a strong and consistent higher risk of type 2 diabetes with lower levels of vitamin D may do so because they have thus far not been able to adequately control for distorting or confounding factors, such as physical activity levels," study author Dr. Nita Forouhi, of the University of Cambridge's School of Clinical Medicine, said in a journal news release.
The findings add to evidence showing that taking vitamin D supplements does not prevent diabetes. The only proven ways to prevent type 2 diabetes are diet and exercise, Forouhi said.
One expert noted that long-term trials that are still looking at any possible connection should be weighed in the final analysis.
The results "need careful interpretation, and long-term randomized trials of vitamin D supplementation, which are underway, remain important," Dr. Brian Buijsse, from the German Institute of Human Nutrition Potsdam-Rehbruecke in Germany, wrote in an accompanying commentary in the journal.
"The results of an [analysis] of 35 short-term trials, however, do not offer much hope that vitamin D supplementation can be used to prevent type 2 diabetes. The sky is becoming rather clouded for vitamin D in the context of preventing type 2 diabetes," he said.
Tomado de :
SOURCE: The Lancet Diabetes & Endocrinology, news release, Sept. 30, 2014

martes, 23 de septiembre de 2014

Discovery of hormone essential for iron supply

US researchers have discovered a new hormone that regulates the iron supply needed for the production of red blood cells. According to a study published in "Nature Genetics", the erythroferrone hormone is produced by red blood-cell progenitors in the bone marrow.
Stimulating the production of erythrocytes increases the release of erythroferrone. Subsequently, the hormone regulates the hormone hepcidin, which controls the absorption of iron from food and its distribution in the body. The higher the erythroferrone level, the higher the likelihood that hepcidin is blocked, which, in turn, makes more iron available for the production of red blood cells.
Both too much as well as too little iron can make a person ill. "Modulating the activity of erythroferrone could be a viable strategy for the treatment of iron disorders of both overabundance and scarcity", explained senior author Tomas Ganz from the University of California, Los Angeles.
The discovery may lead to treatments of other diseases associated with anaemia, such as chronic kidney disease, rheumatic disorders or inflammatory diseases. Under these conditions, hepcidin is increased due to inflammation, whereby the iron is practically "locked up". Erythroferrone, or drugs that have the same effect, could suppress hepcidin and thereby make more iron available for the production of red blood cells.
Tomado de
Ref: Nature Genetics 46678–684 (2014)

miércoles, 17 de septiembre de 2014

Cortical bone microstructure, tibia density deficits seen with type 2 diabetes, high HbA1c

Type 2 diabetes and increased HbA1c are associated with deficits in cortical bone microstructure and bone density at the distal tibia, according to research presented at the American Society for Bone and Mineral Research 2014 Annual Meeting
Although it is still uncertain whether the cortical bone deficits explain increased lower leg fracture risks seen in patients with diabetes, the findings identify target areas to investigate the mechanism responsible for skeletal fragility.
“Diabetic bone may be characterized by specific deficits to cortical bone, which are not captured by traditional DXA bone mineral density tests,” Elizabeth J. Samelson, PhD, of the Institute for Aging Research at Hebrew SeniorLife, Harvard Medical School,
amelson and colleagues conducted a community-based study involving 627 adults (367 women, 260 men; mean age, 65 years) to compare bone microarchitecture by high-resolution peripheral quantitative computed tomography (HRpQCT) in patients with type 2 diabetes (31 women, 40 men) and healthy individuals and determine relationships with HbA1c.
Participants, all from the Framingham Offspring Cohort, were evaluated for type 2 diabetes and had HbA1c measured at baseline; diabetes was defined as glucose >126 mg/dl or use of diabetes medication. They all underwent HRpQCT scanning at the tibia and radius at 6 years.
The researchers used linear regression to calculate means and correlations for the association between volumetric bone mineral density (vBMD), geometry and microstructure indices of trabecular and cortical bone and type 2 diabetes and HbA1C. Adjustments were made for age, sex and weight. 
Patients with type 2 diabetes exhibited higher numbers than healthy patients at the tibia for
total vBMD (291.06 mg/cm3 vs. 284 .53 mg/ cm3), trabecular vBMD (184.13 mg/cm3 vs. 175.09 mg/cm3) and trabecular number (2.15 1/mm vs. 2.07 1/mm); the differences were not significant.
Conversely, patients with type 2 diabetes demonstrated significantly lower numbers than healthy patients for cortical vBMD (796.74 mg/cm3 vs. 814 mg/cm3) and cortical porosity (11.17% vs. 10.03%).
Similar results were seen with increasing HbA1c, with trabecular indices better with higher levels but cortical bone indices worse; the significance was limited to trabecular number.
No other differences were seen in HRpQCT bone indices between groups or based on HbA1c level. At the radius, no significant associations were seen between bone HRpQCT indices and type 2 diabetes or HbA1C.
“Older adults with type 2 diabetes have increased risk of fracture but higher bone mass density than those without diabetes,” Samelson said. “ If deficits to cortical bone explain increased skeletal fragility in type 2 diabetes, then future therapies that target cortical bone strength can reduce fracture risk in this vulnerable and growing population.” — by Allegra Tiver
For more information: Samelson E. Abstract 1083. Presented at: American Society for Bone and Mineral Research 2014 Annual Meeting; Sept. 12-15, 2014; Houston.
Tomado de