Be very careful of what you read: Medical Articles

Why Most Published Research Findings Are False
John P. A. Ioannidis
John P. A. Ioannidis is in the Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece, and Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States of America. E-mail: jioannid@cc.uoi.gr
Competing Interests: The author has declared that no competing interests exist.
I try to keep up with what is happening in my chosen fields of Study: Endocrinology as well as Medical Anthropology, in addition to my craving to know what is happening in this world (I try to read BBC News, The Economist regularly and scan through the internet in search of interesting news items).
I see a medical tendency to exaggerate, and this exaggeration is related to the interest the author has in increasing his prestige or income or career opportunities.
Always look for the Competing Interests.
I am not interested in reading about the Lack of Effect of Oral Medications in Type 2 DM from a professor who has financial relationship with Insulin producing drug companies.
If one researcher has many relationships with many drug companies, the chances are his research results would be WRONG.
I will highlight this article by Dr Ioannidis who has done a favour to all or us by highlighting how often biased results are published and gain in popularity.

Corollary 1: The smaller the studies conducted in a scientific field, the less likely the research findings are to be true.
Corollary 2: The smaller the effect sizes in a scientific field, the less likely the research findings are to be true. Power is also related to the effect size. Thus research findings are more likely true in scientific fields with large effects, such as the impact of smoking on cancer or cardiovascular disease (relative risks 3–20), than in scientific fields where postulated effects are small, such as genetic risk factors for multigenetic diseases (relative risks 1.1–1.5) [7]. Modern epidemiology is increasingly obliged to target smaller effect sizes [16]. Consequently, the proportion of true research findings is expected to decrease.
Corollary 3: The greater the number and the lesser the selection of tested relationships in a scientific field, the less likely the research findings are to be true.
Corollary 4: The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.
Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true.
Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.
Most Research Findings Are False for Most Research Designs and for Most Fields
Claimed Research Findings May Often Be Simply Accurate Measures of the Prevailing Bias

How Can We Improve the Situation?
Is it unavoidable that most research findings are false, or can we improve the situation? A major problem is that it is impossible to know with 100% certainty what the truth is in any research question. In this regard, the pure “gold” standard is unattainable. However, there are several approaches to improve the post-study probability.
Better powered evidence, e.g., large studies or low-bias meta-analyses, may help, as it comes closer to the unknown “gold” standard. However, large studies may still have biases and these should be acknowledged and avoided. Moreover, large-scale evidence is impossible to obtain for all of the millions and trillions of research questions posed in current research. Large-scale evidence should be targeted for research questions where the pre-study probability is already considerably high, so that a significant research finding will lead to a post-test probability that would be considered quite definitive. Large-scale evidence is also particularly indicated when it can test major concepts rather than narrow, specific questions. A negative finding can then refute not only a specific proposed claim, but also a whole field or considerable portion thereof. Selecting the performance of large-scale studies based on narrow-minded criteria, such as the marketing promotion of a specific drug, is largely wasted research. Moreover, one should be cautious that extremely large studies might be more likely to find a formally statistical significant difference for a trivial effect that is not really meaningfully different from the null [32–34].
Second, most research questions are addressed by many teams, and it is misleading to emphasize the statistically significant findings of any single team. What matters is the totality of the evidence. Diminishing bias through enhanced research standards and curtailing of prejudices may also help. However, this may require a change in scientific mentality that might be difficult to achieve. In some research designs, efforts may also be more successful with upfront registration of studies, e.g., randomized trials [35]. Registration would pose a challenge for hypothesis-generating research. Some kind of registration or networking of data collections or investigators within fields may be more feasible than registration of each and every hypothesis-generating experiment. Regardless, even if we do not see a great deal of progress with registration of studies in other fields, the principles of developing and adhering to a protocol could be more widely borrowed from randomized controlled trials.
Finally, instead of chasing statistical significance, we should improve our understanding of the range of R values—the pre-study odds—where research efforts operate [10]. Before running an experiment, investigators should consider what they believe the chances are that they are testing a true rather than a non-true relationship. Speculated high R-values may sometimes then be ascertained. As described above, whenever ethically acceptable, large studies with minimal bias should be performed on research findings that are considered relatively established, to see how often they are indeed confirmed. I suspect several established “classics” would fail the test [36].

It is quite obvious that most of the medical practitioners especially those in private practice have absolutely no idea of what is wrong with evidence based medicine or how certain articles are being touted as the new remedy, especially if they are relying upon drug company salesman or conferences in snow resorts or Hawaii for their continuing medical education. But they can feel that they are “legally” safe, but practice of medicine was supposed to be ethically safe and not legally safe.
As an anthropologist, I look at the published medical literature, even in prestigious journals such as NEJM and see the bias, such as: talking about pregnancy outcomes in San Antonio without mentioning that majority of the people studied there are of Mexican origin and poor, studies from Atlanta talking about High Blood Pressure fail to mention that it is the city with highest proportion of Americans of African Origin, more than once in my travels they have asked me Why do Pima have such high prevalence of Diabetes and people think Pima are the only Indians with Diabetes, such labeling had made pariahs of citizens of Nauru and other Pacific Islands.
Today I was seeing a patient, 38 year old and the note was made that her random Blood sugar was over 400 mg/dl (divide it by 18 to get SI unites i.e. about 22). She was on Long Acting Insulin and also Metformin, Actos and Glipizide.
It would have been so easy to look at the paper and give her more medicine or more of the same medicine and admonish her or label her as a Non Compliant patient. Obviously she was not taking the medications, but the reasons were, all non medical:
Unemployment
Lack of self-esteem in inability to look after family
Food Stamps not allowing her a healthy nutrition.
Bad relationship with Boy friend, who is yet arrested for another DUI (Driving Under Influence).
Alcohol abuse to stave boredom
Depression and lack of interest in her health.
She herself said: if I had a job, most of these problems would disappear.
The approach to this patient is not: more Pioglitazone or more Insulin; it is not a nutrition lecture; it is not Prozac for depression, it is not admission to the in patient ward.
The correct approach is culturally sensitive counseling. How many of our providers can be counted on doing that. I am very lucky since the person I work with, an RN with CDE is extremely competent and takes care of many of the aspects and gives me ample time to do what I think should be done for a Social Disease: Culturally Sensitive Counseling.


I do 5 minutes Continuing Medical Education vignettes for my colleagues. They dismiss the ranting of professors from New Orleans who push vigorously the new generations of drugs (Byetta,ONglyza etc) but are very happy to hear when I give them the summary of article that appeared in Archives of Internal Medicine, Sept 27, 2010
Long Term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk factors in individuals with Type 2 Diabetes
I quote their conclusions
Intensive lifestyle intervention an produce sustained weight loss and improvements in fitness, glycemic control and CDG risk factors in individuals with Type 2 Diabetes.
The study lasted 4 years.
As a good hearted friend of mine from the West Coast said to me: we already know what is good for Diabetes, but so little money goes into the research and implementation of that but millions of dollars are spent by Pharma so that Bald Head professors (Bob Marley would have said that) can go around the world touting that 140 usd per month medications have dubious value over 20 usd per month medications but they certainly reduce something or other from 9.7 to 8.1 and stress the fact that the reduction is 20 per cent! Most of the erudite listeners have no idea that the way it is being presented is an exaggeration and what does 20 per cent mean to most people?
I am currently reading
Diabetes Sugar Coated Crisis
Who gets it, who profits and How to stop it
If you are among those who is not manipulated by the drug companies in your prescribing habits and one of the few who hang on to the youthful hopefulness that you had when you were a medical student, I recommend you read this book…
Within the first few pages, you would read
Social Diseases need Social Approaches….

Hope my doctor friends in the Far East read this blog!



you can read about Dr Ioannides and his great efforts at
http://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-and-medical-science/8269/
to recognize how popular his astringent work has become appealing to the world wide audience that he gets over 1000 invitations internationally to speak! per year..

Why My Airline Food may be Tastier than Yours?

14 October 2010
Background noise affects taste of foods, research shows
By Jason Palmer Science and technology reporter, BBC News
Empty table overlooking vineyard This might be the best place for the tastiest meal

The level of background noise affects both the intensity of flavour and the perceived crunchiness of foods, researchers have found.

Blindfolded diners assessed the sweetness, saltiness, and crunchiness, as well as overall flavour, of foods as they were played white noise.

While louder noise reduced the reported sweetness or saltiness, it increased the measure of crunch.

The research is reported in the journal Food Quality and Preference.

It may go some way to explaining why airline food is notoriously bland - a phenomenon that drives airline catering companies to heavily season their foods.

"There's a general opinion that aeroplane foods aren't fantastic," said Andy Woods, a researcher from Unilever's laboratories and the University of Manchester.

"I'm sure airlines do their best - and given that, we wondered if there are other reasons why the food would not be so good. One thought was perhaps the background noise has some impact," he told BBC News.

"Nasa gives their space explorers very strong-tasting foods, because for some reason thay can't taste food that strongly - again, perhaps it's the background noise.

"There was no previous research on this, so we went about seeing if the hunch was correct."
Tasteful

In a comparatively small study, 48 participants were fed sweet foods such as biscuits or salty ones such as crisps, while listening to silence or noise through headphones.

Meanwhile they rated the intensity of the flavours and of their liking.

In noisier settings, foods were rated less salty or sweet than they were in the absence of background noise, but were rated to be more crunchy.

"The evidence points to this effect being down to where your attention lies - if the background noise is loud it might draw your attention to that, away from the food," Dr Woods said.

Also in the group's findings there is the suggestion that the overall satisfaction with the food aligned with the degree to which diners liked what they were hearing - a finding the researchers are pursuing in further experiments.

Smoking Can Increase Cholesterol and Alter Lipid Profiles

Lipid and lipoprotein profiles among middle aged male smokers: a study from southern India

Ramachandran Meenakshisundaram , Chinnaswamy Rajendiran and Ponniah Thirumalaikolundusubramanian

Tobacco Induced Diseases 2010, 8:11doi:10.1186/1617-9625-8-11

Published:	5 October 2010

Abstract (provisional)

Objectives: The objectives were to investigate into the relationship between lipid profile including Apolipoprotein-A1 (Apo-A1) and Apolipoprotein-B (Apo-B) and smokers and to relate them with smoking pack years. Materials and Methods: A total of 274 active male smokers without any other illnesses and age matched male healthy control subjects (78) with similar socio-cultural background were assessed for clinical details, dietary habits, physical activities, smoking and alcohol consumption. Standard methods were adopted to check the lipid levels. The data were analyzed statistically.

Results

Their ages ranged from 40 to 59 years, systolic BP from 110 to 130 mmHg, and diastolic BP from 76 to 88 mmHg. All of them had similar pattern of diet (vegetarianism with occasional meat). None was on any medication influences lipid level. Their physical activity was moderate. Number of pack years varied from 10 to 14 (mild), 15 to 19 (moderate) and 20 and above (heavy) among 69, 90 and 115 cases, whose mean ages were 43, 44 and 49 respectively. The mean (+SD) values in mg/dl of total cholesterol (TC), Triglyceride (TGL), Apo-B, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and Apo-A1 in mg/dl among mild/ moderate/ heavy smokers and control subjects were 198 (30.6)/ 224 (27.2)/ 240 (24.3) and 160 (20.4); 164(42.6)/ 199 (39.5)/ 223(41.7) and 124 (31.6); 119 (24.9)/ 121 (27)/ 127 (28.3) and 116 (21.4); 94 (19.7)/ 104 (21.8)/ 120 (20.5) and 82 (17.6); 42 (5.9)/ 39 (3.1)/ 35(4.4) and 48 (5.3); and 120 (17)/ 119 (21)/ 115 (25) and 126 (19), respectively. In smokers, there was a rise in TC, TGL, LDL, Apo-B and fall in HDL and Apo-A; these changes were significant (P<0.05).

Conclusion

Number of pack years was directly proportional to abnormal lipid profile. It is also concluded that changes in Apo-A1 and Apo-B were more significant when compared to HDL and LDL cholesterol among smokers. In the view of double risk for smokers (smoking and altered lipid profile) efforts may be made to introduce smoking cessation program.

Where is the Best and Just Medical Care in the World?

FRANCE of course..
A mother is a little anxious that her Little One, 11 months and 17 days old, who has not been sick the entire year has a runny nose and a weeping eye. Coughs but no Fever. The discharge from the nose and the eyes are clear. Being unaccustomed to the Little one, now coughing, she requests an emergency appointment with the local Paediatrician. She called the doctor at 9 30 am and was granted an appointment for the child at 3 45 pm.
The Little One arrives at the consulting rooms of the paediatrician which is on the first floor of a residential building. There are no secretaries or hum of a railway station with people milling around, like I saw in a Gastroenterologists office in Miami, all wearing white coats assigned various jobs, mainly collecting money. There was no one waiting in the waiting room, soon the doctor appears, Bon Jour and come in...It is now 3 40 pm. There are no multiple appointments or overbooking in France, in general and you are seen closer to when you are told you would be seen. The MD checks the child,oral exam, nasal exam, looks into the ears, listens to the heart and the lungs. A few questions and a clinical diagnosis of simple Rhinitis is made. Are you willing to take Homeopathic medications? asks the MD, and prescribes homeopathic eye drops, and four kinds of homepathic pills to be taken at frequent intervals, they are not pills in the regular sense but small pellets which runs out of tubes of medications. A nasal spray is also prescribed in case there is any difficulty in breathing in the coming days, should the child get worse.
The normal fees for consultation with a paediatrician is 28 euros and this time 3 euros was added on because it was an emergency consultation! 31 euros total. You pay the MD and she gives you a preprepared form in which she writes down the name of the patient, the amount paid and her signature. When you send it in to the Social Security, a similar amount is added to your bank account. In fact, today's consultation does not cost the mother any money.
She walks to the nearest pharmacy, In fact there are six pharmacies within walking distance and in Paris, the flashing green signs of pharmacies are a common sight. The prescription and the social security card (Vitale) is given to the assistant, who enters that in the computer and then takes off tubes of homeopathic medications off the shelf. The nasal spray the only concession to western medicine is to be given only if the condition is getting worse. Eye drops were single use containers packed in sums of twenty. The cost of the above prescriptions, should you have no social security as in the case of a visitor from a non EU country..Eye drops 5.15 Euros Nasal Drops 4.19 euros the homeopathic medications were 1.80 euros each, altogehter it would have set a non french person back 17 euros! But since the child is French and the mother is employed, her absolute cost for all the medications were a mere 5.15 euros! In fact the entire urgent expedition to the Paediatrician cost the parent 5 euros! including a consultation and the medications..
Imagine this child with parents who have medical insurance was to get sick in Miami? You can bet that the aggressive medical system there would have included a throat swab, perhaps an Xray and definitely a blood test of some sort and of course the consultation with the paediatrician who could be about one hour late! in the mean time you would be interviewed by the Insurance clerks and also a nurse would have seen and taken all the measurements of the child.
Even if you had insurance, it could set you back 200 dollars for the consultation and the medications. God Forbid, you decided to walk into the Emergency Room of the Baptist hospital, the same consultation which cost the parents 5 euros ie 6.50 us dollars,in France, would end up with multitudes of bills amounting to about 2000 us dollars.
So before you knock the Frenchies, just remember, they have the best health care system in teh world, it is just in that, no one is discriminated because of lack of insurance or income. Like their educational system, which is slightly more elititst, they can take pride of their medical system.
For those doctors practicing in India or Malaysia or Singapore or Thailand or Cambodia or Vietnam, and who wish to follow the American System (results from USA are no better in any field except perhaps in Oncology!), please think of your patients and follow the french system whereby you make clinical diagnosis, do as few tests as possible, and prescribe medications that dont kill the patients ... and dont empty their bank accounts by using a system which is only marginally shown to be better than systems that are so much more humanistic and caring and gentle and less aggressive..

What's New ? Yet another Drug withdrawn?

What Now Brown Cow?
Medications can’t cure Illnesses caused by Society
The Case in Point
Obesity

The agency determined that the CV risks outweighed the marginal benefits associated with the drugs and requested that the manufacturer of sibutramine (Meridia, Abbott Laboratories) voluntarily withdraw the product from the market in the U.S. Abbott Laboratories agreed to the request.
The withdraw came after new data from the approximately 10,000-patient Sibutramine Cardiovascular Outcomes (SCOUT) trial indicated a 16% increased risk for major adverse CV events (a composite of nonfatal MI, nonfatal stroke, resuscitation after MI and CV death) in patients taking sibutramine vs. placebo

When these drugs come out, the companies that manufacture them and the doctors who are their spokespeople put such great pressure on harried General Practitioners that you can see a spike in prescriptions. Whenever poor Indians go to the nearest White City to see a doctor, you can be sure he comes back with a prescription for the newest of the medications, much of which we have low opinion of: Byetta, Januvia, Onglyzia etc etc….

What these purveyors fail to point out is the price of meddling with natural processes within the body, which invariably shows up. Meridia, which was touted as the cure for Obesity now comes with a price tag: Death from Cardiovascular Diseases.

In the past few years, I have seen drugs promoted as panaceas withdrawn when the side effects were too numerous to hide or ignore.
You remember, Vioxx? 80 million people took it, prescribed by god fearing, kindhearted medical personnel, before the heart attack and stroke rate became unacceptable.

Lately, there has been a lot of drugs hastily put into market and withdrawn without much fanfare when they were actually killing the patients with other conditions than the ones they were prescribed for. Avandia Rosiglitazone is banned in the European Union and millions of patients are taking them! The death from cardiovascular disease was unacceptable. This is the second in that class category to be withdrawn and the attention centers on Pioglitazone or Actos. I am certain it would be withdrawn in the future.
The hurry to market widely is driven not by scientific evidence or public health priorities. But Profit.
There is no point in pushing Lantus Insulin in Vietnam someone told me, because they wont be able to afford the 30-euro price tag. In the USA, the same insulin is sold for 140 usd, for those poor people who don't have medical insurance. Detemir is another insulin, which promises to be long acting but is definitely short acting very similar to NPH in its action but not in its price. Lantus has been linked to breast cancer and won’t be long before some more abnormalities discovered. What happened to the old fashioned Insulin? They disappear completely to make room for the expensive alternative, which does have only marginal value.
The case in point is the new drugs in the Incretin Mimetics and DPP4 categories. Not a day goes by without some form or another of pharmaceutically backed thinly disguised as academic material, appears in the mailbox, touting their supremacy. But those who practice medicine in real situations know that these medications have an extremely limited value and of course there are complications, including Pancreatitis and now Lung cancer. Makes you wonder, whatever happened to good old-fashioned NPH and Regular Insulin?
It is not the new medications that we require, but a belief that these diseases are caused by the society and the way we are prodded to live, the so-called Life Style. How can we change when we are asked to follow that path? Drink Soft Drinks, movie stars command from their large posters on roadsides in Asia; high fructose corn syrup which is nothing but poison, little girls are sprouting breasts because of Plastics and other chemicals, hypothyroidism is in on the increase because of pesticides containing peroxidase inhibitors…

Please give me a Good Nurse who has the skill of talking and touching and has the desire to take care of her patients, and just Metformin and the old fashioned NPH and Regular Insulin PLUS enough time to talk to patients (minimum of thirty minutes), I can show you better results than any of these multimillion dollar studies….

The World Overweight and Obesity Rates

This publication has generated a lot of attention around the world. A word of warning, BMI is not a good indicator of health in many asian countries, to begin with in the west 25 kg/m2 and below is considered normal whereas in Asia, it would be more like 22 kg/m2. Plus countries in Asia, especially in India, both Type 2 Diabetes and Cardiovascular diseases are seen in thin people, Waist Circumferences or Waist to Hip ratio may be a better predictor.
Photo shows a normal weight Burmese. Malaysia and Singapore are considered the most overweight/obese nations in Asia. Highest rate of Diabetes kudos goes to India and the lowest rate competition may be won by Bhutan, Laos or North Korea (does anyone have data on North Korea?)


Thirty percent of Mexican adults are obese as are 28% of Americans, the two fattest nations in the world, according to a book just published by the OECD (Organization for Economic Co-operation and Development).



OECD obesity rates have risen from well below 10% before 1980 to at least double that amount in most countries, and triple in others. Obesity has climbed up to the top of the public health policy agenda globally, says the OECD. In nearly half of all OECD countries over half the population is overweight or obese.



The OECD is a Paris-based organization, which brings together 33 of the world's leading economies.

http://www.oecd.org/home/0,2987,en_2649_201185_1_1_1_1_1,00.html A very interesting website.





Obesity rates by country (Source: OECD):



* India 1%

* Indonesia 1 %

* China 2%

* Japan 3%

* Korea 4%

* Switzerland 8%

* Italy 10%

* Norway 10%

* Sweden 10%

* France 11%

* Denmark 11%

* Netherlands 12%

* Austria 12%

* Poland 13%

* Brazil 14%

* Israel 14%

* Belgium 14%

* Turkey 15%

* Portugal 15%

* Finland 16%

* OECD average 16%

* Germany 16%

* Slovenia 16%

* Slovak Rep. 17%

* Czech Rep. 17%

* Spain 17%

* Russian Fed. 17%

* Estonia 18%

* Greece 18%

* Hungary 19%

* Luxembourg 20%

* Iceland 20%

* S. Africa 21%

* Chile 22%

* Ireland 23%

* Canada 24%

* UK 25%

* Australia 25%

* New Zealand 27%

* USA 28%

* Mexico 30%

Long Term Exercise and Diet on Control of Diabetes vs Ordinary Care

From Archives of Internal Medicine

Vol. 170 No. 17, September 27, 2010



The investigators, from the Look AHEAD (Action for Health in Diabetes) Research Group, carried out a multicenter, randomized clinical trial which compared the effects of an intensive lifestyle intervention versus diabetes support and education. The study involved 5,145 obese/overweight people with diabetes Type 2 - their average age was 58.7 years.



* Lifestyle intervention ( ILI ) group - 2,570 of them were assigned to a combination of special diet and physical activity. The aim was to get them to lose 7% of their body weight within 12 months - and to keep the weight off for a period of four years. They were contacted by phone and/or seen at least once a month throughout the 48-month period.

* Diabetes support group (DSE) - 2,575 of them received diabetes support and education. They were encouraged to attend three group sessions annually - these sessions focused on such themes as diet, social support and physical activity.



The ILI group was successful in producing sustained weight losses and improvements in cardiovascular fitness through 4 years of follow-up. The ILI group also experienced significantly greater improvements than the usual-care (DSE) group in A1c, HDL, and blood pressure averaged across this period. The ILI group in the Look AHEAD trial is being offered ongoing intervention activities in an effort to sustain the improvements in risk factors. Cost-effectiveness analyses are being conducted.



The critical question is whether the differences between groups in risk factors will translate into differences in the development of CVD. These results will not be available for several additional years.



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.