The Doctor's Doctor: How To Be An Internist In Five Minutes

Internists are known as the doctor's doctor. The breadth of knowledge for internists is enormous. I often laugh at the computer science folks who do drivebyes on my blog and claim that one day a computer will neatly categorize all illness into neat algorithms and make me expendable. It is simply not possible. As an internist, I manage the whole body. And the evaluation and management I perform on every patient is multi tiered in its breadth and structure. I do this with every patient encounter. All day, every day. If you have five minutes, I'll show you how to do what I do. I interpret my data points across four different organizational structures for every patient, every time. Consistency, consistency, consistency.

• By Organ System. Looking at things by organ system is the first way to conquer disease evaluation and management. Is the disease in the brain? The heart? They thyroid? The lungs? The gallbladder? The bladder? The blood vessels? The blood? The bone marrow? The skin? The neurons? The spinal chord? The colon? The eyes? The hair? The nails? The liver? Disease can affect any organ and an internist's job is to figure out which one.

• By Category of Disease Process. Looking at things by category of disease process is another way an internist must classify the illness. Is it infectious? Is it autoimmune? Is it hormonal? Is it traumatic? Is it genetic? Is it environmental? Is it medication induced? Is it a toxin? Is it allergic? Is it iatrogenic? Is it cancerous? And within each of these categories of disease processes, the internist must ask himself which organ system the disease process is affecting. Is it allergy induced asthma or is it genetic alpha-one antitrypsin induced emphysema. Is it alcohol related cirrhosis or Wilson's disease. Is it myelodysplastic syndrome, a disease of the bone marrow, or is it medication induced pancytopenia. What is the process of the disease?

• Is It Systemic Or Localized? Once you understand the disease process and which organ it affects, you must also know whether the problem is a localized process or a systemic process, and if it is systemic, how else does it present. So much in medicine is lost when you aren't keeping your eyes open. When you focus so strongly on one part of the body and fail to understand the rest. Some infections can be localized in an organ, like an abscess in the liver. Some infections can be systemic and involve multiple organs. Like mononucleosis. Some autoimmune diseases can affect just one organ, like multiple sclerosis and its effect on the neurons of the brain and spinal chord. Other autoimmune diseases, like lupus can span multiple organs, from kidneys and brain to heart and lungs. Lets go back to the cirrhosis example. So it wasn't alcohol related after all. It was hemochromatosis, a genetic disease of iron metabolism that can also affect your skin, joints, pancreas and brain. Is your disease process systemic or localized? Sometimes you find liver disease when your looking for arthritis. It's amazing disease doesn't operate in a cubby hole. And if your disease is a systemic process, you must always be on the look out for its systemic complications.

• Is It Acute Or Chronic? As an internist you want to know if the problem is new or old. Has the patient had heart disease for 25 years, or was it diagnosed last week? Has the patient had diabetes before or is that blood sugar of 350 a new finding? Is that Hgb of 8.9 new or was it there three years ago? Knowing whether something is new or old means all the difference in the world in how you approach it diagnostically. What are you going to do with the information you have in front of you?

What you have here is how I break down every possible illness known to man. Every possible illness can be categorized by organ system, type of disease process, a systemic or localized process and acute or chronic nature. But we aren't done yet. This is just the disease. Full of randomized controlled trials with objective data points. What about the patient? Where do they fall into the loop? Patients don't come to your office complaining of Factor V Leiden. They don't come to your hospital complaining of systemic inflammatory response syndrome. They don't come to your office or hospital complaining of grade II esophageal varices. They come to your office complaining of a swollen leg. They come to your office with dizziness and pain when they pee. They come to your hospital vomiting blood. The goal of all physicians is to try and match the subjective complaints of the patient with the object data points. So you must add in the last component of being an internist

• What Does The Patient Tell You? Are they pointing to one specific point in their belly and saying it hurts right here in my right lower quadrant? Or do they wave their hand over their belly and say it hurts all over? Are they even able to talk? Do they have one complaint? Or a hundred? Do their complaints make sense anatomically? Do they make sense physiologically? Is that pain that jumps from the right leg and makes a right angle turn across the abdomen into the left pinky finger real? Are their complaints believable? Are there too many complaints to believe any of them, the pan positive review of systems? Does mental illness cloud their reality? What the patient tells you can either be diagnostic of a very specific condition or more likely, a generalized constellation of complaints that could be a multitude of disease processes as described above. Great historians are wonderful. Bad historians are painful to work with.

And after the patient has talked with you, Dr Internist, it's your job to try and figure it all out, from the top of the their fro to the bottom of their big toe.
It can be very simple

• I'm coughing, short of breath and have fever and an infiltrate on chest xray which turns out to be a simple pneumonia.

Or it can be something much more complex.

• I'm coughing, short of breath and have fever and an infiltrate on chest xray may in fact be Wegener's granulomatosis, an autoimmune process associated with acute renal failure. It may in fact be a post obstructive infiltrate caused by large lung mass and complicated by an empyema. It may in fact be acute lung injury caused by amiodarone toxicity. It may in fact be tuberculosis. It may in fact be an infarct from a pulmonary embolism. It may be a lot of things.

It may be a lot of things. That's what you can expect from your internist. That's why you should want an internist taking care of you. That's how an internist thinks. That's how they were trained. That's how they manage patients every day of the week. That's why internists won't be replaced with computers. That's why they wont be replaced by extenders. In spite of the folks who say we just need more extenders to manage our health care system. They are not trained to do this type of critical thinking. They do not have the medical foundation or the experience to manage illness through these 4 concurrent stages of evaluation. I know this because I did not fully understand it until the end of my seven year journey to my National Board Exam, which certified my as a physician with expertise in his field of knowledge. A knowledge base you want if you ever get sick.
There you are. That's what your internist does. Every day. That's why the world needs us. Because we have the ability to do something nobody else in the world can. And that is to be the doctor's doctor.

source

Bisphenol A

Bisphenol A (BPA) is a chemical compound used to create polycarbonate plastic and epoxy resins. BPA-derived plastics, commercially produced since the 1950s, have become ubiquitous because of their shatter resistance, visual clarity, high heat resistance, and electrical resistance. Polycarbonate plastics are found in an enormous range of products, including eyeglass lenses, CDs and DVDs, personal computers, appliances, power tools, sports equipment, medical devices, and food and drink containers. Epoxy resins are easily formed and resist chemicals, which makes them useful in products such as printed circuit boards, paints and adhesives, dental sealants, and coatings for the inside of metal cans.

Over time, the chemical bond connecting the BPA building blocks deteriorates, releasing BPA molecules. The quantity released is typically very low, but the plastics are so widespread—they're in baby bottles, water bottles, metal food cans, food storage containers—that people are regularly exposed. In a 2003-2004 study by the U.S. Centers for Disease Control, nearly 93 percent of the people tested, age six and above, had detectable bisphenol A in their urine; females had slightly higher levels than males.

The health effects of bisphenol A are widely disputed. The amounts that leach into food are well below the safety thresholds set by the U.S. Environmental Protection Agency (EPA) and the European Commission Scientific Committee on Food. The EPA safety level is based on toxicity testing conducted in the 1980s that showed weight loss in rats given 50 milligrams of BPA per kilogram of body weight each day.

Traditional toxicity testing, including the EPA study, relied upon the idea that a chemical would have no detrimental effect below a certain dose. Tests were conducted by using relatively high doses and then either increasing the dose until an adverse effect was seen or decreasing it until the adverse effect was no longer observed. But subsequent research suggests that for some chemicals, including BPA, a second threshold exists below which similar or new adverse effects occur.

These low-dose effects are commonly associated with the endocrine system, the chemical communication system found in humans and most wildlife. While the nervous system is the rapid communication system controlling functions such as heartbeat, breathing, and movement, the endocrine system typically handles long-term functions and processes, including the development of the brain, nervous system, and other organs and tissues; growth and metabolism; and the functioning of the reproductive system. Hormones are the chemical messengers of the endocrine system, and chemical compounds that mimic hormones, affect their production, or prevent them from reaching their target are known as endocrine-disrupting compounds, or EDCs.

Critics of BPA cite the potential effects of low doses as a cause for concern. Research has shown that BPA mimics estrogen, a naturally occurring hormone, and therefore can affect the body's endocrine system. BPA's effects are often most pronounced when humans are in stages of rapid development, such as in the womb or during childhood. Laboratory studies conducted since the 1990s have noted that low-dose BPA exposure may be connected to abnormal penis development in males, early sexual maturation in females, an increase in neurobehavioral problems such as attention deficit hyperactivity disorder (ADHD) and autism, an increase in childhood and adult obesity and type 2 diabetes, and an increase in hormonally mediated cancers, such as prostate and breast cancers.

As concerns over the potential health effects of BPA exposure have become publicized, manufacturers, consumers, and governments have taken steps to reduce BPA use and exposure. In April 2008 Canadian regulators announced a ban on the use of BPA plastics in baby bottles. As a result, the European Food Safety Authority is now considering whether to take a similar step, and U.S. lawmakers have introduced a bill to ban its use in children's products. In the meantime, manufacturers and consumers have already begun taking steps to reduce BPA use. Many people are now exchangingBPA-containing plastics—including hard-plastic water bottles and baby bottles—for other plastics, glass, or stainless steel containers. Additionally, retailers such as Wal-Mart and Toys "R" Us have announced that they'll remove BPA-containing baby bottles from their stores. Still, the U.S. Food and Drug Administration released a statement in April 2008 that it isn't recommending that anyone discontinue using products with BPA while it continues to assess the risk.

source

Beta Blockers Worsen Blood Sugar--May Cause Diabetes

 

Many people know that it is a bad idea for anyone who takes insulin or a sulfonylurea drug to take a beta blocker. This is because it has long been known that these drugs block the counter-regulatory response that prevents a dangerous hypo or--if it cannot prevent the hypo--at least gives the victim some warning that one is coming by causing shakes and pounding pulse.

Now evidence from a huge study of almost 20,000 people has learned that beta blockers are dangerous to anyone with any blood sugar abnormality. The study is Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA,). It was published in Diabetes Care in May.

Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial--Blood Pressure Lowering Arm and the relative influence of antihypertensive medication.

It concluded: "Baseline FPG >5 mmol/l, BMI, and use of anatenolol +/- diuretic regimen were among the major determinants of NOD [Non-insulin dependent diabetes i.e. Type 2] in hypertensive patients."

An analysis of the study (which is still only available as an abstract to non-subscribers) published in Irish Medical News explains "Hypertensive patients allocated to amlodipine and perindopril were found 34% less likely to develop NOD [Type 2] compared with those allocated to the β-blocker/diuretic combination."

Diabetes in Control adds the following: "Says Dr Anoop Misra, director and head (diabetes and metabolic diseases) Fortis Hospitals: "In patients with hypertension, beta blocker drugs are no longer frontline therapy. These drugs may not only increase blood sugar levels in those who don't have diabetes, but may worsen sugar control in those with diabetes and also blunt warning symptoms when low sugar occurs."

My mail suggests that American doctors are not aware of the negative impact of beta blockers on the blood sugar of their patients as many people with Type 2 who contact me are taking these drugs. My own doctors have also prescribed beta blockers for me in the past.

Here is a list of commonly prescribed beta blockers:

Generic name/Brand Name

cebutolol- Sectral

Atenolol (G)- Tenormin

Betaxolol- Kerlone

Bisoprolol fumarate- Zebeta

Carteolol hydrochloride- Cartrol

Metoprolol tartrate (G)- Lopressor

Metoprolol succinate- Toprol-XL

Nadolol (G)- Corgard

Penbutolol sulfate- Levatol

Pindolol (G)- Visken

Propranolol hydrochloride (G)- Inderal, Inderal LA

Timolol maleate (G)- Blocadren

CAUTION! Do NOT Stop These Drugs Without Help from Your Doctor

One of the nastier problems with Beta Blockers is that if you are taking one and stop it suddenly you raise the risk of having a heart attack. So if you are taking a beta blocker, you MUST contact your doctor and ask for guidance as to the safe way of getting off of it and onto a drug that is safer for people with diabetes.

There are alternatives to Beta Blockers. ACE inhibitors like Lisinopril do not raise blood sugar and also appear to have some kidney-protective qualities. Those who cannot tolerate ACE inhibitors usually do well on ARB drugs which include Diovan (Valsartan) and Avapro (Irbesartan). ARB drugs besides lowering blood pressure, also lower insulin resistance slightly. Though this effect is not usually detectable in people who are severely insulin resistant, I see an immediate impact on my own blood sugar when I take a dose of Diovan after not having used it in a while.

HCTZ (Hydrocholorothiazide, often abbreviated HCT) is a diuretic which is prescribed alone or combined in pills containing other blood pressure drugs. It has been shown to raise blood sugar. This may be because as a diuretic it eliminates water from the blood stream and this concentrates the glucose that is left. Whatever the explanation, if you can control your blood pressure with medications that do not contain HCT do so. Your blood sugar will thank you. Many doctors immediately prescribe the combination pills that contain this diuretic as a first line treatment, rather than prescribing the other drug alone. But if you cannot get adequate control with just the one pill, HCT may help. Just make sure you drink a lot of water with it.

Blood pressure control is as important as blood sugar control in preventing heart disease and stroke and it is thought that the overall improvement in stroke and heart attack statistics over the past decade are due to patients having better blood pressure control. So don't let this news make you avoid doing something about high blood pressure. Just make sure that the drugs you take to control your blood pressure are ones that are safe for people with pre- and full fledged diabetes.

Other ways to lower blood pressure are:

1. Cut way down on carbohydrates. Many people, though not all, will see dramatic drops in their blood pressure when they cut down on their carbohydrate intake.

2. Exercise.

3. Lose weight.

4. Eliminate salt from your diet. Whether this works depends on your genetic make up. For people whose genes make them salt sensitive, cutting salt causes a dramatic improvement in blood pressure. For others it has no effect.

source

Xylitol May Prevent Early Childhood Tooth Decay

 

Photo courtesy of iStockphoto, Craig Veltri

In a recent clinical trial, researchers report a significant reduction of tooth decay in toddlerstreated with the topical syrupxylitol, a naturally occurring non-cavity-causing sweetener.

Researchers reported that nearly 76% of the children in the group who received xylitol were free of tooth decay by the end of the study, compared with 48% of the children in the group that did not receive the substance.

Xylitol is FDA approved as a food additive, and is classified as safe. For the purpose reported here, it can be administered in the form of chewing gum, lozenges, or syrup.

source

New Tuberculosis Vaccine Goes Into Clinical Trials

After 80 years, a new live vaccine against tuberculosis enters clinical trials this week. The new vaccine, VPM1002, is based on a vaccine that has been in use since 1921, and has been genetically engineered to prevent infection with tuberculosis bacteria much more effectively than its predecessor.

"The BCG tuberculosis vaccine, which was developed by French researchers, is the most frequently administered live vaccine in the world," says Kaufmann. However, BCG (short for the bacterium Bacillus Calmette-Guérind) is now frequently ineffective. The immunologist continues: "BCG has become a blunt weapon. We wanted to use genetic engineering to sharpen it so that, rather than hiding from the human immune system, it would stimulate it as much as possible."
"The vaccine bacteria are taken up by the scavenger cells of the human immune system and end up in their digestion chambers. The genetically engineered modification allows them to escape from the chambers and arm the immune system against the tuberculosis pathogens."

The new vaccine has been developed at the Max Planck Institute for Infection Biology. In 2004, the vaccine was licensed to the Hanover-based VPN, which expedited the clinical study.

source

Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How?

RABIES SURVIVOR: Jeanna Giese plays with her dog Maggie in her yard last summer in Fond du Lac, Wisc. The medical marvel survived rabies without vaccination.
AP Photo/Morry Gash

Four years after she nearly died from rabies, Jeanna Giese is being heralded as the first person known to have survived the virus without receiving a preventative vaccine. But Giese (pronounced Gee-See) says she would gladly share that honor with others if only doctors could show that the treatment used to save her could spare other victims as well. "They shouldn't stop 'till it's perfected," said Giese, now 19, during a recent interview about physicians' quest to refine the technique that may have kept her alive.
Giese's wish may come true. Another young girl infected with rabies is still alive more than a month after doctors induced a coma to put her symptoms on hold, just as they did with Giese. Yolanda Caicedo, an infectious disease specialist at Hospital Universitario del Valle in Cali, Colombia, who is treating the latest survivor, confirmed reports in the Colombian newspaper El País that the victim is an eight-year-old girl who came down with symptoms in August, about a month after she was bitten by an apparently rabid cat. Caicedo said that the family had sought treatment for the bite in Bolivar, at a hospital about three hours by foot from their rural home, but that the child, Nelsy Gomez, did not receive the series of vaccines that can prevent the virus from turning into full-blown rabies.
The five shots contain minute amounts of the dead rabies virus and are designed to nudge the body into developing antibodies to fight it. Patients are also given a shot of immunoglobulin (in this case a synthesized rabies antibody) to protect them while their immune systems produce antibodies to the vaccine virus. But the combination is only effective within six days of infection, before symptoms show up; when Gomez developed signs of the disease, it was too late for the shots. With no other options available, doctors induced a coma.
Caicedo is hopeful, but indicated that Gomez will face a long, slow recovery. She would not say how long Gomez was comatose but told ScientificAmerican.com that she had been awake for "a few days" and is stable. The child can move her fingers but cannot walk or eat on her own, and her eyes are open but she cannot speak yet and physicians are not sure if she can see, Caicedo says.
Giese, informed of the case, says that she "hopes and prays" that Gomez will survive.
Giese was the keynote speaker at a conference last week in Atlanta, where scientists gathered to discuss the latest research being conducted on ways to battle the deadly disease. During her talk, she urged physicians to continue efforts to pin down treatments that work.
Giese was 15 when she was infected after being bitten by a rabid bat she had picked up outside her church in her hometown of Fond du Lac, Wisc.

Her parents cleaned the superficial wound and she says they did not believe it was necessary to seek further medical treatment. "We never thought of rabies," she says. By the time Giese began displaying signs of rabies three weeks later—fatigue, double vision, vomiting and tingling in her left arm—it was too late for the antirabies vaccine cocktail.
Instead of giving her up for dead, the doctors decided to "shut the brain down and wait for the cavalry to come" by inducing a coma to give her own immune system time to build up antibodies against the virus, says Rodney Willoughby, an infectious disease specialist who treated Giese at the Children's Hospital of Wisconsin in Milwaukee. Willoughby devised the treatment credited with saving Giese there, which has since become known as the Milwaukee protocol.
Rabies kills by compromising the brain's ability to regulate breathing, salivation and heartbeat; ultimately, victims drown in their own spit or blood, or cannot breathe because of muscle spasms in their diaphragms. One fifth die from fatal heart arrhythmia. Doctors believed that Giese might survive if they suppressed her brain function by sedating her while her immune system attacked the rabies virus.
This was the first time the therapy was attempted, and doctors had no clue if it would work or, if it did, whether it would leave her brain damaged. But Willoughby says it was the only chance doctors had of saving her.
When she arrived at the hospital, Giese couldn't talk, sit or stand and fell in and out of consciousness—she also needed to be intubated to help her breathe. "She was critically ill," Willoughby recalls, "and looked as if she might die within the day."
In addition to inducing the coma, doctors also gave her the antivirals ribavarin and amantadine. They tapered off the anesthetics after about a week, when tests showed that Giese's immune system was battling the virus. For about six months after awakening from the coma, physicians also gave her a compound called tetrahydrobiopterin that is chemically similar to the B-complex vitamin folic acid, which may have improved her speech and ability to eat, Willoughby says.
He notes that physicians gave her the supplement after tests showed that she had a deficiency of the compound, which is known to boost production of serotonin and dopamine neurotransmitters needed to perform motor, speech and other routine bodily functions.

Remarkably, Giese survived. She recovered most of her cognitive functions within a few months, and other skills within a year, Willoughby says. She got her driver's license and is now a sophomore at Marian University in Fond du Lac, where she is majoring in biology. There are lingering signs of her illness: Giese, once an avid athlete, says she now lists to one side when she runs and walks and no longer plays volleyball, basketball and softball as she once did. She also speaks more slowly and sometimes not as clearly as before her illness, but Willoughby says these effects may fade over time.
Giese is "pretty much normal," says Willoughby, an associate professor of pediatrics at the Medical College of Wisconsin in Milwaukee. "She continues to get better, counter to conventional medical thinking."
Rabies has an incubation period of two weeks to three months and kills within a week of the symptoms showing up. The vaccine series and other immune therapies are useless at this point and may even speed up and increase the severity of the symptoms. Usually, patients are made as comfortable as possible in the hospital or, in countries without sophisticated health care, sent home to die an agonizing death.
Antiviral drugs and immune therapies including steroids, disease-fighting interferon-alpha and poly IC (which stimulates the body's own production of interferon-alpha) have been tried, but none have been shown to be lifesaving on their own, Willoughby says.
Over the past four years, the Milwaukee protocol to differing degrees has been used a dozen times, but until now Giese was the sole survivor. Exactly why she lived—and the others died—is still a mystery.
In a 2005 report on her case in The New England Journal of Medicine, Willoughby speculated that she may have been infected with a rare, weakened version of the virus. Today, he chalks Giese's survival up to aggressive intensive care, the decision to sedate her "and 10 percent sheer luck." Which element of that combination made the difference, and whether the antivirals she was given helped save her is unknown.
"In all honesty, we were probably just pretty lucky," he says. Only another survivor, and then animal and clinical trials, will show if the therapy works, and why, he says. The U.S. Centers for Disease Control and Prevention (CDC) plans to test the protocol on rabies-infected ferrets; Thai and Canadian doctors, who unsuccessfully treated a 33-year-old man with rabies with the Milwaukee protocol, recommended in the Journal of NeuroVirology two years ago that physicians exercise "caution" in using the treatment, because it is too expensive and lacks " a clear scientific rationale." Willoughby says it cost about $800,000 to treat Giese.

Rabies is 100 percent preventable with vaccinations if patients receive them before the onset of symptoms, including hallucinations, delirium, muscle spasms, paralysis and hydrophobia. Yet an estimated 55,000  people, mostly in Asia and Africa, die from it annually because of misdiagnosis or because the illness is not recognized until it has taken hold, according to the journal Neurologic Clinics. Often, patients dismiss the potential seriousness of bites, cannot afford follow-up medical treatment or, in some situations, are unaware they've been bitten, as was the case of a 13-year-old Connecticut girl who died of rabies in 1995.
Vaccine shortages as one manufacturer, Bridgewater, N.J.–based sanofi–aventis, upgrades its factory to meet U.S. Food and Drug Administration requirements, and chronic shortfalls of immunoglobulin also play a role in the fatalities. The vaccine-immunoglobulin regimen costs $1,200 to $2,000 in industrialized nations and $100 to $300 in developing countries—an out-of-reach sum for many people, Willoughby says.
Though it's promising that Gomez is still alive, "The hope that the outcome will necessarily be the same as with Jeanna, particularly in a developing country, is expecting a bit much," laments Charles Rupprecht, chief of the CDC's Rabies Program
Willoughby acknowledges that even if Giese's success is reproducible—and the Milwaukee protocol perfected—it likely will only be available for use in 10 percent of cases, because of limited medical facilities in developing countries.
"Re-creating that in a place stricken with poverty, you get into ethical issues of whether we should do this when we should be about prevention; and does that society have the ability to rehabilitate a patient who may survive but with severe [side effects]?" Rupprecht says. "Jeanna created several ethical issues for all of us to deal with this bug."
Giese says that the fourth-year anniversary of her illness has brought up some bitter memories that she'll probably never shake, but she's glad to be alive—and doing as well as she is.
"It takes some getting used to, but I've kind of come to terms with the fact that I'm the only…[survivor]," she says. "At 15, I never would have thought that anything like this would ever happen, and that I lived is just amazing."
An animal lover who owns a dog, two rabbits and six birds, she hopes to one day open a sanctuary in Fond du Lac for endangered animals, including "big predators like lions and tigers and wolves," and maybe even bats, too.
"I'm not scared of them at all," Giese says of bats. "I'm more passionate about animals than I was before. Animals are my happiness and reason for living."

source

Will More Stroke Patients Receive Thrombolytics Now?

According to this article in the September 25th edition of the New England Journal of Medicine, alteplase improves the outcomes in stroke patients up to 4.5 hours after symptom onset. Previously, the “window” of effectiveness was only three hours. The clinical trial criteria are here.

The percentage of patients having a favorable outcome at 90 days in this study wasn’t huge, but was statistically significant - 52% of patients receiving alteplase had good outcomes compared with 45% of patients who received placebo. At the same time 27% of patients had some type of bleeding after receiving thrombolytics compared with only 17% of patients who had bleeding after receiving placebo. The rate ofsymptomatic bleeding in the brain was 2.4% for thrombolytics versus 0.2% for placebo.

So while you may have an overall improvement in your outcome at 90 days if you get the medication, more than 1 in 4 patients who receive the medication will have bleeding and 1 in 40 patients will have symptomatic bleeding.

Is it worth the risk?

In the editorial article accompanying the study, one of the study authors states that “one cannot help wondering why thrombolytic therapy has traveled such a long, difficult path to wider clinical use.”

I can help wondering.

Thrombolytics are one of the few things that physicians can give that will have an immediate and significant harm on patients. Sure, patients may occasionally have bad outcomes from allergic events or they may have undesirable side effects from some medications. But 2.4% of patients will havesymptomatic bleeding in their brains when they get thrombolytics. Some of those patients will die. Bad outcomes in this society are a plaintiff attorney’s dream.

No health care provider wants to risk their life savings even if there is a “small” chance that they could be sued.

So the choice is …
1. Let patient continue with the stroke symptoms they have already presented with and follow the doctrine of “primum non nocere.” After all, even this study shows that if doctors do nothing, 45% of the patients will get better on their own.
-or-
2. Give a medication that may improve clinical outcome in 7% more of the patients … at the risk of getting dragged through 3-5 years of litigation and losing your life savings if the patient has a bad outcome from the medication.

What would you choose?

Want a simple way to immediately expand the use of thrombolytic therapy?

Grant blanket immunity from liability if thrombolytics are given according to the established guidelines. Create a checklist at “guidelines.gov” and let all healthcare providers download it. If the guidelines are followed, the healthcare providers can’t be sued or have any professional actions taken against them. Period.

If an emergency physician gets a CT report from a radiologist that says “no bleed,” the patient meets the criteria for thrombolytic therapy and doesn’t have any exclusion criteria, then the emergency personnel cannot be held liable for any bad outcomes for giving thrombolytics.

There will still be some docs that philosophically disagree with giving patients a medication that could kill them. Nevertheless, there would be an instant spike in thrombolytic use. I guarantee it.

Plaintiff attorneys will stomp up and down at the thought of this idea.

Then again, 7% more of the stroke victims in this country - some of them attorneys - might be able to stomp up and down if docs weren’t so afraid to give thrombolytics for strokes.

source

Don’t Always Trust The Machines

I’m going through a patient’s chart to find an old EKG and this is what I came across.

Not sure which concerns me more - the fact that the EKG machine reads a blank EKG as sinus bradycardia and nonspecific ST abnormality (at least it got the “abnormal ECG” part correct) or …
the fact that it was confirmed by the cardiologist.

I know the cardiologist that read this EKG is a good doctor and a good guy in general. Most likely this confirmation was just due to a momentary lapse in attentiveness.

Nevertheless, this EKG brings up two important points.

First, look at what you’re doing before you hit the “enter” key on a computer. Having this EKG as “Exhibit A” in a malpractice case would be difficult to explain.

Second, don’t blindly trust the interpretations from the EKG machines. The readings may be there to help, but they’re not always right.

source

Commom Phrases Used in Research Communications and What They Really Mean

“It has long been known”
…. I didn’t look it up
“A definite trend is evident”
… These data are practically meaningless.
“While it has not been possible to provide definite answers to the questions”
… An unsuccessful experiment, but I still hop to get it published.
“Three of the samples were chosen for detailed study”
… The other results didn’t make any sense.
“Typical results are shown”
…This is the prettiest graph.
“In my experience”
… Once
“In case after case”
…Twice.
“In a series of cases”
…Thrice.
“It is believed”
… I think.
“It is generally believed that”
… A couple of others think so too.
“According to statistical analysis”
… Rumor has it.
“A statistically oriented projection of the significance of these findings”
… A wild guess.
“A careful analysis of obtainable data”
… Three pages of notes were obliterated when I knocked over a glass of pop.
“It is clear that much additional work will be required before a complete understanding of this phenomenon occurs”
… I don’t understand it.
“Thanks are due to Joe Blotz for assistance with the experiment and to Cindy Adams for valuable discussions”
… Mr. Blotz did the work and Ms. Adams explained to me what it meant.
“It is hoped that this study will stimulate further investigation in this field”
…I quit

source

Unfortunate Bodies: 7 Unbelievable Genetic Accidents

 

Frog-like Baby (unidentified baby - Nepal)

On 2006, this bizarre-looking baby was born in Charikot, the headquarters of Dolakha district, attracting a huge number of onlookers to witness the astonishing sight.
The neck-less baby with its head almost totally sunk into the upper part of the body and with extraordinarily large eyeballs literally popping out of the eye-sockets, was born to Nir Bahadur Karki and Suntali Karki at the Gaurishnkar Hospital in Charikot. The Karki couple is a permanent resident of Dolakha's Bhirkot VDC.

The bizarre baby, however, died after half an hour of its birth, Suntali, the mother, informed. It was taken to the hospital after its death. The news about such a baby being brought to the hospital spread like wildfire and there were hundreds gathered at the hospital to have a look. The police had to be deployed to control the crowd.
The baby weighed 2kg at birth and was born after the normal nine-month gestation period. Suntali, already a mother of two normal daughters, was not suffering from any illness during the pregnancy. Nir Bahadur, the father, says he does not feel any remorse for the newly-born baby's death. "I am happy that nothing happened to my wife," he said.
NOTE: Our readers, Becca and Andrew, report us that "the baby has a condition called anencephaly, a neural tube defect (like the cyclops baby), with no proper brain formation. The baby would have died a few days later. That's why women are advised to take folate in early pregnancy." --Thank you!

13-inch Tailed Man (Chandre Oram - India)

With a 13-inch tail, Chandre Oram, a tea-estate worker, has become quite an object of devotion in his native Alipurduar, West Bengal and believes that Hanuman is manifest in him. "I was born on Ram Navami (birthday of Lord Ram). People have a lot of faith in me - they get cured of severe ailments when they touch my tail. I believe I can do a lot of good to those who come to me with devotion," says the man, before whom thousands of people queue up each day to seek blessings. In a corner of the courtyard of his home, Oram has set up a small Hanuman temple, where he receives offerings on Ram Navami, which he later offers to the deity.

NOTE: video suggested by our reader Luke, thank you!

However, because of the tail, Oram has found it difficult to get a bride. "Almost 20 women have turned down marriage proposals. They see me and agree to a match. But as soon as I turn around, they see my tail and leave. But I have decided I will marry the woman who accepts me and my tail. Or else, I'll remain a bachelor like Hanuman," he said.
Oram's family is proud of his tail and has turned down offers from doctors for its removal by surgery. "He will not survive without his tail. It has become part of his being, his existence," said Rekha, his sister. Doctors say that true tails are rare. But they are located in the coccygeal end of the vertebral column whereas Oram's tail shoots out from the lumbar region. "The coccyx is a vestige in humans and we stopped growing tails from that region a long time ago when we evolved from monkeys. Oram's case seems an aberration, an offshoot of a congenital defect," said eminent surgeon Dr B Ramana. The medical community reads the monkey man's case as a spina bifida -- a defect in the bone of the spine covered by a hole with lots of hair covering it.

Cyclop Baby (unidentified baby - India)

On 2006, this baby was born with a only one eye in India. Medical staff who helped deliver the child believe that the child's condition was caused by an experimental anti-cancer drug. Another cause written in the report by the hospital was that it could also be the result of a chromosomal disorder. The child was diagnosed with a rare chromosomal disorder, known as cyclopia. She was born with a single eye in the center of her forehead, no nose and her brain fused into a single hemisphere. With such severe deformities, it was a miracle that the girl survived even a few minutes after delivery. The baby died days later.

World's Largest Hand (Lui Hua - China)

Lui Hua suffers from a rare condition known as macrodactyly. When he was hospitalized in Shanghai on July 2007, his left thumb measured 10.2 inches and his index finger measured close to 12. On July 20 surgeons undertook a seven-hour operation to reduce the size of Liu's fingers and thumb. Doctors removed 11 pounds of flesh and bone in the procedure. A second surgery is scheduled to take place. Enlarged limbs can be caused by a number of medical conditions. Lymphedema is perhaps the most common cause and results in some extraordinarily enlarged limbs.

Feet facing backwards (Wang Fang - China)

Wang Fang, 27, of Chongqing city in China, was born with her feet facing the wrong way. She has learned to live with her condition without problems and recently refused a disability pension by being classified as disabled. "I can run faster than most of my friends and have a regular job as a waitress in the family restaurant. There is no reason to class me as disabled."

Baby with Three Arms (Liu Junjie - China)

This 2-month-old baby named Liu Junjie from Anhui Province, China, was born with a third arm on 2006. Doctors successfully removed the extremely rare and well-developed third arm, but the baby required long-term physical therapy to gain function in his remaining hand, which has no palm and flexes in either direction. "We're hoping to exchange information with doctors who've dealt with similar cases anywhere in the world," said Chen, head of the orthopedics department at Shanghai Children's Medical Center. "This is so rare that we have virtually no information to go on."

Nipple on the foot (unidentified 22-year-old woman - Brazil)

The bizarre paper describing the case reads: "A 22-year-old woman sought medical care for a lesion in the plantar region of her left foot, a well-formed nipple surrounded by areola and hair. Microscopic examination of the dermis showed hair follicles, eccrine glands, and sebaceous glands. Fat tissue was noted at the base of the lesion. Clinical and histopathologic findings were consistent with the diagnosis of supernumerary breast tissue, also known as pseudomamma. To our knowledge, this is the first report of supernumerary breast tissue on the foot."

source

Scientific studies show. . .

“Scientific studies have shown. . .”

“Recent research suggests. . .”

“A study presented recently reported. . .”

These types of phrases are used daily in the popular media to report on medical and scientific studies which produce results the general population may find interesting. They’re also used regularly by those trying to convince you to buy certain products (e.g., supplements), follow certain diet plans, or take prescription drugs. Unfortunately, such references to scientific evidence are frequently misleading.

In medicine, there are many different types of studies and reports that are used as evidence to support a given treatment recommendation. The thing that most people (especially those writing media reports) don’t seem to realize is that some types of evidence are considered much stronger than others. Many times the media doesn’t seem willing or capable of distinguishing very weak evidence from very strong. Those who’re trying to sell you snake oil are much worse, and will often mislead you by using such phrases while really referring to virtually nonexistent or at least extremely limited evidence.

Some general categories of clinical medical evidence, presented from weakest to strongest, are reviewed below.

Anecdotal evidence. This is literally when recommendations are just based on the experiences of a few patients. An example would be if a handful of patients posting on a message board reported that their arthritic pain improved because they took a new herbal supplement that’s just come on the market, or when a doctor reports positive results after using a drug in a few patients for a problem for which it’s not FDA approved. This is very weak evidence.

Animal evidence.  This evidence based on experimental findings in animals.  While often interesting and many times spurring subsequent human research, obviously the applicability to the clinical care of humans is very limited.

Theoretical evidence.Physicians and scientists have a certain (albeit limited) understanding of human biochemistry and physiology, and a framework for explaining various diseases when something goes wrong. Based on this understanding it is sometimes theorized or assumed that a given drug or treatment shouldwork, based on our comprehension of the pathophysiology and of how the drug or treatment should interrupt that process. Sometimes these theories turn out to be true upon further testing, sometimes not. Again, this is weak evidence.

Observational evidence. Probably most medical studies fall in this category. Large epidemiological studies(such as the famous Framingham Heart Study or Nurses’ Health Study) are of this type. Such studies usually take very large groups of people and via questionnaires, lab studies, periodic physical exams, etc collect vast amounts of data on them over long stretches of time. The data is then analyzed in an attempt to answer specific questions such as “Do smokers have a higher risk of lung cancer than nonsmokers?” (answer - yes, of course) or “Do those with elevated blood pressure have a higher risk of stroke?” (again, yes).

A different research technique in this category is the case-control study. In this type of study, cases of the disease you’re studying are found and matched to “control” patients who do not have the disease, but are very similar in most other ways. You then look back in their medical histories to determine what factors are more strongly associated with those with the disease compared to those without it. These type of studies are often referred to asretrospective studies as well.

Example: say you want to research whether women who’ve taken birth control pills might have a higher risk of breast cancer than those who haven’t. You could design a case-control study to help answer this question by finding a large number of women with a diagnosis of breast cancer, then finding control subjects who don’t have breast cancer but are similar in most other respects (age, weight, smoking history, family history, etc, etc). You’d then just have to look back in the patient’s charts and determine if the women with breast cancer (the “cases”) had a statistically significantly greater chance of having been on birth control pills at some point in the past than the matched women without breast cancer (the “controls”).

It’s extremely important to understand that observational studies suggest correlation, NOT necessarily causation. When you find a correlation, it could mean that one factor causes the other, or it could mean that some other unknown factor you didn’t measure caused the first two to correlate. The classic example would be the observation that the number of ministers in a city correlates with the number of liquor stores. Presumably, this is not because one causes the other but because a third variable (city population) causes the two to correlate. Bigger towns have more ministers and liquor stores, smaller towns fewer.  The size of the town is the causative variable causing the first two to correlate.

Observational evidence is also subject to many types of biases and flaws in study design which can produce pretty bizarre and conflicting study results at times. The individual studies have to be closely reviewed to determine their quality and relevance. It usually takes several studies of this type with similar results to convince physicians that the conclusion is valid. Sometimes such multiple similar studies of this type are grouped together and the results pooled to produce a more robust conclusion(this is called a meta-analysis).

For these reasons, this type of evidence would have to be considered only perhaps moderately strong.  Many times isolated studies of this type make a splash in the media.  Often they’re poor quality studies, without other studies to corroborate their findings, so take these reports with a grain of salt.  Such studies often grab a lot of headlines and cause concern among many people unfortunately.

Experimental evidence.  These are truly strong studies designed to evaluate a question prospectively.  They are similar to case-control studies described above in that there is generally a control group which is compared to a study group.  However, these studies are designed by recruiting large groups of people who all meet the study selection criteria who are then randomly assigned to receive the test or treatment being studied, or a placebo such as a sugar pill.  In the best such studies, neither the subjects nor the researchers collecting the data know which group is receiving the treatment and which are on placebo until the study is over.  This prevents certain types of bias from being introduced which could corrupt the results.  These are called double-blinded, placebo-controlled, randomized clinic trials and are really the gold standard for clinical evidence.

An example would be let’s say you wanted to know if diabetic men aged 35-65 with certain cholesterol levels (hint:  those would be your selection criteria for potential participants in the study) reduce their rate of heart attack by taking statin-type cholesterol lowering drugs.  You’d find a large group of willing patients who fit those criteria, then give them a numbered bottle of pills, and neither you nor the patient would know whether they’re taking the actual drug or a sugar pill.  You’d then monitor them for a period of time, and after all the data is collected and the study is over, you’d analyze whether the study group had a statistically significant (meaning unlikely to be due to chance) lower rate of heart attacks than the control group.

This type of study is considered very strong evidence.  Unfortunately, not all questions easily lend themselves to being answered by such a study design, and it takes a great deal of money to run such a study.  But when such evidence exists for a given treatment, it is considered the strongest available.

In conclusion, I hope that if you bothered to take the time to read this in the future you’ll stop and consider the quality of the evidence being presented when you read “A recent scientific study has shown. . .” in a popular media article.  Always try to consider the strength of the “proof” you’re being presented, and discuss anything reported in the media with your physician to get a better perspective before you form a strong opinion or take action.

source

Quiz Questions for the USMLE

 

Preparing for the United States Medical Licensing Exam Step 1, 2 or 3 is difficult, time-consuming, and anxiety-provoking. Knowing the information cold is the best way to ace the test. Although the test is multiple-choice, studies have shown that being able to answer unkeyed questions shows a higher level of mastery of the material. Try these to see how you are doing...
Question 1
A mildly mentally handicapped 31 year old male is noted to have 10 café-au-lait spots greater than 2 cm, pigmented iris hamartomas, and multiple peripheral nerve Schwannomas. What enzyme is lacking?

see answer below

GTPase

This is von Recklinghausen’s disease
The defect is on chromosome 17

Question 2
If a patient has increased histamine release, venous telangiectasia, bronchoconstriction,
and edema, what is the best test to confirm the diagnosis?

see answer below

24 hour Urinary 5-HIAA

This is carcinoid syndrome
Lab findings in carcinoid syndrome include:
Increased urinary 5-HIAA
Increased urinary histamine
Increased serum bradykinin
Increase peptide P substance

Question 3
A 17 year old girl has abdominal pain, sweating, headaches, and black urine every time she consumes alcohol. What enzyme is decreased?

see answer below

HMB synthase (PBG deaminase)

This is acute intermittent porphyria
Other gastrointestinal symptoms in acute intermittent porphyria include:
Ileus
Distention
Nausea
Vomiting
Constipation
Diarrhea

Question 4
A 72 year old man has swelling and pain in his left great toe joint which developed over
12 hours. There is no fever or other constitutional systems. What is the best drug to treat this condition?

see answer below

Indomethacin

This is gout
Other drugs used to treat gout include:
Colchines between attacks
Allopurinol
Uricosuric drugs – probenecid, sulfinpyrazone

Question 5
A 28 year old man was taken to the operating room for an abdominal obstruction where it was discovered that his ileum contained four 1 cm smooth, submucosal nodules that were yellowish tan on the cut surface. What is the most likely diagnosis?
see answer below

Ileal carcinoid

30% of ileal carcinoids are multicentric
Anatomic distribution of abdominal carcinoids is:
Appendix – 45%
Jejunum-ileum – 28%
Rectum – 16%
Colon – 2%
Ovary - 1%

Question 6
If a patient has coarsened facial features, prominent supraorbital ridges, large, spadelike hands and feet, soft tissue proliferation and an enlarged sella, what substance is most likely to be secreted in excess?

see answer below

Growth hormone

This is acromegaly
Microanatomy of acromegaly includes:
Well-defined pituitary adenoma – most commonly in lateral wings of sella
Adenomas very rarely in sphenoid sinus or parapharyngeal regions
Ectopic production rarely in pancreatic islet cell tumors or lung tumors

Question 7
If a 6 year old girl has hemorrhagic diarrhea, rapidly progressive renal failure and purpura, what two microorganisms are the most likely cause?

see answer below

E. Coli (serotype 0157:H7)
Shigella dysenteriae

This is hemolytic uremic syndrome
Other signs and symptoms include:
Fever
Pulmonary edema
Seizures

Question 8
A 54 year old man finally died of his progressive dementia after a 15 year course. He had choreoathetoid movements in the last two years. What is the cause of this disease?

see answer below

Excessive repeat of the CAG nucleic acid sequence

This is Huntington’s chorea
Presenting sign of Huntington’s chorea is striking emotional changes years before choreoathetoid movements

Question 9
A 65 year old man has an oat cell neoplasm of the lung. He develops total body edema, lethargy and confusion, and nausea. Overproduction of what substance is the likely cause of this condition?

see answer below

Arginine vasopressin (ADH)

This syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Other signs and symptoms of SIADH include:
Headache
Seizures
Can be asymptomatic and picked up only by low serum sodium

Question 10
If a patient has paroxysmal hypertension, sweating, palpitations and nervousness, and headache, is she more likely to be hypoglycemic or hyperglycemic?

see answer below

Hyperglycemic

This is pheochromocytoma
Lab findings in pheochromocytoma include:
Hyperglycemia
Increased serum epinephrine
Increased serum norepinephrine
Increased metanephrine
Increased VMA

Question 11
A 24 year old man has bilateral anterior conical displacement of the lens, hearing loss, and renal insufficiency. What is the characteristic gene defect?

see answer below

Defect in type 4 collagen alpha-5 gene

This is Alport’s disease
Bilateral anterior conical displacement of the lens is called lenticonus and is pathognomonic for Alport’s syndrome.

Question 12
A 21 year old man develops low back pain with progressive stiffness and later develops pain in his shoulders bilaterally. Serum tests for rheumatoid factor are repeatedly negative. What is his most likely HLA type?

see answer below

HLA-B27

This ankylosing spondylitis
90% of patients with ankylosing spondylitis have HLAB-27 but only 1% of HLA-B27 patients develop ankylosing spondylitis.

Question 13
A 47 year old woman pulls a tick off her back and 48 hours later notices at the tick site a erythematous ring of tissue that slowly expands over the next several days. She also develops a fever and headache. What 4 infections are considered coinfections with this disease?

see answer below

Ehrlichiosis (both granulocytic and monocytic variants)
Babesiosis
Bartonella
Mycoplasma

This is Lyme disease
The most common causative agent of Lyme disease in the United States is Borrelia burgdorferi.

Question 14
If a patient has purple striae, muscle atropy in the upper and lower extremities, borderline diabetes, and menstrual difficulties, is the patient more likely to be hypokalemic or hyperkalemic?

see answer below

Hypokalemic

This is Cushing’s syndrome
Lab findings in Cushing’s syndrome include:
Increased plasma cortisol
Increased urinary cortisol
Increased urinary 17-hydroxycorticoid
Hypochloremia
Metabolic alkalosis

Question 15
A 68 year old man has the onset of angina and then in the next 6 months develops syncope and congestive heart failure. What is the most characteristic finding observed when the patient’s carotid artery is auscultated?

see answer below

Pulsus parvus et tardus (slow, prolonged rise in pulse)

This is aortic stenosis
Aortic stenosis becomes symptomatic when the cross-sectional area of the valve is < 1.0 sq cm

Question 16
If a patient has hypertension, metabolic alkalosis, and hypokalemia, what substance has excess secretion?

see answer below

Aldosterone

This is Conn’s disease
Physiology of Conn’s disease includes:
Increased sodium reabsorption with exchange of potassium and hydrogen
Diastolic hypertension
Extracellular volume expansion

Question 17
A 50 year old white male presents with abdominal pain, fever, skin pigmentation and arthritis in his shoulders bilaterally. The endoscopic biopsy shows flat and thickened villi and a small, gram-positive rod. What is the best treatment for this patient?

see answer below

Trimethomprim-sulfamethoxazole (Bactrim) for 1 year

This is Whipple’s disease
Other signs and symptoms of Whipple’s disease include:
Anemia
Pericarditis/endocarditis
Lymphadenopathy
Hepatitis

Question 18
A previously normal 4 year-old boy seems to have lost muscle strength in his shoulder area, but has developed overly muscular calf muscles with contractures in his heel cords affecting his ambulation. What substance is most likely missing in his muscle fibers?

see answer below

Dystrophin

This is Duchenne’s muscular dystrophy
Histology of Duchenne’s muscular dystrophy includes:
Breakdown of sarcolemma
Degeneration and necrosis of muscle fibers
Type 1 and 2 muscle fibers attempt to repair and regenerate with fibrosis

Question 19
A 72 year old female has pain in her right thumb and index finger. An arteriogram shows a non-obstructing “pipestem” lesion in the right radial artery. What layer of artery is most likely normal in this condition?
see answer below

Intima

This is Monckeberg’s arteriosclerosis
Most typically affects medium-sized muscular arteries

Question 20
A 58-year old female has recurrent angina with left chest pressure and jaw pain. She has three cardiac catheterizations in the last 8 months with completely normal anatomy and no obstructive lesions. Are these episodes of chest pain more likely to occur during exertion or rest?

see answer below

Rest

This is Prinzmetal’s angina
Attacks tend to occur at same time of the day for unknown reason.

Question 21
A 67 year old male has striking splenomegaly, recurring bacterial infections, recurrent epistaxis, and development of a warm antibody hemolytic anemia. What is the most characteristic cell seen on peripheral blood smear?

see answer below

Smudge cell

This chronic lymphocytic leukemia (CLL)
95% of cases are B-cell in origin.

Question 22
A 28 year male was noted on physical exam to have a blood pressure of 200/100. On further investigation he was found to have blood in his urine, a creatinine of 3.2 and enlarged, palpable bilateral flank masses. What is the most likely associated gastrointestinal lesion in this condition?

see answer below

Diverticular disease

This is adult polycystic kidney disease
Diverticular disease occurs in almost 100% of cases.

Question 23
A 14 year old boy has moderate mental retardation, long facies with an overly prominent jaw, arched palate with speech difficulties, protruding ears, and enlarged, non-tender bilateral testicles. A DNA analysis of this patient’s lymphocytes shows what abnormality?

see answer below

CGG repeats

This is Fragile X syndrome
Female carriers may show impaired learning.

Question 24
A 53 year old male drank untreated water from a mountain stream in Kentucky. Two days later he developed abdominal pain and cramps, bloating, and copious foul-smelling diarrhea. He was started on drug therapy by his physician and cautioned against drinking what beverage?
see answer below

Alcohol

This is giardiasis and the treating antibiotic is metronidazole
Alcohol consumed within 3 days of metronidazole use will cause severe vomiting.

Question 25
A 78 year old women falls onto her outstretched right hand and suffers a proximal humeral fracture. On exam post trauma, what is the most likely neurological deficit secondary to her fracture?

see answer below

Inability to abduct her right shoulder

This is an axillary nerve injury
The axillary nerve supplies motor to the deltoid muscle that is used in abduction of the shoulder.

Question 26
A 34 year old woman stranded in a refugee camp with near starvation develops dermatitis on her face, neck, and the dorsum of her hands and feet and also develops chronic diarrhea and mental status changes. What two elements missing from her diet most likely caused these symptoms?
see answer below

Vitamin B3 (niacin and tryptophan)

This is pellagra
Niacin can be synthesized from tryptophan. The three D’s of pellagra are dermatitis, diarrhea, and dementia.

Question 27
An 18 year old male falls asleep in his running car by the side of the road. When the police stop two hours later, the patient has agonal breathing a bright red cherry color to his skin. Which molecule in the body has an extremely high affinity for the causative substance in this case of hypoxic injury?

see answer below

Hemoglobin
This is carbon monoxide poisoning.
Hemoglobin has an affinity for carbon monoxide that is 200 times greater than that for oxygen.

Question 28
A 29 year old female is having her gallbladder removed. Shortly after induction of general anesthesia she develops a tachycardia to 160 beats per minute, a fever to 105 F, hypotension, and an obstructive endotracheal tube due to a clenched jaw. What intracellular substance has a striking increase in this condition?

see answer below

Calcium

This is malignant hyperthermia.
Other signs and symptoms of malignant hyperthermia:
Increased muscle metabolism
Rhabdomyolysis
Acidosis

Question 29
A 38 year old pre-menopausal female developed breast cancer and was given a chemotherapy agent which caused myelosuppression, hair loss, and decreased cardiac ejection fraction. What is the cellular mechanism of action of this drug?

see answer below

DNA breakage and decreased replication of tumor cells via
Non-covalent intercalation.
This is adriamycin (doxorubicin)

Question 30
A 74 year old man was taken to the operating room due to an enlarging bulge that occurred with effort in his right groin. In the operating room the surgeon noted the lesion occurred just medial to the inferior epigastric vessels. What anatomic space did the lesion occupy?

see answer below

Hesselbach’s triangle
This is a direct inguinal hernia and occurs when bowel contents bulge through Hesselbach’s triangle.

Question 31
A 6 month old infant is sent home from daycare with respiratory difficulty which progresses to bronchiolitis and pneumonia. Is the causative agent a DNA or RNA virus and an enveloped or nucleocapsid virus?

see answer below

RNA enveloped virus
This is respiratory synctyial virus (RSV)

Question 32
A 52 year old woman develops increasing dementia. Her mother developed the same symptoms at age 51 years. Her work-up indicates she has the PS-1 and PS-2 genes. What histological lesion is very likely to be found in the cytoplasm of her brain pyramidal cells?

see answer below

Neurofibrillary tangles

This is early onset Alzheimer’s disease.
PS-1 and PS-2 are the presenilin genes found in 50% of early onset, autosomal dominant Alzheimer’s.

Question 33
An 8 year old boy developed a “sore throat” and was culture positive for group A beta hemolytic streptococci on throat swab. He did not receive any treatment for this and 3 weeks later he developed carditis, polyarthritis, and fever. What is the name of the diagnosing criteria for this condition?

see answer below

Jones criteria

This is rheumatic fever. Diagnosis requires presence of two major and one minor or one minor and two major criteria.
Major criteria
Carditis (35%)
Polyarthritis (75%)
Chorea (5%)
Erythema marginatum (10%)
Erythema nodosum (10%)
Minor criteria
Fever
Arthralgia
Increased ESR or C-reactive protein
EKG changes (especially prolonged PR interval)
Preceeding attack of rheumatic fever

 

source

Top Ten Ways to Annoy Your Physician

 

1. Bring a long list of complaints.  Many popular articles I’ve seen recently encourage patients to bring a long list of problems to their doctor appointments.  Don’t.  Physicians just do not have time to appropriately address numerous complaints during one office visit.  If you try to do to much, each complaint does not receive the attention and evaluation it deserves.  Instead, make a list of your complaints and health issues at home, and prioritize it.  Try to address the top two at your next office visit, and schedule a follow up visit soon after to address the next two.  On the other hand, a list of questions pertaining to a single problem is o.k., but wait to start firing them off until your doctor has had his or her say, as he’ll likely answer a number of them in the course of the initial evaluation and discussion.
2. Become irate when you’re doctor is running late.  Understand that your physician is doing his best to stay on time.  Many factors contribute to your doctor running behind schedule.  Emergencies, office visits running longer than expected, multiple patients arriving late, and the constant stream of test results and phone calls that flow in are just a few.  If you’re still in the waiting room thirty minutes after your appointment time and don’t feel like waiting any longer, politely ask to reschedule.  Making a scene or becoming angry with the receptionist will achieve nothing, and trust me word of your behavior will make it back to your physician.
3. Arrive late for your appointment.  This is a corollary to number two above.  One of the reasons I sometimes run late is because of patients who arrive late, and still expect to be seen.  Five or ten minutes may not seem like much, but if several patients early after lunch arrive only that much late, the rest of the afternoon I’ll be at least 20-30 minutes behind schedule and the remainder of the day’s patients won’t be happy about it.  Plan to get to the office at least 10-15 minutes ahead of schedule.
4. Be rude to the office staff.  There is no excuse for this.  Employees in physician’s offices work very hard for relatively little compensation.  This type of behavior is one of the few reasons I sometimes discharge patients from my practice.  If you feel you have a right to be upset about the way you were treated by a staff member, ask to speak to the office manager and voice your concern, and feel free to send a followup letter with a copy to your doctor. 
5. Be non-compliant. If your physician prescribes a given test or treatment, there’s usually a very good reason for it.  Ignoring your doctor’s advice and not following through with their recommendations is called noncompliance.  If you don’t understand why you need a given test or treatment, or you have concerns, ask questions and discuss them frankly and honestly with your doctor.  Good physicians will respond much better to you making an informed decision not to follow their advice and being honest about it than they will if you seem to agree then simply don’t follow through.
6. Put more trust in the Internet than your doctor.  Seems a bit ironic to state this on an Internet health blog, but the truth is there’s a lot of misleading and simply erroneous health information floating around on the Internet.  While mainstream sites like WebMD or the CDC.gov can be extremely useful, many other sites are filled with misinformation, usually fueled by an agenda (often trying to sell you something).  Even when it comes to info obtained from the reputable medical sites, there is no substitute for information given to you by your doctor since it will be tailored to you as an individual, rather than just general information for the masses.
7. Call after hours with non-urgent concerns.  Being on call is the worst part of being a physician, since it usually involves staying up all night or on a weekend answering urgent calls and caring for emergency patients at the hospital after you’ve already put in an exhausting day at the office and have another one to look forward to the next day, functioning on very little sleep.  Trivial phone calls from patients add to the burden.  I’ve had patients awaken me with a phone call at 1 AM in order to cancel an appointment.  If your concern is truly an emergency, call 911; if it’s not serious enough for that, then ask yourself if the question is something that can wait until the office reopens.
8. Constantly complain about the expense of your health-care.  Physicians really don’t have much, if any, control over what your health-care costs you.  If you really can’t afford to follow your physician’s advice, then it’s worth bringing up and we may be able to help you figure out a way to proceed.  However, listening to patients complain about their twenty dollar medication co-pay after they’ve just told you about their recent cruise vacation to the Caribbean while twirling their key-chain with the Lexus key on it and playing with their Blackberry, is fairly annoying.
9. Question your doctor because your treatment is different from your neighbor’s.  Many patients seem to think that since they have similar symptoms or conditions to their spouse or neighbor, that they should receive the same testing or treatment.  Deciding on a given test or treatment for a patient is a very complex process that must be individualized based on age, sex, current medications, allergies, other current or chronic medical problems, insurance formularies, and a multitude of other factors.   For this reason, don’t expect to be prescribed the same treatment for your condition as someone else you know.
10. Take numerous over-the-counter drugs or herbal meds without telling your physician.  We need to know everything you’re taking.  Many people take a lot of supplements and OTC meds without mentioning it.  Make a list of all such compounds and bring it with you to your office visit.  Just because something is touted as ‘all-natural’ like many herbal drugs, does not mean it’s harmless or without side effects and/or prescription drug interactions.  There are plenty of potent poisons that are ‘all-natural.’

source

Medicine the man-whore

Like many young doctors, I get asked a couple of the same questions over and over and over again.

Would you do it again? Any advice to premeds? Would you encourage your children to become doctors? Or some other variation of "Are you happy doing what you do?"
The short answer is 'yes.' I love being a doctor. I love being called 'doctor.' I am proud to tell people I am a doctor. It makes me feel 'satisfied' to know my parents are proud of me...that I have accomplished (in their mind) the epitome of accomplishments. I love it when patients say "your mother (it's always only 'mother') must be so proud of you!!" Yes she is. It really feels good to hear your loved ones brag about you...simply being a doctor is a big deal to most people.
Becoming a doctor doesn't require one to be a genius. You just have to be focused...and do your homework. In high school - go to class and do your homework. In college - ace your exams and do your homework. Medical school certainly isn't about being 'smart' but rather 'organized' and methodical. Studying smart, concentrating on only the most relevant, high yield material. Doing research, and kissing lots of ass. If you study hard, do research, and get good letters of rec, you'll likely get into the field of your choice (especially if you're willing to move anywhere in the country). Once there...you work your ass off. All of this doesn't require you to be smart, per se, just dedicated, passionate, organized, persistent, etc.
I recommend a student go straight thru the process, and not take breaks. If you finish up residency at 26, you still feel like your young adulthood is yours to experience. As a resident, you can have a life (depending on the specialty, of course). You can still go out with friends, date, and hang out. I even endured 2 pregnancies as a resident (afterall, when are you supposed to have those babies?). Residency isn't about studying and learning....it's about working. If you work, you'll finish. You can always study for a test (boards) later. I found residency less stressful than medical school because...in my mind, I'd 'made it' already. I was a doctor. Simply being a medical student makes you....nothing. No pass = No MD. The fact that I'd accomplished a major achievement by simply graduating from medical school, relieved lots of stress for me.
If you go straight thru, you may graduate residency at 29 years old. That's still plenty young. The sacrifices are much less. Afterall, you don't feel as though you've sacrificed 'your entire young adulthood' to medicine if by 30, you're making 6 figures...like many of your professional friends. (Granted they may not have the debt you have).
If you put off medical school, and do a long residency, by the time you're finished...you may feel you've given too much of yourself, of your life. If you decide to put off relationships, marriage, having kids...you may find yourself in a situation where you *can't* have kids, or the family you always dreamed of. You may miss end of life activities with grandparents/parents. You may miss other significant life events of other family members/friends. And, you'll gradually lose your close friends as they have families, and hang out with other people in similar social situations. You may realize that you're the oldest guy/girl at the club. And, it may become increasingly difficult to find a suitable match as a life partner. Young adulthood is the time to lay the foundation, both professionally, and personally, for the rest of your life. If you are a medical student/resident thru this process, you may find yourself, your life, unbalanced. As you pursue this (arguably) awesome career, you lose the opportunity to experience these other aspects...that are much more important in the grand scheme of things.
Being happy in medicine happens as a result of going into it with accurate information, eyes wide open. Forget about the fuzzy 'feel good' I wanna help people bullshit. Forget about the 'privilege' or 'calling' that some try to say is medicine. Realize it is just a job. It is just one aspect of your being. It, in itself, will not make you happy. Realize that patients are no substitute for family. If you can see yourself doing something else, and being happy doing it...you should strongly consider that option. Medicine is like a sexy man-whore. Attractive, alluring, exciting, and seems to have 'everything you'll ever need'. But, the reality is, he will betray you. He will beat you. He will not keep his word. He will not appreciate your greatness. He is selfish. And basically, not what he appeared to be. Likewise, medicine will not be what you thought it'd be. The patients will sue you. The 'purse-holders' will not appreciate you or value your work. You will see plumbers make more per hour than you do. Medicine will not provide the life you thought it would...and you'll feel betrayed.
You'll be happier if you realize that medicine isn't 'everything.' You will not make even the modest money you thought you'd make. Realize that student loans *are* a big deal, and will not be easy to pay off "on a doctor's salary." Realize that you don't have control, and are at the mercy of the powers that be...and the pig-headiness of some arrogant peers who see no value in unionization and advocating for 'physician rights'. Do not put off things in life that you really want to do, like get married, or have children. Develop outside interests, and don't let medicine become your identity - do this and you'll have a strong defense against burn-out and disenchantment (this is why it's so important for residency to be humane. Medicine isn't what it once was. There is no pot-o-gold at the end of the rainbow if you suck it up and sacrifice your young adulthood like back in the day when docs were respected, and paid handsomely for their services.) If you view medicine as a stable job that pays a decent wage....you'll be happier. Do not try to make the man-whore a loving husband. See him as he is, and either accept it, or move on.
Also important is, finding a specialty that fits your personality. If you want to be an involved parent, surgery isn't for you. If you want to have a comfortable lifestyle, you might wanna rethink primary care. If you like to interact with people, radiology/pathology may not bring you satisfaction.
Don't overwork yourself. Even if you enjoy speeding around the ED running codes and trauma, do it too much/often, and at the expense of personal health, relationships, or other recreational activities....I promise it will cease to be fun quite quickly. The check is nice...but your life is suffering. In the end, many docs decide it isn't worth it....
...all because they haven't achieved balance.
So, in review - to increase the likelihood that you'll be happy in medicine:
-get the training over with while you're young; don't take breaks (or alternatively, wait until you're a bit older)
-keep it in perspective. You are not a saint because you are a doctor (don't be arrogant and think more highly of yourself than you should). It is not a calling. See it as a stable, respectable, secure, job. Your work is valuable, but not more valuable than yourself, or your family.
-know the drawbacks, and balance those with the benefits of becoming a doctor today.
-the money *does* matter (both the student loans, and the eventual salary).
-don't sacrifice having children, visiting aging parents, or other significant life events in lieu of becoming a doctor. It will not be worth that sacrifice.
-Choose your specialty with care. Chose based on your personality...not based on what is most prestigious, what other people want you to do. Your specialty will determine your potential work environments, your pay, your lifestyle, and the number of years you spend 'training.'
-Finally, don't work too many hours. If you do, you'll be more tired, less healthy, and more likely to experience dissatisfaction and fatigue.

source

Interpreting the Medical Literature

The science in science-based medicine includes all of science, but relies most heavily on the biomedical literature - published studies that collectively represent our scientific medical knowledge. The scientific basis of medicine is only as good as this body of knowledge and the manner in which it is interpreted and put into practice.

We often discuss on this blog how to evaluate individual studies- the need for blinding, randomization, the importance of study size to meaningful statistical analysis, and other features that distinguish a reliable study from a worthless one. This is important, but only half of the equation. We also at times discuss the medical literature as it relates to a specific medical question or set of related questions - does homeopathy work or are statins beneficial for cholesterol reduction, for example. This requires not only the ability to judge individual studies, but a higher order analysis of the overall pattern of evidence among all relevant studies. Failure to do this, by focusing only on individual studies, results in the failure to see the forest for the trees.

It is this higher order analysis that I wish to discuss in this entry.

The evolution of medical evidence

First, it is important to realize that confident medical judgments or conclusions rarely emerge from single studies - confidence requires a pattern of evidence over many studies. The typical historical course for such evidence is first to begin with clinical observations or plausible hypotheses that stem from established treatments. Based upon this weakest form of evidence preliminary or pilot studies are performed by some interested researchers to see if a new treatment has any potential and is at least relatively safe. If these early studies are encouraging then larger and larger studies, with more tight designs are often performed.

In this early phase of research results are often mixed (some positive, some negative) as researchers explore different ways to use a treatment, different subsets of patients on which to use the treatment, varying doses of medication, or other variables. Outcomes are also variable - should a hard biological outcome be used, or more subjective quality of life outcomes? What about combinations with existing treatments? Is there an additive effect, or is the new treatment an alternative.

It takes time to sort out all the possible variables of even what sound initially like a simple medical question - does treatment A work for condition X. Often different schools of thought emerge, and they battle it out, each touting their own studies and criticizing the others’. This criticism is healthy, and in the best case scenario leads to large, well-designed, multi-center, replicable consensus trials - trials that take into consideration all reasonable concerns where both sides can agree upon the results.

What I just described has often occurred in medical practice, but is also what happens when the system works. There are also many false turns and blind alleys. Sometimes fraud will confuse the literature until it is rooted out by later studies, or a vested interest will skew the studies in one direction, delaying a more definitive and accurate result from emerging from the collective literature.  But it is important to realize that even when the process works well, it is very messy, and it takes years to play out.

That is why medicine is an inherently conservative profession - we cannot allow medical practice to blow in the wind of every new study or fad. It takes time to achieve confidence by working through all the messy variables.

But there’s more.

Systematic Reviews vs Meta-Analysis

Perhaps the most useful type of medical paper is the systematic review.  These take a great deal of time and work, but when well-done are invaluable. Perhaps the most significant contribution of the Cochrane collaboration - an institution of evidence-based medicine - is to provide standards for systematic reviews and to publish many of them.

A good review will look at all high-quality studies, assess their strengths and weaknesses, and look at the overall pattern of results. For example, such a review may find that there are no studies of sufficient quality to make a recommendation - therefore the evidence is still lacking. Or, it may find that the better a study of a certain treatment the smaller the effect, and the best studies tend to be negative - a pattern consistent with a lack of a real effect (despite the fact that there may be individual positive studies). Such reviews may also point out inconsistencies in the literature indicating the need for further research to resolve the conflicts.

Systematic reviews are not without their pitfalls, however. The reviewers still have to decide which studies to include, and this creates the potential to introduce bias in the results.

Even more concerning - systematic reviews are only as good as the literature it analyzes, and there are systematic problems with the literature itself that I will discuss further below.

A meta-analysis is not a systematic review. Rather, this is the statistical technique of combining multiple studies into one large study by pooling their data. This technique is fraught with multiple sources of bias - which studies to include and how to standardize different populations and outcomes being the two most significant. It is important to realize that a meta-analysis is not new data, but simply a re-analysis of old data with new variables potentially introduced.

A 1997 study published in the NEJM looked at published meta-analyses and compared them to later large well-designed trials and found that they failed to predict the outcome of the later trials 35% of the time. This is not very good, considering that 50% would be random chance. The probability of false positive and false negative were roughly equal in this study.

Biases in the Literature and the work of John Ioannidis

The literature itself has higher order structure - meaning that it is not simply a collection of individual studies. There are patterns in which types of studies tend to get published, and therefore added to the literature. The most basic such pattern is called publication bias, or the file-drawer effect. It refers specifically to the tendency to publish positive studies over negative studies. Researchers are more likely to submit positive studies, and journal editors are more likely to accept them. A recent analysis, for example, also showed that pharmaceutical companies are much more likely to submit studies favorable to their drugs for publication than negative studies. Similarly, it is likely that proponents of any treatment or system are more likely to submit for publication studies that support their specialties or favored modalities.

This has a huge effect on the literature. It affects every systematic review and meta-analysis, which typically will analyze only published studies. Cochrane reviews also encourage looking at unpublished data and paper presentations at meetings, but this is only done in the most complete of reviews. If the collection of published studies is skewed toward the positive, then reviews will likewise be skewed positive.

This is further supported by evidence that initial studies of new treatments tend to be positive and have large treatment effects, and as the literature on a particular question evolves there is a distinct trend toward shrinking effect sizes, with some disappearing completely. Taken at face value, what this means is that the medical literature simply cannot be trusted until we get to the mature phase of large, multi-center, randomized, and well-controlled studies - the most definitive study designs.

There are more subtle problems with the medical literature, as discussed by researcher John Ioannidis. In 2005 he published what has become a seminal paper on why most published studies are false. In the summary he writes:

In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true.

The reason for this is actually simple - science is about discovering new things, and most attempts at guessing what will turn out to be true in science are wrong. If most ideas are wrong, then even with a reasonable study design and threshold for statistical significance, you may get more false positives than true positives - in other words, most published studies will be wrong.

It is worth pointing out that this effect gets worse the more implausible the hypothesis. When studying truly speculative or unlikely treatments, the false positive to true positive ratio increases dramatically.

However, it is also worth pointing out that this does not mean that we cannot trust the medical literature at all - after all, Ioannidis is comparing the medical literature to itself. What this really means is that, assuming later large definitive trials to be correct, earlier smaller trials are likely to be false, and more often than not falsely positive. The assumption here is that we can trust mature, well-designed and large trials.

Recently Ioannidis published another paper, this one more of a thought experiment than analysis of the literature. In it he writes:

This essay makes the underlying assumption that scientific information is an economic commodity, and that scientific journals are a medium for its dissemination and exchange. While this exchange system differs from a conventional market in many senses, including the nature of payments, it shares the goal of transferring the commodity (knowledge) from its producers (scientists) to its consumers (other scientists, administrators, physicians, patients, and funding agencies).

This is an interesting idea - thinking of the medical literature in economic terms. I think Ioannidis makes a convincing case that there is some insight to be gained from this approach.  He concludes that positive studies are much more valuable as a commodity than negative studies and therefore this should contribute significantly to the bias in the literature toward not only positive studies, but ones that make bold claims - the very claims that are most likely to later turn out to be incorrect. What this adds up to is yet another reason to be highly suspicious of early studies or bold new claims.

Of course, this analysis is only as good as the stated underlying assumption - is scientific information an economic commodity. One aspect of publication that Ioannidis did not address is peer-review. Journals submit papers to review by experts, who have their own reputations to consider and may not gain from someone else publishing a hot new study. High end journals use this process, and their editorial discretion, ostensibly to filter out bad studies. Yes, they want positive, high-impact publications - but their long term reputation also depends upon these studies not being routinely overturned. This is analogous to the reputation of a judge who is consistently overturned on appeal.

How these competing interests (the desire for exciting press releases while wanting published papers to hold up over time) play out is likely different for each journal, depending upon the editorial competence and temperament.  I do hold out, perhaps naively, that the best medical journals value peer-review and reliability over headlines.

Conclusion

All of these trends and patterns in the published medical literature tend to point toward the same conclusion -  early on in the research of any new idea in medicine, published studies are highly unreliable and have a huge bias towards being positive and exaggerating effect sizes. However, over time the research often works itself out, and highly reliable studies can be achieved (although no question in science is ever closed).

The work of Ioannidis and others also reinforces one of the core premises of SBM - that plausibility is an extremely valuable quality to take into consideration when evaluating any new idea or treatment. The less plausible a treatment, the less reliable early, small, or poorly controlled studies are likely to be, and the greater the bias towards publishing positive outcomes.

There is also a bright spot in all of this - the literature is not hopeless, and all of the problems discussed above have solutions. We need greater transparency in medical research, for example. This could be achieved by having a central registry of all clinical studies involving human subjects that requires the publication online of the study results. This would make all the data (not a biased subset of it) available to researchers for systematic reviews.

Journal editors need to publish more negative studies, and they need to be especially skeptical of new bold claims. Plausibility needs to be factored more prominently into evidence-based medicine - which is precisely what we mean by science-based medicine. More resources should be allocated to high quality systematic reviews.

The medical literature is in many ways our most important tool and resource. Understanding it at its highest level of organization is crucial to reaching reliable medical conclusions that can be applied to practice - which of course is the ultimate purpose of medical research.  Further, it is worth our time and effort to continue to study the literature at this top level with the goal of improving the quality and effectiveness of this critical tool.

source