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J Thomas Lamont MD grand rounds BIDMC

BIDMC Grand Rounds: J. Thomas Lamont, M.D. on Major Advances in Gastroenterology & Hepatology

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J Thomas Lamont MD grand rounds BIDMCIn January 2020, J. Thomas Lamont, M.D. (author of C. Diff In 30 Minutes) gave a grand rounds presentation at the Sherman Auditorium, Beth Israel Deaconess Medical Center, Boston. He was looking back at Major Advances in Gastroenterology & Hepatology over a 50+ year period, which actually stretched back to a much earlier age of scientific and medical discovery. From the introduction by Nezam H. Afdhal, MD, the current Chief of the Division of Gastroenterology, Hepatology and Nutrition at BIDMC:

[Lamont] published a paper that was the cover of Nature that illustrated why the stomach does not digest itself due to the interactions of mucins and the effect of acid on the mucin structure within the stomach. At BIDMC he and his research team worked on the mechanism of action of the toxins for C. difficile. These are just some of his scientific advances. He is a clinician, still sees patients today, and is a well sought after teacher, and has educated innumerable fellows and faculty. He’s been a mentor to many. He’s been a great friend to the GI division here at BIDMC. His lecture this morning is going to be a look back at what has happened in the 50 years of Tom’s career in gastroenterology.

Here is the full presentation with audio, about 45 minutes long:

Some selected quotes by Lamont follow. You can view a full transcript of the Lamont’s Grand Rounds presentation here.

On incremental progress vs. paradigm shifts:

I used to think, and a lot of people believe that discoveries are incremental, that knowledge is added like bricks to a wall which you gradually build. But in fact scientific discoveries are primarily revolutionary not incremental. There’s a paradigm shift which is a radical change in the way we do things. It’s often disruptive, a word borrowed from technology, where the new discovery or invention blows up whatever was there before. Later in the talk I’ll show you some examples of disruptive discoveries and inventions in the field of Gastroenterology.

On convincing the scientific establishment:

A major feature in the field of scientific discovery is resistance from the establishment. I can tell you that Boston has a very powerful medical establishment, and the resistance to some of what I’m going to show you was quite robust. So, if you’re interested in this topic, there’s a very important small book, about 100 pages long, by Thomas Kuhn called “The Structure of Scientific Revolutions”. Kuhn championed the concept of paradigm shift, in which scientists have to move away from something that has been accepted for a long, long time. And the new paradigm replaces the original paradigm, which eventually fades away.

On technology transfer from other fields:

Kapany and colleagues then had the idea that extremely thin flexible glass fibers could transmit endoscopic images. This was picked up by Basil Hirschowitz, a native of South Africa, who in 1953 was a GI fellow at the University of Michigan. He was already trained in endoscopy in England before he went to Michigan. Hirschowitz was trained in the Schindler type of endoscopy that I showed you earlier, but he realized that this older technology was difficult and dangerous because of the rigidity of the Schindler scope.

On the impact of endoscopy:

The impact of fiberoptic endoscopy on practice was massive. Currently about 100-million endoscopies performed a year in the United States, about two thirds of them by GI doctors. Flexible fiberoptic endoscopy has had important impact worldwide in many medical and surgical fields.

On the discovery of the cause of ulcers:

Barry Marshall wrote in his note cards and some of his later publication “Everyone was against me, but I knew I was right.” So who was against him? The acid mafia, a powerful group of senior investigators who championed the idea that hydrochloric acid was the key to formation of stomach ulcers. When we were residents and fellows we had to know a lot about gastric hydrochloric acid secretion. So those who believed in the primacy of stomach acid were definitely strongly opposed to these Australian upstarts, Marshall and Warren. … Marshall and Warren were finally justified in 2005 when they won the Nobel Prize for Medicine. A couple of blokes from Australia who had not done a lot of research at all, with very little support. they used equipment and tools that were right at hand. This seems to be a study that could have been performed by almost anyone. But they were the first, and their persistence in the face of heavy opposition payed off.

 

 

Video: How C diff. spreads

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The following video from a hospital in Colorado shows how C diff. can spread after taking antibiotics and being exposed to Clostridium difficile. It also discusses treating antibiotics and recurrent C diff:

For more detailed information about C diff. as well as treatment options, prevention tips, and C diff. case studies, check out C Diff In 30 Minutes by Dr. J. Thomas Lamont, M.D.

Mrs. E’s C. diff case study: “Do you think I will ever be rid of this awful C. diff?”

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The following C. diff case study was excerpted from C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

Mrs. E was a feisty 80-year-old grandmother living alone in her home with two cats and a canary. She came to my office because she wasn’t sure her C. diff was gone.

Clostridium difficile case study - Mrs. E's storyHer story started three months earlier, after she had a knee replacement. During her recovery, she developed a fever and received the antibiotic Cipro for just three days. A week after discharge, she got a C. diff infection while staying in a rehab hospital. After a week of diarrhea, her doctor tested her stool for C. diff. When the test came back positive, she was started on Flagyl, the same antibiotic taken by both Jeannie and Al. Her response was excellent, and five days later she was no longer having any diarrhea.

After Mrs. E had finished the Flagyl and was back home again, she visited her doctor who decided to test her stool for C. diff to see if it was gone. To his surprise and to Mrs. E’s disappointment, the test came back positive. A second course of Flagyl was started, even though she was feeling fine. A few weeks after that, her stool again tested positive. After several more courses of Flagyl, which had no effect on her stool test, she came to see me for a second opinion. Her first words in the office were “Do you think I will ever be rid of this awful C. diff?”

In fact, it was easy to reassure Mrs. E that she did not need any more stool tests to see if she still had C. diff, and she definitely didn’t need any more Flagyl. And yes, she would eventually get rid of the C. diff. She just needed to be patient and wait for her normal colonic flora to recover, a process that can take one to three months after the last dose of antibiotic.

What is a post-convalescent C. diff carrier state?

Mrs. E’s story is very common, and it’s one that can be confusing to patients and their doctors. Her case is an example of the post-convalescent C. diff carrier state. This occurs when patients recover from diarrhea and other C. diff symptoms, usually in the first week of treatment, However it may take months before the C. diff finally disappears from the stool. During this time the patient is passing C. diff in the stool, which can infect other people. Carriers have no diarrhea or other symptoms because they have developed antibodies to the C. diff toxins. These antibodies neutralize the toxins and prevent diarrhea, fever, and cramps. But the C. diff lingers in the bowel. How? It takes advantage of the lowered resistance of the colonic flora caused by the original antibiotic. In Mrs. E’s case the antibiotic Cipro was used to treat her knee infection, and Flagyl was used to treat her C. diff.

We’ll cover the importance of healthy colonic flora later in the guide, but for the time being, understand that Mrs. E was in a sort of limbo, in which the symptoms of the disease are gone (no diarrhea, pain or fever) but the C. diff lingers for a while (stool test still positive). More information about convalescent carriers can be found in Chapter 2.

To learn more about C. diff, download or purchase a copy of C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

C. diff in hospitals: How it spreads

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C. Diff – hospitals and nursing homes

Clostridium difficile is a contagious disease. However, it usually doesn’t spread directly from one person to another like influenza, strep throat or common colds. Patients pick up C. diff from the environment, typically a hospital or nursing home. The following post will explore C. diff in hospitals and nursing homes, as well as other types of C. diff transmission.

Here’s how C. diff spreads in hospitals. Let’s imagine a C. diff patient, Mrs. Smith, in Room 503 in our hospital. She has acute C. diff infection and is passing liquid stools (diarrhea) 10 times per day. Billions of C. diff organisms are in her stools. Tiny amounts of the C. diff organisms get on the sheets, linen, toilet seat, telephone, and floor in her room.

Doctors come in to Room 503 to examine Mrs. Smith. They may pick up C. diff spores on their hands, clothing or stethoscopes. Depending on how well they wash their hands and clean their stethoscopes, C. diff can hitch a ride to the next patient they examine and infect that patient … especially if that patient is taking an antibiotic.

C. diff hospitals - how C diff spreads in hospitals

Once C. diff leaves the colon of the infected patient in a liquid stool, it usually converts to a spore that is like a seed that lies dormant in the hospital until it gets picked up by a suitable human host. Once swallowed, C. diff germinates (hatches) in the bowel and starts a new cycle of infection.

Since the spores of C. diff are able to survive for months or even years in the hospital environment, it’s possible that spores from one patient can infect another patient admitted to the same hospital room even months later. It is almost impossible to know with certainty how or where a given patient picks up C. diff, because the spores are so common in the hospital environment. Spores of C. diff can be found in soil, in the home, and even in the supermarket. Patients pick them up on their hands and transfer them to their mouth when they eat.

Airborne and person-to-person C. diff transmission

Note, however, that airborne transmission doesn’t happen for a stomach infection, as airborne particles end up in the lungs (like the common cold, which can be transmitted by a sneeze). C. diff germinates in the bowel.

Person-to-person transmission is also rare. It’s extremely unlikely for a husband with a C. diff hospitals infection to pass it to his wife, or for a parent to pass it to his child, unless the wife or the child is taking an antibiotic.

However, spread from one patient to another in the same hospital room can occur. Because of this, patients diagnosed with C. diff are usually moved to a private room.

When patients with C. diff are discharged from the hospital, their room and furniture are cleaned thoroughly with bleach to kill C. diff to prevent the next patient from getting infected. Doctors are required to clean their hands with hand sanitizer or soap and water before and after examining a patient. When this rule is strictly enforced, it reduces the rate of C. diff infection in hospitals and nursing homes.

This article was excerpted from C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

C. diff in babies: an unsolved mystery

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The following article was excerpted from C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

C. diff was originally discovered in healthy babies, who seem to tolerate this nasty bug in their stools without getting sick. About 70% of infants during the first year of life carry C. diff. Why they don’t show signs of disease like diarrhea or fever remains a mystery.

Can babies get C. diff - clostridium difficile in infantsOne theory is that the infant’s bowel doesn’t “recognize” Clostridium difficile or its toxins. C. diff toxins cause diarrhea by hooking on to a special toxin receptor, much like a key opens a lock. Once the toxin (the key) hooks on to its receptor (the lock), it opens the floodgates of diarrhea and causes fever, cramps, and other signs of acute infection. Healthy infants lack this receptor, so they don’t get sick even though they are carrying enough C. diff to cause severe diarrhea in an adult. After the first year of life, babies develop the receptor and can develop C. diff just like adults. So, finding C. diff in the stool of an infant is not worrisome. Eventually, C. diff will disappear from the intestinal tract when the infant reaches 10-12 months.

Can babies make other people sick with C. diff?

Can babies spread C. diff to other family members, babysitters, or health-care workers? The answer is yes, but in practice it’s very rare. Sometimes mothers of newborn babies have to take antibiotics for a urinary tract infection. The antibiotics can damage the protective stool barrier allowing C. diff to get in and cause infection. I have treated a few moms who probably caught C. diff from their newborns. I have also treated a neonatologist (a pediatric specialist in newborn diseases) who probably picked up C. diff at work from one of her sick newborns.

Even though babies can carry C. diff, we don’t recommend any special precautions to mothers or other family members. Catching C. diff from a baby is so rare that enforcing special precautions is probably not necessary. Wearing rubber gloves when diapering, or hand washing after changing diapers, is always recommended, especially if the person changing the diaper is taking an antibiotic.

Being a carrier of C. diff is beneficial to the baby. Healthy babies who are carriers develop an immune reaction to C. diff toxins that results in the formation of antibodies that protect against C. diff infection. Immunity to C. diff developing during the first year of life can last a lifetime and protect patients who later come in contact with C. diff. Those who have antibodies become “carriers” with no diarrhea, while those with no antibody can develop full-blown C. diff. Since about 70% of babies are carriers, this implies that they will likely never get C. diff when they grow up!

To learn more about C. diff, download or purchase a copy of C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

Recurrent C. diff: Why does C. diff sometimes keep coming back?

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Recurrent C. diff: Description and risk factors

Earlier we looked at the C. diff case study of Al, an electrician who contracted Clostridium difficile after receiving dental treatment which required antibiotics. Al’s case illustrates several aspects of recurrent C. diff, a huge problem that occurs in up to 30% of patients who get C. diff after the initial treatment with the antibiotics Flagyl or Vanco. Recurrent C. diff is a huge problem:

  • In cases of recurrent C. diff, the infection comes back or recurs within days or weeks of stopping the antibiotics.
  • Some unlucky patients experience ten or more recurrences and start to think they will never recover.

After initial “cure” of Clostridium difficile with antibiotics, about 15-25% of patients develop a recurrence within a few days to several months. The chance of a recurrence depends in large part on the type of antibiotic being taken, such as Flagyl, Vanco, or Dificid, as well as the age of the patient.

This repeat infection can keep on recurring, even after multiple courses of antibiotics. We have seen some unfortunate patients with 10 or more attacks of C. diff in a two-year period. It can lead to chronic diarrhea, weight loss, and diminished quality of life.

We think that recurrence of C. diff depends on a “Perfect Storm” of several factors:

  • Simultaneous failure of the immune system with inadequate antibody formation
  • Failure of the colonic flora to regenerate, owing to exposure to antibiotics.

Failure of the immune system to generate an antibody response is quite common after age 60. The older the patient, the weaker the response to an infection or to vaccination:

Recurrent C. diff chart showing age as a risk factor

During an initial bout of C. diff infection, a healthy immune system develops antibodies that protect against another bout of C. diff infection. But after age 50 or so, this immune response is diminished. That’s why recurrent C. diff infections are much more common in 80 year olds (35%) vs. 40 year olds (10%).

This article about recurrent C. diff was excerpted from C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D. To learn more about C. diff, download or purchase a copy.

C. diff case study: Al’s story

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The following C. diff case study was excerpted from C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families by Dr. J. Thomas Lamont, M.D.

Al was a very healthy 62-year-old electrician. That is, until he developed an abscess on his wisdom tooth. His dentist prescribed the antibiotic clindamycin for seven days to treat the abscess and scheduled a root canal.

C. difficile symptoms - Al's storyFive days after Al finished the clindamycin, he developed diarrhea, an upset stomach, and pain in the lower abdomen. The diarrhea was severe, occurring up to 10 times per day. He called his doctor who tested his stools for C. diff. The result was positive. Treatment was started with 10 days of Flagyl (one of the same antibiotics taken by Jeannie) four times per day. By the fifth day, his diarrhea was almost gone and Al was ready to go back to work.

Four days later the diarrhea returned. It was as bad as it had been in the beginning. This time, Al’s doctor started him on Vanco (the other antibiotic taken by Jeannie) four times per day. Again, Al appeared to recover, and the diarrhea went away. But eight days after Al stopped the Vanco, it came back — the same smelly diarrhea with lots of mucus and cramps. Al was frustrated now and worried that he might never get rid of his C. diff.

His primary care doctor was frustrated, too. He arranged for Al to see an infectious disease specialist at a teaching hospital in Boston. The specialist recommended a pulse-taper of vancomycin for eight weeks, during which the Vanco was taken in a gradually decreasing dose. It started with one capsule four times per day, and ended with one capsule every other day for the last week.

Al finished the eight weeks of Vanco and followed this up with four weeks of Culturelle, a probiotic. Probiotics are dried bacteria or yeasts that are designed to help the colonic flora, the bacteria and other microorganisms that live in our large bowel (colon), to return to their original state before the patient took antibiotic treatment.

This time, the diarrhea came back two weeks after he stopped taking Vanco. Al’s frustration level went through the roof. He felt that C. diff had taken over his life and he would never get better. He even worried that his C. diff infection was going to be fatal. At that point, his son went online to see what options were available for patients with multiple recurrences of C. diff. He read that many patients like his father got better after a stool transplant.

What is a stool transplant?

Getting a stool transplant is like reseeding a lawn that has been damaged by weeds, drought, and poor soil. The soil is prepared, watered, and seeded, and eventually a new lawn replaces the old. In a stool transplant, the “seeds” are a suspension or “shake” of healthy stool, taken from a healthy donor, and transferred via a medical device to the colon of a person suffering from C. diff. The procedure is straightforward and has a permanent cure rate of 95% among C. diff patients. Chapter 3 describes the procedure in more detail.

Al was eventually referred to a gastroenterologist (GI) specialist at our hospital who had experience with stool transplants to treat C. diff. The doctor explained that the C. diff infection kept coming back because Al’s colonic flora was depleted from all the antibiotics taken over the past three months. The normal colonic flora provides a protective barrier against C. diff, other harmful bacteria, and viruses. That’s why nearly every patient who gets C. diff has taken an antibiotic before the diarrhea starts. But Al’s barrier was so low that the C. diff kept coming back after he stopped the Vanco.

Once patients have had one recurrence, the odds go way up that they will have multiple repeat attacks. We have seen patients with more than 10 such recurrences. They are typically elderly with other illnesses such as heart failure, cancer, or chronic kidney disease, all of which can depress the immune system. Depression, fatigue, and weight loss are very common in so-called “repeaters.”

In order to try a stool transplant, a donor was needed. Al’s wife was healthy, with no diarrhea and no recent antibiotics. The plan was for her to come in with Al on the day of his colonoscopy, and to “donate” a stool sample that would be used to reseed his colon. Her stool was put in a blender with water to make a thin liquid shake, which was then filtered to remove any solid material. The GI doctor then passed a colonoscope to the upper part of Al’s colon and injected some of his wife’s liquefied stool through the scope. Then he slowly withdrew the scope, infusing some of the liquid every four or five inches until he reached the bottom of the colon. Al was instructed to lie quietly for an hour in the recovery area, and then he was discharged home with instructions to take no more vancomycin.

After the transplant Al felt fine. Naturally, he worried that C. diff might come back. When he saw the gastrointestinal doctor three weeks later, he had no diarrhea, the longest time he had been without symptoms since the root canal. Three months after the stool transplant, Al was feeling great and working full time. He was cured!

At our hospital we have performed dozens of stool transplants for patients with recurrent C. diff. All but one were completely successful, and the one patient who failed had a second attempt that was eventually successful.

For C. diff patients who have tried everything, stool transplants can make a huge difference. Some patients are afraid to try a stool transplant because it seems “gross” or “yucky.” But in hundreds if not thousands of patients worldwide the procedure is safe and very effective. The source of the stool is usually a family member or friend. For a lot of our patients who have recurring C. diff, the choice is either a transplant or more antibiotics for a long time.

To read additional C. diff case studies, download or purchase our C. diff book.

C. diff expert: the importance of a healthy colon

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Excerpted from C. Diff In 30 Minutes: A Guide To Clostridium Difficile For Patients And Families, by C. diff expert Dr. J. Thomas Lamont, M.D.
Colon diagram C. diffAlthough it may seem unlikely, the stool in your colon serves a very important function. That’s right, the smelly stuff you flush down the toilet is actually extremely important to your overall health and well-being. Your colon (highlighted in the inset image) is loaded with trillions of microorganisms, including bacteria, viruses, and fungi, which live there in perfect harmony with each other and with you. In fact, these tiny organisms count on you to feed and water them every day, just like your pet cat or dog.

About 90% of the food you eat is absorbed by your intestinal tract. Every cell in your body, from the hair on your head to the skin on the soles of your feet, is made from the food you eat.

What about the rest? The 10% that’s not absorbed feeds the trillions of bowel flora living in your colon. Ten percent of your diet is mostly plant fibers, cereals, and starches, sometimes called roughage, which cannot be digested and absorbed by humans. For centuries, scientists had little knowledge about the colonic flora, but now it’s clear that the organisms in our stools protect us from invaders like C. diff and other causes of bowel infection. These bacteria in the colon are sometimes called “the barrier flora” because they provide a protective shield against harmful organisms. The image below shows a type of barrier flora, magnified by an electron microscope.
C Diff electron microscope
Antibiotics can have a negative impact on the flora in your colon. While antibiotics are used to treat bacterial infections, such as strep throat or tuberculosis, they can also take out the barrier flora and other normal bacteria in your colon.

So, to get C. diff, the first thing that has to happen is that your barrier flora are killed off or weakened by an antibiotic. Once this happens, C. diff can jump in. Clearly this doesn’t happen to everyone who takes an antibiotic. Only about 1 in 100 or 1 in 1,000 people who take an antibiotic will get C. diff. Not all antibiotics are equal in their ability to allow C. diff. Clindamycin, ciprofloxacin, penicillins and cephalosporins are the main offenders, while azithromycin, tetracycline and bactrim are less likely to cause this problem.

The bottom line: Any antibiotic can weaken your barrier flora in the bowel that normally protects you from invasion by C. diff.

To learn more about Clostridium difficile symptoms and treatments, read C. Diff In 30 Minutes: A Guide To Clostridium Difficile For Patients And Families, by C. diff expert Dr. J. Thomas Lamont, M.D.

C. diff fecal transplants: What the research says

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The following excerpt about C. diff fecal transplants is from the journal article “Fecal Transplantation for Recurrent Clostridium difficile Infection in Older Adults: A Review,” from the August 2013 edition of the Journal of the American Geriatrics Society. It was authored by Kristin E. Burke, MD, and J. Thomas Lamont, MD. Used with permission.

C. diff fecal transplants

Recurrent Clostridium difficile infection (CDI) is a common nosocomial infection that has a large effect on morbidity and quality of life in older adults in hospitals and long-term care facilities. Because antibiotics are often unsuccessful in curing this disease, fecal transplantation has emerged as a second-line therapy for treatment of recurrent CDI.

A comprehensive literature search of PubMed, Embase, and Web of Science regarding fecal transplantation for CDI was performed to further evaluate the efficacy and side effects of this promising therapy in older adults. Data were extracted from 10 published articles from 1984 to the present that met inclusion criteria, including nine open-label reports and one randomized controlled trial.

Baseline characteristics and outcomes of individuals undergoing fecal transplantation and effects of fecal transplantation on the fecal microflora were reviewed. Methods of fecal transplantation and donor selection were reviewed. Fecal transplantation was performed in 115 individuals aged 60 to 101, with a female predominance.

CDI cure was achieved in 103 (89.6%) individuals over a follow-up period of 2 months to 5 years (mean 5.9 months). There was no significant difference in cure rate between older and younger participants in included studies. Most failed transplantation occurred in individuals infected with the aggressive NAP1/027 strain of C. difficile.

Microbiological studies of fecal biodiversity before and after fecal transplantation demonstrated greater bacterial diversity and shift in flora species to resemble donor flora after transplantation that correlated with clinical remission. Fecal transplantation provides a safe and durable cure for older adults with recurrent CDI. J Am Geriatr Soc 61:1394–1398, 2013.

Keywords: fecal transplantation; recurrent C. difficile infection; fecal microflora

colonoscope used for c. diff fecal transplants or c diff stool transplants - shutterstock image used under license

Colonoscopes are used for C. diff fecal transplants (Shutterstock)

C diff. slides by J. Thomas Lamont, M.D., of the Harvard Medical School

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The following C diff. slides were created by J. Thomas Lamont, M.D., a professor and researcher at Harvard Medical School and the author of C. Diff In 30 Minutes: A guide to Clostridium difficile for patients and families. The slides were part of a 2013 presentation given to doctors and researchers:

If you are interested in learning more about C. diff, check out the many resources listed on this website.

DISCLAIMER: Nothing in this presentation is intended to constitute medical advice, a clinical diagnosis, or treatment. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions.