Atul Gawande, the surgeon-writer, is outraged (A Lifesaving Checklist 12/30/07.) Apparently an ongoing medical study, that he endorsed, was stopped because of a bureaucratic rule. The study was trying to this question:  Are there fewer hospital infections if doctors follow a checklist, as do airline pilots on take-off (sample: Have you washed your hands? Have you draped the patient with a sterile cover) than if treat patients according to their own rules? This, Dr. Gawande fomented, is bureaucracy at its worst. Stopping the study is outrageous, because the benefit of checklists is so obvious. (He did not ask why, if the benefit is obvious, the study should be done at all.) 

The study asked the doctors for half the patients to use checklists to prepare for a procedure while the doctors for the other half would prepare as they saw fit. The reason the bureaucracy—in this case the Office for Human Research Protections (OHRP)—gave to cancel the study was that the investigators had not asked patients to consent to participate. Some might have refused. After all, if you were the patient, would you want to be under the care of the doctor who did not use a checklist?  It is, of course, possible that using a checklist makes no difference at all, that doctors do the right thing all the time, but, if you are the patient, do you really want to take that chance? Shouldn’t you be asked? 

Dr. Gawande thought that insensitive bureaucracy had stupidly ended a useful study. He missed a larger point. First, we do not know whether the checklist does or does not make a difference (preliminary studies suggests it does), so it is perfectly appropriate to do the test—improving our knowledge is clearly worthwhile. Second, an experiment on a patient is not just good or bad. Human experiments engage several value systems not all of which are easily seen. The conflict between Dr. Gawande’s wish to continue and OHRP’s command to stop was a conflict between, and a different weighting of, these different sets of values. 

In research using patients, probably the highest value is accorded to patient autonomy.  A research patient has a fundamental right: to refuse to participate. This right trumps any perceived benefit of the research. OHRP clearly focused on this value; patients should have been given the right to refuse. 

The second most highly ranked value is that of privacy. This right was emphasized in first days of AIDS, to protect against discrimination or the public release of personal information.  To protect this right, medical researchers now are burdened with cumbersome regulations; all patient-identifying information must be removed from all documents.  Research data must be kept in locked cabinets. Physicians may not transmit information about patients to anyone, including family, except another treating physician, unless a patient expressly consents (a ruling that applies to all aspects of patient care).  This is not only a matter of ethics; in many states it is a matter of law. Researchers and treating physicians find it exhausting to comply with the paperwork engendered by these rules.  Privacy rules delay research; burdensome regulations cause some potential researchers not to enter the field at all.  Since not very much that is private is a risk in the checklist research, Dr. Gawande seems to rate the privacy value low; he would dispense with the bureaucratic needs. 

A third value can be summarized by this sentence: Medical research should provide the greatest good to the greatest number.  The checklist study would do this. The investigators may have assumed that checklists and observation of doctor behavior does not count as research. They may be correct. Audits of practice, whether or not one collects additional data, are usually exempt from research rules.  Furthermore, the agencies that rule over human research exempt some research from consent—studies of population behavior, for instance—and provide expedited approvals for low risk research.    The researchers should have asked for an exemption, but they certainly know that local human research monitoring boards are inconsistent.  When the same research is done in several different sites, as the checklist study was done, one local board may consider it exempt from consent rules, while another may require full consent.  Such inconsistencies exasperate researchers and delay research if not force it to a complete halt. Had OHRP been asked before the experiment began, it might have ruled that checklists are practice audits exempt from consent, or it might not. One does not know until one asks. 

Society values innovation and rapid dissemination of research results.  These values contradict the values of autonomy and privacy. Innovation and dissemination demand flexibility of experiment rules and open and ready access by the public; autonomy and privacy restrict the rate of flow and narrow the volume of information that may be shared.  Even the creation of a widely desired a national medical database is hobbled by privacy concerns. 

The value “do no harm” has a very high priority. Pragmatically, however, the fact of the study is closer to “do less harm” or “do more good” than it is to “do no harm.” Consider the comparison of a new drug with an old; the new one is thought to be safer, but it may not be. If the new drug is better, those receiving the old will be (in one sense) harmed by the experiment; if the new drug turns out to be, in fact, more toxic, those receiving it will be harmed. Or consider the circumstance in which early surgery is thought to give a better cure rate than a medical treatment. Either the surgery or the medical-treated patient group could be harmed or helped, depending what the answer turns out to be. In some cases an experiment demonstrating good yields a very small, one might say trivial, improvement; in another case the difference might be as great as that between death and cure. The amount of potential good or potential harm can be weighed. Committees that judge the overall value of a research study on humans use common sense rules but apply no formal measurement scales to these values. Absent a metric, OHRP’s and Dr. Gawande’s opinions collide. 

So what to do?  Protect the privacy of the research subject?  Facilitate the rapid conduct of research? Protect at all costs against possible harm? Or make possible a public good? 

One cannot reconcile the conflicting demands.  One can try to make the committees more uniform, the rules more efficient, but these are minor fixes. Instead, it would be best to concede that our contradictory rules derive from different societal values, and that no one rule is absolute.  We can assign point systems—degrees of risk—that have positive (for benefit) and negative (for risk of harm) numbers instead of ruling by yes/no criteria. There are different levels of privacy and autonomy, and different degrees of good and harm. Scientific importance can be quantitated. The potential public gain can be as well.  The numbers can be summed, and the potential worth of the research scored. 

The table below gives examples. How the scoring system is actually constructed is not an important point. What is important is that the investigators should document how their proposals address each of the values; what is important is that the committee should systematically weigh each value when it decides to approve or disallow a specific project of human research. When that happens, Dr. Gawande, instead of railing against a faceless bureaucracy, will see its decision from another point of view, and OHRP will understand that some quantitatively small risks can be waived.

There is a Nobel Prize available for the person who can answer your question(s). Current thinking is that lupus (and, by extension, APS) is triggered by a common virus in a susceptible person. The leading suspicious virus is cytomegalovirus (CMV), which causes a mononucleosis-like disease; Epstein-Barr virus (EBV), which causes mononucleosis, is another candidate. There is an extensive medical literature on this topic. John Harley and Judith James, in Oklahoma, have published several papers indicating that the infection likely occurs a decade or more before the disease becomes obvious. You can hunt for these papers at the National Library of Medicine site (PubMed) and search on the terms “Harley J AND lupus” or “lupus AND CMV” or such to find the papers, or, given a day or two, I can compile a list for you.

None of us in my world think of vaccinations as likely virus triggers; on the other hand, if you have no concept of how devastating polio, tetanus, diphtheria, measles, etc. can be (lethal, brain-damaging, permanently disabling) you may underestimate the value of vaccination. If you choose not to vaccinate your children, you rely on “herd immunity”, that is, the luck that others they encounter will be immune and protect them. Loss of herd immunity has resulted in epidemics as recently as this year of these common diseases in fundamentalist communities, Native American communities, and “hippie” colonies in the United States this year, so these diseases are by no means gone.

Bottom line: although your children may have inherited (a degree of) susceptibility from you, they are somewhat protected by their father’s genes; vaccinations are not the things to fear. Rather, common infections, some of which can be prevented by vaccination, are more likely triggers.

ISBN: 9780809053452
ISBN10: 0809053454
Published: Farrar Straus & Giroux
Publish Date: 1998-06-01
Pages: 288
Binding: Hardcover
Dimensions: 1.01 L x 6.31 W x 9.31 H

Description:
When individual and broad social values clash, who should determine the course of action? An important new voice, Michael Lockshin, M.D., speaks out on health care in America today. A noted physician with broad experience in treating long-term, incurable patients, Lockshin shows exactly how our health-care system could be more efficient, less costly, and more humane.
 

• Autoimmune Disease: Does Sex Matter?
  Current Theories
• Gender and Rheumatoid Arthritis
  Summary of a presentation at the Living with RA Workshop at HSS

“My wife and I want to leave our estate to organizations that have made an impact on our lives, such as HSS, especially because we don’t have any children,” says Mr. Coppersmith.

In 2002, Mrs. Coppersmith was diagnosed with a rare but debilitating condition that caused numbness in her legs and arms. After undergoing a series of unsuccessful treatments at another hospital, she was referred to Michael Lockshin, MD, a rheumatology specialist at HSS with a keen interest in Mrs. Coppersmith’s condition. Dr. Lockshin would eventually become Mrs. Coppersmith’s primary care physician. In 2005, he enrolled her in a clinical trial measuring the success of a new therapy for her illness.

“Dr. Lockshin is one of only a few physicians who is familiar with Maria’s condition,” Mr. Coppersmith said. “Under his care, she has found both comfort and relief.”

Born in Colombia, Mrs. Coppersmith immigrated to New York nearly 44 years ago, where she pursued a career in the textile industry. She met Mr. Coppersmith when they lived in the same development in the Bronx, the borough in which he was born and raised. A graduate of Stuyvesant High School and City College of New York, Mr. Coppersmith worked as a mechanical engineer for R. Hoe and Co., where he designed printing press machinery for the New York Times and color presses for Conde Nast. He joined the engineering department at Con Edison in 1971 and remained there until his retirement in 1991. Today, the couple shares a passion for camping in places such as Canada, Mexico, and California.

The Coppersmith’s thoughtful bequest to HSS will serve as an important source of support for future basic science and clinical investigations into rheumatic diseases undertaken by Dr. Lockshin and his colleagues. “I am confident that every penny HSS receives from us will be used in accordance with our wishes,” Mr. Coppersmith remarked.

See the complete news release on the Hospital for Special Surgery’s web site

How many days before a colonoscopy procedure should a person with APS cease taking their prescribed 81mg of aspirin or other similar medications?
The amount of time before a procedure should be approximately 1 week for aspirin, clopidogrel (Plavix) or warfarin (Coumadin). For low molecular weight heparin you need 24 hours and for unfractionated heparin the patient should cease about eight hours before.

What are some symptoms a person with APS should worry about?
Visual changes, speech defect, sudden change of anything, persistently blue digit, unusual bruising or red spots on the skin.

If I have APS, is my immune system overactive or underactive?
There is a technical answer and a conventional answer to this question. The conventional answer is that the immune system is overactive and it produces an antibody that should not be there. The technical answer is that scientists are highly suspicious that the overactivity is an attempt by the body to compensate for an under active part of the immune system that we haven’t yet identified.

If you have lupus without APS, are you at risk for developing it later on? If you have APS without lupus, what are your chances for developing lupus?
In general, if both diseases appear, they do so at about the same time, so the answers to the questions are “no” and “very low,” respectively.

Is oral surgery safe for someone with APS?
In general, yes. But it depends on the specific details for the patient and for the oral surgery procedure. There may be specific precautions necessary, i.e., antibiotics, if heart valves are abnormal, or changes of anticoagulation medicine if the surgery is extensive.

Is a diagnosis of “sticky platelets” the same as APS?
The British, especially those associated with Graham Hughes’s group, use the term “sticky platelets” to describe APS. There are other causes of sticky platelets and I don’t think the term is very accurate, so I don’t use it myself.

How do I know if my doctor is prescribing the right medication for me?
That is always a tough question, because there’s a fair amount of variability in both patients and doctors. The best option is to get another opinion from someone who has a great deal of experience. This applies to any illness - not just antiphospholipid syndrome.

Why don’t doctors use a Greenfield filter as opposed to coumadin?
Greenfield filters are used on occasion when the indication is correct. Clots form on the filter and above it, so you still have to take anticoagulation medication. (For those who don’t know, a Greenfield filter is a sort of mesh that is placed in the big vein leading from the legs to prevent blood clots in the legs or pelvis from traveling to the lungs. It is sometimes used for a short period of time after surgery and then removed when the risk of clotting is over. For someone with APS, the risk of clotting is never over. A Greenfield filter is usually used when the clots in the lower extremities are very big and very threatening and/or have already traveled to the lungs.)

If a pregnant woman has APS and severe preclampsia, should heparin absolutely be used?
There is no history of clots or previous miscarriages.
There are not clear rules on this, but severe preclampsia is considered to be a manifestation of APS, and most physicians who treat APS do advise the use of heparin in this circumstance. There is an additional reason to do so; in the animal models of pregnancy complications heparin appears to be beneficial in ways that are not associated with clot prevention, so the theory is right.

How is preclampsia related to APS?
Early and severe preeclampsia occurs relatively commonly in women with APS whether or not they have had prior symptoms. There are a number of theories about the mechanism, but exactly how they are related biologically is not yet clear. Research in this area is very hot right now and we may have answers in the near future.

How common is it to have miscarriages, strokes, or a heart attack?
Each of these problems can be a manifestation of antiphospholipid syndrome. For one treated patient to have all three to occur would be uncommon, at least over a 10-year period. However, if you ask about these things happening over 30 or 40 years, then there are not really clear answers since we have only known about antiphospholipid syndrome (separate from lupus) for about 15 years.

Is rituximab effective for the kidney disease aspect of APS?
Rituximab is an experimental drug for antiphospholipid syndrome. We are asking this question right now in our current studies and hope to have an answer for this within a few years. At this moment the most honest answer is that we don’t know.

See the complete article on the Hospital for Special Surgery’s web site

What is lupus?
Systemic lupus erythematosus (SLE), commonly called lupus, is a chronic autoimmune disorder that can affect virtually any organ of the body. In lupus, the body’s immune system, which normally functions to protect against foreign invaders, becomes hyperactive, forming antibodies that attack normal tissues and organs, including the skin, joints, kidneys, brain, heart, lungs, and blood. The disease is characterized by periods of illness, called flares, and periods of wellness, or remission.

Because its symptoms come and go and mimic those of other diseases, lupus can be difficult to diagnose. There is no single laboratory test that can definitively prove that a person has this complex illness. Thankfully, awareness of lupus is increasing and is therefore more readily identified.

Who gets lupus?
Lupus is estimated to affect nearly 1.5 million Americans. While it occurs in both sexes, 90 percent are women, and most are diagnosed during the childbearing years. African-American women are three times more likely to get the disease than Caucasian women, and they often suffer more severe disease. National Institutes of Health figures indicate that as many as one in every 250 African-American women has lupus. Lupus is also twice as prevalent in Asian-American and Hispanic women as it is among Caucasian women. Native American women are also disproportionately affected.

How is lupus treated?
While there is no cure for lupus, early diagnosis and appropriate treatment can help in managing the symptoms and lessening the chance of permanent damage to organs or tissues. Once a lupus diagnosis is established, an assessment is made of damage to major organs such as the brain, kidneys, heart, and lungs. Treatment strategies depend on the activity level and extent of the disease and can range from over-the-counter pain relievers and anti-inflammatory drugs to prescription medications, psychotherapy, healthy diet changes, and lifestyle revisions such as staying out of the sun and avoiding stress.

How serious a threat does lupus pose to heart health?
The cardiovascular system is a main target of lupus. It can directly weaken the heart by causing inflammation of the muscle itself (myocarditis) or its inner lining (endocarditis). But the most common heart involvement in people with lupus is inflammation in the sac around the heart (pericarditis), which causes shortness of breath and sharp chest pain. These complications are typically treated with powerful anti-inflammatory and immune system suppressants such as prednisone, a corticosteroid.

What about coronary artery disease?
More than a third of people with lupus are at risk for this complication, primarily because inflammation and various immune system abnormalities cause the coronary arteries to rapidly harden, narrow, and clog, a condition called atherosclerosis. In time, clots can form or bits of plaque can break off from artery linings, interfering with blood flow to the heart and brain. Less common causes of coronary artery problems in people with lupus include inflammation of the artery walls, actual spasms of the arteries, and blood clots. The potential for problems forms a chilling picture, with female lupus patients 50 times more likely than their peers to have chest pain or a heart attack. (Less is known about the increased risk among the 1 in 10 men with lupus.)

But I’m still young, and I take pretty good care of myself.
It appears that having lupus by itself means a person is more likely to develop coronary artery disease. Young women with lupus (under age 40) are nearly five times more likely to have this ailment than their same-age peers—regardless of whether they have other risk factors such as smoking, high blood pressure, diabetes, or excess weight. Over time, lessened blood and oxygen flow to the heart weaken the muscle. Bits of cholesterol can break off from artery linings, interfering with blood flow to the brain as well as the heart. Long-term use of corticosteroids can also cause harm.

What can I do to keep my heart healthy?
See your doctor regularly and always mention new or changing symptoms, including chest pain or shortness of breath. Ask about other warning signs of a heart attack or stroke and what to do if they develop. The goal is to detect and treat lupus flares as early as possible, limit corticosteroid use (in a smart way, with the doctor’s approval), take measures to stop other heart-damaging factors (smoking, high blood pressure, excess weight), get regular exercise (even a 30-minute daily walk helps), and follow a healthy diet. Also key: a close working relationship between you and the doctor, including heart specialists (cardiologists). Some doctors put lupus patients with coronary artery disease on cholesterol-lowering drugs called statins.

Are certain people with lupus at particularly high risk for heart problems?
Certain populations, such as black women, need to be particularly vigilant. Not only is heart disease the number one killer of all black women, but the death rate from heart disease is nearly 70 percent higher in women of color than it is in white women. Black women are also three times more likely than white women to have lupus—which in itself raises the risk for heart damage.

What are the primary areas of research in lupus—and is the cardiovascular system one of them?
With no major new treatment approved in more than 40 years, lupus needs a breakthrough. Researchers have made significant headway recently, however, reporting exciting findings in terms of how the disease works and what can be done to treat it. Among the discoveries are a deeper understanding of the genetic links to lupus and enhanced recognition of how lupus attacks the brain, kidneys, and skin. And several promising advances have also been made in figuring out lupus heart disease. Researchers have learned a lot more about immune system abnormalities that target this organ and have greater insight into biomarkers (predictors) of atherosclerosis. There are also improved techniques for early detection of heart disease, and more options for drug treatment.

Are companies developing new drugs to treat lupus?
Yes, finally. Several pharmaceutical companies are developing new medications. An online search will generate information on these companies and their drugs. You also can find websites that report new drug findings, such as

www.lupusny.org
www.lupusresearchinstitute.org.

How can I help advance research and drug development?
As a person with lupus, you can directly help in advancing lupus science—and simultaneously help yourself—by participating in a clinical trial. A clinical trial is a research project that evaluates the safety and effectiveness of medical treatments, drugs, or devices in human beings. The Food and Drug Administration (FDA) requires that such trials be performed before a product can be prescribed to patients. For information on clinical trials in lupus, try visiting the following websites:www.clinicaltrials.gov
www.lupusresearchinstitute.com
http://www.centerwatch.com/
 

What is the outlook for people with lupus?
There isn’t a cure yet, but every year now researchers are gaining promising new insights into this disease and uncovering promising treatments. Just twenty years ago, only 40 percent of people with lupus were expected to live more than three years following a lupus diagnosis. Now, with earlier diagnosis, refinements in treatments, and careful monitoring, most people with lupus can look forward to a normal lifespan. More than 80 percent of people diagnosed with lupus in 2005 will live for 10 years or more.

See the complete article on the Hospital for Special Surgery’s web site

• What is Clinical Research?
• Conducting Clinical Research: Safety and Confidentiality
• Treatment Trials
• Trial Phases
• Kinds of Drugs Observed in Clinical Trials
• Aims of Lupus Research
• Lupus Clinical Trial Consortium
• Tips for Patients/Participants
• The Good News
• The Bad News/Challenges
• Types of Studies at HSS

What is Clinical Research?
What is clinical research? “A whole doctor and a whole patient in a room at the same time.” This is very different than looking at tissues in a lab. There are several types of clinical research taking place here at Hospital For Special Surgery. These include:
• Treatment trials
• Observations to understand the course of disease
• Interventions to understand the course of disease
• Epidemiology studies that look at how much a population is affected and why
• Psychosocial studies
• Blood or tissue specimens or autopsies

Conducting Clinical Research: Safety and Confidentiality
In order to conduct a clinical research study, a series of regulations that is in the interest of patient safety and confidentiality must be followed. For example, a research project must meet Health Insurance Portability and Accountability Act (HIPAA) regulations that guarantee participants’ privacy. The Institutional Review Board (IRB), which is a hospital based entity, has to approve the process of the study as well as the risks and benefits involved and must grant permission to conduct the study in order to ensure the patient’s safety. This process can take about six months or so. In addition to several other regulatory bodies, an outside monitoring board that is not affiliated with the study must monitor the proceedings (Data and Safety Monitoring Board, DSMB). This board can put a stop to the study if they perceive that a participant’s safety and/or privacy are being compromised.

A substantial amount of time is invested to ensure that participants are safe throughout the research project and that their confidential health information is not compromised.

Treatment Trials
When most people think of clinical research, they usually think of treatment trials. In placebo-controlled studies, treatment is compared to no treatment, and researchers just look to see what happens. These studies usually produce the cleanest and clearest answers. However, an undesirable consequence of this kind of study is that some patients come to realize that they may not receive the treatment under question. More commonly used as a comparison is the standard-therapy controlled approach. In this type of study, a new drug is compared to standard therapy. Although very common and informative, this type of comparison requires more patients to participate than does a placebo-controlled trial because all patients are expected to improve. Lastly, treatment can be compared to how patients did in the past when compared to the new treatment; these comparisons are called historical controls. This involves looking at the history of the treatment of a person over a number of years. This method is not very reliable, however, because the period of time under observation can be influenced by the introduction of other medications in the system, such as antibiotics or blood pressure medications that may also influence a patient’s outcome. …

See the complete article on the Hospital for Special Surgery’s web site

Summary by Jillian Rose, MSW