Volume 90 No. 2 February 2007

UNDER THE JOINT VOLUME 90 NO. 2 February 2007 EDITORIAL SPONSORSHIP OF: Medicine
Health Brown Medical School Eli Y. Adashi, MD, Dean of Medicine HODE SLAND & Biological Science R I Rhode Island Department of Health PUBLICATION OF THE RHODE ISLAND MEDICAL SOCIETY David R. Gifford, MD, MPH, Director Quality Partners of Rhode Island COMMENTARIES Richard W. Besdine, MD, Chief Medical Officer 38 Ethical Guidelines and Guidelines On Ethics Are Not the Same Rhode Island Medical Society Joseph H. Friedman, MD Barry W. Wall, MD, President 39 Blessed Are the Pure of Heart EDITORIAL STAFF Stanley M. Aronson, MD Joseph H. Friedman, MD Editor-in-Chief Joan M. Retsinas, PhD CONTRIBUTIONS Managing Editor Stanley M. Aronson, MD, MPH 40 Spotlight on Claudication: An Important Disease Gets Attention Editor Emeritus Timothy P. Murphy, MD, Gregory Dubel, MD, James Bass, MD, Sun Ho Ahn, MD, Gregory M. Soares, MD, and Joselyn Cerezo, MD EDITORIAL BOARD Stanley M. Aronson, MD, MPH 43 Update on Idiopathic Pulmonary Fibrosis: The Role of Gamma Interferon Jay S. Buechner, PhD and Cytokines John J. Cronan, MD Napoleon A. Puente, MD, Jason M. Aliotta, MD, and Michael A. Passero, MD James P. Crowley, MD Edward R. Feller, MD 46 On Heachache Tablets: Headache Incantations From Ur III (2113–2038 BC) John P. Fulton, PhD Vlad Zayas, MD Peter A. Hollmann, MD Sharon L. Marable, MD, MPH 48 Disruptive Physician Behaviors Anthony E. Mega, MD Marguerite A. Neill, MD Robert S. Crausman, MD, MMS, Alberto Savoretti, MD, and Jeven Conroy Frank J. Schaberg, Jr., MD Lawrence W. Vernaglia, JD, MPH Newell E. Warde, PhD COLUMNS OFFICERS 50 THE CREATIVE CLINICIAN – Giant Cell Mycarditis Presenting As Isolated Right Barry W. Wall, MD Ventricular Dysfunction President Richard Regnante, MD, and Athena Poppas, MD, FACC K. Nicholas Tsiongas, MD, MPH President-Elect 55 GERIATRICS FOR THE PRACTICING PHYSICIAN – Managing the Medication Portfolio & Diane R. Siedlecki, MD Avoiding Polypharmacy in the Older Adult Vice President Ana C. Tuya, MD Margaret A. Sun, MD Secretary 57 HEALTH BY NUMBERS – Hospital Community Benefits, 2005 Mark S. Ridlen, MD Bruce Cryan, MBA, MS Treasurer Kathleen Fitzgerald, MD 59 PUBLIC HEALTH BRIEFING – Taking a Social Marketing Approach To Implementing Immediate Past President Clinical Best Practices: A Pilot Project DISTRICT & COUNTY PRESIDENTS Robert Marshall, PhD, Arthur Frazzano, MD, MMS, Deidre Gifford, MD, MPH, Geoffrey R. Hamilton, MD Marcia Petrillo, MA, Shannon Sansonetti, MA, and Jeffrey Stumpff, MA Bristol County Medical Society Herbert J. Brennan, DO 62 HEALTH INSURANCE UPDATE – National Provider Identifiers – Implications for the Kent County Medical Society Local Provider Community Rafael E. Padilla, MD Patricia E. Huschle, MS Pawtucket Medical Association Patrick J. Sweeney, MD, MPH, PhD 63 ADVANCES IN PHARMACOLOGY – Off-Label Drug Use Providence Medical Association Andrea G. Dooley, PharmD Nitin S. Damle, MD Washington County Medical Society 66 PHYSICIAN’S LEXICON – A Plethora of Pertinent Prefixes Jacques L. Bonnet-Eymard, MD Woonsocket District Medical Society Stanley M. Aronson, MD 66 Vital Statistics Cover: “Summer Love” 18"x18" Oil On Canvas by Bill Chisholm, a Rhode Island art- 68 February Heritage ist who recently received “2006 Best In Show For Fine Art” at Providence Fine Furnishings Show. He exhibits in galleries throughout New England. www.billchisholm.com; Medicine and Health/Rhode Island (USPS 464-820), a monthly publication, is owned and published by the Rhode Island Medical Society, 235 [email protected] Promenade St., Suite 500, Providence, RI 02908, Phone: (401) 331-3207. Single copies $5.00, individual subscriptions $50.00 per year, and $100 per year for institutional subscriptions. Published articles represent opinions of the authors and do not necessarily reflect the official policy of the Rhode Island Medical Society, unless clearly specified. Advertisements do not imply sponsorship or endorsement by the Rhode Island Medical Society. Periodicals postage paid at Providence, Rhode Island. ISSN 1086-5462. POSTMASTER: Send address changes to Medicine and Health/Rhode Island, 235 Promenade St., Suite 500, Providence, RI 02908. Classified Information: RI Medical Journal Marketing Department, P.O. Box 91055, Johnston, RI 02919, phone: (401) 383-4711, fax: (401) 383-4477, e-mail: [email protected]. Production/Layout Design: John Teehan, e-mail: [email protected]. 37 VOLUME 90 NO. 2 FEBRUARY 2007 patients with Parkinson’s disease if they had Commentaries a problem with a runny nose. If they did I then asked if it developed before, with or after the PD. If the patient was accompa- nied by anyone over the age of 50 I asked that person too if they had a runny nose. Ethical Guidelines and Guidelines To be “ethical” I prefaced my first question with the statement that I was doing a sur- On Ethics Are Not the Same vey, which was a research study to deter-  mine if a runny nose was more common in PD than in people without PD. Of course I recently saw a patient who had abused I was annoyed but not dismayed. This I had a strong suspicion that this was the a drug which was not included on the usual came later. I became a site investigator for a case but it’s never been a published obser- toxicology “screen” sent from the emer- pharmaceutical company’s study of a vation, although an ENT colleague told gency departments (ED) of most Ameri- prodrug of gabapentin, to be used to treat them that it’s a well known observation in can hospitals. What made this case impor- restless legs syndrome. This drug has a dif- his field. This isn’t the idiotic question you tant to me was that one of the parents, a ferent kinetic profile, making it possibly su- may think it is. For one thing it turns out physician, told the ED doctor what drug perior, possibly not, but at least different from that it may be very embarrassing. For an- to look for; and when the tox screen came a patent viewpoint. More of a “me too” sort other patients and families are generally very up negative, the patient was then thought of drug than a breakthrough. But I was sur- pleased to know when some oddball symp- to have a neurological disorder and re- prised when I read the protocol. The FDA tom is “part” of the disease and that they ferred to me. had required safety testing that was far more are not being hypochondriacal or “weird” The doctor hadn’t thought to check complex than what was needed to demon- in some way. In this case it turned out to be what drugs the tox screen tests for and what strate that the drug was effective. What is about ten times more common in PD pa- drugs are missed. As it happens, the tar- bizarre is that the safety data required had tients than the controls. This probably has geted drug, dextromethorphan, which is no justifiable basis. In fact, one could argue some clinical importance in that this is most the single most abused drug by children in convincingly that the extensive data on likely the result of early sympathetic dys- the United States, does not appear on the gabapentin should have made it easier rather function that may, in fact, precede the usual tox screen so that an “extended” or than harder to demonstrate safety in the case motor signs of the disease. If true, this would “complete” tox screen must be requested. I of this newer drug. Maybe to compensate provide another “pre-symptom” of the dis- thought this mistake so important that I for their weak post-marketing work they are ease that will be helpful when we find a published a report in a neurology journal doing as much as they can pre-approval? drug that slows the disease progression. The to call attention to the ED oversight. What From an investigator’s standpoint, the only result was submitted as a letter to the editor happened next is what’s bizarre. outcome of the mandated testing will be a of a prestigious journal. The journal was As a result of this report I was con- higher price for the drug when it comes to very interested, asked a number of ques- tacted by two major drug companies that market. tions, but refused to consider a revision market cough medicines containing This caused me then to reflect on a when they learned that I had not obtained dextromethorphan. I was to report to the study I designed for my own center. It re- Institutional Review Board approval. I was Food and Drug Administration an adverse quired FDA approval for testing an old drug not surprised, but had decided a priori to effect of the drug! Now, who in their right on a new patient population. To test low “test” whether common sense was a con- mind would consider an intentional over- doses of extended-release ropinerol, doses sideration in contemporary academic medi- dose for the effect of getting high a side ef- which we routinely give to PD patients in cine. I then consulted the IRB about the fect? And didn’t I already exceed my civic their 60’s or 70’s, in a schizophrenic popu- study. The response was, “You don’t need duty by publishing the case so that anyone lation, of physically healthy people decades IRB approval for a study of this sort, unless at the FDA and anyone who can read En- younger than the PD patients, the FDA you want to publish it. Many journals re- glish would be able to find the effects of asked us to give the dose in the office and quire IRB approval for any study.” When I this drug with a computer search? What monitor the subject for eight hours. This submitted the protocol the IRB stated that was the point? There is a reason for post- will, of course, make recruitment incred- I needed to hand the patient a single page marketing surveillance, possibly even de- ibly difficult. How many people are will- stating what I was studying and that they cades after a drug is released, but the FDA ing to be in a trial if they have to hang didn’t need to participate. As Dave Barry has become increasingly disinterested in around a doctor’s office for eight hours get- says, I am not making this up. true post-marketing surveillance, having ting blood pressures measured every hour? There have been a lot of problems in caved in to Big Pharma. But what is learned And what sort of safety data will be gleaned the clinical trial arena. There is no question from another case of purposeful drug tox- from this when there is a decade of experi- that doctors and pharmaceutical companies icity? Do breweries have to report every case ence using the drug at similar doses in older, have, on occasion, abused their subjects. It is of drunkenness that they hear about? frailer patients? clear that clinical trials need to be policed. It People may drink beer to get drunk. It’s Just recently I completed a “study” in is also clear that the FDA needs to monitor not a side effect. which I asked one hundred consecutive drug safety and that they need to be assidu- 38 MEDICINE & HEALTH/RHODE ISLAND ous in this pursuit. Journals need to be sure ics may do the opposite. Suppressing useful cannot legislate intent, which is the true back- that research results have been obtained ethi- clinical information that harms no one, re- bone of ethical medicine. cally, but there is surely a role for common veals no identities, obtained from willing and sense. Iron clad regulations “mandating” eth- informed subjects cannot be ethical. Rules – JOSEPH H. FRIEDMAN, MD Blessed Are the Pure In Heart

There was a time in the distant past when the heart ruled all. The mobility of the poetic heart is truly astonishing: some- But this was before prosaic scientists envisaged the heart as a con- times it lies deeply embedded within a fierce bosom, sometimes it voluted muscular pump conveying blood through a succession of is worn upon one’s sleeve and sometimes, in times of terror, it mi- four inner chambers with intervening valves, its rhythmic con- grates to one’s mouth. At other times, as in the poetry of Macloed, tractions governed by electric stimulants and its substance nour- it can be a lonely hunter that hunts upon a lonely hill. On rare ished by two critical arteries. The motivating currents came to be occasions, according to Spenser, it might be a source of nutrition: measured, the patency of the coronary arteries determined and he stated “to eat thy heart through comfortless despair.” The ana- amazing interventions then brought this muscular contrivance, tomic site of the heart may be in some doubt, but to some unpo- when ailing, back to a reasonable state of normal function. etic individuals rendering advice to young women, the way to a The downhill odyssey of the heart, from its role as a won- man’s heart is through his stomach. drous spiritual organ to that of a robotic mechanism, is now virtu- The heart, despite its occasional heaviness, can sometimes be ally complete. An American company recently assembled an arti- lifted with joy, bonded to one’s very being [heart and soul] and yet ficial heart, will all its internal valves, that is said to be capable of in times of stress can be weary, humbled, despairing and contrite. replacing the human heart. No longer, then, is the heart the seat And it can be an organ of uncommon eloquence, as in the Book of joy, sorrow and intervening emotions. No longer can the Scrip- of Job, “I caused the widow’s heart to sing for joy.” tural Proverbs declare that “A merry heart maketh a cheerful coun- Washington, our first president, was remembered by Henry tenance, but by sorrow of the heart the spirit is broken.” Lee when he referred to him as first in the hearts of his countrymen. The fragile voice of the poet, exclaiming that the heart is more The third president, Thomas Jefferson, saw an anatomical channel than a mute, compliant muscle, has now been overtaken by the between one’s words and the moral status of the heart. [“Falsehood authoritative declarations of science. Angioplasty, the retooling of of the tongue leads to depravity and falsehood of the heart.”] the coronary arteries, has proven its worth and, accordingly, its Nor have the poets ignored heart disease. Did not the Psalms talk superiority over Wordsworth’s sonnets. of a broken and contrite heart? And did not Shakespeare’s Lear con- The heart, in truth has been the poet’s most reliable, most fide that his heart would break into one hundred thousand fragments? enduring metaphor. It is doubtful that there is any human emo- Even cardiac flutter and fibrillation were known to the poets long tion, from the most evil to the most pious, that has not been as- before the electrocardiographers demonstrated pathologic cribed to the human heart. The heart has been the seat of under- arrhythmias. Crane declared: “ I linger on the flathouse roof, the moon- standing, the source of interpersonal warmth, a place of benevo- light is divine/ But my heart is all aflutter like the washing on the line.” lence and the seat of yearning. But sometimes insubstantial ideas, mere poetry, validate them- We humans regularly experience a change of heart, or worse, a selves long after they have been discarded by the practical people of heart chilled by fright, shrunk by terror, bled in despair or weakened the world. An extensive epidemiological study, conducted by a team by a loss of resolve; but still it remains the ultimate source of courage. of Canadian physicians, tracked 50,000 Ontario patients, each older Robert Burns, the Scot with a sunny disposition, saw the heart as the than age 70, with demonstrated heart disease. They found that site of kindness and benevolence, most resembling God. Yet others recurrent heart attacks, particularly fatal episodes, were 27% more envisioned the organ as mean-spirited, capricious and hard-hearted. common on these patients’ birthdays. Similarly, these patients were Even Exodus beheld a Pharaoh’s heart which had hardened. more vulnerable to cerebral stroke on their birthdays than on any Dostoevski imagined the heart as the arena where God and other day of the year. The researchers found no correlations be- the devil sought combat, “and their battlefield is the heart of man”. tween birthdays and the onset of other organic diseases such as ap- Long before angiography was invented, Ibsen, that northern cynic, pendicitis. They ascribed this “birthday effect” to “psychosocial stres- declared: “Look into any man’s heart and you will always find at least sors” but acknowledged that other forces might be implicated, per- one black spot which he has to keep concealed.” Faulkner agreed, haps even partying and transient overindulgence. Sentimentality, a stating that the heart is where life’s truths and verities are closeted. very unscientific premise, was never mentioned. The heart is an organ that wearies easily, but still, in And finally a study, back in the 1980s, analyzed 22,000 Rhode Wordsworth’s words, it remains “ a fountain of sweet tears, and Island death certificates, demonstrating a relative paucity of deaths love, and thought, and joy.” It is a mobile organ that a credulous just prior to one’s birthday followed by a sudden spike in deaths lover might give away and a sophisticated suitor might casually on or just beyond the birthday. accept. It can be the site of utter purity; although even a president The poetic eye may indeed be more discerning, more discrimi- of sterling character might commit adultery in his heart. [This was nating, than all the awesome instruments of modern medicine. long after Matthew had asserted that he who looks upon a woman with lust has already committed adultery in his heart.] – STANLEY M. ARONSON, MD 39 VOLUME 90 NO. 2 FEBRUARY 2007 Spotlight on Claudication: An Important Disease Gets Attention Timothy P. Murphy, MD, Gregory Dubel, MD, James Bass, MD, Sun Ho Ahn, MD, Gregory M. Soares, MD, and Joselyn Cerezo, MD

Peripheral arterial disease (PAD) stroke, and is a chronic disease that can studies have demonstrated the risk of heart affects 5% of those over the age of 50 profoundly limit physical functioning.4 attacks, strokes, and death to be similar to and up to 29% of those over the age of Reduced physical activity in older indi- those with known coronary artery disease, 70.1 Claudication, the most frequent viduals is associated with increased mark- and medical risk factor reduction has be- symptom of PAD, consists of pain in the ers of cardiovascular disease risk, such as come increasingly sophisticated and rec- leg muscles during walking, usually in the high blood pressure, diabetes, obesity, ommended for claudicators. Finally, if calf.2 US census data indicate that the systemic inflammation, thrombosis, and revascularization is necessary, the value of number of Americans over the age of 65 disorders of lipid metabolism. Physical interventional therapy is currently widely is expected to double by 2030, and the activity is known to be inversely associ- accepted and has 90% less risk than sur- incidence of PAD is expected to increase ated with cardiovascular events.5 Walk- gery. The contemporary practice of medi- as our population ages. Those with clau- ing disability caused by PAD results in a cine requires the importance of PAD to dication experience an increased relative sedentary lifestyle, self-perceived walking be appreciated and thoroughly consid- risk of total mortality that is 2 to 4 fold disability, and lower health-related qual- ered, diagnosed, and managed routinely. greater than those without claudication, ity of life.4 In summary, claudication pre- and have 6-year survival of only 55%, cludes an active, healthy life-style in many DIAGNOSTIC EVALUATION and 10 year survival of only 37%.3 older individuals that may contribute to Claudication usually can be readily The National Heart, Lung, and the observed excess mortality in this diagnosed by history and physical exami- Blood Institute (NHLBI) of the National population. nation; the ankle-brachial index (ABI) Institutes of Health recently recognized examination is done to confirm the clini- the importance of furthering research RECOGNITION OF CLAUDICATION cal impression. Other diagnostic tests and education about PAD. The NHLBI In an era when medications that ad- such as magnetic resonance angiography has increased funding for PAD-related dress symptoms were of limited effective- (MRA) or computed tomographic an- research, and has committed to funding ness, the risk of morbidity and mortality giography (CTA) provide precise ana- a public health awareness campaign were not well known, and when the only tomic vascular images which can be used about PAD (www.aboutpad.org). This revascularization option was surgery, di- for treatment planning, particularly for article will review advances in manage- agnosing and treating claudication was not those patients considered for ment of intermittent claudication, the a high priority in medicine. However, over revascularization. In the past, the more most frequent presentation of PAD, and time compelling arguments for identifica- elaborate diagnostic examinations were discuss new research that will broaden tion of claudication patients have often the purview of the vascular special- our knowledge base in this area. emerged. First, quality of life studies are ist, but increasingly these tests are being increasingly showing the claudication ordered or performed in the primary care THE IMPACT OF CLAUDICATION population to have very low physical qual- setting. In fact, in order to achieve the Claudication is a marker for in- ity of life, comparable to congestive heart goal of increased recognition and risk fac- creased risk of cardiovascular disease and failure4 [Figure 1]. Second, numerous tor management for individuals with clau- dication, evaluation and medical man- agement in the primary care setting is es- sential. A multispecialty consensus panel recently issued recommendations on the evaluation and management of patients with intermittent claudication. 6 [Table 1]

MANAGEMENT OF CLAUDICATION: RISK FACTOR MODIFICATION Figure 1. On the left, SF-36 baseline results for our population, mean age 61+10 years, Patients with PAD should have ag- graphed with the published norms for U.S. population sample age range 55-64 years. gressive medical management of blood On the right, after iliac artery stent placement, SF-36 results compared with U.S. norms pressure (systolic blood pressure goal of for people of similar age. QoL results after stent placement closely reflects results obtained in a cross-section of the population of similar age. (PF=physical functioning, <140 mm Hg, or 130 mm Hg if diabetic 7 RP=role physical, BP=bodily pain, GH=general health, VT=vitality, SF=social or chronic kidney disease) , serum choles- functioning, RE=role-emotional, MH=mental health). terol (LDL <100 mg/dl)8(ideally <70 mg/ 40 MEDICINE & HEALTH/RHODE ISLAND average not when patients are instructed Table 1. Guidelines for Evaluation/Management of Claudicants to exercise on their own.1,13 However, 1. Claudicants should undergo a vascular physical examination including dedicated patients will report improve- measurement of the ABI. ment in symptoms even from home- 2. The ABI should be measured after exercise if resting index is normal. based programs. Supervised exercise re- 3. Arterial imaging should not be performed in patients with normal ABI’s habilitation, which has proven benefits except when other pathology (i.e. popliteal entrapment) suspected. in patients with claudication, is not re- 4. Patients considered for revascularization procedures must have imbursed by Medicare or most private significant functional impairment and reasonable likelihood of symptom- insurance, but is available in Rhode Is- atic improvement and absence of other exercise limiting disease. land for participants in the National In- 5. Patients offered revascularization procedures should stitutes of Health CLEVER (Claudica- a. be provided information of supervised exercise and pharma- tion: Exercise Vs. Endoluminal cological therapy Revascularization) Study (see below). b. receive comprehensive risk factor modification and antiplatelet Supervised exercise therapy and therapy interventional treatment both have the c. have significant impairment not allowing work or important potential of substantially greater improve- activities ment in walking ability than medication d. have anatomy favorable to successful and durable alone. How do they compare to each revascularization other? The roles of angioplasty and exer- cise for claudication have been the sub- dl) , platelet inhibition (aspirin with or ject of a Cochrane Database Review.14 without clopidogrel), tight diabetes man- …claudication This review presented data from two agement, angiotensin-converting enzyme precludes an active, studies that randomized claudication pa- inhibition if tolerated, and smoking cessa- tients to angioplasty or other treatment.15 tion.9 [Table 2] Smoking cessation is often healthy life-style in Results between the two studies were not the most difficult to achieve but can be many older consistent at 6 months, with the the most important measure in terms of Edinburgh study showing better exercise risk reduction. In Rhode Island, the Can- individuals that may performance in the angioplasty group, cer Countil lists free and fee-charging ces- contribute to the but the Oxford experience showing bet- sation programs (www.ricancercouncil. ter results of exercise. org/resources/smoking.php). Studies of observed excess both antiplatelet agents and angiotensin mortality in this THE NIH CLAUDICATION STUDY converting enzyme inhibitors have dem- Given the limited evidence support- onstrated treatment effects of those drugs population ing arterial stenting for claudication, and in reducing cardiovascular events that are the risk and expense of invasive particular strong in those with PAD even gible. However, newer drugs have clear revascularization procedures, the National without known CHD, but not present in and proven clinical benefit in patients Institutes of Health funded a multi-cen- people without PAD or other cardiovas- with claudication. Cilostazol (Pletal, ter randomized clinical trial to study clau- cular disease.10,11 Otsuka Pharmaceuticals), a phosphodi- dication treatment known as the CLEVER esterase inhibitor whose mechanism of (Claudication: Exercise Vs. Endoluminal MANAGEMENT OF CLAUDICATION action on claudication is unknown, has Revascularization) Study. The CLEVER SYMPTOMS been shown to improve walking ability Study has four treatment groups: optimal Historically, management has been 40-60% in people with claudication.1 medical care (OMC), OMC plus super- directed as improvement of symptoms, Cilostazol is prescribed as 100 mg twice vised exercise rehabilitation, OMC plus either through recommendations for ex- daily, and is contraindicated in those with stent, and OMC plus supervised exercise ercise, using medications like cilostazol congestive heart failure. The most fre- rehabilitation and stent. OMC will in- (Pletal, Otsuka Pharmaceuticals) or quent complaint with cilostazol is head- clude cardiovascular risk factor modifica- pentoxyfilline (Trental, Aventis). Surgery ache, which may occur in a quarter of tion including cholesterol, blood pressure, was usually not offered routinely. The prin- patients. If headache occurs, the dose can and diabetes management, dieterary con- ciple of claudication management was, be reduced to 50 mg twice a day (the sultation, and smoking cessation. Approxi- “stop smoking and keep walking.”12 Re- pills will need to be scored and cut in half ) mately half of the participants will partici- cently, interest in identifying individuals for two weeks, and if headache improves, pate in supervised exercise training for 6 has increased due to the proven benefit of a trial of increasing the dose to 100 mg months without charge. Additionally, medical interventions to modify cardiovas- twice a day can be done, or the dose can claudication medication (cilostazol) is pro- cular disease risk in this at-risk population. be continued at the reduced dose. vided for all participants throughout the Pentoxyfilline was the first FDA- Exercise therapy results in significant study without charge. This comprehen- approved drug used for claudication. improvement in walking ability when sive OMC meets and exceeds the Most agree now that its effect is negli- conducted in a supervised setting, but on multispecialty consensus panel recommen- 41 VOLUME 90 NO. 2 FEBRUARY 2007 Medicine and Biology, Society of Interventional Table 2. Optimal Medical Management for PAD/Claudication Patients Radiology, and the ACC/AHA Task Force on Prac- tice Guidelines. J Vasc Interv Radiol 2006; 17:1383- 1. Antiplatelet therapy-reduces the risk of MI, stroke, or vascular death in PAD 97; quiz 1398. patients 7. Chobanian AV, Bakris GL, et al. Seventh report of the Joint National Committee on Prevention, De- • Aspirin 75–325 mg/daily tection, Evaluation, and Treatment of High Blood • Clopidogrel 75 mg/d effective alternative and improves walking distance Pressure. Hypertension 2003; 42:1206-52. in many patients 8. Anonymous. Third Report of the National Choles- terol Education Program (NCEP) Expert Panel on 2. Supervised Exercise-useful initial treatment for claudicants Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) • minimum of 30–45 minute session final report. Circulation 2002; 106:3143-421. • minimum of 3 sessions per week 9. Critchley JA, Capewell S. Mortality risk reduction • for a minimum of 12 weeks associated with smoking cessation in patients with coronary heart disease. JAMA 2003; 290:86-97. 10. Anonymous. A randomised, blinded, trial of 3. Hypertension management- reduces the risk of MI, stroke, CHF, and CV death clopidogrel versus aspirin in patients at risk of • Goal of <140/90 mm Hg in nondiabetics ischaemic events (CAPRIE). CAPRIE Steering • Goal of <130/80 mm Hg in diabetics or those with chronic renal disease Committee. Lancet 1996; 348:1329-39. • Use of ACE inhibitors in claudicants reduces the risk of adverse 11. Anonymous. Effects of ramipril on cardiovascular cardiovascular events. and microvascular outcomes in people with diabe- • ß-adrenergic blocking drugs are effective antihypertensive agents and tes mellitus: results of the HOPE study and MI- are not contraindicated in patients with PAD. CRO-HOPE substudy. Heart Outcomes Preven- tion Evaluation Study Investigators. Lancet 2000; 355:253-9. 4. Lipid Management- indicated for all patients with PAD 12. Housley E. Treating claudication in five words. Br Med J (Clin Res Ed) 1988; 296:1483-4. • HMG-CoA reductase inhibitor (statin) indicated for all patients with PAD 13. Regensteiner JG, Meyer TJ, et al. Hospital vs home- • Target LDL cholesterol <100 mg/dL. based exercise rehabilitation for patients with pe- ripheral arterial occlusive disease. Angiology 1997; 5. Smoking Cessation-patients should be: 48:291-300. • Advised by each of their clinicians to stop smoking 14. Fowkes FG, Gillespie IN. Angioplasty (versus non surgical management) for intermittent claudication. • Offered comprehensive smoking cessation interventions, including Cochrane Database Syst Rev 2000; CD000017 behavior modification therapy, nicotine replacement therapy, or 15. Whyman MR, Fowkes FG, et al. Is intermittent bupropion. claudication improved by percutaneous transluminal angioplasty? J Vasc Surg 1997; 26:551-7. dations for PAD/Claudication. [Table 2] sored by the federal government through Timothy P. Murphy, MD, FSIR, The primary endpoint is maximum walk- the National Institutes of Health should FAHA, FACR, FSVMB, is Director, Vascu- ing duration on a graded treadmill test, further recognition of this important dis- lar Disease Research Institute, and Profes- and there are secondary endpoints that ease. Ground-breaking research is ongoing sor, Research Track, Department of Diag- examine community-based walking, qual- in the pivotal NIH CLEVER Study, which nostic Imaging, Brown Medical School. ity of life, costs, and impact on cardiovas- should definitively determine optimal pa- Gregory Dubel, MD, James Bass, MD, cular risk factors. The study is the first of tient management for many years to come. and Sun Ho Ahn, MD, are all Vascular its kind to compare common therapies for Interventional Radiologists and Assistant claudication and should inform treatment REFERENCES Professors (Clinical) of Radiology at Brown decisions for many years to come. The 1. Stewart KJ, Hiatt WR, et al. Exercise training for Medical School. study is being conducted locally at the Vas- claudication. NEJM 2002; 347:1941-51. 2. Newman AB, Sutton-Tyrrell K, et al. Morbidity Gregory M. Soares, MD, is Assistant cular Disease Research Center at Rhode and mortality in hypertensive adults with a low Professor, Diagnostic Imaging, Brown Medi- Island Hospital (phone: (401) 444-6208). ankle/arm blood pressure index. JAMA 1993; 270:487-9. cal School. Joselyn Cerezo, MD, is Clinical Trials CONCLUSIONS 3. Hirsch AT, Criqui MH, et al. Peripheral arterial dis- ease detection, awareness, and treatment in primary Project Manager, Vascular Disease Research Prior to the availability of effective care. JAMA 2001; 286:1317-24. Institute. medications to treat claudication symptoms, 4. Murphy TP, Soares GM, et al. Quality of life and the evolution of minimally invasive exercise performance after aortoiliac stent placement CORRESPONDENCE interventional treatment options, studies of for claudication. J Vasc Interv Radiol 2005; 16:947- 53; quiz 954. Timothy P. Murphy, MD, FSIR, important quality of life issues for many 5. Tanasescu M, Leitzmann MF, et al. Exercise type FAHA, FACR, FSVMB patients with claudication, and apprecia- and intensity in relation to coronary heart disease in Rhode Island Vascular Institute tion of the need for aggressive risk factor men. JAMA 2002; 288:1994-2000. 6. Hirsch AT, Haskal ZJ, et al. ACC/AHA Guidelines 690 Eddy Street modification, claudication was often under- for the Management of Patients with Peripheral Ar- Providence, RI 02903 recognized in medicine. Fortunately, its terial Disease (lower extremity, renal, mesenteric, and Phone: (401) 421-1924E-mail: prevalence and importance is being increas- abdominal aortic): a collaborative report from the [email protected] ingly recognized, and public health aware- American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular An- ness efforts focusing on claudication spon- giography and Interventions, Society for Vascular 42 MEDICINE & HEALTH/RHODE ISLAND Update On Idiopathic Pulmonary Fibrosis: The Role of Gamma Interferon and Cytokines Napoleon A. Puente, MD, Jason M. Aliotta, MD, and Michael A. Passero, MD Idiopathic Pulmonary Fibrosis (IPF), (IPF), is defined by certain histological tial acute inflammation are seen. The or- one of the Idiopathic Interstitial features including areas of fibrosis with ganizing phase occurs later and is char- Pneumonias (IIP), represents a challenge honeycombing adjacent to areas of nor- acterized by loose organizing fibrosis, es- to clinicians because it is difficult to di- mal-appearing lung and the presence of pecially in the alveolar septa, and type II agnose, has an unfavorable prognosis and fibroblast foci. Fibroblastic foci are mi- pneumocyte hyperplasia. no treatment is available to reverse or at croscopic areas rich in mesenchymal cell Nonspecific Interstitial Pneumonia least stop the progression of the disease. proliferation and extracellular matrix that (NSIP) features a broad spectrum of his- The etiology and pathogenesis of IPF are resemble wound healing. The heteroge- tological presentations with varying de- not completely understood. neity of these findings (honeycombing grees of fibrosis or alveolar wall inflam- and fibroblastic foci) is a hallmark for the mation. There are usually no fibroblastic EVOLUTION OF THE CLASSIFICATION morphologic description of Usual Inter- foci and honeycombing is absent. OF IDIOPATHIC INTERSTITIAL stitial Pneumonia (UIP), the pathology Cryptogenic Organizing Pneumo- PNEUMONIAS found in those with IPF. nia (COP) occurs in a patchy distribu- Noble and Homer reviewed the his- In Respiratory Bronchiolitis (RB), tion with organizing pneumonia that in- tory of changing concepts of IIP.1 They there is an intraluminal accumulation of volves alveoli, alveolar ducts and bron- described how the classification of IIP macrophages in the respiratory bronchi- chioles. Inflammatory cells within the has evolved since first described by oles, alveolar ducts and peribronchiolar interstitium, type II alveolar metaplasia Hamman and Rich between 1941 and alveolar spaces. Mild inflammation and and an increase in alveolar macrophages 1943. Liebow and Carrington presented fibrosis can also be seen. RB is known to are found. One of the important features a new classification in the 1960s that cor- be associated with smoking. of this disease is the relative preservation related histopathological findings with In Desquamative Interstitial Pneu- of the lung architecture. disease prognosis. monia (DIP), diffuse involvement of the Lymphoid Interstitial Pneumonia In 1998, Katzenstein and Myers2 lungs is seen with accumulation of mac- (LIP) is defined by infiltrates that are presented a new classification and more rophages in the lumens of distal airspaces. comprised primarily of T lymphocytes, recently in 2002, the American Thoracic Fibrotic thickening of the alveolar septa plasma cells and macrophages. In addi- Society and the European Respiratory and lymphoid aggregates can also be tion, MALT (Mucosa Associated Lym- Society published a multidisciplinary found. These changes are present in a phoid Tissue) hyperplasia is seen, typi- consensus for the classification of IIP that more uniform pattern cally, in an alveolar septal distribution. defined the clinical diagnosis, the radio- Diffuse Alveolar Damage (DAD), graphic findings and the observed patho- found in Acute Interstitial Pneumonia PATHOPHYSIOLOGY OF INTERSTITIAL logical pattern.3 (AIP), is a diffuse disease that occurs in PULMONARY FIBROSIS The most common and severe form two phases. First, in the exudative phase, Pulmonary Fibrosis is thought to be of IIP, Idiopathic Pulmonary Fibrosis hyaline membranes, edema and intersti- the late stage of a defective inflammatory response within the lung that is charac- Table 1: ATS/ERS Classification of Idiopathic terized by abnormal repair of damaged Interstitial Pneumonias tissue with increased extracellular matrix deposition, vascular remodeling and Pathologic Findings Clinical Diagnosis fibroproliferation. The end result is the Usual Interstitial Pneumonia (UIP) Idiopathic Pulmonary fibrosis (IPF) substitution of functional lung with scar Respiratory Bronchiolitis interstitial Respiratory Bronchiolitis (RP) tissue. Inflammation may arise in response pneumonia (RB-ILD) to a variety of traumatic, allergic, infec- Desquamative Interstitial Pneumonia Desquamative Interstitial Pneumonia tious, toxic or autoimmune factors. How- (DIP) (DIP) ever, the reason why the lung reacts in a Diffuse Alveolar Damage (DAD) Acute Interstitial Pneumonia (AIP) way that causes fibrosis instead of nor- Nonspecific Interstitial Pneumonia Nonspecific Interstitial Pneumonia mal repair of functional lung tissue is (NSIP) (NSIP) unknown and is the target of many in- Organizing Pneumonia (OP) Cryptogenic Organizing Pneumonia vestigations. (COP) The major proinflammatory factors Lymphoid Interstitial Pneumonia (LIP) Lymphoid Interstitial Pneumonia (LIP) in the lung include interleukin (IL)-1, IL- 6, IL-8, monocyte chemoattractant pro- Source: American Thoracic Society/European Respiratory Society. International multidisciplinary consen- sus: classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002; 165:277-304. tein-1, tumor necrosis factor, macroph- age inflammatory protein 1 α, macroph- 43 VOLUME 90 NO. 2 FEBRUARY 2007 age-colony stimulating factor, transform- ROLE OF IFN-γ IN THE less severe lung disease. ing growth factor and platelet derived PATHOPHYSIOLOGY OF PULMONARY The Inspire (International Study of growth factor. Although all of these fac- FIBROSIS Survival Outcomes in Idiopathic Pul- tors have been found in animal or hu- IFN-γ is a cytokine that possesses monary Fibrosis with Interferon man models of pulmonary fibrosis and antifibrotic, antiproliferative and Gamma-1b Early Intervention) trial is possess growth, differentiation, chemot- immunomodulatory effects. ongoing. This will be the largest clinical actic and remodeling capabilities, it is not Gurujeyalakshmi and Giri5 demon- trial ever conducted to evaluate the use known how these factors specifically in- strated that in mice with bleomycin-in- of IFN γ-1b therapy in IPF, hoping to teract. duced fibrosis, treatment with IFN- γ provide a more definitive answer to the Lukacs et al4 reviewed the roles of caused a decrease in the accumulation of utility of this novel therapy. T helper type 1 and type 2 cells in re- collagen in the lung, compared with un- sponse to injury. When naive CD4+ T treated bleomycin-injured mice. THE LINKS BETWEEN IPF, IFN-γ lymphocytes are activated by an antigen, AND CHEMOKINES they can differentiate into two major … future Cellular movement plays a funda- subsets of T helper cells: T helper type mental role in processes such as inflam- 1 (Th1) cells (type 1 response) or T therapeutic mation and immune surveillance. helper type 2 (Th2) cells (type 2 re- modalities used in Chemical mediators, like chemokines, sponse). Each subset of cells secretes dis- induce a receptor-mediated cytoskeletal tinct cytokines that produce a different the treatment of response to produce a directed cellular immune response. Th1 cells synthesize pulmonary fibrosis locomotion. Chemokines are a group of macrophage activating factor, IL-2, chemotactic cytokines that have IFN- γ, lymphotoxin and TNF which could potentially heptahelical G-protein-coupled recep- promote cell-mediated inflammatory take advantage of tors, many of which bind to more than immune response, mainly against intra- one ligand, giving them multiple func- cellular pathogens. Th2 cells secrete IL- the observed role of tions. 4, IL-5, IL-10 and IL-13 which activate CXCR3 and its Four families of chemokines have B cell antibody production such as IgG been identified based on the number and and IgE, and stimulate the differentia- ligands position of their conserved cysteine resi- tion and maturation of eosinophils, pro- dues: 1) CXC or the alpha chemokine viding strong humoral and antiparasitic Ziesche et al6 were the first to exam- family has two N-terminal cysteine (C) responses. ine IFN-γ therapy in patients with IPF. residues separated by one non-conserved An effective response to an antigen Nine patients were treated with a com- amino acid residue (X), 2) CC or the requires the activation of Th1 cells and bination of IFN γ-1b and corticosteroids beta chemokine family has two N-termi- Th2 cells to produce both cell mediated and nine were treated with corticoster- nal cysteine residues in juxtaposition, 3) and humoral immunity. If one of the oids alone. After 12 months of follow up, C or the gamma chemokine family has a subset’s production is unregulated or in- patients that received the combination single cysteine residue in the conserved appropriate, the end result may be harm- therapy had significant improvements in position, and 4) CX3C family has two ful, such as the Th1-induced autoim- total lung capacity and resting and am- N-terminal conserved cysteine residues mune response (type 1 diabetes, multiple bulatory partial pressure of arterial oxy- separated by three non-conserved resi- sclerosis, rheumatoid arthritis) or the gen compared to those receiving corti- dues. Th2-induced allergic response (IgE pro- costeroids alone. Raghu et al7 later pub- The CXC chemokine receptor 3 duction and eosinophil activation in lished a double-blinded, multinational (CXCR3), expressed primarily on Th1 asthma). trial of 330 patients with IPF who were cells, may play an important role in the In IPF, the type 1 response is unresponsive to corticosteroid therapy. regulation of pulmonary fibrosis. CXCR3 thought to modulate tissue repair after One cohort was given IFN γ-1b therapy is a receptor for a family of ligands that a specific injury and reestablish normal and the other received placebo. It was are upregulated by IFN γ-1b. These functional lung tissue, in contrast to the concluded that patients receiving IFN γ- ligands include: 1) the IFN- γ induced type 2 response, which promotes extra- 1b didn’t show any improvement either protein 10-kDa, also known as the CXC cellular matrix deposition and hence, fi- in progression-free survival, pulmonary chemokine ligand 10 (CXCL10), 2) the brosis. The type 2 response cytokines IL- function or quality of life compared to monokine induced by IFN-γ or CXCL9 4, IL-10 and IL-13 have been identi- controls. Subgroup analysis suggested and 3) the IFN-inducible T cell α fied to promote the activation of fibro- that patients with better compliance to chemoattractant or CXCL11. blast and the production of fibroblast- therapy may have benefited; however, In a bleomycin-induced pulmonary derived extracellular matrix. The type 2 investigators could not determine fibrosis model, Jiang et al8 found accel- response predominates in IIP, suppress- whether they responded better because erated progression of fibrosis and in- ing the type 1 response cytokines, IFN- they tolerated the side effects of IFN- γ creased mortality in CXCR3-deficient γ and IL-12. better leading to improved compliance mice when compared to wild-type (WT) or because the subgroup suffered from mice. They observed that in the absence 44 MEDICINE & HEALTH/RHODE ISLAND sus: classification of the idiopathic interstitial Table 2. Treatments currently in different phases of clinical trials pneumonias. Am J Respir Crit Care Med 2002; for the treatment of Idiopathic Pulmonary Fibrosis 165:277-304. 4. Lukacs NW, Hogaboam C, et al. Type 1/type 2 TREATMENTS PROPOSED MECHANISM OF ACTION cytokine paradigm and the progression of pul- monary fibrosis. Chest 2001; 120:5S–8S. IFN-γ Antifibrotic, antiproliferative and inmunomodulatory 5. Gurujeyalakshmi G, Giri SN. Molecular mecha- cytokine nisms of antifibrotic effect of interferon gamma N-acetylcysteine Stimulates Glutathione synthesis. Antioxidant activity. in bleomycin-mouse model of lung fibrosis. Exp Lung Res 1995; 21,791-808. 6. Ziesche R, Hofbauer E, et al. . A preliminary study Pirfenidone Inhibits TGF-β stimulated collagen synthesis. of long-term treatment with interferon gamma- Etacernept Tumor necrosis alpha blocker 1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. NEJM 1999; Imatinib mesylate c-Abl and PDGF receptor tyrosine kinase inhibitor 341:1264–9. Bosentan Nonselective ET(A)/ET(B) receptor antagonist 7. Raghu G, Brown KK, et al. Idiopathic Pulmo- nary Fibrosis Study Group. A placebo-controlled Sildenafil Vasodilator Therapy trial of interferon gamma-1b in patients with id- Iloprost Synthetic analog of prostacyclin PGI2 iopathic pulmonary fibrosis. NEJM 2004; Drug GC1008 Human monoclonal antibody for TGF-β 350:125–33. 8. Jiang D, Liang J, et al. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Data from Selman M, Thannickal VJ, PArdo A, Zisman DA, Martinez FJ, Lynch JPIII. Idiopathic pulmonary Invest 2004; 114:291-9. fibrosis: pathogenesis and therapeutic approaches. Drugs. 2004;64(4):405-430 and IPF research available 9. Pignatti P, Brunetti G, et al. Role of the at www.coalitionforpf.org/IPFResearch/default.asp. Accessed September 19, 2006. chemokine receptors CXCR3 and CCR4 in hu- man pulmonary fibrosis. Am J Respir Crit Care of the CXCR3 receptor, recruitment of monary fibrosis could potentially take Med 2006; 173:310-7. the Natural Killer (NK) and CD8+ lym- advantage of the observed role of phocytes was defective after the CXCR3 and its ligands. To date, IFN- γ Napoleon A. Puente, MD, is a Resi- bleomycin-injury. These mice had fewer injections have not been shown to ben- dent in Medicine, Roger Williams Medi- NK cells in their peripheral blood, unin- efit patients with IPF, in spite of promis- cal Center. jured lung and other organs including ing data obtained from animal injury Jason M. Aliotta, MD, is Assistant the liver. These findings suggest that the models. Professor of Medicine, Boston University CXCR3 receptors may play a role in NK Nonetheless, further research is School of Medicine; Roger Williams Medi- and NK T cell homeostasis and may have needed to better understand the relation- cal Center. a direct impact on the pathogenesis of ship between IFN- γ and CXCR3 and Michael A. Passero, MD, is Associate fibrosis in response to injury. how this impacts the pathogenesis of pul- Professor of Medicine, Boston University Jiang et al8 also reported a decrease monary fibrosis. In addition, a variety of School of Medicine, Roger Williams Medi- in resident NK cell-produced IFN- γ lev- other drugs are being investigated for the cal Center. els found in the bronchoalveolar lavage treatment of IPF. (Table 2) (BAL) fluid of bleomycin-injured CORRESPONDENCE CXCR3-deficient mice compared to WT REFERENCES Dr. Michael A. Passero, MD mice. In addition, they were able to dem- 1. Noble PW, Homer RJ. Back to the future. Am J Department of Medicine onstrate partial reversal of fibrosis in Respi. Cell Mol Biol 2005; 33:113-20. Roger Williams Medical Center 2. Katzenstein AL, Myers JC. Idiopathic pulmonary 825 Chalkstone Avenue bleomycin injured CXCR3-deficient fibrosis. Am J Respir Crit Care Med 1998; mice with the injection of exogenous IFN- 157:1301-15. Providence, RI, 02908 γ or CXCR3+ leukocytes producing en- 3. American Thoracic Society/European Respiratory Phone: (401) 456-2302 dogenous IFN- γ. Society. International multidisciplinary consen- e-mail: [email protected] A link between chemokine receptors and pulmonary fibrosis may also exist in human pulmonary fibrosis, as described by Pignatti et al.9 They found decreased expression of CXCR3 and one of its ligands CXCL10 in BAL fluid CD4 T cells of patients with IPF compared to patients with other pulmonary disorders. This suggests that CXCR3 may play a protective role in the onset and the pro- gression of pulmonary fibrosis and that CXCR3 and CXCL10 levels may help to predict response to IFN- γ therapy. In conclusion, future therapeutic modalities used in the treatment of pul- 45 VOLUME 90 NO. 2 FEBRUARY 2007 On Headache Tablets: Headache Incantations From Ur III (2113-2038 BC) Vlad Zayas, MD A recently published monograph by Johannes J.A. van Dijk and ‘My son, what do you not know?’ Markham J. Geller on Ur III (2113-2038 BC), contains two head- ‘Why…, what can save him?’ ache incantations.1 These scholars translated and analyzed the tab- (After) you have brought the purifying water, lets from the Frau Hilprecht-Sammlung collection in Jena. The and you have poured fat of a pure cow, geographic source of the tablets is the Sumerian city of Nippur. then let one rub (him) with that oil.’ The age of these two incantations is determined by the nature of Asalluhi son of Enki the excavation site and the grammatical structure of the text. May the headache-demon ‘split the river bank’ on (the Much accumulated medical, judicial, mathematical and patient’s) cranium, artistic knowledge has been salvaged from excavations in the may (the demon) break up like a pot. Mesopotamian city-states, including the Sumerian city Ur. It is the incantation of Nin-girimma. Mesopotamia and especially Sumer has been called “the cradle It is the spell of Eridu, shrine of Enki. of Western civilization.” The writing system developed in Mesopotamia, called cunei- The second incantation is called Namtar-demon vs. head- form, required a clay tablet marked with a stylus. That marked aches – HS 1588+1596: (Figure 2) tablet was then baked. This technique preserved an enormous amount of written materials from many periods of Mesopotamian In heaven the wind blows, history including Ur III (2113-2038 BC). However, significant on earth the mice proliferate, numbers of tablets remain uncatalogued and are still not trans- and Namtar inflicts headache. lated. The medical history of Sumer therefore remains somewhat In men’s bodies is found beer, the south wind blows fragmented. It is outside the scope of this article to discuss a full sag-duru on the (alluvial) land. historic picture of medicine in Mesopotamia. This may be found In the mountains, the south [wind] blows the scat- in several large works on the subject.8 tered seed. He (the patient) put his There were two types of Mesopotamian medical practi- trust into (divine) standard. tioners: ashipu—a sorcerer, who dealt with magical aspects of Therefore, the gods of heaven were afraid, they came the treatment, and an asu—a medical practitioner who pro- down from (lit.’in’) heaven, vided pharmaco-therapeutic treatments including herbal con- the gods of earth were afraid, and were standing coctions, bandaging, plasters etc. The exact degree of the in- around the grave, teraction between these two branches of Mesopotamian medi- the great gods themselves made (funerary) offerings. cine remains unclear. It is unknown whether only ashipus were The fish in the river were afraid, and left their habi- allowed to convey therapeutic incantations. Multiple thera- tat, peutic incantations in the medical armamentarium were di- the birds in the heaven were afraid, and smashed into rected against snakebites, paralysis and headaches. (A large the base of the mountains. collection of incantations for headaches is in preparation for The undomesticated animals, creatures of the steppe publication). and wild animals suffered from catalepsys [a disease of domestic animals]. The first incantation in the monograph is called “Amar- Šakan was afraid and retired to the horizon, Suen’s Headache” – HS 2438, Ni 2187: (Figure 1) Nanna was afraid, and retired to the height of heaven. Asalluhi came to his father Enki, The headache (-demon) is directed towards the and he said, man, ‘My son, what don’t you know? What can be added the headache-demon is set to distress the neck to it?’ muscles. The god reconciled the sick man towards the steppe. There is no small opening which can ensnare the galla- Purify … [in a pure] place, demon, take …. of the pen and sheepfold which is not aban- no binding can be tied on the headache(-demon). doned, It is the young lad who is seized by the headache-de- choose a …lamb, mon, choose … a black? goat. it is the young maiden whose diseased neck twitches. Asalluhi sent someone to his father Enki, DISCUSSION (saying), say to my father: Both incantations follow the same standard medical in- The headache (-demon) [is directed toward the cantation formula – “Problem, Dialogue and Ritual Solution.”1 man], The problem is first described. Then Asalluhi presents the prob- [it is set to] distress [the neck muscles].’ lem to his father, the god Enki, who offers the therapeutic regi- [Enki answered] his son, men for the problem. The first incantation is better preserved 46 MEDICINE & HEALTH/RHODE ISLAND There is only one previous Sumerian documents (possibly, as far as 3rd millen- written mention of headaches in the epic nium BC). Therefore, the exact age of the poem Enki and Ninhursag.2 The two lines original texts remains unclear. Within the are: (In Heaven) “the sick-eyed says not limitations of the dating of the sources avail- “I am sick-eyed’/the sick-headed (says) able, this is the first description of head- not ‘I am sick-headed’”. The description ache therapy. As it has been noted by of the headache in the first incantation S.N.Kramer in his comments on another offers a more detailed picture of the head- Sumerian pharmacopoeia tablet, the exact ache including the “distress the neck proportions of the ingredients were not muscles”. The unrelenting nature of the mentioned.6 This, he speculates, could be headache and blowing motif is reminis- due to the desire of the medical practitio- cent of the more recent Mesopotamian ner to protect the trade secret from either incantation: “Headache rometh over the the lay public or from his colleagues. desert, blowing like the wind…” (Fre- As the first people to develop writ- quently, the age of this particular incan- ing, along with many other “firsts,”6 tation is mentioned as 3000BC. The pri- Sumerians provided us with a first writ- mary source of this quotation is The Devils ten word for a headache—“sag-gig” (be- and Evil Spirits of Babylonia by R. C. low in the cuneiform).7 Thompson (3). He states that the docu- ments “were drawn up …about the first half of the seventh century before Christ”. He speculates, however, about possible previous recensions of “not less than six thousand years old”). ABBREVIATIONS It is not entirely clear whether these HS – (Frau-Professor-) Hilprecht- texts describe a primary headache disorder Summlung. or a secondary headache due to a cata- Ni – Museum siglum of the Ar- Figure 1 Figure 2 strophic intracranial process (e.g. infectious chaeological Museum, Istanbul or hemorrhagic). Other sources regarding (Nippur). revealing a recommendation to apply Mesopotamian medicine reveal that medi- topical purified water mixed in the “fat of cal practitioners were familiar with “con- ACKNOWLEDGEMENT 8 pure cow”. tinuous” as well as recurrent headaches. The author would like to thank The end of the second incantation One of the approaches toward these Markham J. Geller, PhD, the reviewers is, unfortunately, fragmentary. However, texts is to see them in the light of today’s and Irina Mirsky-Zayas, PhD, for their the literary value of the second incanta- medical paradigm. It is tempting to label help in the preparation of this article. tion is obvious. The text reveals an apoca- these headaches with current medical ter- lyptic vision of the distress caused by the minology as a particular type of headache REFERENCES demon Namtar inflicting the headache. as some authors do. These translations are 1. van Dijk JJA, Geller JM.. Ur III Incantations from the imperfect, frequently leading to a scholas- Frau Professor Hilprecht-Sammlung Collection, Jena. Even the gods were afraid of the demon Wiesbaden: Harrosowitz Verlag, 2003. Namtar: they lowered themselves for tic discourse and disagreement among the 2. Alvarez WC. Was there sick-headache in 3000 BC. funerary offerings. Various interpreta- Sumerologists. The tablets are often frag- Gastroenterol 1945; 5: 524. tions of the text and translation analysis mentary, cryptic and poorly preserved. Usu- 3. Thompson RC. The Devils and Evil Spirits of Babylonia, ally, this leads to an unsuccessful search of Vol II. Lusac’s Semitic Text and Translation Series, Vol are offered in this scholarly monograph. XV. London: Lusac and Co. 1904. To briefly explain some of the names the pharmaco-therapeutic effects of the 4. Karenberg A, Leitz C. Headaches in magical and medi- mentioned in the incantations: Amar- ingredients used in the ritual (“pure cow” cal papyri of Ancient Egypt. Cephalalgia 2001; 21: and “purifying water” in this case). Another 911-6. Suen (2047-2038 BC) (the patient in the 5. Black J, Green A. Gods, Demons and Symbols of Ancient first incantation) is the third ruler of Ur approach is to analyze these as a part of Mesopotamia. Austin: University of Texas Press, 1992. III state. Nanna is the god of the moon. magical medicine with diseases caused by 6. Kramer SN. History begins at Sumer. Twenty seven “Firsts” Nin-girimma is a deity whose role is un- demons and gods. Yet another approach is in Man’s Recorded History. Garden City, New York: to view this as a literary document inspired Doubleday & Company, 1959. clear. She is frequently invoked in the 7. The Pennsylvania Sumerian Dictionary Project, therapeutic incantations of this period. by certain events, or as medico-poetics. www.psd.museum.upenn.edu/epsd/index.html. She is also associated with water, fish and It is tempting to label these incanta- 8. Scurlock JA, Andersen BR. Diagnoses in Assyrian and tions as the first recorded descriptions of Babylonian medicine : ancient sources, translations, and serpents. Šakan or Šakkan (in Akkadian, modern medical analyses. University of Illinois Press, 2005. Sumequan) is the deity protecting wild headache treatment (either magical or animals. Eridu is a Sumerian city. Namtar therapeutic). Therapeutic options for head- aches are also present in Ancient Egyptian CORRESPONDENCE is the demon of the nether regions, har- Vlad Zayas, MD binger of death. The same name was papyri. The oldest Papyrus Ramesseum III 450 Veterans Memorial Parkway, Bldg 11 given to a minor deity who acted as a is dated 1800 BC (4). However, both East Providence, RI 02914 minister of Ereškigal, queen of the un- sources—Egyptian papyri and Sumerian E-mail: [email protected] derworld.5 clay tablets—are the copies of even older 47 VOLUME 90 NO. 2 FEBRUARY 2007 Disruptive Physician Behaviors Robert S. Crausman, MD, MMS, Alberto Savoretti MD, and Jevon Conroy

The expectation for physicians at large Fortunately, healthcare has evolved adopted a policy on disruptive physician is that they will act in a compassionate considerably over the past few decades behavior in 2001 that recognized the manner so as to facilitate the patient’s well and organizations are now much less tol- AMA opinions and linked disruptive being. The overwhelming majority of erant of unprofessional disruptive behav- physician behavior to patient safety, cit- physicians certainly do, but according to iors by healthcare providers. Fellow pro- ing the Institute of Medicine finding that recent studies there is a thankfully small fessionals on multi-disciplinary teams see healthcare systems must promote team- but nonetheless increasing trend for some the importance of effective interpersonal work and a collaborative approach to individuals to deviate from this standard, skills, and adherence to high professional problem solving if medical errors are to thus earning the moniker “disruptive.” standards; and now hold members ac- be reduced. Unfortunately despite in- The American Medical Association countable. The practice of medicine has creased attention to this problem it re- (AMA) describes personal conduct that become increasingly complex and, in the mains a frustrating one for hospitals, negatively affects or potentially may nega- interests of patient safety, medicine can Medical Boards and other healthcare tively affect patient care as disruptive. It no longer afford to countenance tan- organizations.2 specifically excludes good faith criticism. trums, outbursts, intimidation or a host In Rhode Island, such behavior can It further urges medical staffs to develop of other disruptive behaviors by physi- be reported to one of two professional policies and procedures for addressing cians or other allied healthcare profes- organizations with statewide scope. The physician disruptive behavior.1 sionals. Board of Medical Licensure and Disci- Although collegial interactions are Despite a greater awareness of this pline (BMLD) is a part of State govern- generally the norm, our state is not with- type of professional misconduct and the ment with a primary role to protect the out examples of physician disruptive be- presence of effective community based public and to provide appropriate reper- havior. In January, 2006, the RI Board of resources, many problem physicians are cussion if a physician is not meeting a Medical Licensure and Discipline issued never referred for appropriate evaluation minimum standard of care .3 This regu- a disciplinary action* regarding a senior and treatment. latory body is composed of 6 physicians hospital-based physician. In this order the (including MDs and DOs) and 6 mem- BMLD concluded the Respondent’s be- …medicine can no bers of the public, including a plaintiff’s havior to be “…disruptive to hospital staff attorney and a hospital administrator as members despite the Board’s [previous] longer afford to well as three others not involved in efforts to address this behavior…” In June countenance healthcare. Complaints reach the BMLD and September two additional physicians regarding physician practice from a vari- were sanctioned in RI as reciprocal disci- tantrums, outbursts, ety of sources including dissatisfied pa- plinary actions relating to findings of un- intimidation or a tients, concerned colleagues and professional conduct issued by the Mas- healthcare organizations. The BMLD is sachusetts Medical Board for “…conduct host of other empowered to order medical and men- detrimental to the practice of medicine…” disruptive behaviors tal health evaluation; The BMLD may A reciprocal action is issued by a Medical also sanction as appropriate for unpro- Board in a state in which a physician holds by physicians… fessional conduct. The BMLD also facili- a license for unprofessional conduct com- tates an active, non-public diversion pro- mitted in another state that resulted in a CURRENT STANDARD gram that supports physician health in disciplinary action in that alternate juris- Per AMA opinion E-9.045, disrup- conjunction with the Physician’s Health diction. tive behavior by physicians is defined as Committee [PHC] sponsored by the RI “Personal conduct, whether verbal or Medical Society. HISTORICAL PERSPECTIVE physical, that negatively affects or that The PHC has achieved considerable Historically physicians were offered potentially may negatively affect patient success in the areas of physician impair- a great deal of latitude regarding their care constitutes disruptive behavior. This ment relating to substance abuse, psychi- professional behavior in hospital and of- includes but is not limited to conduct atric or medical illness and is also able to fice settings. Patient care and an ardu- that interferes with one’s ability to work accept referrals regarding disruptive phy- ous, high-stress professional lifestyle pro- with other members of the health care sician behavior. The BMLD, hospitals, vided ample justification for these bad team. However, criticism that is offered physicians, allied health care providers behaviors. Many have commented, if in good faith with the aim of improving and members of the public may make half in jest, that certain maladaptive per- patient care should not be construed as referrals directly to the PHC. The PHC sonality traits if not frank personality dis- disruptive behavior.” will then direct evaluation and, as neces- orders were actually requisite for success The Commonwealth of Massachu- sary, treatment and monitoring. in certain areas of practice. setts Board of Registration in Medicine 48 MEDICINE & HEALTH/RHODE ISLAND SCOPE OF THE PROBLEM care problem due to the physician’s dis- respect foster good communication. Un- The scope of the problem is consid- proportionate or misdirected response; a fortunately, for a variety of reasons some erable. One-third of hospital executives tragic missed opportunity to improve a healthcare professionals have difficulty surveyed by the American College of system after an error. meeting these communal standards of Physician Executives reported weekly or However, while physicians exhibit- behavior. monthly problems relating to disruptive ing disruptive behavior often benefit It is incumbent upon all of us to ad- physician behavior; 95% at least on a from a medical and forensic psychiatric dress these behaviors assertively and to yearly basis.4 evaluation, they often do not have diag- hold all healthcare providers to a high Many physicians have engaged in nosable medical or psychiatric illness. For standard of professionalism. It is impor- behaviors that may be considered disrup- this reason maladaptive personality traits tant that the entire medical community tive on a particular occasion. However, and poor coping skills that may fuel the be aware of both the negative impact of physicians who consistently demonstrate inappropriate behaviors become the fo- disruptive behaviors and the importance these behaviors while few in number can cus for corrective efforts. Fortunately in- of engaging institutions, the BMLD and have widespread impact on a hospital sight-driven psychotherapy, behavioral the PHC to effectively address them. staff or in a practice group. Unfortu- therapy and lifestyle changes can be ef- nately, while most hospital executives, fective for a motivated individual. ENDNOTES hospital chiefs or senior nurse managers * Public information regarding disciplinary actions could agree on the identity of disruptive RECOMMENDED APPROACH of the RI BMLD may be viewed at http:// www.health.ri.gov/hsr/bmld/disciplinary-al.php physicians on a medical staff, few indi- An institutional approach consistent vidual behaviors rise to a sufficient level with the AMA policy on Disruptive Phy- REFERENCES to warrant specific discussion. Only the sicians can be summarized with the help 1. Disruptive physician policy. American Medical most egregious examples lead to formal of the “10 R’s.” (Table 1) First, an insti- Association. H-140.918. available at http:// sanctions reported to State Medical tution must develop a system of Recog- www.ama-assn.org Boards. Consequently, it is very difficult nition predicated on a set of agreed upon 2. Disruptive physician behavior. Commonwealth of Massachusetts Board of Registration in Medi- to gauge the severity of the problem definitions or descriptions of disruptive cine Policy 01-01. adopted June 13, 2001. http:/ across healthcare settings. behavior. Such behaviors must be Re- /www.massmedboard.org/regs/pdf/01- ported via an established process that 01_disruptive_physicians.pdf 3. Crausman RS. Protecting the public and assur- THE UNDERLYING CAUSE appropriately Records the event, assures ing high practice and professional standards in Disruptive physician behavior can be confidentiality, and initiates a process to the physician community: The Rhode Island the result of psychiatric or medical illness, Review and verify the report(s). Once Board of Medical Licensure and Discipline. Vol- substance abuse or personality disorders verified, determination of Responsibility ume 86 number 9 Sep 2003: 79-281 4. Weber D. Poll results. The Physician Executive Sep- or even the occasional acute life stressor through assessment for underlying cause tember-October 2004: 6-14. such as a divorce or family death. In these should be done. Such determination may situations addressing the root cause can require a forensic medical and psychiat- Robert S. Crausman, MD, MMS, is be effective. ric evaluation towards the ultimate goal Chief Administrative Officer, RI Board of It must be recognized that specific of development and implementation of Medical Licensure and Discipline, Rhode disruptive behaviors such as angry out- a Remediation plan. Island Department of Health, and Associ- bursts may be precipitated by genuine Subsequently, there should be a for- ate Professor of Medicine, Brown Medical system problems that impact upon pa- mal process for Rechecking (i.e. moni- School. tient care such as a systems-based medi- toring) behaviors and Reinforcement of Alberto Savoretti, MD, is a medical cation or treatment error. Unfortunately improved interpersonal strategies. senior resident at Memorial Hospital of RI. in the wake of disruptive behavior the Resorting to discipline should be Jevon Conroy is a senior at Wheaton focus often shifts away from a legitimate reserved for truly egregious disruptive College. behaviors or for individuals who have Table 1. 10 R’s failed after an earnest attempt at CORRESPONDENCE: Recognition remediation. Resources should also be Robert S. Crausman MD MMS Report identified in advance. Phone: (401) 222-7888 Record e-mail: [email protected] CONCLUSION Review and verify Physicians and allied healthcare pro- Responsibility viders who exhibit disruptive behaviors Remediation plan. represent an important concern for ev- Rechecking (i.e. monitoring) eryone. Healthcare teams create numer- Reinforcement of improved ous professional interdependencies that interpersonal strategies. require appropriate professional interac- Resorting to discipline tions between providers as a necessary Resources condition for effective patient care. Pro- fessional interactions characterized by 49 VOLUME 90 NO. 2 FEBRUARY 2007 The Creative Clinican Giant Cell Myocarditis Presenting As Isolated Right Ventricular Dysfunction Richard Regnante, MD, and Athena Poppas, MD, FACC

A 56 year old woman with a past medical history of hy- A repeat echocardiogram revealed worsening RV dila- pertension, hyperlipidemia and tobacco abuse presented to the tion and dysfunction with new moderate LV dysfunction hospital with progressive, aching chest and epigastric pain of 3 (LVEF= 35%) when compared with the study from a week weeks duration associated with dyspnea on exertion. She de- prior. The decision was made to perform right ventricular nied palpitations, syncope, orthopnea, paroxysmal nocturnal endomyocardial biopsy. The pathology was consistent with dyspnea or edema. Her presenting vital signs were within nor- Giant-Cell myocarditis (Figure 4). The patient was transferred mal limits. On physical exam she had mild jugular venous dis- to a transplant center where she was started on immunosup- tention and an otherwise normal cardiopulmonary exam. Her pressive therapy with OKT3 (muromanab-CD3) and laboratory values were remarkable for modest elevation of liver cyclosporine. She initially required inotropic support with transaminases as well as elevations of cardiac enzymes (CK-564 milrinone. A prophylactic implantable cardioverter-defibril- IU/L, CKMB-45.9 NG/DL, troponin-232.3 NG/DL). Her lator was placed. After two weeks of intensive therapy, her electrocardiogram revealed normal sinus rhythm, left anterior condition improved to the point where she was discharged fasicular block, non-specific ST-T wave abnormalities and de- home. Her condition however deteriorated further at home creased voltages in the precordial leads. (Figure 1) and she required inotropic support with dobutamine. Ten She was taken electively to the cardiac catheterization labo- months after her initial presentation, she underwent success- ratory. A right heart catheterization was performed. Her right ful orthotopic cardiac transplantation. She is currently two atrial pressure was 16mmHg with a prominent x and y descent. years post transplant without any significant cardiopulmo- Her right ventricular pressure was 27/18 mmHg. Her pulmo- nary symptoms. Her post-operative course has been compli- nary artery pressure was 27/15 mmHg with a mean of 21mmHg cated by difficult-to-control hypertension. and oxygen saturation of 55%. Her pulmonary capillary wedge pressure was 16mmHg. The left ventriculogram revealed nor- DISCUSSION mal left ventricular function (ejection fraction 60%) without any Giant-Cell myocarditis (GCM), also known as Granulo- wall motion abnormalities. Her coronary angiogram showed matous myocarditis, is a rare and frequently fatal disease affect- normal epicardial coronary arteries. A transthoracic ing primarily young to middle-aged adults. The patients usu- echocardiogram revealed normal left ventricular wall thickness, ally present with rapidly progressive congestive heart failure or chamber size and function; there were no valvular abnormali- symptoms of acute coronary syndrome. Patients may present ties, pericardial effusion, or echocardiographic evidence of con- with heart block, refractory ventricular arrhythmias or sudden strictive pericarditis. There was echocardiographic evidence of death.1 Right heart catheterization, coronary angiography and a severely dilated and hypokinetic right ventricle. (Figure 2) endomyocardial biopsy are required to make the diagnosis. Given the isolated right ventricular dysfunction, a helical chest Right heart catheterization usually reveals signs of biventricular CT scan was performed to exclude pulmonary embolism and dysfunction. Coronary angiography usually reveals normal was normal. A presumptive diagnosis of acute myocarditis was coronaries but there have been case reports of moderate to made. Viral serologies were sent and were negative. The cardiac severe coronary disease superimposed on the myocarditis. A enzymes remained moderately elevated, and they persisted in a myocardial tissue sample is the only definitive way to diagnose smoldering fashion. The patient’s symptoms improved with di- GCM.2 Histopathologic features are characteristic with areas uretics and institution of ACE inhibitors and she was discharged of wide spread or multifocal myocardial necrosis, rich cellular home. One week later she returned to the hospital with severe dyspnea at rest. She un- derwent repeat right heart catheterization with further elevation of right heart filling pressures; her right atrial pressure was 24mmHg and a positive Kussmaul sign was noted. Her right ventricular (RV) pressure was 36/24 mmHg, left ventricular (LV) pres- sure was 120/24 mmHg with a pulmonary capillary wedge pressure of 26mmHg and a cardiac output of 2.8L/min. Her left and right ventricular pressures were separated by less than 5 mmHg with restrictive filling pat- tern. (Figure 3) Figure 1. 12 Lead electrocardiogram 50 MEDICINE & HEALTH/RHODE ISLAND as sarcoidosis, systemic lupus erythematosus, inflammatory bowel disease, malignant thymoma, thyrotoxicosis, drug hy- persensitivity and infections such as tuberculosis and syphilis.1 GCM is a very rare disorder and its epidemiology and patho- genesis were not well studied until a Multicenter Giant Cell Myocarditis registry was developed in 1995.1 The cumulative literature of GCM has data on fewer than 100 patients.1 The study consisted of 63 patients with biopsy proven GCM and has provided important data on prognosis and treatment. Un- treated Giant-Cell myocarditis carries an 89% mortality rate in its first 3 months1 with patients rapidly deteriorating to se- vere biventricular dysfunction and ultimately cardiogenic shock.2 Problematic, sustained refractory ventricular arrhythmias occur in 50% of GCM cases at sometime during their acute illness.1 Because of the infrequency of the disease, clinicians have limited evidence on which to base treatment. Conventional therapy for LV dysfunction should be given to all GCM pa- tients with the exception of digoxin. Digoxin has been shown to increase mortality in these subsets of patients. Because of the presumed pathogenesis of GCM, immunosuppression with T lymphocytic cytolytic therapy as a treatment option has been studied. Immunosuppression has shown to be effective in the treatment of GCM as compared to placebo.1,6 The Multicenter Giant Cell myocarditis study group found favorable outcomes with combinations of corticosteroids combined with cyclosporine, azathioprine, OKT3 (muromanab-CD3) but not with steroids alone.1 Combined immunosuppressive therapy has shown a prolonged survival rate of twelve months com- pared to average three month survival in placebo.1 Combined immunosuppression has the ability to prolong survival and thus Figure 2. Apical four chamber view of transthoracic echocardiogram potentially allow cardiac transplantation to be performed. Car- revealing severe dilation and hypokinesis of right ventricle with preserved left ventricular function; (top) diastole, (bottom) systole diac transplantation is frequently required because of failure of immunosuppressive therapy. infiltration with lymphocytes, eosinophils, plasma cells, mac- The Multicenter GCM investigation suggest that early rophages and numerous multinucleated giant cells.1 orthotopic cardiac transplantation is the treatment of choice The pathogenesis of GCM is not well understood. Ex- for most GCM cases.1,2 As soon as the tissue diagnosis of GCM perimental animal models using autoimmunization against car- is made, patients should be placed on the transplant waiting diac myosin in Lewis rats have replicated similar pathology.3 list and transported to a clinical site that can offer ventricular Evidence suggests that GCM is an autoimmune disorder de- support.2,5 GCM transplant recipients should be monitored pendent on CD4-postitive T lymphocytes.1,3 This disease pro- much more closely and frequently than traditional transplant cess frequently occurs in association with systemic diseases such recipients because GCM can recur and clinical status can de- teriorate quickly if intervention is not taken. Trans- plantation for GCM has produced survival out- comes similar to patients with transplant for idio- pathic cardiomyopathy. Unfortunately, of the 34 patients in the GCM study who received cardiac transplant, GCM recurred in 9 patients and 1 pa- tient died. GCM recurrence after transplant has been successfully treated with a strategy of more aggressive immunosuppression.1,4 ,5 This case report highlights two important teaching points. First, to our knowledge, this is the first case reported in the literature, of Giant-Cell myocarditis initially presenting as isolated right ven- tricular dysfunction. Second, the case stresses the Figure 3. Hemodynamic tracings from cardiac catheterization demonstrating crucial role of early endomyocardial biopsy in se- findings of left ventricular and right ventricular interdependence vere or rapidly progressing myocarditis; this is par- 51 VOLUME 90 NO. 2 FEBRUARY 2007 52 MEDICINE & HEALTH/RHODE ISLAND 53 VOLUME 90 NO. 2 FEBRUARY 2007 Figure 4. Right ventricular endomyocardial biopsy revealing multinucleated Giant cells (arrows)

ticularly true when associated with ventricular arrhythmias or heart block. The prognosis and treatment of Giant Cell myo- carditis differ markedly from other myopathic disorders and require early, aggressive use of immunosuppressive therapy agents and evaluation for cardiac transplantation.

REFERENCES 1. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis — natu- ral history and treatment. NEJM 1997;336:1860-6. 2. Davidoff R, Palacios I, et al. Giant cell versus lymphocytic myocarditis. Circu- lation 1991;83:953-61. 3. Kodama M, Matsumoto Y, et al. A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 1990; 57:250. 4. Kong G, Madden B, et al. Response of recurrent giant cell myocarditis in a transplanted heart to intensive immunosuppression. Eur Heart J 1991;12:554- 7.[Medline] 5. Davies RA – Giant cell myocarditis. J Heart Lung Transplant 2002; 21: 674- 9. 6. Levy NT, Olson LJ, et al. Histologic and cytokine response to immunosup- pression in giant-cell myocarditis. Ann Intern Med 1998;128:648-50.

Richard A. Regnante, MD, is a Cardiology fellow, Rhode Island Hospital. Athena Poppas, MD, FACC, is Director of the Echocardiography Department, Rhode Island Hospital.

CORRESPONDENCE Richard Regnante, MD Cardiology Department Rhode Island Hospital 593 Eddy St. Providence, RI 02903 phone: 401-444-8041 e-mail: [email protected]

ACKNOWLEDGEMENT We would like to acknowledge David Denofrio, MD, FACC, of New England Medical Center for providing the pathology slides for this case.

54 MEDICINE & HEALTH/RHODE ISLAND GERIATRICS FOR THE PRACTICING PHYSICIAN Division of Geriatrics Quality Partners of RI Department of Medicine EDITED BY ANA C. TUYA, MD Managing the Medication Portfolio and Avoiding Polypharmacy in the Older Adult Ana C. Tuya, MD

MRS. G IS AN 83-YEAR-OLD WOMAN in pharmaco-kinetics (how the body patic function occur naturally with ag- whom you started seeing one month ago. handles drugs) and -dynamics (how drugs ing (the pure aging syndrome); common Her previous medical records are still in affect the body) that occur with aging. diseases and co-morbidities that increase transit from New York, following her Finally, older adults are not often in- in incidence with aging exacerbate these move to RI in order to live near her cluded in clinical trials of medications; modest decrements. A gradual decline daughter. She presented with a known those that are included tend to be in glomerular filtration rate is seen in history of chronic atrial fibrillation, man- younger and healthier than typical eld- about 70% of the population, although aged on Coumadin and Digoxin; hyper- erly patients, often making use of some there is variation in the degree of the de- tension on Toprol, Diovan and Norvasc; medications a non-evidence-based prac- cline from person to person; about 20% reflux disease on Nexium; congestive tice. Numerous adverse reactions and of persons seem not to show a decline in heart failure on Lasix; insomnia on dose adjustments for older adults are renal function with pure aging, and a Trazadone; hypothyroidism on learned through trial and error use of smaller percentage (5-10%) show accel- Synthroid; and depression on Zoloft. She medications in the clinical setting. erated decline due to renal disease. On also takes over the counter Tylenol as The basic principles of pharmaco- average, the decline is 1ml/min/yr after needed for osteoarthritis, Benadryl as kinetics are important to remember when the age of 40. With the concomitant needed, a daily multivitamin and Cal- prescribing medications to the older decline in creatinine production, serum cium with vitamin D. She is adjusting adult. To start with, drug absorption creatinine is unchanged. For this reason, well to the move, likes being near her appears to be mostly unchanged with creatinine clearance should always be daughter, and enjoys her new apartment aging; however, disease states and other calculated and medications should be on the East Side of Providence. She re- medications can affect absorption (atro- dosed accordingly; normal renal function mains very independent, only requiring phic gastritis, delayed gastric emptying, should not be assumed based on a nor- transportation assistance to get to the decreased splanchnic blood flow). mal serum creatinine. Said another way, store to do grocery shopping. You dis- Changes in drug distribution do have serum creatinine and BUN overestimate cuss wanting to make her medication clinical importance in older adults. Ag- renal function in older persons because regimen simpler, but decide to wait for ing carries with it an increase in body fat of decreased creatinine production in the records from her previous physician; she content, a decrease in lean body mass, a first case, and decreased protein inges- agrees and is to return to the office in decrease in total body water and a small tion in the other. Both arise from de- one month. Two weeks later, after a decline in albumin concentration. Fat- cline in lean body mass with age. In the record-breaking Rhode Island summer soluble drugs will, therefore, have a larger liver, the metabolism of medications, es- heat wave, you receive a panicked call volume of distribution, and water-soluble pecially via phase I reactions (cyto- from the patient’s daughter after finding drugs will have a smaller volume of dis- chrome-mediated) is delayed, leading to her mother on the floor in her apartment tribution. Drugs that bind to albumin plasma and tissue concentrations that are confused and disoriented, and in a pool may have less binding sites available, put- usually increased. Dose reduction is gen- of urine. She is rushed to the Emergency ting older adults at higher risk of toxicity erally required for hepatically metabo- department for evaluation. from increased active drug concentra- lized medications. Managing medications in the older tions; Dilantin is a common example. Polypharmacy is a commonly dis- adult becomes more complex; causes in- These factors combine to produce higher cussed topic among practitioners who clude 1) multiple underlying illness re- blood levels, earlier and more frequent care for older adults. It is common for quiring intricate medications regimens, occurrence of side effects and greater older adults to be on at least three daily 2) multiple physicians – primary, special- clinical impact at lower concentrations in medications, and many are on more. The ist and sub-specialist - prescribing medi- older adults given standard doses of most risk of adverse drug reactions increases cations, and 3) frequent use of over the drugs. Time to reach steady state is often with the number of medications taken, counter or herbal remedies. In addition prolonged several-fold. Accordingly, a and occur twice as often in older adults. to large numbers of concurrently used geriatrics dictum when starting any new In addition to the above physiologic drugs, prescribing medications for older medication is “start low and go slow. “ changes that make medication use com- adults is challenging due to the changes Changes in renal clearance and he- plex, drug-drug and drug-disease inter- 55 VOLUME 90 NO. 2 FEBRUARY 2007 actions are commonly responsible for adverse drug effects. rent drugs before adding new ones to look for potential inter- Polypharmacy can develop easily in the face of multiple practi- actions. For the most part, in older adults, less is more, and tioners prescribing for the same patient, old prescriptions that stopping a medication is usually a better option than adding are kept and used on occasion, use of over the counter medica- one. tions, and the common phenomenon of new prescriptions to For example, our patient would have benefited from a treat side effects of other drugs. Unidentified non-adherence streamlining of her medications; most glaring is the use of (resulting from financial hardship, sensory deficits, cognitive Benadryl in an older adult. Due to its strong anticholinergic impairment, difficulty swallowing, complex regimens) can of- effects, Benadryl is a relatively contraindicated medication in ten lead to the use of additional medications when unneces- the elderly patient population. Classes or particular medica- sary (e.g., the addition of a second or third antihypertensive tions to be aware of are described in the Beers criteria, up- agent, when the original one is not being taken regularly or dated in 2003. A useful website was designed at Duke Uni- correctly). versity that provides a quick reference link to a summary of Drug-related problems commonly seen include delirium, drugs to avoid, and a web-link to the original article. The link hypotension, incontinence, falls, loss of appetite and nephro- is: http://www.dcri.duke.edu/ccge/curtis/beers.html. It is use- toxicity from high drug levels. Furthermore, many drugs have ful to review this list before choosing drugs of certain classes increased adverse effects in older adults—for example, the in- for use in the older adult. Many drugs that are benign in creased risk of gastrointestinal bleeding and fluid retention with younger patients can lead to significant adverse reactions in non-steroidal anti-inflammatory drugs. Mrs. G., described the older patient. above, is a classic example of this phenomenon. What are the In summary, medication profiles should be reviewed regu- likely contributory causes to her crisis event? Most likely her larly, in detail, with older patients as a part of routine office picture is due to the summer heat wave, during which Mrs. G care. Managing the medication regimen of a patient with had increased insensible losses, exacerbated by age-related de- multiple conditions is complicated, and many drugs are neces- crease in thirst perception and baseline elevated ADH levels. sary; however, less is often more. Remembering the basic phar- These led to a clinical picture of dehydration and hypovolemia, macologic principles and the usual changes that occur with worsened by Lasix. Diovan and Digoxin in the setting of hy- aging, as well as reviewing the common danger drugs for older povolemia most likely led to electrolyte disturbances, brady- adults will be a useful start in keeping an older adult’s medica- cardia or conduction disturbances, and acute renal failure. Any tion list optimally beneficial and least likely to produce harm. of these toxicities or a combination is a plausible explanation It is important to critically question each and every medica- for her confusion. tion. This practice will diminish the likelihood of one’s older In addition, the development of incontinence in a previ- patient presenting with adverse drug reactions and complica- ously continent woman can be described as transient inconti- tions such as those demonstrated by Mrs. G. nence. Transient incontinence is often a manifestation of a problem in other organ systems—often acute illness or other REFERENCES stress. This was described in last month’s column as part of the 1. Boxer R, Shorr R. Principles of drug therapy: Changes with aging, polyphar- concept of aging as a progressive restriction of the capacity to macy and drug interaction. In: Landefeld CS, Palmer R, Johnson M, et al. eds., Current Geriatric Diagnosis & Treatment, New York: McGraw-Hill, 2004: maintain homeostasis - “homeostenosis.” Homeostenosis, al- 421-35. though a made up word, vividly describes how, in older adults, 2. Fick DM, Cooper JW, et al. Updating the Beers criteria for potentially inap- only modest severity of physical illness, drug toxicity or trauma propriate medication use in older adults. Arch Intern Med 2003;163:2716- often results in catastrophic declines, leading to a cascade of 24. 3. Steinman MA, Landefeld CS, et al. Polypharmacy and prescribing quality in seemingly unrelated problems (pneumonia presenting with older people. J Amer Geriatr Soc 2006; 54: 1516-23. confusion, falling, urinary incontinence and loss of self-care capacity). One can expect that with resolution of her acute Ana C. Tuya, MD, is Assistant Professor, Division of Geriat- problems, the incontinence will also resolve. rics, Brown Medical School. In order to prevent such crises, laden with risk for irre- trievable functional loss, it has become commonplace in many 8SOW-RIGeriatrics -022007 practices to request that patients “brown bag” their medica- THE ANALYSES UPON WHICH THIS PUBLICATION IS BASED were tions and supplements on the first, if not all visits to the practi- performed under Contract Number 500-02-RI02, funded by tioner. Reviewing in detail all medications, both over the the Centers for Medicare & Medicaid Services, an agency of counter and prescription will allow an accurate inventory of the U.S. Department of Health and Human Services. The con- what the patient is taking. This review allows the practitioner tent of this publication does not necessarily reflect the views to detect and prevent dangerous interactions or adverse effects. or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or In addition, adherence can be assessed, as well as any reasons organizations imply endorsement by the U.S. Government. behind non-adherence. Finally, it is a good opportunity to The author assumes full responsibility for the accuracy and review each medication for continued indication. If no reason completeness of the ideas presented. for use is found, or if a medication is being used to treat the side effect of another, discontinuation should be pursued. When prescribing at any time in an older adult, consider cost, adherence and risk factors for non-adherence, and review cur- 56 MEDICINE & HEALTH/RHODE ISLAND RHODE ISLAND DEPARTMENT OF HEALTH • DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH EDITED BY JAY S. BUECHNER, PHD Hospital Community Benefits, 2005 Bruce Cryan, MBA, MS

The organization of RI’s thirteen community hospitals1 as efits, an annual survey, audited financial statements, and Medi- 501(c)(3) corporations enables them to carry out their chari- care Cost Reports are used to collect descriptive and financial table missions without the tax liabilities imposed on for-profit data. To allow for more valid comparisons between institu- companies. The economic value of this “not-for-profit” desig- tions and over time, the charity care charges reported by hos- nation is considerable, and the community, in waiving its right pitals are cost-adjusted by applying yearly, hospital-specific ‘Ra- to these revenues, implicitly anticipates that it will ben- efit from the “public good” of certain benefits provided in return. Chief among these are healthcare services rendered to all patients regardless of their ability to pay (i..e., charity care). Rhode Island was one of the first states in the na- tion to examine hospital community benefits. Since 1989, the RI Department of Health (HEALTH) has analyzed and reported on this issue.2 In 1997, the General Assembly passed the Hospital Conversions Act (the Act) that further codified the public reporting of these activities.

METHODS The Act and its regulations broadly define com- munity benefits as “…the provision of hospital services that meet the ongoing needs of the community for pri- mary and emergency care” and furthermore state that they “shall …not be limited to charity care and un- compensated care,” but include “programs …that meet the needs of the medically indigent,” “linkages with community partners,” “non-revenue producing ser- vices,” “public advocacy,” and “scientific, medical re- search, or educational activities.” Notwithstanding the Act’s broad definition of com- munity benefits, charity care remains the most funda- mental measure of a hospital’s commu- nity benefits. Charity care is the charges recorded for services delivered but never billed because the hospital determined the patient was incapable of payment. A patient receiving char- ity care is means-tested and found to be medically indigent, or too impov- erished to pay for their care. Bad debt, on the other hand, is often cited as a community benefit but is, in fact, a normal, competitive busi- ness expense incurred by every busi- ness marketing goods or services. In this case, bad debt is the billing for healthcare services rendered to patients capable of payment, but never re- ceived and written off as uncollectible. In order to quantify the hospitals’ Figure 1. Hospital charity care expenses, in dollars and as a percent of patient revenue, efforts in providing community ben- by hospital fiscal year, Rhode Island, 2000-2005. 57 VOLUME 90 NO. 2 FEBRUARY 2007 Figure 2 presents each hospital’s charity care as a percentage of pa- tient revenue for the period 2000- 2005. Aggregating six years of data removes any outliers associated with a single year’s reporting. Presenting the value as a percentage of the hospital’s patient revenue further standardizes the statistic for compari- son purposes. Charity care percentages ranged from highs greater than 1% at Butler (2.2%), Memorial (1.4%), Rhode Island (1.2%), and Newport (1.1%) Hospitals to lows at Rehabili- tation (0.2%) and Bradley (0%) Hos- pitals.

DISCUSSION Figure 2. Average annual hospital charity care expenses, as a percent of patient revenue, Since 1998, HEALTH has had by hospital, Rhode Island, hospital fiscal years 2000-2005. formal data collection efforts to track and quantify hospital community tio of Costs to Charges’ factors to approximate the actual ex- benefits. As the debate over what constitutes a ‘charitable’ or- penses incurred to provide the healthcare services to these pa- ganization continues, policy makers struggle with the need for tients. Also, to further standardize the data, the cost-adjusted more and better information. In response, HEALTH has ex- charity care ‘expenses’ are presented as a percentage of hospital panded its public reporting and revised the metrics used to Patient Revenue to measure the burden of this care on the pro- frame and analyze the issue. viders. 3 In addition, HEALTH uses this opportunity to align the hospitals’ community benefits activities with its own public RESULTS health initiatives. Understandably, not every hospital addresses The Governor’s 2005 Wellness Initiative identified five all of these areas, because each hospital’s priorities should re- goals to focus statewide public health improvement efforts: 1) flect its own community needs, but it does serve to illustrate reduce obesity, 2) reduce smoking, 3) increase consumption of where the industry and the state may work together more ef- fruits & vegetables, 4) increase exercise, and 5) increase seat- fectively. belt use. Table 1 summarizes each hospital’s own grouping of its 2005 support for these objectives, as well as for increasing REFERENCES healthcare access, unreimbursed graduate medical education 1. Rehabilitation Hospital is a Limited Partnership, a wholly owned subsidiary of (GME) expenses, and a final category for all other community Landmark; its net income flows up to tax-exempt Landmark; and its financial statements are consolidated with Landmark’s. benefits activities 2. Cryan B. Uncompensated Care Services in RI’s Community Hospitals. Provi- Regarding ‘Increas(ing) Healthcare Access,’ $29.8 million dence RI: Rhode Island Department of Health. 1989; and Cryan B. Uncom- or 89% was from direct charity care healthcare services to pa- pensated Care and Tax Exemption of RI’s Hospitals. Providence RI: Rhode Island tients. With respect to ‘Reduc(ing) Obesity,’ $3.2 million or Department of Health. 1993. 3. These charity care expenses (and percentages) are reported without regard to 94% was from unfunded research in this field. The ‘Other’ the specialized revenue some hospitals receive to subsidize or otherwise offset category includes such activities as community outreach, health the cost of that care: 1) Medicaid Disproportionate Share Hospital (DSH) screenings, patient education, health clinics, and patient trans- payments, 2) Medicare DSH payments, and 3) restricted endowment income port/financial counseling. donated to fund healthcare for indigent patients. Figure 1 provides the statewide charity care expenses and Bruce Cryan, MBA, MS, is a Health Policy Analyst in the percentages from 2000 through 2005. Over this six-year pe- Center for Health Data & Analysis, Rhode Island Department of riod, the charity care expenses increased fairly consistently, from Health. $14 to $30 million. In the highest year, 2005, the burden of this care was 1.3% of patient revenue statewide.

58 MEDICINE & HEALTH/RHODE ISLAND DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH RHODE ISLAND DEPARTMENT OF HEALTH EDITED BY JOHN P. F ULTON, PHD Taking a Social Marketing Approach To Implementing Clinical Best Practices: A Pilot Project Robert Marshall, PhD, Arthur Frazzano, MD, MMS, Deidre Gifford, MD, MPH, Marcia Petrillo, MA, Shannon Sansonetti, MA, and Jeffrey Stumpff, MA

The past decade demonstrated increasingly broad-based support evolve from academic settings into community practice—of- for the implementation of evidence-based guidelines in every- ten without full consideration of how they fit with the desires day clinical practice in order to improve the management of and needs of the “target audience” (practicing physicians). A the leading causes of US morbidity and mortality.1,2 However social marketing based approach keys on the needs of the the adoption of Evidence Based Medicine (EBM) and other audience, and then redesigns the product (within scientific generally accepted “clinical best practices” (CBP) continues parameters) to achieve a better fit. This pilot project illus- to lag behind at the community level.3,4 Public health agencies, trates both the merits of the approach and the kinds of find- healthcare quality improvement organizations, and medical edu- ings that could be obtained in a full study and used to im- cators share a stake in promoting these practices in order to prove physician adoption of CBP. improve population health. The anticipated benefits depend not only upon regular use by busy clinicians in community METHODS practices, but also upon teaching CBP to medical students The partners in this collaborative effort included the during the preceptorial phase of their education. Rhode Island Department of Health, Quality Partners of One review of 67 studies found that a variety of factors Rhode Island and Qualidigm, Inc. (healthcare quality im- relating to the physician, guidelines, health system or patients provement organizations), the Office of Medical Faculty Af- all influence compliance with CBP.5 Use of a more insightful fairs and the Department of Family Medicine at Brown Medi- theoretical framework for understanding and changing physi- cal School and Policy Studies, Inc. a public health education cian behaviors could help to reduce the gap between knowl- and marketing firm. The focus groups used a specially-de- edge and routine practice. signed facility in a local shopping mall. One researcher served Social marketing entered the professional literature over 30 as group moderator; others observed through a one-way mir- years ago and has been applied to many areas of consumer and ror. professional health behaviors. Social marketing applies “commer- Investigators recruited a total of twelve subjects for two cial marketing technologies to the analysis, planning, execution focus groups using lists from the RI Chapter of the American and evaluation of programs designed to influence voluntary be- College of Physicians, RI Community Health Centers and fam- havior” and improve personal welfare and society.6 Five basic prin- ily practices in the state. The focus groups were segmented into ciples distinguish social marketing from other behavioral change salaried (institution-based) and non-salaried primary care phy- approaches: 1) marketing’s conceptual framework 2) audience seg- sicians and balanced for gender and years of practice. Subjects mentation; 3) focus on the consumers’ desires and needs; 4) will- received $150 to participate. Limited resources severely re- ingness to modify the product and 5) careful, continuous moni- stricted the sample size and precluded conducting additional toring and revision.7 Social marketing has contributed to the un- subsequent group sessions. However, the authors suggest that derstanding of medical education8 and may provide a useful frame- the results, although not generalizable, strongly indicate a re- work for analyzing and changing other professional behaviors, such search approach that lends itself to further study. as the use (and teaching) of clinical best practices. The Guide to Clinical Preventive Services9 contains rigor- In order to explore and understand the gap between guide- ously-evaluated interventions to prevent common illnesses and lines and actual practice, we undertook a pilot qualitative study, conditions seen everyday by primary care providers through- employing physician focus groups—often a useful tool for gath- out the US and Canada. Investigators focused on two guide- ering preliminary data. The overall objective of the study was lines: breast cancer screening and tobacco cessation. Breast to guide future research by addressing the following questions: cancer screening includes a mammography and/or clinical breast exam (CBE) every 1-2 years for women age 50-69. It • How do practicing physicians weigh the “pros” and “cons” suggests that there is insufficient evidence for CBE alone or for of using CBP? routine mammography among younger or older women. The • How do CBP guidelines compete with other influences Guide also recommends routine smoking prevention counsel- on physician behavior? ing for children, adolescents and adults in addition to cessa- • Does a social marketing approach help inform CBP imple- tion for all tobacco users, especially pregnant women and par- mentation? ents with children at home, including the use of nicotine re- placement therapy (patch or gum). We anticipated that the Social marketing exposes the gap between CBP guide- challenges pertaining to the implementation and teaching of lines and everyday practice by focusing on the audience. Tra- these particular guidelines would evoke a range of underlying ditionally, science based medical applications (“products”) issues, behaviors and barriers. 59 VOLUME 90 NO. 2 FEBRUARY 2007 The moderator’s guide addressed the following areas: Table 1: Barriers to implementation of best practices guidelines • Perceived benefits to using and teaching CBP • Current behavior compared to CBP guidelines on breast Breast Cancer Screening cancer screening and tobacco cessation; Lack of consensus on guidelines • Challenges associated with implementing and teaching Guidelines not linked to data on improved health the guidelines; and outcomes • Recommendations for overcoming the challenges. Patient fails to follow through Difficult coordination with specialists Patient fears For the purposes of the focus groups, the terms “best prac- Reimbursement not commensurate with how long it tices” and “clinical guidelines” were used interchangeably. takes Forgetfulness RESULTS Smoking Cessation Counseling Physicians reported that CBP aids practice in several ways— Low success rate helps physicians to stay updated, provides an overview of current Time problems in a busy practice research, improves patient care and alleviates several medical li- Insurance reimbursement/coverage ability concerns. Some physicians prefer guidelines emanating from Patient attitudes professional organizations; others prefer academic or governmen- tal “experts” in the field. They all expressed concern about main- ception is epidemiologically accurate or not, it points out the taining a rigorous science base. Subjects wanted CBP to contain: difficulty of assuring compliance with demanding professional behaviors which may not meet the needs of the practitioner or • A concise overview of the scientific method used to de- where the cost-benefit analysis seems weak. velop the guidelines; During the focus groups, physicians also talked about ways • Information on the impact that the recommended prac- to overcome barriers to implementing best practices. Their tice has on patient outcomes; and recommendations centered on the following areas: • “Tiered” measurement to help them prioritize which prac- tices to implement if they cannot implement all of them. • Improved Office Support: tools such as automated of- fice reminders or a service that summarizes current wait This last item seems particularly important. The Guide to times for getting mammograms at various sites Clinical Preventive Services contains 70 recommendations for • Insurance coverage: gaps between CBP requirements and routine screening, counseling, immunization and chemopro- insurance coverage—such as Zyban for smoking cessa- phylaxis in primary care practice—a daunting number of tasks tion. for any profession. • Acknowledgment that guidelines alone don’t always dic- Physicians also reported numerous barriers to implement- tate physicians’ decisions: Other factors that affect deci- ing best practices. (Table 1) sion-making include their schooling, experience, personal Our focus group physicians also voiced concerns in gen- views, independent research, and the patient’s individual eral about best practice guidelines. These include: situation (family history, etc.). • Multi-faceted approach to changing patient behavior: • Skepticism about following guidelines developed by “spe- Physicians strongly supported smoking cessation but ar- cial interest groups” gued that sustained change in smoking behaviors requires • Impractical guidelines developed by academic physicians community resources such as support groups, patient edu- • Mistrust of the science used to develop some guidelines cation, media campaigns, and legislation, such as ciga- • Rapidly changing guidelines cause physicians to lose cred- rette tax increases and bans on smoking in public places. ibility with patients • Multiple and diverse patient demands because of self-edu- Most physicians reported that they generally teach medical cation students and interns by modeling CBP with their patients but this • Lack of cost/benefit information on implementation of sometimes slowed down the pace of practice and exacerbated some guidelines of their original concerns about routine implementation. • Increased costs of implementing certain guidelines (e.g., cholesterol screening) CONCLUSIONS • Guidelines still need to be adapted depending on patient This pilot study offers several potential implications for circumstances strategies of developing, implementing and teaching CBP. • Complexity of adhering to guidelines (e.g., diabetes care) • Intervention strategies must vary depending on the health One young physician with a modest-sized practice even issue and the barriers confronting implementation of a speculated that it may be possible to go through an entire ca- particular clinical best practice. reer without saving the life of a single patient through steadfast • Operational and reimbursement issues must be acknowl- adherence to mammography guidelines. Whether that per- edged and addressed as part of any intervention strategy. 60 MEDICINE & HEALTH/RHODE ISLAND • Guideline development and implementation could benefit 4. Bates DW, et al. Ten commandments for effective clinical decision support. J Am from using a social marketing (consumer-oriented) approach. Med Inform Assoc 2003; 10:523-30. 5. Tan KB. Clinical practice guidelines. Int J Health Care Qual Assur Inc Leader- ship Health Serv 2006; 19: 195-220. Based on the results of this preliminary study, the investi- 6. Coreil J, Bryant C, Henderson N. Social and Behavioral Foundations of Public gators make the following recommendations for future research. Health. 2000;Thousand Oaks, CA: Sage. Policy makers and medical educators can use a social market- 7. Kotler P, Roberto N, Lee N. Social Marketing: Improving the Quality of Life (2nd ed.) 2002, Thousand Oaks, CA: Sage. ing approach to improve provider behaviors regarding the rou- 8. Sean P. David, David S. Greer, Social Marketing: Application of Medical Educa- tine use of clinical guidelines. Social marketing can also help tion, Annuals of Internal Medicine 2001; 134, 125-127. redesign clinical guidelines overall—taking practitioner’s needs 9. US Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd into account. By doing so, additional formative research could Edition. Baltimore: Williams & Wilkins, 1996. improve the fit between guidelines and clinical practice, hence Robert Marshall, PhD, is Assistant Director of Health, Of- reduce barriers to physician compliance and improve popula- fice of Public Health Research Training and Practice, Rhode Is- tion health outcomes. land Department of Health, and Clinical Associate Professor of Finally, this study suggests that the use of informed medi- Community Health, Brown Medical School. cal trainees to help providers/preceptors keep up to date on Arthur Frazzano, MD, MMS, is Associate Dean of Medi- the science and implementation of the latest clinical guidelines cine (Clinical Faculty), Associate Professor of Medicine (Clini- can be an effective strategy for improving both their clinical cal), and Director, Division of Health Policy and Advocacy De- and preceptorial behavior. Given the small sample size, the partment of Family Medicine, Brown Medical School. authors anticipate conducting additional research to fully con- Deidre Gifford, MD, MPH, is Director of Outpatient Qual- firm these findings and design interventions to demonstrate ity Improvement, Quality Partners of Rhode Island. the application of these recommendations. Marcia Petrillo, MA, is Chief Executive Officer, Qualidigm. Shannon Sansonetti, MA, is a Senior Consultant, Policy REFERENCES 1. Audet AM, Greenfield S, Field M. Medical practice guidelines: Ann Intern Med Studies Inc. (PSI). 1990; 113:709-14. Jeffrey Stumpff, MA, is a Research Analyst, Department of 2. Chassin MR. Practice guidelines. J Occup Med 1990;32:1199-206. Family Medicine, and Clinical Teaching Associate, Brown Medi- 3. Cabana MD, et al. Why don’t physicians follow clinical practice guidelines. cal School. JAMA 1999; 282:1458-65.

61 VOLUME 90 NO. 2 FEBRUARY 2007 Health Insurance Update National Provider Identifiers – Implications for the Local Provider Community Patricia E. Huschle, MS The Administrative Simplification provisions of the Health Insur- Who needs to be given NPI information? ance Portability and Accountability Act of 1996 (HIPAA) mandated Once the physician or the group has obtained the NPI, the num- the adoption of standard unique identifiers for health care providers. On ber must be provided to billing agents, clearinghouses and all health January 23, 2004, the Centers for Medicare and Medicaid Services plans and insurance companies with whom the provider does business. (CMS) published its Final Rule adopting the National Provider Identi- Requirements as to how to communicate NPI information to these fier (NPI) as the HIPAA-mandated provider identifier. NPIs are de- entities may vary. The health plan and insurance company web sites or signed to provide a unique identifying number for each health care pro- provider representatives will be able to provide more detail. vider, to be used for certain standard transactions, such as the submission Providers that use business associates or agents to conduct stan- of claims for reimbursement for the provision of health care services. dard transactions on their behalf must require those business associates Under the 2004 Final Rule, every HIPAA-covered health care pro- to use their NPIs appropriately for those transactions. vider1 must obtain his or her own NPI, even if he or she uses a billing Rhode Island health plans are reporting that they have received agency to prepare the covered transactions. Likewise, all health plans, only a fraction of the NPIs from local providers. Of the 7,000 NPIs including Medicare and Medicaid, must use the NPIs to identify health currently issued in the state of Rhode Island, less than half that number care providers in standard transactions. The deadline to implement the has been reported to the local health plans. use of NPI in standard transactions is May 23, 2007. Thus, by mid- 2007, the NPI will be the only permissible provider identifier in stan- What is the deadline to obtain an NPI and what are dard transactions by HIPAA-covered entities, replacing any other health the implications if the deadline is missed? plan-specific provider numbers that may currently be in use.2 As required by HIPAA, covered entities will require the NPI on all transactions after May 23, 2007. Small health plans must do so by Why implement a new number? May 23, 2008. Claims submitted after this date without an NPI may The implementation of one single provider identifier is one com- be rejected. Therefore to insure no disruption in cash flow or business ponent in the establishment of national standards for electronic data ex- operations, providers must obtain and communicate their NPIs in ad- change for all health care related transactions. Similar to other national vance of the May 23rd deadline. industries that have moved toward promoting electronic commerce, na- tional standards in the health care industry will make electronic data in- Part of the statutory obligation of Office of the Health Insurance terchange a preferable alternative to paper processing. Physician’s offices Commissioner is to encourage fair treatment of health care providers. will benefit from the administrative simplification of needing only one A single unique identifier is one step toward simplifying the adminis- number when dealing with any health plan or insurance company in the tration of the health care system and reducing some administrative United States including Medicare and Medicaid. burden on physician offices. This Office strongly encourages the pro- vider community comply with the Federal Final Rule and obtain and How do physicians obtain their NPI? communicate its National Provider Identifier to all business partners CMS has developed the National Plan and Provider Enumera- well in advance of the deadline. tion System (NPPES) to assign NPI numbers. Providers may obtain NPIs in the following ways: For more information about the OHIC please visit www.dbr.state.ri.us/health_insurance.html • A paper application • A web-based application REFERENCES • An Electronic File Interchange (EFI) process that offers a bulk 1. For the purposes of the NPI Rule, a “covered health care provider” means any health care enumeration through which a health care provider or group of provider, including any physician, who transmits any health information in electronic form in connection with a transaction covered by HIPAA. 45 C.F.R. §§ 160.103, 162.402. providers can have a particular organization apply for NPIs on 2. The compliance date for all covered entities except small health plans is May 23, 2007; their behalf. the compliance date for small health plans is one year later—May 23, 2008.

Further information about each of these processes may be found Patricia E. Huschle, MS, is Provider Liaison, Office of the Health on the NPPES Web site: https://nppes/cms.hhs.gov. Insurance Commissioner.

What is the difference between a Type 1 and Type CORRESPONDENCE: 2 NPI? Patricia E. Huschle, MS Whether to apply for a Type 1 or Type 2 NPI has caused some Office of the Health Insurance Commissioner confusion. Although physicians ultimately make the decision on how 233 Richmond Street they want to be enumerated, in most cases individual practitioners Providence, RI 02903 should obtain a Type 1 NPI, while physicians in a group should also phone: (401) 222-5424 obtain a Type 2 NPI for the group. e-mail: [email protected] 62 MEDICINE & HEALTH/RHODE ISLAND ADVANCES IN PHARMACOLOGY Off-Label Drug Use Andrea G. Dooley, PharmD The formulation of drug products has been monitored since the cians observe unapproved uses of medications it is important early 19th century. The United States Pharmacopoeia (USP) to report the drug use experiences,8 thereby allowing clinical was developed in 1820 to set the “standards” for drug prod- information on the subject to be disseminated to other ucts including indications of these drug products.1 Over the healthcare practitioners. In addition to the primary literature, last century, regulations were set in place to further monitor resources that contain off-label uses of medications include the and evaluate the use of prescription medications. The Pure American Hospital Formulary Service-Drug Information Food and Drug act was responsible for the creation of the (AHFS-DI), United States Pharmacopeia-Drug Information United States Food and Drug Administration (FDA) in 1938.1 (USP-DI), DRUGDEX® drug information system, and oth- Today the FDA governs the regulation, evaluation, and ap- ers.1 A standard of practice in off-label drug prescribing in- proval of drug products. The FDA, under the regulation of cludes the use of these references as reputable sources of clini- the Food, Drug, and Cosmetic Act (FDCA), is responsible for cal, off-label drug use information. Some insurers base reim- ensuring that prescription drug products are both safe and bursement on whether or not an off-label drug use is found in effective for use in the population.1,2 either the AHFS-DI or USP-DI compendia. Insurers con- When the FDA approves the drug product, the approval sider items included in these drug compendia as “approved” is solely for the studied indication, dosage, and patient popula- off-label uses (approved because it is found within these texts, tion. Certain drug classes are more frequently used off-label not approved by the FDA).9,10 than other drug products. Some of these drug classes include In 1997, the FDA Modernization Act (FDAMA) changed anticonvulsants, antipsychotics, antihistamines, antiasthmatics, the way the pharmaceutical industry could promote the off- and cardiovascular agents.2 When reviewing prescribing trends label use of a drug, allowing manufacturers to use published for office-based physicians, approximately 21% of medications peer-reviewed articles and reference textbooks in discussions were prescribed for an off-label indication.2 When specifically of off-label drug uses with healthcare providers.1,4,7,11 If a phar- reviewing drug usage in chemotherapy and pediatric patients, maceutical company initiates the process and provides off-la- approximately 85% of medications are prescribed for an off- bel information to clinicians, the pharmaceutical company must label indication.3 The regulations, legal and ethical aspects, submit the information that was provided, and to whom it was and importance of off-label drug use are discussed below. provided, to the FDA.4,7 The off-label use presented in the articles should be regarding a new indication that the manu- OFF-LABEL DRUG USE facturer plans to submit in a supplemental application to the Off-label drug use has been defined as the “use of a drug FDA within the next 36 months.4,12 Companies are exempt product outside the conditions specified within the FDA-ap- from submitting the application if the cost of performing stud- proved product insert”4,5 and may include use of a drug at a ies on the new indication is more expensive than the expected lower or higher dose than recommended, in a population or monetary returns from the newly approved indication.4 age group that was not studied, for an indication that was not Professional organizations have established their own poli- evaluated, or by a route of administration that differs from the cies regarding the off-label use of medications. The two lead- package insert.5 The term off-label does not mean that the ing professional pharmacy organizations, American Pharma- drug product is used inappropriately, but that tolerability, cists Association (APhA) and the American Society of Health safety, and efficacy data are not available for that particular System Pharmacists (ASHP), both support off-label drug use. usage.5 New or off-label uses may arise directly from clinician ASHP’s position is, “freedom and responsibility to make drug observation or “therapeutic innovation”.4,6 therapy decisions consistent with a patient’s needs are funda- Off-label drug use by clinicians is permitted because of mental”.9 They also support the responsibilities of a pharma- “medicine exemption,”4 which states that “a physician may law- cist to provide drug information and clinical practice standards fully vary the conditions of use from those approved in the regarding off-label drug use.9 The position statement and poli- package insert without informing or receiving approval from cies of APhA state that a collaboration should be formed be- the FDA”.4 Additionally, the FDCA does not limit how a cli- tween the pharmacist and other healthcare providers to evalu- nician may use an approved drug.6 “Medicine exemption” lets ate off-label information and the organization also supports a clinician prescribe medication for what is considered an ap- reimbursement by third party payers for therapies used off- propriate use without worry of legal ramifications. However, a label.13 The American Medical Association (AMA) takes the clinician must use evidence and/or practice experience when same stance as the pharmacy organizations in addition to unre- prescribing outside the product labeling.4,7 stricted prescribing by a provider, regardless of approved or When evaluating the use of medication for an off-label off-label use.14 indication, published information may be limited. As clini- 63 VOLUME 90 NO. 2 FEBRUARY 2007 LEGAL AND ETHICAL CONSIDERATIONS especially if the off-label medication is frequently used for the Physicians who prescribe medications for off-label drug particular indication in clinical practice.4 This concern is espe- use are not at risk for allegations of negligence or malpractice if cially true when treating cancer patients with chemotherapeutic decisions are based on clinical evidence and are consistent with agents that have many indications for use, some of which may community practice.4 An off-label indication for a medication not be in the product labeling. In such instances, a patient would may be the standard of care for a particular disease state.4,7 have to “pay out of pocket” for the clinically preferred regimen. Therefore, it is important that a provider does not limit pre- scribing to FDA-approved uses because there may be instances SAFETY where an off-label product is the best treatment option.4,7 The adverse events for approved or “labeled” uses are Off-label drug usage is frequently seen in special popula- found in the package insert and result from observations made tions including children and pregnant women because clinical during clinical and post-marketing trials. When using a drug trials are not routinely conducted in these populations. Few tri- product off-label there are concerns relating to patient safety als are conducted in pediatric patients because informed con- and cost to the healthcare system.2 A greater risk of adverse sent needs to be obtained from the guardian of children less effects is anticipated when medications are used off-label.5,12 than 16 years old.5 Also, there is no financial incentive for phar- The theoretical increase in risk results from a lack of infor- maceutical companies to perform trials in mation about the off-label use in medi- the limited pediatric population (i.e., the “An off-label cal literature and that medications that companies will not have a monetary return may be used in a particular population that will cover the costs of the clinical trial).5 indication for a or at a different dose for the first time. Trials are not performed in pregnant medication may be An example that epitomizes the un- women due to the potential for teratogenic known risks when medications are used effects in the fetus. Since off-label uses are the standard of off-label is the controversy surrounding not evaluated, it is not known what safety care for a particular “fen-phen.” As a treatment for obesity, problems may arise from off-label use, es- fenfluramine and phentermine were pecially in pregnant women. The thalido- disease state.” combined. Both were FDA-approved for mide tragedy is a reminder of the impor- short-term use in the treatment of obe- tance of drug use evaluation in these sensitive populations. sity4,7,12; however, combined use and the longer treatment The vast majority of medications used in the pediatric duration represented an off-label use which resulted in car- population are prescribed off-label because clinical trial infor- diac valve damage in some patients.4,12 Clinicians should in- mation is lacking. An additional component of the FDAMA is form patients who are using medications off-label of the an- an incentive for pharmaceutical manufacturers to perform clini- ticipated adverse effects seen with the labeled use of a drug cal trials in the pediatric population. The FDAMA offers a 6- product.7 This may not be possible in the provider’s practice month patent extension to a pharmaceutical company that will setting and a pharmacist’s services can be utilized to ensure perform clinical trials in the pediatric population.2,4 Compa- the patient is aware of risks associated with the medication. nies receive patent extensions regardless of whether or not the If an adverse event arises from off-label drug use, it is impor- pediatric information actually gets approved by the FDA for tant to report it to the FDA (via Medwatch) as well as the inclusion in the approved product labeling.15 manufacturer to further establish the adverse effect profile An additional ethical concern arising from off-label drug of the medication. use is reimbursement from third party payers. Some managed care organizations may deny coverage for off-label indications IMPORTANCE OF OFF-LABEL DRUG USE because they consider the use investigational or experimental.16 The clinician plays an important role in discovering off- Many state insurance programs, such as Medicaid, deny pay- label indications and reporting observations. The majority of ment for drugs used off-label. Denial occurs even though the new indications discovered for approved drug products are off-label drug use may be deemed appropriate.4,10 Some states made by practicing clinicians, rather than researchers involved may pay for the medication if the off-label indication is listed in in the initial drug development.3 A review evaluated the quan- a recognized drug reference as mentioned earlier, AHFS-DI or tity and initial discovery of new therapeutic uses for approved USP-DI.4,10 A population where this is a concern is in patients drug products. Of the new indications, with applications for undergoing cancer chemotherapy. Government programs, labeling inclusion submitted to the FDA, approximately 57% Medicare and Medicaid, are required to cover “medically ap- were discovered by clinicians practicing in the field.3 This reit- propriate” chemotherapy.16 These programs use the compendia erates the importance of continued drug development and system to determine if a use is medically appropriate, meaning evaluation for innovative therapeutic indications. that the indication must be listed in either AHFS-DI or USP- Discovering new uses for approved drug products, espe- DI.16 However, there are no coverage regulations for private cially in instances where there are limited treatment options, is health insurance companies. A private health insurer, such as an necessary. Innovation is also important in those populations Employee Retirement Income Security Act (ERISA) health that frequently receive medication off-label, including pediat- plan, which is self-funded, is not required to cover off-label drug ric patients, cancer patients, and human immunodeficiency uses, even for chemotherapy.16 A concern surrounding the de- virus (HIV) patients. Patients may want access to new treat- nial of payment is that patients may receive suboptimal care, ments as soon as possible, rather than wait for a drug to un- 64 MEDICINE & HEALTH/RHODE ISLAND dergo extensive clinical testing.10 Investigations into off-label drug usage will continue to advance drug utilization. It is im- portant to publish experiences with off-label drug use to en- hance the literature available for peers to review.

CONCLUSION Off-label prescription drug use is important for the ad- vancement of pharmacotherapeutic treatment options. The identification of additional uses of a medication may encour- age further studies of the drug product and/or disease state. The use of medications is not without risk; however, the more off-label information that is available to a clinician, the more likely the medication can be used safely in patients. Contin- ued evaluation of drug products in the future will only im- prove patient care, especially in those populations with limited therapeutic options.

REFERENCES 1. Blum RS. Legal considerations in off-label medication prescribing. Arch Intern Med 2002;162:1777-9. 2. Henry V. Off-label prescribing: legal implications. J Leg Med 1999;20:365- 83. 3. Conroy S. Unlicensed and off-label drug use. Paediatr Drugs 2002:4:353-9. 4. McEvoy GK, Snow EK, et al. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc. 2005. 5. O’Reilly J, Dalal A. Off-label or out of bounds? Ann Health Law 2003; 12:295- 324. 6. Committee on Drug. Unapproved uses of approved drugs: the physician, the package insert, and the food and drug administration. Pediatrics 1996;98:143- 5. 7. American Society of Health System Pharmacists. ASHP statement on the use of medications for unlabeled uses. Am J Hosp Pharm 1992;49:2006-8. 8. Academy of Managed Care Pharmacy. Off-label use of pharmaceuticals: re- vised. URL: http://www.amcp.org/pf.ark?c=legislative&sc=position&id=12 [accessed 2006 Sep 27]. 9. Boos J. Off label use- label off use. Ann Oncol 2003;14:1-5. 10. Landow L. Off-label use of approved drugs. Chest 1999;116:589-91. 11. American Pharmacists Association. 2004 House of Delegates: Report of the Policy Review Committee; p. 27-28. URL: http://www.aphanet.org/AM/ Template.cfm?Section=Search§ion=About_APhA1&template=/CM/ ContentDisplay.cfm&ContentFileID=224 [accessed 2006 Sep 27]. 12. Wilson CB. AMA testifies at senate drug safety hearing [testimony]. 2005 Mar 3. URL: http://ama.assn.org/ama/pub/category/print/14777.html [ac- cessed 2006 Sep 27]. 13. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office- based physicians. Arch Intern Med 2006;166:1021-6. 14. Benjamin DK, Smith PB, et al. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA 2006;296(:1266-73. 15. American Society of Clinical Oncology. Reimbursement for cancer treatment. J Clin Oncol 2006;24:3206-8. 16. DeMonaco HJ, Ali A, von Hippel E. The major role of clinicians in the discov- ery of off-label drug therapies. Pharmacotherapy 2006;26:323-32.

Andrea G. Dooley, PharmD, is a Primary Care Pharmacy Practice Resident, Department of Pharmacy, Veterans Affairs Medical Center.

CORRESPONDENCE: Andrea G. Dooley, PharmD Veterans Affairs Medical Center 830 Chalkstone Avenue Providence, RI 02908 phone: (401) 273.7100 x 2249 e-mail: [email protected]

65 VOLUME 90 NO. 2 FEBRUARY 2007 Physician’s Lexicon A Plethora of Pertinent Prefixes Prefixes play an important role in de- older word for encephalitis], phrenology herd named Syphilis, who ultimately was fining words used in a medical context. [the pseudoscience of interpreting a victim of what the poet called de morbo As they narrow the meaning of the root, person’s character by studying the con- Gallico, the French disease [an earlier de- they add character, direction and mag- tour and bumps of his head], schizophre- scription of syphilis.] nitude to the words to which they are ap- nia, phrenetic [sometimes spelled, fre- The Greek prefix, pan- or panto-, pended. Prefixes may begin with any let- netic] and frantic, originally meaning meaning all, appears in words such as ter of the alphabet from “a” [anti-] to “z” delerious. panacea [universal remedy], pandemic, [zymo-] but for no apparent reason a The Greek prefix, phen-, means de- pancreas [literally, all flesh], panegyric, great plurality of them begin with the rived from or pertaining to and is found pantheon, pantomime [literally, all imi- letter “p”; and most of these are of Greek in both common words such as pheno- tating] and pantothenate. origin. copy, phenobarbital and phenomenon Para-, a Greek prefix meaning be- Consider the prefix, poly-, [Greek, and obscure words such as phenology side, contrary to or abnormal, begins meaning, much or many]: English words [the study of the environment] and phen- such words as paracentesis [to pierce at with this prefix include such terms as acetin. the side], parachute [that which protects polygraph, polymer, polymorph, poly- Philo-, a Greek prefix meaning love from falling], paradox [contrary to be- dactyl, polymath and polygamy [and its of, may also serve as a suffix [as in Anglo- liefs], paragraph, parallel and paranoia. male-oriented partner, polyandry.] phile]. It is part of such words as philoso- The word, parasite, means a pathologic The Greek prefix, phren- , sometimes phy, philanderer, philanthropist and organism, literally a guest who eats food. refers to the diaphragm, sometimes to the syphilis [literally, a lover of pigs. The 16th The Greek root, sitos, meaning food is heart, but usually to the brain. It appears Century Italian physician-poet Girolamo seen in obscure words such as sitotoxin in such medical terms as phrenitis [an Fracastoro,wrote a poem about a shep- (continued on page 60)

RHODE ISLAND D EPARTMENT OF H EALTH VITAL STATISTICS DAVID GIFFORD, MD, MPH DIRECTOR OF H EALTH EDITED BY COLLEEN FONTANA, STATE REGISTRAR

Underlying Reporting Period Rhode Island Monthly February Cause of Death 12 Months Ending with February 2006 Vital Statistics Report 2006 Number (a) Number (a) Rates (b) YPLL (c) Provisional Occurrence Diseases of the Heart 213 2,765 258.5 4448.5 Malignant Neoplasms 176 2,297 214.7 6,324.0** Data from the Cerebrovascular Diseases 32 453 42.3 677.5 Division of Vital Records Injuries (Accidents/Suicide/Homicde) 35 434 40.6 6,722.0 COPD 37 489 45.7 407.5

Reporting Period (a) Cause of death statistics were derived from the underlying cause of death reported by Vital Events August 12 Months Ending with physicians on death certificates. 2006 August 2006 (b) Rates per 100,000 estimated population of Number Number Rates 1,069,725 Live Births 1,028 13,009 12.2* Deaths 794 9,807 9.2* (c) Years of Potential Life Lost (YPLL) Infant Deaths (2) (92) 7.1# Neonatal Deaths (2) (74) 5.7# Note: Totals represent vital events which occurred in Rhode Marriages 857 7,116 6.7* Island for the reporting periods listed above. Monthly pro- Divorces 262 3,127 2.9* visional totals should be analyzed with caution because the numbers may be small and subject to seasonal variation. Induced Terminations 394 4,783 367.7# Spontaneous Fetal Deaths 29 927 71.3# * Rates per 1,000 estimated population Under 20 weeks gestation (27) (877) 67.4# # Rates per 1,000 live births 20+ weeks gestation (2) (50) 3.8# ** Excludes 2 deaths of unknown age 66 MEDICINE & HEALTH/RHODE ISLAND advertisement

67 VOLUME 90 NO. 2 FEBRUARY 2007  

The Official Organ of the Rhode Island Medical Society

Issued Monthly under the direction of the Publications Committee

VOLUME 1 PER YEAR $2.00

  NUMBER 1PROVIDENCE, R.I., JANUARY, 1917 SINGLE COPY, 25 CENTS

NINETY YEARS AGO, FEBRUARY 1917 TWENTY-FIVE YEARS AGO, FEBRUARY 1982 Lucius F.C. Garvin, MD, in “Prevention of Disease,” drew “a Charles E. Millard, MD, President of the RI Medical Soci- logical analogy between the human body and the body politic.” ety, in “President’s Corner,” discussed “Cost Sharing is Termino- Specifically, he noted the value of “the public till” – a value that logical Legerdemain.” “Cost sharing and cost shifting are euphe- rose as land values rose, that a community could capture via taxa- misms which disguise the …fact that Medicare, Medicaid and tion, to pay for roads, schools, etc. He urged a tax on “land value,” Blue Cross do not pay full charges for hospital services in some calling it “nature’s law for public revenue.” cases, and in other cases do not pay any charges for services.” At Isaac Gerber, MD, in “Modern X-Ray Therapy,” praised the Rhode Island Hospital, an estimated 4-5% of the $50 million in improvements over the “old-time coil,” with its weak electrical en- annual costs for Medicare patients was not reimbursed. ergy and an unstable output of x-rays. In particular he praised the Kate Kiley MD, and L.R. Jenkyn, MD, in “Progress in Neu- Coolidge tube, the use of filters, and the adequate system of dosage. rology: Electrocardiograhic and Cardiac Enzyme Abnormalities An Editorial noted that “The Society for the Scientific Re- in Acute Cerebrovascular Disease,” presented a brief review of search and the Obliteration of Common Sense and Things Taught the literature. by Experience,” still exists. The Editorial told the tale of a man Mary Ann Passero, MD, Richard Frates, MD, and Don B. who was getting fat. “His story was soon told: a hearty breakfast, a Singer, MD, contributed “Clinical Pathological Conference: Res- ride to his office and close application to business for 10 hours, piratory Distress and Severe Cyanosis in a Full Term Neonate.” broken only by a few minutes for pie and milk, serving as a lunch, Peter P. Yu, MD, Deborah White, MD, and Edward A. a hurry home for a big dinner with an antiprandial cocktail and Iannuccilli, MD, FACP, in “The Mallory-Weiss Syndrome in the then an evening spent either at the office, in committee or church Pediatric Population,” urged physicians to consider this “rare con- work, or some of the inevitable banquets. Why was he getting fat? dition … in the presence of hematemesis.” Why was he short of breath?” His physician ordered blood pres- Tom J. Wachtel, MD, in “Thyrotoxic Subacute Thyroiditis sure tests, put him on a daily doses of medication: “He returned, Associated with Hepatitis,” noted that the “pathological relation- now with real symptoms.” More tests {“a tracing of his pulse,” a ship between the disorders is not clear.” Wasserman} followed, with more treatments. Eventually the pa- tient truly was sick.

FIFTY YEARS AGO, FEBRUARY 1957 In “Traumatic Neuromata of the Digital Nerves,” Stanley D. Simon, MD, and Carroll M. Silver, MD, described the technique they had used in 70 cases, with 2 failures. Robert R. Baldridge, MD, President, Providence Medical LEXICON Association, discussed “The Problem of the Foreign-Trained Phy- (continued from page 58) sician.” There were 595 medical schools worldwide. From 1941- [food poison] and sitophobia [a fear of food.] 1950, 18 foreign-medical gradates took the exam;16 passed. In The Greek prefix, peri- , appears in common words such 1955, 47 took the exam; 35 passed. Over the past five years RI as perimeter, pericellular, periphery, pericardium, periorbital, had licensed 159 foreign medical graduates via the exam, 128 peritonitis and perineum. via reciprocity. Half will remain in RI to practice. States’ require- Plia- is a prefix of Latin origin [plicare, meaning to fold] ments varied. Dr. Baldridge observed: “The listing of acceptable and appears in English words such as plica, duplicate, pliers foreign medical schools as a guide to state licensing bodies or to and pliable. hospitals has been largely disregarded in this state and through- Less common Greek prefixes beginning with the letter “p” out the country.” include parvi- [meaning small, in words such as parvicellular], Edwin Dunlop, MD, Assistant Medical Director, Fuller phono- [meaning sound, as in telephone], photo-, meaning light, Memorial Sanitarium, argued the benefits of the Funkenstein test as in words such as photograph. And poikilo- [meaning varied of the autonomic nervous system in “Selectivity of Treatment in or multicolored, in words such as poikilocytosis. Psychiatric Patients: 500 Autonomic Nerve Reactions.” And then there are still other prefixes beginning with “p”: An Editorial, “Atherosclerosis – The Price of Prosperity,” dis- pneumo-, pleuro-, pseudo-, pachy-, pedo- , paleo-, papillo-, partho-, cussed the “number one killer,” noting the perils of “hard fat” patho-, pecto-, pedi-, peno-, pento-, per-, picto-, pitheco-, pisci-, ingestion: “…just as the diabetic can lengthen his life by diet and plagio-, plano-, platin-, pluri-, pod-, pre-, post-, pro-, and countless insulin, so the aging population of our country, by a bit of selective others. dieting…can extend the expectancy of life…” – STANLEY M. ARONSON, MD 68 MEDICINE & HEALTH/RHODE ISLAND

integrity

whatdrivesyou?

Whatever it is that sustains you through the daily challenges of your profession, know that you have an ally in NORCAL.

(800) 652-1051 ● www.norcalmutual.com

Call RIMS Insurance Brokerage Corporation at (401) 272-1050 to purchase NORCAL coverage.