Transplantation

Volume 90 No. 3 March 2007

Transplantation

UNDER THE JOINT VOLUME 90 NO. 3 March 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 COMMENTARIES Quality Partners of Rhode Island 70 Summing Up Richard W. Besdine, MD, Chief Medical Officer Joseph H. Friedman, MD Rhode Island Medical Society 71 Euphemisms, Dysphemisms and Blasphemy Barry W. Wall, MD, President Stanley M. Aronson, MD EDITORIAL STAFF CONTRIBUTIONS Joseph H. Friedman, MD Editor-in-Chief SPECIAL ISSUE: TRANSPLANTATION Joan M. Retsinas, PhD Guest Editor: Paul Morrissey, MD Managing Editor 72 Solid Organ Transplantation – Overview Stanley M. Aronson, MD, MPH Kevin Tan, MD, and Paul Morrissey, MD Editor Emeritus 76 Transplantation at Rhode Island Hospital: A Decade of Commitment EDITORIAL BOARD Paul Morrissey, MD Stanley M. Aronson, MD, MPH Jay S. Buechner, PhD 78 Pediatric Renal Transplantation – Historic and Current Perspectives John J. Cronan, MD M. Khurram Faizan, MD, and Andrew S. Brem, MD James P. Crowley, MD 80 Immunosuppression Strategies In Kidney Transplantations Edward R. Feller, MD Angelito Yango, MD, and Amit Johnsingh, MD John P. Fulton, PhD Peter A. Hollmann, MD 84 Considerations for the Inpatient Care of Solid Organ Recipients Sharon L. Marable, MD, MPH Kevin M. Lowery, MD, and Reginald Y. Gohh, MD Anthony E. Mega, MD 89 Is There a Rational Solution to the Kidney Shortage? Marguerite A. Neill, MD Frank J. Schaberg, Jr., MD Anthony P. Monaco, MD Lawrence W. Vernaglia, JD, MPH 91 The National Organ Transplantation Breakthrough Collaborative – Newell E. Warde, PhD A Rhode Island Hospital Perspective OFFICERS Kevin M. Dushay, MD, FCCP, and Suzanne Duni Walker, Esq, RN, BSN Barry W. Wall, MD President COLUMNS K. Nicholas Tsiongas, MD, MPH 94 GERIATRICS FOR THE PRACTICING PHYSICIAN – The Assessment and Management of President-Elect Falls Among Older Adults Living In the Community Diane R. Siedlecki, MD Michael P. Gerardo, DO Vice President Margaret A. Sun, MD 96 HEALTH BY NUMBERS – Classification of Emergency Department Visits: How Many Secretary Are Necessary? Mark S. Ridlen, MD Jay S. Buechner, PhD, and Karen A. Williams, MPH Treasurer Kathleen Fitzgerald, MD 98 PUBLIC HEALTH B RIEFING – Bloodborne Pathogen Transmission Potential From Immediate Past President Neurological Pinwheels Robert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian DISTRICT & COUNTY PRESIDENTS Geoffrey R. Hamilton, MD 100 LETTERS TO THE EDITOR Bristol County Medical Society 101 IMAGES IN MEDICINE – Post-transplant Lymphoproliferative Disorder Following Herbert J. Brennan, DO Renal Transplant Kent County Medical Society Courtney A. Woodfield, MD Rafael E. Padilla, MD Pawtucket Medical Association 102 PHYSICIAN’S LEXICON – The Vocabulary of Paralysis in Anglo-Saxon England Patrick J. Sweeney, MD, MPH, PhD James T. McIlwain, MD Providence Medical Association 102 Vital Statistics Nitin S. Damle, MD Washington County Medical Society 104 March Heritage Jacques L. Bonnet-Eymard, MD Woonsocket District Medical Society This issue is being mailed to selected physicians who are not members of Cover: “After Life,” 17-inch wooden box, com- the Rhode Island Medical Society. The expanded mailing has been made posed of mixed media mish-mash of materials, possible by a grant from the Ultimate Gift Fund, Transplant Services, Rhode by Melissa Ferreira, a Providence artist who Island Hospital. teaches part-time in the IllustrationDepartment at Rhode Island School of Design. “When not making commissioned pieces for clients, I create Medicine and Health/Rhode Island (USPS 464-820), a monthly publication, is owned and published by the Rhode Island Medical Society, 235 objects and images that interpret these spectacu- 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 lar human bodies of ours—inside and out— Medical Society, unless clearly specified. Advertisements do not imply sponsorship or endorsement by the Rhode Island Medical Society. Periodicals postage but in ways that resemble physiological models paid at Providence, Rhode Island. ISSN 1086-5462. POSTMASTER: Send address changes to Medicine and Health/Rhode Island, 235 Promenade St., from the Middle Ages rather than the informed Suite 500, Providence, RI 02908. Classified Information: RI Medical Journal Marketing Department, P.O. Box 91055, Johnston, RI 02919, imaging we have today.” www.melissaferreira.net. phone: (401) 383-4711, fax: (401) 383-4477, e-mail: [email protected]. Production/Layout Design: John Teehan, e-mail: [email protected]. 69 VOLUME 90 NO. 3 MARCH 2007 Commentaries

Summing Up

This is the 99th column that I’ve written the medical journal. Nor has any student in-chief of any journal, let alone the state for Medicine & Health/Rhode Island, and every quoted or asked about an article. journal of a very small place, I’d receive I hope to keep supplying them, one per Aside from writing my column, what some “respect.” But no. Even junior month. It might seem that a summing do I do? Mainly two things. The most people ignore me. I used to think that up would be better suited for the 100th important is to recruit guest editors. Most bad manners in doctors was a uniquely column, or when I retire from this posi- of our issues are devoted to single topics Harvard quality, but Brown doctors, per- tion; however, I’ve always written an (e.g., autism, brain stimulation, atrial fi- haps believing this is a desirable Ivy “April fool’s” column, which will be the brillation, etc). I therefore need to think League tradition, confusing bad manners 100th, making a serious venture inoppor- of topics that I believe will be of interest with eminence, seem to be emulating tune, and I’m not planning on stepping to most of our readers. I then try to find their more famous colleagues. I recently down from this position for a while yet. someone in the medical community who received several manuscripts from authors Since being editor-in-chief of this jour- can pull together enough authors cover- who clearly had never even scanned the nal is not the most highly sought after ing enough topics to make a full issue journal and had no idea of what articles position, it is unlikely that I will be forced possible. I try, whenever possible, to high- in the journal should look like, another from the job by an unexpected palace light an area that Rhode Islanders excel form of disrespect. But for people who intrigue. What “palace?” What sort of an in, but for which we may not be known. do read the journal it appears to be get- “intrigue?” Sometimes a new service comes to Rhode ting more favorable reviews. And the This journal is a small venture. It is Island but local doctors, unaware, con- Medical Society is happy with its mem- sent to the thousand plus members of the tinue sending their patients to Boston or bers’ feedback. RIMS and is given free to all Brown elsewhere, not knowing that the service We endeavor to “advertise” local ac- medical students. Some medical libraries is readily available here. The authors are tivities. We have a policy of publishing subscribe, because they have contractual generally located in RI or have recently book reviews of every book with a RI arrangements with other libraries in their moved from Rhode Island and are col- author, if the book is brought to our at- collaborative “systems” to subscribe to all laborating with Rhode Islanders. Some- tention. Almost none have been. We wel- designated journals. The contents of our times I ask someone to review recent ad- come purveyors of new tests, new treat- journal are included in Index Medicus vances, with reference to services avail- ments or new ideas to write scholarly ar- and therefore in Pub Med, so all the ar- able in RI, in a discipline, such as cardi- ticles to educate the community, and ticles show up in literature searches. ology, urology or radiology. make their own expertise known. We The journal’s work is done almost We receive some unsolicited mate- welcome letters to the editor. We have entirely by the managing editor, Joan rial, but not a lot. We encourage these. published few because we haven’t re- Retsinas, and myself. Stan Aronson, The journal is a good venue for fellows, ceived many. Brown Medical School’s founding dean residents and students to begin their pub- Our goal is to keep our local doc- and editor-in-chief emeritus of this jour- lishing careers. Our turn-around time is tors informed about what’s going on in nal, writes a monthly column related to unrivaled, and the chances for publica- Rhode Island. We aim to encourage medicine in history, a half column on the tion are higher than in national journals. young doctors to make observations and etymology of medical terminology, and When I began to edit the journal, Dr. then publish them. A scholarly medical edits my columns. The editors are unpaid. Aronson, who had been editor for over group raises community standards. The The journal is subsidized by the ten prior years, told me that he would trip to Boston is not too long, but it’s not RIMS, the RI Department of Health, define me as successful when I was able easy and parking’s worse. Our goal is to Brown Medical School and the RI Qual- to reject a submission as unworthy. That help our community make that trip un- ity Partners. In a recent survey of RIMS hurdle was crossed long ago. However, necessary. members, the journal received a surpris- in the case of student and trainee sub- ing recognition as being one of several missions, we try to work with the authors – JOSEPH H. FRIEDMAN, MD aspects of the medical society that they to improve the article sufficiently to merit liked. It is not clear if Brown medical stu- publication. Generally this is possible. dents share that enthusiasm, as they’ve not It may not seem so difficult to get been surveyed. Having taught Brown this done. And generally it’s not, but it is medical students for many years, I can a never-ending surprise how often doc- state that no student ever asked me if I tors will not return phone calls, e-mails was the same Joseph Friedman who edits or even letters. You’d think that as editor- 70 MEDICINE & HEALTH/RHODE ISLAND Euphemisms, Dysphemisms and Blasphemy

Politeness often impels us to choose a congenial synonym In terms of governmental activities, for example, state mur- when a more accurate term, sometimes vulgar, might offend the der is called “capital punishment” or “judicially sanctioned ex- listener. Thus we may perspire rather than sweat, call a funeral ecution”; neither of these semantic alternatives, of course, lessens director a grief therapist, call a military retreat a tactical deploy- the end-result of the action. If, in reporting deaths due to mili- ment or refer to a recently deceased individual as the dearly de- tary action, the word “kill” seems offensive, there are more be- parted rather than one who has kicked the bucket, bought the nign substitutes such as “neutralize,” “pacify,” “victim of collat- farm or assumed room temperature. eral action” or “ one who is terminated with prejudice.” The Greeks had a word for such a benevolent transforma- Many figures of speech modify the character and endur- tion: euphemos, meaning a good word; in English, euphemism. ance of the message: such methods as irony, understatement, [And blasphemy to define its opposite.] The English language is metaphor, allegory, hyperbole [often employed in advertising or now thoroughly saturated with relaxing, socially sanctioned as an inflation of job-titles], periphrasis, word deformation [sub- phrases to temper the harshness of reality by employing circum- stituting a modified word such as “darn” instead of “damn”] all locution instead of brevity, clarity and directness. Given the gen- in the interests of degrading truth as an option rather than a erous plasticity of our language, unreality may now be cloaked requirement. in the guise of reality and madness with the aura of sanity. Graf- Consider, for example, a recent story from the Maine De- fiti, for example, has been called authentic, socially-relevant art, partment of Health and Human Resources. During the 2000 – garbage dumps are referred to as sanitary landfills, nuclear bombs 2004 interval, there were 22,516 automobile accidents on the renamed as radiation enhancement devices and homeland resi- Maine roads involving feral animals; and 3,400 of these were dents are now called natives, indigenous nationals or aborigines, motor vehicle collisions with moose. These collisions resulted in depending upon the degree to which they have been colonized. 1,583 injuries to humans and 17 deaths. The moose casualty Dysphemism, the antonym of euphemism, defines verbiage rate, of course, was substantially higher. Most of these accidents that is intentionally and unduly offensive rather than merely took place after dark, particularly during the moose mating sea- quaintly descriptive or quietly obfuscating. Dysphemic terms are son of September and October. particularly employed in sports journalism where, for example, The Maine Department of Motor Vehicles has recently the losing team may be annihilated, trounced or slaughtered undertaken a number of measures to lessen this problem. First, but rarely just defeated. by clearing much of the underbrush lining the highways and Euphemisms, when consciously used to conceal the truth, thus improving driver vision, particularly at night. Second, by are now called doublespeak as a silent homage to George Orwell’s placing road signs where there have been frequent moose-ve- newspeak and doublethink. Nor is doublespeak confined to the hicle collisions, under the presumption that either the drivers or vocabulary of used car salesmen [when used cars are called pre- the moose are literate. And third, by moose herd management. owned vehicles] or real estate agents who now rename down [The Department defines “herd management” as the increased payments as “initial investments” and “rural settings” to hide long issuance of moose-hunting permits, by state sanction, in those driveways that require snow plowing in the winter. state areas with the highest frequencies of moose-vehicle colli- Some euphemisms can bring humor into the choice of ac- sions.] ceptable synonyms. Fishermen off the coast of New England have It is comforting to know that the estimated 29,000 moose sometimes been call “cod fathers,” a cowboy in the Midwest may of Maine are not mindlessly slaughtered, savagely hunted down jokingly be renamed as a “bovine attendant,” those who steal or indiscriminately struck by motor vehicles but are having their books from college libraries are identified, in Freudian English, numbers scientifically diminished through “herd management.” as “victims of bibliomania” and a botanical garden may be la- Mercy and the art of bureaucratic euphemisms are not dead. beled as “plant parenthood.” Euphemisms are standard props in the language of govern- – STANLEY M. ARONSON, MD ment, the military, certainly newspaper columns and the domains of sex and bodily functions [it is a sad day for spontaneous love when foreplay is paraphrased as an “antecedent to interpersonal transaction.”] The National Committee on Public Doublespeak, headed by Professor William Lambdin, has found such euphemisms as “escalated interpersonal altercation” for domestic mur- der, “plural relations” for the apartheid activities in South Africa, “personal flotation device” for a life-saver and “involuntarily lei- sured” for the unemployed.

71 VOLUME 90 NO. 3 MARCH 2007 Solid Organ Transplation – Overview Kevin Tan, MD, and Paul Morrissey, MD

Solid organ transplantation is the treatment National Organ Transplant Act (NOTA), organ donation are discussed in a sepa- of choice for many patients with end- to be operated by a private, non-profit rate chapter in this issue. stage organ failure from a wide variety of organization under federal contract. causes. This area of medicine has ad- UNOS was awarded the OPTN contract ORGAN DONATION vanced over the last 50 years, improving to administer the OPTN under contract The practice and terminology of or- patient survival and quality of life. The with the Health Resources and Services gan donation have changed over the de- main problem today is not allograft re- Administration of the US Department cades. The term “organ harvest” was rejection or infectious complications after of Health and Human Services (HHS). placed by “organ procurement” and most transplantation, but the limited supply of The primary goals of the OPTN are to recently by “organ recovery.” In the early organs that prohibits broader application (1) ensure the effectiveness, efficiency and days of transplantation asystolic deceased of this therapy. (Figure 1, Table 1) De- equity of organ sharing and (2) increase donors were the primary source of organs. spite an ever-increasing number of trans- the supply of donated organs available for The concept of brain death arose in plants performed yearly, the waiting list transplantation. The national waiting list 1968, first as a medical definition arrived outpaces the modest incremental im- was 25% greater than the number of at by a Harvard colloquium and later as provements in deceased organ donation. transplants recorded in 1988 and more the legal equivalent of death. Through The United Network for Organ than 50% greater by 1994. The tre- the early 1990s brain dead donors were Transplant (UNOS) tracks transplanta- mendous clinical success of transplanta- primarily standard criteria donors tion statistics in the United States under tion has created disparity in the number (young, previously healthy with good or- contract from the federal government.1 of patients waiting for transplantation gan function). As the gap between the The Organ Procurement and Transplan- and the availability of organs for trans- supply and demand for organs grew, the tation Network (OPTN) is the unified plant. In November 2006, there were margins of acceptability were extended transplant network established by the over 93,000 listed candidates for organ to include donors with reduced function United States Congress under the 1984 transplant. UNOS’s efforts to improve and high-risk characteristics (prisoners, history of drug use, and history of cancer, e.g.); so called marginal and expanded criteria donors (older, depressed organ function). Recently there has been a re-emergence of cardiopulmonary ar- rested donors, referred to as donation after cardiac death (DCD). Today these donors, all with severe irreversible brain injury, undergo end-of-life standard practices (extubation, discontinuation of IV fluids and vasopressors) with recovery of organs (usually kidneys and liver) after a five-minute documentation of ces- sation of cardiopulmonary function. At Rhode Island Hospital, 55 kidney trans- Figure 1. Solid Organ Transplantations Performed in the United States versus plants have been performed from DCD Growth of the Transplant Waiting List (all organs) donors. The vast majority of solid organs are procured from deceased donors with in- tact circulation and a clinical diagnosis of brain death. These donors have either died from traumatic brain injury, cerebrovascular accidents or secondary CNS injury (e.g., anoxia). Since 1988, the number of donors who died from motor vehicle collision or gunshot wound has steadily declined while the number of donors who died from primary central nervous events has increased.2 The rea- sons for this include improved identifi- 72 MEDICINE & HEALTH/RHODE ISLAND cation and referral of older donors, in- cold ischemic time. These data also proved pects of patient care were poorly under- creased acceptance of older donors by that HLA matching is of minor significance. stood; and most patients died within a transplant units, and improved automo- Indeed only five criteria are essential for few weeks of surgery. The initial enthu- bile and handgun safety in the United successful live donor transplantation: (1) siasm of the cardiac surgery community States. There are in fact fewer young overall good health, (2) normal renal func- was tempered by the familiar nemeses of donors available than in years past rather tion, (3) ABO compatibility, (4) HLA transplantation - rejection and infection. than donors being overlooked or fami- (crossmatch) compatibility, and (5) a will- In the ensuing decade approximately 20- lies refusing consent at higher rates lim- ing donor free of undue coercion. For fur- 30 heart transplant operations were per- iting access to such donors.3 ther information potential donors may re- formed annually, one-third of them at The transplant community in the fer to http://www.lifespan.org/rih/services/ Stanford University. Long-term survivors United States has embraced living dona- transplant/donor/. were rare. Only 35% of cardiac trans- tion as a source of organs.1 Worldwide plant recipients survived 3 months.4 This practices vary greatly with nearly all kid- OUTCOMES OF TRANSPLANTS changed with the introduction of neys transplanted in Japan and Korea Initially patient survival was poor; cyclosporine in the early 1980s. The coming from live donors, a distinct mi- however there were few medical alterna- greater specificity of this agent controlled nority of kidneys from live donors in Eu- tives. The technology of dialysis was ru- acute rejection with fewer morbid side rope and an increasing number of kid- dimentary, and most patients faired effects than prednisone. Favorable re- neys (now over 40%) of kidneys from liv- poorly. The early experience with car- sults were rapidly achieved for kidney, ing donors in the United States. In 2001, diac transplantation illustrates this point. liver, heart and pancreas transplantation. for the first time ever, the number of liv- Following the publicity of the first suc- Both short term and long term survival ing donors in the United States (6607) cessful heart transplant in South Africa rates improved. According to the 2005 exceeded the number of deceased donors and the first successful heart transplant OPTN/SRTR report, one-year survival (6100). Living donors may be related or in the United States one month later un- was highest for kidneys and pancreas re- unrelated to the recipient. Unrelated der the direction of Norman Shumway cipients, which ranged from 94.6 to donors include spouses, distant relatives, at Stanford, surgeons performed 167 97.9%. One-year and five-year survivals friends, co-workers and altruistic strang- cardiac transplant procedures at 58 cen- are impressively high. (Tables 2 and 3) ers. The number of organs procured ters over the next two years. While the Graft survival rates are generally from living donors has plateaued in re- technical aspects of cardiac transplanta- lower than patient survival rates because cent years. Live donors primarily donate tion were within the capabilities of many patients may receive a second transplant a kidney (6647 in 2004), but also include surgeons, clinical and immunological as- or be supported by an alternative therapy liver (323), partial lung (24) and infre- quently intestine (6) or pancreas (2) donors. Just over 40 % of transplanted kidneys nationwide come from living donors. Com- pared to deceased kidneys, kidneys from living donors demonstrate superior long- term outcomes. (Tables 2 and 3) The observation that the results for living unrelated kidney donors were equivalent to living-related (and more closely HLA matched) revolutionized the field. The most common living unrelated kidney donor is a spouse; more commonly a wife as men outnumber women with end-stage renal disease and women make up a disproportion- ate percentage of altruistic donors. Inter- estingly, this analysis showed that the rate of graft survival at 3 years was higher for kidneys from spousal donors than for deceased transplants (85% versus 70%) despite a greater degree of HLA mismatch- ing. The improved function of kidneys from living unrelated donors compared with deceased donors is attributed to improved organ quality, reduced ischemia- reperfusion injury, the absence of systemic aberrations due to brain death and reduced 73 VOLUME 90 NO. 3 MARCH 2007 (dialysis). Of note, five-year patient sur- transplant is the need for immunosup- cohol. The proportion of active patients vival is considerably better than allograft pression, considered by most an unaccept- on the waiting list with non-cholestatic survival for kidney recipients, highlight- able trade-off with the need for chronic chronic liver disease has been increasing. ing two important points: first, in the insulin therapy. Therefore, pancreas In 1995, 65% of patients waiting for event of loss of allograft function patients transplantation is performed in diabetic liver transplantation had cirrhosis second- may return to dialysis; second, one-half patients with kidney failure who are can- ary to a non-cholestatic liver disease. In of all allografts are lost to chronic allograft didates for a kidney transplant and will 2004, this had increased to 72% prima- nephropathy (formerly termed chronic require immunosuppressive drug to pre- rily driven by patients with HCV (40% rejection) with the recipient considerably vent kidney rejection. The options for of all listed patients). In 2004, cholestatic outliving the functional allograft. Nota- pancreas transplant are (1) deceased do- liver disease (sclerosing cholangitis, pri- bly, 15% of the patients waiting for a kid- nor, simultaneous pancreas-kidney trans- mary biliary cirrhosis), acute hepatic ne- ney transplant have already lost one pre- plant (SPK), (2) living donor kidney crosis, biliary atresia, and metabolic liver vious kidney. Kidneys transplanted from transplant, followed by a deceased donor disorders accounted for 11%, 4.5%, a live donor source result in superior long- pancreas transplant and far less com- 1.7%, and 1.5% of patients on the ac- term function. (Table 3) monly (3) a pancreas transplant alone tive liver transplant waiting list, respec- (PTA). tively. KIDNEY TRANSPLANTATION In the United States there are over Transplantation is the treatment of …15% of the 120 centers performing liver transplan- choice for patient with end-stage renal tation, including eight in New England disease (ESRD), providing longer sur- patients waiting for (Hartford Hospital, UMMC, Yale, vival, superior quality of life and reduced a kidney Lahey and four centers in Boston). Ap- medical expenses compared with dialy- proximately 8-12 people from Rhode Is- sis. There are very few absolute transplanted have land receive a liver transplant each year. contraindications to kidney transplant, already lost one Given the proximity to other centers our therefore most patients younger than age administrators and we have not pursued 60 and many under the age of 70 with previous kidney. liver transplantation at Rhode Island ESRD should be considered for trans- Hospital. Such a pursuit would require plant evaluation. Nevertheless, only one LIVER TRANSPLANT enormous resources including more ICU of every six patients with ESRD is on the Liver transplant is the treatment of beds, specialists in hepatology and pa- waiting list for a kidney transplant. Most choice for patient with acute fulminant thology and dedicated teams in anesthe- are excluded because of advanced age and chronic liver failure. Patient survival siology and nursing. It appears that the and prohibitive co-morbid medical con- at one year posttransplant has increased number of liver transplants would be in- ditions. The survival advantage after from 30% in the early 1980s to more sufficient to maintain satisfactory skills for transplant compared with continued di- than 80% at present. This has led to an optimal transplant care. alysis has been shown for all age groups increase in number of liver transplants and all causes of ESRD; the greatest ad- performed (approximately 2000 in THORACIC ORGAN TRANSPLANTATION vantage is for diabetic patients.5 Allograft 1990, 4000 in 1997 and over 6000 last Heart transplantation is generally survival for deceased donor and living year). In 2005, 6443 liver transplants performed in patients with life expect- donor transplants averages 65 and 80% were performed among over 16,000 ancy less than one year. From 1995 to at 5 years and 45 and 65% at 10 years, people on the waiting list. Most of this 2004, the number of patients on the respectively. growth was achieved through the more heart waiting list declined, primarily a aggressive pursuit and recovery of de- reflection of the decline in the percent- PANCREAS TRANSPLANTATION ceased donor organs with a lesser contri- age of transplant candidates with a coro- Successful pancreas transplant re- bution (about 5%) from living donors. nary artery disease classification. This may sults in insulin independence and Live liver donors include left lateral seg- reflect better outcomes resulting from euglycemia, as well as the halt of progres- mentectomy in parent-to-child transplan- improvements in medical, interventional, sion in diabetic retinopathy, neuropathy tation and right hepatectomy for adult- and surgical treatments for coronary dis- and notable improvements in to-adult liver transplantation (AALT). ease. The number of heart donors has gastroparesis. Most importantly, pancreas The donor mortality for AALT (0.5-1.0 remained stable over recent years, with transplantation substantially enhances the %) introduced appropriate caution in approximately 2000-2200 heart trans- patient’s quality of life and obviates the adopting this procedure; there were 519 plants performed annually, of which 20% need for glucose monitoring and insulin living liver segment donors in 2001, how- are in children. The most common cause administration. In accomplishing ever there have been only 330 on aver- is ischemic or dilated cardiomyopathy, euglycemia, pancreas transplantation age in the past five years.2 follow by valvular disease and congenital becomes the optimal therapy for dia- The leading indication for liver heart disease. Lung transplantation is betic, ESRD patients with hypoglycemic transplant is cirrhosis caused by non- newer field than heart transplantation. unawareness. cholestatic liver disease, primarily due to Currently, chronic obstructive pulmo- The major drawback for pancreas chronic hepatitis C virus (HCV) and al- nary disease (COPD) is the most com- 74 MEDICINE & HEALTH/RHODE ISLAND mon indication, followed by pulmonary THE ECONOMICS OF CONCLUSION fibrosis, cystic fibrosis, primary pulmo- TRANSPLANTATION This overview demonstrates that the nary hypertension and alpha-1 antit- Funding sources for organ trans- field of transplantation continues to im- rypsin deficiency. There are three major plantation include private health insur- prove as a surgical (technical) and medi- approaches: single-lung, bilateral sequen- ance, Medicare, Medicaid and the Vet- cal discipline. Improvements in the pre- tial lung transplant and transplantation erans Administration system. Additional and post-transplant care of patients with of lobes from living donors (less than 25 funding is available through charitable organ failure and the continued progress cases annually). For six consecutive years, organizations, advocacy groups, and pre- in immunosuppression make this one of the number of patients on the active wait- scription drug assistance programs. The the most exciting areas in clinical medi- ing list for a heart-lung transplant has latter includes programs established by cine. Undoubtedly, improvements will decreased, from a high of 179 patients private drug companies and a variety of continue in this “new” field, which cel- in 1998 to only 83 in 2004. Most wait- state-funded initiatives. Residents of ebrated its 50th anniversary in 2004.7 ing list patients for heart-lung transplan- Rhode Island for at least one year prior tation (81%) were adults older than 18 to the date of the transplant operation REFERENCES years. The most common diagnoses were and with a household income less than 1. Organ Procurement and Transplantation Network. congenital heart disease (35%), primary $66,309.82 are eligible for monies www.optn.org. Accessed November 20, 2006. 2. 2005 OPTN/SRTR report. www.ustransplant.org. pulmonary hypertension (18%), and cys- through the Rhode Island Organ Trans- Accessed November 20, 2006. tic fibrosis. plant Fund. After the recipient’s insurer 3. Hauptman PJ, O’Connor KJ. Procurement and has made payment, any remaining costs allocation of solid organs for transplantation. INTESTINAL TRANSPLANT are considered for reimbursement. NEJM 1997; 336: 422. 4. Pennock JL, Oyer PE, et al. Cardiac transplanta- Intestinal transplantation is the least Organ transplantation costs, on av- tion in perspective for the future. J Thorac frequently performed solid organ trans- erage, $250,000 for liver, $150,000 for Cardiovasc Surg 1982; 83:168. plant and associated with the highest re- heart and $80,000 for kidney (deceased 5. Wolfe RA, Ashby VB, et al. Comparison of mortality in all patients on dialysis. NEJM 1999; 341: jection rates and lowest graft survival. It or live donor). Obtaining health insur- 1725. is reserved for patient with poor intesti- ance is a prerequisite for patients with 6. Guidelines for referral and management of pa- nal function who cannot be maintained organ failure. Insurance coverage is not tients eligible for solid organ transplantation. on parenteral nutrition (TPN), or those available to undocumented aliens and Transplantation 2001; 71: 1189. 7. Sayegh MH, Carpenter CB. Transplantation 50 with TPN-associated complications, in- organ transplantation is denied unless the years later—progress, challenges, and promises. cluding hepatic dysfunction. There is individual can cover the cost of transplan- NEJM 2004; 351: 2761. evidence that the majority of patients tation or the money is raised thorough with progressive organ failure are re- charitable appeals. Kevin Tan, MD, is a resident in sur- ferred to transplant centers at a later Kidney transplantation is more cost- gery, Rhode Island Hospital. stage of their disease. As a result the effective than hemodialysis for the Medi- Paul Morrissey, MD, is Associate Pro- Clinical Practice Committee of the care program. The initially higher costs of fessor of Surgery, Brown Medical School, American Society of Transplantation has transplantation are fully recouped by and Division of Organ Transplantation, made the following recommendations: Medicare within three years after surgery. Rhode Island Hospital. (1) early referral to a transplant center Unfortunately, Medicare coverage for for patients with organ insufficiency, (2) immunosuppressants ends 36 months af- CORRESPONDENCE: close cooperation with the primary care ter transplantation. At that time patients Paul Morrissey, MD doctor regarding follow-up and appro- must obtain private insurance, qualify for Rhode Island Hospital APC 921 priate referral to the transplant center Medicaid or enter patient assistance pro- 593 Eddy Street with disease progression and (3) regu- grams to obtain funds for transplant im- Providence RI 02903 lar communication about any changes munosuppression; the yearly cost ranges phone: 401-444-5285 in the condition of patient that affect from $2000 – $12,000. E-mail: [email protected] eligibility for transplantation.6 The Medicaid Program requires Transplantation of the intestine, ei- states to cover “categorically needy indi- ther isolated or in combination with other viduals,” which typically includes low- abdominal organs, is being performed income families with children and preg- with increasing success. The number of nant women. A second category, Medi- patients who received a small intestine cally Needy, allows one to subtract medi- transplant has gradually increased over cal expenses from income. A “spend the past 10 years from 46 in 1995 to 152 down” is the process of using medical in 2004. In 2004, 443 patients were expenses to reduce income to the level alive with a functioning intestine graft. that qualifies for Medicaid. Through These numbers point to the need for these mechanisms the majority of people highly specialized care for these complex with end-stage organ failure obtain cov- patients. erage for transplantation.

75 VOLUME 90 NO. 3 MARCH 2007 Transplantation at Rhode Island Hospital: A Decade of Commitment Paul Morrissey, MD Kidney transplantation for residents of the first living related transplant was un- land; often we also recover the liver and Rhode Island has a long and interesting dertaken. I joined the program at that pancreas for use within the region or na- history. After training at the Peter Bent time and since then we have expanded to tionally. Rhode Island Hospital was the Brigham, Joseph Chazan, MD, opened include specialists in infectious disease, psy- fourth center in New England to adopt a the first dialysis unit in Rhode Island in chiatry, social work, pharmacology, nutri- policy for donation after cardiac death 1970. The unit was established at the tion and research programs. Since 2004, (kidney recovery after withdrawal of me- Rhode Island Hospital and shortly there- the Transplant Team includes 9 physicians, chanical ventilation in patients with dev- after the first freestanding unit was opened 5 nurses, 7 allied health care professionals astating head injury) and such donors have in the “six corners” location in East Provi- and 5 office assistants. Transplant volume provided a valuable source of kidneys dence. Shortly thereafter a transplant unit is shown in Figure 1. (n=63) for transplantation. was established at the Miriam Hospital. Just over 45 % (296/640) of trans- Robert Hopkins performed six kidney ORGAN DONATION AND THE LOCAL planted kidneys at Rhode Island Hospital transplants between 1973 and 1975. The WAITING LIST come from living donors. Most are from program closed thereafter. For the next 21 As the only Level 1 Trauma Center relatives. The most common living unre- years patients were referred to transplant in the state, Rhode Island Hospital is the lated kidney donor is a friend (n=35), fol- centers in Boston and Connecticut for predominant site for deceased organ do- lowed by a spouse or fiancé (34); more transplantation. Tony Monaco, MD, at nation. In the past 10 years, 239 kidneys commonly a wife (22) as men outnumber the New England Deaconess Hospital, were recovered at Rhode Island Hospital, women with end-stage renal disease and transplanted the majority of Rhode Island- compared with 14 at Kent, 8 at Roger Wil- women always make up a disproportion- ers with end-stage renal disease. With the liams and 4 each at Miriam and Newport ate percentage of living donors. In 1999, encouragement of Joseph Chazan in the Hospitals. These stark differences are re- our program became one of the first in community and the assistance of Peter lated to differing patient populations with the country to accept a stranger King, MD, Lance Dworkin, MD, and conditions that result in organ donor po- (nondirected, altruistic) donor. We now Kirby Bland, MD, then Chief of Surgery, tential – trauma, cerebrovascular accidents boast, on behalf of our generous donors, a transplant program was established at and other causes of irreversible brain in- the second largest reported series of Good the Rhode Island Hospital in 1996. The jury or brain death. The majority of kid- Samaritan and nondirected donors (22) program was first a satellite of the NEDH neys recovered in Rhode Island are trans- in the United States. 1 The University of with Reg Gohh, MD, serving as medical planted within the state as allocation in Minnesota has the most (around 40). director and Bette Hopkins, RN, as Trans- New England is heavily biased toward ge- With these strong efforts in living plant Coordinator. Pre- and post-trans- ography. Rhode Island Hospital is consis- and deceased donor organ donation, the plant patients from Rhode Island were tently a leader in deceased organ dona- latter elaborated in greater detail by Kevin cared for at the clinic. In March 1997, tion in the region. (Table 1) Our surgical Dushay, MD, in an accompanying ar- the first transplants were performed from group is assigned primary responsibility for ticle, the wait-list for kidney transplanta- a deceased donor in Rhode Island; in June kidney recovery throughout Rhode Is- tion in Rhode Island is shorter than at Yale and the Boston programs. Even so, we have a crucial need. Rhode Island patients on the active UNOS wait list include: kidney (128), pancreas (22), liver (92), heart (18) and lung (12).

76 MEDICINE & HEALTH/RHODE ISLAND PANCREAS REFERENCES TRANSPLANTATION 1. Morrissey PE, Dube C, et al. Good Samaritan Successful pancreas kidney donation. Transplantation 2005; 80: 1369. transplant results in in- 2. Morrissey PE, Yango A. Renal transplantation: sulin independence and older recipients and donors. Clin Geriatr Med substantially enhances 2006; 22: 687. the patient’s quality of 3. Morrissey PE, Flynn M, Lin S. Medication noncompliance and its implications in transplant re- life. Therefore, pancreas cipients. Drugs 2007; in press. transplantation is the 4. Reddy KS, Stablein D, et al. Long-term survival optimal therapy for dia- following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in IDNEY RANSPLANTATION K T betic, ESRD patients with hypoglycemic patients with type 1 diabetes mellitus and renal Transplantation is the treatment of unawareness. For many patients with dia- failure. Am J Kidney Dis 2003; 41: 464. choice for patients with end-stage renal betes and renal failure the opportunity for disease (ESRD), providing better patient deceased donor kidney-pancreas will pro- Paul Morrissey, MD, is Associate Pro- survival, superior quality of life and re- vide optimal survival and quality of life.4 fessor of Surgery, Brown Medical School, and duced medical expenses compared with The options for pancreas transplant are Division of Organ Transplantation, Rhode dialysis. There are very few absolute deceased donor, simultaneous pancreas- Island Hospital. contraindications to kidney transplant, kidney transplant (SPK) and living donor therefore most patients younger than age kidney transplant; followed by deceased do- CORRESPONDENCE: 60 and many under the age of 70 with nor pancreas transplant—pancreas after Paul Morrissey, MD ESRD should be considered for trans- kidney (PAK) transplantation. To date, 24 Rhode Island Hospital APC 921 plant evaluation. In fact, only one of ev- patients with ESRD and diabetes have re- 593 Eddy Street ery six patients with ESRD is on the wait- ceived a pancreas transplant (19 PAK, 5 Providence RI 02903 ing list for a kidney transplant (153 pa- SPK) since 2002. With a mean follow-up Phone: (401) tients of 950 on chronic dialysis in Rhode of 30 months, 23 patients are alive with a E-mail: [email protected] Island). Most are excluded because of functioning kidney and 15 (62%) are in- advanced age and prohibitive co-morbid sulin-free. As islet cell transplantation, conditions. xenotransplantation and optimal insulin Kidney allograft survival rates are pump technologies continue to require re- lower than patient survival as recipients finement, pancreas transplantation for pa- with a failed kidney allograft may receive tients with diabetes who already require im- a second transplant or return to dialysis. munosuppression for a kidney allograft re- Our overall patient and graft survival is mains an appealing option. shown in Table 2. The majority of deaths were due to sepsis and cardiovascular causes, particularly in the subgroup of older recipients.2 Additional allograft losses were due to chronic allograft nephropathy, infection (BK virus, e.g.), and allograft rejection often related to medication nonadherence. This occurrence, whether related to psychological illness, economic hardships or immaturity, is an unfortunate consequence of the need for chronic immunosuppression.3

77 VOLUME 90 NO. 3 MARCH 2007 Pediatric Renal Transplantation – Historic and Current Perspectives M. Khurram Faizan, MD, and Andrew S. Brem, MD Renal transplantation is the preferred with renal failure. Over the next twenty- common than deceased donor trans- mode of therapy for pediatric patients five to thirty years, advances in immu- plants for pediatric patients.4 Outcomes with chronic kidney disease. Successful nosuppression, living donor transplan- in our program have compared favorably kidney transplantation offers children tation, and changes in deceased donor to national data4 with 100% patient sur- with end stage renal disease (ESRD) the organ allocation criteria have established vival and a one-year graft survival of 95%. opportunity for normalization of growth kidney transplantation as the treatment The one loss was due to recurrent dis- and development. Obstructive uropathy of choice for children with chronic re- ease (focal segmental glomerulosclerosis), and associated renal dysplasia remain the nal failure. a known risk factor.5 The relatively small commonest causes of ESRD in the pedi- numbers of pediatric transplants reflect atric age group.1, 2 According to the PEDIATRIC RENAL the low incidence of ESRD in children - United Network of Organ Sharing TRANSPLANTATION PROGRAM AT approximately 2 to 3 cases per million (UNOS) database, approximately 700 RHODE ISLAND HOSPITAL population. pediatric renal transplants are performed The Rhode Island Hospital initiated each year. Since 1988, a total of 13,163 its own kidney transplant program in UNIQUE ASPECTS OF PEDIATRIC successful pediatric renal transplants have 1997. Prior to that time, all adult and END STAGE RENAL DISEASE AND been carried out in the United States pediatric patients were required to travel RENAL TRANSPLANTATION (www.unos.org). out of state for renal transplantation. Children undergoing long-term di- Pediatric centers in Minnesota and Our pediatric transplant program was alysis face a multitude of problems. California were the first to offer kidney launched in 1998 with an 11-year old Chronic dialysis although life-saving, is transplantation to children with end boy receiving a kidney from his mother. not a panacea. Clearance of excess fluid stage renal failure in the late 1960s. Since then, 20 patients ranging from 2 and waste products by dialysis is cyclic Those pioneering pediatric to 18 years have received 21 renal trans- and not the same for all toxins. Chil- nephrologists and transplant surgeons plants. (Table 1) Approximately 60% of dren on dialysis often have limited ap- recognized that renal failure in children these renal transplants were done with petites especially given necessary dietary was a functional death sentence3 since living donors. In contrast to adult expe- restrictions. With inadequate caloric chronic dialysis was not readily available rience, living donor transplants are more intake, normal growth is unlikely. Ad- at that time. Immunosup- pression was primitive, kidney donors were few, and medical insurance covering the expense was not always available. The Congressional passage of the Medicare End Stage Renal Disease entitlement program in 1973 funda- mentally changed the dy- namic by, at the least, guaranteeing payment for the transplant. Other pediatric centers soon began offering transplant services with the assurance that their expenses would be defrayed. Pediatric dialysis services also improved with Medicare funding, but chronic dialysis treatment could never fully compensate for the multiple medical and psycho- SLE = Systemic Lupus Erthematosus, FSGS = Focal Segmental Glomerulosclerosis, social problems associated RPGN = Rapidly Progressive Glomerulonephritis, PCKD = Polycystic Kidney Disease. 78 MEDICINE & HEALTH/RHODE ISLAND ditionally, multiple medications are ate volume expansion in the operating larly and maintain clinical follow-up af- needed to augment the dialysis treat- room to prevent hypo-perfusion and ter transplantation. A multi-disciplinary ments including erythropoietin for con- thrombosis. Young patients often me- approach is essential, with the pediatric trol of anemia and calcium supplements tabolize immunosuppressive medica- renal transplant team comprising of with 1,25 (OH)2 vitamin D to ensure tions more quickly than adults and re- transplant surgeons, pediatric proper bone mineralization. From a quire close monitoring of drug levels in nephrologists, social workers, transplant psycho-social perspective, the time re- the post-operative period. Hypertension coordinators, nurses and counselors to quired to undergo hemodialysis, usually both from medications and/or from ensure a successful outcome post-trans- 3 to 4 hours for three sessions per week, prior volume expansion is a frequently plant. Most pediatric patients do very well imposes a heavy hardship on children encountered problem. In the short- in the United States with a five-year graft removing them from the usual childhood term, we accept higher blood pressures survival of about 82% and a five-year activities of school and play. Working in transplant patients as long as they are patient survival of 92%. parents also have the burdens of trans- asymptomatic to avoid the risk of throm- portation and caretaking. Families per- bosis in the graft. The risk of infection REFERENCES forming peritoneal dialysis (PD) at is ever present in children post-trans- 1. Lewy JE. Treatment of children in the U.S. with home must care for a sick child and deal plant; the infections come from outside end-stage renal disease (ESRD). Med Arch 2001; 55:201-2. with the infectious and nutritional com- exposures or can be inadvertently ac- 2. Seikaly MG, Ho PL, et al. Chronic renal insuffi- plications of PD. Successful renal trans- quired from the donor in the transplant ciency in children. Pediatr Nephrol 2003; 18:796- plantation in children allows for resto- process. 804. Epub 2003 Jun 14. ration of growth and development, im- 3. McDonald SP, Craig JC. Long-term survival of children with end-stage renal disease. NEJM provement in school performance and Most pediatric 2004; 350:2654-62. cognitive abilities, an increase in the 4. Long-term graft survival in pediatric renal trans- physical activity level, and allows fami- patients do very plant patients based upon primary disease. Trans- plantation 2006; 82:100. lies to lead a more normal life with their well in the United 5. Baum MA, Ho M, et al. Outcome of renal trans- children at home. States with a five- plantation in adolescents with focal segmental Parents are often ready and willing glomerulosclerosis. Pediatr Transplant 2002; to serve as candidates for living donor year graft survival 6:488-92. 6. Halloran PF. Immunosuppressive drugs for kid- transplantation when their own children of about 82% and a ney transplantation. NEJM 2004; 351:2715-29. are involved as patients. The United five-year patient Network for Organ Sharing (UNOS) M. Khurram Faizan, MD, is Clini- also has recognized the special needs of survival of 92%. cal Assistant Professor of Pediatrics, Brown children with ESRD and favors allocat- Medical School. ing deceased donor organs to children More mundane issues surface in Andrew S. Brem, MD, is Professor of under 18 years of age when possible. our patients as time passes. Immuniza- Pediatrics, Brown Medical School. These two advantages increase organ tions often have been deferred and need availability and most children fortu- to be considered. As a rule, most trans- CORRESPONDENCE nately now spend a relatively brief time plant centers, including our own, do not M. Khurram Faizan, MD undergoing dialysis prior to transplan- recommend giving attenuated live virus Section of Pediatric Nephrology tation. Currently, most transplant cen- vaccines to patients. Patients frequently Rhode Island Hospital APC 942 ters in the United States use an immu- are concerned about their delayed lin- 593 Eddy Street nosuppressive regimen in pediatric pa- ear growth, which resulted from prior Providence RI 02903 tients that mimics their adult counter- renal failure. Fortunately, newer im- phone: (401) 444-5672 parts. However, a few centers have at- mune-modulating protocols now limit e-mail: [email protected] tempted to minimize the use of post- glucocorticoid exposure6 and many chil- transplant steroids in children due to dren will resume a normal growth ve- their negative effect on growth. Unfor- locity or even exhibit “catch up” growth tunately, teenagers comprise the high- after transplant. We encourage patients est risk of acute transplant rejection to begin regular exercise once their amongst any age group (including both wounds are healed. Regular exercise for children and adults). This is due to a high as little as 30 minutes a day helps pa- rate of medical non-compliance seen in tients lower their risk for hypertension, this age group. excessive weight gain, and diabetes post Pediatric renal transplantation is a transplant. labor-intensive exercise with attendant pitfalls and potential complications. CONCLUSIONS Kidneys from adult donors are preferred Active participation and cooperation even for the youngest patients. This of the parents are necessary to ensure that means that the patient needs appropri- children receive prescribed drugs regu- 79 VOLUME 90 NO. 3 MARCH 2007 Immunosuppression Strategies in Kidney Transplantation Angelito Yango, MD, and Amit Johnsingh, MD

The development of immunosuppressive demonstrate any evidence of rejection. In visiting fellow in the laboratory of Joseph drugs heralded new and exciting possi- the group’s sixth case, the protocol was Murray. bilities in kidney transplantation. More modified for a living related renal trans- Significant progress has been made

than half a century ago, initial attempts plant from a fraternal twin. A lack of iden- in surgical techniques as well as medical at kidney transplantation resulted in im- tity was clinically apparent and immuno- management of renal transplant recipi- munologic destruction of the graft logic disparity was proven by preoperative ents. Advances in transplant immunol-

within a few weeks and eventual death and postoperative skin grafts that were rap- ogy paved the way for the development of the recipient from renal failure, leav- idly rejected. Given the closeness of the of immunosuppressive agents that are in- ing little hope for optimism. Such senti- relation, 450 Gray of total body irradia- tegral to successful allograft function. ment changed, however, with the suc- tion, a reduction from earlier transplants, With the use of azathioprine and corti- cessful non-twin kidney transplantation was administered eight days preopera- costeroids in combination, the average 1-

in the late 1950s at the Peter Bent tively. The allograft was accepted repre- year graft survival was less than 35%. This Brigham Hospital.1 Previously the senting the first successful living related improved to 50% with the use of Brigham team and groups in France had renal transplant under immunosuppres- polyclonal antibodies that were produced performed successful kidney transplants sion.1 French surgeons soon replicated the in laboratories and animal facilities asso- among identical twins. Overcoming im- successful protocol, first in the identical ciated with the individual transplant cen- munologic barriers between genetically setting of living related renal fraternal ters. The next major breakthrough oc- dissimilar individuals by immunosup- twins and a year later in a sister-to-brother curred with the identification of potent pression, however, ranks as this group’s immunosuppression from a product of a greatest achievement. The next major soil fungus identified in the Arctic Circle. Equipped with the knowledge that This compound, cyclosporine A, was rejection was an immunologic phenom- breakthrough originally purified in an effort to identify enon, efforts were taken to weaken the occurred with the antifungal medications by Sandoz Labo- immune system. Prior to the publication ratories in Basel Switzerland. of acquired tolerance, Medawar and oth- identification Cyclosporine, it turns out, had weak an- ers reported on the immunosuppressive of potent tifungal properties, but was fortuitously effects of total body irradiation and of the noted to suppress immune function in a newly synthesized hormone immunosuppression hemagglutinin assay. This wonderful coricosteroids. In 1952, Frank Dixon re- from a product of a agent may have been lost to clinical medi- ported in the Journal of Immunology that cine had it not been for the self-experi- x-rays could depress immune responsive- soil fungus identified mentation of Jean Borel and H. Stahelin. ness. The first use of clinical immunosup- in the Arctic Circle. The oral bioavailability of this pression was at the Peter Bent Brigham endecapeptide was so poor that its im- Hospital (1958 - 1960), using total body combination. Several other long-term suc- munosuppressive properties were lost in irradiation with subsequent reconstitution cesses were reported with protocols with vivo. However, by dissolving the com- by a bone marrow allograft. Protocols were total body irradiation; and Jean Ham- pound in oil prior to ingestion the scien- derived from experimental studies con- burger, founding president of the Inter- tists were able to detect significantly ducted by Joseph Murray and others in national Society of Nephrology, showed greater levels in their serum. Roy Calne,

skin grafted rabbits. It was suggested that that further radiation could reverse acute now at Cambridge, took the compound by infusing donor specific lymphoid cells rejection in the allograft. This strategy to the transplant laboratory and then to into a recipient depleted of its own lym- was soon widely applied at Denver, UCLA, the clinic and proved its efficacy as an phocyte by irradiation, one might create University of Minnesota, Edinburgh, immunosuppressive agent.2 Refinements a “chimeric” subject tolerant of organs and Hammersmith, the Massachusetts Gen- in clinical immunosuppression with the tissues from the donor of the allogeneic eral Hospital and the Medical College of combination of cyclosporine, azathio- marrow. The initial cases were associated Virginia. The following year, a second prine and prednisone set the stage for with short-term success and a high rate of strategy in clinical immunosuppression modern immunosuppression with 1-year

complications related to the transplant op- arose from the development of 6-mercap- allograft survival approaching 80%. The eration, renal failure or bone marrow sup- topurine in the laboratory. Subsequently, current state of the art immunosuppres- pression. One patient with profound azathioprine was developed in collabora- sion regimens have now achieved 1-year

thrombocytopenia succumbed to bleed- tion with clinicians interested in transplan- patient and graft survival rates of greater ing complications one month after renal tation and applied to the clinical arena than 95% and 88%, respectively.

transplantation. Two postoperative biop- after careful experiments in animal mod- In this brief review we will focus on sies and the kidney at autopsy failed to els conducted by Sir Roy Calne while a current immunosuppressive regimens in 80 MEDICINE & HEALTH/RHODE ISLAND nonspecific agents azathioprine and prednisone. In the maintenance phase different classes of immunosuppressive agents are prescribed to target different stages in T cell activation. The major combination used in most centers, including ours, is a calcineurin inhibitor (cyclosporine or tacrolimus) augmented by an antiproliferative agent (azathioprine or mycophenolate mofetil) and corticosteroids. (Table 1) Calcineurin inhibitors (cyclosporine or tacrolimus) remain the cornerstone of immunosuppression in renal use as well as evolving strategies and regi- Currently, Thymoglobulin is the pre- transplantation. They act by inhibiting mens in renal transplantation. ferred agent for induction, being supe- calcineurin, a key enzyme in T cell acti- In general, allograft rejection is me- rior to ATGAM in reversing acute rejec- vation. Cyclosporine (CsA; Neoral; diated by activated T lymphocytes, which tion.3 The use of anti T-cell antibody Sandimmune; Novartis) was first intro- infiltrate the graft leading to inflamma- preparations does come with a price. It is duced in the 1980s and brought about tion and eventual destruction. The best associated with profound and prolonged significant reduction in acute rejection immunosuppressive drugs target T cell lymphopenia risking serious opportunis- rates and dramatic improvement in one activation, cytokine production and pro- tic infections, bone marrow suppression year cadaveric graft survival rates from liferation. This is achieved by combining and malignancy. Therefore, induction 50% to 80%. In 1999, Tacrolimus two to three drugs that act at different therapy should be reserved for patients (Prograf; Astellas), a macrolide antibiotic stages of T cell activation. Following kid- at high risk of acute rejection or admin- was approved for kidney transplantation ney transplantation, immunosuppression istered as a strategy to reduce mainte- and was shown in large multicenter trials is typically administered in three distinct nance immunosuppression. to be superior to cyclosporine in prevent- phases. For patients who are at low risk for ing acute rejection.4 By 2004 tacrolimus early acute rejection, such as the elderly was the calcineurin inhibitor used by INDUCTION IMMUNOSUPPRESSION and unsensitized first-time recipients, one 80% of kidney transplant recipients. This phase involves intense immu- may elect to withhold induction therapy. Because the mechanism of action is nosuppression in the immediate post Alternatively, one may use a nondepleting similar, cyclosporine and tacrolimus can- transplant period when the risk of acute antibody that is specific only to activated not be used synergistically. In addition, rejection is at its highest. Typically, stan- T-lymphocytes. The prototypes for this while both drugs are equally nephrotoxic, dard immunosuppressive drugs used in class of agents are basiliximab (Simulect, their side effect profiles are distinct from the maintenance phase are also given at Novartis) and daclizumab (Zenapax, one another. For example, tacrolimus is higher doses. For patients at high risk for Roche), which block interleukin-2 recep- more neurotoxic and likely to induce post rejection, such as those who are highly tors expressed in activated T-cells. Since transplant diabetes. On the other hand, sensitized or have had previous organ these drugs do not affect resting T cells, compared to cyclosporine, tacrolimus is transplants, the immunosuppression may they do not deplete T cells and have mini- less likely to induce hypertension, hyper- be further intensified by the administra- mal side effects. lipidemia, hirsutism and gingival hyper- tion of anti-T cell antibodies. These anti- trophy. Familiarity with these toxicities is bodies act by binding to specific lympho- MAINTENANCE important as the decision to choose one cyte cell surface receptors causing lym- IMMUNOSUPPRESSION drug over the other is influenced by the phocyte depletion by way of phagocyto- Following the initial phase of avid drug’s side effect profile - avoiding CsA sis or complement-mediated cell lysis. immunosuppression, patients begin a in adolescents or tacrolimus in Type II T cell depleting antibodies include maintenance regimen to prevent late al- diabetes mellitus, for example. the polyclonal antilymphocyte antibod- lograft rejection. Over the last decade, Antiproliferative agents are key ad- ies – equine ATGAM (Pharmacia) and transplant immunosuppressive therapy juncts in transplant immunosuppression rabbit ATG (Thymoglobulin, Genzyme) has focused on T-cell specific immuno- based on their ability to curb immune and the monoclonal antibodies OKT3 suppression including tacrolimus, response by inhibiting proliferation of (Ortho Pharmaceutical) and mycophenolate mofetil and sirolimus; activated T and B cells. Azathioprine Alemtuzumab (Campath, Genzyme). each proven more efficacious than the (Imuran, Prometheus), an inhibitor of 81 VOLUME 90 NO. 3 MARCH 2007 nucleotide synthesis, has been used in Corticosteroids are nonspecific TRENDS renal transplantation since 1962. anti-inflammatory agents that partially For many years, the transplant com- Mycophenolate mofetil (MMF) disrupt activation of T cells and mac- munity relied on very potent immuno- (CellCept, Roche), a potent inhibitor of rophages by inhibiting key cytokines in suppression to prevent rejection with the the de novo pathway for purine synthe- the inflammatory cascade. These drugs notion that the benefits from heavy im- sis was introduced in 1995 and quickly have been a key part of our immuno- munosuppression far outweigh the risks. gained wide acceptance based on its su- suppressive regimen since the 1960s However, despite impressive reduction in periority to azathioprine in preventing and continue to be used in combina- acute rejection rates, there have been only acute rejection when combined with ei- tion with newer agents although at modest improvements in long term graft ther cyclosporine or tacrolimus.5 As such, much lower doses. Corticosteroids are outcomes. The main causes of late allograft the use of azathioprine has significantly associated with a myriad of side effects failure are chronic allograft damage declined and the combination of that increase the risk of serious cardio- (chronic nephropathy, coronary tacrolimus and MMF (with or without vascular disease and other morbidities. vasculopathy, recurrent HCV, e.g.) and corticosteroids) is the preferred combi- These include hypertension, death from cardiovascular disease, which nation after kidney transplantation in dyslipidemia, glucose intolerance, os- is exacerbated by chronic immunosup- most centers. teoporosis and weight gain to name a pression. Immunosuppressive medica- Major side effects of MMF are gas- few. These serious adverse effects tions promote infection, glucose intoler- trointestinal and hematologic. Diarrhea prompted earlier attempts at steroid ance, dyslipidemia and nephrotoxicity. can occur in up to one third of patients withdrawal after kidney transplanta- Hence, there is at present a shift in focus and maybe associated with nausea, bloat- tion. However, investigators noted a towards striking a balance between ad- ing and vomiting. Although MMF spe- substantial increase in acute rejection equate immunosuppression on one hand cifically targets lymphocytes, leukopenia, rates prompting reluctance in adapting and minimization of adverse effects on anemia and thrombocytopenia may also such protocols. More recently, under the other. occur. These side effects generally re- the protection of stronger induction The development of newer immu- spond to dose reduction. Recently, an immunosuppression, favorable results nosuppressive agents has substantially enteric-coated mycophenolic acid has have been achieved with rapid steroid increased treatment options. In the pipe- been introduced to reduce gastrointesti- withdrawal within the first week after line are drugs that selectively inhibit only nal symptoms associated with transplantation or with complete ste- T cells that react to donor antigens thus, mycophenolate mofetil. Thus far the new roid avoidance. Corticosteroids, once achieving a state of donor specific toler- agent has shown equal efficacy with the mainstay of transplant immunosup- ance while maintaining a fully functional MMF but failed to reduce GI com- pression, are now usually used in small immune system. Other agents that are plaints, implying that the toxicity is re- doses (< 0.1 mg/kg/d) or not at all. being developed are those that selectively lated to the systemic levels of the active block accessory molecules crucial in the compound mycophenolic acid rather TREATMENT OF ESTABLISHED recruitment of inflammatory cells into the than a local effect. REJECTION allograft; as well as agents that alter T-cell Sirolimus (Rapamune, Wyeth) is also Acute rejection is a major risk fac- trafficking by driving T-cells into lym- a macrolide antibiotic, discovered in a soil tor for reduced short- and long-term phoid tissues and away from the graft.7 sample on Easter Island and named for graft survival. These episodes reflect in- How these newer agents will apply to the indigenous population, the Rapanui. adequate immunosuppression either clinical practice remains to be seen. The drug, approved by the FDA in 1999 from aggressive weaning of immunosup- Newer strategies are also emerging. for use in prophylaxis of rejection in re- pression or patient noncompliance. In The concept of “one size fits all” has been nal transplant patients,6 is structurally most cases, the patient is asymptomatic; abandoned for a more individualized similar to tacrolimus, but its action is dis- the only clue being a precipitous rise in approach, taking into account the tinct from that of the calcineurin inhibi- the serum creatinine. Definitive diagno- patient’s immunologic and comorbid tors. Sirolimus inhibits signal transduc- sis rests on a tissue biopsy and treatment risks. While maintaining low rejection tion pathways resulting in inhibition of involves intensifying immunosuppres- rates remains crucial in the early stages T-cell proliferation. sion by giving high doses of corticoster- of engraftment, minimizing immuno- The major side effects of rapamycin oids, increasing the doses of mainte- suppression after 6-12 months is as im- are myelosuppression and hyperlipi- nance therapy and converting to more portant in improving long term out- demia. The main advantage of sirolimus potent agents such as tacrolimus and comes. The availability of newer agents over calcineurin inhibitors is its lack of MMF. In more aggressive cases, use of has substantially increased treatment op- nephrotoxicity. This drug has been used anti-T cell antibodies may be indicated. tions and potential combinations allow- either as primary therapy (calcineurin Recent data show a significant drop in ing greater flexibility in tailoring immu- inhibitor avoidance) or to facilitate with- both early and late acute rejection rates, nosuppression based on the patient’s drawal of calcineurin inhibitor. However, a trend largely attributed to the intro- clinical profile. To this objective, several as a primary agent sirolimus showed dis- duction of new and more potent immu- strategies such as tolerance induction (per- appointingly higher rates of rejection and nosuppressive agents. manent acceptance of the graft without significant problems with wound healing. need for chronic immunosuppression), 82 MEDICINE & HEALTH/RHODE ISLAND early minimization of steroid exposure or REFERENCES Angelito Yango, MD, is Assistant Pro- even complete avoidance, minimizing 1. Merrill JP, Murray JE, et al. Successful homotrans- fessor of Medicine, Brown Medical School. exposure to calcineurin inhibitors, utili- plantation of the kidney between nonidentical Amit Johnsingh, MD, is a Renal Fel- twins. NEJM 1960;262:1251. zation of highly potent induction therapy 2. Calne RY, White DJ, et al. Cyclosporine A in pa- low, Brown Medical School. followed by low dose immunosuppression tients receiving renal allografts from cadaver do- monotherapy are all being actively pur- nors. Lancet 1978; 2: 1323-7. CORRESPONDENCE sued. Valuable data from all these trials 3. Gaber AO, First MR, et al. Results of the double Angelito Yango, MD blind, randomized, multicenter, phase III clinical are accumulating; from this flurry of new trial of thymoglobulin versus ATGAM in the treat- Rhode Island Hospital APC 921 information there is optimism for im- ment of acute graft rejection episodes after renal 593 Eddy Street proved long-term patient outcomes. transplantation. Transplantation 1998; 66: 29-37. Providence RI 02903 4. Mayer A, Dmitrewski J, et al. Multicenter ran- These evolving protocols and options domized trial comparing tacrolimus (FK506) and phone: (401) 444-8345 highlight the requirement for lifelong cyclosporine in the prevention of renal allograft E-mail: [email protected] follow-up of allograft recipients by a team rejection. Transplantation 1997; 64: 436-43. of transplant specialists. 5. The Tricontinental Mycophenolate Mofetil Re- nal Transplantation Study Group A. A blinded, randomized, clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029-37. 6. Kahan BD. The Rapamune US Study Group. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection. Lancet 2000; 356: 194-202. 7. Hardinger KL, Koch MJ, Brennan D. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy 2004; 24:1159-76.

83 VOLUME 90 NO. 3 MARCH 2007 Considerations for the Inpatient Care of Solid Organ Recipients Kevin M. Lowery, MD, and Reginald Y. Gohh, MD

Advances in the management of patients that this growing population presents. able as IV preparations. Sirolimus is not with solid organ transplants and improve- This article will summarize these chal- available in IV form in the United States, ments in immunosuppression have re- lenges and review the most recent rec- and can either be transiently discontin- sulted in prolonged patient and allograft ommendations for the inpatient manage- ued or supplanted with increased IV dos- survival. These advancements have, in ment of solid organ recipients. ing of other immunosuppressive medi- turn, led to an increase in the number of Many physicians have some educa- cations when oral administration is not patients undergoing solid organ trans- tion related to solid organ transplanta- feasible. Furthermore, it may be neces- plantation: in 2005, over 28,000 patients tion, but few have sufficient experience sary to temporarily discontinue all immu- in the United States received a solid or- to adjust immunosuppressive agents. In nosuppressive medications in circum- gan transplant. 1 Because the majority sur- most instances, maintenance of the stances where it is felt a more robust im- vive more than 10 years after transplan- patient’s oral immunosuppressive medi- mune response may alter a life-threaten- tation, physicians in all fields will care for cation is preferred; however, several cir- ing situation. Although no specific these patients in their practices. While cumstances may arise where this is either guidelines are available for medical man- most interactions will likely involve out- not necessary or not an option. Whether agement in these situations, there is some patient evaluations and procedures, these a plan of care for a clinical situation or a evidence that the upsurge of cytokines encounters will offer the largest variety pre-test precaution, inpatients frequently associated with sepsis and severe illness of challenges in the inpatient setting. are required to maintain a Nothing Per may protect against allograft rejection.2 Most transplant centers utilize a team ap- Oral (NPO) status. When an NPO sta- In such instances, clinical monitoring is proach to managing post-transplant pa- tus is expected to be minimal in duration of chief importance, as immunosuppres- tients. This “team” often includes, but is (less than 12 hours), it is often accept- sion should be reintroduced as soon as not limited to, transplant surgeons, medi- able to withhold the administration of the clinical recovery begins to avoid al- cal sub-specialists in the transplanted oral immunosuppressive agents until the lograft rejection. organ’s field, infectious disease specialists, status is changed and re-start with the The dosing and administration of pharmacists, social workers, and nurses. prescribed dosing schedule at that time. immunosuppressive medications in the While close interaction with this trans- For longer durations, however, conver- inpatient setting can also be potentially plant team remains of utmost importance sion to an intravenous (IV) preparation problematic with regards to poly-phar- in all aspects of allograft recipient’s care, is recommended. Corticosteroids, macy. While immunosuppressive regi- it is important that all physicians become cyclosporine, tacrolimus, azathioprine, mens will vary, calcineurin inhibitors familiar with the select facets of medicine and mycophenolate mofetil are all avail- (CNI) remain a mainstay for the major-

84 MEDICINE & HEALTH/RHODE ISLAND ity of solid organ transplant recipients. cell insulin production through inhibition ney transplant recipients rarely exceeds The two CNIs in use today (cyclosporine of specific cellular proteins.8 While 50 mL/min/2.73m2 as estimated by an and tacrolimus) and the antimetabolite PTDM can be treated similarly to Type II equation derived from the Modification drug sirolimus are primarily metabolized diabetes mellitus, special considerations re- of Diet in Renal Disease (MDRD) and eliminated by the cytochrome P450- garding contraindications or potential side study.12 Recipients of other solid organ IIIA4 enzyme system. Therefore, pa- effects of the available oral agents must be transplants are at risk for diminished tients utilizing these medications are at made. Impaired liver or renal function renal function as well; most likely a re- high-risk for numerous drug interactions. may pose increased risks of hypoglycemia sult of the nephrotoxicity related to Use of medications that induce or inhibit with sulfonylurea agents, and are long-term exposure to immunosuppres- the cytochrome P450 system are not con- contraindications, along with congestive sive agents, in particular calcineurin in- traindicated for these patients, but close heart failure, for use of metformin. Given hibitors. Approximately 32% of heart monitoring of organ function as well as the limitations of oral agents, and the nec- recipients, 20% of lung recipients, and cyclosporine, tacrolimus, or sirolimus lev- essary exposure to immunosuppressive 18% of liver recipients have chronic els should be maintained when introduc- medications, a majority of patients with kidney disease (CKD) at 5 years post- ing or discontinuing such medications. PTDM eventually require exogenous in- transplantation; and up to 29% of these Additionally, many medications may insulin treatment.8 During episodes where individuals will eventually require some hibit or enhance absorption of immuno- immunosuppressive doses (in particular form of renal replacement therapy.13 In suppressive medications and alter the lev- corticosteroids) are altered, large variations an inpatient setting, this underlying els of these medications. (Table 1) in blood glucose levels can be expected and CKD may predispose patients to fluid Cardiovascular disease (CVD) re- diligence in monitoring is of paramount and electrolyte abnormalities and to mains a major cause of morbidity in or- importance. toxic accumulation of anesthetic or an- gan transplant recipients and remains the algesic medications. It is important to leading cause of death among kidney al- …most physicians also keep in mind that renal allografts lograft recipients.3 The elevated risk of lose their innate ability to autoregulate CVD in this population is due to a variety will likely at some renal blood flow due to functional den- of factors related to both pre-existing (pre- point be involved in ervation of a transplanted kidney, thus transplant) risk factors as well as variables predisposing these patients to episodes specific to the post-transplant setting. In the routine care of of ischemic acute renal failure. renal allograft recipients, the pre-trans- such patients. Infection remains one of the most plantation prevalence of hypertension, common complications of immunosup- diabetes mellitus, hypercholesterolemia, Because most transplant recipients pressive therapy. Since the vulnerability and obesity are 80%, 55%, 60%, and are maintained on corticosteroids, adre- to infection is related to both pathogenic 30% respectively.4 Additionally, a num- nal insufficiency is a theoretical concern exposure and the overall immunosup- ber of these CVD risk factors are associ- in the inpatient setting, but rarely a prac- pressive state, the risk for developing spe- ated with or exacerbated by immunosup- tical one. Since the current standard of cific types of infections is dependent on pressive drugs. Calcineurin inhibitors and care for routine maintenance immuno- the time period post-transplant. Imme- corticosteroids are associated with an in- suppression generally involves relatively diately post-transplant, patients will be creased risk of hypertension, diabetes mel- low corticosteroid doses (5-10mg of pred- most at risk for pathogens commonly litus, and lipid abnormalities and sirolimus nisone daily) patients usually have suffi- seen in non-immunosuppressed surgical commonly causes hyperlipidemia .5, 6 cient reserve to respond to stress. Several patients. From 1-6 months post-trans- While mortality secondary to CVD in non- prospective studies demonstrated that plant, while immunosuppression dosing renal solid organ allograft recipients is augmentation of baseline steroid doses in remains relatively high, viral and oppor- lower than renal allograft recipients, the various settings of stress (sepsis, surgery, tunistic infections become more preva- complications seen with these immunosup- metabolic abnormalities) is unnecessary lent. The majority of patients receive pressive agents is universal, and the preva- and may not entirely be benign.9-11 How- prophylaxis against cytomegalovirus lence of CVD will likely rise in these popu- ever, if the patient has signs or symptoms (valganciclovir), pneumocystis carinii and lations as well with longer allograft surviv- of adrenal insufficiency, the use of high- nocardia (TMP-SMZ) and fungal infec- als being seen today. dose steroids (50-100 mg of hydrocorti- tion during this period. Beyond six Corticosteroids and CNI predispose sone every 8 hours) should be initiated months, for patients with stable allograft patients to developing post-transplanta- with a return to baseline dosage over a function and lower immunosuppressive tion diabetes mellitus (PTDM). Corti- period of 2-3 days as clinical status per- regimens, infections seen in the general costeroids impair insulin production, im- mits. population are again most common, al- pede the activation of the glucose/FFA Although, when available, renal though viral pathogens can appear at any cycle, impair glucose uptake in the mus- transplantation remains the treatment of time and the clinical course for viral and culature, and decrease the number and choice for end-stage renal disease, trans- bacterial infections is often prolonged.14 affinity of insulin receptors.7 The plantation usually falls short of replac- As a result, these patients often require a calcineurin inhibitors, cyclosporine and ing renal function to normal levels. The longer duration of antibiotics and antivi- tacrolimus, are postulated to diminish beta average glomerular filtration rate of kid- ral medications. 85 VOLUME 90 NO. 3 MARCH 2007 86 MEDICINE & HEALTH/RHODE ISLAND 87 VOLUME 90 NO. 3 MARCH 2007 Immunosuppression also predis- of all such patients, it is important that 11. Kehlet H, Binder C. Adrenocortical function and poses all transplant recipients to delayed all physicians obtain a general under- clinical course during and after surgery in unsupplemented glucocorticoid-treated patients. wound healing as a result of diminished standing of the unique aspects of care Brit Med J 1973; 2: 147-9. tensile strength and tissue integrity. Even presented by this population. 12. Poge U, Gerhardt T, et al. MDRD equations for at low doses, corticosteroids impair tissue estimation of GFR in renal transplant recipients. integrity and are associated with capillary REFERENCES Am J Transplantation 2005; 5: 1306-11. 13. Ojo AO, Held PJ, et al. Chronic renal failure after 15, 16 and tissue friability. For this reason, 1. Organ Procurement and Transplantation Network. transplantation of a nonrenal organ. NEJM 2003; it is recommended that skin staples be www.optn.org. Accessed October 26, 2006. 349: 931-40. 2. Burke GW, Ciancio G, et al. Association of kept in place 2-3 times longer in the 14. Fishman JA, Rubin RH. Infection in organ-trans- interleukin-10 with rejection-sparing effect in plant recipients. NEJM 1998; 338: 1741-51. transplant recipient and many transplant septic kidney transplant recipients. Transplanta- 15. Anstead GM. Steroids, retinoids and wound surgeons recommend the use of nonab- tion 1996; 61: 1114-6. healing. Adv Wound Care 1998; 11: 277-85. sorbable sutures whenever possible. Re- 3. Foley RN, Parfrey PS, Sarnak MJ. Clinical epide- 16. Meadows EC, Prudden JF. A study of the influ- miology of cardiovascular disease in chronic renal cent information has implicated the use ence of adrenal steroids on the strength of healing disease. Am J Kidney Dis 1998; 32: S112-9. wounds. Surgery 1953; 33: 841-8. of sirolimus with delayed wound healing 4. Ojo AO. Cardiovascular complications after re- 17. Dean PG, Lung WJ, et al. Wound-healing com- in the immediate post-transplantation nal transplantation and their prevention. Trans- plications after kidney transplantation. Transplan- plantation 2006; 82: 603-11. tation 2004; 77: 1555-61. setting when compared to the use of 5. Kasiske BL. Epidemiology of cardiovascular dis- 17 tacrolimus. No data are available thus ease after renal transplantation. Transplantation far as to whether or not this increased 2001; 72: S5-8. Kevin M. Lowery, MD, is a Renal propensity toward delayed wound heal- 6. Brattstrom C, Wilczek HE, et al. Fellow, Brown Medical School. Hypertriglyceridemia in renal transplant recipi- Reginald Y. Gohh, MD, is Associate ing with sirolimus carries over to subse- ents treated with sirolimus. Transplantation Pro- quent surgeries, but this should be con- ceedings 1998; 30: 3950-1. Professor of Medicine, Brown Medical sidered in these situations. 7. Bialas MC, Routledge PA. Adverse effects of cor- School. In conclusion, the number of solid ticosteroids. Adverse Drug Reactions Toxicological Reviews 1998; 17: 227-35. CORRESPONDENCE organ transplant recipients in the United 8. Montori VM, Velosa JA, et al. Posttransplantation States is steadily increasing. As a result, diabetes. Diabetes Care 2002; 25: 583-92. Reginald Gohh, MD most physicians will likely at some point 9. Bromberg JS, Alfrey EJ, et al. Adrenal suppression Rhode Island Hospital APC 921 be involved in the routine care of such and steroid supplementation in renal transplant 593 Eddy Street patients. Transplantation 1991; 51: 385-90. Providence RI 02903 patients. While close involvement of a 10. Glowniak JV, Loriaux DL. A double-blind study team of transplant specialists during these of perioperative steroid requirements in secondary phone: 401-444-8345 interactions remains the standard for care adrenal insufficiency. Surgery 1997; 121: 123-9. E-mail: [email protected]

88 MEDICINE & HEALTH/RHODE ISLAND Is There a Rational Solution to the Kidney Shortage? Anthony P. Monaco, MD

The treatment of mortal and morbid transplants exceeded those for deceased prohibits any person to acquire any hu- diseases with organ replacement is one donors. The dramatic improvement in man organ for valuable consideration of the great medical miracles of the 20th effective immunosuppression has elimi- (money) for use in human transplanta- century. This is particularly true in the nated the need for reduced histocompat- tion or face fines and imprisonment. case of kidney transplantation, the com- ibility (consanguinous living related do- This legislation was well intentioned, and monest solid organ transplant, where nor-recipient pairs); in landmark studies basically was designed to protect the poor transplantation produces not only a bet- by Terasaki et al6 kidney transplants from and disenfranchised from potentially dan- ter quality of life, but also prolongs lon- friends, spouses, lovers, and other unre- gerous and unhealthy exploitation by un- gevity compared to dialysis.1 This happy lated donors survived as well as living re- scrupulous middlemen and avaricious circumstance has dramatically increased lated donor kidneys. The risks of donor brokers. Such legislation has been quite the number of patients eligible for kid- nephrectomy (perioperative morality of effective in the United States, but an ex- ney transplantation but at the same time 0.03% and morbidity of <2%) are well tensive black market to obtain living do- has underscored the severe shortage of established and generally well accepted.2 nor kidneys—many of marginal quality, kidneys for transplantation. Less than The number of living kidney donors transplanted under less than optimal con- 15% of some 70,000 Americans on the transplanted now approaches 40-50% in ditions, frequently by surgeons of limited kidney waiting list in 2005 received many programs. Every effort is employed quality and experience—has flourished transplants; by 2010 the waiting list will to utilize appropriate willing donors. A in a number of countries around the exceed 100,000.2 As a direct conse- number of thoughtful, well-intentioned world.10 The number of American pa- quence of the kidney shortage, waiting strategies have been implemented.7 tients that utilize these organ black mar- times on dialysis, already 5-10 years in Thus, totally altruistic donors—unique kets has grown; the presence of such pa- some regions of the country, continue to individuals who volunteer to donate a kid- tients seeking post-transplant care is now increase, leading to increased dialysis-as- ney to any deserving person—are now commonplace in most American pro- sociated cardiovascular morbidities and considered acceptable (after appropriate grams. mortality in those patients who are even- psychological evaluation). Similarly, ex- Government prohibition of the un- tually transplanted.3 Sadly annual death changes (swaps) between one or more regulated sale of kidneys and other or- rates on the dialysis waiting list have in- ABO-incompatible living-donor recipi- gans to protect the poor from exploita- creased by almost 25% over the past four ent-donor pairs or crossmatch incompat- tion is appropriate and certainly justified. years.4 ible pairs (or even combinations thereof ) On the other hand, the idea that any In the face of this kidney shortage have been pursued. Dr. Paul Morrissey type of gain, reward, or compensation— there have been only modest increases in of our Rhode Island Transplant Group financial or otherwise—for organ dona- the number of deceased donor (DD) kid- has been a national leader in these two tion is unethical and inherently undesir- neys in recent years, essentially achieved concepts. These maneuvers add a few able does not necessarily follow. Rewards by using so-called marginal donors, i.e., additional transplants to all programs, for doing good, for making self-sacrifices, extended criteria donors (older, hyper- but their overall effect in extending the for taking personal risks to help others in tensive donors frequently dying of cere- donor pool, in my experience, is limited. one’s family, community, or country are brovascular causes) and donors after car- Advances in basic science research evident in every fabric of modern West- diac death (donors who expire without that would facilitate generation and ern society. Numerous examples can be controlled cardiorespiratory support), growth of human solid organs (kidneys) given but perhaps the most obvious ex- both circumstances contributing to kid- in vitro and/or permit transplantation of ample in the United States is voluntary neys of lesser quality. Recently, the US xenogeneic organs are no doubt years military service. The overwhelming ma- Department of Health and Human Ser- away. The extraordinary effectiveness of jority of volunteers for the United States vices initiated the Organ Donation kidney transplantation, especially living military are motivated by idealism and Breakthrough Collaborative, a national kidney transplants, to cure kidney disease patriotism, but they are also encouraged drive to increase the number of deceased for a very long time has brought into to volunteer with inducements of paid donors. This effort will have the addi- prime focus the need to consider possible college educations, enlistment bonuses, tional benefit of increasing the availabil- alternatives in the form of rewards and/ reenlistment bonuses, and substantial fi- ity of non-renal solid organ transplants or financial compensation to expand the nancial recovery for injury or mortality.11 as well as kidneys. It is estimated that only donor pool.2,8,9 Financial compensation It is not surprising that minority group approximately 50% of eligible deceased (as opposed to reimbursement for ex- members with limited financial resources donors eventually come to organ dona- penses incurred or loss of income) for are numerically disproportionately rep- tion.5 There has been a more substantial organ donation has been strictly prohib- resented in the military. Likewise, signifi- increase in the use of living kidney do- ited in the United States by the National cant numbers of non-citizen immigrants nors: in the past year living donor kidney Organ Transplant Act (NOTA) which volunteer for military service, eventually 89 VOLUME 90 NO. 3 MARCH 2007 being rewarded for their service by sively as buying and selling organs. Buy- REFERENCES American citizenship (a route taken by ing and selling implies financial negotia- 1. Wolfe RA, Ashby VB, et al. Comparison of mor- my own father in World War I). Thus, tion between recipient (buyer) and do- tality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of first ca- the concept of encouraging and reward- nor (seller), suggests higher or lower daveric transplant. NEJM 1999; 341: 1725-30. ing acts of self-sacrifice and personal risk prices in the face of variations in value 2. Gaston RS, Danovitch GM, et al. Limiting finan- taking to help others—acts essentially and quality, and may involve middlemen cial disincentives in live organ donation. Am J Trans- motivated by love, altruism, idealism, or brokers. Certainly this is not desirable. plant 2006; 6: 2458-555. 3. Meier-Kriesche HV, Kaplan B. Waiting time on patriotism or the like—with valuable con- We need a government regulated, scru- dialysis as the strongest modifiable risk factor for siderations (money, etc.) is unequivocally pulously supervised program in which a renal transplant outcomes. Transplantation 2002; established and considered ethically ac- person or his/her estate receives a fixed 74: 1377-81. 4. Merion RM, Ashby VB, et al. Deceased-donor ceptable, even with the realization that valuable enhancement or reward for or- characteristics and the survival benefit of kidney more poorer people will undertake self- gan donation. Transplant pioneer, Paul transplantation. JAMA 2005; 294: 2726-33. sacrifice and personal risk in part to gain Terasaki, MD of UCLA, suggested that 5. Sheehy E, Conrad SL, et al. Estimating the num- the financial rewards. donors be rewarded with a valuable gold ber of potential organ donors in the United States. NEJM 2003; 349: 667-74. It is accepted that donor evaluation medal; the implication being that it could 6. Terasaki PI, Cecka JM, et al. High survival rates of 14 and workup, operative and postoperative be kept or sold if so desired. I envision kidney transplants from spousal and living unre- care should be covered by the recipient’s a scheme in which a government insur- lated donors. NEJM 1995; 333: 333-6. medical insurance. Also considered ac- ance trust fund is established and admin- 7. Wessel D. Easing the kidney shortage. Wall Str J 17 June 2004. ceptable is reimbursement of donors for istered by a federal agency or commis- 8. Friedman E, Friedman A. Payment for donor kid- travel costs and lost wages. A recent pro- sion. A direct financial incentive would neys. Kidney Int 2006; 69: 960-2. posal has suggested that donor benefits be paid to both living donors and heirs 9. Monaco AP. Rewards for organ donation. Kidney also include short-term (one year) term of deceased donors as a reward or hono- Int 2006; 69: 955-7. 10. Tilney NL. Transplant: From Myth to Reality. Yale life insurance (to cover possible operative rarium for organ donation. The reward University Press, New Haven and London mortality) and additional lifetime (Medi- would be dispersed by the federal agency 2003:364-74. care) medical insurance.2 The inclusion after confirmation of organ donation, 11. Brooke J. On the farthest US shores, Iraq is a way of a direct financial payment subsidy has similar to the payment of an insurance to a dream. NY Times 31 July 2005. 12. Fox MD. The price is wrong:. Am J Transplant been considered exploitive and problem- policy. Importantly, in this era of expand- 2006; 6: 2529-30. atical.12 I think the biggest problem in ing medical expenditures, the reduced fi- 13. Delmonico F. Commentary: The WHO resolu- initiating a system of financial rewards for nancial burden of dialysis costs derived tion on human organ and tissue transplantation. Transplantation 2005; 79: 639-40. kidney/organ donation is the fact that from increased kidney transplantation 14. Terasaki PA. Congressional gold medal for trans- 12,13 2,8 both opponents and proponents of would make the program revenue neu- plant donors and families. Am J Transplant 2005; the concept refer to this activity exclu- tral. 5: 1167.

Anthony P. Monaco, MD, is Professor of Surgery, Harvard Medical School, and Director of Transplant Services, Rhode Is- land Hospital.

CORRESPONDENCE Anthony Monaco, MD Rhode Island Hospital APC 921 593 Eddy Street Providence, RI 02903 Phone: (617) 632-9822 e-mail: [email protected]

90 MEDICINE & HEALTH/RHODE ISLAND The National Organ Transplantation Breakthrough Collaborative – A Rhode Island Hospital Perspective Kevin M. Dushay, MD, FCCP, and Suzanne Duni Walker, Esq, RN, BSN

As of November 27, 2006, close to Rhode Island Hospital/Hasbro Advisory Committee meetings, and 94,000 people in the United States were Children’s Hospital, the only organ trans- meets with its members to provide waiting for organ transplants, compared plant center in Rhode Island, has been a administrative backing and support to fewer than 75,000 in 2000. The num- member of all three breakthrough col- ber of patients dying while waiting for laborative sessions, represented by teams 3. Deploy a Self-Organizing OPO/ transplants rose from 6,500 in 2000 to consisting of Rhode Island Hospital Hospital Team 7,300 in 2004. In New England (Maine, (RIH) and New England Organ Bank A Hospital Relations Coordinator New Hampshire, Vermont, Massachu- (NEOB) staff. The NEOB is the organ (HRC), Suzanne Walker, Esq, RN, setts, Rhode Island, and Connecticut) procurement organization (OPO) that BSN, and two Family Service Co- nearly 4,000 individuals are wait-listed serves Rhode Island and most of New ordinators (FSC), Leo Trevino and for organ transplants; in Rhode Island the England. This article is a report to the Darlene Fiotto, all employed by the figure is over 250. In 2004, only 51% of Rhode Island medical community of the New England Organ Bank, work potential organ donors provided organs organ donation and transplantation prac- from an NEOB satellite office for transplantation.1 tices that have been implemented over within the RIH complex to respond This disparity spearheaded the first the past year at RIH. We also describe quickly to referrals of potential do- Organ Donation Breakthrough Collabo- opportunities for physicians to increase nors. In addition, they are valuable rative (ODBC) in October 2003. Rep- the supply of donor organs. resources for information and edu- resentatives of the US Department of cation regarding organ donation. Health and Human Services along with HIGH LEVERAGE CHANGES The HRC regularly analyzes hospi- organ transplantation and hospital pro- The ODBC, and later the OTBC, tal-specific data through death fessionals began a year-long program to stressed these goals: 1,2 record reviews and “After Action achieve greater access to donor organs for Reviews” to identify missed oppor- transplantation. A second Organ Dona- 1. Advocate Organ Donation as the tunities for organ donation. The tion Breakthrough Collaborative fol- Mission FSCs are trained requestors, as well lowed, and over the past year, the first Those involved with the entire pro- as liaisons to the community, meet- Organ Transplantation Breakthrough cess, from identifying potential or- ing with religious and secular lead- Collaborative (OTBC) was convened. gan donors, to informing families ers and providing or coordinating Collaborative members have used tech- about the opportunity to provide a community-directed educational niques developed at the Institute for potentially life-saving organ dona- programs. Completing the OPO Healthcare Improvement under the di- tion, to caring for the donor, must team are the NEOB Donation Co- rection of Donald M. Berwick, MD, to be enthusiastic about, committed ordinators (DCs), who provide on- disseminate best practices for increasing to, and skilled in the practices of site continuous management of the both the number of organ donors and organ donation. organ donor and the donation pro- the number of organs procured per do- cess. The DC collaborates with the nor. Principally these changes involved 2. Involve Senior Leadership to get health care team in the critical care increasing consent rates and relaxing ar- Results of the organ donor, including test- bitrary exclusion criteria when data indi- At RIH, the Senior Vice President ing, requesting consults, and direct- cate acceptable recipient and graft sur- of Medical Affairs, Boyd P. King, ing therapy. At the same time, in con- vival rates. MD, attends the Organ Donation junction with Newton-based Organ

91 VOLUME 90 NO. 3 MARCH 2007 Clinical Coordinators (OCC), they must ensure that the family under- organ donor and should be discussed are responsible for allocation and stands that their loved one is not with the NEOB (phone: 800-446- placement of all recovered organs. going to survive, before they are ap- NEOB). The suitability of a donor or- The DCs coordinate the surgical proached regarding organ or tissue gan depends on the prognosis of each teams, technicians, operating room donation, regardless of who is do- potential recipient without it; therefore, staff, and transplant centers. ing the requesting. the decision to reject a possible donor RIH has developed and is expand- organ should be made in consultation ing a cadre of critical care nurse The patient should with transplant centers. organ donation champions, who provide education and support to be fully supported Donation Team Huddles their colleagues. Furthermore, until organ donation These brief meetings, involving the there are RIH respiratory therapists NEOB on-site coordinator(s), the and an Intensivist Physician Cham- has been absolutely patient’s nurse and/or physician(s) and/ pion who have designated them- ruled out if we are to or other healthcare providers, the unit selves as available for assistance in social worker, and any other appropriate the management of organ donors. reduce the number individuals, are held as soon as possible RIH social workers join the OPO/ of patients dying on after referral of a potential organ donor, Hospital organ donation team to and periodically thereafter, in order to provide family support. the waiting list. determine the best manner and timing for approaching the family to discuss the 4. Practice Early Referral, Rapid Re- 6. Implement Donation after Car- opportunity for donation. sponse diac Death Families are rarely prepared for end The number of brain-dead poten- After Action Reviews of life decisions when a loved one is tial donors has always been less than These meetings review the course of a victim of trauma or a sudden neu- the number of patients waiting for recent referrals to the NEOB. Previously, rologic event. Information often transplants. Even with optimal con- these meetings were held quarterly, but must be presented several times. sent rates and optimal numbers of will now be held weekly or biweekly so Success in obtaining consent for organs procured, some patients will staff will have a clear memory of cases. organ donation is enhanced when be on waiting lists. Patients not suc- This will minimize the risk of losing sub- families do not feel rushed by cumbing to brain death should still sequent donors to repeated suboptimal health-care professionals, when ex- have the right to donate their or- practices. pert, sensitive, and confident indi- gans to others who will otherwise viduals answer questions, and when die. In addition, their families are Real Time Death Record information is available at the time entitled to the solace that comes Reviews it is requested.3 from the donation of life-saving or- These reviews identify potential do- gans. However, many donor hospi- nors who were not referred to the NEOB 5. Master Effective Requesting tals do not have policies to provide at all. The patients’ healthcare providers are Studies have shown that the high- the option of donation after cardiac informed of these missed opportunities. est consent rates are achieved when death to their patients who wish to physicians refer families to OPO do so. This is a disservice, not only Identify Physician/Clinician personnel for discussion regarding to patients who wish to bestow this Champions the opportunity to donate a loved gift, but to other patients who For the most part, physicians com- one’s organs. In addition, physicians might be recipients of that gift. mitted to increasing the number of do- should support the offer of organ nor organs are not born, they are made. donation as an opportunity to save ACTIONS TAKEN OVER THE PAST Until recently, most OPOs had their DCs a life, rather than as a legal require- YEAR AT RHODE ISLAND HOSPITAL relieve physicians of the responsibility of ment at the time of a patient’s an- caring for their patients once they had ticipated death.3 Physicians must Clinical Triggers died and made the transition from pa- recognize the possibility of an ap- A set of criteria indicating a patient tient to organ donor. As a result, most pearance of a conflict of interest in is appropriate for referral to the NEOB physicians have little to no experience the family’s mind when they tell a have been developed, printed on lami- caring for patients following brain death. family that their loved one’s prog- nated pocket-sized cards, and distributed A profound series of pathophysiologic nosis is poor and then speak of or- to staff in the Emergency Room and derangements occur in the brain dead gan donation. First and foremost, Critical Care Units. Any patient < 85 patient.4,5 Superimposed on the patho- families want to hear from their years old with a Glasgow Coma Scale of physiology of brain death are the iatro- doctor that he or she is doing ev- = 4 due to neurologic insult, or in whom genic complications often present follow- erything possible for their loved terminal extubation or no resuscitation ing unsuccessful resuscitation of the se- one. After an interval, the doctor status is being considered, is a potential verely brain injured patient. The Organ 92 MEDICINE & HEALTH/RHODE ISLAND Transplantation Breakthrough Collabo- SUMMARY 6. Personal communication, Christopher C. Curran, rative has promoted the need to involve Patients needing organ transplants Organ Operations, New England Organ Bank, Newton, Massachusetts. intensivists in the management of organ still exceed the number of organs, and 7. Rosendale JD, Chabalewski FL, et al. Increased donors, based on data demonstrating each year some patients on waiting lists transplanted organs from the use of a standard- more organs transplanted per donor die. A series of national collaborative ized donor management protocol. Am J Trans- when intensivists care for donors, and meetings identified practices shown to plant 2002; 2:761. 8. Rosendale JD, Kauffman M, et al. Aggressive when donor management guidelines are increase organ donation consent rates and pharmacologic donor management results in more followed and achieved.6-8 organs procured per donor. A partner- transplanted organs. Transplantation 2003; Even prior to obtaining consent for ship between the NEOB and donor hos- 75:482. 9. Personal communication, Jim Bradley, Clinical In- organ donation, physicians can potentially pitals is important to achieve these goals. formation Systems, New England Organ Bank, help increase the number of organs pro- By following best practices set forth by Newton, Massachusetts. cured per donor. Often physicians become the Collaborative movement and put in less aggressive in patient management af- place by NEOB, physicians can increase Kevin M. Dushay, MD, FCCP, is As- ter telling a family the patient’s poor prog- the supply of donor organs in New En- sistant Professor of Medicine, Brown Medi- nosis and discussing the option of with- gland and nationally. cal School. drawing cardiopulmonary support. Phy- Suzanne Duni Walker, Esq, RN, sicians do not want to prolong the dying REFERENCES BSN, is Hospital Relations Coordinator, process for the patient or the suffering of 1. Organ Transplantation Breakthrough Collaborate nd New England Organ Bank. the family. However, the process of ob- Charter, 2 Annual National Learning Congress on Organ Donation & Transplantation. New taining consent for organ donation may Orleans, LA, October 2006. CORRESPONDENCE: require multiple discussions extending over 2. Organ Donation Breakthrough Collaborative, Kevin M. Dushay, MD, FCCP hours, even days. During this time, po- First Annual National Learning Congress. Pitts- Pulmonary, Critical Care & Sleep tential organ donors may fall into a “thera- burgh, PA, May 2005. 3. Siminoff LA, Gordon N, et al. Factors influenc- Disorder Medicine peutic hole” with worsening hemodynam- ing families’ consent for donation of solid organs Rhode Island Hospital ics, metabolic derangements, and failing for transplantation. JAMA 2001; 286:71. 593 Eddy Street – APC 7 organs. Once consent for organ donation 4. Szabó G. Physiologic changes after brain death. J Providence, RI 02903 Heart Lung Transplant 2004; 23: S223. is obtained, the NEOB Donation Coor- 5. Wood KE, Becker BN, et al. Care of the potential phone: 401-444-3565 dinator and/or physician may resume ag- organ donor. NEJM 2004; 351:2730. E-mail: [email protected] gressive care only to find irreversible organ damage precluding donation. The patient should be fully supported until organ donation has been absolutely ruled out if we are to reduce the number of patients dying on the waiting list.

RESULTS Over the years 2003, 2004, and 2005, the number of organ donors and organ transplants in New England remained relatively stable, but at levels higher than those in 2000 and earlier. (Table I) At the 2nd Annual National Learning Congress on Organ Donation and Transplantation in October 2006, the NEOB was recognized for its sus- tained high rate of Donation after Car- diac Death (DCD) donors over the past year, given a Donation Service Area performance award for outstanding performance in multiple aspects of organ donation, and a National Improvement Leader Award. The staff of the NEOB developed and implemented the second largest DCD program among 58 OPOs in the United States. At the same event, RIH won an Organ Donation Medal of Honor for its high rate of obtaining consent for organ donations. 93 VOLUME 90 NO. 3 MARCH 2007 GERIATRICS FOR THE PRACTICING PHYSICIAN Division of Geriatrics Quality Partners of RI Department of Medicine EDITED BY ANA C. TUYA, MD The Assessment and Management of Falls Among Older Adults Living In the Community Michael P. Gerardo, DO

A 78-year-old man presents to your office age of 80.1,2 The sequelae from a fall are tors for falling increases sharply after age for the first time. A review of his medical of important consequence. One in ten 70.7 Physicians should at least once a year record reveals a problem list that includes falls results in a serious injury (e.g. frac- ask older patients about any falls or the hypertension, atrial fibrillation, osteoar- ture, subdural hematoma, soft tissue or fear of falling. This yearly screen should thritis, depression and a previous transient head injury).3 Falling is the leading cause include questions about and observation ischemic attack. His medication list in- of injury, and the 6th leading cause of for difficulties with balance or gait. The cludes metoprolol, warfarin, acetami- death among individuals over the age of “Get-Up and Go” test is a short screen- nophen, omeprazole, escitalopram ox- 65.4 Individuals may acquire disability ing tool that tests for balance and strength. alate, and aspirin. He tells you that al- from injury, fear of falling, or restriction It involves asking the patient to rise from though he has been educated on the in ambulation, either self-imposed or a chair, walk ten feet, turn, return to the proper use of his cane, and encouraged to imposed by family members to prevent chair and sit. Performing the task longer use it, he does so intermittently; “when I subsequent falls. In addition to restric- than 9 seconds confers a two-fold risk of feel off-balance.” He adds that his vision tion in mobility, falls place a previously falling. Difficulty with any part of the is not as good as it used to be. On more independent person at risk of nursing test may increase risk as well. A timed direct questioning, he reports that he has home placement.5,6 Falls account for 6% score that is greater than 30 seconds in- been afraid of falling since last winter. He of urgent hospitalizations, and only 50% dicates that the patient is at high risk of stumbled on a patch off ice and since then of those admitted to the hospital after falling, and will require assistance due to has noticed that he is not as quick or steady falling are alive one year later.2 impaired mobility. Those patients who on his feet as he would like. The majority of falls result from pre- have not experienced a fall and do not This case illustrates the typical predisposing risk factors or acute perturba- exhibit any balance or gait difficulties sentation of older adults at risk of falling. tions to the limited physiologic reserve of should be encouraged by their physician The exact cause of falling is often difficult an older person.7 Impairments in balance, to participate in exercise programs that to pinpoint because numerous contribut- gait, vision and muscle strength increase include balance and strength training. ing factors (such as age-related changes, the risk of falling. In addition, depression, For those patients who have fallen, diseases commonly occurring with aging, impaired cognition, postural hypotension, are afraid of falling, or exhibit difficul- multiple co-morbidities and the medica- the use of four or more medications, and ties with gait or balance, identifying rel- tions used to treat them) can be identified arthritis independently increase the risk of evant risk factors should be the first step in an older adult. The goal of this edition falling.3 Certain classes of drugs have a in fall prevention. The most successful of the column is to provide an evidenced- clear association with the risk of falling: approach to prevention has been a mul- based approach to fall prevention. I be- serotonin reuptake inhibitors, tricyclic tifactorial assessment for risk factors, fol- gin with a discussion of the scope of the antidepressants, neuroleptic agents, ben- lowed by interventions targeting the problem facing clinicians, and proceed to zodiazepines, anticonvulsants, class IA an- identified risk factors. It is estimated that a model for assessment and intervention; tiarrhythmic medications, and digoxin.8 this approach can reduce the risk of fall- at the conclusion of this article are the well- Older persons can be particularly suscep- ing by as much as 39% among older per- established clinical guidelines for fall pre- tible to falls during episodes of acute ill- sons living in the community.11 The cli- vention among older adults living in the ness or de-compensated chronic illness, nician should diagnose the underlying community. and in the first month following hospital cause or refer for an evaluation of a prob- discharge.9 Environmental hazards, such lem with gait or balance. The most suc- IMPACT & ETIOLOGY as rugs, improper footwear, poor lighting, cessful interventions studied in clinical Falls represent an enormous psycho- and stairs have been associated with an in- trials include reducing psychoactive logical, social and financial cost to the creased risk of falling.3,10 medications; reviewing the medication individual, family and society. It is esti- portfolio for inappropriate or unneces- mated that more than one third of com- ASSESSMENT & INTERVENTION sary medications; using physical or occu- munity-dwelling persons age 65 or older The exact age at which to begin pational therapy for strengthening, bal- experience a fall each year, that number screening for the risk of falling is uncer- ance and proper use of assistive devices; increases to 50% among persons over the tain; however, the prevalence of risk fac- management of orthostatic hypotension; 94 MEDICINE & HEALTH/RHODE ISLAND home safety evaluation for environmental hazards; and refer- REFERENCES ral for evaluation of visual impairments.12 1. Bergland A., Wyller TB. Risk factors for serious fall-related injury in elderly women living at home. Injury Prevention 2004; 10: 308-13. 2. Sattin RW. Falls among older persons. Annual Rev Public Health 1992; 13: GUIDELINES & RECOMMENDATIONS 489-508. The US Preventive Services Task Force (UPSTF) recom- 3. Tinnetti ME, Doucette J, et. al. Risk factors for serious injury during falls by mends that all persons 75 years of age or older be counseled older persons living in the community. J Ameri Griatrics Soc 1995; 43: 1214- about specific measures to reduce the risk of falling.13 Persons 21. 4. Centers for Disease Control and Prevention. Web-based Injury Statistics Query between the ages of 70 to 74 who have at least one risk factor and Reporting System (WISQARS) [database online]. National Center for for falling should also receive the same counseling about risk Injury Prevention and Control, CD). 2001. reduction measures. The American Geriatrics Society, the Brit- 5. Tinnetti ME, William CS. The effect of falls and fall injuries on functioning in community-dwelling older persons. J Gerontol A Biological Medical Sciences ish Geriatrics Society and the American Academy of Orthope- 1998; 53: M112-M9. dic Surgeons concertedly recommend that on a yearly basis 6. Tinnetti ME, William CS. Falls, injuries due to falls, and the risk of admission clinicians should not only ask their older patients about any to a nurisng home. NEJM 1997;1279-84. falls which occurred over the previous year, but also test gait 7. Tinetti ME, Speechley M, Ginter SF. Risk factor for falls among elderly persons living in the community. NEJM 1988; 319: 1701-7. and balance. For those who screen positive by having either 8. Leipzig RM, Cummings RG. Tinetti ME. Drugs and falls in older people. J experienced a fall or exhibit difficulty with gait or balance, it is Amer Geriatric Society 1999; 47: 30-50. recommended that physicians perform a comprehensive assess- 9. Mahoney J, Sager M, Johnson J. Risk of falls after hospital discharge. J Ameri ment, followed by interventions targeting the identified risk Geriatric Society 1994. 42: 269-74. 14 10. Tinnetti ME, Preventing falls in elderly persons. NEJM 2003; 348:42-9. factors. 11. Gillespie LD, Gillespie WJ, et. al. Interventions for preventing falls in elderly Let us return to the patient described at the introduction people. Cochrane Database Systemic Review 2001; 3: CD000340. of this column. This patient has experienced a fall and should 12. Tinnetti ME. Gordon C, et. al. Fall-risk evaluation and management, Geron- undergo a comprehensive assessment for relevant risk factors. tologist 2006. 46: 717-25. 13. USPSTF, Guide to clinical preventive services: report of the U.S. Preventive A detailed history reveals the following risk factors for falling: Services Task Force. Preventive Service Task Force. 1996, Baltimore: William depression, arthritis, use of more than four medications, and and Wilkins: 659-85. improper use of an assistive device. On physical exam, you con- 14. American Geriatrics Society, American Academy of Orthopaedic Surgeons Panel firm visual impairment and difficulties with gait and balance, on Falls Prevention, Guide for the Prevention of Falls in Older Persons. J Amer Geriatric Society 2001. 49: 664-72. but do not document orthostasis. He does have atrial fibrillation and the rate is well controlled with Metoprolol. His neu- Michael P. Gerardo, DO, is a Postdoctoral Research Fellow rologic (proprioception, cognition, and muscle strength) ex- in Community Health, and a Clinical Fellow in Geriatric Medi- amination was found to be normal. After considering other cine, Rhode Island and Miriam Hospitals. causes of gait disturbance and based on his musculoskeletal examination, you suspect that his gait impairment, which re- 8SOW-RI-GERIATRICS -032007 quires the use of a cane, is due to degenerative joint disease. Based on this comprehensive assessment, a targeted interven- THE ANALYSES UPON WHICH THIS PUBLICATION IS BASED were tion plan would include 1) referral to a physical therapist for performed under Contract Number 500-02-RI02, funded by the Centers for Medicare & Medicaid Services, an agency of gait, balance, and strength training and the proper use of an the U.S. Department of Health and Human Services. The con- assistive device, 2) occupational therapy for a home safety evalu- tent of this publication does not necessarily reflect the views ation to reduce the number of environmental hazards, and 3) or policies of the Department of Health and Human Services, an ophthalmologic exam. The medication portfolio was criti- nor does mention of trade names, commercial products, or cally evaluated, but the number of medications was not re- organizations imply endorsement by the U.S. Government. The author assumes full responsibility for the accuracy and duced because the patient required all six medications to effec- completeness of the ideas presented. tively manage his chronic illnesses; neither was dosage reduction needed. A year later, after having complied with the recommendations, the patient returns to your office and reports greater confidence in walking with his cane and no falls.

WEB BASED RESOURCES American Geriatrics Society (http://www.americangeriatrics.org/ education/forum) Centers for Disease Control and Prevention (http://www.cdc.gov) National Institute on Aging (http://www.nia.nih.gov)

95 VOLUME 90 NO. 3 MARCH 2007 RHODE ISLAND DEPARTMENT OF HEALTH • DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH EDITED BY JAY S. BUECHNER, PHD Classification of Emergency Department Visits: How Many Are Necessary? Jay S. Buechner, PhD, and Karen A. Williams, MPH

In a recent year, hospital emergency departments (EDs) in METHODS Rhode Island provided care to over 380,000 patients who did Under licensure regulations, the eleven acute-care gen- not require subsequent admission to an inpatient or observa- eral hospitals and two psychiatric facilities in Rhode Island re- tion bed.1 Many ED visits are for true emergencies that could port to the Department of Health a defined set of data items not be treated in other health care settings, but there has been on each emergency department visit beginning with visits oc- much discussion among providers, payers, and policy makers curring January 1, 2005. The data reported includes patient- on whether some of these patients could have been treated in level demographic and clinical information. This analysis cov- less intensive and more appropriate settings, had those settings ers ED visits occurring January 1 – December 31, 2005 and is been available, and whether additional ED visits could have limited to ED visits not resulting in admission to the hospital. been avoided had the patient’s primary care been adequate. A Due to complexities in the manner in which hospitals report recent study has classified ED visits based on whether they are ED data, the data presented here are subject to change as meth- medical emergencies, whether they require care from an emer- ods to distinguish ED visits that result in inpatient admission at gency department, and whether they are preventable or avoid- acute-care facilities from those that do not are improved. able with adequate primary care.2 The results of this study Billings, et al., reviewed approximately 5,700 medical have been applied to emergency department visit data from records of ED visits in New York and classified them according hospitals in Rhode Island for presentation here. to three standards – (1) emergent cases vs. non-emergent cases, (2) cases requiring a level of care provided only by a hospital ED vs. cases treatable in a primary care setting, and (3) cases that were preventable or avoidable with adequate primary care vs. those not preventable or avoidable.2 (Figure 1) Cases where the first-listed diagnosis was injury, mental health-related, or alcohol or drug-related were not classified. The algorithm resulting from that study has been applied Figure 1. Classification of emergency department visits to the ED visit data submitted from Rhode Island hospitals for calendar year 2005 to produce the estimates presented here. (The Cen- ter for Health and Public Service Research at New York University makes available a computer program for use with ED databases,3 and that program was adapted for use with Rhode Island ED data.)

RESULTS In 2005, there were 382,247 visits to EDs in Rhode Island’s acute-care general and psychiatric hospitals that did not result in an inpatient stay. Of these, an estimated 44% were in one of the three categories indicating the ED visit was either unnecessary or avoidable, including 19.8% non-emergent cases, 18.8% emergent cases not requiring the facilities of a hospital ED, and 5.4% emergent cases requiring the facilities of a hospital ED but preventable or avoidable with adequate primary care. (Figure 2) Of the remaining Figure 2. Emergency department visits by classification category, 56% of visits, the majority were for injuries, and a small Rhode Island, 2005 proportion were related to mental health and substance 96 MEDICINE & HEALTH/RHODE ISLAND providing a working estimate to inform changes in policy and operation that may result in better care and better outcomes for these patients. Hospital emergency departments have an important role in ambulatory care, but other care settings are better organized to provide continuity of care, patient education, and management of chronic conditions, all of which are hallmarks of a good primary care system.

REFERENCES 1. Williams KA, Buechner JS. Utilization of hospital emergency departments, Rhode Island 2005. Medicine & Health / Rhode Island 2006;89:415-6. 2. Billings J, Parikh N, Mijanovich T. Emergency department use in New York City: a substitute for primary care? Issue Brief. The Commonwealth Fund. November 2000. 3. http://www.nyu.edu/wagner/chpsr/index.html?p=25. Accessed February 6, 2007.

Jay S. Buechner, PhD, is Chief, Center for Health Data and Analysis, and Assistant Profes- Figure 3. Percent of emergency department visits that are non-emergent, sor of Community Health, Brown Medical School. primary-care treatable, or preventable/avoidable, by selected patient characteristics, Karen A. Williams, MPH, is Public Health Epi- Rhode Island, 2005 demiologist, Center for Health Data and Analysis. abuse. Approximately 10% fell into categories that could not be classified according to the Billings scheme. The proportion of ED visits that fell into one of the three categories representing unnecessary or avoidable utilization of the ED varied with patient characteristics. Higher than average proportions were seen among patients who resided in one of the six core cities in Rhode Island (47.1%), who were enrolled in the state’s Medicaid Program (49.9%), or who were Hispanic (50.4%), Black (47.7%), or Asian (47.2%). (Figure 3) The lowest proportions were seen among those who were uninsured (41.7%), who lived outside the core cities (41.9%), who had private insurance coverage (42.6%), or who were White (42.6%).

DISCUSSION The Billings algorithm classified just over half (54.4%) of ED visits at Rhode Island hospitals that did not result in an inpatient admission by whether they were emergent, treatable in a primary care setting, and preventable or avoidable with adequate primary care. Fewer than one-fifth of the classified visits were classified as emergent, not treatable in a primary care setting, and not preventable or avoidable with adequate primary care. The remaining visits can be looked at as an upper-bound estimate of the volume of ED visits in Rhode Island that may be avoidable or treated in other settings under the right circumstances. There are clearly some caveats needed in applying the Bill- ings methodology to Rhode Island ED data. The classification scheme is based on medical record reviews of 5,700 ED visits during 1994 and 1999 in Bronx Borough, New York City, where access to medical care and patterns of care may be much different than in Rhode Island in 2005. In addition, the data from the 5,700 examined records were used to apportion visits with 659 different principal diagnosis codes, so that most proportions used in the algorithm are based on small numbers of cases and therefore may be imprecise. However, the algorithm is useful in 97 VOLUME 90 NO. 3 MARCH 2007 DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH RHODE ISLAND DEPARTMENT OF HEALTH EDITED BY JOHN P. F ULTON, PHD Bloodborne Pathogen Transmission Potential From Neurological Pinwheels Robert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian The Occupational Safety and Health Administration (OSHA) logic testing must be considered a potential vehicle for person- defines contaminated sharps as “….any contaminated object to-person spread of blood borne pathogens such as HIV, Hepa- that can penetrate the skin including, but not limited to, needles, titis B and Hepatitis C. Moreover, with as many as 20 pins per scalpels, broken glass, broken capillary tubes and exposed ends pinwheel the risk is further increased. Fortunately, disposable of dental wires.” [29 CFR 1910.1030(a)] and or sterilizable devices exist. Examples include the As such the classic neurological pinwheel qualifies as a CleanWheel trademark ®, Cronin pinwheel ™ and others*. sharp. Thus, the use of the neurologic pinwheel for neuro- The reusable safety pin should also be considered a potentially contaminated sharp. Although the specific risk for iatrogenic transmission of Hepatitis B, C, and HIV with the use of these neurologic testing instruments has not been clearly defined it is clear that the use of nondisposable or unsterilized reusable pinwheel devices or pins is inconsistent with OSHA regulations which exist to protect both patients and caregivers.

* This reference to named products should not be misconstrued as an endorsement for any specific product by the RI Department of Health.

REFERENCES Occupational Safety and Health Standards. Toxic and hazardous substances. Bloodborne pathogens. 29 CFR 1910.1030(a) http://osha.gov/SLTC/bloodbornepathogens/index.html Durham D, Wasserburger J. Disposable needles should be the only instrument used to test sensation in neurologic examinations. West J Med 1997. 166:216-7. http://www.pubmedcentral.nih.gov/tocrender.fcgi?iid=124762

Robert S. Crausman, MD, MMS, is Chief Administrative Officer, RI Board of Medical Licensure and Discipline, Rhode Island Department of Health, and Associate Professor of Medi- cine, Brown Medical School. Utpala Bandy, MD, MPH, is Assistant Medical Director, Center for Epidemiology, Rhode Island Department of Health. Linda Julian is Complaint Investigator, Health Services Regu- lation, Rhode Island Department of Health.

CORRESPONDENCE Robert S. Crausman MD Chief Administrative Officer RI Board Medical Licensure and Discipline 3 Capitol Hill Figure 1. Lower extremity of a patient demonstrating tissue damage Providence RI 02908 after neurologic examination using a pinwheel device e-mail: [email protected]

Figure 2 – Neurologic pinwheel 98 MEDICINE & HEALTH/RHODE ISLAND 99 VOLUME 90 NO. 3 MARCH 2007 Call for Manuscripts: Choosing a Specialty What made you want to be a pathologist? a urologist? an orthopedic surgeon?

Medicine & Health/Rhode Island plans to feature articles from physicians, describing how they chose their areas of expertise—including articles from physicians who have switched specialties. Please e-mail manuscripts (maximum 1200 words) to Joan Retsinas (e-mail: [email protected]).

Letters to the Editor

TO THE EDITOR, TO THE EDITOR, Dr. Joseph Friedman’s stimulating and insightful com- I am sorry that you stifled your opinion on house of- mentary, “Dreams In Neurological Diseases,” [December, ficer dress codes in the face of your daughter’s naïve idea 2006 ] reminded me of the widespread interest in dreams of youthful feminist freedom. [January 2007] This is the and dreaming in American culture in the 20th Century, precise situation in which the gray heads must stick to their expressed by poets and by composers and lyricists who have guns. pondered the fearful, hopeful, painful, wistful, happy, sad Those of us actively engaged in teaching have a pro- and other Freudian complexities of the dream state in many prietary interest in the overall education of our medical popular songs. A representative but not comprehensive students and residents. This includes professional appear- list would include the following : ance and behavior as much as how to do a physical exam or close an abdomen. Dress is as much a part of patient I’ll See You In My Dreams interaction as interviewing skills and empathy. I would be Dream A Little Dream Of Me just as remiss allowing my charges to dress inappropriately When My Dreamboat Comes Home on the wards as wearing street clothes in the OR. Dream Dancing (one of Cole Porter’s best) The doctor-patient relationship is primarily one of Don’t Believe Everything You Dream (music by the extraordinary trust on the part of the patient. We must do talented Jimmy McHugh and cautionary lyric everything in our power to make sure that the level of re- by Harold Adamson) spect accorded our patients is not besmirched by some All I Do Is Dream Of You (the whole night through) misguided paean to individual expression or the current Lights Out (Close Your Eyes And Dream Of Me) modern fashion. We must lead by example and guidance, Dreamin’ Of You (sung by the popular Selena) regardless of the discomfort it may bring. I Dreamed A Dream Out Of My Dreams (and in to your arms). – STEPHEN E GLINICK, MD Lyrics by Oscar Hammerstein, from “Oklahoma”

Modern poet John Berryman (1914-1972) received universal acclaim for his “The Dream Songs” (Pulitzer Prize, 1964), an expression of his lifelong struggles with literary creativity, alcoholism, sexual promiscuity, failed marriages, depression, and suicide attempts (finally successful in 1972, when he jumped off a bridge in Minneapolis). These po- etic dream songs would have given Dr. Freud much to con- template. Compliments to Dr. Friedman for his interesting essay.

– MELVIN HERSHKOWITZ, MD

100 MEDICINE & HEALTH/RHODE ISLAND Images In Medicine Post-transplant Lymphoproliferative Disorder Following Renal Transplant Courtney A. Woodfield, MD

A 46 year-old male 8 months status post renal transplant for autosomal dominant polycystic kidney disease presented to the emergency department with fever and was found to have normal renal function. An enhanced CT examination of the abdomen and pelvis demonstrated a homogeneous soft tissue attenuation mass (arrow Figure 1) centered on the hilum and encasing the central vessels of a right lower quadrant double pediatric (en bloc) cadaveric transplant. Ultrasound guided percutaneous biopsy of the perinephric mass confirmed post- transplant lymphoproliferative disorder (PTLD), polyclonal subtype. The patient was treated with decreased immunosuppression with subsequent mass regression on follow up CT imaging. PTLD is a spectrum of lymphoid disorders resulting from immunosuppression after organ transplantation, ranging from B-cell hyperplasia to aggressive (usually B-cell) lymphoma. PTLD is associated with Ebstein-Barr virus infection of recipient B-cells with unopposed B-cell proliferation. Any nodal or extranodal site may be involved.1 Imaging plays an important role in the detection and diagnosis of PTLD as early lesions have a better prognosis and can often be managed with immunosuppression alone. More advanced PTLD lymphoma has a poorer prognosis with need for chemotherapy. PTLD of the transplant kidney typically manifests as a hi- lar-centered mass or less commonly as a diffuse, low attenuation infiltrative process of the kidney. (Figure 2) Imaging evaluation of renal transplants usually begins with ultrasound which can depict PTLD as hypoechoic mass(es) adjacent to the transplant kidney. CT or MRI is useful for indeterminate ultrasound exams and for establishing the size and extent of disease. Figure 3 is an enhanced axial T1-weighted fat saturated MR image of renal transplant PTLD with enhancing soft tissue mass of the renal hilum (long arrow) encasing the right iliac vessels. The low signal transplant ureter is also dilated (short arrow). . CORRESPONDENCE Courtney A. Woodfield, MD Department of Diagnostic Imaging Brown Medical School e-mail:[email protected]

REFERENCES 1. Kew CE, Lopez-Ben R, et al. Postransplant lymphoproliferative disorder local- ized near the allograft in renal transplantation. Transplantation 2000;68:809- 14. 2. Scarsbrook AF, Warakaulle DR, et al. Post-transplantation lymphoproliferative disorder. Clin Radiol 2005;60:47-55.

101 VOLUME 90 NO. 3 MARCH 2007 Physician’s Lexicon The Vocabulary of Paralysis in Anglo-Saxon England

Old English, the ancestor of the language occurs in the vivid Old English expres- færdeath, sudden death, suggesting that we speak today, was first written down sion for hemiplegia, healfdead adl. This treatment could often be futile, as about thirteen hundred years ago by is paralysis that comes “on the right half Hippocrates had discerned. Paralysis people we call the Anglo-Saxons. Sur- of the body or the left where the sinews might also leave one spæcleas or suffering viving Old English texts from this period, are powerless,” as one of the Anglo-Saxon from dumbnes, although this seems to including some medical leechbooks or leechbooks describes it. Old English have been blamed primarily on paralysis læcebocas, are rich in terms associated with seonu, sinew, was used indiscriminately for of the tongue, a very old and persistent paralysis, many of which we hear echoed what are now called nerves, tendons and notion. Depressed skull fracture follow- in our own speech and others which have ligaments. In this the Anglo-Saxon au- ing a blow to the brægenpanne could also fallen from the language or are scarcely thors differed little from their Latin mod- cause one to go silent. recognizable. Although paralysin, a bor- els who used nervus in the same way. The prevailing explanation for pa- rowing from Greek via Latin, occurs in That lyftadl could also include loss ralysis, including healfdead adl, was that some Old English texts, the most com- of sensation is reflected in other terms ap- harmful humors, yfel wæta, clogged pre- mon term for paralysis was lyftadl, mean- plied to a paralyzed part such as aslapen sumptive channels in the sinews by which ing weak disease. The first element of or adeadod, much as we might say a limb the brægen communicated with the rest this word is derived from Old English lef, feels asleep or dead. These terms may also of the body and vice versa. Treatment weak, and is related to our word for the have been used for paralytic stroke, along was directed at removing the offending weaker hand in those who are dextrals. with aslegen, which has the basic mean- humors from the paralyzed part by ap- (The right hand in Old English was the ing of stricken and is an ancestor of our plication of healing sealfas and other plas- swithere, the stronger.) Adl had the gen- words slay and slain. One instance of eral meaning of ailment or sickness, and Greek apoplexia is glossed by Old English (continued on page 102)

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 March Cause of Death 12 Months Ending with March 2006 Vital Statistics Report 2006 Number (a) Number (a) Rates (b) YPLL (c) Provisional Occurrence Diseases of the Heart 249 2,757 257.7 4276.0 Malignant Neoplasms 189 2,281 213.2 6,364.0** Data from the Cerebrovascular Diseases 41 446 41.7 680.0 Division of Vital Records Injuries (Accidents/Suicide/Homicde) 40 445 41.6 6,857.5 COPD 46 469 43.8 352.5

Reporting Period (a) Cause of death statistics were derived from the underlying cause of death reported by Vital Events September 12 Months Ending with physicians on death certificates. 2006 September 2006 (b) Rates per 100,000 estimated population of Number Number Rates 1,069,725 Live Births 1,155 12,996 12.1* Deaths 783 9,850 9.2* (c) Years of Potential Life Lost (YPLL) Infant Deaths (4) (89) 6.8# Neonatal Deaths (2) (70) 5.4# Note: Totals represent vital events which occurred in Rhode Marriages 986 7,129 6.7* Island for the reporting periods listed above. Monthly pro- Divorces 269 3,130 2.9* visional totals should be analyzed with caution because the numbers may be small and subject to seasonal variation. Induced Terminations 433 4,792 368.7# Spontaneous Fetal Deaths 86 921 70.9# * Rates per 1,000 estimated population Under 20 weeks gestation (71) (862) 66.3# # Rates per 1,000 live births 20+ weeks gestation (15) (59) 4.5# ** Excludes 2 deaths of unknown age 102 MEDICINE & HEALTH/RHODE ISLAND advertisement

103 VOLUME 90 NO. 3 MARCH 2007

The Official Organ of the Rhode Island Medical Society

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VOLUME 1 PER YEAR $2.00

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

NINETY YEARS AGO, MARCH 1917 TWENTY-FIVE YEAS AGO, MARCH 1982 In “A Study of Empyema or Pyothorax,” John W. Keefe, MD, In a “Current Commentary” column, Paul T. Welch, MD, FACS, bemoaned the “lack of investigating interest on the part of asked readers to support “A Uniform Determination of Death Act.” the profession at large.” He cited a high mortality, even “for this For the past five years, the General Assembly had shelved those bills. enlightened age.” “The cases of so-called recovery with a deformed Rebecca Silliman, MD, Mary Ann Passero, MD, David Kaplan, chest, a displaced heart, or a curved spine, an impaired function MD, Mary Condry, RN, Constance Pass, Philip Robzyk, Michael of lung or diaphragm, make the word ‘recovery’ a travesty.” Passero, MD, contributed “Acute Cardio-respiratory Morbidity, Air In “Hookworm Disease in Rhode Island, Alex M. Bur- Quality, Temperature and Pollen Concentration in RI.” They cited gess, MD, and Perry D. Meader, ScM, discussed the state’s 8 the results from a study that suggested a relationship between air diagnosed patients: 4 had lived in Providence for 2 years, 1 for pollutants and temperature and the incidence of bronchospasm. 1 year, 2 had recently arrived, and 1 had probably lived in RI The study sample included all patients admitted to Roger Williams for at least 2 years, but had returned to his native Portugal. General Hospital or treated as an outpatient with complaints of Because of the chilly winter temperatures, the authors were cardiopulmonary disease, during the warm months of 1980. not concerned about contagion. David H. Nichols, MD, FACS, FACOG, in “Clinical Harry S. Bernstein, MD, Consulting Pathologist, contrib- Pelvic Anatomy, the Types of Genital Prolapse and the Choice uted “Case of Tuberculous Meningitis” [from the Medical of Operation for Repair, “ advised: “In most instances a trans- Clinic of St. Joseph’s Hospital]. A 14 year-old girl arrived at vaginal operation is indicated.” the hospital in a coma. Her medical history included whoop- ing cough, measles at age 2, chicken pox at age 5, diphtheria at (continued from page 100) age 8, bronchitis at age 13. Ten days prior to admission, she felt drowsy and weak. Two days later, she complained of severe ters, while purging them from the entire body by a clænsung. headaches. Soon afterward, she started vomiting, became in- The latter could be effected by an appropriate blodlæting, by continent. Three days after admission, she died. The physi- provoking emesis with the aid of a spiwdrenc, or, if the face was cians considered poliomyelitis and encephalitis in the differen- involved, by drawing the yfel wæta from the head through the tial diagnosis; a lumbar puncture excluded infections due to nose and mouth with special concoctions and causing the pa- pyogenic organisms. To know the “character of the infection,” tient to sneeze, gefnesan. the author inoculated 2 guinea pigs with a centrifugalized speci- Those left permanently impaired by paralysis and forced men of spinal fluid. The author concluded: “It is difficult to to hobble or pull themselves along the ground were called distinguish tuberculous meningitis from acute poliomyelitis …” creopere, crypel, or, most evocatively, eorthcrypel, all words related semantically to the notion of creeping. The lama and the FIFTY YEARS AGO, MARCH 1957 healt could perambulate with the aid of a crycc and included Anthony V. Migliaccio, MD, and J. Robert Bowen, MD, not only the partially paralyzed but those, for example, made in “Tears of the Mesentery,” discussed 6 such patients treated at limleas by traumatic injury. The most gravely impaired were Rhode Island Hospital in the past 15 years. (One patient died.) the beddridan, destined to ‘ride’ their beds until freed by death Anthony Carditi, MD, in “Rheumatic Carditis in late Adult or the intervention of a saint. Life,” discussed 3 cases (ages 54, 64, and 70). He stressed the importance of early diagnosis: “…underlying atherosclerotic or inactive – JAMES T. M CILWA I N , MD rheumative heart disease itself may confuse the clinical picture.” J. Merrill Gibson, Jr, MD, discussed “Breast Carcinoma James T. McIlwain, MD, is Professor of Medical Science with Pregnancy or Lactation,” a rare occurrence (2% of breast Emeritus, Brown Medical School. cancer patients), with a poor prognosis (5-year survival 17%). The basic treatment was the same for patients, regardless of pregnancy: biopsy and radical mastectomy; but the decisions Figure 1 in the article entitled “Biohybrid Limbs: New revolved around timing and termination. Five-year survivals Materials and New Properties,” (p.4) of the January 2007 almost doubled when the pregnancies were terminated. issue was not credited. The scanning electron micrograph An Editorial supported “chemical testing of motorists al- images were courtesy of J. Dennis Bobyn, PhD, Jo Miller leged to have driven vehicles while under the influence of al- Orthopaedic Research Laboratory, Montreal General cohol.” The Rhode Island Council on Highway Safety had Hospital, McGill University. introduced such legislation in the General Assembly. 104 MEDICINE & HEALTH/RHODE ISLAND

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