Disease Specialists Research Articles

Context, ethics and pharmacogenetics

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, ‘traditional’ genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer’s disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice.

Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients

An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.

Telling about the stolen mind

Art forms (music, painting, sculpture, literature and theatre) are essential components in all social and human contexts. The role of art, in this case of theatre, is to express a visual event that aims to help the spectator identify himself/herself in the characters. The play presented here is "A...come non so" and shows the characteristic aspects of Alzheimer's disease from the first stage of the disease to the last stage: amnesia, aphasia, agnosia and apraxia. It tells the story of Carlo Pontercoli, a gerontologist and specialist in cardiovascular disease, who, while writing his paper on "The elderly and sexuality", manifests the first signs of the disease that killed his mother not so long before. The monologue aims to be a new contribution to the whole understanding of the problems concerning Alzheimer's disease through observation and visual communication of those problems.

Recurrent Vulvar Itching

CASE: A 25-year-old woman requests a second opinion about management of recurrent vaginal infections. Her local gynecologist suspects a “resistant infectious process” because the patient has recurrent vulvovaginal discharge and irritation despite the use of “various topical and oral anti-infectives.” Over the past 18 months, she has been treated with 7 courses of antibiotics, with either a brief response or no improvement of her symptoms. On questioning, the patient describes severe intermittent vulvar burning, intermittent itching, and constant mild-to-moderate vulvar pain. Additionally, she notes occasional dysuria and urinary frequency, but urine cultures have been negative. She denies urinary or fecal incontinence. Although she is currently using no medications or over-the-counter products, over the past half year she has used metronidazole and clindamycin vaginal creams, clindamycin vaginal ovules, Burow’s solution (Bayer Consumer Care, Morris Township, NJ) soaks, over-the-counter vaginal moisture solution, perineal cleansing pads, and panty shields with baking soda. Her medical history is remarkable for migraines and a laparoscopic tubal ligation. She is married, monogamous, and does not smoke, drink alcohol, or use illicit drugs. The patient reports using the following household products: scented dryer sheets, various laundry detergents depending on which is on sale, deodorant soap, scented liquid body wash, and topical lubricating jelly before intercourse. On examination (Fig.1), the vulva is markedly erythematous, without lesions, ulcerations, or excoriations. The skin markings are exaggerated, and there is mild edema. When the labia minora are separated, significant erythema is noted. The vestibule is also erythematous. Microscopy is normal, without yeast, clue cells, trichomonads, or inflammatory changes. The maturation is normal, and lactobacilli are present. A yeast culture is subsequently found to be negative. The woman is referred to a specialist in vulvar disease.

Caring for people with Parkinson's disease

Dr Clive Bowman, Medical Director of BUPA Care Services and Parkinson's disease specialist, discusses the importance of caring for people with this disease.

Enzymatic Replacement Therapy (ERT) with Low Doses in Gaucher Disease in the State of Sao Paulo (Brazil).

Abstract INTRODUCTION: The authors, who are members of the Gaucher Disease (GD) Specialists Committee of Sao Paulo State, Brazil, provide demographic data and report the evolution of patients from this Brazilian State, who were treated according to the Clinical Protocol and Therapeutic Instructions for GD treatment created by the Health Department www.saude.gov.br, Notice SAS/MS 449 of 08/07/2002. METHODS: In May 2004, 130 patients were analysed. One hundred and thirteen of the the130 received Enzymatic Replacement Therapy (ERT) with imiglucerase and 75% of them (85 /113) were > 12 years old. The GD symptoms were investigated in patients above this age who received 15–30 U/kg/2 weeks, according to the Health Department Protocol between August 2002 and November 2003. OBJECTIVES: Present the evolution of patients > 12 years old having a dose reduction in ERT following said Protocol. RESULTS: For the 85 patients > 12 years, the mean dose of ERT was 37,6 U/kg/2 weeks (13 to 62 U/kg/2weeks), 4 cases improved without sign of pain and maintained a low dose. Fourteen cases again suffered from bone pain. One of them developed bone infarct and 1 experienced a painless bone lytic lesion. The patients who were in a worse condition received a dose increase (up to 60 U/kg/2 weeks). Of the patients taking doses between 20 and 30 U/kg/2 weeks, 6 had bone pain again and 1 case experienced Parkinsons’ disease. The latter received a dose increase up to 60 U/kg/2 weeks CONCLUSION: The authors concluded that the dose in ERT must be individualised and that in many times, low doses (15 U/kg/2 weeks) are not enough to avoid GD complications.

Refractive Surgery Survey 2003

To determine the refractive surgery preferences of ophthalmologists worldwide, questionnaires were sent to 8920 members of the American Society of Cataract and Refractive Surgery. A total of 1174 questionnaires was returned by the deadline. The practice distribution included 30.0% cataract surgeons, 47.3% comprehensive ophthalmologists, 14.4% refractive surgery (RS) specialists, 4.5% corneal/external disease specialists, 1.9% glaucoma specialists, and <1% retinal/oculoplastics/pediatrics/neurophthalmologists/researchers/retired. Responses were compared with those in the 2001 and 2002 surveys and demonstrate that RS practice patterns continue to evolve.

Abraham Horwitz (1910-2000) Padre de la Salud Pública Panamericana

The Chilean physician Abraham B Horwitz (1910-2000) was an outstanding personality of World and Pan American public health during the second half of the twentieth century. He was member of a family that, emigrating due to ethnic persecutions in Russia, took refuge in Chile. He became a relevant physician, a specialist in infectious diseases and public health. He was highly influential in the birth of the Public Health School at the University of Chile and the Chilean Health Service. He became Executive Director of the Pan American Health Organization, holding that position for 16 years. During this period, the institution experienced a great development. He stimulated research in the areas of basic sanitation, nutrition and eradication of transmissible diseases. He also opened unexplored areas such as the relation between economy, modern administration and health. During his last years, he chaired a successful Nutrition Committee at the United Nations. The most outstanding achievement of this Committee was the promotion of widespread vitamin A use. His intellectual and social deed is continued by The Pan American Foundation for Health and Education and this institution established an annual prize in his memory.

The Role of Herman Hoppe of Cincinnati in the Initial Clinical Recognition of Myasthenia Gravis

One of the earliest papers describing a case of what came to be known as myasthenia gravis was written in 1892 in the German language by an American, Herman Hoppe, who at the time was an assistant in the Berlin polyclinic of the prominent German neurologist, Hermann Oppenheim. At Oppenheim’s instigation, Hoppe published the pathology of a case that Oppenheim had diagnosed during life; he collected all the reported similar cases and tried to establish a symptom-complex, for which he was given credit in Oppenheim’s great neurology textbook of 1894. Upon his return to Cincinnati, Ohio, Hoppe’s European experience qualified him as a specialist in nervous and mental diseases. His private practice of “neuropsychiatry” was his main occupation, but he also volunteered to teach as Professor of Nervous and Mental Diseases at the University of Cincinnati. In 1901 Oppenheim published the first monograph about what he called “ Die Myasthenische Paralyse (Bulbarparalyse ohne anatomischen Befund) ”, summarizing 60 cases described in the medical literature up to that time. Hoppe, on the other hand, wrote on myasthenia gravis only once again, a review article in 1914 in a Cincinnati weekly, giving Oppenheim credit for the establishment of the disease as a clinical entity.

Clinical and immunologic components of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that affects the lungs and the lymphatic system. It is seen by specialists in allergy, rheumatology, and pulmonary disease. Although there are no clues to etiology, an environmental basis has been implicated primarily on the basis of epidemiologic and anecdotal data. The majority of patients are very readily diagnosed and should not be confused with other pulmonary disorders. Sarcoidosis can become an issue if it occurs in the presence of other significant pulmonary disease, such as patients with asthma or hypersensitivity pneumonitis. Most patients remain asymptomatic and many are diagnosed when picked up on a routine screening exam. Steroids can be used to manage some patients but caution should be exercised to choose the appropriate dose and to treat patients for a limited period of time to avoid the complications of steroids. A minority of patients do progress to significant disease, including morbidity and mortality, and further research is needed to determine more appropriate and specific therapy for such situations.

Henry Ingersoll Bowditch and Oliver Wendell Holmes: Stethoscopists and Reformers

Two Bostonians, Henry Ingersoll Bowditch (1808-1892) and Oliver Wendell Holmes (1809-1894), went to Paris for advanced medical training and came home ardent disciples of Pierre Charles Alexandre Louis, leader of the French school that derived its eminence from expert auscultation and careful correlation of bedside and autopsy findings. Both Bowditch and Holmes became leaders in 19th-century American medicine. Bowditch, a successful practitioner and prolific medical writer, wrote the first important American text on physical examination and became our first specialist in pulmonary disease. He pioneered in the public health movement, was a charter member and later president of the American Medical Association, and was an abolitionist and an advocate for equal rights for women in medicine. Holmes left practice to become a medical educator. As Dean of Harvard Medical School, he tried unsuccessfully to admit white women and free black men to the school. Although his greatest fame came as a man of letters, Holmes considered himself first a physician and medical educator, and was justifiably proud of his definitive study, "The Contagiousness of Puerperal Fever" (1843). Today, Bowditch and Holmes are little appreciated as pioneers and reformers, but we remain in debt to them both.

Benefit of nurse specialists in Parkinson's disease

Benefit of nurse specialists in Parkinson's disease

Detection of ophthalmoscopically occult maculopathy by focal electroretinography.

We performed focal electroretinography (FERG) in 10 patients with reduced vision of unknown cause. No patient gave a family history of uncorrectably reduced vision, and none had taken any drug known to damage the retina. Visual acuity claims ranged from 20/40 to finger counting. Color discrimination was reduced in all but one patient. Visual field sensitivity was reduced nonspecifically in five of the six patients who could perform perimetry reliably. Ophthalmoscopy showed no pertinent abnormality in four of 10 patients, mildly reduced foveal reflex in two of 10, arteriolar narrowing in two of 10, foveal pigment disturbance in one of 10, and preretinal gliosis in one of 10. Flash visual evoked potential (VEP) testing showed no abnormality in seven of 7 patients. The pattern VEP was reduced or delayed in five of 5 patients, only one of whom showed the expected amplitude loss with decreasing check size. Five patients completed full-field electroretinography, six patients completed fluorescein angiography, and none showed pertinent abnormality on either test. FERG was performed in both eyes of seven patients and in one eye of three others. Signals were non-recordable from four eyes, abnormal in nine, equivocal in three, and normal in one. The severity of FERG abnormality did not correlate with the severity of acuity loss. FERG abnormalities were found in fourteen of 17 eyes of 10 patients with vision loss out of proportion to clinical findings. In these patients only one of 5 pattern VEP tests, none of 5 full-field ERGs, and none of 7 fluorescein angiograms suggested correspondingly severe maculopathy. The FERG results in these cases mitigated suspicions of nonorganic vision loss and permitted speedier referral to retinal disease and low vision specialists.

PRESCRIBING SYRINGES TO PREVENT HIV: A SURVEY OF INFECTIOUS DISEASE AND ADDICTION MEDICINE PHYSICIANS IN RHODE ISLAND

This article describes the assessment of physicians' attitudes and practices regarding prescribing syringes to injection drug users (IDUs). A brief, anonymous, self-administered questionnaire was sent to all Infectious Disease and Addiction Medicine specialists in Rhode Island. Of 49 eligible physicians, 39 responded (response rate 80%). Most (95%) indicated that there is a legitimate medical reason for IDUs to obtain sterile syringes. Many (71%) agreed that they would prescribe syringes to prevent disease in IDUs if it were clearly legal to do so. We can conclude that physician syringe prescription to IDUs may be an acceptable supplement to existing HIV prevention strategies.

Termination of Psychotherapy: A Training Perspective

The author describes the histories of three patients with panic-like episodes that turned out to be related to underlying, previously unsuspected tick-borne diseases. Each woman experienced symptoms that are not usual in panic disorder but are typical of neurological Lyme disease, including exquisite sensitivity to light, touch, and sounds, joint pain often in combination with cognitive changes including mental fogginess and loss of recent memory, and some degree of bizarre, shifting, and often excruciating neurological pain. Because these symptoms are atypical of primary panic disorder, they were very helpful in alerting the clinician to suspect an underlying physical illness. In each case, the results of testing revealed positive hallmarks of disseminated Lyme and other tick-borne diseases, including Lyme borreliosis caused by the spirochete, Borrelia burgdorferi, babesiosis, and ehrlichiosis. Since beginning treatment with intensive doses of appropriate antimicrobial medications for their tick-borne infections, all three patients have become free of panic attacks. Treatment of their infections by a specialist in Lyme disease allowed one of the women to discontinue anti-anxiety medication completely and another to reduce the dose of medication to occasional use only. The third patient is no longer anxious but her depression is resolving more slowly despite the ongoing use of an antidepressant. Two of the patients have also needed ongoing medication for pain and other symptoms of late-stage, neurological Lyme disease.

Ambulatory Intravenous Antibiotic Therapy in Quebec: The Hôpital Charles LeMoyne Experience in 1996

From January 1, 1996 to December 31, 1996, 343 patients received outpatient intravenous antibiotic therapy at Charles LeMoyne Hospital, a 436‐bed, acute care hospital in Greenfield Park, south of Montréal, Québec. The infectious diseases department saved 2660 bed‐days using outpatient therapy. The mean duration of outpatient therapy was 7.76 days; 81.6% of patients were admitted to the program directly from the emergency room, or outpatient hospital clinics or private offices in the community. Hospitalized patients constituted only 18.4% of admissions to the outpatient intravenous antibiotic therapy program. Forty per cent of the surgical/medical staff participated in the program and they were able to generate a significant impact by diverting patients to outpatient therapy. Two types of patients can benefit from an outpatient intravenous antibiotic therapy program. One group of patients needs empirical short term therapy and can be switched to oral sequential therapy after two to five days of outpatient intravenous antibiotic therapy. A second group of patients needs specific long term therapy for the full duration of the antibiotic therapy. Empirical short term therapy can be managed by emergency department or hospital‐based primary physicians, or medical/surgical specialists. Specific long term therapy can be managed by microbiology/infectious disease specialists or medical/surgical specialists. Hospitals that want to relieve pressure on emergency rooms and hospital bed demands should create facilities for both types of patients. Cefazolin and gentamicine/tobramycine were the most commonly used antibiotics in empirical short term therapy and in terms of number of patients treated. Ceftriaxone and vancomycin were most commonly used for long term therapy. The Drug acquisition antibiotic cost was $73,117 but constituted only 20% of the total outpatient intravenous antibiotic therapy cost. The per diem ambulatory cost was $140/patient/day.

Consult with the Specialists in Infectious Disease

Consult with the Specialists in Infectious Disease

Ethical issues in the history of prophylactic antibiotic use in neurosurgery

There has always been controversy about the indications for prescribing antibiotics to prevent postoperative sepsis in patients undergoing cranial and spinal surgery. The earlier specialists in infectious diseases warned that the effectiveness of antimicrobial drugs was leading to indiscriminate administration for the prevention of wound infection. Three clinical researchers present a review of the history of prophylactic antibiotic use in neurosurgery, including their own work, and raise a number of ethical issues not previously discussed in the literature about: (1) scientific methodology; (2) random selection; (3) prospective study; (4) blinded control; (5) placebo medication; (6) professional equipoise; (7) statististical analysis; (8) informed consent; (9) utilitarian philosophy; and (10) managed care. Also discussed are the dual role of physician and investigator and the ethical dilemma of depending upon meticulous technique versus adopting regimens of prophylactic antibiotics.

Antibiotic Stewardship at North York General Hospital

This article summarizes selected points from the presentation given at the First Antibiotic Stewardship Program in September 1997 at Niagara-on-the-Lake. The author’s opinions regarding a novel system of antibiotic monitoring called pharmLINK, as used in North York General Hospital (NYGH), are represented. NYGH is a mid-sized, regional referral hospital in Toronto, Ontario with approximately 450 beds (varying up to a capacity of 650 beds) involved largely in the secondary-level care of patients with a few select tertiary care level units. General medical, surgical, obstetrical/gynecological and paediatric services are provided at the hospital. While physician autonomy in the prescribing of medications was the norm in the early 1980s, the increasing number of available antibiotics and acknowledgement that both cost effectiveness and rising bacterial resistance were clinically relevant problems spurred the establishment of a Subcommittee on Antibiotic Usage in October, 1987. The committee was established to monitor and control antibiotic use through direct intervention and information bulletins, and by developing policies pertaining to the promotion of appropriate use. A number of mechanisms of intervention described in the literature have been tried with varying success. Some practitioners viewed direct restrictions or mandatory automatic substitution policies as a threat to the integrity of their practices. The fear of litigation if a ‘less broad-spectrum’ (implied to be less effective) antibiotic were prescribed was often cited as the reason to prescribe more costly medications. Reluctance to complete paperwork to justify the use of a particular agent and overall unwillingness to accept therapeutic suggestions from other health care professionals were other reasons for incomplete success in employing these interventions. Unlike in most institutions, prescribing of certain antibiotics has never required consultation or review by the Infectious Diseases (ID) specialist thus leading in certain cases to clinically less optimal or more costly outcomes. Staff education by means of ‘in-services’, grand rounds or seminars, while effective for brief periods of time, required repetition and commitment to maintain an adequate level of awareness. As the 1990s brought the issues of cost containment and responsible prescribing more urgently to the forefront in Canadian hospitals, alternative mechanisms of antibiotic stewardship were attempted. Joint efforts among the microbiology laboratory, the infection control practitioner, the (ID) specialist and the pharmacy resulted in the publication of a free handbook for staff that provided guidelines for antimicrobial use. Similar to handbooks available in other institutions, this publication was customized to the environment of the NYGH by using abbreviated information found in known published manuals. Through tables identifying types, frequencies and susceptibility patterns of the most common bacteria isolated at NYGH, as well as the best antimicrobial choices according to common diagnoses, physicians were provided with options and direction rather than inflexible rules. This handbook is periodically updated to reflect changes in bacterial susceptibility trends and as new agents are introduced to the formulary. To facilitate better prescribing practices and monitor antibiotic use more efficiently a new computer system and software were acquired, linking the microbiology and pharmacy department databases and allowing timely intervention in drug use. The purchase of pharmLINK (Dade MicroScan, West Sacramento) enabled improved antibiotic prescribing and, ultimately, better patient care. Cost savings were realized, and overall satisfaction with this system has been high. A specially trained drug utilization (DU) pharmacist was assigned the task of implementing the system.

The Rational Use of Antibiotics: The Princess Margaret Hospital Experience

In the past decade, there has been an alarming trend towards increased antimicrobial resistance in many human pathogens. Of the many possible factors responsible for these developments, the overuse and inappropriate prescribing of broad-spectrum antibiotics has been implicated (1). Rational, cost effective drug use needs to be promoted to begin controlling this problem. A structured drug use evaluation (DUE) process involving clinical pharmacists, staff physicians and infectious disease (ID) specialists has been reported to be effective in promoting appropriate drug prescribing (2). During the past 20 years, hospital-based retrospective and prospective DUE studies have played an integral role in health care delivery. Retrospective DUE involves an analysis of drug use after therapy has been administered. Prospective studies usually begin with the development of guidelines for the appropriate use of the agent in question (2,3). A formal evaluation process is initiated where pharmacists monitor drug therapy over a specified period of time. Interventions necessary to correct inappropriate prescribing patterns are then implemented before therapy is administered. The results of such studies are usually presented as the proportion of drug orders meeting guidelines following the intervention. The primary objective of many DUE studies is to improve physician prescribing within a set of hospital-approved guidelines for drug use. Theoretically, this should reduce the annual usage of broad-spectrum antimicrobials, thereby limiting the development of antimicrobial resistance. The DUE approach has demonstrated its ability to alter physician prescribing patterns in several drug classes, such as antiemetics, H2-receptor antagonists and antimicrobials (4-6). In one report, Lazor-Bajcar and Fowler (7) conducted a prospective DUE on the use of intravenous metronidazole in a community hospital. In that study, an initial retrospective audit of metronidazole determined that approximately 50% of all prescriptions did not meet hospital guidelines. A pharmacist-driven intervention program was initiated for all orders outside of the guidelines. Subsequent drug use within hospital guidelines increased to 86%, and there was an annual reduction in intravenous metronidazole usage by approximately 70% (7).