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Biomedical subjects

Neil H Shear

Publications and source records attributed to Neil H Shear.

At least 19 recordsLinked to original sources
PubMed2006

Dermatology postgraduate training in Canada: CanMEDS competencies.

Medical residency education and the development of formalized training objectives in Canada have evolved continuously, especially with the introduction of the Canadian Medical Education Directions for Specialists (CanMEDS) competencies by the Royal College of Physicians and Surgeons of Canada (RCPSC) in 1996. In order to evaluate the effectiveness of implementation of CanMEDS competencies in Canadian postgraduate dermatology training programs from the residents' perspective, a comprehensive national survey of all Canadian core dermatology residents was conducted in June 2004. One hundred percent of core (PGY3-5) dermatology residents across the country (n = 48) completed the survey. Forty eight percent of residents were familiar with the CanMEDS competencies. Within the CanMEDS framework, the competencies were felt to be taught adequately by the following proportion of residents: medical expert (78 %), professional (66 %), communicator (52 %), collaborator (48 %), health advocate (48 %), scholar (48 %), and manager (28 %), with notable differences based on the year of training. This is the first national Canadian survey examining dermatology postgraduate education from the residents' perspective with a focus on CanMEDS competencies. While the RCPSC CanMEDS project implementation is presently in the faculty development phase, further work must be accomplished to enhance awareness of CanMEDS competencies and to incorporate these into dermatology residency programs across the country. Particular targeting of the roles perceived to be poorly taught is needed.

Canada↗
PubMed2006

Efalizumab, a reversible T-cell modulator for psoriasis.

The humanized monoclonal antibody (MAb) efalizumab (Raptiva) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells--including pathogenic CD8 memory T cells that are prominent in psoriatic lesions-- are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab's pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.

Antibodies, Monoclonal↗
PubMed2006

Socioeconomic status influences care of patients with acne in Ontario, Canada.

BACKGROUND: Canada's universal health care system is designed to ensure equitable access to medical care based on need rather than socioeconomic status, although a number of studies indicate a preferential access and greater use of specialist services for those patients in higher socioeconomic groups. OBJECTIVES: The primary objective of this study was to determine whether socioeconomic status influences access to specialist care by a dermatologist for the management of acne in Ontario, Canada. A secondary objective was to determine whether the urban-rural dwelling status of patients affects access to specialty care. METHODS: We conducted a population-based cohort study using administrative health care databases covering more than 12 million residents of Ontario. Individuals age 12 to 27 years with a new diagnosis of acne by a general practitioner were identified as belonging to 1 of 5 socioeconomic groups based on median annual neighborhood household income. Patients were then observed for 2 years after the index visit to identify visits to a dermatologist. The main outcome measure was visitation to a dermatologist within 2 years of an initial diagnosis of acne. RESULTS: The study cohort consisted of 295,469 patients given a diagnosis of acne by their primary care physician of which 59,799 (20%) were subsequently referred to a dermatologist. Of those in the lowest income group of less than Can dollars 20,000, 17% were referred to a dermatologist, as compared with 24% in the highest income group of greater than Can dollars 80,000 (P value for trend < .001). Furthermore, patients living in an urban area had a 43% greater likelihood of being referred to a dermatologist (odds ratio 1.43, 95% confidence interval 1.39-1.48) as compared with patients in a rural location. LIMITATIONS: Limitations of our study include imputing socioeconomic status of patients on the basis of median income at the neighborhood level rather than on the basis of data on individual patients. Furthermore, our use of administrative databases did not allow us to characterize the severity of acne in our population cohort and whether that would affect referral patterns. CONCLUSION: Within Canada's universal health care system, those likely to be in lower socioeconomic groups are significantly less likely to visit a dermatologist for specialist consultation.

Acne Vulgaris↗
PubMed2006

Povidone-iodine-induced burn: case report and review of the literature.

Burns are a rare but potentially serious complication of povidone-iodine use. This rare adverse drug reaction developed in a 38-year-old woman who underwent laparoscopic right ovarian cystectomy and endometrial ablation as a day procedure involving application of the topical antiseptic 10% povidone-iodine solution. Two days later, the patient was admitted to the hospital with burning, pain, itching, marked redness, and blistering extending from her midback to buttocks. A stain on her back also was evident. Partial-thickness chemical burn was diagnosed. Review of the literature yielded 13 other cases of povidone-iodine-induced burn. This underrecognized adverse effect of povidone-iodine application typically occurs when the povidone-iodine has not been allowed to dry or has been trapped under the body of a patient in a pooled dependent position. The burn is usually seen immediately after the procedure or on the next day, and typically heals with minimum scarring within 3-4 weeks with conservative treatment. The commonly postulated mechanism is a chemical burn due to irritation coupled with maceration, friction, and pressure. Given the widespread use of povidone-iodine and the potential for development of infection after a burn, clinicians need to be aware of this possible povidone-iodine-associated adverse drug reaction, and of preventive measures.

Adult↗
PubMed2006

Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability?

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohn's disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohn's disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of >2.5 years' continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm.

Biological Products↗
PubMed2005

Clinical and immunogenetic correlates of abacavir hypersensitivity.

A patch test (PT) may be useful in defining true abacavir hypersensitivity syndrome (AHS). Seven previously PT-positive patients remote from the original AHS were shown to have robust 24 h responses, supporting PT durability. HLA-B*5701 was present in all seven PT-positive versus one of 11 controls tolerating abacavir (P < 0.001). Five of seven PT (71%) versus one of 11 controls (9%) (P = 0.005) showed significant abacavir-specific CD8 proliferation, suggesting a direct role for HLA-B*5701-restricted CD8 cells in the pathophysiology of AHS.

Anti-HIV Agents↗
PubMed2005

National appraisal of dermatology residency training: a Canadian study.

OBJECTIVES: To provide the first comprehensive assessment of dermatology residency training in Canada based on the residents' perspective; to examine and elucidate trends in current residents' envisioned career paths and aspirations. DESIGN: A national survey conducted in June 2004. PARTICIPANTS: All Canadian dermatology residents. MAIN OUTCOME MEASURES: Cross-sectional analysis of (1) satisfaction with and importance placed by the trainees on the various curriculum components as measured by a 5-point Likert-type scale and (2) current residents' career and practice plans. RESULTS: One hundred percent of dermatology residents across the country (n = 48) responded to the survey. The greatest discrepancies between ranked importance and corresponding satisfaction were observed for the teaching from faculty (both didactic and clinic based) and for the practice management exposure and training. Residents were most satisfied with dermatopathology education (score, 4.4 of 5.0) and least satisfied with cosmetic dermatology (2.7 of 5.0) and dermoscopy training (2.8 of 5.0). Men indicated more interest than women in academics (71% [n = 12] vs 45% [n = 14]), research (41% [n = 7] vs 16% [n = 5]), and teaching (71% [n = 12] vs 42% [n = 13]), while female residents were more inclined toward pediatric dermatology (42% [n = 13] vs 29% [n = 5]) and cosmetic dermatology (48% [n = 15] vs 29% [n = 5]). An overall trend of decreased interest in academic and hospital-based practice was noted with progression through residency training. CONCLUSIONS: This study provides a current picture of dermatology postgraduate education in Canada from the residents' perspective. Above all, dermatology residents desire more teaching (clinic, didactic, and practice management) and mentorship from their faculty. Recruitment and retention of women in academic dermatology may benefit from early intervention during residency. The data are intended to assist dermatology programs with development, evaluation, and improvement of their curricula and can serve as a reference point to gauge future trends.

Attitude of Health Personnel↗
PubMed2005

Adverse drug interactions and reactions in dermatology: current issues of clinical relevance.

This article highlights several adverse drug interactions and reactions relevant to current dermatologic practice. Absorption interactions between drugs and compounds containing polyvalent cations, potential interactions between herbal and conventional medicines, the meaning of sulfa allergy, and adverse cutaneous reactions caused by epidermal growth factor receptor inhibitors are discussed.

Drug Eruptions↗
PubMed2005

Clindamycin skin testing has limited diagnostic potential.

We examined the role of clindamycin prick and intradermal skin testing in a tertiary care clinic population. Experience with diagnostic modalities such as prick and intradermal testing has been limited with clindamycin. A retrospective chart review was conducted for patients with immunologic reactions temporally associated with clindamycin who were referred to the Drug Safety Clinic (Toronto, Ontario). A total of 31 patients were identified who had undergone prick and intradermal skin testing. All 31 negative immediate prick and intradermal tests were followed by a 150 mg oral dose of clindamycin. 10/31 (32%) subjects had significant reactions to the oral clindamycin provocation. 2 patients reported delayed reactions at the clindamycin intradermal test sites. Our experience suggests that prick and intradermal skin testing is not adequate in identifying patients with previous allergic reactions associated with clindamycin. Oral provocation tests can be used in patients with histories of clindamycin adverse reactions; however, it should be offered on a risk-benefit basis.

Administration, Oral↗
PubMed2005

Hydrochlorothiazide-induced noncardiogenic pulmonary edema: an underrecognized yet serious adverse drug reaction.

Noncardiogenic pulmonary edema is a rare but potentially life-threatening complication of hydrochlorothiazide therapy. We describe three patients who developed this serious adverse reaction. A 64-year-old woman developed dypsnea and hypotension within 60 minutes of taking a single dose of hydrochlorothiazide 25 mg. She was admitted to the critical care unit with acute respiratory failure and subsequent multiple-organ dysfunction. The second patient was a 56-year-old woman who experienced sudden onset of shortness of breath that developed 10 minutes after taking a single dose of hydrochlorothiazide 25 mg. The third was a 59-year-old woman who developed sudden onset of shortness of breath, nausea, vomiting, and diarrhea after her first dose of hydrochlorothiazide-triamterene. All three women had a history of a similar, albeit minor, reaction to a thiazide diuretic. Review of the literature identified 36 additional cases of noncardiogenic pulmonary edema after thiazide use. The patients developed symptoms 10-150 minutes after ingestion of hydrochlorothiazide or another thiazide. Symptoms can occur on first exposure to the drug or in patients taking the drug intermittently. Of interest, 90% of documented cases occurred in women. With the increasing use of thiazide diuretics in the treatment of hypertension, clinicians need to be aware of the possible association of these drugs with the development of noncardiogenic pulmonary edema.

Diuretics↗
PubMed2004

Psoriasis and the new biologic agents: interrupting a T-AP dance.

Psoriasis is an immune-mediated skin disease in which chronic T-cell stimulation by antigen-presenting cells (APC) occurs in the skin. This interplay between the T-cell and APC has been likened to a "T-AP dance" where specific steps must occur in sequence to result in T-cell activation and the disease phenotype; otherwise T-cell anergy would occur. Several novel engineered proteins designed to block specific steps in immune activation (biologic agents) have demonstrated efficacy in the treatment of psoriasis. These agents include fusion proteins, monoclonal antibodies and recombinant cytokines. These medications act at specific steps during the T-AP dance either to inhibit T-cell activation, costimulation and subsequent proliferation of T-cells, lead to immune deviation or induce specific cytokine blockades. The potential increased selectivity for specific pathways in immune activation, clinical efficacy and relative safety of these new agents offers an alternative for the treatment of moderate to severe psoriasis.

Antibodies, Monoclonal↗
PubMed2004

Objective psychological measurement and clinical assessment of anxiety in adverse drug reactions.

BACKGROUND: A confounding factor in the diagnosis of adverse drug reactions (ADRs) is the psychological state of the patient. Patients with underlying anxiety and related disorders may present with psychogenic reactions, which involve physiologic responses originating from psychological, rather than organic factors. OBJECTIVE: To examine the contribution of anxiety and related disorders to adverse drug events. METHODS: Participants from an adverse drug reaction clinic completed the Trauma Symptom Checklist-40 (TSC-40), a 40-item questionnaire consisting of six subscales: anxiety, depression, dissociation, sexual abuse trauma index (SATI), sexual problems, and sleep disturbance. Physicians assessed the likelihood that adverse events were due to anxiety or drug(s) by providing an anxiety score (0 to 10) and an ADR score (0 to 10), respectively, for each participant. RESULTS: Patients clinically assessed as having "high anxiety" (anxiety score 7-10 and ADR score 0-3; n = 11) scored higher than patients clinically assessed as having a "true ADR" (anxiety score 0-3 and ADR score 7-10; n = 19) on the TSC-40 total (P = 0.006) as well as anxiety (P = 0.012), depression (P = 0.007), and SATI subscales (P = 0.016). CONCLUSION: This study is the first to use a validated psychological measurement to indicate that a substantial percentage of reported adverse drug events may in fact be a manifestation of underlying anxiety and/or related disorders. We suggest that mechanisms of symptom generation may be analogous to those operative in idiopathic environmental intolerance.

Adolescent↗
PubMed2004

Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a life-threatening adverse drug reaction (ADR) that is primarily the result of drug exposure (incidence 0.4-1.3 per million person-years). Life-threatening ADRs such as TEN should be reported to ADR monitoring programmes, which collect reports for suspected ADRs and alert the public and medical practitioners to new drug hazards. In Canada, reports are made to the Canadian Adverse Drug Reaction Monitoring Program (CADRMP). OBJECTIVE: To examine the extent of under-reporting for TEN in Canada. DESIGN: A retrospective case series design was used to collect all TEN cases for the period January 1995 to December 2000. METHODS: The CADRMP and 22 burn centres across Canada were contacted for all TEN patients treated during the specified time period. PATIENT GROUPS STUDIED: The study population consisted of patients admitted to burn treatment sites across Canada, patient cases reported to the CADRMP and patient cases recorded by the Canadian Institute for Health Information (CIHI) hospital discharge summaries as the International Classification of Diseases Version 9 Clinical Modification (ICD-9-CM) code 695.1. RESULTS: Twenty-five TEN cases (six fatal) were reported to CADRMP from January 1995 to December 2000. During this period, 14 (63.6%) burn treatment sites reported admission of 250 TEN cases. Hospital discharge summaries using the ICD-9-CM code 695.1 indicated that 4349 cases were admitted to hospital during this time period and it was estimated that 15.5% (n = 674) of these cases were TEN. Using the burn facility data as the denominator, 10% (25 of 250) of TEN cases were reported to CADRMP. Using CIHI data as a denominator, only 4% (25 of 674) of TEN cases were reported to CADRMP. CONCLUSIONS: There is serious under-reporting of TEN. Lack of reporting of life-threatening ADRs can compromise population safety. There is a need to increase awareness of ADR reporting programmes.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Topical calcineurin inhibitors in the treatment of atopic dermatitis: a meta-analysis of current evidence.

PURPOSE: To summarize success rates of the topical calcineurin inhibitors tacrolimus and pimecrolimus in treating atopic dermatitis. METHODS: Randomized controlled trials (RCTs) comparing either drug to themselves (i.e. dose-ranging studies), each other, the vehicle (or placebo), or corticosteroids were obtained from Medline, EMBASE, and Cochrane databases. Two reviewers identified studies and extracted data, a third reviewer adjudicated disagreements. Outcomes included success, as defined by 90%, 75%, or 50% reductions from baseline in Eczema Area and Severity Index (EASI) scores or equivalent at 1, 3, 6, and 12 months, and also the difference between drug and vehicle (placebo). Rates were combined using a random effects meta-analytic model. RESULTS: Of 180 articles identified, 165 were rejected (142 not RCTs/inappropriate outcome, 23 inappropriate/unextractable data). We included 15 articles reporting on 16 trials (nine tacrolimus and seven pimecrolimus trials) involving a total of 5301 patients, of whom 2107 received tacrolimus, 1225 received pimecrolimus and 1969 patients were controls. Tacrolimus reduced EASI scores by 65.6% at 1 month and 73.0% at 3 months; pimecrolimus reduced scores by 61.5% at 1 month, 60.3% at 6 months, and 61.9% at 12 months. When the difference in EASI score reductions were compared between active drug and placebo, tacrolimus success was 51.5% above placebo at 1 month and pimecrolimus was 45.9% higher at 1 month, 24.9% at 6 months, and 16.1% at 12 months. CONCLUSIONS: Success rates for tacrolimus and pimecrolimus were statistically similar. However, tacrolimus rates were consistently higher numerically than those for pimecrolimus, and tacrolimus was used in patients with more severe disease. A head-to-head RCT is required to determine if true differences exist between these drugs.

Administration, Cutaneous↗