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Biomedical subjects

N H Shear

Publications and source records attributed to N H Shear.

At least 73 records · Page 4Linked to original sources
PubMed1998

Lamotrigine-induced severe cutaneous adverse reactions.

PURPOSE: We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions. METHODS: We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite. RESULTS: We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS). CONCLUSIONS: The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs.

Adolescent↗
PubMed1998

Quantifying the costs of serious adverse drug reactions to antiepileptic drugs.

PURPOSE: We assessed from an institutional perspective the direct costs of severe adverse cutaneous or hypersensitivity reactions due to antiepileptic drug (AED) therapy that led to hospitalization or prolonged hospital stay. METHODS: Patients admitted for or developing severe AED-induced cutaneous or hypersensitivity reactions while in hospital from January 1990 through June 1996 were identified by ICD-9 codes E936, E937, E693, E695.1, E995.1, and E995.2. Identified cases were analyzed retrospectively by chart review and were included in the analysis if a causal relationship was determined to be possible, probable, or definite. Clinical outcomes were abstracted and related direct costs of the adverse drug reactions (ADRs) calculated. RESULTS: A total of 384 cases were identified by ICD-9 codes, of which 13 cases (mean age +/- SD 52.9+/-21.0 years) were included for further analysis. Eight patients (62%) were admitted because of an ADR (median length of stay 9.5 days; range 4-43), five (38%) experienced an ADR during hospitalization (median duration of ADR episodes 8.5 days; range: 7-21 days). The median direct medical costs of the ADRs were Canadian (CDN) $3,128 (range 1,149-21,293) per patient. CONCLUSIONS: The management of serious cutaneous and hypersensitivity ADRs due to AEDs is associated with considerable direct medical costs. These figures should be considered along with drug acquisition costs and treatment of clinical successes and failures in the overall assessment of the economic impact of pharmacotherapy. Prospective collection of direct costs associated with ADRs in clinical trials would be of value.

Adolescent↗
PubMed1998

Gender differences in adverse drug reactions.

The objective of this study is to identify gender-related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 +/- 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin-related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

Administration, Oral↗
PubMed1998

Lamotrigine-associated anticonvulsant hypersensitivity syndrome.

We systematically reviewed and analyzed published and unpublished cases of lamotrigine-associated adverse drug reactions consistent with the features of the anticonvulsant hypersensitivity syndrome (AHS) to identify characteristics of the syndrome. We identified 26 cases (mean age, 28+/-18 years; range, 3.5 to 74 years; 54% female), of which nine were published. The characteristics of the syndrome associated with lamotrigine are comparable to AHS induced by older aromatic anticonvulsants.

Adolescent↗
PubMed1998

An overview of topical antifungal therapy in dermatomycoses. A North American perspective.

Dermatophytes cause fungal infections of keratinised tissues, e.g. skin, hair and nails. The organisms belong to 3 genera, Trichophyton, Epidermophyton and Microsporum. Dermatophytes may be grouped into 3 categories based on host preference and natural habitat. Anthropophilic species predominantly infect humans, geophilic species are soil based and may infect both humans and animals, zoophilic species generally infect non-human mammals. It is important to confirm mycologically the clinical diagnosis of onychomycosis and other tinea infections prior to commencing therapy. The identity of the fungal organism may provide guidance about the appropriateness of a given topical antifungal agent. Special techniques may be required to obtain the best yield of fungal organisms from a given site, especially the scalp and nails. It is also important to realise the limitations of certain diagnostic aids e.g., Wood's light examination is positive in tinea capitis due to M. canis and M. audouinii (ectothrix organisms); however, Wood's light examination is negative in T. tonsurans (endothrix organism). Similarly, it is important to be aware that cicloheximide in culture medium will inhibit growth of non-dermatophytes. Appropriate media are therefore required to evaluate the growth of some significant non-dermatophyte moulds. For tinea infections other than tinea capitis and tinea unguium, topical antifungals may be considered. For effective therapy of tinea capitis an oral antifungal is generally necessary. Similarly, oral antifungals are the therapy of choice, especially if onychomycosis is moderate to severe. Furthermore, where the tinea infection involves a large area, in an immunocompromised host or if infection is recurrent with poor response to topical agents, then oral antifungal therapy may be necessary. Topical antifungal agents may be broadly divided into specific and nonspecific agents. The former group includes the polyenes, azoles, allylamines, amorolfine, ciclopirox and butenafine. Generally the topical agent is available as a cream, sometimes for use intravaginally. Less commonly, the formulation may be in the form of a powder, lacquer, spray, gel or solution. Many of these agents have a broad spectrum of activity, being effective against dermatophytes, yeasts and Malassezia furfur. For the treatment of tinea corporis, tinea cruris tinea versicolor and cutaneous candidosis, once or twice daily application may be required, the most common duration of therapy being 2 to 4 weeks. For tinea pedis the most common treatment duration is 4 to 6 weeks.

Administration, Topical↗
PubMed1997

Drug-related mortality in Canada (1984-1994).

OBJECTIVE: To examine drug-related deaths due to adverse drug reactions between 1984 and 1994. DATA SOURCE: Voluntary reports of deaths due to adverse events as reported to the Adverse Drug Reaction Monitoring Program, Drugs Directorate, Health Protection Branch, Health Canada. METHODS: Drugs were classified according to the Anatomical, Therapeutic, Chemical (ATC) coding system. Descriptive statistics were utilized. RESULTS: One thousand four hundred and seventeen drug-related deaths were reported (700 male, 685 female, 32 unknown). The mean+/-SD age of patients was 54.6+/-21.7 years (range 1 month-97 years). In total, 2131 medications were implicated as suspect drugs (1.5+/-1.0, range 1-7). The most commonly reported categories of suspect drugs were the nervous system agents (50.6%), followed by cardiovascular system agents (9.0%), general antiinfectives for systemic use (8.8%) and musculoskeletal system agents (8.3%). One thousand and eighty-six deaths were classified as non-suicides. For non-suicide deaths, the most commonly reported suspect drugs were classified as nervous system agents (37.9%), followed by general antiinfectives for systemic use (12.3%), musculoskeletal system (11.5%) and cardiovascular system agents (10.2%). Three hundred and thirty-one (23.3%) reports were identified as suicides. For suicides, the most commonly reported suspect drugs were the nervous system agents (81.1%), followed by the respiratory system agents (8.5%) and the cardiovascular system agents (6.0%). CONCLUSION: Nervous system agents, musculoskeletal medications and general antiinfectives for systemic use figured prominently in deaths reported to HPB between 1984 and 1994.

Journal Article↗
PubMed1997

Multivesicular stellate cells in primary biliary cirrhosis.

Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We used electron microscopy and morphometry to perform a qualitative and quantitative examination of lipid-storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. Parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increase in the total number of lipid vesicles in stellate cells in all PBC patients when compared to livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 out of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell from 1 micromol/L to 5 micromol/L in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 out of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid-storage that involves stellate cells in PBC, which could be an early manifestation of this disease. Its significance remains to be determined.

Adult↗
PubMed1997

The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis.

BACKGROUND: To determine the efficacy, safety and tolerability of antidepressants in depressed elderly patients. METHODS: Search for randomized controlled double-blind studies evaluating atypical antidepressants (ATYPs), reversible inhibitors of monoamine oxidase-A, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants in moderate/severe depressed patients > or = 60 years for > or = four weeks. The random effects model (single-arm; comparative) was used to aggregate efficacy, safety and dropout. RESULTS: No difference in single-arm aggregation of outcomes for four antidepressant classes. Comparative analyses showed no statistical difference between outcomes, except SSRIs had a higher response rate than ATYPs. CONCLUSION: Elderly show no differences in antidepressant class outcomes. LIMITATIONS: Heterogeneity and lack of power. CLINICAL RELEVANCE: There is little advantage for antidepressant classes over another in the aged.

Age Factors↗
PubMed1997

Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: four case reports and a review of drug-induced psoriasis.

Adverse effects may occur in 10.4% of patients receiving terbinafine therapy, with cutaneous reactions in 2.7%. We describe the development of psoriasis in four patients who took oral terbinafine. Two patients had plaque-type psoriasis that flared 12 and 17 days, respectively, after starting terbinafine. Another patient developed pustular-type psoriasis de novo after 27 days of terbinafine therapy. The fourth patient was a psoriatic with stable plaque disease who experienced a pustular flare after taking terbinafine for 21 days. We are aware of only one report in the literature in which a patient developed pustular psoriasis de novo after 5 days of terbinafine therapy. In all patients the psoriasis cleared or lessened after discontinuation of terbinafine and institution of antipsoriatic therapy.

Adult↗
PubMed1997

Terbinafine: an update.

Oral terbinafine was first introduced in the United Kingdom in February 1991 and was approved for the treatment of onychomycosis in the United States in May 1996. It is estimated that 4 million patients worldwide have been treated with oral terbinafine as of December 1996. The efficacy of terbinafine in the treatment of onychomycosis and other dermatomycoses is reviewed. The adverse-effects profile of oral terbinafine is evaluated.

Adult↗
PubMed1997

Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.

BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options. OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

Abdominal Pain↗
PubMed1997

Cytochrome P-450 3A: interactions with dermatologic therapies.

Recent case reports and studies suggest that interactions involving the cytochrome P-450 mixed function oxidase system are important causes of medication toxicity and decreased efficacy during combination drug therapy. The cytochrome P-450 3A3/4 isoenzyme is involved in many significant drug interactions. New and familiar drugs continue to be implicated as having potentially serious interactions with this group of enzymes. An understanding of the basic principles of these interactions may have a major impact on patient outcome.

Anti-Bacterial Agents↗
PubMed1997

Onychomycosis in children: prevalence and treatment strategies.

BACKGROUND: Onychomycosis is observed less frequently in children than adults. Until recently management of onychomycosis in children included topical formulations, oral griseofulvin, and in some cases deferral of treatment. OBJECTIVE: We attempted to determine the prevalence of onychomycosis in North American children 18 years old or younger attending our dermatology offices (three Canadian, two U.S.) and to report the group's experience using fluconazole, itraconazole, and terbinafine for onychomycosis. METHODS: We undertook a prospective, multicenter survey in which all children, regardless of presenting complaint, were examined for onychomycosis by a dermatologist. In instances of clinical suspicion appropriate nail samples were obtained for light microscopy and culture. RESULTS: A total of 2500 children under age 18 were examined in the five-center survey (1117 males and 1383 females, mean +/- S.E. age: 11.2 +/- 0.1 years). There was one child with fingernail and ten with mycologically confirmed toenail dermatophyte onychomycosis. The overall prevalence of onychomycosis was 0.44%. Considering those children whose primary or referring diagnosis was not onychomycosis or tinea pedis, the prevalence of onychomycosis was 0.16%. Outside the survey we have seen six other children with dermatophyte onychomycosis; these 17 cases form the basis for the remainder of the report. Of the 17 children, eight (47%) had concomitant tinea pedis infection, and in 11 (65%) a sibling, parent, or grandparent had onychomycosis or tinea pedis. Management included topical terbinafine (two patients: one cured, one failed therapy), topical ketoconazole (one patient: clinical improvement), oral fluconazole (two patients: one cured, one had Down's syndrome and was noncompliant), oral itraconazole (four patients: three cured with subsequent recurrence at follow-up in one patient, one lost to follow-up), oral terbinafine (five patients: four cured with subsequent recurrence at follow-up in one patient, one failed therapy). One child received no therapy following discussion with the parents, one was lost to follow-up and one was found to have asymptomatic hepatic dysfunction with hepatitis C at pretherapy bloodwork. CONCLUSION: The prevalence of onychomycosis in our sample of North American children 18 years old or younger was 0.44% (n = 2500). In the subset of children whose primary or referring diagnosis was not onychomycosis, the prevalence of onychomycosis was 0.16%. Children with onychomycosis should be carefully examined for concomitant tinea pedis, and their parents and siblings checked for onychomycosis and tinea pedis. The newer oral antifungal agents fluconazole, itraconazole, and terbinafine may be effective and well-tolerated in the treatment of onychomycosis in this age group. These drugs should be carefully evaluated in a larger cohort of children with onychomycosis.

Adolescent↗