RESUMO
PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.
Assuntos
Antídotos/administração & dosagem , Alho/química , Intoxicação por Chumbo/tratamento farmacológico , Penicilamina/administração & dosagem , Compostos Fitoquímicos/administração & dosagem , Succímero/administração & dosagem , Adulto , Antídotos/economia , Análise Custo-Benefício , Estudos Transversais , Quimioterapia Combinada , Humanos , Irã (Geográfico) , Chumbo/sangue , Intoxicação por Chumbo/sangue , Masculino , Penicilamina/economia , Compostos Fitoquímicos/economia , Estudos Retrospectivos , Succímero/economia , Resultado do TratamentoRESUMO
BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.
Assuntos
Quelantes/administração & dosagem , Quelantes/economia , Redução de Custos , Substituição de Medicamentos , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/administração & dosagem , Penicilamina/economia , Sulfato de Zinco/administração & dosagem , Sulfato de Zinco/economia , Adolescente , Adulto , Criança , Pré-Escolar , Cobre/urina , Feminino , Seguimentos , Degeneração Hepatolenticular/urina , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Treatment of Wilson's disease (WD) with anti-copper agents is effective in most compliant patients. During long-term treatment with chelating agents, a two-day interruption of the treatment should result in normal urinary copper concentrations (<50 µg/dl). The aim of this study was to establish the usefulness of this method as a compliance assessment in these patients. We examined consecutive patients treated with d-penicillamine (DPA) undergoing routine follow-up studies at our center. We performed 24-h urinary copper excretion analysis 48 h after interruption of chelating therapy. Thirty-two patients were enrolled. After DPA cessation, normalization of copper excretion was observed in 91% of reportedly compliant patients. The specificity and sensitivity values of this test were 87% and 77%, respectively. Measurement of 24-h urinary copper excretion after a 48-h interruption of DPA therapy in patients with WD is a reliable method for confirming patients' compliance.
Assuntos
Quelantes/uso terapêutico , Cobre/urina , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/uso terapêutico , Adulto , Idoso , Quelantes/administração & dosagem , Feminino , Seguimentos , Degeneração Hepatolenticular/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Penicilamina/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Penicillamine, once considered the cornerstone of treatment for Wilson disease (WD), is rather expensive and toxic, and often causes neurological worsening. Zinc sulphate, aiming at the treatment of free-copper toxicosis, has emerged as effective, safe and cheap alternative. AIM: To assess the effect of withdrawal of penicillamine from maintenance treatment with penicillamine and zinc sulphate. PATIENTS AND METHODS: 45 patients of WD (M:F: 28:17; age at diagnosis: 13.5+/-63 years), on both penicillamine (P) and zinc sulphate (Zn), couldn't continue penicillamine due to financial constraints. Their clinical data, disability and impairment scores (Schwab and England (S&E) score, Neurological Symptom Score (NSS), and Chu staging) and follow-up data of patients maintained only on zinc sulphate were recorded. RESULTS: Majority of patients (84.4%) had neuropsychiatric manifestations. The mean duration of treatment with penicillamine (P) and zinc sulphate (P+Zn), before stopping penicillamine, was 107.4+/-67.3 months. 40 patients improved variably, while the rest didn't. They received only zinc sulphate for 27.2+/-8.5 months (range: 12 to 34) and 44 patients (97.7%) remained status quo or improved marginally. Only one patient reported worsening in dysarthria. Their disability and impairment scores during combination (penicillamine and zinc sulphate) and Zn alone were: Chu (1.3+/-0.5 vs. 1.5+/-1.9; p=0.4), NSS (1.8+/-3.1 vs. 1.5+/-2.3; p=0.03) and S&E (96.4+/-5.6 vs. 98.6+/-3.5; p=0.03). There were no adverse effects. CONCLUSIONS: Withdrawal of penicillamine from zinc sulphate/penicillamine maintenance therapy for patients with Wilson's disease was effective, safe and economic, for almost all patients. This retrospective study reiterates that zinc sulphate may be used as a preferred mode of treatment for patients with Wilson's disease.
Assuntos
Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/administração & dosagem , Sulfato de Zinco/administração & dosagem , Adolescente , Adulto , Adstringentes/administração & dosagem , Adstringentes/economia , Quelantes/administração & dosagem , Quelantes/efeitos adversos , Quelantes/economia , Terapia por Quelação/efeitos adversos , Terapia por Quelação/economia , Terapia por Quelação/métodos , Criança , Pré-Escolar , Cobre/metabolismo , Cobre/toxicidade , Feminino , Degeneração Hepatolenticular/metabolismo , Degeneração Hepatolenticular/fisiopatologia , Humanos , Masculino , Transtornos Neurocognitivos/induzido quimicamente , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/fisiopatologia , Penicilamina/efeitos adversos , Penicilamina/economia , Estudos Retrospectivos , Resultado do Tratamento , Sulfato de Zinco/economiaRESUMO
OBJECTIVE: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). PARTICIPANTS AND METHODS: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. RESULTS: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score. CONCLUSION: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.
Assuntos
Antirreumáticos/administração & dosagem , Indicadores Básicos de Saúde , Penicilamina/administração & dosagem , Esclerodermia Difusa/tratamento farmacológico , Adulto , Antirreumáticos/uso terapêutico , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Penicilamina/uso terapêutico , Esclerodermia Difusa/reabilitação , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the clinical implications of a score of > or =1.0 on the Disability Index of the Health Assessment Questionnaire (HAQ DI) at the first patient visit, and to examine the implications of improvement in HAQ DI score over 2 years in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: SSc skin and visceral involvement was assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD disease duration of 10 +/- 4 months) when they entered a multicenter drug trial and again 2 years later. Mortality and the occurrence of scleroderma renal crisis were assessed for a mean +/- SD of 4.0 +/- 1.1 years. Logistic and linear regression analyses were used to examine the relationship of the baseline HAQ DI score to morbidity, mortality, and visceral involvement, as well as the relationship of changes in the HAQ DI score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline HAQ DI score of > or =1.0 was predictive of mortality (odds ratio 3.22, 95% confidence interval 1.097-9.468) over 4 years. Multivariate linear regression demonstrated that a model which included the erythrocyte sedimentation rate at baseline (P = 0.005) and changes at 2 years in the swollen joint count (P = 0.002), total skin score (P = 0.005), and white blood cell count (P = 0.005) best explained the change in HAQ DI score over 2 years (R2 = 0.528). The HAQ DI score and total skin score at baseline were highly correlated (correlation coefficient 0.368), as were changes in the HAQ DI score and the total skin score over 2 years (correlation coefficient 0.492). Although the HAQ DI score was heavily influenced by hand dysfunction at baseline and at 2 years, improvement (reduction) in the HAQ DI score over 2 years was related to factors other than hand dysfunction. CONCLUSION: A baseline HAQ DI score of > or =1.0 predicted mortality over 4 years. Improvement in the HAQ DI score in these patients with diffuse scleroderma was associated with improvement in skin thickening, hand function, oral aperture, lung function, signs of arthritis, serum creatinine level, and the investigator's global assessment of improvement. The HAQ DI is a self-administered questionnaire that SSc patients can complete easily and rapidly and that gives the practicing physician important information about prognosis, patient status, and changes in disease course over time.
Assuntos
Avaliação da Deficiência , Penicilamina/administração & dosagem , Escleroderma Sistêmico/fisiopatologia , Relação Dose-Resposta a Droga , Indicadores Básicos de Saúde , Humanos , Modelos Logísticos , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/mortalidade , Inquéritos e Questionários , Resultado do TratamentoRESUMO
One hundred consultant rheumatologists were sent a questionnaire on their prescribing pattern, and dose and monitoring schedules of four disease modifying antirheumatoid drugs (DMARDs). Seventy-five completed questionnaires were received. Sulphasalazine was the most popular first choice DMARD. There was general agreement on dose schedules which were similar to those recommended in the data sheets although for each drug a minority used different dose schedules. There was, however, marked variation among respondents in what was accepted as an adequate trial of therapy, in monitoring schedules and in the interpretation of results of toxicity monitoring. In many cases these practices differed significantly from the data sheet recommendations. These differences in stated practice could have financial and medicolegal as well as clinical implications.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Monitoramento de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Reumatologia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Esquema de Medicação , Prescrições de Medicamentos , Tiomalato Sódico de Ouro/administração & dosagem , Tiomalato Sódico de Ouro/uso terapêutico , Humanos , Penicilamina/administração & dosagem , Penicilamina/uso terapêutico , Sulfassalazina/administração & dosagem , Sulfassalazina/uso terapêutico , Inquéritos e Questionários , Reino UnidoRESUMO
Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.
Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Degeneração Hepatolenticular/fisiopatologia , Administração Oral , Adulto , Química Encefálica , Criança , Cobre/análise , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Monitorização Fisiológica , Penicilamina/administração & dosagem , Penicilamina/uso terapêutico , Estudos Prospectivos , Fatores de TempoRESUMO
The administration of certain drugs to patients with established rheumatoid arthritis frequently results in improvement that is slow to appear but persists for long periods, even after the drug is discontinued. The three main drugs with this effect, whose efficacy and toxicity are reviewed in this paper, are gold salts, D-penicillamine and chloroquine. The cytotoxic agents used to treat rheumatoid arthritis, which likely have nonspecific anti-inflammatory actions and have serious long-term side effects, are also briefly reviewed. A new drug, levamisole, is currently being tested in patients with rheumatoid arthritis. It is suggested that the time for considering the introduction of a remission-inducing drug in patients with progressive rheumatoid arthritis is after an adequate trial of therapy with salicylates or other nonsteroidal anti-inflammatory agents, or both, and before the oral administration of steroids. It is difficult, however, on the basis of rigorous clinical comparisons, to recommend which of the three main remission-inducing drugs should be tried first, although gold salts have been used the most. Patients who have improved with 6 months of chrysotherapy may continue treatment for at least 3 years, during which time the frequency of mucocutaneous and renal toxic effects will steadily decrease. Some aspects of the medical economics of therapy with remission-inducing drugs for rheumatoid arthritis are discussed.