RESUMO
BACKGROUND: Aminosalicylates are the most frequently prescribed drugs for patients with Crohn's disease (CD), yet evidence to support their efficacy as induction or maintenance therapy is controversial. AIMS: To quantify aminosalicylate use in CD clinical trials, identify factors associated with use and estimate direct annual treatment costs of therapy. METHODS: MEDLINE, Embase and CENTRAL were searched to April 2017 for placebo-controlled trials in adults with CD treated with corticosteroids, immunosuppressants or biologics. The proportion of patients co-prescribed aminosalicylates in placebo arms was pooled using a random-effects model. Meta-regression was used to identify factors associated with aminosalicylate use. Annual treatment costs were estimated using the 2016 Ontario Drug Benefit Program. RESULTS: Forty-two induction and 10 maintenance trials were included. The pooled proportion of patients co-prescribed aminosalicylates was 44% [95% CI: 39%-49%] in induction trials and 49% [95% CI: 35%-64%] in maintenance trials. There was substantial to considerable heterogeneity (I2 = 86.0%, 91.8% for induction and maintenance trials, respectively). In multivariable meta-regression, aminosalicylate use has decreased over time in induction trials (OR 0.50 [95% CI: 0.34-0.74] per 10-year increment). While a decline has been seen over time, 35% of CD patients were still using aminosalicylates in contemporary trials from the last 5 years. The estimated annual cost for the lowest price mesalazine (mesalamine) formulation is approximately $32 million for the Canadian CD population. CONCLUSIONS: Over one-third of CD patients entering clinical trials are still co-prescribed aminosalicylates. A definitive trial is needed to inform the conventional practice of using aminosalicylates as CD maintenance therapy.
Assuntos
Doença de Crohn/tratamento farmacológico , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Mesalamina/economia , Mesalamina/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Corticosteroides/economia , Adulto , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/economia , Custos de Medicamentos , Quimioterapia Combinada/economia , Quimioterapia Combinada/estatística & dados numéricos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/economia , Ontário/epidemiologia , Padrões de Prática Médica/economia , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Indução de Remissão , Fatores de RiscoAssuntos
Doenças Inflamatórias Intestinais , Pancreatite , Azatioprina , Genótipo , Humanos , FenótipoRESUMO
BACKGROUND: Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis. AIM: To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. METHODS: A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype. RESULTS: The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients. CONCLUSIONS: The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD.
Assuntos
Azatioprina/efeitos adversos , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Pancreatite/induzido quimicamente , Pancreatite/genética , Adulto , Azatioprina/uso terapêutico , Canadá , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo de Nucleotídeo Único , Estudos RetrospectivosRESUMO
BACKGROUND: Thiopurines (Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are considered a well-established therapy for patients with Inflammatory Bowel Disease (IBD) including ulcerative colitis (UC) and Crohn's Disease (CD). However, nearly 20% of patients discontinue thiopurines due to adverse events. Functional polymorphisms of several enzymes involved in the metabolism of thiopurines have been linked with toxicity. The clinical value of variant carriers such as TPMT, ITPA and GSTs in predicting toxicity and adverse events for IBD patients treated with thiopurines remains to be clarified. OBJECTIVES: To determine if variation in TPMT, ITPA and GST genotypes can predict adverse effects such as neutropenia, pancreatitis, liver enzyme elevation, as well as clinical response for patients with IBD treated with thiopurines. METHODS: Patients known to have IBD and treated with AZA or 6MP were enrolled. Adverse effects were calculated and their correlation with TPMT, ITPA and GST genotypes was evaluated. Further, the correlation between clinical response and TPMT, ITPA and GST genotypes were assessed. RESULTS: A total of 53 patients were enrolled. 16/53 patients (28.6%) responded to AZA therapy. 17 patients experienced adverse events with 10 having to discontinue treatment. Three patients (5.4%) developed severe myelosuppression (WBC< 2.0 or neutrophils <1.0). Loss of function TPMT genotype was associated with adverse events (OR 3.64, 95% CI 0.55 - 24.23, p=0.0313). ITPA and GST polymorphisms were not associated with toxicity. GSTM1 deletion was associated with poor clinical response to therapy (OR 3.75, 95% CI 0.940 - 14.97, p=0.1028), however, neither TPMT*3A nor ITPA polymorphisms were associated with clinical response. CONCLUSION: In addition to TPMT for adverse events, genotyping for GSTM1 appears to predict clinical response in IBD patients treated with thiopurines.
Assuntos
Azatioprina/efeitos adversos , Marcadores Genéticos/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diarreia/induzido quimicamente , Feminino , Seguimentos , Glutationa Transferase/genética , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Methotrexate (MTX) is administered subcutaneously to Crohn's Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80-125% of the bioavailability of the standard (US Food and Drug Administration - FDA). AIM: To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes. METHODS: Eleven patients received a PO and an SC MTX dose (25 mg) separated by one week over a two-week interval. Blood samples were collected at specified times over a 24-h period for each patient on two separate days. MTX plasma levels were obtained using sensitive mass spectrometry. Areas under the curve (AUC) were compared between the two routes. RESULTS: The mean AUC values were 3375 ng/mL × h (PO MTX) and 3985 ng/mL × h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62-1.08). This correlates with a relative PO bioavailability of 86% in comparison to SC. The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). There were no adverse events. CONCLUSIONS: The mean MTX AUC (PO/SC) in these patients falls outside the 90% confidence interval for the bioequivalence limit. SC MTX is more bioavailable than PO MTX; however, the mean relative MTX bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX could be proposed in responders who would prefer this route.
Assuntos
Doença de Crohn/metabolismo , Imunossupressores/farmacocinética , Metotrexato/farmacocinética , Administração Cutânea , Administração Oral , Adulto , Área Sob a Curva , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Ontário , Equivalência TerapêuticaRESUMO
BACKGROUND: Some patients with ulcerative colitis (UC) require immunosuppressants as maintenance therapy. AIM: To assess epidemiological, clinical and disease factors at diagnosis that predict immunosuppressant use in UC. METHODS: All UC patients diagnosed between 1992 and 2005 and currently managed in the inflammatory bowel disease (IBD) clinic were included. Forty-three patients who currently or previously received azathioprine (AZA) or mercaptopurine (MP) for UC were compared with 130 controls. Charts were reviewed and logistic regression analyses were applied to identify factors associated with AZA or MP use. RESULTS: In univariate model, seven factors at diagnosis correlated with AZA use: male gender [odds ratio (OR) 2.2]; left-sided or extensive colitis or pancolitis (OR 8.7-14.1); systemic steroid use within the first 6 months of diagnosis (OR 5.1); more than 10 bowel movements daily (OR 6.4); persistent or mostly blood in stool (OR 2.8); endoscopic proven moderate to severe disease (OR 7.2-12.0) and requirement of hospitalization (OR 2.7) on diagnosis. In multivariate model, the first three factors were shown to be statistically significant. CONCLUSION: Male gender, initial presentation with severe and extensive disease clinically and endoscopically, requirement of hospitalization on diagnosis or systemic steroids within 6 months of diagnosis are predictive factors for immunosuppressant use in UC.
Assuntos
Antimetabólitos/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Mercaptopurina/uso terapêutico , Adulto , Estudos de Casos e Controles , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do TratamentoRESUMO
BACKGROUND: Chronic radiation proctopathy (CRP) is a troublesome complication of radiotherapy to the pelvis for which current treatment modalities are suboptimal. Currently, the application of formalin to the rectal mucosa (AFR) and thermal ablation with argon plasma coagulation (APC) are the most promising options. OBJECTIVE: To compare the efficacy and safety of AFR with APC for CRP. PATIENTS AND METHODS: Records of 22 patients (male to female ratio, 19:3; mean age, 74 years) who received either APC or AFR for chronic hematochezia caused by CRP, and who were evaluated and treated between May 1998 and April 2002, were reviewed. Complete evaluations were made three months after completion of each therapeutic modality. Patients were considered to be responders if there was a 10% increase in hemoglobin from baseline or complete normalization of hemoglobin (male patients, higher than 130 g/L; female patients, higher than 115 g/L) without the requirement for blood transfusion. RESULTS: The mean hemoglobin level before therapy was 107 g/L. Patients received an average of 1.78 sessions for APC and 1.81 sessions for AFR. Eleven patients (50%) were treated with APC alone, eight patients (36%) with AFR alone and three (14%) with both modalities (two with AFR followed by APC, and one with APC followed by AFR). Eleven of 14 patients (79%) in the APC group were responders, compared with three of 11 patients (27%) in the AFR group (P=0.017). In the APC group, seven of 11 responders required only a single session, while in the AFR group, only one patient responded after a single session. Adverse events (nausea, vomiting, flushing, abdominal cramps, rectal pain and fever) occurred in two patients after APC and in nine patients after AFR (P=0.001). In the APC group, the mean hemoglobin level increase was 20 g/L at three months follow-up, compared with 14 g/L in the AFR group. CONCLUSION: This retrospective study suggests that APC is more effective and safe than topical AFR to control hematochezia caused by CRP. Further studies are needed to confirm this observation.
Assuntos
Fotocoagulação a Laser , Lasers de Gás/uso terapêutico , Lesões por Radiação/terapia , Reto/efeitos da radiação , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Fixadores , Formaldeído/administração & dosagem , Humanos , Mucosa Intestinal/efeitos da radiação , Masculino , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The goals of this study were to assess the extent of human intestinal drug transporter expression, determine the subcellular localization of the drug uptake transporter OATP1A2, and then to assess the effect of grapefruit juice consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1. Expression of drug uptake and efflux transporters was assessed using human duodenal biopsy samples. Fexofenadine uptake by different transporters was measured in a transporter-transfected cell line. We investigated the influence of grapefruit juice on pharmacokinetics of orally administered fexofenadine. The effect of grapefruit juice on the expression of intestinal transporters was determined using real-time polymerase chain reaction and Western blot analysis. In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake and efflux transporters was expressed. Importantly, uptake transporters thought to be liver-specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were expressed in the intestine. However, among OATP transporters, only OATP1A2 was capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice concomitantly or 2 h before fexofenadine administration was associated with reduced oral fexofenadine plasma exposure, whereas intestinal expression of either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug uptake and efflux transporters are expressed in the human intestine. OATP1A2 is likely the key intestinal uptake transporter for fexofenadine absorption whose inhibition results in the grapefruit juice effect. Although short-term grapefruit juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or MDR1 expression was unaffected.
Assuntos
Bebidas/efeitos adversos , Proteínas de Transporte/biossíntese , Citrus paradisi/efeitos adversos , Interações Alimento-Droga , Mucosa Intestinal/metabolismo , Preparações Farmacêuticas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Disponibilidade Biológica , Western Blotting , Citocromo P-450 CYP3A/biossíntese , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/biossíntese , Sistema Enzimático do Citocromo P-450/genética , Feminino , Imunofluorescência , Antagonistas dos Receptores Histamínicos H1/sangue , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Transportadores de Ânions Orgânicos/biossíntese , Transportadores de Ânions Orgânicos/genética , RNA/biossíntese , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Terfenadina/análogos & derivados , Terfenadina/sangueRESUMO
OBJECTIVE: Cancer Care Ontario has recommended a program to screen for colorectal cancer using fecal occult blood testing (FOBT). Patients who test positive on FOBT will require further investigation. We examined the cost of finding an advanced adenoma in these patients using four different strategies. METHODS: Using decision analysis software (DATA 3.5, TreeAge Software, Boston, MA), we considered four strategies for evaluating patients referred for a positive FOBT: 1) flexible sigmoidoscopy to the splenic flexure, 2) flexible sigmoidoscopy with air contrast barium enema (ACBE), 3) virtual colonoscopy, and 4) colonoscopy. If an adenoma was found in any of the first three methods, colonoscopy and polypectomy were performed. An advanced adenoma was defined as a villous adenoma, tubular adenoma > or = 10 mm, high grade dysplasia, or cancer. Values for probabilities, test characteristics and costs ($CDN) were estimated from a MEDLINE literature review, local costs, and OHIP fee codes. Patients with adenomas identified as well as direct medical costs from a third party payer perspective were calculated. RESULTS: Assuming a probability of adenoma of 16.9%, the cost for each strategy (compared to no investigation) was as follows: flexible sigmoidoscopy to the splenic flexure, $226; flexible sigmoidoscopy with ACBE, $424; virtual colonoscopy, $597; and colonoscopy, $387. The cost to clear a patient of adenoma(s) was $1,930, $2,840, $3,681, and $2,290, respectively. Despite being most cost-effective, the sigmoidoscopy strategy was predicted to detect 69% of cases of advanced adenomas. The radiological strategies would be less expensive if ACBE cost less than $115 or virtual colonoscopy cost less than $291. The colonoscopy strategy was more cost-effective if the probability of an adenoma was > or = 33.5%. When the incremental costs were considered to investigate 1000 patients, virtual colonoscopy and sigmoidoscopy with ACBE were both more costly then colonoscopy, and neither detected as many cases of advanced adenomas. CONCLUSION: Improved access to colonoscopy seems to be the preferred approach to deal with increased referrals.
Assuntos
Adenoma/economia , Adenoma/prevenção & controle , Neoplasias Colorretais/economia , Neoplasias Colorretais/prevenção & controle , Árvores de Decisões , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Sulfato de Bário , Canadá , Colonoscopia/economia , Meios de Contraste , Análise Custo-Benefício , Enema/economia , Humanos , Sangue Oculto , Sensibilidade e Especificidade , Software , Interface Usuário-ComputadorRESUMO
Infection with hepatitis A virus (HAV) occasionally leads to acute liver failure and has a higher fatality rate in patients with chronic hepatitis C virus (HCV). Vaccination of patients with HCV against HAV is effective and well tolerated. This study examines the cost-effectiveness of HAV vaccination in North American patients with chronic HCV. A decision analysis model was constructed to compare 3 HAV vaccination strategies in adult patients with chronic HCV over a period of 5 years: (1) vaccinate no patients (treat none); (2) vaccinate only susceptible (anti-HAV negative) patients (selective); or (3) vaccinate all patients without prior testing of immune status (universal). Probabilities and direct costs were estimated from hospital data and the literature. The cost per patient for the 3 vaccination strategies were: treat none, $2.00; selective, $56.00; and universal, $82.00. For every 1,000,000 patients with HCV vaccinated over a 5-year period, the selective strategy prevented 128 symptomatic cases of HAV, 3 liver transplantations, and 3 deaths owing directly to HAV compared with the treat none strategy. In addition, the selective strategy costs an additional $427,000 per patient with HAV prevented, and $23 million per HAV-related death averted, compared with the treat none strategy. The results were most sensitive to the incidence of HAV infection; vaccination increased costs if the annual rate of infection was less than 0.56% (baseline, 0.01%). Vaccination of North American patients with chronic HCV against HAV infection is not a cost-effective therapy.
Assuntos
Análise Custo-Benefício , Hepatite A/prevenção & controle , Hepatite C Crônica/complicações , Vacinas contra Hepatite Viral/economia , Adulto , Hepatite A/complicações , Hepatite A/epidemiologia , Vacinas contra Hepatite A , Hepatite C Crônica/mortalidade , Humanos , Transplante de FígadoAssuntos
Benzimidazóis/economia , Inibidores Enzimáticos/economia , Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Benzimidazóis/administração & dosagem , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Inibidores Enzimáticos/administração & dosagem , Esofagite Péptica/etiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/fisiopatologia , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/economia , Humanos , Omeprazol/análogos & derivados , Rabeprazol , Estados UnidosRESUMO
BACKGROUND: Pneumatic dilatation or intrasphincteric botulinum toxin injection provide effective symptom relief for patients with achalasia. Although intrasphincteric botulinum toxin injection is simple and safe, its efficacy may be short-lived. Pneumatic dilatation lasts longer, but esophageal perforation is a risk. We compared treatment costs for pneumatic dilatation and intrasphincteric botulinum toxin injection using a decision analysis model to determine whether the practical advantages of intrasphincteric botulinum toxin injection outweigh the economic impact of the need for frequent re-treatment. METHODS: Probability estimates for intrasphincteric botulinum toxin injection were derived from published reports. Probability estimates for the pneumatic dilatation strategy were obtained by retrospective review of our 10-year experience using the Rigiflex dilator. Direct, "third-party payer" costs were determined in Canadian dollars. RESULTS: Intrasphincteric botulinum toxin injection was significantly more costly at $5033 compared with $3608 for the pneumatic dilatation strategy, yielding an incremental cost of $1425 over the 10-year period considered. Sensitivity analysis showed that pneumatic dilatation is less expensive across all probable ranges of costs and probability estimates. The intrasphincteric botulinum toxin injection strategy is less costly if life-expectancy is less than 2 years. CONCLUSIONS: Intrasphincteric botulinum toxin injection is more costly than pneumatic dilatation for the treatment of achalasia. The added expense of frequent re-treatment with intrasphincteric botulinum toxin injection outweighs the potential economic benefits of the safety of the procedure, unless life-expectancy is 2 years or less.
Assuntos
Toxinas Botulínicas/economia , Cateterismo/economia , Acalasia Esofágica/terapia , Adolescente , Adulto , Idoso , Toxinas Botulínicas/administração & dosagem , Canadá , Criança , Redução de Custos , Análise Custo-Benefício , Custos e Análise de Custo , Técnicas de Apoio para a Decisão , Acalasia Esofágica/economia , Junção Esofagogástrica , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Recent studies have suggested that patients receiving omeprazole for prophylaxis against peptic esophageal stricture recurrence have less dysphagia and require fewer repeat dilations than patients receiving ranitidine. OBJECTIVE: To estimate the incremental utility gain and associated incremental cost of omeprazole compared with those of ranitidine for the maintenance therapy of patients with peptic stricture who required esophageal dilation. METHODS: Decision analysis using SMLTREE software was used to compare the incremental cost-utility of omeprazole 20 mg once daily with that of ranitidine 150 mg bid for one year. Variables were estimated from the literature, hospital data, and utility analyses involving patients with peptic stricture and health professionals. The primary outcome measure was cost per quality-adjusted life-years (QALYs) gained. RESULTS: The incremental cost of omeprazole compared with that of ranitidine was $556 per patient treated. The incremental utility gain of omeprazole was 0.0112 QALYs. Overall, the incremental cost:utility ratio of omeprazole in the maintenance therapy of patients with peptic stricture was $49,600 per QALY gained. A sensitivity analysis revealed that the estimates with the greatest impact on the cost:utility ratio were disutility associated with dysphagia and dilation, the probability of requiring redilation and the cost of medications. CONCLUSIONS: Omeprazole 20 mg once daily is associated with greater utility and higher cost than ranitidine 150 mg bid when used as prophylaxis against stricture recurrence. Omeprazole may be considered clinically and economically sufficient enough to warrant widespread use in this setting.
Assuntos
Antiulcerosos/economia , Antiulcerosos/uso terapêutico , Estenose Esofágica/tratamento farmacológico , Estenose Esofágica/economia , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/economia , Omeprazol/uso terapêutico , Ranitidina/economia , Ranitidina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Transtornos de Deglutição/etiologia , Estenose Esofágica/complicações , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Prevenção Secundária , Índice de Gravidade de DoençaRESUMO
SUMMARY: : We evaluated the use of utility measurements to assess the quality of life of patients with Crohn's disease. Utility scores were obtained using the Time Trade-Off (TTO), Standard Gamble, and Visual Analog Scale (VAS) methods in 180 consecutive patients with Crohn's disease. The mean utility scores of patients with a spectrum of disease severity were compared with other measures of disease activity to assess the operating properties of these instruments. All methods of utility estimation yielded lower mean scores in patients with more severe disease. (Remission versus chronically active, therapy resistant disease: TTO 0.96 versus 0.88; Standard Gamble 0.88 versus 0.74; VAS 0.84 versus 0.61). TTO scores were consistently higher than those derived by the other methods (p = 0.001). The utility scores were reliable in patients who were stable (intraclass correlation coefficient 0.55-0.84), but were less responsive than the Crohn's Disease Activity Index (responsiveness ratio 0.97-1.3 versus 2.10) to changes in disease severity. Patients with active Crohn's disease have decreased quality of life as measured by utility scores. Although utilities are valid and reliable quality of life assessments, they are less responsive than other measures of outcome used for clinical trials.
RESUMO
Idiopathic acute pancreatitis is common. Recent evidence suggests that biliary sludge may be the etiology in many patients with this disorder. In this case-control study, admission ultrasound examinations of patients with idiopathic pancreatitis, patients with acute alcohol-associated pancreatitis and a control group were compared. Biliary sludge was found in seven of 21 patients (33%) with idiopathic pancreatitis, two of 25 (8%) with acute alcohol-associated pancreatitis and one of 63 controls (1.6%). Comparison of idiopathic pancreatitis patients with both acute alcohol-associated pancreatitis patients and controls for the presence of sludge revealed odds ratios of 31.0 (95% CI 3.5 to 273) and 5.8 (95% CI 1.1 to 32.0), respectively. Also observed was a trend towards higher levels of liver enzymes, bilirubin and amylase in patients with idiopathic pancreatitis who had sludge identified. This study provides further evidence linking biliary sludge with a significant proportion of patients with idiopathic acute pancreatitis.
Assuntos
Bile , Pancreatite/etiologia , Doença Aguda , Adulto , Idoso , Amilases/sangue , Bilirrubina/sangue , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatite/sangue , Pancreatite/diagnóstico por imagem , Pancreatite Alcoólica/sangue , Pancreatite Alcoólica/diagnóstico por imagem , Pancreatite Alcoólica/etiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , UltrassonografiaRESUMO
BACKGROUND: Patients often recover from an episode of acute pancreatitis with conservative therapy and without an identified cause. The options include proceeding with ERCP to identify and treat an occult common bile duct stone or performing the procedure only after a second episode of idiopathic pancreatitis occurs. METHODS: Decision analysis (SMLTREE software) was used to determine incremental cost-utility. Variables were estimated from a search of the literature, a utility analysis involving health professionals familiar with the question, and a retrospective review of hospital charts and costs. RESULTS: This model estimates an incremental utility gain for the prompt ERCP approach of 1.0 quality-adjusted life weeks per patient at an incremental cost of $245 (Canadian). This yields a cost-utility ratio of $12,740 (Canadian) per quality-adjusted life year. The result was highly sensitive to the probability of finding an occult common bile duct stone. CONCLUSION: Routine ERCP is of marginal overall benefit, but is of more substantial benefit and is more cost-effective in a subgroup of patients with a greater probability of having an occult common duct stone.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/economia , Cálculos Biliares/diagnóstico , Pancreatite/etiologia , Doença Aguda , Análise Custo-Benefício/métodos , Feminino , Cálculos Biliares/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeAssuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças do Colo/induzido quimicamente , Indometacina/efeitos adversos , Obstrução Intestinal/induzido quimicamente , Biópsia , Colectomia , Doenças do Colo/diagnóstico , Doenças do Colo/cirurgia , Colonoscopia , Feminino , Seguimentos , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: The high prevalence, morbidity, premature death, and benefit of early diagnosis and treatment make hemochromatosis a prime target for screening in the white population. Decision analysis techniques were used to compare the outcome, utility, and incremental cost savings of a plan to screen voluntary blood donors for hemochromatosis. METHODS: The screening strategy includes sequential testing of serum unsaturated iron-binding capacity, serum transferrin saturation, serum ferritin, and either hepatic iron index or venesections to measure exchangeable body iron. Estimates of prevalence, asymptomatic intervals, probabilities of life-threatening clinical complications, symptom-specific life expectancy, and sensitivity and specificity of screening tests are based on our database of 170 hemochromatosis homozygotes and the published literature. RESULTS: The screening strategy led to an incremental increase in utility of 0.84 quality-adjusted life days with an incremental cost savings of $3.19 per blood donor screened. When the potential of identifying asymptomatic homozygous siblings was included, these values increased to 1.18 quality-adjusted life days and $12.57 per person screened. Screening remained a dominant strategy given a prevalence of hemochromatosis of > 0.0026 or an initial screening test cost of < $8. CONCLUSIONS: Screening blood donors for hemochromatosis has the potential to improve overall societal health status and decrease third-party payer health care costs over the long-term.
Assuntos
Doadores de Sangue , Técnicas de Apoio para a Decisão , Hemocromatose/prevenção & controle , Sistemas de Informação , Programas de Rastreamento , Adolescente , Adulto , Idoso , Criança , Custos e Análise de Custo , Árvores de Decisões , Feminino , Ferritinas/sangue , Hemocromatose/epidemiologia , Hemocromatose/genética , Homozigoto , Humanos , Ferro/sangue , Ferro/metabolismo , Expectativa de Vida , Fígado/metabolismo , Masculino , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Prevalência , Sensibilidade e Especificidade , Transferrina/análiseRESUMO
A 74 year old woman became progressively confused and developed visual hallucinations and delusions over a six day period, after the institution of routine oral trimethoprim-sulfamethoxazole therapy for a urinary tract infection. The medication was discontinued, and a marked improvement was noted 36 hours later. There was a complete return to normal mental functioning 60 hours after therapy was discontinued. The relationship between the patient's symptoms with the initiation and discontinuation of the medication suggests that the drug had a causal effect.