RESUMO
OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.
Assuntos
Colectomia , Colite Ulcerativa , Doença de Crohn , Fator de Necrose Tumoral alfa , Humanos , Masculino , Feminino , Adulto , Colectomia/estatística & dados numéricos , Colectomia/métodos , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Doença de Crohn/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Colite Ulcerativa/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Infliximab/uso terapêutico , Adulto Jovem , Resultado do Tratamento , Estudos Retrospectivos , Idoso , Pontuação de Propensão , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Genomic medicine enables the identification of patients with rare or ultra-rare monogenic forms of inflammatory bowel disease (IBD) and supports clinical decision making. Patients with monogenic IBD frequently experience extremely early onset of treatment-refractory disease, with complex extraintestinal disease typical of immunodeficiency. Since more than 100 monogenic disorders can present with IBD, new genetic disorders and variants are being discovered every year, and as phenotypic expression of the gene defects is variable, adaptive genomic technologies are required. Monogenic IBD has become a key area to establish the concept of precision medicine. Clear guidance and standardised, affordable applications of genomic technologies are needed to implement exome or genome sequencing in clinical practice. This joint British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition guideline aims to ensure that testing resources are appropriately applied to maximise the benefit to patients on a national scale, minimise health-care disparities in accessing genomic technologies, and optimise resource use. We set out the structural requirements for genomic medicine as part of a multidisciplinary team approach. Initiation of genomic diagnostics should be guided by diagnostic criteria for the individual patient, in particular the age of IBD onset and the patient's history, and potential implications for future therapies. We outline the diagnostic care pathway for paediatric and adult patients. This guideline considers how to handle clinically actionable findings in research studies and the impact of consumer-based genomics for monogenic IBD. This document was developed by multiple stakeholders, including UK paediatric and adult gastroenterology physicians, immunologists, transplant specialists, clinical geneticists, scientists, and research leads of UK genetic programmes, in partnership with patient representatives of several IBD and rare disease charities.
Assuntos
Gastroenterologia , Doenças Inflamatórias Intestinais , Humanos , Criança , Adulto , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/terapia , Estado Nutricional , GenômicaRESUMO
INTRODUCTION: Population-based studies of inflammatory bowel disease (IBD) in Cardiff have recorded data back to 1930 for Crohn's disease (CD) and 1968 for ulcerative colitis (UC). This study compares incidence and phenotype for 2005-2016 with past data. METHODS: All new IBD cases resident in the Cardiff at diagnosis were collected retrospectively for the 12-year period 2005-2016, and compared with previous Cardiff data for trends in incidence and phenotype. Overall incidence was age/sex corrected to the UK population. RESULTS: There were 991 new patients: 34% had CD, 5.4% IBD unclassified (IBD-U) and 60.5% had UC. The corrected incidence of CD was 7.7 per 100,000 person years [95% CI 6.9-8.6]. CD incidence is significantly higher than previous Cardiff studies, but the annual percentage change (APC) for 1980-2016 of 0.06; [95%CI -0.02 to 0.14] is not significant, with a previous higher APC for 1953-1980 of 0.18, [95%CI 0.13 to 0.23]. Uncorrected IBD-U incidence was 1.3 per 100,000 person years [95% CI 1.0-1.7]. UC corrected incidence was 14.4 per 100,000 person years [95% CI 13.3-15.6]. Incidence of UC is greater than in previous studies but did not increase during the current 12-year period. CD distribution at diagnosis continues to change as in previous Cardiff studies, with further increase in colonic disease and ileocolonic, (42% L2, 28% L3) and reduction in isolated terminal ileal disease (29% L1). CONCLUSIONS: Incidence of both CD and UC are no longer rising significantly, but the location of CD at diagnosis continues to change with an increase in colonic location.Key messagesWhat is already known? It is unclear whether the incidence of IBD has now plateaued in urbanised nations. Changes in Crohn's disease location are often not reported in incidence studies and terminal ileal disease has usually been reported as the commonest site of diseaseWhat is new here? The incidence of UC and Crohn's is no longer rising in Cardiff UK, but the phenotype has changed progressively over time with a continuing increase in colonic disease location and decrease in isolated terminal ileal diseaseHow can this study help patient care? Understanding that Crohn's colitis is the predominant location has implications for diagnostic tests and implications for treatment optionsIMPACT STATEMENTThis work shows that although IBD incidence is no longer rising, the pattern of Crohn's disease is changing with more colonic disease and less isolated terminal ileal disease.PRACTITIONER RELEVANCE STATEMENTThe changing pattern of Crohn's disease location has implications for diagnostic assessment and treatment of this disease.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças do Íleo , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/epidemiologia , Doença de Crohn/diagnóstico , Estudos Retrospectivos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/diagnóstico , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Healthcare service provision in inflammatory bowel disease (IBD) is often designed to meet targets set by healthcare providers rather than those of patients. It is unclear whether this meets the needs of patients, as assessed by patients themselves. AIMS: To assess patients' experience of IBD and the healthcare they received, aiming to identify factors in IBD healthcare provision associated with perceived high-quality care. METHODS: Using the 2019 IBD standards as a framework, a national benchmarking tool for quality assessment in IBD was developed by IBD UK, comprising a patient survey and service self-assessment. RESULTS: 134 IBD services and 9757 patients responded. Perceived quality of care was lowest in young adults and increased with age, was higher in males and those >2 years since diagnosis. No hospital services met all the national IBD standards for recommended workforce numbers. Key metrics associated with patient-reported high- quality care were: identification as a tertiary centre, patient information availability, shared decision- making, rapid response to contact for advice, access to urgent review, joint medical/surgical clinics, and access to research (all p < 0.001). Higher numbers of IBD nurse specialists in a service was strongly associated with patients receiving regular reviews and having confidence in self-management and reporting high- quality care. CONCLUSIONS: This extensive patient and healthcare provider survey emphasises the importance of aspects of care less often measured by clinicians, such as communication, shared decision- making and provision of information. It demonstrates that IBD nurse specialists are crucial to meeting the needs of people living with IBD.
Assuntos
Doenças Inflamatórias Intestinais , Pré-Escolar , Doença Crônica , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Medidas de Resultados Relatados pelo Paciente , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Reino Unido , Adulto JovemRESUMO
Introduction: Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities. Objectives: Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies ("biologics") in a single, publicly funded, healthcare system. Results: We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21. Conclusions: We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.
Assuntos
Produtos Biológicos , Colite Ulcerativa , Cuidados de Saúde Baseados em Valores , Humanos , Colite Ulcerativa/tratamento farmacológico , Ciência de Dados , Política de SaúdeRESUMO
The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Doenças Inflamatórias Intestinais , Pandemias , Pneumonia Viral , Antivirais/efeitos adversos , Antivirais/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Medição de Risco , SARS-CoV-2 , Reino Unido , Tratamento Farmacológico da COVID-19RESUMO
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
Assuntos
Consenso , Tratamento Conservador/normas , Gerenciamento Clínico , Gastroenterologia , Doenças Inflamatórias Intestinais/terapia , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas , Adulto , Humanos , Reino UnidoRESUMO
BACKGROUND: Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness. METHODS: In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589. FINDINGS: Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group vs 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group). INTERPRETATION: There was no significant difference between ciclosporin and infliximab in clinical effectiveness. FUNDING: NIHR Health Technology Assessment programme.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Colite Ulcerativa/economia , Análise Custo-Benefício , Ciclosporina/economia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Hidrocortisona/uso terapêutico , Imunossupressores/economia , Infliximab/economia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
BACKGROUND: Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs. METHODS/DESIGN: This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs. DISCUSSION: The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters. TRIAL REGISTRATION: Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).
Assuntos
Anti-Inflamatórios/uso terapêutico , Doença de Crohn/terapia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Drenagem/métodos , Fármacos Gastrointestinais/uso terapêutico , Fístula Retal/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/economia , Terapia Combinada , Análise Custo-Benefício , Doença de Crohn/diagnóstico , Doença de Crohn/economia , Doença de Crohn/imunologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/economia , Drenagem/efeitos adversos , Drenagem/economia , Quimioterapia Combinada , Europa (Continente) , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/economia , Custos de Cuidados de Saúde , Humanos , Imageamento por Ressonância Magnética , Mercaptopurina/uso terapêutico , Qualidade de Vida , Fístula Retal/diagnóstico , Fístula Retal/economia , Fístula Retal/imunologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Adherence to medication is an issue of great importance for patients with ulcerative colitis. Once daily mesalazine seems to be no worse than divided doses in preventing relapse in remitting patients. Although this has been attributed to improved adherence, detailed measures of adherence have been lacking from previous studies. METHODS: A 1-year substudy was conducted alongside a trial that compared 2 different dosing regimens (once daily versus three times daily) of mesalazine for patients in remission with ulcerative colitis. Participants in the substudy had their adherence monitored electronically using the medication event monitoring system, self-report, and tablet counts. We compared measures, determined factors associated with adherence and associations between adherence and relapse, modeled adherence over time, and explored behavioral aspects. RESULTS: We included 58 participants. Adherence was high across all measures (89.3% self-report, 96.7% tablet counts, and 89.2% medication event monitoring system). Agreement between the measures was poor at times. Adherence according to the medication event monitoring system best distinguished between the participants who relapsed (71.4%) and those who remained in remission (93.4%), although this difference was not statistically discernible at the 5% level. Adherence deteriorated over the study period, with three times daily participants generally less adherent than once-daily participants (odds ratio, 0.03; 95% confidence interval, 0.01-0.08). Adherence was higher on weekdays (odds ratio, 1.47; 95% confidence interval, 1.31-1.65) and around clinic visit dates (odds ratio, 1.43; 95% confidence interval, 1.18-1.72). CONCLUSIONS: Simple dosing regimens are preferable to multiple daily dosing regimens. Electronic monitoring of adherence should be used more often in clinical studies. Self-reported adherence and tablet counts may underestimate adherence. Adherence declined over time, and adherence was generally lower and more varied for those allocated to the three times daily regimen.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Monitoramento de Medicamentos , Adesão à Medicação , Mesalamina/administração & dosagem , Sistemas Microeletromecânicos , Administração Oral , Adulto , Colite Ulcerativa/psicologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Prognóstico , Recidiva , Indução de RemissãoRESUMO
BACKGROUND: Mesalazine (Asacol) is still widely prescribed in divided doses for ulcerative colitis (UC), despite evidence that adherence is improved by once-daily (OD) prescribing. We aimed to investigate whether OD Asacol was as effective as three times (TDS) daily dosing, and to evaluate the role of treatment adherence. METHODS: An investigator-blind randomized trial was undertaken comparing OD Asacol (three 800 mg tablets) versus one 800 mg TDS in maintenance of remission of UC over 1 year. The primary endpoint was relapse rate, and noninferiority would be concluded if the lower limit of the two-sided 95% confidence interval (CI) of the difference in proportions relapsing (TDS-OD) exceeded -10%. Adherence was measured by tablet counts and self-reported adherence. A subgroup of patients used a bottle cap that recorded all bottle opening events. RESULTS: In all, 213 patients were randomized. In the intention-to-treat (ITT) population, relapse rates were 31% (95% CI 22%-40%) in the OD and 45% (95% CI 35%-54%) in the TDS group. Primary analysis confirmed the noninferiority of OD dosing. Two of the study populations, ITT and per-protocol (PP), showed potential superiority of OD dosing. All measures of adherence showed that it was significantly better in the OD group. Multivariate analysis, however, showed OD dosing was associated with lower relapse risk independently of adherence. CONCLUSIONS: OD dosing with Asacol 2.4 g is as safe and effective as TDS dosing, and secondary analysis confirmed significantly reduced relapse rates. The benefit, however, was clinically borderline and may relate in part to ease of adherence.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Pesquisadores , Administração Oral , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Método Simples-Cego , Fatores de TempoRESUMO
Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the most widely used immunosuppressive therapies in inflammatory bowel disease. Pretreatment measurement of thiopurine methyltransferase (TPMT) activity is recommended and although conventional practice is to use a dose of 2 mg/kg AZA (1 mg/kg 6-MP), higher doses of 2.5 mg/kg AZA or more may be required in some patients, particularly if TPMT activity is high. Dose raising is limited by toxicity, and a robust monitoring system is mandatory. Patients with side effects to AZA may tolerate 6-MP but pancreatitis is a contraindication to switching. Metabolite monitoring is not widely available but may be useful, particularly if non-compliance is possible or where metabolite shunting to 6-methylmercaptopurine is suspected, on the basis of non-response or toxicity. It may allow dose optimisation before switching to alternative immunosuppressants. The drug appears safe in pregnancy and breast feeding. Long term duration of therapy is a balance between benefits in relation to the underlying disease extent, activity and aggressiveness, and the risk of neoplasia, particularly lymphoma.
RESUMO
BACKGROUND AND AIMS: The success rate of unguided nasojejunal feeding tube insertion is low, thus often requiring endoscopic or radiological assistance. The spiral end of the Bengmark nasojejunal tube is supposed to aid post-pyloric placement, but no comparative trial has been performed. METHODS: Patients requiring nasojejunal feeding were randomised to have either Medicina (straight) or Bengmark (spiral) nasojejunal tube placed after stratification into those with normal gastric emptying or clinical evidence of delayed gastric emptying. Nasojejunal tubes were placed at the bedside in a standard fashion without radiological guidance by the same person for pre- and/or post-operative feeding. Bolus intravenous metaclopromide (10mg) was given prior to insertion in the abnormal gastric emptying group. Abdominal radiographs were obtained at 4 and 24h, and the primary end-point was jejunal placement at 24h. RESULTS: Forty-seven patients were randomised of which 17 (11 straight, 6 spiral) could not tolerate the nasojejunal tube. Of the 30 remaining patients, 16 had normal gastric emptying. In patients with normal gastric emptying, successful placement at 24h was achieved in 78% (spiral tube), vs 14% (straight tube) (P=0.041). In the abnormal gastric emptying group, success rates were 57% and 0%, respectively (P=0.07). CONCLUSION: Spiral nasojejunal tubes are preferable to straight tubes for bedside unguided post-pyloric feeding in patients with normal gastric emptying.
Assuntos
Nutrição Enteral/instrumentação , Esvaziamento Gástrico/fisiologia , Intubação Gastrointestinal/instrumentação , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal , Nutrição Enteral/métodos , Feminino , Humanos , Intubação Gastrointestinal/métodos , Masculino , Pessoa de Meia-Idade , Radiografia AbdominalRESUMO
Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.