RESUMO
BACKGROUND: Dysplasia surveillance in inflammatory bowel disease (IBD) is often suboptimal and deviates from guidelines. AIMS: To assess dysplasia surveillance behaviours and adherence to guidelines amongst a large tertiary teaching health network with a specialised IBD unit to identify areas where dysplasia surveillance could be improved. METHODS: A retrospective audit of IBD surveillance colonoscopy practice over an 18-month period was performed using the Provation Endoscopy Database and the hospital's primary sclerosing cholangitis database. RESULTS: The audit identified 115 dysplasia surveillance colonoscopies. A total of 37% of index dysplasia colonoscopies were outside recommended guidelines. A total of 10% had inadequate bowel preparation and only 40% had excellent bowel preparation. A total of 28% of patients underwent dye-based chromoendoscopy and 69% underwent high-definition white-light endoscopy. Dye chromoendoscopy was more likely to be used by IBD specialists than interventional endoscopists (P = 0.008) and other endoscopists (P = 0.004). Only IBD specialists and interventional endoscopists used dye chromoendoscopy. Dysplasia or colorectal cancer was detected in 3.4% of the colonoscopies. Overall, the several dysplasia examinations were lower than expected. CONCLUSIONS: Dysplasia surveillance in the IBD population remains an area of improvement given the current national guidelines. IBD specialists are more likely to perform dye chromoendoscopy than other endoscopists/gastroenterologists. Dysplasia rates in this real-world contemporary setting are less than expected in historical studies and may represent improvements in IBD management principles and medications.
Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Colonoscopia , Colo , Endoscopia Gastrointestinal , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologiaRESUMO
BACKGROUND: Thiopurines are effective therapies for inflammatory bowel disease (IBD); however, treatment comes with safety concerns and adverse effects. Knowledge of the impact of pharmacists performing thiopurine monitoring is limited. AIMS: To determine the impact of a pharmacist-led monitoring service in patients with IBD commencing thiopurine therapy managed in the ambulatory care setting. METHODS: Patients commencing thiopurine therapy for IBD pre- and post-introduction of a pharmacist-led monitoring intervention were assessed. Pre-intervention patients received standard of care, while the post-intervention cohort was managed by the pharmacist. Data were acquired via retrospective audit of hospital medical records. The primary end-point was the proportion of patients with documented review for thiopurine adverse effects within the initial 3 weeks. Secondary end-points included achievement of therapeutic drug levels, persistence with thiopurine therapy, IBD-related episodes of care and number of outpatient medical reviews. RESULTS: Pre- and post-intervention cohorts comprised of 37 and 33 patients respectively. Pharmacist intervention increased the proportion of patients with documented monitoring within 3 weeks from 8.1% to 84.8% (P < 0.01). No difference in thiopurine dose optimisation was seen (27% vs 27.3%). Persistence with thiopurine therapy increased from 65.7% to 87.9% (P < 0.03) at 6 months. IBD-related emergency department presentations were not significantly decreased (8.1% vs 3%; P = 0.62). No significant change was observed in hospital admissions (16.2% vs 12.1%; P = 0.74) or outpatient medical reviews. CONCLUSIONS: Pharmacist monitoring of thiopurine therapy initiation in IBD outpatients improves adverse effect monitoring and increases medication persistence.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Inflamatórias Intestinais , Humanos , Pacientes Ambulatoriais , Farmacêuticos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Mercaptopurina/uso terapêutico , Azatioprina/uso terapêuticoRESUMO
BACKGROUND & AIMS: Helicobacter pylori induces strong inflammatory responses that are directed at clearing the infection, but if not controlled, these responses can be harmful to the host. We investigated the immune-regulatory effects of the innate immune molecule, nucleotide-binding oligomerization domain-like receptors (NLR) family CARD domain-containing 5 (NLRC5), in patients and mice with Helicobacter infection. METHODS: We obtained gastric biopsies from 30 patients in Australia. We performed studies with mice that lack NLRC5 in the myeloid linage (Nlrc5møKO) and mice without Nlrc5 gene disruption (controls). Some mice were gavaged with H pylori SS1 or Helicobacter felis; 3 months later, stomachs, spleens, and sera were collected, along with macrophages derived from bone marrow. Human and mouse gastric tissues and mouse macrophages were analyzed by histology, immunohistochemistry, immunoblots, and quantitative polymerase chain reaction. THP-1 cells (human macrophages, controls) and NLRC5-/- THP-1 cells (generated by CRISPR-Cas9 gene editing) were incubated with Helicobacter and gene expression and production of cytokines were analyzed. RESULTS: Levels of NLRC5 messenger RNA were significantly increased in gastric tissues from patients with H pylori infection, compared with patients without infection (P < .01), and correlated with gastritis severity (P < .05). H pylori bacteria induced significantly higher levels of chemokine and cytokine production by NLRC5-/- THP-1 macrophages than by control THP-1 cells (P < .05). After 3 months of infection with H felis, Nlrc5mø-KO mice developed gastric hyperplasia (P < .0001), splenomegaly (P < .0001), and increased serum antibody titers (P < .01), whereas control mice did not. Nlrc5mø-KO mice with chronic H felis infection had increased numbers of gastric B-cell follicles expressing CD19 (P < .0001); these follicles had features of mucosa-associated lymphoid tissue lymphoma. We identified B-cell-activating factor as a protein that promoted B-cell hyperproliferation in Nlrc5mø-KO mice. CONCLUSIONS: NLRC5 is a negative regulator of gastric inflammation and mucosal lymphoid formation in response to Helicobacter infection. Aberrant NLRC5 signaling in macrophages can promote B-cell lymphomagenesis during chronic Helicobacter infection.
Assuntos
Infecções por Helicobacter/complicações , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma de Zona Marginal Tipo Células B/imunologia , Neoplasias Gástricas/imunologia , Animais , Linfócitos B/imunologia , Biópsia , Proliferação de Células , Modelos Animais de Doenças , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica/imunologia , Técnicas de Inativação de Genes , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter felis/imunologia , Helicobacter pylori/imunologia , Humanos , Hiperplasia/imunologia , Hiperplasia/microbiologia , Imunidade Inata , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Tecido Linfoide/imunologia , Tecido Linfoide/microbiologia , Tecido Linfoide/patologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/imunologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Células THP-1RESUMO
BACKGROUND: Quality of care in inflammatory bowel disease (IBD) has received much attention internationally; however, the available surveys focus on health professionals rather than patients. AIMS: To assess the experiences of healthcare for people living with IBD against established Australian IBD Standards. METHODS: An online cross-sectional survey was conducted with Australians ≥16 years old recruited via Crohn's & Colitis Australia membership, public and private clinics and the Royal Flying Doctor Service. Participants completed a questionnaire incorporating items addressing the Australian IBD Standards 2016, the Picker Patient Experience Questionnaire, IBD Control Survey and the Manitoba Index. RESULTS: Complete data were provided by 731 respondents (71.5% female, median age 46 years, ranging from 16 to 84 years). While the majority (74.8%) were satisfied with their IBD healthcare, the care reported did not meet the Australian IBD Standards. Overall, 32.4% had access to IBD nurses, 30.9% to a dietician and 12% to a psychologist in their treating team. Participants managed by public IBD clinics were most likely to have access to an IBD nurse (83.7%), helpline (80.7%) and research trials (37%). One third of respondents reported waiting >14 days to see a specialist when their IBD flared. Participants received enough information, mostly from medical specialists (88.8%) and IBD nurses (79.4%). However, 51% wanted to be more involved in their healthcare. CONCLUSIONS: These data show discordance between expectations of patients and national standards with current levels of service provision, which fail to deliver equitable and comprehensive IBD care.
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Colite , Doenças Inflamatórias Intestinais , Adolescente , Austrália/epidemiologia , Estudos Transversais , Feminino , Serviços de Saúde , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Padrões de ReferênciaRESUMO
BACKGROUND: Australia has among the highest prevalence of Crohn disease and ulcerative colitis in the world. Management of the chronic gastrointestinal disorders results in significant societal costs and the standard of care is inconsistent across Australia. AIM: To audit the quality of care received by patients admitted for inflammatory bowel disease (IBD) across Australia against national IBD standards. METHODS: A retrospective cross-sectional survey and clinical audit was undertaken assessing organisational resources, clinical processes and outcome measures. This study was conducted in Australian hospitals that care for inpatients with Crohn disease or ulcerative colitis. The main outcome measures were adherence to national IBD standards and comparison of quality of care between hospitals with and without multidisciplinary IBD services. RESULTS: A total of 71 hospitals completed the organisational survey. Only one hospital had a complete multidisciplinary IBD service and 17 had a partial IBD service (IBD nurse, helpline and clinical lead). A total of 1440 inpatient records was reviewed from 52 hospitals (mean age 37 years; 51% female, 53% Crohn disease), approximately 26% of IBD inpatient episodes over a 12-month period in Australia. These patients were chronically unwell with high rates of anaemia (30%) and frequent readmissions (40% within 2 years). In general, care was inconsistent, and documentation was poor. Hospitals with a partial IBD service performed better in many processes and outcome measures: for example, 22% reduction in admissions through emergency departments and greater adherence to standards for safety monitoring of biological (89% vs 59%) and immunosuppressive drugs (79% vs 55%) in those hospitals than those without. CONCLUSION: Patients admitted to hospital suffering from IBD are young, chronically unwell and are subject to substantial variations in clinical documentation and quality of care. Only one hospital met accepted standards for multidisciplinary care; hospitals with even a minimal IBD service provided improved care.
Assuntos
Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Auditoria Médica/normas , Qualidade da Assistência à Saúde/normas , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Estudos Transversais , Feminino , Hospitalização/tendências , Hospitais Gerais/normas , Hospitais Gerais/tendências , Hospitais Pediátricos/normas , Hospitais Pediátricos/tendências , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Auditoria Médica/tendências , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde/tendências , Estudos Retrospectivos , Inquéritos e Questionários/normas , Adulto JovemRESUMO
BACKGROUND: Recent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long-term data is limited. AIM: To assess whether anti-tumour necrosis factor alpha (anti-TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real-world cohort with long-term follow up. METHODS: A retrospective audit was conducted of inflammatory bowel disease patients receiving anti-TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti-TNF commencement and adequate correspondence to determine end-points were included. Outcomes measured included time to first LOR, causes and biochemical parameters. RESULTS: Two hundred and twenty-four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty-five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti-TNF agents. CONCLUSION: In this large cohort of patients in a real-world setting, patients treated with anti-TNF monotherapy had similar rates of LOR as patients on anti-TNF combination therapy, at both short- and long-term follow up.
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Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Falha de Tratamento , Vitória , Adulto JovemRESUMO
BACKGROUND AND AIM: Acute severe ulcerative colitis (ASUC) is a medical emergency requiring prompt therapeutic intervention. Although infliximab has been used as salvage therapy for over 15 years, clinical predictors of treatment success are lacking. We performed a retrospective analysis to identify factors that predict colectomy and may guide dose intensification. METHODS: Fifty-four hospitalized patients received infliximab for ASUC at seven Australian centers (April 2014-May 2015). Follow-up was over 12 months. The data were primarily analyzed for predictors of colectomy. Accelerated (AI) versus standard (SI) infliximab induction strategies were also compared. RESULTS: Of 54 patients identified, the overall colectomy rate was 15.38% (8/52) at 3 months and 26.92% (14/52) at 12 months. Two patients were lost to follow-up. There was a numerically higher colectomy rate in those treated with AI compared with SI (P = 0.3); however, those treated with AI had more severe biochemical disease. A C-reactive protein (CRP)/albumin ratio cut-off of 0.37 post-commencement of infliximab and before discharge was a significant predictor of colectomy with an area under receiver operating curve of 0.73. Pretreatment CRP and albumin levels were not predictive of colectomy. A Mayo Endoscopic Score of 2 had a 94% PPV for avoidance of colectomy following infliximab salvage. CONCLUSIONS: The baseline Mayo Endoscopic Score and the CRP/albumin ratio following infliximab salvage are significant predictors of treatment response for ASUC and identify patients at high risk of colectomy. Whether this risk can be mitigated using infliximab dose intensification requires prospective evaluation before the CRP/albumin ratio can be integrated into ASUC management algorithms.
Assuntos
Colectomia , Colite Ulcerativa/terapia , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Terapia de Salvação , Doença Aguda , Adulto , Biomarcadores/sangue , Proteína C-Reativa , Estudos de Coortes , Colite Ulcerativa/diagnóstico , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Risco , Albumina Sérica , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with a poor prognosis and is associated with a high prevalence of cachexia, a metabolic syndrome of muscle wasting due to complex mechanisms. In addition to loss of muscle mass, cancer patients also experience functional deterioration. The aim of this study is to determine whether there is an association between muscle mass and function and clinical outcomes, particularly survival. METHODS: We performed a prospective cohort study including all patients with PDAC at Monash Health from March 2016 to December 2017. We conducted body composition analysis for myopenia and handgrip strength testing. We constructed Kaplan-Meier curves to estimate whether myopenia and low hand grip strength were associated with poorer survival. RESULTS: Myopenia was not associated with a significant difference in PDAC-specific survival (log-rank P = 0.60). However, low handgrip strength was associated with significantly worse PDAC-specific survival compared with other patients (log-rank hazard ratio, 1.88; 95% confidence interval, 1.15-3.09; P = 0.004). CONCLUSIONS: The relationship between survival in PDAC and handgrip strength, but not anatomical muscle mass, suggests that functional testing of strength may be important in prognostication of patients with PDAC, alongside existing tools such as the Eastern Cooperative Oncology Group performance status.
Assuntos
Carcinoma Ductal Pancreático , Força da Mão , Neoplasias Pancreáticas , Humanos , Força da Mão/fisiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/fisiopatologia , Prognóstico , Composição Corporal , Estimativa de Kaplan-Meier , Idoso de 80 Anos ou mais , Caquexia/fisiopatologia , Caquexia/mortalidade , Caquexia/diagnóstico , Caquexia/etiologiaRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. METHODS: Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. RESULTS: Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (Pâ <â 0.001) and severe ulcerative colitis (UC) (Pâ <â 0.0001) and active Crohn's disease (CD) (Pâ <â 0.001). In UC in remission, LBP was less than in active disease (Pâ =â 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (Pâ =â 0.030) and as severe UC was brought into remission at weeks 2 and 12 (Pâ ≤â 0.022). Response to treatment was associated with higher baseline levels of LBP (Pâ =â 0.019) and soluble-CD14 (Pâ =â 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. CONCLUSION: While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Sindecana-1/uso terapêutico , Receptores de Lipopolissacarídeos/uso terapêutico , Lipopolissacarídeos , Estudos Prospectivos , Estudos Transversais , Doenças Inflamatórias Intestinais/complicações , Biomarcadores , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Inflamação/complicaçõesRESUMO
OBJECTIVES: Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged. METHODS: Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150â µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks. RESULTS: Total fat mass was higher in 54 patients with IBD (56% Crohn's disease, 61% male) than in 30 controls (median 25.1 vs. 18.7â kg, P â =â 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P â =â 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% ( P â =â 0.004) and BMI by 6.4% ( P â =â 0.012) in 9 responders to therapy. CONCLUSION: DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice.
Assuntos
Força da Mão , Doenças Inflamatórias Intestinais , Humanos , Masculino , Feminino , Absorciometria de Fóton , Estudos Prospectivos , Índice de Massa Corporal , Composição Corporal , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Músculo Esquelético , InflamaçãoRESUMO
Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5â ×â 106/kg hAEC in one IV infusion. Cohort 2 patients received 1â ×â 106/kg hAEC in one IV infusion. The patients in cohort 3 received 1â ×â 106/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy. Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).
Assuntos
Âmnio , Células Epiteliais , Cirrose Hepática , Humanos , Feminino , Âmnio/transplante , Cirrose Hepática/terapia , Cirrose Hepática/complicações , Pessoa de Meia-Idade , Masculino , Adulto , IdosoRESUMO
INTRODUCTION: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring. METHODS AND ANALYSIS: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants. ETHICS AND DISSEMINATION: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment. TRIAL REGISTRATION NUMBER: ACTRN12622001458729.
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Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Infliximab , Humanos , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Infliximab/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Prospectivos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Injeções Subcutâneas , Administração Intravenosa , Estudos Multicêntricos como Assunto , Adulto , Austrália , Monitoramento de Medicamentos/métodos , Feminino , MasculinoAssuntos
Colite Ulcerativa/terapia , Comissão Para Atividades Profissionais e Hospitalares , Doença de Crohn/terapia , Atenção à Saúde , Qualidade da Assistência à Saúde , Austrália , Análise Custo-Benefício , Humanos , Comunicação Interdisciplinar , Estado Nutricional , Admissão do Paciente/estatística & dados numéricos , Equipe de Assistência ao Paciente , Prognóstico , Apoio SocialAssuntos
Adalimumab/efeitos adversos , Úlcera de Buruli/diagnóstico , Úlcera de Buruli/etiologia , Doença de Crohn/tratamento farmacológico , Mycobacterium ulcerans/isolamento & purificação , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Úlcera de Buruli/imunologia , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Mycobacterium ulcerans/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy. Secondary aims included hAEC efficacy, feasibility of the protocol and impact on quality of life. METHODS: A phase I open label study of ten adults with active complex Crohn's perianal fistulas refractory to conventional treatment, including anti-tumour necrosis factor alpha therapy, was undertaken. A single dose of hAEC was injected into the fistula tract(s) after surgical closure of the internal opening(s). Study outcomes were assessed at week 24 with follow up for at least 52 weeks. FINDINGS: Local injection of hAEC was safe, well tolerated and the injection procedure was feasible. Complete response occurred in 4 patients, and a partial response in an additional 4 patients. There was a mean reduction in the Perianal Disease Activity Index of 6.5 points (95% CI -9.0 to -4.0, p = 0.0002, paired t-test), modified Van Assche MRI Index of 2.3 points (95% CI -3.9 to -0.6, p = 0.012, paired t-test) and a mean improvement of 15.8 points (95% CI 4.9 to 26.8, p = 0.010, paired t-test) in quality of life using the Short IBD-Questionnaire in complete responders. INTERPRETATION: Local injection of hAEC therapy for refractory complex perianal fistulising Crohn's disease appears safe, well-tolerated, feasible and demonstrated improvement. Quality of life is improved in those who achieve complete fistula healing. FUNDING: This study was funded by competitive research grant funding from the Gastroenterological Society of Australia Seed Grant 2018.
Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Fístula Retal , Adulto , Humanos , Âmnio , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Células Epiteliais , Seguimentos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Qualidade de Vida , Fístula Retal/terapia , Fístula Retal/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Disturbance of skeletal muscle mass has clinically important implications in patients with inflammatory bowel disease (IBD), but accurate quantification requires radiation-intense techniques. AIMS: We aimed to compare point-of-care muscle assessments and their change with therapy with those using reference-standard whole-body dual energy X-ray absorptiometry (DXA). METHODS: Adult patients with IBD and healthy controls underwent prospective assessment of muscularity by ultrasound of the dominant arm and both thighs, bioelectrical impedance analysis (BIA), anthropometric measurements, and DXA. Patients with active IBD were assessed again ≥13 weeks after initiating biologic induction therapy. RESULTS: In 54 patients with IBD and 30 controls, all muscle assessments correlated significantly with DXA-derived skeletal muscle index (SMI). In IBD, ultrasound of the arm and legs had the best agreement with DXA-derived SMI (mean difference 0 kg/m2 , 95% limits of agreement -1.3 to 1.3), while BIA overestimated DXA-derived SMI by 1.07 (-0.16 to +2.30) kg/m2 . In 17 patients who underwent biologic therapy, the percentage change in DXA-derived SMI correlated significantly with the percentage change in all other muscle assessment techniques. Responders (n = 9) increased SMI from baseline to follow-up when derived from DXA (mean 7.8-8.5 kg/m2 , p = 0.004), ultrasound of the arm and legs (300-343 cm2 , p = 0.021) and BIA (9.2-9.6 kg/m2 , p = 0.011). CONCLUSIONS: Ultrasound of the arm and legs out-performed other point-of-care methods in its accuracy of measuring muscle mass. All methods, except mid-arm circumference, were responsive to therapy-induced change. Ultrasound is the preferred non-invasive test for measuring muscle mass in patients with IBD.
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Composição Corporal , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Humanos , Composição Corporal/fisiologia , Índice de Massa Corporal , Impedância Elétrica , Estudos Prospectivos , Antropometria , Absorciometria de Fóton/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologiaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with visceral adiposity. We assessed the effectiveness of time-restricted fasting (TRF) for 16 h daily without calorie restrictions compared to standard care (SC; diet and lifestyle advice) in improving visceral adiposity and steatosis via controlled attenuation parameter (CAP). METHODS: In a prospective single-blind randomized controlled trial, 32 participants with NAFLD were randomly assigned to TRF or SC for 12 weeks. The secondary endpoints were changes in liver stiffness, anthropometry, blood pressure, and other metabolic factors. RESULTS: Twenty-eight participants completed the first arm of the study (TRF = 14, SC = 14), with 23 completing the crossover arm (TRF = 10, SC = 13). The baseline demographics were similar between the groups. Intermittent fasting caused a significant decrease in hepatic steatosis (p = 0.038), weight (p = 0.005), waist circumference (p = 0.001), and BMI (p = 0.005) compared to standard care. Intermittent fasting also resulted in additional within-group changes that were not seen in the standard care intervention. CONCLUSION: TRF offers superior improvements in patients with NAFLD, improving steatosis, weight, and waist circumference despite a lack of change in overall caloric intake. Time-restricted fasting should be considered as a primary weight loss intervention in the context of NAFLD. TRIAL REGISTRATION: ACTRN12613000935730.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Jejum Intermitente , Estudos Cross-Over , Estudos Prospectivos , Método Simples-Cego , Fígado/metabolismoRESUMO
Autoimmune and inflammatory disorders, including inflammatory bowel disease (IBD), commonly affect women of childbearing age, warranting the use of immunomodulatory agents at a time where pregnancy may be desired. In utero exposure to pro-inflammatory mediators from maternal IBD, IBD-associated intestinal dysbiosis, and immunomodulatory drug use may impact neonatal immune system development during what is considered to be a critical period, with potential long-lasting impacts on susceptibility to disease. Both the innate and adaptative immune systems of the neonatal differ to that of the adult in terms of both cellular composition and sensitivity to antigenic and innate stimulation. The infant immune system gradually develops to more closely resemble that of the adult. Exposure to maternal inflammation in utero may aberrantly impact this period of infant immune system development, with maternal autoimmune and inflammatory disorders shown to affect the physiologic changes in serum cytokine abundance observed during pregnancy. The maternal and neonatal intestinal microbiome greatly influence infant mucosal and peripheral immune system development, and thereby impact the susceptibility to short-term inflammatory diseases, the adequacy of vaccine response, and later life risk of atopic and inflammatory disorders. Maternal disease, mode of delivery, method of feeding, time of weaning to include solid foods in the diet, and neonatal antibiotic exposure all influence the composition of the infant microbiome, and thereby infant immune system maturation. How exposure to specific immunosuppressive medications in utero alters infant immune cell phenotype and response to stimulation has been explored, but with existing studies limited by the time at which samples are performed, heterogenicity in methods, and small sample size. Furthermore, the impact of more recently introduced biologic agents have not been explored. Evolving knowledge in this field may influence therapeutic preferences for individuals with IBD planning to conceive, particularly if substantive differences in the risk of infant infection and childhood immune disease are identified.
Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Gravidez , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Citocinas , InflamaçãoRESUMO
BACKGROUND AND AIMS: Post traumatic stress disorder (PTSD) is common in individuals with inflammatory bowel diseases (IBD). Living with a medical condition has been linked to the development of PTSD and to adversely impact patient outcomes. The aim of this study is to extend the common sense model (CSM) and evaluate trauma as an additional psychosocial process in the relationship between IBD symptoms and quality of life (QoL). METHOD: A cross-sectional online study exploring trauma and IBD was performed. RESULTS: 68 (32.2%) of the sample met the criteria for PTSD. Of this trauma group, 37 (54.4%) reported IBD related trauma, 21 (30.9%) reported non-IBD related trauma and 10 (14.7%) did not identify the trauma type. A structural equation model (SEM) based upon the CSM was found to have an excellent fit (χ2 (3)=1.10, p=0.35, RMSEA=0.02, SRMR=0.02, CFI=1.00, GFI=0.99). Results showed that trauma symptoms partially mediated the relationship between illness perceptions and QoL and fully mediated the relationship between maladaptive coping and QoL. CONCLUSION: This study extended the CSM and found that trauma symptoms functioned as a mediator between IBD activity and QoL. These results highlight the need for a holistic approach including psychological assessment and intervention in IBD.