Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study.

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.

Changes in incidence and clinical features of inflammatory bowel disease in Cardiff, UK over 50 years: an update for 2005-2016.

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.

A Novel Automated System Yields Reproducible Temporal Feeding Patterns in Laboratory Rodents.

BACKGROUND: The impact of temporal feeding patterns remains a major unanswered question in nutritional science. Progress has been hampered by the absence of a reliable method to impose temporal feeding in laboratory rodents, without the confounding influence of food-hoarding behavior. OBJECTIVE: The aim of this study was to develop and validate a reliable method for supplying crushed diets to laboratory rodents in consistent, relevant feeding patterns for prolonged periods. METHODS: We programmed our experimental feeding station to deliver a standard diet [StD; Atwater Fuel Energy (AFE) 13.9% fat] or high-fat diet (HFD; AFE 45% fat) during nocturnal grazing [providing 1/24th of the total daily food intake (tdF/I) of ad libitum-fed controls every 30 min] and meal-fed (3 × 1-h periods of ad libitum feeding) patterns in male rats (Sprague-Dawley: 4 wk old, 72-119 g) and mice [C57/Bl6J wild-type (WT): 6 mo old, 29-37 g], and ghrelin-null littermates (Ghr-/-; 27-34 g). RESULTS: Grazing yielded accurate, consistent feeding events in rats, with an approximately linear rise in nocturnal cumulative food intake [tdF/I (StD): 97.4 ± 1.5% accurate compared with manual measurement; R2 = 0.86; tdF/I (HFD): 99.0 ± 1.4% accurate; R2 = 0.86]. Meal-feeding produced 3 nocturnal meals of equal size and duration in StD-fed rats (tdF/I: 97.4 ± 0.9% accurate; R2 = 0.90), whereas the second meal size increased progressively in HFD-fed rats (44% higher on day 35 than on day 14; P < 0.01). Importantly, cumulative food intake in grazing and meal-fed rats was identical. Similar results were obtained in WT mice except that less restricted grazing induced hyperphagia (compared with meal-fed WT mice; P < 0.05 from day 1). This difference was abolished in Ghr-/- mice, with meal initiation delayed and meal duration enhanced. Neither pattern elevated corticosterone secretion in rats, but meal-feeding aligned ultradian pulses. CONCLUSIONS: We have established a consistent, measurable, researcher-defined, stress-free method for imposing temporal feeding patterns in rats and mice. This approach will facilitate progress in understanding the physiologic impact of feeding patterns.