Adherence to 5-aminosalicylic acid maintenance treatment in young people with ulcerative colitis: a retrospective cohort study in primary care

BACKGROUND: Maintenance treatment with 5-aminosalicylic acid (5-ASA) is recommended in ulcerative colitis (UC), but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking. AIM: To determine rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults 1 year following diagnosis of UC. DESIGN AND SETTING: Observational cohort study using the UK Clinical Practice Research Datalink among adolescents and young adults (aged 10-24 years) diagnosed with UC between 1 January 1998 and 1 May 2016. METHOD: Time to oral 5-ASA discontinuation (days) and adherence rates (proportion of days covered) were calculated during the first year of treatment using Kaplan-Meier survival analysis. Cox regression models were built to estimate the impact of sociodemographic and health-related risk factors. RESULTS: Among 607 adolescents and young adults starting oral 5-ASA maintenance treatment, one-quarter (n = 152) discontinued within 1 month and two- thirds (n = 419) within 1 year. Discontinuation was higher among those aged 18-24 years (74%) than younger age groups (61% and 56% in those aged 10-14 and 15-17 years, respectively). Adherence was lower among young adults than adolescents (69% in those aged 18-24 years versus 80% in those aged 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] = 1.10 to 1.92). Early corticosteroid use for an acute flare lowered the likelihood of oral 5-ASA discontinuation (aHR 0.68, 95% CI = 0.51 to 0.90). CONCLUSION: The first year of starting long-term therapies in adolescents and young adults diagnosed with UC is a critical window for active follow-up of maintenance treatment, particularly in those aged 18-24 years and those living in deprived postcodes

Antidepressant medication use in Inflammatory Bowel Disease: a nationally representative population-based study.

BACKGROUND: Despite high rates of depression and anxiety, little is known about the use of antidepressants amongst individuals diagnosed with inflammatory bowel disease (IBD). AIMS: To evaluate temporal trends in the use of antidepressants; rates of antidepressant initiation and adherence of antidepressant use to international guidelines amongst individuals with IBD. METHODS: This is a study of 14,525 incident IBD cases from 2004 to 2016 compared with 58,027 controls matched 1:4 for age and sex from the Clinical Practice Research Datalink. After excluding tricyclic antidepressants, we performed a Cox regression analysis to determine the risk associated with antidepressant use and logistic regression analysis to determine risk associated with antidepressant undertreatment. RESULTS: Antidepressant use amongst individuals with IBD increased by 51% during the 12-year study period, who were 34% more likely to initiate antidepressants in the year after IBD diagnosis compared with controls (aHR:1.34, 95% CI 1.21-1.49). In those with IBD starting antidepressants, 67% received treatment lasting less than the duration recommended in international guidelines, of which 34% were treated for 1 month or less. 18-24 year olds were twice as likely to discontinue treatment within 1 month compared with those aged 40-60 years (aHR:2.03, 95% CI 1.40-2.95). Socioeconomic deprivation was also associated with early treatment discontinuation (aHR:1.40, 95% CI 1.07-1.83). CONCLUSIONS: In the year following IBD diagnosis individuals are significantly more likely to start antidepressants compared with controls, but treatment duration fell short of recommendations in the majority. Better integration of services may benefit individuals with IBD and psychiatric comorbidity

Assessment on the use of high capacity “Sn 4 P 3 ”/NHC composite electrodes for sodium‐ion batteries with ether and carbonate electrolytes

This work reports the facile synthesis of a Sn–P composite combined with nitrogen doped hard carbon (NHC) obtained by ball-milling and its use as electrode material for sodium ion batteries (SIBs). The “Sn4P3”/NHC electrode (with nominal composition “Sn4P3”:NHC = 75:25 wt%) when coupled with a diglyme-based electrolyte rather than the most commonly employed carbonate-based systems, exhibits a reversible capacity of 550 mAh gelectrode−1 at 50 mA g−1 and 440 mAh gelectrode−1 over 500 cycles (83% capacity retention). Morphology and solid electrolyte interphase formation of cycled “Sn4P3”/NHC electrodes is studied via electron microscopy and X-ray photoelectron spectroscopy. The expansion of the electrode upon sodiation (300 mAh gelectrode−1) is only about 12–14% as determined by in situ electrochemical dilatometry, giving a reasonable explanation for the excellent cycle life despite the conversion-type storage mechanism. In situ X-ray diffraction shows that the discharge product is Na15Sn4. The formation of mostly amorphous Na3P is derived from the overall (electro)chemical reactions. Upon charge the formation of Sn is observed while amorphous P is derived, which are reversibly alloying with Na in the subsequent cycles. However, the formation of Sn4P3 can be certainly excluded

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. METHODS: We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. RESULTS: Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95 % CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95 % CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95 % CI 1.3-12.4). CONCLUSIONS: The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

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

Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS)

An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120–160 Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology

Exome sequencing and genotyping identify a rare variant in NLRP7 gene associated with ulcerative colitis.

Background and Aims Although genome-wide association studies [GWAS] in inflammatory bowel disease [IBD] have identified a large number of common disease susceptibility alleles for both Crohn’s disease [CD] and ulcerative colitis [UC], a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein-altering genetic variants are associated with susceptibility to IBD. Methods Whole-exome sequencing was carried out in 10 families in whom three or more individuals were affected with IBD. A stepwise filtering approach was applied to exome variants, to identify potential causal variants. Follow-up genotyping was performed in 6025 IBD cases [2948 CD; 3077 UC] and 7238 controls. Results Our exome variant analysis revealed coding variants in the NLRP7 gene that were present in affected individuals in two distinct families. Genotyping of the two variants, p.S361L and p.R801H, in IBD cases and controls showed that the p.S361L variant was significantly associated with an increased risk of ulcerative colitis [odds ratio 4.79, p = 0.0039] and IBD [odds ratio 3.17, p = 0.037]. A combined analysis of both variants showed suggestive association with an increased risk of IBD [odds ratio 2.77, p = 0.018]. Conclusions The results suggest that NLRP7 signalling and inflammasome formation may be a significant component in the pathogenesis of IBD

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD