Short-term outcomes of surgical treatment for primary ileocaecal Crohn's disease: Results of the Crohn's(urg) study, a multicentre, retrospective, comparative analysis between inflammatory and complicated phenotypes.

AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

Tackling healthcare access barriers for individuals with autism from diagnosis to adulthood.

Most individuals with autism spectrum disorder (ASD)-a complex, life-long developmental disorder-do not have access to the care required to address their diverse health needs. Here, we review: (1) common barriers to healthcare access (shortage/cost of services; physician awareness; stigma); (2) barriers encountered primarily during childhood (limited screening/diagnosis; unclear referral pathways), transition to adulthood (insufficient healthcare transition services; suboptimal physician awareness of healthcare needs) and adulthood (shortage of services/limited insurance; communication difficulties with physicians; limited awareness of healthcare needs of aging adults); and (3) advances in research/program development for better healthcare access. A robust understanding of barriers to accessing healthcare across the lifespan of autistic individuals is critical to ensuring the best use of healthcare resources to improve social, physical, and mental health outcomes. Stakeholders must strengthen healthcare service provision by coming together to: better understand healthcare needs of underserved populations; strengthen medical training on care of autistic individuals; increase public awareness of ASD; promote research into/uptake of tools for ASD screening, diagnosis, and treatment; understand specific healthcare needs of autistic individuals in lower resource countries; and conduct longitudinal studies to understand the lifetime health, social, and economic impacts of ASD and enable the evaluation of novel approaches to increasing healthcare access. IMPACT: Despite the growing body of evidence, our understanding of barriers to healthcare encountered by individuals with ASD remains limited, particularly beyond childhood and in lower resource countries. We describe current and emerging barriers to healthcare access encountered by individuals with ASD across the lifespan. We recommend that stakeholders develop evidence-informed policies, programs, and technologies that address barriers to healthcare access for individuals with ASD and consider broad, equitable implementation to maximize impact.

Clozapine discontinuation in early schizophrenia: a retrospective case note review of patients under an early intervention service.

AIM: Research in patients with treatment-resistant schizophrenia has demonstrated that clozapine discontinuation is associated with poor outcomes. There is, however, a paucity of research investigating the impact of clozapine discontinuation specifically in younger patients with more recent onset schizophrenia. A case note review was therefore conducted to ascertain medium-term prognoses in patients with treatment-resistant schizophrenia under an early intervention service (EIS) following clozapine discontinuation. METHODS: The case notes of 25 patients under the care of Birmingham EIS who discontinued clozapine were examined retrospectively. Reasons for discontinuation were recorded. Clinical outcomes including total duration of inpatient or home treatment admission, antipsychotic dose, number of alternative antipsychotics prescribed and adverse events were recorded for both the year before and the year after stopping clozapine. Statistical comparisons of pre- and post-discontinuation clinical outcomes determined whether discontinuation had negative effects. RESULTS: There was no significant difference between the pre- and post-discontinuation clinical status following clozapine discontinuation. More than half (56%) of patients remained stable after stopping clozapine. Mean inpatient or home treatment stay rose from 29.7 to 62.6 days (p = 0.155), total antipsychotic dose from 50.1% of British National Formulary (BNF) limits to 60.5% (p = 0.627), number of alternative antipsychotics prescribed from 1.28 to 1.80 (p = 0.186), number of hospital/home treatment episodes from 0.20 to 0.44 (p = 0.083) and number of adverse events from 0 to 0.20 (p = 0.059). Non-compliance was the main reason for discontinuation (44%, n = 11). CONCLUSIONS: This is the first clozapine discontinuation study specifically considering EIS patients. Discontinuation did not lead to significant effects on 1 year outcomes, though the study is underpowered. These findings may be used to inform future prospective cohort discontinuation studies.

Type I interferon promotes cell-to-cell spread of Listeria monocytogenes.

Type I interferons (IFNs) play a critical role in antiviral immune responses, but can be deleterious to the host during some bacterial infections. Listeria monocytogenes (Lm) induces a type I IFN response by activating cytosolic antiviral surveillance pathways. This is beneficial to the bacteria as mice lacking the type I IFN receptor (IFNAR1-/- ) are resistant to systemic infection by Lm. The mechanisms by which type I IFNs promote Lm infection are unclear. Here, we show that IFNAR1 is required for dissemination of Lm within infection foci in livers of infected mice and for efficient cell-to-cell spread in vitro in macrophages. IFNAR1 promotes ActA polarization and actin-based motility in the cytosol of host cells. Our studies suggest type I IFNs directly impact the intracellular life cycle of Lm and provide new insight into the mechanisms used by bacterial pathogens to exploit the type I IFN response.