Diagnostic Delay in Pediatric Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Delays in diagnosing pediatric inflammatory bowel disease (IBD) are common, but the extent of this delay remains unclear due to variations in reported time-periods between studies. The objectives of this systematic review were to examine the extent of diagnostic delay in pediatric IBD and examine any association between specific characteristics and length of diagnostic delay. METHODS: We identified studies from several medical bibliographical databases (EMBASE, Medline and CINAHL) from their inception to April 2021. Studies examining pediatric cohorts (< 18 years old) defined as having a diagnosis of Crohn's Disease (CD), ulcerative colitis (UC), or by the more general definition of IBD, and reporting a median time-period between the onset of symptoms and a final diagnosis (diagnostic delay) were included. Two reviewers selected each study, extracted data, and assessed their quality using the Newcastle-Ottawa scale. Narrative synthesis was then used to examine the extent of overall diagnostic delay and delay associated with specific sample characteristics. RESULTS: Of the 10,119 studies initially identified, 24 were included in the review. The overall median diagnostic delay range was 2-10.4 months for IBD, 2.0-18.0 months for UC and 4.0-24.0 months for CD. However, for approximately two thirds of UC (68.8%) and CD (66.7%) studies, delay ranged from 2.0-3.0 and 4.0-6.3 months, respectively. A longer delay was significantly associated with several sample characteristics; however, these were too infrequently examined to draw robust conclusion on their role. CONCLUSION: Children continue to wait several months for a final diagnosis of IBD, and those with CD experience longer delay than those with UC. The role of specific characteristics on delay needs further exploration.

Patients' views and experiences of delayed diagnosis of inflammatory bowel disease: a qualitative study.

BACKGROUND: Diagnosing inflammatory bowel disease (IBD) can be challenging. Patients have been found to experience significant diagnostic delay, which can lead to poorer clinical outcomes. The reasons for this delay are not fully understood, and exploring patients' perspectives can offer important insights. AIM: To explore the views and experiences of patients who self-report a delay in IBD diagnosis. DESIGN & SETTING: Qualitative methodology using semi-structured interviews. Participants were recruited via social media and a national IBD charity. METHOD: Interviews were conducted by telephone between December 2018 and February 2019. Data were analysed using thematic analysis and drawing on the constant comparison method. RESULTS: Sixteen interviews were carried out. Ten participants were female and six were male; participants were aged 20-65 years. Four main themes were identified: patient factors contributing to delay; primary care factors contributing to delay; systemic factors contributing to delay; and perceived consequences of delayed diagnosis. Participants reported initially not seeking help due to embarrassment or normalising their symptoms. Having consulted, participants reported further delay in receiving a diagnosis due to their perception that GPs had either mislabelled symptoms, expressed uncertainty, or not taken symptoms seriously. Systemic factors, including lack of access to test results and communication issues across primary and secondary care, were also cited as contributing to delayed diagnosis. Several participants felt that their delayed diagnosis led to poorer clinical outcomes. CONCLUSION: These findings can support patients and GPs in their conversations about symptoms that may indicate IBD, and potentially contribute to reducing diagnostic delay, as well as informing future primary care interventions.

Diagnostic delay in adult inflammatory bowel disease: A systematic review.

BACKGROUND: The extent of diagnostic delay in inflammatory bowel disease (IBD) is incompletely understood. We aimed to understand the extent of diagnostic delay of IBD in adults and identify associations between patient or healthcare characteristics and length of delay. METHODS: Articles were sourced from EMBASE, Medline and CINAHL from inception to April 2021. Inclusion criteria were adult cohorts (18 ≥ years old) reporting median time periods between onset of symptoms for Crohn's disease (CD), ulcerative colitis (UC) or IBD (i.e. CD and UC together) and a final diagnosis (diagnostic delay). Narrative synthesis was used to examine the extent of diagnostic delay and characteristics associated with delay. Sensitivity analysis was applied by the removal of outliers. RESULTS: Thirty-one articles reporting median diagnostic delay for IBD, CD or UC were included. After sensitivity analysis, the majority of IBD studies (7 of 8) reported a median delay of between 2 and 5.3 months. From the studies examining median delay in UC, three-quarters (12 of 16) reported a delay between 2 and 6 months. In contrast, three-quarters of the CD studies (17 of 23) reported a delay of between 2 and 12 months. No characteristic had been examined enough to understand their role in diagnostic delay in these populations. CONCLUSIONS: This systematic review provides robust insight into the extent of diagnostic delay in IBD and suggests further intervention is needed to reduce delay in CD particularly. Furthermore, our findings provide a benchmark value range for diagnostic delay, which such future work can be measured against.

The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection.

The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686-694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141-143).

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.