Next generation sequencing to understand norovirus in immunocompromised children

Norovirus is a leading cause of gastroenteritis worldwide, causing self-limited vomiting and diarrhoea in immunocompetent people and chronic infections with significant morbidity in immunocompromised patients. Data presented in this thesis uses deep sequencing to increase our understanding of norovirus in a hospital paediatric population with a large proportion of immunocompromised patients. Real-time PCR reveals that norovirus is the most prevalent gastrointestinal virus in this population, causing infection with a higher viral titre than other gastrointestinal viruses. Norovirus is most common in immunocompromised patients and is the virus most commonly associated with chronic infections, which occur primarily in immunocompromised patients. The performance of a novel method for deep sequencing norovirus full genomes is described; this overcomes the limitations of previously published methods and achieves full genomes with >12000-fold read depth regardless of genotype or viral titre. This method is applied to sequence the complete genomes of every new norovirus case at Great Ormond Street Hospital (GOSH) over a 19 month period. Full genomes reveal a broad range of circulating genotypes, more akin to genotypes circulating in the community than those typically seen in hospitals. Phylogenetic analysis shows that the majority (69%) of cases are not acquired from another patient. This suggests multiple introductions of different norovirus strains, with limited nosocomial transmission. Full genome sequencing of longitudinally collected samples shows that chronic norovirus infections may involve super- or re-infection with a different genotype, although this does not affect the duration of infection. Deep sequencing is used to investigate changes in the norovirus intra-host mutation frequency in chronically infected immunosuppressed patients who were and were not treated with oral ribavirin, revealing a possible role for ribavirin in the treatment of chronic norovirus infections. However interpretation of in vivo data is confounded by fluctuating mutation frequencies observed over time in all patients

Public health interventions to promote oral health and well-being in patients with type 2 diabetes: a systematic review

Background and objective: Poor oral health and type 2 diabetes mellitus (T2DM) are chronic conditions affecting a wide proportion of the population. Both conditions share many risk factors and are linked by a chronic inflammation state. This review aimed at identifying public health interventions that could promote oral health and diabetes control in patients with poor oral health and T2DM. Methods: The systematic review was performed according to the PRISMA Statement and registered in the International Prospective Register of Systematic Reviews (PROSPERO registration: CRD42022310974). Seven electronic databases were searched (PubMed, Scopus, Embase, Web of Science, CINAHL, PsycInfo, Cochrane Library) from inception to 21 January 2022, and additional hand searching was performed across reviews’ references. A qualitative analysis was conducted, including all primary studies on diabetic patients, about interventions whose effectiveness and/or feasibility was measured for at least one outcome related to oral health or T2DM. Results: Of the 3153 records obtained after deduplication, 89 studies were considered eligible for inclusion. The most frequently evaluated outcomes were HbA1c and fasting glucose for T2DM, and parameters such as probing depth, bleeding on probing and clinical attachment loss for periodontitis. Most studies assessed the use of non-surgical periodontal treatment (especially scaling and root planing, sometimes corroborated by antibiotics): evidence confirmed effectiveness on periodontal parameters, but was more contrasting regarding T2DM outcomes. Three studies evaluated interventions involving group education for lifestyle modification, which showed to be effective on both outcomes. Also, community-based oral hygiene interventions and glycaemic control appeared to improve T2DM and periodontal outcomes. Conclusions: A variety of interventions are described in the literature. Of those included in this review, many indicated that there is a potential opportunity to promote good oral health alongside T2DM. An integrated approach involving health education, oral hygiene and glycaemic control may offer synergic improvement of both conditions

Pharmacokinetics of Extended vs Intermittent Intravenous Infusion of Meropenem in Critically Ill Patients Receiving Continuous Veno-Venous Haemofiltration

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ESICM LIVES 2022: part 2.

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