Prolonged and Recurrent Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy is one of the most common disorders of pregnancy, which typically resolves in the postpartum period. Intrahepatic cholestasis is characterized by elevated bile acid levels that present as pruritus. The maternal clinical significance of recurrent and prolonged cholestasis is unknown. We discuss the longest reported case of postpartum cholestasis of 125 weeks.

Mitigating inequalities in community care needs of older adults with dementia: a qualitative case study of an integrated model of community care operated under the proportionate universalism principle.

BACKGROUND: Population ageing and community care on older adults, as well as the marked social inequalities in health, have received growing concern by the government and the community. This study evaluated the medico-social integrated day care model of the Cadenza Hub for older adults with dementia. We also examined whether services subsidized by the publicly funded graded financial support of the Community Care Service Voucher for the Elderly (CCSV) could mitigate social inequalities in community care needs, from the perspective of the caregivers. METHODS: In this qualitative case study, we adopted purposeful sampling strategy to recruit 14 caregivers of active day care service users with dementia, with different socioeconomic background and duration of service use, for face-to-face semi-structured in-depth interviews between June and August 2021. The transcribed data were closely read to capture key themes using thematic analyses. RESULTS: Caregivers faced tremendous caregiving burden in the absence of community care support and struggled in choosing care services. Most informants benefited from the day care service, whereas the financial support of CCSV was crucial to ensure equitable access to community care. Non-governmental organizations and social workers were the key to bridging the information gap. CONCLUSION: The integrated day care of the Cadenza Hub appeared to have addressed the unmet needs of older adults with dementia and their caregivers, including the socioeconomically disadvantaged with the CCSV support. The community care service delivery model might be applicable to address other health inequalities problems.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-{lambda}1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1. We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.

Change in Pneumococcus Serotypes but not Mortality or Morbidity in Pre- and Post-13-Valent Polysaccharide Conjugate Vaccine Era: Epidemiology in a Pediatric Intensive Care Unit over 10 Years.

Aim: Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. Methods: A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. Results: There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. Conclusions: SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.

A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations.

OBJECTIVE: Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations. METHODS: MEDLINE (1966-February 2008), EMBASE (1980-February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0-100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality. RESULTS: Twenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62-76%)], scope/purpose [62% (95% CI 55-68%)], rigor of development [51% (95% CI 42-60%)], editorial independence [39% (95% CI 26-52%)], stakeholder involvement [32% (95% CI 26-37%)] and applicability [19% (95% CI 12-26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations. CONCLUSION: Variation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.