Acute liver failure in Still's disease relapse during pregnancy: case report and discussion of a possible trigger role of DILI.

BACKGROUND: Still's disease is a rare systemic inflammatory disease with frequent but generally mild liver involvement. The most common cause of acute liver failure in western countries is drug-induced liver injury, while it has rarely been reported in subjects suffering from Still's disease. CASE PRESENTATION: We report a case of a young woman presenting with SD reactivation in pregnancy and acute liver failure after delivery with a possible triggering role of drug induced liver injury. CONCLUSIONS: The prompt recognition of Still's disease reactivation allowed early introduction of steroid therapy and resolution of the clinical picture. We discuss potential factors precipitating ALF in this case, and implications for the diagnosis and management of such patients.

Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes.

Recent large-scale exome sequencing studies have identified mutations in several members of the CHD (Chromodomain Helicase DNA-binding protein) gene family in neurodevelopmental disorders. Mutations in the CHD2 gene have been linked to developmental delay, intellectual disability, autism and seizures, CHD8 mutations to autism and intellectual disability, whereas haploinsufficiency of CHD7 is associated with executive dysfunction and intellectual disability. In addition to these neurodevelopmental features, a wide range of other developmental defects are associated with mutants of these genes, especially with regards to CHD7 haploinsufficiency, which is the primary cause of CHARGE syndrome. Whilst the developmental expression of CHD7 has been reported previously, limited information on the expression of CHD2 and CHD8 during development is available. Here, we compare the expression patterns of all three genes during mouse development directly. We find high, widespread expression of these genes at early stages of development that gradually becomes restricted during later developmental stages. Chd2 and Chd8 are widely expressed in the developing central nervous system (CNS) at all stages of development, with moderate expression remaining in the neocortex, hippocampus, olfactory bulb and cerebellum of the postnatal brain. Similarly, Chd7 expression is seen throughout the CNS during late embryogenesis and early postnatal development, with strong enrichment in the cerebellum, but displays low expression in the cortex and neurogenic niches in early life. In addition to expression in the brain, novel sites of Chd2 and Chd8 expression are reported. These findings suggest additional roles for these genes in organogenesis and predict that mutation of these genes may predispose individuals to a range of other, non-neurological developmental defects.

Promising algorithms to perilous applications: a systematic review of risk stratification tools for predicting healthcare utilisation.

OBJECTIVES: Risk stratification tools that predict healthcare utilisation are extensively integrated into primary care systems worldwide, forming a key component of anticipatory care pathways, where high-risk individuals are targeted by preventative interventions. Existing work broadly focuses on comparing model performance in retrospective cohorts with little attention paid to efficacy in reducing morbidity when deployed in different global contexts. We review the evidence supporting the use of such tools in real-world settings, from retrospective dataset performance to pathway evaluation. METHODS: A systematic search was undertaken to identify studies reporting the development, validation and deployment of models that predict healthcare utilisation in unselected primary care cohorts, comparable to their current real-world application. RESULTS: Among 3897 articles screened, 51 studies were identified evaluating 28 risk prediction models. Half underwent external validation yet only two were validated internationally. No association between validation context and model discrimination was observed. The majority of real-world evaluation studies reported no change, or indeed significant increases, in healthcare utilisation within targeted groups, with only one-third of reports demonstrating some benefit. DISCUSSION: While model discrimination appears satisfactorily robust to application context there is little evidence to suggest that accurate identification of high-risk individuals can be reliably translated to improvements in service delivery or morbidity. CONCLUSIONS: The evidence does not support further integration of care pathways with costly population-level interventions based on risk prediction in unselected primary care cohorts. There is an urgent need to independently appraise the safety, efficacy and cost-effectiveness of risk prediction systems that are already widely deployed within primary care.

Pharmacological Predictors of Morbidity and Mortality in COVID-19.

The interaction of coronavirus disease (COVID-19) with the majority of common prescriptions is broadly unknown. The purpose of this study is to identify medications associated with altered disease outcomes in COVID-19. A retrospective cohort composed of all adult inpatient admissions to our center with COVID-19 was analyzed. Data concerning all antecedent prescriptions were collected and agents brought forward for analysis if prescribed to at least 20 patients in our cohort. Forty-two medications and 22 classes of medication were examined. Groups were propensity score matched and analyzed by logistic and linear regression. The majority of medications did not show a statistically significant relationship with altered disease outcomes. Lower mortality was associated with use of pregabalin (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01-0.92; P = .049) and inhalers of any type (HR, 0.33; 95%CI, 0.14-0.80; P = .015), specifically beclomethasone (HR, 0.10; 95%CI, 0.01-0.82; P = .032), tiotropium (HR, 0.07; 95%CI, 0.01-0.83; P = .035), and steroid-containing inhalers (HR, 0.35; 95%CI, 0.15-0.79; P = .013). Gliclazide (HR, 4.37; 95%CI, 1.26-15.18; P = .020) and proton pump inhibitor (HR, 1.72; 95%CI, 1.06-2.79; P = .028) use was associated with greater mortality. Diuretic (HR, 0.07; 95%CI, 0.01-0.37; P = .002) and statin (HR, 0.35; 95%CI, 0.17-0.73; P = .006) use was associated with lower rates of critical care admission. Our data lends confidence to observing usual practice in patients with COVID-19 by continuing antecedent prescriptions in the absence of an alternative acute contraindication. We highlight potential benefits in investigation of diuretics, inhalers, pregabalin, and statins as therapeutic agents for COVID-19 and support further assessment of the safety of gliclazide and proton pump inhibitors in the acute illness.

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019.

PURPOSE: Due to the affinity of severe acute respiratory syndrome coronavirus 2 for the human angiotensin-converting enzyme 2 (ACE2) receptor, use of ACE inhibitors and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in patients with severe acute respiratory syndrome coronavirus 2 infection. To date, only a limited number of studies have directly evaluated the safety of inpatient prescription of ACE inhibitors/ARBs during acute coronavirus disease 2019 (COVID-19) illness. METHODS: A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACE inhibitors/ARBs on morbidity and mortality in patients admitted to the hospital with COVID-19. Relationships were explored by using linear and logistic regression. FINDINGS: A total of 612 adult patients met the inclusion criteria, of whom 151 (24.7%) patients were established on ACE inhibitors/ARBs. Despite correction for known confounders, discontinuation of ACE inhibitors/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in the hospital was significantly associated with increased mortality (OR, 9.59; 95% CI, 2.55-36.09; P < 0.001), maximum National Early Warning Score 2 (OR, 1.66; 95% CI, 1.27-2.17; P < 0.001), maximum oxygen requirements (OR, 3.00; 95% CI, 1.83-4.91; P < 0.001), and maximum C-reactive protein concentration (OR, 1.83; 95% CI, 1.06-3.17; P = 0.030). IMPLICATIONS: Our data show a strong association between missed ACE inhibitor/ARB doses with increased morbidity and mortality. The available evidence supports continuation of currently accepted practice surrounding ACE inhibitor/ARB therapy in acute illness, which is to limit drug omission to established acute contraindications, to actively monitor such decisions, and to restart therapy as soon as it is safe to do so. (Clin Ther. 2021;43:e97-e110) © 2021 Elsevier HS Journals, Inc.