Factors associated with hospital admission in adult patients with asthma exacerbations: A systematic review.

OBJECTIVES: A variable proportion of patients presenting to the emergency department (ED) with acute asthma require admission to hospital. Previous studies have identified select factors associated with admission following ED presentation; however, no review has synthesized the evidence in this regard. This systematic review summarizes the evidence regarding factors associated with hospital admission following ED presentation. METHODS: Searches were conducted in seven electronic databases and common sources of grey literature. Studies reporting disposition for adults after ED presentation were included. Admission proportions and factors associated with hospitalization that remained statistically significant in multivariable analyses (p < 0.05) were reported. RESULTS: Out of an initial 5865 identified articles, 15 articles met full inclusion criteria and 11 were included in the analyses. Female sex (n = 2) and older age (n = 2) were individual factors associated with admission. Patient vital signs and severity followed by patient attributes were the two most frequent domains associated with admission. Admission proportions were analyzed in 10 studies at an median of ∼20% with no clear change between 1996 and 2012. CONCLUSIONS: Factors such as patient demographics (e.g., female sex, older age), patient vital signs/severity, and history are associated with admission following ED presentation for acute asthma. These can be employed by ED clinicians to effectively discern patients at high risk for admission and lead to more evidence-based decision-making.

Factors associated with relapse in adult patients discharged from the emergency department following acute asthma: a systematic review.

A significant proportion of patients discharged from the emergency department (ED) with asthma exacerbations will relapse within 4 weeks. This systematic review summarises the evidence regarding relapses and factors associated with relapse in adult patients discharged from EDs after being treated for acute asthma. Following a registered protocol, comprehensive literature searches were conducted. Studies tracking outcomes for adults after ED management and discharge were included if they involved adjusted analyses. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Risk of Bias (RoB) Tool. Results were summarised using medians and IQRs or mean and SD, as appropriate. 178 articles underwent full-text review and 10 studies, of various methodologies, involving 32 923 patients were included. The majority of the studies were of high quality according to NOS and RoB Tool. Relapse proportions were 8±3%, 12±4% and 14±6% at 1, 2 and 4 weeks, respectively. Female sex was the most commonly reported and statistically significant factor associated with an increased risk of relapse within 4 weeks of ED discharge for acute asthma. Other factors significantly associated with relapse were past healthcare usage and previous inhaled corticosteroids (ICS) usage. A median of 17% of patients who are discharged from the ED will relapse within the first 4 weeks. Factors such as female sex, past healthcare usage and ICS use at presentation were commonly and significantly associated with relapse occurrence. Identifying patients with these features could provide clinicians with guidance during their ED discharge decision-making.

Cowden syndrome-related mutations in PTEN associate with enhanced proteasome activity.

Germline mutations in PTEN have been described in a spectrum of syndromes that are collectively known as PTEN hamartoma tumor syndrome (PHTS). In addition to being mutated in the germline in PHTS, somatic loss-of-function PTEN mutations are seen in a wide range of sporadic human tumors. Here, we show evidence of upregulated proteasome activity in PHTS-derived lymphoblasts, Pten knock-in mice and cell lines expressing missense and nonsense PTEN mutations. Notably, elevated nuclear proteasome activity occurred in cells expressing the nuclear mislocalized PTEN-K62R mutant, whereas elevated cytosolic proteasome activity was observed in cells expressing the cytosolic-predominant mutant PTEN (M3M4 and C136R). Treatment with proteasome inhibitor MG-132 was able to restore both nonsense and missense mutant PTEN protein levels in vitro. PHTS patients with destabilizing PTEN mutations and proteasome hyperactivity are more susceptible to develop neurologic symptoms such as mental retardation and autism than mutation-positive patients with normal proteasome activity. A detailed molecular and functional analysis shows that PTEN mutants most likely cause proteasome hyperactivity via 2 different mechanisms, namely, induction of proteotoxic stress and loss of protein phosphatase activity. These results provide novel insights into the cellular functions of PTEN and reveal molecular mechanisms whereby PTEN mutations increase proteasome activity and lead to neurologic phenotypes.