Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review.

BACKGROUND: Currently, there is a lack of guidelines for the use of short-acting bronchodilators (SABD) in people admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), despite routine use in practice and risk of cardiac adverse events. AIM: To review the evidence that underpins use and optimal dose, in terms of risk versus benefit, of SABD for inpatient management of AECOPD and collate the results for future guidelines. METHODS: Medline, Embase, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and International Clinical Trials Registry Platform were searched (inception to November 2017) for published and ongoing studies. Included studies were randomised controlled trials or controlled clinical trials investigating the effect of SABD (ß2-agonist and/or ipratropium) on inpatients with a diagnosis of AECOPD. This review was undertaken in accordance with PRISMA guidelines and a pre-defined protocol. Due to heterogeneous methodologies, meta-analysis was not possible so the results were synthesised qualitatively. RESULTS: Of 1378 studies identified, 10 met inclusion criteria. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser, and type of ß2-agonist used. However, some evidence demonstrated significantly increased cardiac side effects with increased dosage of ß2-agonist (45% versus 24%), P<0.05). CONCLUSION: This review identified a paucity of methodologically rigorous evidence evaluating use of SABD among AECOPD. The available evidence did not identify any additional benefits for participants receiving higher doses of short-acting ß2-agonists compared to lower doses, or based on type of delivery method or ß2-agonists used. However, there was a small increase in some adverse events for participants using higher doses of ß2-agonists.

A novel regulatory relationship between RIPK4 and ELF3 in keratinocytes.

Keratinocytes are central to the barrier functions of surface epithelia, such as the gingiva and epidermis. RIPK4 is a key regulator of keratinocyte differentiation; however, the signalling pathways in which it functions remain poorly defined. In this study, we identified a regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor. RIPK4 was shown to be important for the upregulation of ELF3 gene expression by the PKC agonist PMA in both oral and epidermal keratinocytes. RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor. Significantly, silencing of IRF6 inhibited the PMA-inducible expression of ELF3. A role for the GRHL3 transcription factor, a downstream target gene of IRF6, in the regulation of ELF3 expression was similarly demonstrated. ELF3 has previously been shown to regulate the expression of SPPR1A and SPRR1B, small proline-rich proteins that contribute to the cornification of keratinocytes. Consistently, RIPK4 and IRF6 were important for the PMA-inducible expression of SPRR1A and SPRR1B. They were also important for the upregulation of TGM1, a transglutaminase that catalyses the cross-linking of proteins, including small proline-rich proteins, during keratinocyte cornification. RIPK4 was also shown to upregulate the expression of TGM2 independently of IRF6. Collectively, our findings position RIPK4 upstream of a hierarchal IRF6-GRHL3-ELF3 transcription factor pathway in keratinocytes, as well as provide insight into a potential role for RIPK4 in the regulation of keratinocyte cornification.

A meta-analysis of "hospital in the home".

OBJECTIVE: To assess the effect of "hospital in the home" (HITH) services that significantly substitute for inhospital time on mortality, readmission rates, patient and carer satisfaction, and costs. DATA SOURCES: MEDLINE, Embase, Social Sciences Citation Index, CINAHL, EconLit, PsycINFO and the Cochrane Database of Systematic Reviews, from the earliest date in each database to 1 February 2012. STUDY SELECTION: Randomised controlled trials (RCTs) comparing HITH care with inhospital treatment for patients aged > 16 years. DATA EXTRACTION: Potentially relevant studies were reviewed independently by two assessors, and data were extracted using a collection template and checklist. DATA SYNTHESIS: 61 RCTs met the inclusion criteria. HITH care led to reduced mortality (odds ratio [OR], 0.81; 95% CI, 0.69 to 0.95; P = 0.008; 42 RCTs with 6992 patients), readmission rates (OR, 0.75; 95% CI, 0.59 to 0.95; P = 0.02; 41 RCTs with 5372 patients) and cost (mean difference, -1567.11; 95% CI, -2069.53 to -1064.69; P < 0.001; 11 RCTs with 1215 patients). The number needed to treat at home to prevent one death was 50. No heterogeneity was observed for mortality data, but heterogeneity was observed for data relating to readmission rates and cost. Patient satisfaction was higher in HITH in 21 of 22 studies, and carer satisfaction was higher in and six of eight studies; carer burden was lower in eight of 11 studies, although not significantly (mean difference, 0.00; 95% CI, -0.19 to 0.19). CONCLUSION: HITH is associated with reductions in mortality, readmission rates and cost, and increases in patient and carer satisfaction, but no change in carer burden.