Evaluation of emergency department performance:A systematic review on recommended performance and quality-in-care measures

BACKGROUND: Evaluation of emergency department (ED) performance remains a difficult task due to the lack of consensus on performance measures that reflects high quality, efficiency, and sustainability. AIM: To describe, map, and critically evaluate which performance measures that the published literature regard as being most relevant in assessing overall ED performance. METHODS: Following the PRISMA guidelines, a systematic literature review of review articles reporting accentuated ED performance measures was conducted in the databases of PubMed, Cochrane Library, and Web of Science. Study eligibility criteria includes: 1) the main purpose was to discuss, analyse, or promote performance measures best reflecting ED performance, 2) the article was a review article, and 3) the article reported macro-level performance measures, thus reflecting an overall departmental performance level. RESULTS: A number of articles addresses this study’s objective (n = 14 of 46 unique hits). Time intervals and patient-related measures were dominant in the identified performance measures in review articles from US, UK, Sweden and Canada. Length of stay (LOS), time between patient arrival to initial clinical assessment, and time between patient arrivals to admission were highlighted by the majority of articles. Concurrently, “patients left without being seen” (LWBS), unplanned re-attendance within a maximum of 72 hours, mortality/morbidity, and number of unintended incidents were the most highlighted performance measures that related directly to the patient. Performance measures related to employees were only stated in two of the 14 included articles. CONCLUSIONS: A total of 55 ED performance measures were identified. ED time intervals were the most recommended performance measures followed by patient centeredness and safety performance measures. ED employee related performance measures were rarely mentioned in the investigated literature. The study’s results allow for advancement towards improved performance measurement and standardised assessment across EDs

Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants - identification of 11 novel mutations in CYBB

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X-linked CGD (X91-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910, X91- or X91+), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910-CGD and two X91--CGD). One X910-CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91--CGD were also novel; one deletion, c.-67delT, was localized in the promoter region of CYBB; the second c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91--CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three-dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91--CGD patients correlates with mild clinical forms of CGD, whereas X910-CGD and X91+-CGD cases remain the most clinically severe forms.</p

A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine-Serine rich domain and causing the hyper-activation of the receptor and the responsivity to the non-canonical ligand, Activin A. In the present study, we described a 3-years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods: Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection-based assays. Results and Conclusions: We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A&gt;T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A-mediated signaling, as observed for the gene variants associated with FOP

Post hoc analysis of SUSTAIN 6 and PIONEER 6 trials suggests that people with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo.

Glucagon-like peptide-1 receptor agonists reduce albuminuria and may stabilize the estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). In this post hoc analysis of the SUSTAIN 6/PIONEER 6 trials encompassing 6480 participants at high cardiovascular risk (semaglutide, 3239 participants; placebo, 3241 participants), we investigated the effects of semaglutide versus placebo on eGFR decline. Pooled data by treatment were evaluated for annual eGFR change (total annual eGFR slope in ml/min per 1.73 m2) from baseline to end of treatment and time to persistent eGFR reductions of 30%, 40%, 50% and 57% or more, including subgroup analyses by baseline eGFR (30 to under 60 or 60 and over ml/min per 1.73 m2). In the overall population, the estimated treatment difference (ETD; semaglutide versus placebo) in annual eGFR slope was significant at 0.59 ml/min per 1.73 m2 (95% confidence interval 0.29; 0.89). The ETD was numerically largest in the 30 to under 60 ml/min per 1.73 m2 eGFR subgroup, 1.06 ml/min per 1.73 m2 (0.45; 1.67), but no significant interaction was observed for treatment effect by subgroup. Hazard ratios (semaglutide versus placebo) for time to persistent eGFR decline were under 1.0 for all eGFR thresholds in the overall population; and were numerically lower in the baseline eGFR 30 to under 60 ml/min per 1.73 m2 subgroup versus the overall population, although no significant interaction was observed for treatment effect by subgroup. Thus, pooled analyses of clinical trial data in patients with T2D suggest that semaglutide may reduce the rate of eGFR decline

Influence of comorbidities in idiopathic normal pressure hydrocephalus:Research and clinical care. A report of the ISHCSF task force on comorbidities in INPH

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes

Telemedicine strategy of the European Reference Network ITHACA for the diagnosis and management of patients with rare developmental disorders

Background: The European Reference Networks, ERNs, are virtual networks for healthcare providers across Europe to collaborate and share expertise on complex or rare diseases and conditions. As part of the ERNs, the Clinical Patient Management System, CPMS, a secure digital platform, was developed to allow and facilitate web-based, clinical consultations between submitting clinicians and relevant international experts. The European Reference Network on Intellectual Disability, TeleHealth and Congenital Anomalies, ERN ITHACA, was formed to harness the clinical and diagnostic expertise in the sector of rare, multiple anomaly and/or intellectual disability syndromes, chromosome disorders and undiagnosed syndromic disorders. We present the first year results of CPMS use by ERN ITHACA as an example of a telemedicine strategy for the diagnosis and management of patients with rare developmental disorders. Results: ERN ITHACA ranked third in telemedicine activity amongst 24 European networks after 12 months of using the CPMS. Information about 28 very rare cases from 13 different centres across 7 countries was shared on the platform, with diagnostic or other management queries. Early interaction with patient support groups identified data protection as of primary importance in adopting digital platforms for patient diagnosis and care. The first launch of the CPMS was built to accommodate the needs of all ERNs. The ERN ITHACA telemedicine process highlighted a need to customise the CPMS with network-specific requirements. The results of this effort should enhance the CPMS utility for telemedicine services and ERN-specific care outcomes. Conclusions: We present the results of a long and fruitful process of interaction between the ERN ITHACA network lead team and EU officials, software developers and members of 38 EU clinical genetics centres to organise and coordinate direct e-healthcare through a secure, digital platform. The variability of the queries in just the first 28 cases submitted to the ERN ITHACA CPMS is a fair representation of the complexity and rarity of the patients referred, but also proof of the sophisticated and variable service that could be provided through a structured telemedicine approach for patients and families with rare developmental disorders. Web-based approaches are likely to result in increased accessibility to clinical genomic services