RESUMO
The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in humans. We identified eight individuals harboring heterozygous variants in CAMK2D who display symptoms of intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms. Together, we describe a cohort of individuals with neurodevelopmental disorders and cardiac anomalies, harboring pathogenic variants in CAMK2D, confirming an important role for the CAMK2D isozyme in both heart and brain function.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Cardiomiopatia Dilatada , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Animais , Humanos , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Coração , Transtornos do Neurodesenvolvimento/genéticaRESUMO
OBJECTIVE: Mutations in the genes encoding neuronal ion channels are a common cause of Mendelian neurological diseases. We sought to identify novel de novo sequence variants in cases with early infantile epileptic phenotypes and neurodevelopmental anomalies. METHODS: Following clinical diagnosis, we performed whole exome sequencing of the index cases and their parents. Identified channel variants were expressed in Xenopus oocytes and their functional properties assessed using two-electrode voltage clamp. RESULTS: We identified novel de novo variants in KCNA6 in four unrelated individuals variably affected with neurodevelopmental disorders and seizures with onset in the first year of life. Three of the four identified mutations affect the pore-lining S6 α-helix of KV 1.6. A prominent finding of functional characterization in Xenopus oocytes was that the channel variants showed only minor effects on channel activation but slowed channel closure and shifted the voltage dependence of deactivation in a hyperpolarizing direction. Channels with a mutation affecting the S6 helix display dominant effects on channel deactivation when co-expressed with wild-type KV 1.6 or KV 1.1 subunits. SIGNIFICANCE: This is the first report of de novo nonsynonymous variants in KCNA6 associated with neurological or any clinical features. Channel variants showed a consistent effect on channel deactivation, slowing the rate of channel closure following normal activation. This specific gain-of-function feature is likely to underlie the neurological phenotype in our patients. Our data highlight KCNA6 as a novel channelopathy gene associated with early infantile epileptic phenotypes and neurodevelopmental anomalies.
Assuntos
Epilepsia , Transtornos do Neurodesenvolvimento , Humanos , Epilepsia/genética , Mutação/genética , Convulsões/genética , Canal de Potássio Kv1.6/genéticaRESUMO
Thousand and one amino-acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen-activated protein kinase pathways, thereby modulating a multitude of processes in the cell. Given the recent finding of TAOK1 involvement in neurodevelopmental disorders (NDDs), we investigated the role of TAOK1 in neuronal function and collected a cohort of 23 individuals with mostly de novo variants in TAOK1 to further define the associated NDD. Here, we provide evidence for an important role for TAOK1 in neuronal function, showing that altered TAOK1 expression levels in the embryonic mouse brain affect neural migration in vivo, as well as neuronal maturation in vitro. The molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant-negative effect on TAOK1, expanding the potential underlying causative mechanisms resulting in NDD. Taken together, our data indicate that TAOK1 activity needs to be properly controlled for normal neuronal function and that TAOK1 dysregulation leads to a neurodevelopmental disorder mainly comprising similar facial features, developmental delay/intellectual disability and/or variable learning or behavioral problems, muscular hypotonia, infant feeding difficulties, and growth problems.
Assuntos
Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Aminoácidos , Animais , Humanos , Deficiência Intelectual/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Hipotonia Muscular , Transtornos do Neurodesenvolvimento/genéticaRESUMO
Over the years, library collections have vastly changed due to an ever-growing presence of resources available online. Many libraries have experienced a dramatic decrease in the circulation of physical materials with the shift to online availability of materials. It is of great value to ensure libraries are meeting the needs of their users, and this can be accomplished by identifying their information-seeking patterns. The aim of this article is to examine how faculty use the library and to identify what services and resources are of value to their work.
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Docentes de Medicina , Comportamento de Busca de Informação , Humanos , Bibliotecas Médicas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Idiopathic hyperammonemia syndrome (IHS) is an uncommon, often deadly complication of solid organ transplantation. IHS cases in solid organ transplantation seem to occur predominantly in lung transplant (LTx) recipients. However, to the best of our knowledge, the occurrence of IHS has not been systematically evaluated. We set out to identify all reported cases of IHS following nonliver solid organ transplantations. METHODS: Retrospective review of our institutional experience and systematic review of the literature. RESULTS: At our institution six cases (of 844 nonliver solid organ transplants) of IHS were identified: five occurred following LTx (incidence 3.9% [lung] vs 0.1% [nonlung], P=.004). In the systematic review, 16 studies met inclusion criteria, reporting on 32 cases of IHS. The majority of IHS cases in the literature (81%) were LTx-recipients. The average peak reported ammonia level was 1039 µmol/L occurring on average 14.7 days post-transplant. Mortality in previously reported IHS cases was 69%. A single-center experience suggested that, in addition to standard treatment for hyperammonemia, early initiation of high intensity hemodialysis to remove ammonia was associated with increased survival. In the systematic review, mortality was 40% (four of 10) with intermittent hemodialysis, 75% (nine of 12) with continuous veno-venous hemodialysis, and 100% in six subjects that did not receive renal replacement to remove ammonia. Three reports identified infection with urease producing organisms as a possible etiology of IHS. CONCLUSION: IHS is a rare but often fatal complication that primarily affects lung transplant recipients within the first 30 days.
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Hiperamonemia/etiologia , Pneumopatias/fisiopatologia , Transplante de Órgãos/efeitos adversos , Humanos , Metanálise como Assunto , Prognóstico , Estudos RetrospectivosRESUMO
In 2015, two librarians at the Hardin Library for the Health Sciences at the University of Iowa turned their dreams into a reality and secured funding to build a zombie-themed evidence-based medicine game. The game features a "choose your own adventure" style that takes students through a scenario where a disease outbreak is taking place and a resident is asked to use evidence-based medicine skills to select a screening and diagnostic tool to use on potentially infected patients. Feedback on the game has been positive, and future plans include building additional modules on therapy, harm, and prognosis.
Assuntos
Educação Médica/métodos , Medicina Baseada em Evidências/educação , Treinamento por Simulação/métodos , Jogos de Vídeo , Humanos , IowaRESUMO
A systematic literature review and meta-analysis was performed to identify effectiveness of mupirocin decolonization in prevention of Staphylococcus aureus infections, among nonsurgical settings. Of the 15 662 unique studies identified up to August 2015, 13 randomized controlled trials, 22 quasi-experimental studies, and 1 retrospective cohort study met the inclusion criteria. Studies were excluded if mupirocin was not used for decolonization, there was no control group, or the study was conducted in an outbreak setting. The crude risk ratios were pooled (cpRR) using a random-effects model. We observed substantial heterogeneity among included studies (I(2) = 80%). Mupirocin was observed to reduce the risk for S. aureus infections by 59% (cpRR, 0.41; 95% confidence interval [CI], .36-.48) and 40% (cpRR, 0.60; 95% CI, .46-.79) in both dialysis and nondialysis settings, respectively. Mupirocin decolonization was protective against S. aureus infections among both dialysis and adult intensive care patients. Future studies are needed in other settings such as long-term care and pediatrics.
Assuntos
Antibacterianos/uso terapêutico , Mupirocina/uso terapêutico , Infecções Estafilocócicas/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Nariz/microbiologia , Diálise RenalRESUMO
Pathogenic variants in the mitofusin 2 gene (MFN2) are the most common cause of autosomal dominant Charcot-Marie-Tooth (CMT2) disease, which is typically characterized by axonal sensorimotor neuropathy. We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2. A review of the literature reveals that sporadic and familial cases of compound heterozygous or homozygous pathogenic MFN2 variants have been infrequently described, which indicates that MFN2 can also be inherited in a recessive manner. This case highlights several clinical findings not typically associated with MFN2 pathogenic variants, including young age of onset and rapidly progressing diaphragmatic paresis that necessitated tracheostomy and mechanical ventilation, and adds to the growing list of features identified in autosomal recessive MFN2-related CMT2. Our patient with MFN2-related CMT2 expands the clinical and mutational spectrum of individuals with autosomal recessive CMT2 and identifies a new clinical feature that warrants further observation. © 2016 Wiley Periodicals, Inc.
Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Diafragma/fisiopatologia , GTP Fosfo-Hidrolases/genética , Genes Recessivos , Proteínas Mitocondriais/genética , Debilidade Muscular/genética , Mutação , Alelos , Feminino , Estudos de Associação Genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Linhagem , FenótipoRESUMO
Due to an identified need for formal assessment, a small team of librarians designed and administered a survey to gauge the quality of customer service at their academic health sciences library. Though results did not drive major changes to services, several important improvements were implemented and a process was established to serve as a foundation for future use. This article details the assessment process used and lessons learned during the project.
Assuntos
Serviços de Informação/normas , Bibliotecas Médicas , Bibliotecários , Biblioteconomia , Serviços de BibliotecaRESUMO
Many studies have evaluated bundled interventions to improve hand hygiene compliance. However, there are few evidence-based recommendations on optimal interventions for implementation. We aimed to systematically review all studies on interventions to improve hand hygiene compliance to evaluate existing bundles and identify areas of promise to target high-quality studies. Adjusted risk ratios were pooled to assess common bundles. Of the 8148 studies evaluated, 6 randomized controlled trials and 39 quasi-experimental studies met inclusion criteria. Three studies evaluated the interventions education, reminders, feedback, administrative support, and access to alcohol-based hand rub as a bundle, which was associated with improved hand hygiene compliance (pooled odds ratio [OR], 1.82; 95% confidence interval [CI], 1.69-1.97). Another bundle of education, reminders, and feedback evaluated in 3 studies was associated with improved compliance (pooled OR, 1.47; 95% CI, 1.12-1.94). These bundles should be further studied using high-quality study designs and compared with other interventions.
Assuntos
Higiene das Mãos/métodos , Instalações de Saúde , Pessoal de Saúde , Controle de Infecções/métodos , Pacotes de Assistência ao Paciente/métodos , Fidelidade a Diretrizes/estatística & dados numéricos , HumanosRESUMO
As distance education and blended learning grows, so does the need for health sciences librarians to become involved with course management systems. This article will provide some information on how to become involved with course management systems and will also provide information on a few of the more popular systems available.
Assuntos
Educação a Distância/organização & administração , Bibliotecas Médicas/organização & administração , Humanos , Biblioteconomia/educação , Software , Integração de SistemasRESUMO
In 2010, the University of Iowa's library system administration created a task force to conduct a reevaluation of tools and spaces used for video tutorial creation across a multi-library system. Following this effort, a working group was charged with improving documentation and staff awareness of resources for developing video tutorials. The group observed that librarians were often independently creating videos that were variable in quality, lacked consistent branding, and were not often shared with others. This article will describe experiences at the Hardin Library for the Health Sciences at the University of Iowa in selecting video tutorial software, and striving to establish a more structured process, including team-developed guidelines, for tutorial creation in a multi-library system. Project limitations and areas for future work will also be presented.
Assuntos
Instrução por Computador , Serviços de Biblioteca/organização & administração , Gravação em Vídeo , Comportamento Cooperativo , Guias como Assunto , Humanos , Internet , Iowa , Sistemas Multi-Institucionais , Software , Inquéritos e QuestionáriosRESUMO
As the number of online library tutorials increases, so does the need to create active learning experiences and options for self-assessment. This article looks at embedding short Flash quizzes into tutorials created with Camtasia as a way to address this need. It also attempts to determine how quiz placement affects desire to view online tutorials and information retention.
Assuntos
Instrução por Computador , Educação de Graduação em Medicina/métodos , Aprendizagem Baseada em Problemas , Autoavaliação (Psicologia) , Humanos , Internet , Aprendizagem , Estudantes de MedicinaRESUMO
OBJECTIVES: This research project aims to determine the potential differential impact of two curricular approaches to teaching evidence-based medicine (EBM) on student performance on an EBM assignment administered during the first year of clerkship. A meaningful result would be any statistically significant difference in scores on the assignment given to measure student performance. DESIGN: In order to assess and compare student learning under the different curricula, the principal investigator and a team of five faculty members blinded to assignment date and other possibly identifying details used a modified version of the previously validated Fresno rubric to retrospectively grade 3 years' worth of EBM assignments given to students in clerkship rotations 1-3 (n=481) during the Internal Medicine clerkship. Specifically, EBM performance in three separate student cohorts was examined. SETTING: The study took place at a large Midwestern medical school with nine campuses across the state of Indiana. PARTICIPANTS: Study participants were 481 students who attended the medical school and completed the Internal Medicine clerkship between 2017 and 2019. INTERVENTIONS: Prior to the inception of this study, our institution had been teaching EBM within a discrete 2-month time period during medical students' first year. During a large-scale curricular overhaul, the approach to teaching EBM was changed to a more scaffolded, integrated approach with sessions being taught over the course of 2 years. In this study, we assess the differential impact of these two approaches to teaching EBM in the first 2 years of medical school. MAIN OUTCOME MEASURES: We used clerkship-level EBM assignment grades to determine whether there was a difference in performance between those students who experienced the old versus the new instructional model. Clerkship EBM assignments given to the students used identical questions each year in order to have a valid basis for comparison. Additionally, we analysed average student grades across the school on the EBM portion of step 1. RESULTS: Four hundred and eighty-one assignments were graded. Mean scores were compared for individual questions and cumulative scores using a one-way Welch Analysis of Variance test. Overall, students performed 0.99 of a point better on the assignment from year 1 (Y1), prior to EBM curriculum integration, to year 3 (Y3), subsequent to EBM integration (p≤0.001). Statistically significant improvement was seen on questions measuring students' ability to formulate a clinical question and critically appraise medical evidence. Additionally, on the United States Medical Licensing Examination (USMLE) step 1, we found that student scores on the EBM portion of the examination improved from Y1 to Y3. CONCLUSIONS: Results of this study suggest that taking a scaffolded, curriculum-integrated approach to EBM instruction during the preclinical years increases, or at the very least does not lessen, student retention of and ability to apply EBM concepts to patient care. Although it is difficult to fully attribute students' retention and application of EBM concepts to the adoption of a curricular model focused on scaffolding and integration, the results of this study show that there are value-added educational effects to teaching EBM in this new format. Overall, this study provides a foundation for new research and practice seeking to improve EBM instruction. TRIAL REGISTRATION NUMBER: IRB approval (Protocol number 1907054875) was obtained for this study.
Assuntos
Estágio Clínico , Faculdades de Medicina , Currículo , Medicina Baseada em Evidências/educação , Humanos , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Estados UnidosRESUMO
OBJECTIVE: To evaluate the difference in pharygocutaneous fistula (PCF) development between pectoralis major flap onlay and interpositional reconstructions after salvage total laryngectomy (STL). DATA SOURCES: Medline, Cochrane, Embase, Web of Science, CINAHL, and ClinicalTrials.gov. REVIEW METHODS: A systematic review was performed during January 2020. English articles were included that described minor and major PCF rates after STL reconstructed with pectoralis major onlay or interposition. PCFs were classified as major when conservative therapy was unsuccessful and/or revision surgery was needed. Articles describing total laryngopharyngectomies were excluded. Meta-analyses of the resulting data were performed. RESULTS: Twenty-four articles met final criteria amassing 1304 patients. Three articles compared onlay with interposition, and 18 compared onlay with primary closure. Pectoralis interposition demonstrated elevated odds ratio (OR) of PCF formation as compared with onlay (OR, 2.34; P < .001). Onlay reconstruction reduced overall (OR, 0.32; P < .001) and major (OR, 0.21; P < .001) PCF development as compared with primary pharyngeal closure alone. Data were insufficient to compare interposition against primary closure. CONCLUSIONS: This research shows evidence that pectoralis onlay after STL diminishes the odds of total and major PCF development. Pectoralis interposition reconstruction showed elevated odds of PCF formation as compared with pectoralis onlay.
Assuntos
Fístula Cutânea/epidemiologia , Laringectomia/métodos , Músculos Peitorais/transplante , Doenças Faríngeas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Fístula do Sistema Respiratório/epidemiologia , Retalhos Cirúrgicos , Humanos , Terapia de SalvaçãoRESUMO
SPTBN1 encodes ßII-spectrin, the ubiquitously expressed ß-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal ßII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect ßII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of ßII-spectrin in the central nervous system.
Assuntos
Genes Dominantes , Predisposição Genética para Doença , Variação Genética , Transtornos do Neurodesenvolvimento/genética , Espectrina/genética , Animais , Estudos de Associação Genética/métodos , Heterozigoto , Humanos , Camundongos , Transtornos do Neurodesenvolvimento/diagnóstico , Fenótipo , Espectrina/metabolismoRESUMO
Importance: An understanding of the incidence and outcomes of Clostridium difficile infection (CDI) in the United States can inform investments in prevention and treatment interventions. Objective: To quantify the incidence of CDI and its associated hospital length of stay (LOS) in the United States using a systematic literature review and meta-analysis. Data Sources: MEDLINE via Ovid, Cochrane Library Databases via Wiley, Cumulative Index of Nursing and Allied Health Complete via EBSCO Information Services, Scopus, and Web of Science were searched for studies published in the United States between 2000 and 2019 that evaluated CDI and its associated LOS. Study Selection: Incidence data were collected only from multicenter studies that had at least 5 sites. The LOS studies were included only if they assessed postinfection LOS or used methods accounting for time to infection using a multistate model or compared propensity score-matched patients with CDI with control patients without CDI. Long-term-care facility studies were excluded. Of the 119 full-text articles, 86 studies (72.3%) met the selection criteria. Data Extraction and Synthesis: Two independent reviewers performed the data abstraction and quality assessment. Incidence data were pooled only when the denominators used the same units (eg, patient-days). These data were pooled by summing the number of hospital-onset CDI incident cases and the denominators across studies. Random-effects models were used to obtain pooled mean differences. Heterogeneity was assessed using the I2 value. Data analysis was performed in February 2019. Main Outcomes and Measures: Incidence of CDI and CDI-associated hospital LOS in the United States. Results: When the 13 studies that evaluated incidence data in patient-days due to hospital-onset CDI were pooled, the CDI incidence rate was 8.3 cases per 10â¯000 patient-days. Among propensity score-matched studies (16 of 20 studies), the CDI-associated mean difference in LOS (in days) between patients with and without CDI varied from 3.0 days (95% CI, 1.44-4.63 days) to 21.6 days (95% CI, 19.29-23.90 days). Conclusions and Relevance: Pooled estimates from currently available literature suggest that CDI is associated with a large burden on the health care system. However, these estimates should be interpreted with caution because higher-quality studies should be completed to guide future evaluations of CDI prevention and treatment interventions.
Assuntos
Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Tempo de Internação/estatística & dados numéricos , Humanos , Incidência , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pontuação de Propensão , Estados Unidos/epidemiologiaRESUMO
Background: An important measure of successful sarcoma treatment is the surgical tumor margin, yet defining and reporting the tumor margin has remained a source of controversy. Our study sought to determine whether there is a need to be more specific in classifying a margin by distinguishing a 'close' margin, or if simply calling a margin positive or negative is sufficient. Methods: We performed a comprehensive literature search in which all studies were reviewed independently by two separate reviewers. Studies eligible for inclusion and data analysis consisted of those that reported on at least ten patients with a primary sarcoma of the extremities who received limb-salvage or amputation surgery with a report of the final surgical margin as well as the histologic grade. Only studies that provided local recurrence outcomes with a minimum follow-up of two years were included. Results: Our literature search and article exclusion process resulted in 22 articles that contained 498 patients for data analyses. We found that the Enneking classification system distinguishes between intralesional, marginal, and wide/ radical margins, and that a close margin behaves closer to a positive margin than a negative margin. When all tumors were analyzed, a marginal margin gave a recurrence rate of 50.48% compared to an intralesional margin recurrence rate of 75.76% and a wide/ radical margin of 7.22%. A marginal margin set to a positive margin gave the highest sensitivity compared to comparing marginal margins to wide and intralesional margins alone. This was also observed when tumors were stratified into high-grade osteosarcomas treated with chemotherapy. In addition, we found that chemotherapy dramatically reduced local recurrence rates in osteosarcoma. Conclusions: Our literature search and data analysis showed that the Enneking classification system was able to give more information on local recurrence compared to a simple dichotomous system, and therefore may be considered a more successful predictor of treatment outcomes. As a result, this investigation may lead a suggestion of a practice-changing proposal of how surgical margins in sarcoma should be reported universally amongst multiple disciplines and institutions.Level of Evidence: II.
Assuntos
Neoplasias Ósseas/patologia , Sarcoma/patologia , Neoplasias Ósseas/cirurgia , Humanos , Margens de Excisão , Sarcoma/cirurgiaRESUMO
Background: Although acute myocardial infarction is a common cause of out-of-hospital cardiac arrest (OHCA), the role of early coronary angiography in OHCA remains uncertain. We conducted a meta-analysis of observational studies to determine the association of early coronary angiography with survival in OHCA. Methods: We searched multiple electronic databases for published studies on early coronary angiography in OHCA between 1 January 1990 and 18 January 2017. Studies were included if (1) restricted to only OHCA, (2) included an exposure group that underwent early coronary angiography within 1 day of arrest onset and a concurrent control group that did not undergo early coronary angiography, and (3) reported survival outcomes. We used a random-effects model to obtain pooled OR. I2 statistics and Cochran's Q test were used to determine between-study heterogeneity. Results: A total of 17 studies with 14 972 patients were included, of whom 6424 (44%) received early coronary angiography. Early coronary angiography was associated with higher odds of survival (pooled OR 2.54 (95% CI 1.94 to 3.33)) and survival with favourable neurological outcome (pooled OR 2.37 (95% CI 1.71 to 3.28)). However, there was substantial heterogeneity in our pooled estimate (I2=88% and p value for Cochran's test <0.0001 for both outcomes). The large heterogeneity in pooled estimates was reduced after including adjusted estimates when available, and was explained by differences in methodological rigour and characteristics of included studies. Conclusion: Among patients resuscitated from OHCA, early coronary angiography is associated with increased survival to discharge and favourable neurological outcome.
RESUMO
Background: Carbapenem-resistant Enterobacteriaceae (CRE) pose an urgent public health threat in the United States. An important step in planning and monitoring a national response to CRE is understanding its epidemiology and associated outcomes. We conducted a systematic literature review of studies that investigated incidence and outcomes of CRE infection in the US. Methods: We performed searches in MEDLINE via Ovid, CDSR, DARE, CENTRAL, NHS EED, Scopus, and Web of Science for articles published from 1/1/2000 to 2/1/2016 about the incidence and outcomes of CRE at US sites. Results: Five studies evaluated incidence, but many used differing definitions for cases. Across the entire US population, the reported incidence of CRE was 0.3-2.93 infections per 100,000 person-years. Infection rates were highest in long-term acute-care (LTAC) hospitals. There was insufficient data to assess trends in infection rates over time. Four studies evaluated outcomes. Mortality was higher in CRE patients in some but not all studies. Conclusion: While the incidence of CRE infections in the United States remains low on a national level, the incidence is highest in LTACs. Studies assessing outcomes in CRE-infected patients are limited in number, small in size, and have reached conflicting results. Future research should measure a variety of clinical outcomes and adequately adjust for confounders to better assess the full burden of CRE.