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BACKGROUND: The profound changes wrought by coronavirus disease 2019 (COVID-19) on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates. METHODS: In 148 HCA Healthcare-affiliated hospitals, from 1 March 2020 to 30 September 2020, and a subset of hospitals with microbiology and cluster data through 31 December 2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month. RESULTS: Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% confidence interval [CI]: 23-108%) more CLABSI, 43% (95% CI: 8-90%) more CAUTI, and 44% (95% CI: 10-88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus, and Gram-negative organisms, were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased. CONCLUSIONS: COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.
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Bacteriemia , COVID-19 , Infecções Relacionadas a Cateter , Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Pneumonia Associada à Ventilação Mecânica , Infecções Urinárias , Enterococos Resistentes à Vancomicina , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , COVID-19/epidemiologia , Teste para COVID-19 , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/microbiologia , Atenção à Saúde , Humanos , Pandemias , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções Urinárias/epidemiologiaRESUMO
AIM: Diabetes has been identified as a risk factor for poor outcomes in patients with COVID-19. We examined the association of hyperglycaemia, both in the presence and absence of pre-existing diabetes, with severity and outcomes in COVID-19 patients. METHODS: Data from 74,148 COVID-19-positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre-existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl). RESULTS: Among patients with and without a pre-existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70-180 mg/dl) in both groups (non-diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre-existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52-2.07); among patients without a pre-existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79-3.37). CONCLUSION: This retrospective analysis identified hyperglycaemia in COVID-19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID-19 morality in the inpatient environment.
Assuntos
Glicemia , COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperglicemia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Coronavirus disease 2019 (COVID-19) has migrated to regions that were initially spared, and it is likely that different populations are currently at risk for illness. Herein, we present our observations of the change in characteristics and resource use of COVID-19 patients over time in a national system of community hospitals to help inform those managing surge planning, operational management, and future policy decisions.
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COVID-19/epidemiologia , COVID-19/terapia , Hospitalização/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/etnologia , COVID-19/mortalidade , Feminino , Hispânico ou Latino/estatística & dados numéricos , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Virginia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To determine risk factors for mortality among COVID-19 patients admitted to a system of community hospitals in the United States. DESIGN: Retrospective analysis of patient data collected from the routine care of COVID-19 patients. SETTING: System of >180 acute-care facilities in the United States. PARTICIPANTS: All admitted patients with positive identification of COVID-19 and a documented discharge as of May 12, 2020. METHODS: Determination of demographic characteristics, vital signs at admission, patient comorbidities and recorded discharge disposition in this population to construct a logistic regression estimating the odds of mortality, particular for those patients characterized as not being critically ill at admission. RESULTS: In total, 6,180 COVID-19+ patients were identified as of May 12, 2020. Most COVID-19+ patients (4,808, 77.8%) were admitted directly to a medical-surgical unit with no documented critical care or mechanical ventilation within 8 hours of admission. After adjusting for demographic characteristics, comorbidities, and vital signs at admission in this subgroup, the largest driver of the odds of mortality was patient age (OR, 1.07; 95% CI, 1.06-1.08; P < .001). Decreased oxygen saturation at admission was associated with increased odds of mortality (OR, 1.09; 95% CI, 1.06-1.12; P < .001) as was diabetes (OR, 1.57; 95% CI, 1.21-2.03; P < .001). CONCLUSIONS: The identification of factors observable at admission that are associated with mortality in COVID-19 patients who are initially admitted to non-critical care units may help care providers, hospital epidemiologists, and hospital safety experts better plan for the care of these patients.
Assuntos
COVID-19/patologia , Sinais Vitais , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: While adequate pain relief is central to patient recovery and satisfaction, opioid use is associated with side effects, adverse drug events and opioid use disorder and therefore is under increased scrutiny. Enhanced surgical recovery protocols include multimodal pain management as a key process, but the impact of opioid dose as an independent variable has not been examined. METHODS: Retrospective analysis of 51,824 hip and knee arthroplasty encounters in a large healthcare system. RESULTS: Overall, patients receiving treatment with lower doses of opiates had shorter median length of stay (p < 0.001); this earlier discharge had no negative consequences on readmission rates. In particular, patients discharged on day 1 received a lower median morphine milligram equivalent (MME) per day than those who were not discharged (32.5 [IQR: 19.0-50.0] versus 45.0 [26.7-71.2], respectively, p < 0.001). The probability of discharge on day 1 was 41.2% and 19.6% for those patients on lower versus higher MME/day, respectively. Similarly, there was a reduction in odds of readmission of 15.2% (95% CI 5.8-23.6%) for patients on lower doses of MME/day. CONCLUSION: Lower MME/day following joint arthroplasty is linked to the probability of discharge on both days 1 and 2 post-surgery as well as reduced odds of readmission. These findings persisted even when adjusting for all other factors, including participation in the enhanced surgical recovery program, the use of a multi-modal analgesic regimen, the presence of complications, patient demographics, and other baseline characteristics. Efforts to reduce opioid use in the peri- and immediate post-operative period, regardless of the mechanism, demonstrated a significant effect on patient outcomes.
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OBJECTIVES: The prevention of hospital-acquired pressure ulcers (PrUs) has significant consequences for patient outcomes and the cost of care. Providers are challenged with evaluating available evidence and best practices, then implementing programs and motivating change in various facility environments. METHODS: In a large system of community hospitals, the Reducing Hospital Acquired-PrUs Program was developed to provide a toolkit of best practices, timely and appropriate data for focusing efforts, and continuous implementation support. Baseline data on PrU rates helped focus efforts on the most vulnerable patients and care situations. Facilities were empowered to use and adapt available resources to meet local needs and to share best practices for implementation across the system. Outcomes were measured by the rate of hospital-acquired PrUs, as gathered from patient discharge records. RESULTS: The rate of hospital-acquired stage III and IV PrUs decreased 66.3% between 2011 and 2013. Of the 149 participating facilities, 40 (27%) had zero hospital-acquired stage III and IV PrUs and 77 (52%) had a reduction in their PrU rate. Rates of all PrUs documented as present on admission did not change during this period. A comparison of different strategies used by the most successful facilities illustrated the necessity of facility-level flexibility and recognition of local workflows and patient demographics. CONCLUSIONS: Driven by the combination of a repository of evidence-based tools and best practices, readily available data on PrU rates, and local flexibility with processes, the Reducing Hospital Acquired-PrUs Program represents the successful operationalization of improvement in a wide variety of facilities.
Assuntos
Hospitais Comunitários/normas , Segurança do Paciente/normas , Úlcera por Pressão/prevenção & controle , Melhoria de Qualidade/tendências , Gestão de Riscos/métodos , Hospitalização , Hospitais Comunitários/tendências , Humanos , Doença Iatrogênica/epidemiologia , Doença Iatrogênica/prevenção & controle , Avaliação de Processos e Resultados em Cuidados de Saúde , Segurança do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Gestão de Riscos/organização & administração , Estados Unidos/epidemiologiaRESUMO
Emergency departments (EDs) in the United States are expected to provide consistent, high-quality care to patients. Unfortunately, EDs are encumbered by problems associated with the demand for services and the limitations of current resources, such as overcrowding, long wait times, and operational inefficiencies. While increasing the effectiveness and efficiency of emergency care would improve both access and quality of patient care, coordinated improvement efforts have been hindered by a lack of timely access to data. The ED Dashboard and Reporting Application was developed to support data-driven process improvement projects. It incorporated standard definitions of metrics, a data repository, and near real-time analysis capabilities. This helped acute care hospitals in a large healthcare system evaluate and target individual improvement projects in accordance with corporate goals. Subsequently, there was a decrease in "arrival to greet" time--the time from patient arrival to physician contact--from an average of 51 minutes in 2007 to the goal level of less than 35 minutes by 2010. The ED Dashboard and Reporting Application has also contributed to data-driven improvements in length of stay and other measures of ED efficiency and care quality. Between January 2007 and December 2010, overall length of stay decreased 10.5 percent while annual visit volume increased 13.6 percent. Thus, investing in the development and implementation of a system for ED data capture, storage, and analysis has supported operational management decisions, gains in ED efficiency, and ultimately improvements in patient care.
Assuntos
Benchmarking/organização & administração , Eficiência Organizacional , Serviço Hospitalar de Emergência/organização & administração , Gestão da Informação/organização & administração , Sistemas Multi-Institucionais , Estudos de Casos Organizacionais , Estados UnidosRESUMO
The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.
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The developmental lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor). However, the functional significance of continued reelin expression in the postnatal brain remains poorly understood. Here, we show that reelin application to adult mice hippocampal slices leads to enhanced glutamatergic transmission mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs) through distinct mechanisms. Application of recombinant reelin enhanced NMDAR-mediated currents through postsynaptic mechanisms, as revealed by the variance-mean analysis of synaptic NMDAR currents, assessment of spontaneous miniature events, and the levels of NMDAR subunits at synaptic surface. In comparison, nonstationary fluctuation analysis of miniature AMPAR currents and quantification of synaptic surface proteins revealed that reelin-induced enhancement of AMPAR responses was mediated by increased AMPAR numbers. Reelin enhancement of synaptic NMDAR currents was abolished when receptor-associated protein (RAP) or the Src inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) was bath applied and was abrogated by including PP1 in the recording electrodes. In comparison, including RAP or an inactive PP1 analog PP3 in the recording electrode was without effect. Interestingly, the increased AMPAR response after reelin application was not blocked by PP1 but was blocked by the phosphoinositide-3' kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride]. Furthermore, reelin-induced, PI3K-dependent AMPAR surface insertion was also observed in cultured hippocampal neurons. Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus.
Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Hipocampo/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Serina Endopeptidases/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/genética , Linhagem Celular , Células Cultivadas , Potenciais Pós-Sinápticos Excitadores/fisiologia , Proteínas da Matriz Extracelular/genética , Feminino , Hipocampo/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Receptores de AMPA/agonistas , Receptores de AMPA/fisiologia , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/fisiologia , Proteína Reelina , Serina Endopeptidases/genética , Transdução de Sinais/genética , Quinases da Família src/fisiologiaRESUMO
The heterozygote reeler mouse (HRM) shows many neuroanatomical and biochemical features that are also present in some human cognitive disorders, such as schizophrenia. In the present study, hippocampal dependent plasticity and cognitive function of the HRM were characterized in detail in an attempt to reveal phenotypic functional differences that result from Reelin haploinsufficiency. The HRM and wild type mice show similar levels of overall activity, coordination, thermal nociception, startle responses, and anxiety-like behavior. In addition, both genotypes show similar shock threshold, identical cued freezing behavior and comparable spatial learning in Morris water maze tasks. However, a significant reduction in contextual fear conditioned learning was observed in the HRM. Electrophysiological studies in hippocampal CA1 synapses revealed a plethora of differences between genotypes. The HRM exhibits reduced field excitatory postsynaptic potentials in responses to similar synaptic inputs, lowered paired pulse facilitation ratio and impaired long-term depression and tetanus-induced long-term potentiation (LTP). Also, deficits were detected in LTP elicited by theta burst stimulation or by a whole cell pairing protocol. These physiologic differences could not be accounted for by changes in the overall amount of glutamate receptor subunits. In addition, it was determined that network-driven excitatory and inhibitory activities recorded in CA1 pyramidal neurons showed that the HRM had comparable amplitude and frequency of spontaneous excitatory postsynaptic currents, but a marked reduction in spontaneous inhibitory postsynaptic currents. Thus, the HRM exhibits a specific hippocampal-dependent learning deficit accompanied with a pronounced impairment of hippocampal plasticity and functional inhibitory innervation.
Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Proteínas da Matriz Extracelular/metabolismo , Haploidia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Proteínas do Tecido Nervoso/metabolismo , Serina Endopeptidases/metabolismo , Sinapses/metabolismo , Animais , Condicionamento Psicológico , Medo , Feminino , Genótipo , Heterozigoto , Hipocampo/citologia , Masculino , Aprendizagem em Labirinto , Camundongos , Inibição Neural/fisiologia , Proteína Reelina , Sinapses/fisiologiaRESUMO
The well-known family of low-density lipoprotein receptors represents a collection of ancient membrane receptors that have been remarkably conserved throughout evolution. These multifunctional receptors, known to regulate cholesterol transport, are becoming increasingly interesting to the neuroscience community due to their ability to transduce a diversity of extracellular signals across the membrane in the adult CNS. Their roles in modulating synaptic plasticity and necessity in hippocampus-specific learning and memory have recently come to light. In addition, genetic, biochemical and behavioral studies have implicated these signaling systems in a number of human neurodegenerative and neuropsychiatric disorders involving loss of cognitive ability, such as Alzheimer's disease, schizophrenia and autism. This review describes the known functions of these receptors and discusses their potential role in processes of synaptic regulation and memory formation.
Assuntos
Transtornos Cognitivos/metabolismo , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Receptores de LDL/metabolismo , Transdução de Sinais/fisiologia , Sinapses/metabolismo , Animais , Apolipoproteínas E/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Integrinas/metabolismo , Proteínas Relacionadas a Receptor de LDL , Lipoproteínas VLDL/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Lipoproteínas/metabolismo , Proteína Reelina , Serina Endopeptidases/metabolismoRESUMO
Reelin is a secreted protein that regulates brain layer formation during embryonic development. Reelin binds several receptors, including two members of the low-density lipoprotein (LDL) receptor family, the apolipoprotein E receptor 2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR). Despite the high level of expression of Reelin and ApoER2 in the postnatal brain, their functions in the adult CNS remain elusive. Here, using electrophysiological, immunocytochemical, and biochemical approaches in cultured postnatal hippocampal neurons, we show that Reelin controls the change in subunit composition of somatic NMDA glutamate receptors (NMDARs) during maturation. We found that maturation is characterized by the gradual decrease of the participation of NR1/2B receptors to whole-cell NMDAR-mediated currents. This maturational change was mirrored by a timely correlated increase of both Reelin immunoreactivity in neuronal somata and the amount of secreted Reelin. Chronic blockade of the function of Reelin with antisense oligonucleotides or the function-blocking antibody CR-50 prevented the decrease of NR1/2B-mediated whole-cell currents. Conversely, exogenously added recombinant Reelin accelerated the maturational changes in NMDA-evoked currents. The maturation-induced change in NMDAR subunits also was blocked by chronic treatment with an inhibitor of the Src kinase signaling pathway or an antagonist of the LDL receptors, but not by inhibitors of another class of Reelin receptor belonging to the integrin family. Consistent with these results, immunocytochemistry revealed that NR1-expressing neurons also expressed ApoER2 and VLDLR. These data reveal a new role for Reelin and LDL receptors and reinforce the idea of a prominent role of extracellular matrix proteins in postnatal maturation.
Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Hipocampo/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/fisiologia , Receptores de LDL/fisiologia , Receptores de Lipoproteínas/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Serina Endopeptidases/fisiologia , Animais , Técnicas de Cultura de Células , Meios de Cultura , Hipocampo/crescimento & desenvolvimento , Imuno-Histoquímica , Integrinas/fisiologia , Proteínas Relacionadas a Receptor de LDL , Camundongos , Neurônios/citologia , Receptores de N-Metil-D-Aspartato/química , Proteína ReelinaRESUMO
Deficiencies in Complex I have been observed in Parkinson's disease (PD) patients. Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures. However, it remains unclear why rotenone seems to affect dopaminergic cells more adversely. Therefore, the role of dopamine (DA) in rotenone-induced PC12 cell toxicity was examined. Rotenone (1.0 muM) caused significant toxicity in differentiated PC12 cells, which was accompanied by decreases in ATP levels, changes in catechol levels, and increased DA oxidation. To determine whether endogenous DA makes PC12 cells more susceptible to rotenone, cells were treated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT) to reduce DA levels prior to rotenone exposure, and then cell viability was measured. No changes in rotenone-induced toxicity were observed with or without AMPT treatment. However, a potentiation of toxicity was observed following coexposure of PC12 cells to rotenone and methamphetamine. To determine whether this effect was due to DA, PC12 cells were depleted of DA prior to methamphetamine and rotenone cotreatment, resulting in a large attenuation in toxicity. These findings suggest that DA plays a role in rotenone-induced toxicity and possibly the vulnerability of DA neurons in PD.