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1.
J Card Fail ; 30(5): 728-733, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38387758

RESUMO

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.


Assuntos
Mortalidade Hospitalar , Choque Cardiogênico , Humanos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Mortalidade Hospitalar/tendências , Unidades de Cuidados Coronarianos/estatística & dados numéricos , Cuidados Críticos/métodos , Causas de Morte/tendências , Unidades de Terapia Intensiva
2.
Aust Crit Care ; 37(2): 281-287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37537125

RESUMO

BACKGROUND: Intensive care outreach nurses are required to work as part of an ad hoc team to review and manage patients who are deteriorating outside of critical care environments. Nontechnical skills, such as those encompassed by crisis resource management principles, are essential when working in these situations. Used commercially for entertainment, escape rooms have recently been utilised by clinical educators to teach both technical and nontechnical skills. OBJECTIVE: This exploratory study evaluates how advanced clinicians, intensive care outreach nurses, experience an escape room scenario designed to consolidate crisis resource management (CRM) principles. METHODS: Three escape room sessions were conducted in a 1038-bed metropolitan tertiary referral hospital. A purposive sample of 12 intensive care outreach nurses were invited to participate. The participant's experience of the escape room scenario was determined by their responses to a post-escape room survey and focus group discussion. Transcripts of the audio recordings from focus group discussions were analysed using an inductive coding approach. RESULTS: Two primary categories emerged from analysis of the focus group discussions: (i) the clinicians' experiences of the escape room and (ii) CRM principles. The first category included descriptions of emotions, including confusion, frustration, and a dislike for puzzles. The second category included both the participants understanding of the CRM principles, and how the principles influence the work within the escape room. CONCLUSIONS: Escape rooms have shown promise as novel educational environments, which challenge participants. Despite initial negative descriptions of the escape room, focus group discussions demonstrated that the participants were able to recognise the impact of CRM principles and acknowledge how these affect their clinical work in an ad hoc team.


Assuntos
Projetos Piloto , Humanos
3.
MMWR Morb Mortal Wkly Rep ; 72(15): 391-397, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37053125

RESUMO

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.


Assuntos
Poliomielite , Poliovirus , Criança , Adolescente , Humanos , Poliovirus/genética , Vigilância da População , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Surtos de Doenças , Malaui , Vacina Antipólio Oral , Programas de Imunização , Erradicação de Doenças
4.
Genet Med ; 23(7): 1281-1287, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33782553

RESUMO

PURPOSE: Variants in MYBPC3 causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3 VUS associated with increased clinical risk. METHODS: Among 7,963 patients in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), 120 unique missense VUS in MYBPC3 were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and a MYBPC3 missense VUS. RESULTS: We demonstrated that patients carrying a MYBPC3 VUS predicted to cause subdomain misfolding (STRUM+, ΔΔG ≤ -1.2 kcal/mol) exhibited a higher rate of adverse events compared with those with a STRUM- VUS (hazard ratio = 2.29, P = 0.0282). In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding. CONCLUSION: STRUM identifies patients with HCM and a MYBPC3 VUS who may be at higher clinical risk and provides supportive evidence for pathogenicity.


Assuntos
Cardiomiopatias , Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Humanos , Mutação , Mutação de Sentido Incorreto , Medição de Risco
5.
Pflugers Arch ; 471(5): 781-793, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30456444

RESUMO

Mutations in cardiac myosin binding protein C (MYBPC3) represent the most frequent cause of familial hypertrophic cardiomyopathy (HCM), making up approximately 50% of identified HCM mutations. MYBPC3 is distinct among other sarcomere genes associated with HCM in that truncating mutations make up the vast majority, whereas nontruncating mutations predominant in other sarcomere genes. Several studies using myocardial tissue from HCM patients have found reduced abundance of wild-type MYBPC3 compared to control hearts, suggesting haploinsufficiency of full-length MYBPC3. Further, decreased mutant versus wild-type mRNA and lack of truncated mutant MYBPC3 protein has been demonstrated, highlighting the presence of allelic imbalance. In this review, we will begin by introducing allelic imbalance and haploinsufficiency, highlighting the broad role each plays within the spectrum of human disease. We will subsequently focus on the roles allelic imbalance and haploinsufficiency play within MYBPC3-linked HCM. Finally, we will explore the implications of these findings on future directions of HCM research. An improved understanding of allelic imbalance and haploinsufficiency may help us better understand genotype-phenotype relationships in HCM and develop novel targeted therapies, providing exciting future research opportunities.


Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Haploinsuficiência , Animais , Cardiomiopatia Hipertrófica/metabolismo , Proteínas de Transporte/metabolismo , Humanos
8.
J Pharmacol Exp Ther ; 362(1): 85-97, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28442582

RESUMO

LX2761 is a potent sodium/glucose cotransporter 1 inhibitor restricted to the intestinal lumen after oral administration. Studies presented here evaluated the effect of orally administered LX2761 on glycemic control in preclinical models. In healthy mice and rats treated with LX2761, blood glucose excursions were lower and plasma total glucagon-like peptide-1 (GLP-1) levels higher after an oral glucose challenge; these decreased glucose excursions persisted even when the glucose challenge occurred 15 hours after LX2761 dosing in ad lib-fed mice. Further, treating mice with LX2761 and the dipeptidyl-peptidase 4 inhibitor sitagliptin synergistically increased active GLP-1 levels, suggesting increased LX2761-mediated release of GLP-1 into the portal circulation. LX2761 also lowered postprandial glucose, fasting glucose, and hemoglobin A1C, and increased plasma total GLP-1, during long-term treatment of mice with either early- or late-onset streptozotocin-diabetes; in the late-onset cohort, LX2761 treatment improved survival. Mice and rats treated with LX2761 occasionally had diarrhea; this dose-dependent side effect decreased in severity and frequency over time, and LX2761 doses were identified that decreased postprandial glucose excursions without causing diarrhea. Further, the frequency of LX2761-associated diarrhea was greatly decreased in mice either by gradual dose escalation or by pretreatment with resistant starch 4, which is slowly digested to glucose in the colon, a process that primes the colon for glucose metabolism by selecting for glucose-fermenting bacterial species. These data suggest that clinical trials are warranted to determine if LX2761 doses and dosing strategies exist that provide improved glycemic control combined with adequate gastrointestinal tolerability in people living with diabetes.


Assuntos
Compostos Benzidrílicos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peptídeo 1 Semelhante ao Glucagon/antagonistas & inibidores , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipoglicemiantes/farmacologia , Tioglicosídeos/farmacologia , Animais , Compostos Benzidrílicos/química , Relação Dose-Resposta a Droga , Índice Glicêmico/efeitos dos fármacos , Índice Glicêmico/fisiologia , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tioglicosídeos/química
10.
12.
Sci Am ; 326(6): 21, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-39017007
14.
Genet Med ; 23(10): 2011-2012, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34135487
17.
Sci Am ; 324(2): 35, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-39020726
18.
Sci Am ; 325(2): 20, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39020773
19.
Sci Am ; 323(5): 20, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39014786
20.
J Relig Health ; 54(1): 3-19, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24005316

RESUMO

The present study investigated the connections between religious affiliation, quality of life (QOL) and measures of academic performance. Participants (n = 275) were recruited from the School of Medicine within a New Zealand university. Religious affiliation was classified according to three subcategories: Christian (n = 104), Eastern religion (n = 34) and non-religious (n = 117). The participants completed the World Health Organisation quality of life questionnaire (WHOQOL-BREF) and the World Health Organisation Spiritual, Religiousness, and Personal Beliefs questionnaire immediately before their lecture time. The main findings of the study indicated that participants from different religious affiliations expressed different spiritual QOL perceptions. However, these different expressions did not translate into their perceptions related to hours of study and academic achievement. In addition, the QOL measures did not relate to academic achievement estimation but did predict hours of study. Greater hours of study were related to greater physical health but lower psychological health and poorer engagement in developing social relationships. Data from a small focus group (n = 4) revealed that these students believed that having a belief system assisted them when coping with the academic learning environment, although little difference could be found between external religious orientations and internal belief systems.


Assuntos
Logro , Qualidade de Vida/psicologia , Religião e Medicina , Religião e Psicologia , Religião , Estudantes de Medicina/psicologia , Adaptação Psicológica , Adulto , Feminino , Grupos Focais , Nível de Saúde , Humanos , Masculino , Nova Zelândia , Ajustamento Social , Espiritualidade , Inquéritos e Questionários , Adulto Jovem
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