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1.
PLoS One ; 16(11): e0259858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34797847

RESUMO

BACKGROUND: Professional burnout represents a significant threat to the American healthcare system. Organizational and individual factors may increase healthcare providers' susceptibility or resistance to burnout. We hypothesized that during the COVID-19 pandemic, 1) higher levels of perceived organizational support (POS) are associated with lower risk for burnout and anxiety, and 2) anxiety mediates the association between POS and burnout. METHODS: In this longitudinal prospective study, we surveyed healthcare providers employed full-time at a large, multihospital healthcare system monthly over 6 months (April to November 2020). Participants were randomized using a 1:1 allocation stratified by provider type, gender, and academic hospital status to receive one of two versions of the survey instrument formulated with different ordering of the measures to minimize response bias due to context effects. The exposure of interest was POS measured using the validated 8-item Survey of POS (SPOS) scale. Primary outcomes of interest were anxiety and risk for burnout as measured by the validated 10-item Burnout scale from the Professional Quality (Pro-QOL) instrument and 4-item Emotional Distress-Anxiety short form of the Patient Reported Outcome Measurement Information System (PROMIS) scale, respectively. Linear mixed models evaluated the associations between POS and both burnout and anxiety. A mediation analysis evaluated whether anxiety mediated the POS-burnout association. RESULTS: Of the 538 participants recruited, 402 (75%) were included in the primary analysis. 55% of participants were physicians, 73% 25-44 years of age, 73% female, 83% White, and 44% had ≥1 dependent. Higher POS was significantly associated with a lower risk for burnout (-0.23; 95% CI -0.26, -0.21; p<0.001) and lower degree of anxiety (-0.07; 95% CI -0.09, -0.06; p = 0.010). Anxiety mediated the associated between POS and burnout (direct effect -0.17; 95% CI -0.21, -0.13; p<0.001; total effect -0.23; 95% CI -0.28, -0.19; p<0.001). CONCLUSION: During a health crisis, increasing the organizational support perceived by healthcare employees may reduce the risk for burnout through a reduction in anxiety. Improving the relationship between healthcare organizations and the individuals they employ may reduce detrimental effects of psychological distress among healthcare providers and ultimately improve patient care.

2.
Ann Am Thorac Soc ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644242

RESUMO

RATIONALE: Extremity threat and amputation following sepsis is a well-publicized and devastating event. However, there is a paucity of data exists surrounding theabout the epidemiology of extmreityextremity threat following sepsis onset. OBJECTIVES: We aim toTo estimate the incidence of extremity threat with or without surgical amputation in community sepsis. METHODS: Multihospital Rretrospective cohort study of adults with Sepsis-3 hospitalized at XX14 academic and community sites from 2013 to 2017. Vasopressor-dependent sepsis was identified by administration epinephrine, norepinephrine, phenylephrine, vasopressin, or dopamine for >1 hour during the 48 hours before to 24 hours following sepsis onset. Outcomes included the incidence of extremity threat, defined as acute onset ischemia, with or without amputation in the 90 days following sepsis onset. The association between extremity threat, and demographics, comorbid conditions, and, and time-varying sepsis treatment factorss were evaluated using a Cox-proportional hazards model. RESULTS: Among 24,365 adults with sepsis, 12,060 (54%) were vasopressor-dependent (mean±standard deviation SD age, 64±16 years; male, 6,548 [54%]; sequential organ failure assessment (SOFA), 10±4). Of these, 231 (2%) patients had a threatened extremity with 26 undergoing 37 amputations, a risk of 2.2 (95% CI: 1.4-3.2) per 1,000, and 205 not undergoing amputation, a risk of 17.0 (95% CI: 14.8-19.5) per 1,000. 95% of the total 37Most amputations occurred in lower extremities (95%), a median (interquartile range) of 16 (6.3-4039.9) days after sepsis onset. Compared to patients with no extremity threat, patients with threat had a higher sequential organ failure assessmentSOFA score (11±4 vs 10±4; P < 0.001), serum lactate (4.6 mmol/L [2.4-8.7] vs 3.1 [1.7-6.0]; P < 0.001), and more bacteremia (n = 37 [37%??] vs n = 2,087 [26%]; P < 0.001) at sepsis onset. Peripheral vascular disease, congestive heart failure, sequential organ failure assessmentSOFA score, and norepinephrine equivalents were significantly associated with the risk of extremity threat. CONCLUSIONS: The evaluation of a threatened extremity resulting in surgical amputation occurred in 2 per 1,000 patients with vasopressor-dependent sepsis.

3.
JAMA Netw Open ; 4(9): e2123389, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468755

RESUMO

Importance: Although patients with emergency general surgery (EGS) conditions frequently undergo interhospital transfers, the transfer patterns and associated factors are not well understood. Objective: To examine whether patients with EGS conditions are consistently directed to hospitals with more resources and better outcomes. Design, Setting, and Participants: This cohort study performed a network analysis of interhospital transfers among adults with EGS conditions from January 1 to December 31, 2016. The analysis used all-payer claims data from the 2016 Healthcare Cost and Utilization Project state inpatient and emergency department databases in 8 states. A total of 728 hospitals involving 85 415 transfers of 80 307 patients were included. Patients were eligible for inclusion if they were 18 years or older and had an acute care hospital encounter with a diagnosis of an EGS condition as defined by the American Association for the Surgery of Trauma. Data were analyzed from January 1, 2020, to June 17, 2021. Exposures: Hospital-level measures of size (total bed capacity), resources (intensive care unit [ICU] bed capacity, teaching status, trauma center designation, and presence of trauma and/or surgical critical care fellowships), EGS volume (annual EGS encounters), and EGS outcomes (risk-adjusted failure to rescue and in-hospital mortality). Main Outcomes and Measures: The main outcome was hospital-level centrality ratio, defined as the normalized number of incoming transfers divided by the number of outgoing transfers. A higher centrality ratio indicated more incoming transfers per outgoing transfer. Multivariable regression analysis was used to test the hypothesis that a higher hospital centrality ratio would be associated with more resources, higher volume, and better outcomes. Results: Among 80 307 total patients, the median age was 63 years (interquartile range [IQR], 50-75 years); 52.1% of patients were male and 78.8% were White. The median number of outgoing and incoming transfers per hospital were 106 (IQR, 61-157) and 36 (IQR, 8-137), respectively. A higher log-transformed centrality ratio was associated with more resources, such as higher ICU capacity (eg, >25 beds vs 0-10 beds: ß = 1.67 [95% CI, 1.16-2.17]; P < .001), and higher EGS volume (eg, quartile 4 [highest] vs quartile 1 [lowest]: ß = 0.78 [95% CI, 0-1.57]; P = .01). However, a higher log-transformed centrality ratio was not associated with better outcomes, such as lower in-hospital mortality (eg, quartile 4 [highest] vs quartile 1 [lowest]: ß = 0.30 [95% CI, -0.09 to 0.68]; P = .83) and lower failure to rescue (eg, quartile 4 [highest] vs quartile 1 [lowest]: ß = -0.50 [95% CI, -1.13 to 0.12]; P = .27). Conclusions and Relevance: In this study, EGS transfers were directed to high-volume hospitals with more resources but were not necessarily directed to hospitals with better clinical outcomes. Optimizing transfer destination in the interhospital transfer network has the potential to improve EGS outcomes.

4.
J Surg Res ; 268: 532-539, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34464890

RESUMO

BACKGROUND: Under-triage in trauma remains prevalent, in part because of decisions made by physicians at non-trauma centers. We developed two digital behavior change interventions to recalibrate physician heuristics (pattern recognition), and randomized 688 emergency medicine physicians to use the interventions or to a control. In this observational follow-up, we evaluated whether exposure to the interventions changed physician performance in practice. METHODS: We obtained 2016 - 2018 Medicare claims for severely injured patients, linked the names of trial participants to National Provider Identifiers (NPIs), and identified claims filed by trial participants for injured patients presenting to non-trauma centers in the year before and after their trial. The primary outcome measure was the triage status of severely injured patients. RESULTS: We linked 670 (97%) participants to NPIs, identified claims filed for severely injured patients by 520 (76%) participants, and claims filed at non-trauma centers by 228 (33%). Most participants were white (64%), male (67%), and had more than three years of experience (91%). Patients had a median Injury Severity Score of 16 (IQR 16 - 17), and primarily sustained neuro-trauma. After adjustment, patients treated by physicians randomized to the interventions experienced less under-triage in the year after the trial than before (41% versus 58% [-17%], P = 0.015); patients treated by physicians randomized to the control experienced no difference in under-triage (49% versus 56% [-7%], P = 0.35). The difference-in-the-difference was non-significant (10%, P = 0.18). CONCLUSIONS: It was feasible to track trial participants' performance in national claims. Sample size limitations constrained causal inference about the effect of the interventions.

5.
Surgery ; 170(5): 1298-1307, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34147261

RESUMO

BACKGROUND: Emergency general surgery conditions are common, require urgent surgical evaluation, and are associated with high mortality and costs. Although appropriate interhospital transfers are critical to successful emergency general surgery care, the performance of emergency general surgery transfer systems remains unclear. We aimed to describe emergency general surgery transfer patterns and identify factors associated with potentially avoidable transfers. METHODS: We performed a retrospective cohort study of emergency general surgery episodes in 8 US states using the 2016 Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases and the American Hospital Association Annual Surveys. We identified Emergency Department-to-Inpatient and Inpatient-to-Inpatient interhospital emergency general surgery transfers. Potentially avoidable transfers were defined as discharge within 72 hours after transfer without undergoing any procedure or operation at the destination hospital. We examined transfer incidence and characteristics. We performed multilevel regression examining patient-level and hospital-level factors associated with potentially avoidable transfers. RESULTS: Of 514,410 adult emergency general surgery episodes, 26,281 (5.1%) involved interhospital transfers (Emergency Department-to-Inpatient: 65.0%, Inpatient-to-Inpatient: 35.1%). Over 1 in 4 transfers were potentially avoidable (7,188, 27.4%), with the majority occurring from the emergency department. Factors associated with increased odds of potentially avoidable transfers included self-pay (versus government insurance, odds ratio: 1.26, 95% confidence interval: 1.09-1.45, P = .002), level 1 trauma centers (versus non-trauma centers, odds ratio: 1.24, 95% confidence interval: 1.05-1.47, P = .01), and critical access hospitals (versus non-critical access, odds ratio: 1.30, 95% confidence interval: 1.15-1.47, P < .001). Hospital-level factors (size, trauma center, ownership, critical access, location) accounted for 36.1% of potentially avoidable transfers variability. CONCLUSION: Over 1 in 4 emergency general surgery transfers are potentially avoidable. Understanding factors associated with potentially avoidable transfers can guide research, quality improvement, and infrastructure development to optimize emergency general surgery care.


Assuntos
Emergências/epidemiologia , Serviço Hospitalar de Emergência/normas , Tratamento de Emergência/estatística & dados numéricos , Pacientes Internados , Transferência de Pacientes/normas , Melhoria de Qualidade , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
6.
Am Surg ; : 31348211011131, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33866864

RESUMO

BACKGROUND: Study of telemedicine and telerounding in surgical specialties is limited. The push for telemedicine during the COVID-19 pandemic has challenged the face-to-face rounding paradigm and creates an opportunity for reflection on the benefits of telemedicine, especially for balancing competing corporate and clinical demands. METHODS: The 117-month video-based inpatient telerounding experience of a colorectal surgeon in an academic medical system was recorded, including patient characteristics, diagnoses, technology, content of telerounding encounters, and logistical considerations. Data were analyzed using descriptive statistics. RESULTS: 163 patients were seen in 201 telerounding encounters, primarily for routine postoperative care (90.5%). Most were admitted for inflammatory bowel disease (63.2%). Changes were made to plans of care during 28.9% of encounters, and discharge planning was part of 26.4%. Encounters were conducted primarily from the surgeon's administrative office (68.7%) or other work-related locations (10.9%), while 6.5% originated from the surgeon's home. Technologic issues occurred in 5.5% of encounters. 89.1% of patient feedback was positive and none was negative. CONCLUSION: Telerounding is technologically feasible and has clinical value, including for patients with complex surgical problems. Technologic problems are rare and patient satisfaction is high. Surgeons should consider telerounding as a means to balance competing demands.

7.
Kidney Int ; 99(3): 498-510, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33637194

RESUMO

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Adulto , Humanos , Rim , Medicina de Precisão , Estudos Prospectivos , Proteômica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
8.
iScience ; 24(1): 102009, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33490917

RESUMO

Circadian rhythms regulate adaptive alterations in mammalian physiology and are maximally entrained by the short wavelength blue spectrum; cataracts block the transmission of light, particularly blue light. Cataract surgery is performed with two types of intraocular lenses (IOL): (1) conventional IOL that transmit the entire visible spectrum and (2) blue-light-filtering (BF) IOL that block the short wavelength blue spectrum. We hypothesized that the transmission properties of IOL are associated with long-term survival. This retrospective cohort study of a 15-hospital healthcare system identified 9,108 participants who underwent bilateral cataract surgery; 3,087 were implanted with conventional IOL and 6,021 received BF-IOL. Multivariable Cox proportional hazards models that included several a priori determined subgroup and sensitivity analyses yielded estimates supporting that conventional IOL compared with BF-IOL may be associated with significantly reduced risk of long-term death. Confirming these differences and identifying any potential causal mechanisms await the conduct of appropriately controlled prospective translational trials.

9.
Ann Surg ; 274(6): 1081-1088, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714316

RESUMO

BACKGROUND: 30% of elderly patients who require emergency general surgery (EGS) die in the year after the operation. Preoperative discussions can determine whether patients receive preference-sensitive care. Theoretically, surgeons frame their conversations after systematically assessing the risks and benefits of management options based on the clinical characteristics of each case. However, little is known about how surgeons actually deliberate about those options. OBJECTIVE: To identify variables that influence surgeons' assessment of management options for critically-ill EGS patients. METHODS: We conducted semi-structured interviews with 40 general surgeons in western Pennsylvania who worked in a variety of hospital settings. Interviews explored perioperative decision-making by asking surgeons to think aloud about selected memorable cases and a standardized case vignette of a frail patient with acute mesenteric ischemia. We used constant comparative methods to analyze interview transcripts and inductively developed a framework for the decision-making process. RESULTS: Surgeons averaged 13 years (standard deviation (SD) 10.4) of experience; 40% specialized in trauma/acute care surgery. Important themes regarding the main topic of "perioperative decision-making" included many considerations beyond the clinical characteristics of cases. Surgeons described the importance of variables ranging from the availability of institutional resources to professional norms. Surgeons often remarked on their desire to achieve individual flow, team efficiency, and concordant expectations of treatment and prognosis with patients. CONCLUSIONS: This is the first study to explore how surgeons decide among management options for critically-ill EGS patients. Surgeons' decision-making reflected a broad array of clinical, personal, and institutional variables. Effective interventions to ensure preference-sensitive care for EGS patients must address all of these variables.

10.
JAMA Surg ; 156(1): 103, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33084887
11.
J Trauma Acute Care Surg ; 90(3): 477-483, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075028

RESUMO

BACKGROUND: The significance of pneumatosis intestinalis (PI) remains challenging. While certain clinical scenarios are predictive of transmural ischemia, risk models to assess the presence of pathologic PI are needed. The aim of this study was to determine what patient factors at the time of radiographic diagnosis of PI predict the risk for pathologic PI. METHODS: We conducted a retrospective cohort study examining patients with PI from 2010 to 2016 at a multicenter hospital network. Multivariate logistic regression was used to develop a predictive model for pathologic PI in a derivation cohort. Using regression-coefficient-based methods, the final multivariate model was converted into a five-factor-based score. Calibration and discrimination of the score were then assessed in a validation cohort. RESULTS: Of 305 patients analyzed, 102 (33.4%) had pathologic PI. We identified five factors associated with pathologic PI at the time of radiographic diagnosis: small bowel PI, age 70 years or older, heart rate 110 bpm or greater, lactate of 2 mmol/L or greater, and neutrophil-lymphocyte ratio 10 or greater. Using this model, patients in the validation cohort were assigned risk scores ranging from 0 to 11. Low-risk patients were categorized when scores are 0 to 4; intermediate, score of 5 to 6; high, score of 7 to 8; and very high risk, 9+. In the validation cohort, very high-risk patients (n = 17; 18.1%) had predicted rates of pathologic pneumatosis of 88.9% and an observed rate of 82.4%. In contrast, patients labeled as low risk (n = 37; 39.4%) had expected rates of pathologic pneumatosis of 1.3% and an observed rate of 0%. The model showed excellent discrimination (area under the curve, 0.90) and good calibration (Hosmer-Lemeshow goodness-of-fit, p = 0.37). CONCLUSION: Our score accurately stratifies patient risk of pathologic pneumatosis. This score has the potential to target high-risk individuals for expedient operation and spare low-risk individuals invasive interventions. LEVEL OF EVIDENCE: Prognostic Study, Level III.


Assuntos
Pneumatose Cistoide Intestinal/diagnóstico , Pneumatose Cistoide Intestinal/etiologia , Idoso , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumatose Cistoide Intestinal/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
12.
J Clin Invest ; 131(1)2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32941182

RESUMO

Macrophages are main effectors of heme metabolism, increasing transiently in the liver during heightened disposal of damaged or senescent RBCs (sRBCs). Macrophages are also essential in defense against microbial threats, but pathological states of heme excess may be immunosuppressive. Herein, we uncovered a mechanism whereby an acute rise in sRBC disposal by macrophages led to an immunosuppressive phenotype after intrapulmonary Klebsiella pneumoniae infection characterized by increased extrapulmonary bacterial proliferation and reduced survival from sepsis in mice. The impaired immunity to K. pneumoniae during heightened sRBC disposal was independent of iron acquisition by bacterial siderophores, in that K. pneumoniae mutants lacking siderophore function recapitulated the findings observed with the WT strain. Rather, sRBC disposal induced a liver transcriptomic profile notable for suppression of Stat1 and IFN-related responses during K. pneumoniae sepsis. Excess heme handling by macrophages recapitulated STAT1 suppression during infection that required synergistic NRF1 and NRF2 activation but was independent of heme oxygenase-1 induction. Whereas iron was dispensable, the porphyrin moiety of heme was sufficient to mediate suppression of STAT1-dependent responses in human and mouse macrophages and promoted liver dissemination of K. pneumoniae in vivo. Thus, cellular heme metabolism dysfunction negatively regulated the STAT1 pathway, with implications in severe infection.


Assuntos
Eritrócitos/imunologia , Regulação da Expressão Gênica/imunologia , Heme/imunologia , Tolerância Imunológica , Fagocitose/imunologia , Fator de Transcrição STAT1/imunologia , Sepse/imunologia , Animais , Eritrócitos/patologia , Heme/genética , Humanos , Camundongos , Camundongos Knockout , Fator de Transcrição STAT1/genética , Sepse/genética , Sepse/patologia
13.
JAMA Surg ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016996

RESUMO

Importance: In-hospital administration of tranexamic acid after injury improves outcomes in patients at risk for hemorrhage. Data demonstrating the benefit and safety of the pragmatic use of tranexamic acid in the prehospital phase of care are lacking for these patients. Objective: To assess the effectiveness and safety of tranexamic acid administered before hospitalization compared with placebo in injured patients at risk for hemorrhage. Design, Setting, and Participants: This pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized clinical trial included injured patients with prehospital hypotension (systolic blood pressure ≤90 mm Hg) or tachycardia (heart rate ≥110/min) before arrival at 1 of 4 US level 1 trauma centers, within an estimated 2 hours of injury, from May 1, 2015, through October 31, 2019. Interventions: Patients received 1 g of tranexamic acid before hospitalization (447 patients) or placebo (456 patients) infused for 10 minutes in 100 mL of saline. The randomization scheme used prehospital and in-hospital phase assignments, and patients administered tranexamic acid were allocated to abbreviated, standard, and repeat bolus dosing regimens on trauma center arrival. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. Results: In all, 927 patients (mean [SD] age, 42 [18] years; 686 [74.0%] male) were eligible for prehospital enrollment (460 randomized to tranexamic acid intervention; 467 to placebo intervention). After exclusions, the intention-to-treat study cohort comprised 903 patients: 447 in the tranexamic acid arm and 456 in the placebo arm. Mortality at 30 days was 8.1% in patients receiving tranexamic acid compared with 9.9% in patients receiving placebo (difference, -1.8%; 95% CI, -5.6% to 1.9%; P = .17). Results of Cox proportional hazards regression analysis, accounting for site, verified that randomization to tranexamic acid was not associated with a significant reduction in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59-1.11, P = .18). Prespecified dosing regimens and post-hoc subgroup analyses found that prehospital tranexamic acid were associated with significantly lower 30-day mortality. When comparing tranexamic acid effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when tranexamic acid was administered within 1 hour of injury (4.6% vs 7.6%; difference, -3.0%; 95% CI, -5.7% to -0.3%; P < .002). Patients with severe shock (systolic blood pressure ≤70 mm Hg) who received tranexamic acid demonstrated lower 30-day mortality compared with placebo (18.5% vs 35.5%; difference, -17%; 95% CI, -25.8% to -8.1%; P < .003). Conclusions and Relevance: In injured patients at risk for hemorrhage, tranexamic acid administered before hospitalization did not result in significantly lower 30-day mortality. The prehospital administration of tranexamic acid after injury did not result in a higher incidence of thrombotic complications or adverse events. Tranexamic acid given to injured patients at risk for hemorrhage in the prehospital setting is safe and associated with survival benefit in specific subgroups of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02086500.

14.
Cell Calcium ; 92: 102286, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932146

RESUMO

Sepsis and shock states impose mitochondrial stress, and in response, adaptive mechanisms such as fission, fusion and mitophagy are induced to eliminate damaged portions of or entire dysfunctional mitochondria. The mechanisms underlying these events are being elucidated; yet a direct link between loss of mitochondrial membrane potential ΔΨm and the initiation of fission, fusion and mitophagy remains to be well characterized. The direct association between the magnitude of the ΔΨm and the capacity for mitochondria to buffer Ca2+ renders Ca2+ uniquely suited as the signal engaging these mechanisms in circumstances of mitochondrial stress that lower the ΔΨm. Herein, we show that the calcium/calmodulin-dependent protein kinase (CaMK) IV mediates an adaptive slowing in oxidative respiration that minimizes oxidative stress in the kidneys of mice subjected to either cecal ligation and puncture (CLP) sepsis or endotoxemia. CaMKIV shifts the balance towards mitochondrial fission and away from fusion by 1) directly phosphorylating an activating Serine616 on the fission protein DRP1 and 2) reducing the expression of the fusion proteins Mfn1/2 and OPA-1. CaMKIV, through its function as a direct PINK1 kinase and regulator of Parkin expression, also enables mitophagy. These data support that CaMKIV serves as a keystone linking mitochondrial stress with the adaptive mechanisms of mitochondrial fission, fusion and mitophagy that mitigate oxidative stress in the kidneys of mice responding to sepsis.


Assuntos
Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/metabolismo , Dinâmica Mitocondrial , Sepse/patologia , Animais , Ceco/patologia , Células HEK293 , Humanos , Córtex Renal/patologia , Córtex Renal/ultraestrutura , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Mitofagia , Estresse Oxidativo , Proteínas Quinases/metabolismo , Punções , Ubiquitina-Proteína Ligases/metabolismo
15.
J Am Coll Surg ; 231(5): 536-545.e4, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32822886

RESUMO

BACKGROUND: Incisional hernia develops in up to 20% of patients undergoing abdominal operations. We sought to identify characteristics associated with poor outcomes after acute incisional hernia incarceration. STUDY DESIGN: We performed a retrospective cohort study of adult patients with incisional hernias undergoing elective repair or with acute incarceration between 2010 and 2017. The primary end point was 30-day mortality. Logistic regression was used to determine adjusted odds associated with 30-day mortality. The American College of Surgeons Surgical Risk Calculator was used to estimate outcomes had these patients undergone elective repair. RESULTS: A total of 483 patients experienced acute incarceration; 30-day mortality was 9.52%. Increasing age (adjusted odds ratio 1.05; 95% CI, 1.02 to 1.08) and bowel resection (adjusted odds ratio 3.18; 95% CI, 1.45 to 6.95) were associated with mortality. Among those with acute incarceration, 231 patients (47.9%) had no documentation of an earlier surgical evaluation and 252 (52.2%) had been evaluated but had not undergone elective repair. Among patients 80 years and older, 30-day mortality after emergent repair was high (22.9%) compared with estimated 30-day mortality for elective repair (0.73%), based on the American College of Surgeons Surgical Risk Calculator. Estimated mortality was comparable with observed elective repair mortality (0.82%) in an age-matched cohort. Similar mortality trends were noted for patients younger than 60 years and aged 60 to 79 years. CONCLUSIONS: Comparison of predicted elective repair and observed emergent repair mortality in patients with acute incarceration suggests that acceptable outcomes could have been achieved with elective repair. Almost one-half of acute incarceration patients had no earlier surgical evaluation, therefore, targeted interventions to address surgical referral can potentially result in fewer incarceration-related deaths.


Assuntos
Abdome/cirurgia , Herniorrafia , Hérnia Incisional/mortalidade , Hérnia Incisional/cirurgia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Doença Aguda , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
16.
Ann Surg ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32773624

RESUMO

OBJECTIVE: The aim of the study was to quantify the risk of incarceration of incisional hernias. BACKGROUND: Operative repair is the definitive treatment for incisional ventral hernias but is often deferred if the perceived risk of elective operation is elevated secondary to comorbid conditions. The risk of incarceration during nonoperative management (NOM) factors into shared decision making by patient and surgeon; however, the incidence of acute incarceration remains largely unknown. METHODS: A retrospective analysis of adult patients with an International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis of incisional hernia was conducted from 2010 to 2017 in 15 hospitals of a single healthcare system. The primary outcome was incarceration necessitating emergent operation. The secondary outcome was 30-, 90-, and 365-day mortality. Univariate and multivariate analyses were used to determine independent predictors of incarceration. RESULTS: Among 30,998 patients with an incisional hernia (mean age 58.1 ±â€Š15.9 years; 52.7% female), 23,022 (78.1%) underwent NOM of whom 540 (2.3%) experienced incarceration, yielding a 1- and 5-year cumulative incidence of 1.24% and 2.59%, respectively. Independent variables associated with incarceration included: age older than 40 years, female sex, current smoker, body mass index 30 or greater, and a hernia-related inpatient admission. All-cause mortality rates at 30, 90, and 365 days were significantly higher in the incarceration group at 7.2%, 10%, and 14% versus 1.1%, 2.3%, and 5.3% in patients undergoing successful NOM, respectively. CONCLUSIONS: Incarceration is an uncommon complication of NOM but is associated with a significant risk of death. Tailored decision making for elective repair and considering the aforementioned risk factors for incarceration provides an initial step toward mitigating the excess morbidity and mortality of an incarceration event.

17.
JAMA Surg ; 155(7): 552-560, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432669

RESUMO

Importance: Factors contributing to underrepresentation of women in surgery are incompletely understood. Pro-male bias and stereotype threat appear to contribute to gender imbalance in surgery. Objectives: To evaluate the association between pro-male gender bias and career engagement and the effect of stereotype threat on skill performance among trainees in academic surgery. Design, Setting, and Participants: A 2-phase study with a double-blind, randomized clinical trial component was conducted in 3 academic general surgery training programs. Residents were recruited between August 1 and August 15, 2018, and the study was completed at the end of that academic year. In phase 1, surveys administered 5 to 6 months apart investigated the association of gender bias with career engagement. In phase 2, residents were randomized 1:1 using permuted-block design stratified by site, training level, and gender to receive either a trigger of or protection against stereotype threat. Immediately after the interventions, residents completed the Fundamentals of Laparoscopic Surgery (FLS) assessment followed by a final survey. A total of 131 general surgery residents were recruited; of these 96 individuals with academic career interests met eligibility criteria; 86 residents completed phase 1. Eighty-five residents were randomized in phase 2, and 4 residents in each arm were lost to follow-up. Intervention: Residents read abstracts that either reported that women had worse laparoscopic skill performance than men (trigger of stereotype threat [A]) or had no difference in performance (protection against stereotype threat [B]). Main Outcomes and Measures: Association between perception of pro-male gender bias and career engagement survey scores (phase 1) and stereotype threat intervention and FLS scores (phase 2) were the outcomes. Intention-to-treat analysis was conducted. Results: Seventy-seven residents (38 women [49.4%]) completed both phases of the study. The association between pro-male gender bias and career engagement differed by gender (interaction coefficient, -1.19; 95% CI, -1.90 to -0.49; P = .02); higher perception of bias was associated with higher engagement among men (coefficient, 1.02; 95% CI, 0.19-2.24; P = .04), but no significant association was observed among women (coefficient, -0.25; 95% CI, -1.59 to 1.08; P = .50). There was no evidence of a difference in FLS score between interventions (mean [SD], A: 395 [150] vs B: 367 [157]; P = .51). The response to stereotype threat activation was similar in men and women (interaction coefficient, 15.1; 95% CI, -124.5 to 154.7; P = .39). The association between stereotype threat activation and FLS score differed by gender across levels of susceptibility to stereotype threat (interaction coefficient, -35.3; 95% CI, -47.0 to -23.6; P = .006). Higher susceptibility to stereotype threat was associated with lower FLS scores among women who received a stereotype threat trigger (coefficient, -43.4; 95% CI, -48.0 to -38.9; P = .001). Conclusions and Relevance: Perception of pro-male bias and gender stereotypes may influence career engagement and skill performance, respectively, among surgical trainees. Trial Registration: ClinicalTrials.gov Identifier: NCT03623009.


Assuntos
Cirurgia Geral/educação , Sexismo , Estereotipagem , Método Duplo-Cego , Feminino , Humanos , Masculino
18.
JAMA Surg ; 155(6): e200416, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32267474

RESUMO

Importance: Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention. Objective: To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin. Design, Setting, and Participants: This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018. Exposures: Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure. Main Outcomes and Measures: All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort. Results: Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding. Conclusions and Relevance: This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Período Pré-Operatório , Medição de Risco , Estresse Fisiológico/efeitos dos fármacos
19.
J Trauma Acute Care Surg ; 88(6): 847-854, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118818

RESUMO

BACKGROUND: Platelet transfusion has been utilized to reverse platelet dysfunction in patients on preinjury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication. METHODS: Controlled, observational and randomized, prospective and retrospective studies describing tICH, preinjury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression. RESULTS: Twelve of 18,609 screened references were applicable to our questions and were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.76-2.18; p = 0.346; I = 32.5%). There was no significant reduction in hemorrhage progression (OR, 0.88; 95% CI, 0.34-2.28; p = 0.788; I = 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR, 1.00; 95% CI, 0.53-1.90, p = 0.996; I = 59.1%; p = 0.032). CONCLUSION: Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets, highlighting the need for a prospective evaluation of this practice. LEVEL OF EVIDENCE: Systematic Reviews and Meta-Analyses, Level III.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hemorragia Intracraniana Traumática/terapia , Inibidores da Agregação Plaquetária/efeitos adversos , Transfusão de Plaquetas/normas , Guias de Prática Clínica como Assunto , Aspirina/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Clopidogrel/efeitos adversos , Progressão da Doença , Humanos , Hemorragia Intracraniana Traumática/sangue , Hemorragia Intracraniana Traumática/mortalidade , Fatores Desencadeantes , Resultado do Tratamento
20.
Anesthesiology ; 132(2): 280-290, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939843

RESUMO

BACKGROUND: Concern remains over reliable point-of-care testing to guide reversal of rivaroxaban, a commonly used factor Xa inhibitor, in high-acuity settings. Thromboelastography (TEG), a point-of-care viscoelastic assay, may have the ability to detect the anticoagulant effect of rivaroxaban. The authors ascertained the association of apparent rivaroxaban concentration with thromboelastography reaction time, i.e., time elapsed from blood sample placement in analyzer until beginning of clot formation, as measured using TEG and TEG6S instruments (Haemonetics Corporation, USA), hypothesizing that reaction time would correlate to degree of functional factor Xa impairment. METHODS: The authors prospectively performed a diagnostic accuracy study comparing coagulation assays to apparent (i.e., indirectly assessed) rivaroxaban concentration in trauma patients with and without preinjury rivaroxaban presenting to a single center between April 2016 and July 2018. Blood samples at admission and after reversal or 24 h postadmission underwent TEG, TEG6S, thrombin generation assay, anti-factor Xa chromogenic assay, prothrombin time (PT), and ecarin chromogenic assay testing. The authors determined correlation of kaolin TEG, TEG6S, and prothrombin time to apparent rivaroxaban concentration. Receiver operating characteristic curve compared capacity to distinguish therapeutic rivaroxaban concentration (i.e., greater than or equal to 50 ng/ml) from nontherapeutic concentrations. RESULTS: Eighty rivaroxaban patients were compared to 20 controls. Significant strong correlations existed between rivaroxaban concentration and TEG reaction time (ρ = 0.67; P < 0.001), TEG6S reaction time (ρ = 0.68; P < 0.001), and prothrombin time (ρ = 0.73; P < 0.001), however reaction time remained within the defined normal range for the assay. Rivaroxaban concentration demonstrated strong but not significant association with coagulation assays postreversal (n = 9; TEG reaction time ρ = 0.62; P = 0.101; TEG6S reaction time ρ = 0.57; P = 0.112) and small nonsignificant association for controls (TEG reaction time: ρ = -0.04; P = 0.845; TEG6S reaction time: ρ = -0.09; P = 0.667; PT-neoplastine: ρ = 0.19; P = 0.301). Rivaroxaban concentration (area under the curve, 0.91) and TEG6S reaction time (area under the curve, 0.84) best predicted therapeutic rivaroxaban concentration and exhibited similar receiver operating characteristic curves (P = 0.180). CONCLUSIONS: Although TEG6S demonstrates significant strong correlation with rivaroxaban concentration, values within normal range limit clinical utility rendering rivaroxaban concentration the gold standard in measuring anticoagulant effect.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Testes Imediatos/normas , Rivaroxabana/administração & dosagem , Tromboelastografia/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Imediatos/tendências , Estudos Prospectivos , Rivaroxabana/sangue , Tromboelastografia/tendências
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