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1.
Int J Cancer ; 144(1): 26-33, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098208

RESUMO

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.


Assuntos
Ordem de Nascimento , Peso ao Nascer , Idade Paterna , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos
2.
Paediatr Perinat Epidemiol ; 32(6): 568-583, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30466188

RESUMO

BACKGROUND: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. METHODS: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. RESULTS: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. CONCLUSIONS: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

3.
Am J Respir Crit Care Med ; 198(11): 1406-1412, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30189749

RESUMO

RATIONALE: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock. OBJECTIVES: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock. METHODS: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P < 0.001), whereas among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk and reliability-adjusted mortality. CONCLUSIONS: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.

4.
JAMA ; 320(4): 358-367, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30043064

RESUMO

Importance: The death of a pediatric patient with sepsis motivated New York to mandate statewide sepsis treatment in 2013. The mandate included a 1-hour bundle of blood cultures, broad-spectrum antibiotics, and a 20-mL/kg intravenous fluid bolus. Whether completing the bundle elements within 1 hour improves outcomes is unclear. Objective: To determine the risk-adjusted association between completing the 1-hour pediatric sepsis bundle and individual bundle elements with in-hospital mortality. Design, Settings, and Participants: Statewide cohort study conducted from April 1, 2014, to December 31, 2016, in emergency departments, inpatient units, and intensive care units across New York State. A total of 1179 patients aged 18 years and younger with sepsis and septic shock reported to the New York State Department of Health who had a sepsis protocol initiated were included. Exposures: Completion of a 1-hour sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour. Main Outcomes and Measures: Risk-adjusted in-hospital mortality. Results: Of 1179 patients with sepsis reported at 54 hospitals (mean [SD] age, 7.2 [6.2] years; male, 54.2%; previously healthy, 44.5%; diagnosed as having shock, 68.8%), 139 (11.8%) died. The entire sepsis bundle was completed in 1 hour in 294 patients (24.9%). Antibiotics were administered to 798 patients (67.7%), blood cultures were obtained in 740 patients (62.8%), and the fluid bolus was completed in 548 patients (46.5%) within 1 hour. Completion of the entire bundle within 1 hour was associated with lower risk-adjusted odds of in-hospital mortality (odds ratio [OR], 0.59 [95% CI, 0.38 to 0.93], P = .02; predicted risk difference [RD], 4.0% [95% CI, 0.9% to 7.0%]). However, completion of each individual bundle element within 1 hour was not significantly associated with lower risk-adjusted mortality (blood culture: OR, 0.73 [95% CI, 0.51 to 1.06], P = .10; RD, 2.6% [95% CI, -0.5% to 5.7%]; antibiotics: OR, 0.78 [95% CI, 0.55 to 1.12], P = .18; RD, 2.1% [95% CI, -1.1% to 5.2%], and fluid bolus: OR, 0.88 [95% CI, 0.56 to 1.37], P = .56; RD, 1.1% [95% CI, -2.6% to 4.8%]). Conclusions and Relevance: In New York State following a mandate for sepsis care, completion of a sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour was associated with lower risk-adjusted in-hospital mortality among patients with pediatric sepsis and septic shock.


Assuntos
Mortalidade Hospitalar , Programas Obrigatórios , Pacotes de Assistência ao Paciente , Sepse/mortalidade , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Serviço Hospitalar de Emergência , Tratamento de Emergência , Feminino , Fidelidade a Diretrizes , Humanos , Lactente , Recém-Nascido , Masculino , New York , Razão de Chances , Guias de Prática Clínica como Assunto , Risco Ajustado , Sepse/terapia , Fatores de Tempo
6.
Int J Crit Illn Inj Sci ; 8(1): 22-27, 2018 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29619336

RESUMO

Background: Vancomycin and linezolid are standard treatment options for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. While acute kidney injury (AKI) is commonly attributed to vancomycin, existing data has not definitely confirmed vancomycin as an independent risk factor for AKI. Aims: This study aimed to quantify the incidence of AKI in Surgical Intensive Care Unit (ICU) patients receiving empiric vancomycin or linezolid for nosocomial pneumonia and to identify risk factors for AKI with a focus on MRSA antibiotic therapy. Materials and Methods: A retrospective cohort analysis of surgical ICU patients who received at least 48 h of vancomycin or linezolid for pneumonia was performed. Patients who received vancomycin were compared to those who received linezolid with a primary endpoint of AKI as defined by the risk/injury/failure/loss/end-stage renal disease (RIFLE) criteria. A modified RIFLE criteria assessing only changes in serum creatinine was also used. Results: One hundred one patients were evaluated (63 vancomycin and 38 linezolid). AKI occurred in 51 (81.0%) and 32 (84.2%) patients in the vancomycin and linezolid groups (P = 0.79), respectively. Using the modified RIFLE criteria, AKI occurred in 19 (30.2%) and 14 (36.8%) patients in the vancomycin and linezolid groups (P = 0.448). After adjustment for age, diabetes mellitus, Charlson comorbidity index, and concomitant nephrotoxins, there was no difference in risk of AKI between groups (P = 0.773). Conclusions: Patients who received empiric vancomycin or linezolid for nosocomial pneumonia experienced high, but similar rates of AKI. The results suggest MRSA antibacterial therapy in this setting may not be independently indicative of AKI risk, rather the risk is likely multifactorial.

7.
Heart Lung ; 47(2): 115-121, 2018 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29361341

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) has a delay in diagnosis that makes time since diagnosis of interest in this population. OBJECTIVES: To assess psychological conditions, perceived stress, QOL, and interpersonal support and to explore whether these factors may correlate with time since diagnosis in patients with PAH. METHODS: Participants at an academic medical center (n = 108) completed psychological questionnaires (Cambridge Pulmonary Hypertension Outcome Review, Patient Health Questionnaire-9, Perceived Stress Scale-10, and Interpersonal Support Evaluation List-Short Form). RESULTS: Prevalence of psychiatric disorder, major depression, and "other depressive disorder" were 29.6%, 15.7%, and 9.3%, respectively. Participants reported adequate social support, high perceived stress, and average quality of life. Time since diagnosis was positively associated with greater perceived social support (ρ = 0.174, p = .075) and greater perceived stress (ρ = 0.191, p = .048), but no other psychological factor. CONCLUSIONS: Routine psychological assessment and timely referral for mental health services are suggested. Social support may buffer patients from stress.

8.
Crit Care Med ; 46(5): 674-683, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29206765

RESUMO

OBJECTIVES: In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. DESIGN: Retrospective evaluation of prospectively collected data. PATIENTS: Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. SETTINGS: Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. CONCLUSIONS: The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult patients with severe sepsis and septic shock.

9.
N Engl J Med ; 376(23): 2235-2244, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28528569

RESUMO

BACKGROUND: In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS: We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS: Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS: More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).


Assuntos
Antibacterianos/uso terapêutico , Tratamento de Emergência , Hidratação , Sepse/mortalidade , Sepse/terapia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Auditoria Clínica , Terapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Choque Séptico/mortalidade , Choque Séptico/terapia
10.
Front Immunol ; 8: 35, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28167948

RESUMO

We crafted human immunodeficiency virus (HIV)-like particles of diameter about 140 nm, which expressed two major HIV-1 proteins, namely, env and gag gene products, and used this reagent to simulate the rate of decay of HIV from the blood stream of BALB/c male mice. We found that most (~90%) of the particles were eliminated (cleared) from the blood by the liver sinusoidal endothelial cells (LSECs), the remainder from Kupffer cells; suggesting that LSECs are the major liver scavengers for HIV clearance from blood. Decay was rapid with kinetics suggesting second order with respect to particles, which infers dimerization of a putative receptor on LSEC. The number of HIV-like particles required for saturating the clearance mechanism was approximated. The capacity for elimination of blood-borne HIV-like particles by the sinusoid was 112 million particles per minute. Assuming that the sinusoid endothelial cells were about the size of glass-adherent macrophages, then elimination capacity was more than 540 particles per hour per endothelial cell.

11.
J Immunol ; 197(6): 2390-9, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27534554

RESUMO

During Gram-negative bacterial infections, excessive LPS induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2-4 min in mice, and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ∼75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ∼25% with KC. Notably, the ratio of LSEC-KC-associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor C, an LPS binding protein, competitively inhibits high-density lipoprotein (HDL)-mediated LPS association with LSEC early in the process. Supporting the previous notion, 3 min postinfusion, 75% of infused fluorescently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis.


Assuntos
Células Endoteliais/fisiologia , Lipopolissacarídeos/sangue , Lipopolissacarídeos/metabolismo , Lipoproteínas HDL/metabolismo , Fígado/citologia , Proteínas da Fase Aguda/imunologia , Proteínas da Fase Aguda/metabolismo , Animais , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Células Endoteliais/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Meia-Vida , Inflamação/imunologia , Inflamação/prevenção & controle , Cinética , Macrófagos do Fígado/imunologia , Lipopolissacarídeos/imunologia , Lipoproteínas HDL/imunologia , Fígado/imunologia , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Sepse/imunologia
12.
J Clin Psychiatry ; 77(5): 661-7, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27249075

RESUMO

OBJECTIVE: This study examined the association between benzodiazepine use alone or in combination with antipsychotics and risk of mortality in patients with schizophrenia. METHODS: A retrospective longitudinal analysis was performed using Medicaid claims data merged with death certificate data for 18,953 patients (aged 18-58 years) with ICD-9-diagnosed schizophrenia followed from July 1, 2006, to December 31, 2013. Cox proportional hazard analyses were used to estimate the risk of all-cause mortality associated with benzodiazepine use; adjustment was made for a wide array of fixed and time-varying confounders, including demographics, psychiatric and medical comorbidities, and other psychotropic medications. RESULTS: Of the 18,953 patients diagnosed with schizophrenia, 13,741 (72.5%) were not prescribed a benzodiazepine, 3,476 (18.3%) were prescribed benzodiazepines in the absence of antipsychotic medication, and 1,736 (9.2%) were prescribed benzodiazepines in combination with antipsychotics. Controlling for a wide array of demographic and clinical variables, the hazard of mortality was 208% higher for patients prescribed benzodiazepines without an antipsychotic (HR = 3.08; 95% CI, 2.63-3.61; P < .001) and 48% higher for patients prescribed benzodiazepines in combination with antipsychotics (HR = 1.48; 95% CI, 1.15-1.91; P = .002). Benzodiazepine-prescribed patients were at greater risk of death by suicide and accidental poisoning as well as from natural causes. CONCLUSIONS: Benzodiazepine use is associated with increased mortality risk in patients with schizophrenia after adjusting for a wide range of potential confounders. Given unproven efficacy, physicians should exercise caution in prescribing benzodiazepines to schizophrenic patients.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/mortalidade , Adolescente , Adulto , Causas de Morte , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
13.
J Clin Psychiatry ; 77(7): e950-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27314252

RESUMO

OBJECTIVE: This study examines the association between antidepressant use and risk of fracture in depressed youth and assesses whether fracture incidence varies over the course of antidepressant treatment. METHOD: A retrospective cohort analysis of Ohio Medicaid claims data was conducted for youth ages 6-17 years with a new episode of ICD-9-diagnosed depression from 2001-2009. The primary outcome variable was time to fracture. Fracture rates were compared between depressed youth treated with antidepressant medication and untreated depressed youth. Time categories of no use, past use, and current use were compared. RESULTS: Of 50,673 depressed youths, 5,872 (11.6%) experienced a fracture. Of those who had a fracture, 2,228 (37.9%) were exposed to antidepressants, 80% of which were selective serotonin reuptake inhibitors. The adjusted hazard ratio (HR) was 3% higher in those currently prescribed antidepressants (HR = 1.03; 95% CI, 1.00-1.06; P = .03). The risk ratio (RR) for adjusted fracture rates per 10,000 persons was twice as high during the first 30 days of antidepressant use compared to the other time periods (RR = 2.0; 95% CI, 1.2-3.3; P = .007). The number of fractures for those with past antidepressant use did not differ from those with no history of antidepressant use. CONCLUSIONS: Antidepressant use may be associated with a small but significant increase in fracture risk, particularly within the first 30 days of treatment. Findings underscore a need for additional prospective and mechanistic research. Prescribers should consider other risks for fracture in antidepressant-treated youth, particularly disability and the concomitant use of other medications that increase fracture risk.


Assuntos
Antidepressivos/efeitos adversos , Fraturas Ósseas/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Fraturas Ósseas/induzido quimicamente , Humanos , Incidência , Masculino , Medicaid/estatística & dados numéricos , Ohio/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos
14.
JAMA ; 315(8): 775-87, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26903336

RESUMO

IMPORTANCE: Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE: To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING, AND PARTICIPANTS: The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES: Evidence for and agreement on septic shock definitions and criteria. RESULTS: The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. CONCLUSIONS AND RELEVANCE: Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.


Assuntos
Consenso , Choque Séptico/diagnóstico , Adulto , Comitês Consultivos , Biomarcadores/sangue , Determinação da Pressão Arterial , Estudos de Coortes , Técnica Delfos , Hidratação , Humanos , Hipotensão/diagnóstico , Lactatos/sangue , Estudos Observacionais como Assunto , Ressuscitação/métodos , Literatura de Revisão como Assunto , Choque Séptico/sangue , Choque Séptico/epidemiologia , Choque Séptico/terapia , Vasoconstritores/uso terapêutico
15.
Urology ; 87: 114-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26505834

RESUMO

OBJECTIVE: To evaluate the viability of glomeruli in the peritumor parenchyma of partial nephrectomy specimens removed for renal cell carcinoma (RCC) and relate it to kidney function, to better understand the contribution of peritumor parenchyma to renal function. MATERIALS AND METHODS: A retrospective analysis of 53 partial nephrectomies containing RCC was performed. Glomeruli within 0.25-cm increments from the tumor were quantified and histologically assessed for viability. Tumor size, minimum and maximum margin size, and pre- and postoperative estimated glomerular filtration rate (eGFR) were obtained. RESULTS: Glomerular viability positively correlated with distance from tumor with mean viable glomeruli in successive 0.25-cm increments of 0-0.25 cm, 58%; 0.25-0.5 cm, 80%; 0.5-0.75 cm, 90%; and 0.75-1.0 cm, 92%. Glomerular viability near the tumor did not correlate with preoperative eGFR, whereas decreased viability further from the tumor did correlate with worse preoperative eGFR. Tumor size showed a nonstatistically significant positive trend with minimum (median 0.15 cm) and maximum margin (median 0.7 cm) sizes. Percent change of glomerular filtration rate did not correlate with margin size (P = .190). CONCLUSION: Renal parenchyma immediately adjacent to RCC contains fewer viable glomeruli compared with the parenchyma further from the tumor. Based on this information, attempts to preserve all non-neoplastic renal parenchyma via a surgical margin approaching zero may not necessarily result in clinically relevant differences in the amount of viable glomeruli remaining or the renal function preserved.


Assuntos
Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular/fisiologia , Glomérulos Renais/patologia , Neoplasias Renais/cirurgia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/fisiopatologia , Sobrevivência Celular , Humanos , Testes de Função Renal , Neoplasias Renais/diagnóstico , Neoplasias Renais/fisiopatologia , Nefrectomia , Tamanho do Órgão , Período Pós-Operatório , Estudos Retrospectivos
16.
Am J Obstet Gynecol ; 213(6): 824.e1-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26226551

RESUMO

OBJECTIVE: Burnout is specific to the work domain and in physicians is indicative of emotional exhaustion, depersonalization in relationships with coworkers and detachment from patients, and a sense of inadequacy or low personal accomplishment. The purpose of this study was to determine the burnout rate among gynecologic oncologists and evaluate other personal, professional, and psychosocial factors associated with this condition. STUDY DESIGN: This study used a cross-sectional design. Current members of the Society of Gynecologic Oncology were sent an anonymous email survey including 76 items measuring burnout, psychosocial distress, career satisfaction, and quality of life. RESULTS: A total of 1086 members were invited, 436 (40.1%) responded, and 369 (84.6%) of those completed the survey. Of physicians, 30% scored high for emotional exhaustion, 10% high for depersonalization, and 11% low for personal accomplishment. Overall, 32% of physicians scored above clinical cutoffs indicating burnout. In all, 33% screened positive for depression, 13% endorsed a history of suicidal ideation, 15% screened positive for alcohol abuse, and 34% reported impaired quality of life. Nonetheless, 70% reported high levels of personal accomplishment, and results suggested most were satisfied with their careers, as 89% would enter medicine again and 61% would encourage their child to enter medicine. Respondents with high burnout scores were less likely to report they would become a physician again (P = .002) or encourage a child to enter medicine (P < .001), and more likely to screen positive for depression (P < .001), alcohol abuse (P = .006), history of suicidal ideation (P < .001), and impaired quality of life (P < .001). CONCLUSION: Burnout is a significant problem associated with psychosocial distress and lower levels of career satisfaction in gynecologic oncologists. Burnout in obstetrics-gynecology and gynecologic oncology is of particular concern as young age and female gender are often identified as risk factors for this significant problem. Interventions targeted at improving quality of life, treatment of depression, or alcohol abuse may have an impact on burnout. However, significant barriers may exist as 44.5% of respondents in this study reported that they would be reluctant to seek medical care for depression, substance use, or other mental health issues due to concerns about their medical license.


Assuntos
Esgotamento Profissional/epidemiologia , Ginecologia , Oncologia , Médicos/psicologia , Adulto , Alcoolismo/epidemiologia , Esgotamento Profissional/psicologia , Escolha da Profissão , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sociedades Médicas , Estresse Psicológico/epidemiologia , Ideação Suicida , Inquéritos e Questionários , Estados Unidos/epidemiologia
17.
Clin Lung Cancer ; 16(6): 466-74, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26123189

RESUMO

UNLABELLED: In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population. BACKGROUND: The combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab. PATIENTS AND METHODS: We conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1). RESULTS: Sixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for SPARC expression in tumor or stroma with RR or OS, we found that higher Cav-1 levels in tumor-associated stroma was associated with improved RR and OS. CONCLUSION: Carboplatin and nab-paclitaxel every 21 days demonstrated promising efficacy with tolerable toxicity in NSCLC patients ineligible for bevacizumab therapy. Further analysis and validation of Cav-1 and SPARC expression in tumor and stromal compartments as prognostic and/or predictive biomarkers of NSCLC or nab-paclitaxel treatment is warranted.


Assuntos
Biomarcadores Farmacológicos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Caveolina 1/metabolismo , Neoplasias Pulmonares/diagnóstico , Nanopartículas/administração & dosagem , Paclitaxel/administração & dosagem , Células Estromais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/química , Bevacizumab , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Contraindicações , Quimioterapia Combinada , Fadiga/etiologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Nanopartículas/efeitos adversos , Nanopartículas/química , Estadiamento de Neoplasias , Doenças do Sistema Nervoso/etiologia , Paclitaxel/efeitos adversos , Paclitaxel/química , Análise de Sobrevida
18.
JAMA Pediatr ; 169(5): 466-73, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25751611

RESUMO

IMPORTANCE: Little is known about recent trends in rural-urban disparities in youth suicide, particularly sex- and method-specific changes. Documenting the extent of these disparities is critical for the development of policies and programs aimed at eliminating geographic disparities. OBJECTIVE: To examine trends in US suicide mortality for adolescents and young adults across the rural-urban continuum. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal trends in suicide rates by rural and urban areas between January 1, 1996, and December 31, 2010, were analyzed using county-level national mortality data linked to a rural-urban continuum measure that classified all 3141 counties in the United States into distinct groups based on population size and adjacency to metropolitan areas. The population included all suicide decedents aged 10 to 24 years. MAIN OUTCOMES AND MEASURES: Rates of suicide per 100,000 persons. RESULTS: Across the study period, 66,595 youths died by suicide, and rural suicide rates were nearly double those of urban areas for both males (19.93 and 10.31 per 100,000, respectively) and females (4.40 and 2.39 per 100,000, respectively). Even after controlling for a wide array of county-level variables, rural-urban suicide differentials increased over time for males, suggesting widening rural-urban disparities (1996-1998: adjusted incidence rate ratio [IRR], 0.98; 2008-2010: adjusted IRR, 1.19; difference in IRR, P = .02). Firearm suicide rates declined, and the rates of hanging/suffocation for both males and females increased. However, the rates of suicide by firearm (males: 1996-1998, 2.05; and 2008-2010: 2.69 times higher) and hanging/suffocation (males: 1996-1998, 1.24; and 2008-2010: 1.63 times higher) were disproportionately higher in rural areas, and rural-urban differences increased over time (P = .002 for males; P = .06 for females). CONCLUSIONS AND RELEVANCE: Suicide rates for adolescents and young adults are higher in rural than in urban communities regardless of the method used, and rural-urban disparities appear to be increasing over time. Further research should carefully explore the mechanisms whereby rural residence might increase suicide risk in youth and consider suicide-prevention efforts specific to rural settings.


Assuntos
População Rural , Suicídio/estatística & dados numéricos , População Urbana , Adolescente , Asfixia , Feminino , Armas de Fogo , Humanos , Estudos Longitudinais , Masculino , Estados Unidos/epidemiologia , Adulto Jovem
19.
Crit Care Med ; 43(3): 567-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25479113

RESUMO

OBJECTIVE: The Surviving Sepsis Campaign guidelines recommend obtaining a serum lactate measurement within 6 hours of presentation for all patients with suspected severe sepsis or septic shock. A lactate greater than 4 mmol/L qualifies for administration of early quantitative resuscitation therapy. We evaluated lactate elevation (with special attention to values > 4 mmol/L) and presence or absence of hypotension as a marker of clinical outcome. DESIGN AND SETTING: The Surviving Sepsis Campaign developed a database to assess the overall effect of the sepsis bundles as a performance improvement tool for clinical practice and patient outcome. This analysis focuses on one element of the Surviving Sepsis Campaign's resuscitation bundle, measuring serum lactate in adult severe sepsis or septic shock patients and its interaction with hypotension. This analysis was conducted on data submitted from January 2005 through March 2010. SUBJECTS: Data from 28,150 subjects at 218 sites were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unadjusted analysis of the 28,150 observations from the Surviving Sepsis Campaign database demonstrated a significant mortality increase with the presence of hypotension in conjunction with serum lactate elevation greater than 2 mmol/L. On multivariable analysis, only lactate values greater than 4 mmol/L, in conjunction with hypotension, significantly increased mortality when compared with the referent group of lactate values less than 2 mmol/L and not hypotensive. Mortality was 44.5% in patients with combined lactate greater than 4 mmol/L and hypotension when compared with 29% mortality in patients not meeting either criteria. CONCLUSIONS: Serum lactate was commonly measured within 6 hours of presentation in the management of severe sepsis or septic shock in this subset analysis of the Surviving Sepsis Campaign database in accordance with the Surviving Sepsis Campaign guidelines. Our results demonstrate that elevated lactate levels are highly associated with in-hospital mortality. However, only patients who presented with lactate values greater than 4 mmol/L, with and without hypotension, are significantly associated with in-hospital mortality and is associated with a significantly higher risk than intermediate levels (2-3 and 3-4 mmol/L). This supports the use of the cutoff of greater than 4 mmol/L as a qualifier for future clinical trials in severe sepsis or septic shock in patient populations who use quantitative resuscitation and the Surviving Sepsis Campaign bundles as standard of care.


Assuntos
Protocolos Clínicos , Mortalidade Hospitalar , Lactatos/sangue , Sepse/sangue , Sepse/terapia , Biomarcadores , Humanos , Hipotensão/epidemiologia , Melhoria de Qualidade , Sepse/mortalidade , Choque Séptico/sangue , Choque Séptico/mortalidade
20.
Ann Am Thorac Soc ; 12(6): 914-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25211346

RESUMO

RATIONALE: Multidetector-row chest computed tomography scan is a common initial imaging modality and endobronchial ultrasound is a minimally invasive diagnostic tool used to evaluate enlarged lymph nodes, but comparisons of imaging results are lacking. OBJECTIVES: To determine the size of thoracic lymph nodes and the strength of agreement between each measurement from coronal plane computed tomography and static endobronchial ultrasound images. METHODS: A retrospective review of consecutive patients who underwent endobronchial ultrasound-transbronchial needle aspiration of their lymph nodes because of clinical suspicion of benign or malignant thoracic disease. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-four lymph nodes from the mediastinal (74.2%) and hilar (25.8%) stations were measured in 59 patients (mean age, 64.5 yr; 33 males). The mean (standard deviation) short-axis diameter on computed tomography was 14.1 (6.7) mm compared with 12.6 (6.6) mm on endobronchial ultrasound. Benign lymph nodes (n = 42) were larger on computed tomography than on endobronchial ultrasound (14.1 [6.2] vs. 11.5 [6.2] mm). Malignant lymph nodes (n = 35) were larger on endobronchial ultrasound than on computed tomography (17.3 [6.4] vs. 16.2 [6.7] mm). Sixty-five percent of the lymph nodes that were initially interpreted as not enlarged on axial computed tomography images measured greater than 10 mm on each imaging modality (12.5 [5.9] mm on computed tomography and 10.5 [5.6] mm on endobronchial ultrasound) and 24% of the sampled lymph nodes from this group contained malignant cells. Random-effects maximal likelihood linear regression showed a statistically significant difference between endobronchial ultrasound and the computed tomography method for measuring short-axis diameter in all 124 lymph nodes. There was a weak agreement (intraclass correlation, rho: 0.44 [95% confidence interval, 0.31-0.59]) between short-axis diameter measurements from each imaging modality. CONCLUSIONS: Our single-center study shows that there was poor correlation between computed tomography and endobronchial ultrasound for the measurement of mediastinal and hilar lymph nodes. Malignant cells were recovered by ultrasound-guided needle aspiration from a substantial fraction of lymph nodes that were initially interpreted as normal in size. If these findings are confirmed, new criteria may be needed for lymph node measurement on computed tomography that will guide selection of lymph nodes for endobronchial ultrasound-transbronchial needle aspiration.


Assuntos
Linfonodos , Mediastino/patologia , Doenças Torácicas/diagnóstico , Idoso , Broncoscopia/métodos , Pesquisa Comparativa da Efetividade , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Avaliação de Resultados (Cuidados de Saúde) , Doenças Torácicas/classificação , Ultrassonografia de Intervenção/métodos
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