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1.
JAMA ; 322(13): 1261-1270, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573637

RESUMO

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.


Assuntos
Ácido Ascórbico/administração & dosagem , Insuficiência de Múltiplos Órgãos/prevenção & controle , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Sepse/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Escores de Disfunção Orgânica , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Sepse/complicações , Sepse/mortalidade , Trombomodulina/sangue , Vitaminas/uso terapêutico
2.
Artigo em Inglês | MEDLINE | ID: mdl-31593766

RESUMO

Gender differences in the natural history of chronic liver disease have been well-described. Women have lower rates of chronic liver disease and slower fibrosis progression, yet higher rates of waitlist mortality.1,2 Although previous studies have identified several clinical factors including height and creatinine that explain some of this transplant disparity, most have used data from administrative records, which are limited in their ability to identify clinically relevant differences and opportunities for intervention to reduce disparities.3-5 Additionally, most studies have focused on the period between waitlist and transplant, failing to capture gender differences in access to transplant.3,6 In the present study, we took advantage of a multicenter inpatient cohort with granular clinical data to characterize how women and men with cirrhosis differ, to stimulate future research aimed at reducing the well-established gender disparity in liver transplantation.

3.
PLoS One ; 14(9): e0223061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560724

RESUMO

BACKGROUND: Cirrhosis can alter several metabolic pathways. Metabolomics could prognosticate outcomes like hepatic encephalopathy (HE), transplant, hospitalization and death. AIM: Determine changes in serum and urine metabolomics in cirrhotics who develop outcomes. METHODS: Cirrhotic outpatients underwent data, serum/urine collection and were followed for 90 days. Demographics, cirrhosis details and medications were collected. Metabolomics was performed on urine/serum using GC/MS with subsequent bioinformatics analyses (ChemRICH, MetaMAPP and PLS-DA). Logistic regression adjusting for covariates (demographics, alcohol etiology, prior HE, PPI, SBP prophylaxis, rifaximin/lactulose) were performed and ROC curves comparing MELD to adjusted serum & urine metabolites were created. RESULTS: 211 patients gave serum, of which 64 were hospitalized, 19 developed HE, 13 were transplanted and 11 died. 164 patients gave urine of which 56 were hospitalized, 18 developed HE, 12 were transplanted and 11 died. Metabolomics: Saturated fatty acids, amino acids and bioenergetics-related metabolites differentiated patients with/without outcomes. After regression, 232, 228, 284 and 229 serum metabolites were significant for hospitalization, HE, death and transplant. In urine 290, 284, 227 & 285 metabolites were significant for hospitalization, HE, death and transplant respectively. AUC was higher for serum metabolites vs MELD for HE (0.85 vs.0.76), death (0.99 vs.0.88), transplant (0.975 vs.0.94) and hospitalizations (0.84 vs.0.83). Similarly, urinary metabolite AUC was also higher than MELD for HE (0.87 vs.0.72), death (0.92 vs 0.86), transplant (0.99 vs.0.90) and hospitalizations (0.89 vs.0.84). CONCLUSIONS: In this exploratory study, serum and metabolites focused on lipid, bioenergetics and amino acid metabolism are altered in cirrhotics who develop negative outcomes.

4.
Clin Transl Sci ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411365

RESUMO

A nontargeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with FM (n = 20) and comparative data collected from newly recruited age-matched women (n = 20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with fold change (>2 or <0.5) and variable importance of projection scores ≥1 revealed statistically significant metabolites comparing samples from women with and without FM. Metabolite profiles in patients with FM differed from the comparison group in energy, lipid and amino acid metabolites reflecting heightened oxidative stress, inflammation, and tryptophan degradation in patients with FM. Study results may contribute to further identification of unique metabolomic profiles enhancing understanding of the pathophysiology of FM and for the development of effective therapeutic options.

5.
Am J Gastroenterol ; 114(7): 1091-1100, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180922

RESUMO

OBJECTIVES: Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. METHODS: North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. RESULTS: The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death. DISCUSSION: NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.

6.
Aliment Pharmacol Ther ; 49(12): 1518-1527, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31032966

RESUMO

BACKGROUND: Hepatic encephalopathy (HE) can adversely affect outcomes in both in-patients and out-patients with cirrhosis. AIM: To define targets for improving quality of care in HE management in the multi-centre North American Consortium for End-Stage Liver Disease (NACSELD) cohort. METHOD: NACSELD in-patient cohort was analysed for (a) medication-associated precipitants, (b) aspiration pneumonia development, (c) HE medication changes, and (d) 90-day HE recurrence/readmissions. Comparisons were made between patients on no-therapy, lactulose only, rifaximin only or both. Ninety-day HE-readmission analysis was adjusted for MELD score. RESULTS: Two thousand eight hundred and ten patients (1102 no-therapy, 659 lactulose, 154 rifaximin, 859 both) were included. HE on admission, and HE rates during hospitalisation were highest in those on lactulose only or dual therapy compared to no-therapy or rifaximin only (P < 0.001). Medications were the most prevalent precipitants (32%; 21% lactulose over/underuse, 5% benzodiazepines, 4% opioids, 1% rifaximin underuse, 1% hypnotics). Patients with medication-associated precipitants had a better prognosis compared to other precipitants. A total of 23% (n = 217) reached grade 3/4 HE, of which 16% developed HE-related aspiration pneumonia. Two thousand four hundred and twenty patients were discharged alive without liver transplant (790 no-therapy, 639 lactulose, 136 rifaximin, 855 both); 12.5% (n = 99) of no-therapy patients did not receive a discharge HE therapy renewal. Ninety-day HE-related readmissions were seen in 16% of patients (9% no-therapy, 9% rifaximin only, lactulose only 18%, dual 21%, <0.001), which persisted despite MELD adjustment (P = 0.009). CONCLUSION: Several targets to improve HE management were identified in a large cohort of hospitalised cirrhotic patients. Interventions to decrease medication-precipitated HE, prevention of aspiration pneumonia, and optimisation of HE medications are warranted.

7.
AJOB Empir Bioeth ; 10(2): 113-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002584

RESUMO

BACKGROUND: As ongoing research explores the impact of moral distress on health care professionals (HCPs) and organizations and seeks to develop effective interventions, valid and reliable instruments to measure moral distress are needed. This article describes the development and testing of a revision of the widely used Moral Distress Scale-Revised (MDS-R) to measure moral distress. METHODS: We revised the MDS-R by evaluating the combined data from 22 previous studies, assessing 301 write-in items and 209 root causes identified through moral distress consultation, and reviewing 14 recent publications from various professions in which root causes were described. The revised 27-item scale, the Measure of Moral Distress for Healthcare Professionals (MMD-HP), is usable by all HCPs in adult and pediatric critical, acute, or long-term acute care settings. We then assessed the reliability of the MMD-HP and evaluated construct validity via hypothesis testing. The MMD-HP, Hospital Ethical Climate Survey (HECS), and a demographic survey were distributed electronically via Qualtrics to nurses, physicians, and other health care professionals at two academic medical centers over a 3-week period. RESULTS: In total, 653 surveys were included in the final analysis. The MMD-HP demonstrated good reliability. The four hypotheses were supported: (1) MMD-HP scores were higher for nurses (M 112.3, SD 73.2) than for physicians (M 96.3, SD 54.7, p = 0.023). (2) MMD-HP scores were higher for those considering leaving their position (M 168.4, SD 75.8) than for those not considering leaving (M 94.3, SD 61.2, p < 0.001). (3) The MMD-HP was negatively correlated with the HECS (r = -0.55, p < 0.001). (4) An exploratory factor analysis revealed a four-factor structure, reflective of patient, unit, and system levels of moral distress. CONCLUSIONS: The MMD-HP represents the most currently understood causes of moral distress. Because the instrument behaves as would be predicted, we recommend that the MMD-HP replace the MDS-R.

8.
Liver Transpl ; 25(4): 571-579, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30724010

RESUMO

Acute-on-chronic liver failure (ACLF) characterized with ≥2 extrahepatic organ failures in cirrhosis carries a high mortality. Outcomes of patients listed for liver transplantation (LT) after ACLF and after LT are largely unknown. The North American Consortium for the Study of End-Stage Liver Disease prospectively enrolled 2793 nonelectively hospitalized patients with cirrhosis; 768 were listed for LT. Within 3 months, 265 (35%) received a LT, 395 remained alive without LT, and 108 died/delisted. Compared with nonlisted patients, those listed were younger and more often had ACLF, acute kidney injury, and a higher admission Model for End-Stage Liver Disease (MELD) score. ACLF was most common in patients who died/delisted, followed by those alive with and without LT respectively, (30%, 22%, and 7%, respectively; P < 0.001). At LT, median MELD was 27.9% and 70% were inpatients; median time from hospitalization to LT was 26 days. Post-LT survival at 6 months was unchanged between those with and without ACLF (93% each at 6 months). There was no difference in 3- and 6-month mean post-LT creatinine in those with and without ACLF, despite those with ACLF having a higher mean pre-LT creatinine and a higher rate of perioperative dialysis (61%). In conclusion, patients with and without ACLF had similar survival after transplant with excellent renal recovery in both groups.

9.
Am J Gastroenterol ; 114(4): 599-606, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30694868

RESUMO

OBJECTIVES: Antibiotic prophylaxis is recommended for prevention of the first episode of spontaneous bacterial peritonitis (SBP; primary prophylaxis 1°) and subsequent episodes (secondary prophylaxis 2°). We aimed to compare outcomes in cirrhotic inpatients on 1° vs 2° SBP prophylaxis. METHODS: Data from North American Consortium for the Study of End-Stage Liver Disease were evaluated for cirrhosis details, reasons for admission/medications, inpatient course recorded, and outcomes over 90 days. Outcomes (intensive care units, acute kidney injury, inpatient/90-day mortality) were compared between the 2 groups after propensity-matching on admission model for end-stage liver disease (MELD) score and serum albumin. RESULTS: Among the 2,731 patients enrolled, 305 were on 1° and 187 on 2° SBP prophylaxis. After propensity-matching, 154 patients remained in each group. Patients on 1° prophylaxis were more likely to have admission systemic inflammatory response syndrome (P = 0.02), with higher intensive care unit admissions (31% vs 21%; P = 0.05) and inpatient mortality (19% vs 9%; P = 0.01) than the 2° prophylaxis group. Patients on 2° prophylaxis had higher total (22% vs 10%; P = 0004), readmission (16% vs 9%; P = 0.03), and nosocomial (6% vs 0.5%; P = 0.01) SBP rates with predominant Gram-negative organisms compared to 1° prophylaxis patients. At 90 days, 1° prophylaxis patients had a higher mortality (35% vs 22%; P = 0.02) and acute kidney injury incidence (48% vs 30%; P = 0.04) compared to 2° prophylaxis patients. DISCUSSION: In this inpatient cirrhosis study, despite prophylaxis, a high proportion of patients developed SBP, which was associated with mortality. Cirrhotic inpatients on 1° prophylaxis had worse outcomes than those on 2° prophylaxis when propensity-matched for the MELD score and serum albumin during the index admission and 90-day follow-up.

10.
Metab Brain Dis ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30506333

RESUMO

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30036646

RESUMO

BACKGROUND & AIMS: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. METHODS: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. RESULTS: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. CONCLUSION: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

13.
J Transcult Nurs ; : 1043659618783235, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29957137

RESUMO

INTRODUCTION: Arab Americans are a growing population in the United States. In the 2011 American Community Survey, the U.S. Census Bureau reported there were close to 1.8 million Arab Americans living within the United States, a 47% increase in population size from 2000. According to the Arab American Institute, currently, that estimate has grown to approximately 3.7 million. They have high rates of smoking and low rates of smoking cessation. In this study, the researchers investigated factors influencing desire to quit smoking among Arab Americans, and their association with acculturation and health beliefs. METHODOLOGY: Cross-sectional descriptive study investigating smoking behaviors and factors influencing the desire to quit smoking among adult Arab American. Data were collected to measure tobacco use, nicotine dependence, desire to quit smoking, acculturation, and health beliefs. RESULTS: The sample ( N = 96) was 55% female, mean age of 44 years (±14.79). The desire to quit smoking was positively associated with perceived severity (p < .05) and susceptibility to cancer (p < .05), perceived benefits of quitting smoking ( p < .01); and negatively associated with smoking barriers (addiction barriers p < .05, external barriers p = .27, internal barriers p < .05), and nicotine dependence (p < .05). Being female, having a lower level of nicotine dependence, and a higher perception of cancer severity predicted higher desire to quit smoking ( p < .01). DISCUSSION: Smoking cessation intervention studies need to target appropriate health beliefs, especially the high risk of cancer caused by smoking among Arab Americans.

14.
Am J Gastroenterol ; 113(9): 1339-1344, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29880972

RESUMO

OBJECTIVES: Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia. METHODS: Hospitalized cirrhotic patients included in the NACSELD (North American Consortium for End-Stage Liver Disease) cohort with hyponatremia (Na <130mmol/L) were divided into those receiving intravenous albumin or not. Determinants of hyponatremia resolution (Na ≥135 meq/L) and 30-day survival were analyzed using regression and ANCOVA models. RESULTS: Overall, 2435 patients, of whom 1126 had admission hyponatremia, were included. Of these, 777 received 225 (IQR 100,400) g of albumin, while 349 did not. Patients given albumin had a higher admission MELD score, and serum creatinine and lower admission Na and mean arterial pressure (MAP). However they experienced a higher maximum Na and hyponatremia resolution (69% vs 61%, p = 0.008) compared to those who did not. On regression, delta Na was independently associated with admission creatinine, MAP and albumin use. On ANCOVA with logistic regression, there was a significant difference in hyponatremia resolution between those who did or did not receive albumin, even after adjustment for admission Na and GFR (85.41% vs 44.78%, p = 0.0057, OR: 1.50 95% CI: 1.13-2.00). Independent predictors of 30-day survival were hyponatremia resolution, age, ACLF, and admission GFR. CONCLUSION: Hospitalized patients with cirrhosis and hyponatremia who received intravenous albumin had a higher rate of hyponatremia resolution independent of renal function and baseline sodium levels, which was in turn associated with a better 30-day survival.

15.
JCI Insight ; 3(5)2018 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-29515036

RESUMO

BACKGROUND: Cirrhosis is associated with gut microbial changes, but current 16S rDNA techniques sequence both dead and live bacteria. We aimed to determine the rRNA content compared with DNA from the same stool sample to evaluate cirrhosis progression and predict hospitalizations. METHODS: Cirrhotics and controls provided stool for RNA and DNA analysis. Comparisons were made between cirrhotics/controls and within cirrhosis (compensated/decompensated, infected/uninfected, renal dysfunction/not, rifaximin use/not) with respect to DNA and RNA bacterial content using linear discriminant analysis. A separate group was treated with omeprazole for 14 days with longitudinal microbiota evaluation. Patients were followed for 90 days for hospitalizations. Multivariable models for hospitalizations with clinical data with and without DNA and RNA microbial data were created. RESULTS: Twenty-six controls and 154 cirrhotics (54 infected, 62 decompensated, 20 renal dysfunction, 18 rifaximin) were included. RNA and DNA analysis showed differing potentially pathogenic taxa but similar autochthonous taxa composition. Thirty subjects underwent the omeprazole study, which demonstrated differences between RNA and DNA changes. Thirty-six patients were hospitalized within 90 days. In the RNA model, MELD score and Enterococcus were independently predictive of hospitalizations, while in the DNA model MELD was predictive and Roseburia protective. In both models, adding microbiota significantly added to the MELD score in predicting hospitalizations. CONCLUSION: DNA and RNA analysis of the same stool sample demonstrated differing microbiota composition, which independently predicts the hospitalization risk in cirrhosis. RNA and DNA content of gut microbiota in cirrhosis are modulated differentially with disease severity, infections, and omeprazole use. TRIAL REGISTRATION: NCT01458990. FUNDING: VA Merit I0CX001076.

16.
BMC Pediatr ; 18(1): 46, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426320

RESUMO

BACKGROUND: While therapy services may start in the Neonatal Intensive Care Unit (NICU) there is often a gap in therapy after discharge. Supporting Play Exploration and Early Development Intervention (SPEEDI) supports parents, helping them build capacity to provide developmentally supportive opportunities starting in the NICU and continuing at home. The purpose of this single blinded randomized pilot clinical trial was to evaluate the initial efficacy of SPEEDI to improve early reaching and exploratory problem solving behaviors. METHODS: Fourteen infants born very preterm or with neonatal brain injury were randomly assigned to SPEEDI or Usual Care. The SPEEDI group participated in 5 collaborative parent, therapist, and infant interventions sessions in the NICU (Phase 1) and 5 at home (Phase 2). Parents provided daily opportunities designed to support the infants emerging motor control and exploratory behaviors. Primary outcome measures were assessed at the end of the intervention, 1 and 3 months after the intervention ended. Reaching was assessed with the infant supported in an infant chair using four 30 s trials. The Early Problem Solving Indicator was used to evaluate the frequency of behaviors during standardized play based assessment. Effect sizes are including for secondary outcomes including the Test of Infant Motor Performance and Bayley Scales of Infant and Toddler Development. RESULTS: No group differences were found in the duration of toy contact. There was a significant group effect on (F1,8 = 4.04, p = 0.08) early exploratory problem-solving behaviors with infants in the SPEEDI group demonstrating greater exploration with effect sizes of 1.3, 0.6, and 0.9 at the end of the intervention, 1 and 3 months post-intervention. CONCLUSIONS: While further research is needed, this initial efficacy study showed promising results for the ability of SPEEDI to impact early problem solving behaviors at the end of intervention and at least 3 months after the intervention is over. While reaching did not show group differences, a ceiling effect may have contributed to this finding. This single blinded pilot RCT was registered prior to subject enrollment on 5/27/14 at ClinicalTrials.Gov with number NCT02153736.


Assuntos
Desenvolvimento Infantil , Continuidade da Assistência ao Paciente , Intervenção Precoce (Educação)/métodos , Recém-Nascido Prematuro/psicologia , Unidades de Terapia Intensiva Neonatal , Pais/educação , Ludoterapia/métodos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Avaliação de Resultados (Cuidados de Saúde) , Projetos Piloto , Resolução de Problemas , Método Simples-Cego
17.
Hepatology ; 68(1): 234-247, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29350768

RESUMO

The relative ranking of cirrhosis-related deaths differs between high-/middle-income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes. Outpatient compensated/decompensated patients with cirrhosis and controls from Turkey and the United States underwent dietary and stool microbiota analysis. Patients with cirrhosis were followed till 90-day hospitalizations. Shannon diversity and multivariable determinants (Cox and binary logistic) of microbial diversity and hospitalizations were studied within/between groups. Two hundred ninety-six subjects (157 U.S.: 48 controls, 59 compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43 decompensated) were included. Patients with cirrhosis between cohorts had similar Model for End-Stage Liver Disease (MELD) scores. American patients with cirrhosis had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol etiologies. Coffee intake was higher in Americans whereas tea, fermented milk, and chocolate intake were higher in Turkey. The entire Turkish cohort had a significantly higher microbial diversity than Americans, which did not change between their controls and patients with cirrhosis. In contrast, microbial diversity changed in the U.S.-based cohort and was the lowest in decompensated patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted a higher diversity whereas MELD score, lactulose use, and carbonated beverage use predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90-day hospitalizations. On Cox and binary logistic regression, microbial diversity was protective against 90-day hospitalizations, along with coffee/tea, vegetable, and cereal intake. CONCLUSION: In this study of patients with cirrhosis and healthy controls from the United States and Turkey, a diet rich in fermented milk, vegetables, cereals, coffee, and tea is associated with a higher microbial diversity. Microbial diversity was associated with an independently lower risk of 90-day hospitalizations. (Hepatology 2018;68:234-247).

18.
Hepatology ; 67(6): 2367-2374, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29315693

RESUMO

The North American Consortium for the Study of End-Stage Liver Disease's definition of acute-on-chronic liver failure (NACSELD-ACLF) as two or more extrahepatic organ failures has been proposed as a simple bedside tool to assess the risk of mortality in hospitalized patients with cirrhosis. We validated the NACSELD-ACLF's ability to predict 30-day survival (defined as in-hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We used the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 2,675). The cohort was randomly split 60%/40% into training (n = 1,605) and testing (n = 1,070) groups. Organ failures assessed were (1) shock, (2) hepatic encephalopathy (grade III/IV), (3) renal (need for dialysis), and (4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years and a diagnosis of alcohol-induced cirrhosis (45%), and 1,079 patients had an infection during hospitalization. The mean Model for End-Stage Liver Disease score was 19, and the median Child score was 10. No demographic differences were present between the two split groups. Multivariable modeling revealed that the NACSELD-ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, Model for End-Stage Liver Disease score, and presence of infection. The c-statistics were 0.8073 for the training set and 0.8532 for the validation set. CONCLUSION: Although infection status remains an important predictor of death, NACSELD-ACLF was independently validated in a separate large multinational prospective cohort as a simple, reliable bedside tool to predict 30-day survival in both infected and uninfected patients hospitalized with a diagnosis of cirrhosis. (Hepatology 2018;67:2367-2374).


Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Escores de Disfunção Orgânica , Insuficiência Hepática Crônica Agudizada/complicações , Feminino , Cuidados Paliativos na Terminalidade da Vida , Mortalidade Hospitalar , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Distribuição Aleatória , Taxa de Sobrevida , Fatores de Tempo
19.
J Womens Health (Larchmt) ; 27(3): 369-376, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29240527

RESUMO

INTRODUCTION: Major depression during the peripartum (MDP) period carries significant public health impact due to the potential adverse effects on maternal, infant, and family outcomes. METHODS: As part of a larger longitudinal study, this cross-sectional observational study sought to build upon the current literature on the prevalence and predictors of depression in the early second trimester of pregnancy, as related to generally accepted risk factors and other less explored risk factors. RESULTS: The findings from this study suggest that in this sample of 230 black and white women at ∼14 weeks gestation, ∼19% endorsed depressive symptoms and that the most important predictors of depression in pregnancy were a preconception history of a mental health issue (e.g., lifetime depressive episode) and perceived stress. Other relevant predictors were pregnancy-related anxiety, income, and stressful life events. CONCLUSION/CLINICAL RELEVANCE: It is important for clinicians not only to screen for MDP during prenatal visits by asking about current depressive, stress, and anxiety symptoms but also to identify patients at risk for MDP by asking simple questions about history of preconception/lifetime episodes of depression and stressful life events. Given the variance accounted for by lifetime depression, additional research into how clinicians may approach this important topic is warranted. For example, checklists given in the waiting room may be less likely to elicit endorsement compared with conversations aimed to normalize the range of depressive histories that may have relevance to obstetric health.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Complicações na Gravidez/psicologia , Adolescente , Adulto , Afro-Americanos , Ansiedade/psicologia , Estudos Transversais , Depressão/psicologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Segundo Trimestre da Gravidez , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Virginia/epidemiologia
20.
Transplantation ; 102(3): 461-470, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29087971

RESUMO

BACKGROUND: There is evidence of brain recovery on brain magnetic resonance imaging (MRI) early postliver transplant (LT), but the longer-term impact is unclear. The aim of this study was to determine the change in brain MRI parameters, cognition, and health-related quality of life (HRQOL) between 6 and 12 months post-LT. METHODS: Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre-LT, 6 months (post-LT1), and 1-year (post-LT2) post-LT. Assessment of MRI changes between visits was performed for ammonia-associated metabolite changes using magnetic resonance spectroscopy, white matter changes using tract-based spatial statistics analysis on diffusion tensor imaging data and grey matter changes using voxel-based morphometry analysis on 3D high resolution T1-weighted images. RESULTS: Forty-five patients were included, of which 23 were tested at all visits. Cognitive and HRQOL scores improved between all visits compared with pre-LT values. This trend continued on magnetic resonance spectroscopy with reduced glutamine + glutamate and higher myoinositol, choline between pre-LT/post-LT1 but lower degrees of improvement between post-LT1/post-LT2. On diffusion tensor imaging, mean diffusivity, linear diffusivity and mode of anisotropy continued to increase in the posterior internal capsule at both post-LT visits. On voxel-based morphometry, a continued increase was seen in basal ganglia grey matter between both post-LT visits was seen. CONCLUSIONS: HRQOL and cognition continue to improve compared with pre-LT values up to 1 year post-LT, although the rate of improvement slows down after 6 months. Grey matter increase is steady over time at 1 year although changes in ammonia-related metabolites and white matter integrity improve at a slower pace at 1 year post-LT.


Assuntos
Encéfalo/patologia , Cognição , Transplante de Fígado , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Transplante de Fígado/psicologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo
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