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PURPOSE: Albumin is widely used during and after on-pump cardiac surgery, although it is unclear whether this therapy improves clinical outcomes. METHODS: This observational study utilized the Cerner Health Facts® database (a large HIPAA-compliant clinical-administrative database maintained by Cerner Inc., USA) to identify a cohort of 6,188 adults that underwent on-pump cardiac surgery for valve and/or coronary artery procedures between January 2001 and March 2013. Of these, 1,095 patients who received 5% albumin with crystalloid solutions and 1,095 patients who received crystalloids alone on the day of or the day following cardiac surgery were selected by propensity-score matching. The primary outcome was all-cause in-hospital mortality. Three secondary outcomes analyzed include acute kidney injury severity, major morbidity composite, and all-cause 30-day readmissions. RESULTS: In the propensity-score matched cohort, receipt of perioperative 5% albumin was associated with decreased risk of in-hospital mortality (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3 to 0.9; P = 0.02) and lower all-cause 30-day readmission rates (OR, 0.7; 98.3% CI, 0.5 to 0.9; P < 0.01). Albumin therapy was not associated with differences in overall major morbidity (OR, 0.9; 98.3% CI, 0.7 to 1.2; P = 0.39; composite) or acute kidney injury severity (OR, 0.9; 98.3% CI, 0.6 to 1.4; P = 0.53) compared with therapy with crystalloid solutions. CONCLUSIONS: In this large retrospective study, use of 5% albumin solution was associated with significantly decreased odds of in-hospital mortality and all-cause 30-day readmission rate compared with administration of crystalloids alone in adult patients undergoing on-pump cardiac surgery. These results warrant further studies to examine fluid receipt, including 5% albumin, in surgical populations via randomized-controlled trials.
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Albuminas/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/métodos , Soluções Cristaloides/administração & dosagem , Injúria Renal Aguda/epidemiologia , Idoso , Procedimentos Cirúrgicos Cardíacos/mortalidade , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Although evidence suggests significant clinical benefits of home noninvasive ventilation (NIV) for management of severe chronic obstructive pulmonary disease (COPD), economic analyses supporting the use of this technology are lacking. OBJECTIVES: To evaluate the economic impact of adopting home NIV, as part of a multifaceted intervention program, for severe COPD. METHODS: An economic model was developed to calculate savings associated with the use of Advanced NIV (averaged volume assured pressure support with autoexpiratory positive airway pressure; Trilogy100, Philips Respironics, Inc., Murrysville, PA) versus either no NIV or a respiratory assist device with bilevel pressure capacity in patients with severe COPD from two distinct perspectives: the hospital and the payer. The model examined hospital savings over 90 days and payer savings over 3 years. The number of patients with severe COPD eligible for home Advanced NIV was user-defined. Clinical and cost data were obtained from a quality improvement program and published reports. Scenario analyses calculated savings for hospitals and payers covering different COPD patient cohort sizes. RESULTS: The hospital base case (250 patients) revealed cumulative savings of $402,981 and $449,101 over 30 and 90 days, respectively, for Advanced NIV versus both comparators. For the payer base case (100,000 patients), 3-year cumulative savings with Advanced NIV were $326 million versus no NIV and $1.04 billion versus respiratory assist device. CONCLUSIONS: This model concluded that adoption of home Advanced NIV with averaged volume assured pressure support with autoexpiratory positive airway pressure, as part of a multifaceted intervention program, presents an opportunity for hospitals to reduce COPD readmission-related costs and for payers to reduce costs associated with managing patients with severe COPD on the basis of reduced admissions.
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Ventilação não Invasiva/economia , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/terapia , Autocuidado/economia , Análise Custo-Benefício , Custos de Cuidados de Saúde , Custos Hospitalares , Hospitalização/economia , Humanos , Modelos Econométricos , Ventilação não Invasiva/métodos , Respiração com Pressão Positiva/economia , Respiração com Pressão Positiva/métodos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Autocuidado/métodosRESUMO
INTRODUCTION: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. METHODS: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98%) received 0.9% saline whereas 1706 (2%) received a calcium-free balanced solution as the primary fluid. RESULTS: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27% vs. 1.03%, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P < 0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P < 0.001). No differences were found in acute renal failure. CONCLUSIONS: In this large electronic health record, the predominant use of 0.9% saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. TRIAL REGISTRATION: NCT02083198 clinicaltrials.gov; March 5, 2014.
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Hidratação/métodos , Síndrome de Resposta Inflamatória Sistêmica/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Soluções Cristaloides , Feminino , Humanos , Infusões Intravenosas , Soluções Isotônicas/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
STUDY OBJECTIVES: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects. METHODS: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models. RESULTS: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway (P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization. CONCLUSIONS: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects. CITATION: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med. 2024;20(4):505-514.
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Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Adulto , Humanos , Estados Unidos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Síndromes da Apneia do Sono/complicações , Sono , Polissonografia/métodos , Apneia do Sono Tipo Central/complicaçõesRESUMO
OBJECTIVE: A monitoring pulmonary artery catheter (PAC) is utilized in approximately 34% of the US cardiac surgical procedures. Increased use of PAC has been reported to have an association with complication rates: significant decreases in new-onset heart failure (HF) and respiratory failure (RF), but increases in bacteremia and urinary tract infections. We assessed the impact of increasing PAC adoption on hospital costs among cardiac surgery patients for US-based healthcare systems. METHODS: An Excel-based economic model calculated annualized savings for a US hospital with various cardiac surgical volumes and PAC adoption rates. A second model, for an integrated payer-provider health system, analyzed outcomes/costs resulting from the cardiac surgical admission and for the treatment of persistent HF and RF complications in the year following surgery. Model inputs were extracted from published literature, and one-way and probabilistic sensitivity analyses were performed. RESULTS: For an acute care hospital with 500 procedures/year and 34% PAC adoption, annualized savings equalled $61,806 vs no PAC utilization. An increase in PAC adoption rate led to increased savings of $134,751 for 75% and $170,685 for 95% adoption. Savings ranged from $12,361 to $185,418 at volumes of 100 and 1500 procedures/year, respectively. For an integrated payer-provider health system with the base-case scenario of 3845 procedures/year and 34% PAC adoption, estimated savings were $596,637 for the combined surgical index admission and treatment for related complications over the following year. CONCLUSION: PAC utilization in adult cardiac surgery patients results in reduced costs for both acute care hospitals and payer-provider integrated health systems.
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BACKGROUND: Knee osteoarthritis (OA) is a painful condition affecting >250 million people worldwide and is a leading cause of disability. Intra-articular (IA) corticosteroids and/or oral opioids are often recommended for the management of knee OA pain. There are, however, concerns regarding their safety and tolerability. STUDY QUESTION: Do patients diagnosed with knee OA show a decrease in opioids or IA corticosteroid injections prescribed/administered in hospitals following hylan G-F 20 treatment? STUDY DESIGN: This case-crossover, retrospective study using Health Facts®, a de-identified electronic health records database, enrolled patients ≥18 years with knee OA treated with hylan G-F 20 between January 1, 2000 and March 31, 2016, with data within 6 months before/after treatment. MEASURES AND OUTCOMES: Primary endpoints compared days on opioids, amounts of opioids, and number of IA corticosteroid injections before/after hylan G-F 20 treatment via paired t-tests. RESULTS: A total of 513 patients were qualified for analysis. In the opioid cohort, the average total number of days on opioids (N = 50; 5.0 vs 13.5 days; P = 0.007) and average total amount of opioids (N = 44; 165.4 morphine mg equivalents [MME] vs 493.7 MME; P = 0.013) were lower 6 months after hylan G-F 20 treatment than 6 months before treatment. In the IA corticosteroid cohort, the average number of IA corticosteroid injections decreased after hylan G-F 20 treatment (N = 36; 0.56 in the 6-month follow-up vs 1.39 before treatment; P < 0.0001). Additional time frames of 1-5 months before and after treatment were examined; similar conclusions were drawn for patients with >2 months of data. CONCLUSION: Patients with knee OA previously treated with opioids or IA corticosteroid injections who received hylan G-F 20 demonstrated statistically significant decreases in these medications >2 months following hylan G-F 20 treatment versus >2 months before treatment.
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PURPOSE: To assess the predictive value of a single abnormal shock index reading (SI ≥0.9; heart rate/systolic blood pressure [SBP]) for mortality, and association between cumulative abnormal SI exposure and mortality/morbidity. MATERIALS AND METHODS: Cohort comprised of adult patients with an intensive care unit (ICU) stay ≥24-h (years 2010-2018). SI ≥0.9 exposure was evaluated via cumulative minutes or time-weighted average; SBP ≤100-mmHg was analyzed. Outcomes were in-hospital mortality, acute kidney injury (AKI), and myocardial injury. RESULTS: 18,197 patients from 82 hospitals were analyzed. Any single SI ≥0.9 within the ICU predicted mortality with 90.8% sensitivity and 36.8% specificity. Every 0.1-unit increase in maximum-SI during the first 24-h increased the odds of mortality by 4.8% [95%CI; 2.6-7.0%; p < .001]. Every 4-h exposure to SI ≥0.9 increased the odds of death by 5.8% [95%CI; 4.6-7.0%; p < .001], AKI by 4.3% [95%CI; 3.7-4.9%; p < .001] and myocardial injury by 2.1% [95%CI; 1.2-3.1%; p < .001]. ≥2-h exposure to SBP ≤100-mmHg was significantly associated with mortality. CONCLUSIONS: A single SI reading ≥0.9 is a poor predictor of mortality; cumulative SI exposure is associated with greater risk of mortality/morbidity. The associations with in-hospital mortality were comparable for SI ≥0.9 or SBP ≤100-mmHg exposure. Dynamic interactions between hemodynamic variables need further evaluation among critically ill patients.
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Injúria Renal Aguda/complicações , Estado Terminal , Traumatismos Cardíacos/complicações , Choque/diagnóstico , Choque/mortalidade , Injúria Renal Aguda/sangue , Adulto , Idoso , Pressão Sanguínea , Estudos de Coortes , Cuidados Críticos , Feminino , Frequência Cardíaca , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Morbidade , Valor Preditivo dos Testes , Probabilidade , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Choque/complicações , Resultado do TratamentoRESUMO
PURPOSE: This study examined postoperative heart failure (HF) and respiratory failure (RF) complications and related healthcare utilization for one year following cardiac surgery. METHODS: This study identified adult patients undergoing isolated coronary artery bypass graft (CABG) and/or valve procedures from the Cerner Health Facts® database. It included patients experiencing postoperative HF or RF complications. We quantified healthcare utilization using the frequency of inpatient admissions, emergency department (ED) visits with or without hospital admission, and outpatient visits. We then determined direct hospital costs from the determined healthcare utilization. We analyzed trends over time for both HF and RF and evaluated the association between surgery type and HF complication. RESULTS: Of 10,298 patients with HF complications, 1,714 patients (16.6%) developed persistent HF; of the 10,385 RF patients, 175 (1.7%) developed persistent RF. Healthcare utilization for those with persistent complications over the one-year period following index hospital discharge comprised an average number of the following visit types: Inpatient (1.49 HF; 1.55 RF), Outpatient (2.02, 0.51), ED without hospital admission (0.33, 0.13), ED + Inpatient (0.08, 0.06). Per patient annual costs related to persistent complications of HF and RF were $20,857 and $30,745, respectively. There was a significant association between cardiac surgical type and the incidence of HF, with risk for isolated valve procedures (adjusted OR 2.60; 95% CI: 2.35-2.88) and CABG + valve procedures (adjusted OR 2.38; 95% CI: 2.17-2.61) exceeding risk for isolated CABG procedures. CONCLUSIONS: This study demonstrates that HF and RF complication rates post cardiac surgery are substantial, and complication-related healthcare utilization over the first year following surgery results in significant incremental costs. Given the need for both payers and providers to focus on healthcare cost reduction, this study fills an important gap in quantifying the mid-term economic impact of postoperative cardiac surgical complications.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Custos e Análise de Custo , Insuficiência Cardíaca/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/economia , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/economia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Utilização de Procedimentos e Técnicas/economia , Insuficiência Respiratória/economia , Estados UnidosRESUMO
BACKGROUND: The utility of pulmonary artery catheters (PACs) and their measurements depend on a variety of factors including data interpretation and personnel training. This US multi-center, retrospective electronic health record (EHR) database analysis was performed to identify associations between PAC use in adult cardiac surgeries and effects on subsequent clinical outcomes. METHODS: This cohort analysis utilized the Cerner Health Facts database to examine patients undergoing isolated coronary artery bypass graft (CABG), isolated valve surgery, aortic surgery, other complex non-valvular and multi-cardiac procedures, and/or heart transplant from January 1, 2011, to June 30, 2015. A total of 6844 adults in two cohorts, each with 3422 patients who underwent a qualifying cardiac procedure with or without the use of a PAC for monitoring purposes, were included. Patients were matched 1:1 using a propensity score based upon the date and type of surgery, hospital demographics, modified European System for Cardiac Operative Risk Evaluation (EuroSCORE II), and patient characteristics. Primary outcomes of 30-day in-hospital mortality, length of stay, cardiopulmonary morbidity, and infectious morbidity were analyzed after risk adjustment for acute physiology score. RESULTS: There was no difference in the 30-day in-hospital mortality rate between treatment groups (OR, 1.17; 95% CI, 0.65-2.10; p = 0.516). PAC use was associated with a decreased length of stay (9.39 days without a PAC vs. 8.56 days with PAC; p < 0.001), a decreased cardiopulmonary morbidity (OR, 0.87; 95% CI, 0.79-0.96; p < 0.001), and an increased infectious morbidity (OR, 1.28; 95% CI, 1.10-1.49; p < 0.001). CONCLUSIONS: Use of a PAC during adult cardiac surgery is associated with decreased length of stay, reduced cardiopulmonary morbidity, and increased infectious morbidity but no increase in the 30-day in-hospital mortality. This suggests an overall potential benefit associated with PAC-based monitoring in this population. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT02964026) on November 15, 2016.
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PURPOSE: Current guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury. METHODS: We conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury. RESULTS: In total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg. CONCLUSIONS: Risks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients.
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Injúria Renal Aguda/terapia , Traumatismos Cardíacos/terapia , Mortalidade Hospitalar , Hipotensão/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/complicações , Sepse/mortalidade , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Morbidade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: There is growing evidence of the benefits of intravenous fluid therapy with balanced crystalloids over 0.9% 'normal' saline. This analysis evaluated the economic impact of increasing usage of a calcium-free balanced crystalloid solution (BAL) in patients with systemic inflammatory response syndrome (SIRS) on an annual hospital budget. METHODS: An Excel®-based economic model was developed to estimate costs associated with increased BAL usage (i.e., use in a greater proportion of patients), from the US hospital perspective, over a 5-year time horizon. Clinical inputs were based on the results of a retrospective Electronic Health Record (EHR) database analysis identifying significantly fewer complications among SIRS patients receiving predominantly BAL versus saline. Complication-associated costs, adjusted to 2015, were obtained from published reports. Scenario analyses examined cost impacts for hospitals of various sizes, with different BAL adoption levels and rates. RESULTS: Base-case scenario analysis (300-bed hospital, 80% occupancy, current and year 5 BAL usage in 5 and 75% of SIRS patients, respectively, exponential year-over-year adoption) showed year 1 hospital savings of US$29,232 and cumulative 5-year savings of US$1.16M. Cumulative 5-year pharmacy savings were US$172,641. Scenario analyses demonstrated increasing cumulative 5-year savings with increasing hospital size, year 5 BAL usage in greater proportions of patients, and rapid/early BAL adoption. CONCLUSIONS: Increased BAL usage represents an opportunity for hospitals and pharmacy departments to reduce complication-related costs associated with managing SIRS patients. The model suggests that savings could be expected across a range of scenarios, likely benefiting hospitals of various sizes and with different adoption capabilities.
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PURPOSE: Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered. METHODS: We conducted a retrospective analysis of 109,836 patients ≥ 18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the 'volume-adjusted chloride load' and in-hospital mortality. RESULTS: In general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7%) among patients with minimal increases in serum chloride concentration (0-10 mmol/L) and when the total administered chloride load was low (3.5% among patients receiving 100-200 mmol; P < 0.05 versus patients receiving ≥ 500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6%) when the volume-adjusted chloride load was 105-115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95% CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥ 105 mmol/L). CONCLUSIONS: Among patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.
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Cloretos/administração & dosagem , Coloides/administração & dosagem , Hidratação , Mortalidade Hospitalar , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cloretos/efeitos adversos , Cloretos/sangue , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Hidratação/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Ressuscitação , Estudos Retrospectivos , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/prevenção & controle , Adulto JovemRESUMO
The mechanism by which tumor necrosis factor-alpha (TNF) differentially modulates type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well understood. CD4+CD25+ T cells have been implicated as mediators of self-tolerance. We show (i) NOD mice have a relative deficiency of CD4+CD25+ T cells in thymus and spleen; (ii) administration of TNF or anti-TNF to NOD mice can modulate levels of this population consistent with their observed differential age-dependent effects on diabetes in the NOD mouse; (iii) CD4+CD25+ T cells from NOD mice treated neonatally with TNF show compromised effector function in a transfer system, whereas those treated neonatally with anti-TNF show no alteration in ability to prevent diabetes; and (iv) repeated injection of CD4+CD25+ T cells into neonatal NOD mice delays diabetes onset for as long as supplementation occurred. These data suggest that alterations in the number and function of CD4+CD25+ T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice.