RESUMO
BACKGROUND: Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk. METHODS: The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476. FINDINGS: 5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64-0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47-0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90-1·51], p=0·26). INTERPRETATION: In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk. FUNDING: The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland.
Assuntos
Desnutrição/prevenção & controle , Apoio Nutricional/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Assistência Centrada no Paciente/métodos , Doença Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Comorbidade , Ingestão de Energia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Medição de RiscoRESUMO
BACKGROUND: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted. METHODS: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers. DISCUSSION: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.
Assuntos
Benchmarking/normas , Múltiplas Afecções Crônicas/terapia , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Pesquisa Comparativa da Efetividade , Atenção à Saúde/estatística & dados numéricos , Prestação Integrada de Cuidados de Saúde/normas , Hospitalização/estatística & dados numéricos , Humanos , Relações Interprofissionais , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Alta do Paciente/normas , Readmissão do Paciente/normas , Transferência de Pacientes/normas , Ensaios Clínicos Pragmáticos como Assunto , Estudos Prospectivos , Qualidade da Assistência à Saúde , Alocação de Recursos , Adulto JovemRESUMO
BACKGROUND: Adrenal hormone metabolite levels are altered in acute illnesses such as community-acquired pneumonia (CAP). Our aim was to investigate associations of sex and mineralocorticoid hormone metabolites with short- and long-term mortality and severity of CAP in male and female patients. METHODS: We prospectively followed 285 patients (60.4% male, mean age 71 years) with CAP from a previous multicenter trial. At baseline, levels of different metabolites of sex hormones and mineralocorticoids were measured by liquid chromatography coupled to tandem mass spectrometry. We calculated Cox regression models adjusted for age and comorbidities. RESULTS: All-cause mortality was 5.3% after 30 days and increased to 47.4% after 6 years. In males, high levels of dihydrotestosterone were associated with higher 6-year mortality (adjusted HR 2.84, 95%CI 1.15-6.99, p = 0.023), whereas high levels of 17-OH-progesterone were associated with lower 6-year mortality (adjusted HR 0.72, 95%CI 0.54-0.97, p = 0.029). Testosterone levels in males correlated inversely with inflammatory markers (CRP rho = - 0.39, p < 0.001; PCT rho = - 0.34, p < 0.001) and disease severity as assessed by the Pneumonia severity index (PSI) (rho = - 0.23, p = 0.003). No similar association was found for female patients. CONCLUSION: Whereas in males with CAP, sex and mineralocorticoid hormone metabolite levels correlated with inflammation, disease severity and long-term survival, no similar association was found for females. Further study of sex and mineralocorticoid hormones in acute illness could generate predictive signatures with implementation in clinical practice.
Assuntos
Di-Hidrotestosterona/sangue , Pneumonia/sangue , Pneumonia/mortalidade , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pneumonia/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality. RESULTS: Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index [PSI], BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216). CONCLUSIONS: Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies. TRIAL REGISTRATION: ISRCTN95122877. Registered 31 July 2006.
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Infecções Comunitárias Adquiridas/epidemiologia , Admissão do Paciente/estatística & dados numéricos , Pneumonia/epidemiologia , Tirosina/análogos & derivados , Tirosina/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/metabolismo , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Mortalidade , Pneumonia/diagnóstico , Pneumonia/metabolismo , Pneumonia/mortalidade , Prognóstico , Fatores de Risco , Suíça/epidemiologia , Fatores de Tempo , Tirosina/metabolismoRESUMO
BACKGROUND: The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients. METHODS: We prospectively followed 172 COPD patients (median age 75 years, 62% male) from a previous Swiss multicenter trial. At baseline, we measured levels of a comprehensive spectrum of adrenal hormone metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by liquid chromatography coupled with tandem mass spectrometry (MS). We calculated Cox regression models adjusted for gender, age, comorbidities and previous corticosteroid therapy. RESULTS: Mortality was 6.4% after 30 days and increased to 61.6% after 6 years. Higher initial androgen hormones predicted lower long-term mortality with significant results for dehydroepiandrosterone (DHEA) [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.98; p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI, 0.50-0.91; p=0.009). An activation of stress hormones (particularly cortisol and cortisone) showed a time-dependent effect with higher levels pointing towards higher mortality at short term, but lower mortality at long term. Activation of the mineralocorticoid axis tended to be associated with increased short-term mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79-9.65; p=0.111). CONCLUSIONS: Independent of age, gender, corticosteroid exposure and exacerbation type, adrenal hormones are associated with mortality at short and long term in patients with COPD exacerbation with different time-dependent effects of glucocorticoids, androgens and mineralocorticoids. A better physiopathological understanding of the causality of these effects may have therapeutic implications.
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Corticosteroides/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: During infection, there is an activation of the L-arginine-nitric-oxide pathway, with a shift from nitric oxide synthesis to a degradation of L-arginine to its metabolites, asymmetric and symmetric dimethylarginine (ADMA and SDMA). However, the prognostic implications for short-term or long-term survival remains unclear. We investigated the association of L-arginine, ADMA, and SDMA with adverse clinical outcomes in a well-defined cohort of patients with community-acquired pneumonia (CAP). METHODS: We measured L-arginine, ADMA, and SDMA in 268 CAP patients from a Swiss multicenter trial by mass spectrometry and used Cox regression models to investigate associations between blood marker levels and disease severity as well as mortality over a period of 6 years. RESULTS: Six-year mortality was 44.8%. Admission levels of ADMA and SDMA (µmol/L) were correlated with CAP severity as assessed by the pneumonia severity index (r = 0.32, p < 0.001 and r = 0.56, p < 0.001 for ADMA and SDMA, respectively) and higher in 6-year non-survivors versus survivors (median 0.62 vs. 0.48; p < 0.001 and 1.01 vs. 0.85; p < 0.001 for ADMA and SDMA, respectively). Both ADMA and SDMA were significantly associated with long-term mortality (hazard ratios [HR] 4.44 [95% confidence intervals (CI) 1.84 to 10.74] and 2.81 [95% CI 1.45 to 5.48], respectively). The effects were no longer significant after multivariate adjustment for age and comorbidities. No association of L-arginine with severity and outcome was found. CONCLUSIONS: Both ADMA and SDMA show a severity-dependent increase in patients with CAP and are strongly associated with mortality. This association is mainly explained by age and comorbidities. TRIAL REGISTRATION: ISRCTN95122877 . Registered 31 July 2006.
Assuntos
Arginina/análogos & derivados , Arginina/sangue , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/mortalidade , Pneumonia/sangue , Pneumonia/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Pneumonia/diagnóstico , Prevalência , Modelos de Riscos Proporcionais , Medição de Risco/métodos , Fatores de Risco , Análise de Sobrevida , Suíça/epidemiologiaRESUMO
BACKGROUND: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. RESULTS: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin. CONCLUSIONS: In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation.
Assuntos
Pneumonia/sangue , Pneumonia/diagnóstico , Serotonina/sangue , Triptofano/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Pneumonia/enzimologia , Pneumonia/mortalidade , PrognósticoRESUMO
BACKGROUND: The hypothalamic-pituitary-adrenal stress axis plays a crucial role in community-acquired pneumonia (CAP), with high cortisol being associated with disease severity and corticosteroid treatment resulting in earlier time to recovery. Our aim in the present study was to compare different glucocorticoid hormones, including cortisol, 11-deoxycortisol, cortisone, and corticosterone, regarding their association with short- and long-term adverse outcomes in a well-defined CAP cohort. METHODS: We prospectively followed 285 patients with CAP from a previous Swiss multicenter trial for a median of 6.1 years and measured different admission glucocorticoid serum levels by liquid chromatography coupled with tandem mass spectrometry. We used adjusted Cox regression models to investigate associations between admission hormone levels and all-cause mortality at different time points. RESULTS: Mortality was 5.3% after 30 days and increased to 47.3% after 6 years. High admission cortisol was associated with adverse outcome after 30 days (adjusted OR 3.85, 95% CI 1.10-13.49, p = 0.035). In the long term (i.e.,), however, high admission cortisol was associated with better survival (adjusted HR after 3 years 0.53, 95% CI 0.32-0.89, p = 0.017; adjusted HR after 6 years 0.57, 95% CI 0.36-0.90, p = 0.015). Compared with 11-deoxycortisol, cortisone, and corticosterone, cortisol showed the highest association with mortality. CONCLUSIONS: Among different glucocorticoid hormones, cortisol showed the highest association with mortality in CAP. Whereas a more pronounced glucocorticoid stress response on hospital admission was associated with higher short-term adverse outcome, long-term outcome was favorable in these patients. These data should support the correct interpretation of glucocorticoid blood data.
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Biomarcadores/análise , Infecções Comunitárias Adquiridas/tratamento farmacológico , Glucocorticoides/efeitos adversos , Pneumonia/tratamento farmacológico , Fatores de Tempo , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Corticosterona/análise , Corticosterona/sangue , Cortodoxona/análise , Cortodoxona/sangue , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia/mortalidade , Prognóstico , Estudos Prospectivos , Análise de Regressão , SuíçaRESUMO
INTRODUCTION: In chronic obstructive pulmonary disease (COPD), there is an activation of the L-arginine nitric oxide pathway. Pulmonary obstruction causes to elevated nitric oxide (NO) levels, which lead to higher production of the NO-inhibiting metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). METHODS: We investigated the association of L-arginine, ADMA, and SDMA with clinical outcomes in a well-defined observational cohort of 150 patients with acute exacerbation of COPD. We measured L-arginine, ADMA, and SDMA by mass spectrometry in patients with pneumonic or non-pneumonic exacerbation of COPD included in a Swiss multicenter trial. We used Cox regression models to investigate the associations between blood marker levels and disease severity as well as all-cause mortality over a follow-up of 6.1 years. RESULTS: Six-year all-cause mortality was 54%. Admission levels of ADMA and SDMA (µmol L-1) were increased in 6-year non-survivors compared to survivors' median (0.60 vs. 0.46, p = 0.004; and 1.05 vs. 0.85, p = 0.012). In a multivariate Cox regression analysis, ADMA was associated with long-term mortality resulting in an age- and comorbidity-adjusted hazard ratio (HR) of 4.55 (95% confidence interval 1.02-20.43, p = 0.048). SDMA was only associated in univariate models and no association of L-arginine with outcome was found. CONCLUSION: ADMA was found to be an independent risk factor for long-term all-cause mortality in patients with acute exacerbation of COPD. Whether therapeutic modification of the L-arginine-nitric oxide pathway has the potential to improve outcome should be evaluated in future interventional trials.
Assuntos
Arginina/análogos & derivados , Arginina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/mortalidade , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida , Suíça/epidemiologia , Fatores de TempoRESUMO
BACKGROUND/INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation. METHODS: We measured tryptophan, serotonin, and kynurenine on admission plasma samples in patients with a COPD exacerbation from a previous trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). IDO and TPH were calculated as ratios of kynurenine over tryptophan, and serotonin over tryptophan, respectively. We studied their association with parameters measured in clinical routine at emergency department admission representing inflammation (C-reactive protein [CRP]), infection (procalcitonin [PCT]), oxygenation (SpO2), as well as patients' clinical outcome, confirmed by structured phone interviews. RESULTS: Mortality in the 149 included patients was 53.7% within six years of follow-up. While IDO activity showed strong positive correlations, tryptophan was negatively correlated with CRP and PCT. For 30-day adverse outcome defined as death and/or intensive care unit (ICU) admission, a multivariate regression analysis adjusted for age and comorbidities found strong associations for IDO activity (adjusted odds ratios of 31.4 (95%CI 1.1-857), p = 0.041) and TPH (adjusted odds ratios 27.0 (95%CI 2.2-327), p = 0.010). TPH also showed a significant association with mortality at 18 months, (hazard ratio 2.61 (95%CI 1.2-5.8), p = 0.020). CONCLUSION: In hospitalized patients with a COPD exacerbation, higher IDO and TPH activities independently predicted adverse short-term outcomes and TPH levels were also predictive of 18-month mortality. Whether therapeutic modulation of the serotonin pathway has positive effects on outcome needs further investigation.
Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Serotonina/sangue , Triptofano Hidroxilase/metabolismo , Triptofano/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Cromatografia Líquida , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Oxigênio/sangue , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Suíça , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
BACKGROUND: Most clinical research investigated prognostic biomarkers for their ability to predict cardiovascular events or mortality. It is unknown whether biomarkers allow prediction of quality of life (QoL) after survival of the acute event. Herein, we investigated the prognostic potential of well-established inflammatory/cardiovascular blood biomarkers including white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), pro-adrenomedullin (proADM) and pro-atrial natriuretic peptide (proANP) in regard to a decline in QoL in a well-defined cohort of patients with community-acquired pneumonia (CAP). METHODS: Within this secondary analysis including 753 patients with a final inpatient diagnosis of CAP from a multicenter trial, we investigated associations between admission biomarker levels and decline in QoL assessed by the EQ-5D health questionnaire from admission to day 30 and after 6 years. RESULTS: Admission proADM and proANP levels significantly predicted decline of the weighted EQ-5D index after 30 days (n=753) with adjusted odds ratios (ORs) of 2.0 ([95% CI 1.1-3.8]; p=0.027) and 3.7 ([95% CI 2.2-6.0]; p<0.001). Results for 6-year outcomes (n=349) were similar with ORs of 3.3 ([95% CI 1.3-8.3]; p=0.012) and 6.2 ([95% CI 2.7-14.2]; p<0.001). The markers were associated with most of the different QoL dimensions including mobility, self-care, and usual activities, but not pain/discomfort and to a lesser degree anxiety/depression and the visual analogue scale (VAS). Initial WBC, PCT and CRP values did not well predict QoL at any time point. CONCLUSIONS: ProADM and proANP accurately predict short- and long-term decline in QoL across most dimensions in CAP patients. It will be interesting to reveal underlying physiopathology in future studies.
Assuntos
Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients. METHODS: We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission]. RESULTS: Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information. CONCLUSIONS: This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.
Assuntos
Proteína C-Reativa/metabolismo , Calcitonina/sangue , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Contagem de Leucócitos , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/diagnóstico , Precursores de Proteínas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Estudos de Coortes , Infecções Comunitárias Adquiridas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Pneumonia Bacteriana/terapia , PrognósticoRESUMO
Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.
Assuntos
Doença Pulmonar Obstrutiva Crônica/mortalidade , Adrenomedulina/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Calcitonina/sangue , Dispneia/classificação , Dispneia/epidemiologia , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Precursores de Proteínas/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Medição de Risco , Fumar/epidemiologia , Suíça/epidemiologiaRESUMO
AIMS/HYPOTHESIS: Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients. METHODS: This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission). RESULTS: In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p < 0.05, ANOVA, all days). In diabetic patients (n = 156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels ≥ 9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p = 0.03). No effect modification by insulin treatment was detected (interaction terms p > 0.2 for all analyses). CONCLUSIONS/INTERPRETATION: Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus/imunologia , Hiperglicemia/sangue , Inflamação/sangue , Pneumonia/sangue , Estresse Fisiológico/imunologia , Idoso , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Infecções Comunitárias Adquiridas/sangue , Diabetes Mellitus/sangue , Feminino , Hospitalização , Humanos , Hiperglicemia/imunologia , Inflamação/imunologia , Contagem de Leucócitos , Masculino , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Prognóstico , Estudos Prospectivos , Precursores de Proteínas/sangue , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Blood biomarkers are increasingly used to diagnose, guide therapy in, and risk-stratify community-acquired pneumonia (CAP) patients in emergency departments (EDs). How pre-analytic factors affect these markers' initial levels in this population is unknown. METHODS: In this secondary analysis of consecutive ED patients with CAP from a large multicentre antibiotic stewardship trial, we used adjusted multivariate regression models to determine the magnitude and statistical significance of differences in mean baseline concentrations of five biomarkers (procalcitonin [PCT], C-reactive protein [CRP], white blood cells count [WBC], proadrenomedullin [ProADM], copeptin) associated with six pre-analytic factors (antibiotic or corticosteroid pretreatment, age, gender, chronic renal failure or chronic liver insufficiency). RESULTS: Of 925 CAP patients (median age 73 years, 58.8% male), 25.5% had antibiotic pretreatment, 2.4%, corticosteroid pretreatment, 22.3%, chronic renal failure, 2.4% chronic liver insufficiency. Differences associated with pre-analytic factors averaged 6.1% ± 4.6%; the three largest statistically significant changes (95% confidence interval) were: PCT, +14.2% (+2.1% to +26.4%, p = 0.02) with liver insufficiency; ProADM, +13.2% (+10.2% to +16.1%, p < 0.01) with age above median; CRP, -12.8% (-25.4% to -0.2%, p = 0.05) with steroid pretreatment. In post hoc sensitivity analyses, reclassification statistics showed that these factors did not result in significant changes of biomarker levels across clinically used cut-off ranges. CONCLUSIONS: Despite statistically significant associations of some pre-analytic factors and biomarker levels, a clinically relevant influence seems unlikely. Our observations reinforce the concept of using biomarkers in algorithms with widely-separated cut-offs and overruling criteria considering the entire clinical picture. TRIAL REGISTRATION: Identifier ISRCTN95122877.
Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/sangue , Glucocorticoides/uso terapêutico , Pneumonia/sangue , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pneumonia/tratamento farmacológico , Estudos Prospectivos , Análise de RegressãoRESUMO
BACKGROUND & AIM: CT-derived measures of muscle mass may help to identify patients with sarcopenia. We investigated the prognostic significance of CT-derived sarcopenia and muscle attenuation with nutritional markers, clinical outcomes and response to nutritional support in medical in-patients at nutritional risk. METHOD: Within this secondary analysis of the randomized-controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) comparing individualized nutritional support with usual care nutrition in medical inpatients, we investigated associations of CT-based sarcopenia and muscle attenuation at the level L3 with different nutritional and clinical outcomes, and the response to the nutritional intervention. The primary composite endpoint was adverse clinical outcome within 30 days of hospital admission. RESULTS: We included 573 of 2028 EFFORT patients with available CT scans, of which 68.4% met the CT-based definition of sarcopenia and 72.9% had low muscle attenuation. In multivariate analysis, low skeletal muscle index was associated with higher nutritional risk (coefficient per NRS class -0.94 (95%CI -1.87 to -0.01) p = 0.049) and higher risk for adverse clinical outcomes (adjusted odds ratio 1.59 (95% CI 1.06 to 2.38), p = 0.024). Low muscle attenuation was also associated with adverse clinical outcome (adjusted odds ratio 1.67 (95%CI 1.08 to 2.58), p = 0.02). Nutritional support tended to be more effective in reducing mortality in non-sarcopenic patients compared to patients with CT-based sarcopenia (p for interaction 0.058). CONCLUSIONS: Within a population of medical patients at nutritional risk, CT-based sarcopenia and muscle attenuation were associated with several nutritional parameters and predicted adverse clinical outcomes. Information from CT scans, thus may help to better characterize these patients, and may be helpful in guiding therapeutic interventions.
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Fragilidade , Desnutrição , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/terapia , Sarcopenia/complicações , Fragilidade/complicações , Pacientes Internados , Desnutrição/diagnóstico , Desnutrição/terapia , Desnutrição/complicações , Apoio Nutricional , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) recently suggested specific criteria to standardize the diagnosis of malnutrition. There is need for validation of these criteria regarding response to nutrition treatment. Our aim was to validate modified GLIM (mGLIM) criteria among medical inpatients at risk of disease related malnutrition for prediction of outcome and response to nutritional therapy. METHODS: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicenter randomized controlled trial conducted between April 2014 and February 2018. Adult medical inpatients at nutritional risk (Nutrition Risk Score 2002 ≥ 3 points) were randomly assigned to receive nutritional therapy according to an algorithm based on individualized nutritional requirements (intervention group) or standard hospital food (control group). We included all participants with available information regarding mGLIM criteria. The primary outcome was adverse clinical outcome, which was a composite of 30-day all-cause mortality, ICU-admission, rehospitalization rate, major complications and decline in functional status. RESULTS: Of 1917 eligible participants at nutritional risk, 1181 (61.6%) met the diagnosis of malnutrition based on mGLIM criteria. The incidence of adverse clinical outcome was significantly higher in mGLIM-positive participants compared with mGLIM-negative participants [330/1181 (27.9%) versus 140/736 (19.0%); multivariable adjusted odds ratio [OR] 1.53; 95% CI 1.22-1.93; p < 0.001]. Regarding the effect of nutritional therapy, the reduction in adverse clinical outcomes was higher in mGLIM-positive participants [180/581 (31.0%) vs. 150/600 (25.0%), OR 0.69; 95% CI 0.53-0.9, p = 0.007], compared with mGLIM-negative participants [75/379 (19.8%) versus 65/357 (18.2%), OR 0.95; 95% CI 0.65-1.40, p = 0.797], a finding that was, however, not significant in interaction analysis (p for interaction = 0.217). CONCLUSION: Data from this secondary analysis of a multicenter randomized trial involving medical inpatients at nutritional risk validate the strong prognostic value of mGLIM criteria regarding adverse clinical outcomes and other long-term outcomes. However, further research is needed to improve the ability of GLIM criteria to predict therapeutic response to nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.
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Liderança , Desnutrição , Adulto , Hospitalização , Humanos , Desnutrição/complicações , Desnutrição/diagnóstico , Desnutrição/terapia , Avaliação Nutricional , Estado Nutricional , Apoio NutricionalRESUMO
Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial. Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity. Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022. Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning. Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals. Results: There were 54â¯695 hospitalizations at intervention hospitals, with 27â¯219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14â¯400 [52.9%] men) and 27â¯476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14â¯448 [52.6%] men) and 438â¯791 at control hospitals, with 216â¯261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109â¯770 [50.8%] men) and 222â¯530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113â¯053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time. Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge. Trial Registration: isrctn.org Identifier: ISRCTN83274049.
Assuntos
Registros Eletrônicos de Saúde , Alta do Paciente , Idoso , Feminino , Hospitais , Humanos , Tempo de Internação , Masculino , Multimorbidade , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Screening for malnutrition upon hospital admission is the first crucial step for proper nutritional assessment and treatment. While several nutritional screening and assessment instruments exist, there is a lack of head-to-head validation of these instruments. We studied the ability of five different nutrition screening and assessment instruments to predict 1-year mortality and response to nutritional treatment in participants of the EFFORT randomized trial. METHODS: In this secondary analysis of a Swiss-wide multicenter, randomized clinical trial comparing individualized nutritional support with usual care nutrition in medical inpatients, we prospectively classified patients as low, intermediate, and high nutritional risk based on five nutritional screening and assessment instruments (NRS 2002, SGA, SNAQ, MNA and MUST). RESULTS: Overall mortality at 1-year in the 1866 included patients was 30.4%. There were significant correlations and a significant concordance between all instruments with r-values ranging from 0.23 to 0.55 and kappa values ranging from 0.10 to 0.36. While high nutritional risk was associated with higher mortality in all instruments, SGA and MNA showed the strongest association with adjusted odds ratios of 3.17 (95%CI, 2.18 to 4.61, p < 0.001) and 3.45 (95%CI, 2.28 to 5.22, p < 0.001). When comparing mortality in intervention group patients to control group patients stratified by severity of malnutrition, there was overall no clear trend towards more benefit in patients with more severe malnutrition, with NRS 2002 and SGA showing the most pronounced relationship between the severity of malnutrition and reduction in mortality as a response to nutritional support. CONCLUSION: Among all five screening and assessment instruments, higher nutritional risk was associated with higher risk for mortality and adverse clinical outcome, but not with more or less treatment response from nutritional support with differences among scores. Adding more specific parameters to these instruments is important when using them to decide for or against nutritional support interventions in an individual patient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02517476.
Assuntos
Desnutrição , Avaliação Nutricional , Humanos , Pacientes Internados , Desnutrição/complicações , Desnutrição/diagnóstico , Desnutrição/terapia , Estado Nutricional , Apoio NutricionalRESUMO
BACKGROUND: Historically, admission serum albumin concentrations have been considered useful biochemical markers for nutrition assessment. However, there is a lack of randomised trial data investigating whether low albumin concentrations are helpful for identifying patients benefitting from nutritional support. METHODS: This study was a secondary analysis of the EFFORT trial, a Swiss-wide multicentre, randomised controlled trial comparing individualised nutritional support with usual care nutrition in medical inpatients from April 1, 2014, to February 1, 2018. 1389 of 2028 patients at nutritional risk with available albumin concentrations on admission were included. The primary endpoint was all-cause mortality within 30 and 180 days. Patients were stratified into groups of low or normal albumin based on the albumin cut-off of 30 g/L. ClinicalTrials.gov number, NCT02517476. FINDINGS: 1389 patients (mean age, 73.1 (SD 3.5) years; 747 (53.8%) men) were included and 676 (48.7%) had low serum albumin concentrations at admission (<30 g/L). Mortality at 180 days was significantly increased in the low albumin group compared with patients with normal albumin concentrations (219/676 (32.4%) vs. 162/713 (22.7%), fully adjusted HR 1.4, 95%CI 1.11 to 1.77, p = 0.005]. Effects of nutritional support on 30-day mortality were similar for patients with low compared to patients with normal albumin concentrations (HR 0.68, 95%CI 0.44 to 1.05 vs. HR 0.70, 95%CI 0.41 to 1.20), with no evidence for a subgroup effect (p for interaction=0.97). INTERPRETATION: Based on this secondary analysis of a randomised trial, low admission serum albumin concentrations in hospitalised, non-critically ill, medical patients at nutritional risk had prognostic implications and indicated higher mortality risk but were not helpful in selecting patients for nutritional interventions. FUNDING: The Swiss National Science Foundation (SNSF) (PP00P3_150531) and the Research Council of the Kantonsspital Aarau (1410.000.058 and 1410.000.044) provided funding for the EFFORT trial.