Nutritional parameters associated with prolonged hospital stay among ambulatory adult patients

Background

Comprehensive evaluations of the nutritional parameters associated with length of hospital stay are lacking. We investigated the association between malnutrition and length of hospital stay in a cohort of ambulatory adult patients.

Methods

From September 2006 to June 2009, we systematically evaluated 1274 ambulatory adult patients admitted to hospital for medical or surgical treatment. We evaluated the associations between malnutrition and prolonged hospital stay (> 17 days [> 75th percentile of distribution]) using multivariable log-linear models adjusted for several potential nutritional and clinical confounders recorded at admission and collected during and at the end of the hospital stay.

Results

Nutritional factors associated with a prolonged hospital stay were a Nutritional Risk Index score of less than 97.5 (relative risk [RR] 1.64, 95% confidence interval [CI] 1.31–2.06) and an in-hospital weight loss of 5% or greater (RR 1.60, 95% CI 1.30–1.97). Sensitivity analysis of data for patients discharged alive and who had a length of stay of at least three days (n = 1073) produced similar findings (adjusted RR 1.51, 95% CI 1.20–1.89, for Nutritional Risk Index score < 97.5). A significant association was also found with in-hospital starvation of three or more days (RR 1.14, 95% CI 1.01–1.28).

Interpretation

Nutritional risk at admission was strongly associated with a prolonged hospital stay among ambulatory adult patients. Another factor associated with length of stay was worsening nutritional status during the hospital stay, whose cause–effect relationship with length of stay should be clarified in intervention trials. Clinicians need to be aware of the impact of malnutrition and of the potential role of worsening nutritional status in prolonging hospital stay.Choosing the most appropriate approach to clinical management for patients admitted to hospital may not only improve clinical outcomes but also result in early discharge.^1–4 Several factors associated with prolonged hospital stay include the clinical setting, the type and the severity of disease, the presence of comorbidities, the quality and number of interventions, and the patient’s age.^5,6 There is a growing body of evidence that nutritional factors, both related and unrelated to the leading diseases, also affect length of hospital stay and overall health care costs.^7–11 A poor nutritional status at the time of admission can contribute to a prolonged hospital stay, and inadequate nutritional support may negatively affect both nutritional status and prognosis.^7,8 However, these factors have been frequently analyzed independently, and comprehensive and multivariable evaluations of the nutritional parameters associated with a prolonged hospital stay are lacking. Moreover, the potential effect of other confounders occurring during the hospital stay, such as worsening nutritional status, is unknown.We identified the nutritional parameters associated with prolonged hospital stay in a representative sample of ambulatory adult patients. We investigated the association between nutritional risk at the time of admission and length of stay after controlling for several confounders recorded at admission and during the hospital stay.     

Development of egg PC/cholesterol/α-tocopherol liposomes with ionic gradients to deliver ropivacaine

Context: Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required.

Objective: This study therefore aimed to provide extended RVC release and increased upload using modified liposomes.

Materials and methods: Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07?mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5?+?(NH₄)₂SO₄ and pH 7.4?+?(NH₄)₂SO₄) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4).

Results and discussion: An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5_in) or pH 7.4 with 250?mM (NH₄)₂SO₄ in the inner aqueous core (LMVV 7.4_in?+?ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ～70%) and sustained release (～25?h).

Conclusion: The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.     

Beckwith–Wiedemann syndrome prenatal diagnosis by methylation analysis in chorionic villi

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder that can be prenatally suspected or diagnosed based on established clinical guidelines. Molecular confirmation is commonly performed on amniocytes. The possibility to use fresh (CVF) and cultured (CVC) chorionic villi has never been investigated. To verify whether CVF and CVC are reliable sources of DNA to study fetal methylation, we used pyrosequencing to test the methylation level of a number of differentially methylated regions (DMRs) at several imprinted loci (ICR1, ICR2, H19, PWS/AS-ICR, GNASXL, GNAS1A, ZAC/PLAGL1, and MEST) and at non-imprinted MGMT and RASSF1A promoters. We analyzed these regions in 19 healthy pregnancies and highlighted stable methylation levels between CVF and CVC at ICR1, ICR2, GNASXL, PWS/AS-ICR, and MEST. Conversely, the methylation levels at H19 promoter, GNAS1A and ZAC/PLAGL1 were different in CVC compared to fresh CV. We also investigated ICR1 and ICR2 methylation level of CVF/CVC of 2 BWS-suspected fetuses (P1 and P2). P1 showed ICR2 hypomethylation, P2 showed normal methylation at both ICR1 and ICR2. Our findings, although limited to one case of BWS fetus with an imprinting defect, can suggest that ICR1 and ICR2, but not H19, could be reliable targets for prenatal BWS diagnosis by methylation test in CVF and CVC. In addition, PWS/AS-ICR, GNASXL, and MEST, but not GNAS1A and ZAC/PLAGL1, are steadily hemimethylated in CV from healthy pregnancies, independently from culture. Thus, prenatal investigation of genomic imprinting in CV needs to be validated in a locus-specific manner.     

Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination

We have previously shown that the suppressive function of regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) is enhanced in patients with prostate cancer when compared with healthy individuals. Two phase II studies using the PSA-TRICOM vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC) showed evidence of patient benefit in terms of enhanced survival. The Halabi nomogram has been used to predict survival (HPS) of patients with mCRPC treated with conventional chemotherapy or second-line hormonal therapy. Tregs from PBMCs of patients (n = 23) with mCRPC were obtained pre- and post-three monthly vaccinations, and analyzed for number, phenotype, and suppressive function. Changes post- versus pre-vaccination in these parameters were compared with 3-year survival and HPS. No differences in Treg numbers were observed post- versus pre-vaccination. Trends (P = 0.029) were observed between overall survival (OS) and a decrease in Treg suppressive function post- versus pre-vaccination. Trends were also observed in analyzing effector:Treg (CD4⁺CD25⁺CD127⁻FoxP3⁺CTLA4⁺) ratio post- versus pre-vaccination with OS versus HPS. These data provide preliminary evidence for a possible association between improved OS and a decrease in Treg function when PBMCs are analyzed after three monthly vaccinations. Patients with an OS > HPS were more likely to have decreased Treg function following vaccine. Larger studies to confirm and extend these findings are warranted.