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.     

Strength, drag, and dislodgment of two competing intertidal algae from two wave exposures and four seasons

Intertidal macroalgae often experience greater risk of dislodgment with increasing size because of underscaling of breaking force of their stipes relative to drag on their thalli. This ratio (breaking force/drag) indicates safety from breakage at a given flow speed, with values greater than one indicating safety from breakage and values lower than one indicating danger of breakage. We examined this force ratio for the largest thalli of two species of co-dominant, red algae, Chondrus crispus Stackhouse and Mastocarpus stellatus Stack. In With. (Guiry), in four seasons at two wave exposures. During fall and winter, the largest thalli in both populations were dislodged resulting in a decrease in mass of the largest thalli found. This decrease was greater for Chondrus than for Mastocarpus, but their mass-specific force ratios (at 0.55 m s⁻¹) were equal indicating similar size-specific risk of dislodgment. The equality of force ratios was underlain by two similarities: (1) breaking force was independent of mass and not different between species; (2) mass-specific drag was not different between species. These similarities were underlain by dissimilar causes: (i) similarity in breaking force (the product of cross-sectional area and material strength) occurred because greater material strength of Mastocarpus compensated for greater mass-specific cross-sectional area of Chondrus; (ii) similarity in mass-specific drag (a function of planform area and the coefficient of drag) occurred because greater drag coefficients for Mastocarpus compensated for greater mass-specific planform areas of Chondrus. The similarity in force ratio, if it held at season- and site-relevant flow speeds, would suggest that during seasons of minimal growth and high wave exposure, the mass of the largest thalli of both species should be the same. Chondrus, however, had a greater mass at both sites in all seasons. Chondrus experienced greater decreases in mass probably because it grew larger and larger thalli are less safe. Extrapolation of a site-relevant force ratio for Chondrus in the fall revealed (1) that the site-relevant force ratio did not differ between exposures even though the mass-specific force ratio was greater at the protected site, and (2) a paradoxical result that all Chondrus thalli studied ought to have dislodged, but had not. This paradox may be resolved by consideration of the protection conferred by canopies of Chondrus: a canopy may effectively raise its site-relevant force ratio. Perhaps differences in protection conferred by different canopies explain why larger Chondrus persist with Mastocarpus even given a similarity in mass-specific force ratio.     

A Flexible Docking Scheme Efficiently Captures the Energetics of Glycan-Cyanovirin Binding

Cyanovirin-N (CVN), a cyanobacterial lectin, exemplifies a class of antiviral agents that inhibit HIV by binding to the highly glycosylated envelope protein gp120. Here, we investigate the energetics of glycan recognition using a computationally inexpensive flexible docking approach, backbone perturbation docking (BP-Dock). We benchmarked our method using two mutants of CVN: P51G-m4-CVN, which binds dimannose with high affinity through domain B, and CVN^(mutDB), in which binding to domain B has been abolished through mutation of five polar residues to small nonpolar side chains. We investigated the energetic contribution of these polar residues along with the additional position 53 by docking dimannose to single-point CVN mutant models. Analysis of the docking simulations indicated that the E41A/G and T57A mutations led to a significant decrease in binding energy scores due to rearrangements of the hydrogen-bond network that reverberated throughout the binding cavity. N42A decreased the binding score to a level comparable to that of CVN^(mutDB) by affecting the integrity of the local protein structure. In contrast, N53S resulted in a high binding energy score, similar to P51G-m4-CVN. Experimental characterization of the five mutants by NMR spectroscopy confirmed the binding affinity pattern predicted by BP-Dock. Despite their mostly conserved fold and stability, E41A, E41G, and T57A displayed dissociation constants in the millimolar range. N53S showed a binding constant in the low micromolar range, similar to that observed for P51G-m4-CVN. No binding was observed for N42A. Our results show that BP-Dock is a useful tool for rapidly screening the relative binding affinity pattern of in silico-designed mutants compared with wild-type, supporting its use to design novel mutants with enhanced binding properties.     

Hsp90‐mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling

Stress granules (SGs) are dynamic condensates associated with protein misfolding diseases. They sequester stalled mRNAs and signaling factors, such as the mTORC1 subunit raptor, suggesting that SGs coordinate cell growth during and after stress. However, the molecular mechanisms linking SG dynamics and signaling remain undefined. We report that the chaperone Hsp90 is required for SG dissolution. Hsp90 binds and stabilizes the dual‐specificity tyrosine‐phosphorylation‐regulated kinase 3 (DYRK3) in the cytosol. Upon Hsp90 inhibition, DYRK3 dissociates from Hsp90 and becomes inactive. Inactive DYRK3 is subjected to two different fates: it either partitions into SGs, where it is protected from irreversible aggregation, or it is degraded. In the presence of Hsp90, DYRK3 is active and promotes SG disassembly, restoring mTORC1 signaling and translation. Thus, Hsp90 links stress adaptation and cell growth by regulating the activity of a key kinase involved in condensate disassembly and translation restoration.     

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.     

Factor Structure of the Eating Disorder Examination Interview in Patients With Binge‐eating Disorder

Despite the widespread use of the Eating Disorder Examination (EDE) as a primary assessment instrument in studies of eating and weight disorders, little is known about the psychometric aspects of this interview measure. The primary purpose of this study was to evaluate the factor structure of the EDE interview in a large series of patients with binge‐eating disorder (BED). Participants were 688 treatment‐seeking patients with BED who were reliably administered the EDE interview by trained research clinicians at three research centers. Exploratory factor analysis (EFA) performed on EDE interview data from a random split‐half of the study group suggested a brief 7‐item 3‐factor structure. Confirmatory factor analysis (CFA) performed on the second randomly selected half of the study group supported this brief 3‐factor structure of the EDE interview. The three factors were interpreted as Dietary Restraint, Shape/Weight Overvaluation, and Body Dissatisfaction. In this series of patients with BED, factor analysis of the EDE interview did not replicate the original subscales but revealed an alternative factor structure. Future research must further evaluate the psychometric properties, including the factor structure, of the EDE interview in this and other eating‐disordered groups. The implications of these factor analytic findings for understanding and assessing the specific psychopathology of patients with BED are discussed.     

Overall and allele-specific expression of the SMC1A gene in female Cornelia de Lange syndrome patients and healthy controls

Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, limb anomalies, and growth and cognitive deficits. Mutations in genes encoding subunits (SMC1A, SMC3, RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex account for approximately 65% of clinically diagnosed CdLS cases. The SMC1A gene (Xp11.22), responsible for 5% of CdLS cases, partially escapes X chromosome inactivation in humans and the allele on the inactive X chromosome is variably expressed. In this study, we evaluated overall and allele-specific SMC1A expression. Real-time PCR analysis conducted on 17 controls showed that SMC1A expression in females is 50% higher than in males. Immunoblotting experiments confirmed a 44% higher protein level in healthy females than in males, and showed no significant differences in SMC1A protein levels between controls and patients. Pyrosequencing was used to assess the reciprocal level of allelic expression in six female carriers of different SMC1A mutations and 15 controls who were heterozygous at a polymorphic transcribed SMC1A locus. The two alleles were expressed at a 1:1 ratio in the control group and at a 2:1 ratio in favor of the wild type allele in the test group. Since a dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. An extension of this study to a larger cohort containing mild to borderline cases could enhance our understanding of the clinical spectrum of SMC1A-linked CdLS.