Rates of readmission and death associated with leaving hospital against medical advice: a population-based study

Background:

Leaving hospital against medical advice may have adverse consequences. Previous studies have been limited by evaluating specific types of patients, small sample sizes and incomplete determination of outcomes. We hypothesized that leaving hospital against medical advice would be associated with increases in subsequent readmission and death.

Methods:

In a population-based analysis involving all adults admitted to hospital and discharged alive in Manitoba from Apr. 1, 1990, to Feb. 28, 2009, we evaluated all-cause 90-day mortality and 30-day hospital readmission. We used multivariable regression, adjusted for age, sex, socioeconomic status, year of hospital admission, patient comorbidities, hospital diagnosis, past frequency of admission to hospital, having previously left hospital against medical advice and data clustering (patients with multiple admissions). For readmission, we assessed both between-person and within-person effects of leaving hospital against medical advice.

Results:

Leaving against medical advice occurred in 21 417 of 1 916 104 index hospital admissions (1.1%), and was associated with higher adjusted rates of 90-day mortality (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.18–2.89), and 30-day hospital readmission (within-person OR 2.10, CI 1.99–2.21; between-person OR 3.04, CI 2.79–3.30). In our additional analyses, elevated rates of readmission and death associated with leaving against medical advice were manifest within 1 week and persisted for at least 180 days after discharge.

Interpretation:

Adults who left the hospital against medical advice had higher rates of hospital readmission and death. The persistence of these effects suggests that they are not solely a result of incomplete treatment of acute illness. Interventions aimed at reducing these effects may need to include longitudinal interventions extending beyond admission to hospital.Patients leaving hospital against medical advice have been discussed in the medical literature for more than 50 years.¹ Reported to occur in 1%–2% of patients in general hospitals,^2,3 the numbers are large; in the United States, 368 000 patients left against medical advice in 2007,³ and rates higher than 10% have been documented in certain subgroups, including Canadian patients with HIV and predominantly poor residents of inner city areas.^4,5 The main concern over leaving hospital against medical advice is that it may increase morbidity or mortality. Previous studies attempting to assess this effect^2,4–13 have all been restricted to specific types of patients, and most studies were limited by small sample sizes and incomplete determination of outcomes. In this study, we used data that avoided these limitations to test the hypothesis that patients who leave hospital against medical advice have higher rates of hospital readmission and death.     

Cranial morphology of an Early Cretaceous Monjurosuchid (Reptilia: Diapsida) from Liaoning Province of China and evolution of the choristoderan palate

A new specimen of Philydrosaurus proseilus from the Early Cretaceous Chiufotang (Jiufotang) Formation preserves the first complete palate of a monjurosuchid choristodere. As in other choristoderes, the palate of Philydrosaurus is akinetic, extended by a broad contact between the vomer and maxilla, and equipped with multiple batteries of palatal teeth. This specimen provides phylogenetically significant information and clarifies the distribution of many apomorphies within Choristodera. Philydrosaurus is primitive relative to the Neochoristodera in that it exhibits only a moderate degree of posterior displacement of the choanae and retains a relatively large interpterygoid vacuity. However, Philydrosaurus also exhibits several derived features previously considered diagnostic of the Neochoristodera, including establishment of a long midline contact of the pterygoids and development of a distinct nasopalatal trough extending from the choana. The choristodere palate exhibits significant modification of the primitive diapsid condition, including elongation of the vomers, establishment of a vomer–maxilla contact, posterior displacement of the choanae, development of the nasopalatal trough, and reduction of the interpterygoid vacuity.     

Kairomonal Responses of Natural Enemies and Associates of the Southern Ips (Coleoptera: Curculionidae: Scolytinae) to Ipsdienol, Ipsenol and Cis-Verbenol

Bark beetle infested pines are an ephemeral habitat utilized by a diverse assemblage of insects. Although many bark beetle insect associates have little or no measurable impact on bark beetle brood production, some reduce brood production by either competing with brood for the limited phloem tissue or by feeding on brood. Several studies have observed synchrony between the colonization of hosts by bark beetles and the arrival of insect associates. Some insect associates mediate synchrony with bark beetle mass attacks with kairomonal responses to bark beetle aggregation pheromones. The objectives of this study were to document the community of Coleoptera associated with the southern Ips (Ips avulsus, Ips calligraphus and Ips grandicollis) and to test the hypothesis that synchrony of insect associates with the southern Ips is mediated by kairomonal responses to aggregation pheromones. A large community of Coleoptera (109 species) was recorded from traps baited with southern Ips pheromones. A significant treatment effect was observed for the guilds of meristem feeders, natural enemies and woodborers. The southern Ips pheromone ipsenol was broadly attractive to meristem feeders, natural enemies and woodborers and in general blends were more attractive than individual compounds. These results demonstrate that a diverse community of Coleoptera is associated with the southern Ips and that several members of this community facilitate synchrony with kairomonal responses to southern Ips aggregation pheromones.     

Two-Dimensional 1H NMR Study of a Tetradecapeptide with the Consensus Sequence Arg5-Asp-Val-Arg-Gly9: Structural Effects of the Outside Substitution Ser12 by Ala12

Abstract

Conformation of a tetradecapeptide with a RXVRG consensus sequence, Arg^s-Asp-Val-Arg-Gly⁹, found in several precursors of antibacterian peptides, was investigated in dimethylsulfoxide solution by proton NMR spectroscopy. Complete resonance assignments and conformational parameters were obtained through correlated (COSY) and nuclear Overhauser (NOESY) techniques. The ³J(αH, βH) coupling constants and the intramolecular NOE, NH…βH, were used to analyse the conformers around the Cα-Cβ bond and, in four cases, to obtain stereospecific assignments.

Use of restraints derived from NOE connectivities and ³J(NH, αH) coupling constants allows the determination of a range of φ and ψ dihedral angles for all the residues in the sequence. The present NMR results provide favourable evidence for the formation of two bends in the consensus sequence of the tetradecapeptide. The first one has most of the features of a Glu⁴- Val⁷ β–turn (low temperature coefficient of the Val⁷NH chemical shift, Arg⁵αH…Val⁷NH and Asp⁶NH.-.Val⁷NH NOE correlations). The second one exhibits only the Asp⁶αH…Arg⁷NH and Val⁷NH…Arg⁸NH NOE interactions. These consensus sequence organizations proposed were confirmed by molecular modeling based on low potential energy structure on the [4–9] fragment with high agreement of NOE data.

Overall, the substitution of Ser¹² by Ala¹² shifts the conformation of the hydrophobic moiety [10–14] towards a quite random coil structure in this fragment and strongly destabilizes the folded structures of the consensus domain where only one NH (Val⁷) is solvent-shielded opposed to three (Asp⁶ to Arg⁸) in the [Ser¹²] tetradecapeptide. These conformational changes could be related to the processing enzyme activities on these model oligopeptides.     

Novel insights into the dynamics behavior of glucagon-like peptide-1 receptor with its small molecule agonists

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of therapeutics industries for the treatment of various metabolic diseases like type 2 diabetes and obesity. The structural–functional relationships of small molecule agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R. In this study, we explored the dynamics, intrinsic stability, and binding mechanisms of these molecules through computational modeling, docking, molecular dynamics (MD) simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) binding free energy estimation. Molecular docking study depicted that hydrophobic interaction (pi–pi stacking) plays a crucial role in maintaining the stability of the complex, which was also supported by intermolecular analysis from MD simulation study. Principal component analysis suggested that the terminal ends along with the turns/loops connecting adjacent helix and strands exhibit a comparatively higher movement of main chain atoms in most of the complexes. MM/PBSA binding free energy study revealed that non-polar solvation (van der Waals and electrostatic) energy subsidizes significantly to the total binding energy, and the polar solvation energy opposes the binding agonists to GLP-1R. Overall, we provide structural features information about GLP-1R complexes that would be conducive for the discovery of new GLP-1R agonists in the future for the treatment of various metabolic diseases.

Communicated by Ramaswamy H. Sarma     

Synthesis and FTIR Conformational Studies of Peptides From the Basic Region of c-Jun: a Critical Analysis on the Basis of CD and NMR Data

Abstract

The peptide (35 residues) corresponding to the basic subdomain (bSD) of c-Jun (residues 252–281) and its fragments NP (N-terminal peptide, 1–19) and CP (C-terminal peptide, 1635) were synthesized in stepwise solid-phase using the tert-butyloxycarbonyl/benzyl strategy. In a previous paper, we have shown that during its binding to the DNA site CRE (cAMP- responsive element) the bSD structure was converted into α-helix from an initial random coil conformation [Krebs, D., Dahmani, B., El Antri, S., Monnot, M., Convert, O., Mauffret, O., Troalen, F. & Fermandjian, S. Eur. J. Biochem. 231, 370–380 (1995)]. Our results suggested both a high flexibility and a helical potential in bSD, these two properties seeming crucial for the accommodation of the basic subdomain of c-Jun to its specific DNA targets. In this work, we assessed the conformational variability of bSD through the study of the secondary structures of its NP and CP fragments in trifluoroethanol (TFE)/²H₂O mixtures, using Fourier transform infrared (FTIR) spectroscopy. The IR results were critically analyzed in light of our previously reported circular dichroism (CD) and NMR data [Krebs, D., Dahmani, B., Monnot, M., Mauffret, O., Troalen, F. & Fermandjian, S. Eur. J. Biochem. 235, 699–712 (1996)]. Upon addition of TFE, the relative areas of the seven components of the amide I band (1700–1620 cm^?1) reflected the conversion of a large amount of random coil conformation into α-helix for the two fragments and bSD. This effect was accompanied by more subtle variations of the less populated structures, in agreement with the results of CD and NMR experiments. The IR results stipulated the conservation of the parent bSD secondary structures in both fragments; however, NP and CP peptides did not display similar random-to-α-helix stabilization pattern upon additions of TFE to aqueous solutions. The profile from CD signal at 222 nm was found sigmoidal for NP and almost linear for CP, while that corresponding to the parent peptide bSD was just in between those of its fragments. Thus, the present study confirms the high flexibility and helix propensity of the c-Jun basic subdomain and suggests that the N- and C-terminal parts of the peptide do not follow the same random-to-helix conversion profile during their complexation with DNA.     

Base Pairing at the Stem-loop Junction in the SL1 Kissing Complex of HIV-1 RNA: A Thermodynamic Study Probed by Molecular Dynamics Simulation

Abstract

The thermodynamics of the opening/closure process of a GC base pair located at the stem-loop junction of the SL1 sequence from HIV-1_Lai genomic RNA was investigated in the context of a loop-loop homodimer (or kissing complex) using molecular dynamics simulation. The free energy, enthalpy and entropy changes for the closing reaction are 0 kcal·mol^?1, ?11 kcal·mol^?1and ?0.037 kcal·mol^?1-K^?1 at 300° K respectively. Furthermore it is found that the free energy change is the same for the formation of a 11 nucleotide loop closed with UG and for the formation of a 9 nucleotide loop closed with GC. Our study evidences the high flexibility of the nucleotides at the stem-loop junction explaining the weak stability of this structure.     

Intensity Changes of Base and Backbone Raman Modes in the B to Z Transition of poly(dG-dm5C)

Abstract

Raman spectroscopy was employed to investigate the temperature-induced B to Z transition of poly(dG-dm-⁵C). The transition midpoint was about 37°C for a solvent containing 20 mM Mg²⁺. A 10-fold change in Mg²⁺ concentration altered the transition midpoint by at least 60°C. Raman spectra of the B and Z forms of poly(dG-dm⁵C) exhibited characteristics similar to those observed with poly(dG-dC). The 682 cm^?1 guanine mode and 835 cm^?1 backbone mode were present in the B conformation. In the Z form the intensities of these two bands decrease substantially and new peaks were observed at 621 cm^?1, 805 and 819 cm¹. Several bands unique to poly(dG-dm⁵C) were also observed. Transition profiles of band intensity vs. temperature were determined for fourteen Raman bands. The curves of all of the base vibrations and one backbone mode had the same slope and midpoint. This indicates that conformational changes in the guanine and methycytosine bases occur concurrently.