A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery.

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87-4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. STATEMENT OF SIGNIFICANCE: A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87-4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.

A polyethylene glycol-grafted pullulan polysaccharide adhesive improves drug loading capacity and release efficiency.

In this study, polyethylene glycol was grafted onto pullulan polysaccharides, resulting in the development of a novel adhesive termed PLUPE, offering superior drug loading capacity and rapid release efficiency. The efficacy of PLUPE was rigorously evaluated through various tests, including the tack test, shear strength test, 180° peel strength test, and human skin adhesion test. The results demonstrated that PLUPE exhibited a static shear strength that was 4.6 to 9.3 times higher than conventional PSAs, ensuring secure adhesion for over 3 days on human skin. A comprehensive analysis, encompassing electrical potential evaluation, calculation of interaction parameters, and FT-IR spectra, elucidated why improved the miscibility between the drug and PSAs, that the significant enhancement of intermolecular hydrogen bonding in the PLUPE structure. ATR-FTIR, rheological, and thermodynamic analyses further revealed that the hydrogen bonding network in PLUPE primarily interacted with polar groups in the skin. This interaction augmented the fluidity and free volume of PSA molecules, thereby promoting efficient drug release. The results confirmed the safety profile of PLUPE through skin irritation tests and MTT assays, bolstering its viability for application in TDDS patches. In conclusion, PLUPE represented a groundbreaking adhesive solution for TDDS patches, successfully overcoming longstanding challenges associated with PSAs.

Rhamnose-PEG-induced supramolecular helices: Addressing challenges of drug solubility and release efficiency in transdermal patch.

Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87-4098 and Duro-Tak@ 87-2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems.

A Rhamnose-PEG-Modified Dendritic Polymer for Long-Term Efficient Transdermal Drug Delivery.

This study introduces a dendronized pressure-sensitive adhesive, TMPE@Rha, addressing Food and Drug Administration (FDA) concerns about traditional pressure-sensitive adhesives (PSAs) in transdermal drug delivery systems. The unique formulation, composed of rhamnose, trihydroxypropane, and poly(ethylene glycol), significantly enhances cohesion and tissue adhesion. Leveraging rhamnose improves intermolecular interactions and surface chain mobility, boosting tissue adhesion. Compared to acrylic pressure-sensitive adhesive 87-DT-4098, TMPE@Rha shows substantial advantages, with up to 5 to 6 times higher peel strength on porcine and wood substrates. Importantly, it maintains strong human skin adhesion beyond 7 days without the typical "dark ring" phenomenon. When loaded with diclofenac, the adhesive exhibits 3.12 times greater peeling strength than commercial alternatives, sustaining human adhesion for up to 6 days. Rigorous analyses confirm rhamnose's role in increasing interaction strength. In vitro studies and microscopy demonstrate the polymer's ability to enhance drug loading and distribution on the skin, improving permeability. Biocompatibility tests affirm TMPE@Rha as nonirritating. In summary, TMPE@Rha establishes a new standard for PSAs in transdermal drug delivery systems, offering exceptional adhesion, robustness, and biocompatibility. This pioneering work provides a blueprint for next-generation, highly adhesive, drug-loaded PSAs that meet and exceed FDA criteria.

Design of a tulobuterol patch with improved mechanical properties: effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesives.

The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe3+). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC0-t and Cmax of the optimized patch were 1045 ± 89 ng/mL·h and 106.8 ± 28.5 ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications.

Probing the mechanism of release process from metal coordination-based acrylic pressure-sensitive adhesives: Synergistic effect of coordination and hydrogen bonding for controlled drug release.

Hydrogen bonding, ionic interactions, and dipole-dipole interactions have been extensively studied to control drug release from patches. However, metal coordination bonding has not been fully explored for the control of transdermal drug release. In this study, metal coordination-based acrylic pressure-sensitive adhesives (PSAs) were designed and synthesized in order to systemically elucidate the effect of metal coordination on drug release from acrylic PSAs. Ketoprofen (KET) and donepezil (DNP) were selected as model drugs. Results showed that the burst release rate of KET was controlled by N-[tris(hydroxymethyl)methyl]acrylamide (NAT) and Fe3+, while the DNP release rate had no significant changes. It was found that the PSA-drug interaction, rather than the molecular mobility of PSA, played a dominant role in the controlled release process of KET. The hydrogen bond interaction between NAT and KET controlled the release process, while the coordination bond interaction between Fe3+ and KET further slowed down the release of KET. In conclusion, it was found that the controlled release of KET was achieved by the synergistic effect of coordination bonding and hydrogen bonding, which opens up a facile but powerful avenue for the design of brand-new controlled release systems and new opportunities for their application in transdermal drug delivery.

Development and validation of a model for the prediction of disease-specific survival in patients with oral squamous cell carcinoma: based on random survival forest analysis.

OBJECTIVE: To establish a model for predicting the disease-specific survival (DSS) of patients with oral squamous cell carcinoma (OSCC). METHODS: Patients diagnosed with OSCC from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled and randomly divided into development (n = 14,495) and internal validation cohort (n = 9625). Additionally, a cohort from a hospital located in Southeastern China was utilized for external validation (n = 582). RESULTS: TNM stage, adjuvant treatment, surgery, tumor sites, age, grade, and gender were used for RSF model construction based on the development cohort. The effectiveness of the model was confirmed through time-dependent ROC curves in different cohorts. The risk score exhibited an almost exponential increase in the hazard ratio of death due to OSCC. In development, internal, and external validation cohorts, the prognosis was significantly worse for patients in groups with higher risk scores (all log-rank P < 0.05). CONCLUSION: Based on RSF, a high-performance prediction model for OSCC prognosis was created and verified in this study.

Prognostic value of pretreatment lymphocyte percentage in oral cancer: A prospective cohort study.

OBJECTIVE: To assess the prognostic role of pretreatment lymphocyte percentage (LY%) for patients with oral squamous cell carcinoma (OSCC). METHODS: A large-scale prospective cohort study between July 2002 and March 2021 was conducted. Propensity score-matched (PSM) analysis and inverse probability of treatment weighting (IPTW) analysis were performed to adjust for potential confounders. Using random survival forest (RSF), the relative importance of pretreatment LY% in prognosis prediction was also assessed. RESULTS: A total of 743 patients were enrolled and followed up (median: 2.75 years, interquartile range: 1.25-4.42 years). A high pretreatment LY% was significantly associated with better disease-specific survival of patients with OSCC (Hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.42, 0.84). The same tendency was observed in PSM (HR = 0.57, 95% CI: 0.38, 0.85) and IPTW analysis (HR = 0.57, 95% CI: 0.40, 0.82). RSF showed that LY% ranked the fifth among importance ranking of all prognostic factors. CONCLUSION: Pretreatment LY% showed a moderate predictive ability, suggesting it might be a valuable tool to predict prognosis for patients with OSCC.

A skin pharmacokinetics study of permeation enhancers: The root cause of dynamic enhancement effect on in vivo drug permeation.

Skin pharmacokinetics (SPK) of permeation enhancers can answer the question of why enhancement effects different at the kinetic level. Herein, SPK of permeation enhancers were classified into two categories, namely, lateral elimination (elimination to surrounding stratum corneum (SC)) and longitudinal elimination (elimination to deep epidermal (EP)). They were evaluated with a specific parameter for permeation enhancers, diffusion ratio (DRSC-EP), according to results of tissue-distribution test, molecular dynamic (MD) simulation, and confocal laser scanning microscopy (CLSM). The linear relationship between ke-enahcer and Δ Cmax-drug (R2 = 0.92), MRTenhancer and Δ Tmax-drug (R2 = 0.97), AUCt-enhancer and Δ AUCt-drug (R2 = 0.90) suggesting that SPK of permeation enhancers precisely controlled dynamic process of drug permeation in vivo. The molecular mechanisms of the dynamic effect of SPK process on drug transdermal behaviors were characterized by modulated-temperature differential scanning calorimetry (MTDSC), dielectric spectroscopy, small-angle X-ray scattering (SAXS), solid-state NMR. Permeation enhancers with high molecular weight (M.W.) and high polar surface area (P.S.A.) had good compatibility and strong interaction strength with SC, leading their lateral-elimination behavior, causing their low DRSC-EP and resulting in low ke-enhancer, long MRTenhancer, and large AUCt-enhancer. Consequently, skin barrier can be rapidly opened fast and to a great extent. In summary, compared with SPK of permeation enhancers with longitudinal elimination, SPK of permeation enhancers with lateral elimination can enable more sustainable and greater drug permeation. The information about SPK of permeation enhancers offered a criterion to estimate its permeation-enhancement effect on the drug and its subsequent application in transdermal formulations.

Unique ghost surface phonon polaritons in biaxially hyperbolic materials.

We predicted peculiar ghost surface phonon polaritons in biaxially hyperbolic materials, where the two hyperbolic principal axes lie in the plane of propagation. We took the biaxially-hyperbolic α-MoO3 as one example of the materials to numerically simulate the ghost surface phonon polaritons. We found three unique ghost surface polaritons to appear in three enclosed wavenumber-frequency regions, respectively. These ghost surface phonon polaritons have different features from the surface phonon polaritons found previously, i.e., they are some hybrid-polarization surface waves composed of two coherent evanescent branch-waves in the α-MoO3 crystal. The interference of branch-waves leads to that their Poynting vector and electromagnetic fields both exhibit the oscillation-attenuation behavior along the surface normal, or a series of rapidly attenuated fringes. We found that the in-plane hyperbolic anisotropy and low-symmetric geometry of surface are the two necessary conditions for the existence of these ghost surface polaritons.

Spin angular momentum and nonreciprocity of ghost surface polariton in antiferromagnets.

We investigated the spin angular momentum (SAM) and nonreciprocity of ghost surface polariton (GSP) at the surface of an antiferromagnet (AF) in the normal geometry, where the AF easy axis and external field (H0) both are normal to the AF surface. We found that the dispersion equation is invariant when the inversions of wavevector and external magnetic field, k→-k and H0→-H0, are taken. However, its polarization and SAM are nonreciprocal. The SAM is vertical to the propagation direction of GSP, and consists of two components. We analytically found that the in-plane component is locked to H0, or it is changed in sign due to the inversion of H0. The out-plane one is locked to k since it is changed in sign as the inversion of k is taken. Either component contains an electric part and a magnetic part. Above the AF surface, the two electric parts form the left-handed triplet with the wavevector k, but the two magnetic parts form the right-handed triplet with k. In the AF, the chirality of the SAM changes with the distance from the surface. The SAM is very large on or near the surface and it may be very interesting for the manipulation of micron and nano particles on the AF surface. These are obviously different from the relevant features of conventional surface polaritons. The SAM also is field-tunable.

Transdermal Enhancement Strategy of Lappaconitine: Alteration of Keratin Configuration by Counter-Ion.

The objective of this study was to develop a lappaconitine (LA) transdermal patch with counter-ion to increase the transdermal permeability of the drug, and a theory of counter-ion altering the conformation of the skin keratin was put forward based on the in vitro skin permeation study and physicochemical properties of ion-pairs. Formulation factors including pressure sensitive adhesives (PSAs), drug-loading, counter-ions and molar ratios of counter-ion were screened by in vitro skin permeation study. The optimized formulation was composed of 7% LA, 1.5 mole cinnamic acid and AAOH (PSA containing hydroxyl group synthesized by our laboratory) as an adhesive matrix. The optimized patch was evaluated by the pharmacokinetic and analgesic pharmacodynamic studies. AUC0-t and pain inhibition ratio of the optimized patch were 2450.40 ± 848.52 h ng/mL and 81.18%, which showed good absorption into the skin and excellent analgesic effect. The mechanism of facilitated transdermal drug permeation by counter-ion was investigated by ATR-FTIR, thermal analysis, FTIR, XPS and molecular docking. The results indicated that after the formation of ion-pairs, the excess counter-ions would alter the conformation of the skin keratin, thus increasing the transdermal penetration of LA. In conclusion, the LA patch was successfully optimized, and the effect of counter-ions on the skin was clarified at the molecular level. These findings provided additional references for the application of counter-ion in the transdermal drug delivery system.

Effect of the combination of permeation enhancer and ion-pairs strategies on transdermal delivery of tofacitinib.

The aim of the present study was to develop a tofacitinib (TOF) transdermal patch by the combination of ion-pairs and chemical permeation enhancer strategies. And a theory of controlled release of chemical permeation enhancers by counterion was proposed on the basis of in vitro skin permeation and skin retention study. Through the in vitro skin permeation study, the formulation factors such as counterion, pressure sensitive adhesive (PSA), drug loading and patch thickness were investigated, and the optimized patch (6.5% LA-TOF, 15% POCC and thickness = 50 µm) was evaluated by the pharmacokinetic study. The AUC0-t of the optimized patch was 529.89 ± 45 h ng/mL. Special attention has been paid to the molecular mechanism of the effects of counterion concentration on the release and permeation enhancement effect of penetration enhancer. FTIR study, 13C NMR, XPS and molecular modeling were conducted to investigate the molecular interaction between POCC and LA. Raman Imaging and ATR-FTIR were used to explore the POCC content in the skin and the interference degree to lipid. The results revealed that a strong hydrogen bond appeared between LA and the hydroxyl group of POCC, which inhibited the release of POCC, thus reducing the lipid disturbance and permeation enhancement effect of POCC. In conclusion, this TOF patch was successfully developed. The effect of counterion on permeation enhancers was clarified at molecular level, and these results provided references for the development of TOF patch.

Sustainable and efficient skin absorption behaviour of transdermal drug: The effect of the release kinetics of permeation enhancer.

At present, how the release kinetics of permeation enhancers affected their enhancement efficacy on drug skin absorption and its molecular mechanisms remained unclear. Herein, the release kinetics of permeation enhancer (Plurol Oleique CC (POCC)) which involved release percent (PR), release duration (RD) and release kinetic constant (k) and its enhancement efficacy on drug skin absorption were investigated with in vitro skin retention study and in vitro skin permeation study, respectively. POCC released from the acidic-drug loading patches followed with the Higuchi release model and had short RD (8-16 h), resulting in its unsustainable enhancement efficiency for acidic drugs. However, POCC released from the basic-drug loading patches followed with zero-order model with long RD (12-24 h), inducing a sustainable and efficient enhancement efficiency for basic drugs. The lower variance of an innovative parameter permeation enhancement coefficient (CPE) represented the relatively sustainable and effective enhancement effect and was listed as followed: 0.20 (Zaltoprofen (ZPF)), 0.31 (Diclofenac (DCF)), 0.27 (Indomethacin (IMC)), 0.07 (Azasetron (AST)), 0.11 (Oxybutynin (OBN)) and 0.06 (Donepezil (DNP)). According to the results of FT-IR, MTDSC, 13C NMR spectra, molecular dynamics simulation, SAXS and Raman imaging, the Higuchi release model was caused by strong interaction between the acid drugs and pressure sensitive adhesive (PSA). This strong interaction induced faster diffusion speed of POCC from acidic-drug loading patches and make the swell degree of long periodicity phase (LPP) of stratum corneum (SC) lipids reached plateau early. The zero-order release model was because the weak interaction between basic drugs and PSA making most of POCC was still bound to PSA, which in turn lead to LPP swelled at a slow but sustainable process. In conclusion, zero-order release kinetic of POCC lead to sustainable and efficient penetration enhancement efficiency on basic drug, while the Higuchi release kinetic showed opposite effect for acidic drugs. A deep understanding of release kinetics of enhancer and its enhancement efficiency may drive the ideal selection of permeation enhancers and rational optimization of transdermal patches.

Large spatial shifts of reflective beam at the surface of graphene/hBN metamaterials.

We theoretically studied the Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts of reflective beam at the surface of graphene/hBN metamaterials. The results show that the GH-shift is significantly enhanced and also possesses the large reflectivity when the light beam is incident at the critical angle near the Brewster angle. We found that the IF-shift is the largest when the reflective beam is a special polarized-beam or the reflective coefficients satisfy the conditions |rs | = |rp | and φs - φp = 2jπ (j is an integer). By changing the chemical potential, filling ratio and tilted angle, the position and width of frequency windows obtaining the maximum values of shifts can be effectively adjusted. The large and tunable GH- and IF-shifts with the higher reflectivity provide an alternative scheme to develop new nano-optical devices.

Cisplatin-crosslinked glutathione-sensitive micelles loaded with doxorubicin for combination and targeted therapy of tumors.

The delivery of combination chemotherapy by nanoscale platforms has been demonstrated to enhance cancer treatment in the clinic. Cisplatin (CDDP)-crosslinked, glutathione-sensitive, tumor-targeting micelles based on carboxymethyl chitosan were designed for synergistic cisplatin-doxorubicin (DOX) combination chemotherapy. In our study, DOX was conjugated to carboxymethyl chitosan through a disulfide bond, which was structurally characterized by 1H NMR. The micelles formed by self-assembly were spherical, with the mean diameter of 274nm. The in vitro release studies revealed that the micelles were highly glutathione-sensitive. Cytotoxicity analysis demonstrated that the cisplatin-crosslinked micelles loaded with DOX exhibited enhanced therapeutic efficacy compared with the DOX-loaded nanoparticles, free DOX, and free CDDP. Cellular uptake and intracellular release revealed that the cisplatin-crosslinked micelles loaded with DOX could efficiently deliver and release DOX into the cancer cells. These results clearly indicate that tumor-targeting and glutathione-sensitive micelles provide means for combination drug delivery in cancer treatment.

Glutathione-dependent micelles based on carboxymethyl chitosan for delivery of doxorubicin.

Novel glutathione (GSH)-dependent micelles based on carboxymethyl chitosan (CMCS) were developed for triggered intracellular release of doxorubicin (DOX). DOX-33'-Dithiobis (N-hydroxysuccinimidyl propionate)-CMCS (DOX-DSP-CMCS) prodrugs were synthesized. DOX was attached to the amino group on CMCS via disulfide bonds and drug-loaded micelles were formed by self-assembly. The micelles formed core-shell structure with CMCS and DOX as the shell and core, respectively, in aqueous media. The structure of the prodrugs was confirmed by IR and proton nuclear magnetic resonance (1H NMR) spectroscopy. The drug-loading capacity determined by UV spectrophotometry was 4.96% and the critical micelle concentration of polymer prodrugs determined by pyrene fluorescence was 0.089 mg/mL. Micelles were spherical and the mean size of the nanoparticles was 174 nm, with a narrow polydispersity index of 0.106. Moreover, in vitro drug release experiments showed that the micelles were highly GSH-sensitive owing to the reductively degradable disulfide bonds. Cell counting kit (CCK-8) assays revealed that DOX-DSP-CMCS micelles exhibited effective cytotoxicity against HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) demonstrated that DOX-DSP-CMCS micelles could efficiently deliver and release DOX in the cancer cells. In conclusion, the DOX-DSP-CMCS nanosystem is a promising drug delivery vehicle for cancer therapy.

Length of Hospital Stay Prediction at the Admission Stage for Cardiology Patients Using Artificial Neural Network.

For hospitals' admission management, the ability to predict length of stay (LOS) as early as in the preadmission stage might be helpful to monitor the quality of inpatient care. This study is to develop artificial neural network (ANN) models to predict LOS for inpatients with one of the three primary diagnoses: coronary atherosclerosis (CAS), heart failure (HF), and acute myocardial infarction (AMI) in a cardiovascular unit in a Christian hospital in Taipei, Taiwan. A total of 2,377 cardiology patients discharged between October 1, 2010, and December 31, 2011, were analyzed. Using ANN or linear regression model was able to predict correctly for 88.07% to 89.95% CAS patients at the predischarge stage and for 88.31% to 91.53% at the preadmission stage. For AMI or HF patients, the accuracy ranged from 64.12% to 66.78% at the predischarge stage and 63.69% to 67.47% at the preadmission stage when a tolerance of 2 days was allowed.

Hyponatremia and sodium picosulfate bowel preparations in older adults.

OBJECTIVES: Bowel preparations are commonly prescribed drugs. Case reports and our clinical experience suggest that sodium picosulfate bowel preparations can precipitate severe hyponatremia in some older adults. At present, this risk is poorly quantified. We investigated the association between sodium picosulfate use and the risk of hyponatremia in older adults. METHODS: We conducted a population-based retrospective cohort study using six linked administrative databases in Ontario, Canada. All Ontario residents over the age of 65 years who filled an outpatient bowel preparation prescription before colonoscopy were eligible. We enrolled new users of either sodium picosulfate (n=99,237) or polyethylene glycol (n=48,595). The primary outcome was hospitalization with hyponatremia within 30 days of the bowel preparation assessed by database codes. The secondary outcomes were hospitalization with urgent head computed tomography (CT) (a proxy for acute central nervous system disturbance) and all-cause mortality. RESULTS: The baseline characteristics of the two groups, including patient demographics, comorbid conditions, and concomitant medications, were nearly identical. Compared with polyethylene glycol, sodium picosulfate was associated with a higher risk of hospitalization with hyponatremia (absolute risk increase: 0.05%, 95% confidence interval (CI): 0.04-0.06%, relative risk (RR): 2.4, 95% CI: 1.5-3.9), but not hospitalization with urgent CT head (RR: 1.1, 95% CI: 0.7-1.4) or mortality (RR: 0.9, 95% CI: 0.7-1.3). CONCLUSIONS: Sodium picosulfate bowel preparations lead to more hyponatremia than polyethylene glycol. There was no evidence of increased risk of acute neurologic symptoms or mortality. The absolute increase in risk of hospitalization with hyponatremia remains low but may be avoidable through appropriate fluid intake or preferential use of polyethylene glycol in some older adults.