Toward a Learning Health Care System: A Systematic Review and Evidence-Based Conceptual Framework for Implementation of Clinical Analytics in a Digital Hospital

Objective  A learning health care system (LHS) uses routinely collected data to continuously monitor and improve health care outcomes. Little is reported on the challenges and methods used to implement the analytics underpinning an LHS. Our aim was to systematically review the literature for reports of real-time clinical analytics implementation in digital hospitals and to use these findings to synthesize a conceptual framework for LHS implementation. Methods  Embase, PubMed, and Web of Science databases were searched for clinical analytics derived from electronic health records in adult inpatient and emergency department settings between 2015 and 2021. Evidence was coded from the final study selection that related to (1) dashboard implementation challenges, (2) methods to overcome implementation challenges, and (3) dashboard assessment and impact. The evidences obtained, together with evidence extracted from relevant prior reviews, were mapped to an existing digital health transformation model to derive a conceptual framework for LHS analytics implementation. Results  A total of 238 candidate articles were reviewed and 14 met inclusion criteria. From the selected studies, we extracted 37 implementation challenges and 64 methods employed to overcome such challenges. We identified common approaches for evaluating the implementation of clinical dashboards. Six studies assessed clinical process outcomes and only four studies evaluated patient health outcomes. A conceptual framework for implementing the analytics of an LHS was developed. Conclusion  Health care organizations face diverse challenges when trying to implement real-time data analytics. These challenges have shifted over the past decade. While prior reviews identified fundamental information problems, such as data size and complexity, our review uncovered more postpilot challenges, such as supporting diverse users, workflows, and user-interface screens. Our review identified practical methods to overcome these challenges which have been incorporated into a conceptual framework. It is hoped this framework will support health care organizations deploying near-real-time clinical dashboards and progress toward an LHS.     

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.     

Effective screen-printed potentiometric devices modified with carbon nanotubes for the detection of chlorogenic acid: application to food quality monitoring

All-solid state screen-printed electrodes were fabricated for chlorogenic acid (CGA) detection. The screen-printed platforms were modified with multi-walled carbon nanotubes (MWCNTs) to work as a lipophilic solid-contact transducer. The sensing-membrane was plasticized with a suitable solvent mediator and incorporating [Ni^II(bathophenanthroline)₃][CGA]₂ complex as a sensory material. In a 30 mM phosphate solution (buffer, pH 6), the sensor revealed a Nernstian-response towards CGA ions with a slope of −55.1 ± 1.1 (r² = 0.9997) over the linear range 1.0 × 10⁻⁷ to 1.0 × 10⁻³ (0.035–354.31 μg mL⁻¹) with a detection limit 7.0 × 10⁻⁸ M (24.8 ng mL⁻¹). It revealed a stable potentiometric response with excellent reproducibility and enhanced selectivity over several common ions. Short-term potential stability and the interfacial sensor capacitance was estimated using both electrochemical-impedance spectroscopy (EIS) and chronopotentiometry techniques. The presented electrochemical platform revealed the merits of design simplicity, ease of miniaturization, good potential-stability, and cost-effectiveness. It is successfully applied to CGA determination in different coffee beans extracts and juice samples. The data obtained were compared with those obtained by liquid chromatography reference method (HPLC).

All-solid state screen-printed electrodes were fabricated for chlorogenic acid (CGA) detection.     

Chemical and biological studies on the soft coral Nephthea sp.

Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti-proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n-butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC₅₀ values of 2.30 ± 0.07 and 3.12 ± 0.10 μg ml⁻¹, respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC₅₀ = 2.78 ± 0.09 μg ml⁻¹). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC₅₀ values of 0.72 ± 0.06 and 9.32 ± 0.57 μg ml⁻¹, respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.

The cytotoxic potential of the crude extract, different fractions, and green synthesized nanoparticles of the soft coral Nephthea sp. was studied, supported by LC-HR-ESI-MS metabolomics analysis and molecular docking of the dereplicated compounds.     

Paper-based potentiometric sensing devices modified with chemically reduced graphene oxide (CRGO) for trace level determination of pholcodine (opiate derivative drug)

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized. A printed pholcodinium (PHL)²⁺/5-nitrobarbiturate (NB)⁻ ion-association complex as a sensory material-based all-solid-state ion-selective electrode (ISE) on a chemically reduced graphene oxide (CRGO) solid-contact, and a printed all-solid-state Ag/AgCl reference electrode, has been combined on a hydrophobic paper substrate coated with fluorinated alkyl silane (CF₃(CF₂)₇CH₂CH₂SiCl₃, C^F₁₀). The sensors revealed a potentiometric slope of 28.7 ± 0.3 mV dec⁻¹ (R² = 0.9998) over a linear range starting from 2.0 × 10⁻⁷ M to 1.0 × 10⁻² M and a detection limit of 0.04 μg mL⁻¹. The repeatability and stability of the pholcodine paper-based sensor was found to be 2.32%. The RSD% (n = 6) was found to be 2.67% when using five different paper-based sensors. The sensor revealed an excellent selectivity towards PHL over dextromethorphan, codeine, ephedrine, carbinoxamine, caffeine, ketamine, and K⁺, Na⁺ and Ca²⁺ ions. It showed a good recovery (94–104%) for the determination of PHL in different artificial serum samples. The presented paper-based analytical device was successfully introduced for PHL determination in different pharmaceutical formulations (i.e. syrups and suspensions) containing pholcodine. The current work can be considered as a promising possible analytical tool to obtain cost-effective and disposable paper-based potentiometric sensing devices. These devices can be potentially manufacturable at large scales in pharmaceutical, clinical and forensic applications for opiate drug assessment.

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized.     

Locally advanced tongue squamous cell carcinoma in epidermolysis simplex bullosa patient: a therapeutic conundrum

Epidermolysis bullosa simplex (EBS) is a debilitating condition affecting the skin and mucous membranes that is characterised by frequent ulceration and blistering on trivial trauma. In EBS, oral cavity mucosal injuries lead to a high propensity for developing squamous cell carcinomas. Locally advanced tongue carcinoma arising in this background presents a challenging therapeutic conundrum. To our knowledge, this is the first case of aggressive locally advanced tongue carcinoma that has developed sporadically in a patient with EBS and no family history. Routine screening of oral mucosal lesions will lead to early detection and timely management of this debilitating condition.