N-of-1 medicine.

ABSTRACT: The fields of precision and personalised medicine have led to promising advances in tailoring treatment to individual patients. Examples include genome/molecular alteration-guided drug selection, single-patient gene therapy design and synergy-based drug combination development, and these approaches can yield substantially diverse recommendations. Therefore, it is important to define each domain and delineate their commonalities and differences in an effort to develop novel clinical trial designs, streamline workflow development, rethink regulatory considerations, create value in healthcare and economics assessments, and other factors. These and other segments are essential to recognise the diversity within these domains to accelerate their respective workflows towards practice-changing healthcare. To emphasise these points, this article elaborates on the concept of digital health and digital medicine-enabled N-of-1 medicine, which individualises combination regimen and dosing using a patient's own data. We will conclude with recommendations for consideration when developing novel workflows based on emerging digital-based platforms.

Comparing the Performance of Multiple Small-Data Personalized Tacrolimus Dosing Models for Pediatric Liver Transplant: A Retrospective Study.

Tacrolimus is a potent immunosuppressant used after pediatric liver transplant. However, tacrolimus's narrow therapeutic window, reliance on physicians' experience for the dose titration, and intra- and inter-patient variability result in liver transplant patients falling out of the target tacrolimus trough levels frequently. Existing personalized dosing models based on the area-under-the-concentration over time curves require a higher frequency of blood draws than the current standard of care and may not be practically feasible. We present a small-data artificial intelligence-derived platform, CURATE.AI, that uses data from individual patients obtained once daily to model the dose and response relationship and identify suitable doses dynamically. Retrospective optimization using 6 models of CURATE.AI and data from 16 patients demonstrated good predictive performance and identified a suitable model for further investigations.Clinical Relevance- This study established and compared the predictive performance of 6 personalized tacrolimus dosing models for pediatric liver transplant patients and identified a suitable model with consistently good predictive performance based on data from pediatric liver transplant patients.

Stretchable and Sensitive Silver Nanowire-Hydrogel Strain Sensors for Proprioceptive Actuation.

Safer human-robot interactions mandate the adoption of proprioceptive actuation. Strain sensors can detect the deformation of tools and devices in unstructured and capricious environments. However, such sensor integration in surgical/clinical settings is challenging due to confined spaces, structural complexity, and performance losses of tools and devices. Herein, we report a highly stretchable skin-like strain sensor based on a silver nanowire (AgNW) layer and hydrogel substrate. Our facile fabrication method utilizes thermal annealing to modulate the gauge factor (GF) by forming multidimensional wrinkles and a layered conductive network. The developed AgNW-hydrogel (AGel) sensors sustain and exhibit a strain-sensitive profile (max. GF = ∼70) with high stretchability (200%). Due to its conformability, the sensor demonstrates efficacy in integration and motion monitoring with minimal mechanical constraints. We provide contextual cognizance of tooltip during a transoral procedure by incorporating AGel sensors and showing the fabrication methodology's versatility by developing a hybrid self-sensing actuator with real-time performance feedback.

Deployable Telescopic Tubular Mechanisms With a Steerable Tongue Depressor Towards Self-Administered Oral Swab.

Swabbing tests have proved to be an effective method of diagnosis for a wide range of diseases. Potential occupational health hazards and reliance on healthcare workers during traditional swabbing procedures can be mitigated by self-administered swabs. Hence, we report possible methods to apply closed kinematic chain theory to develop a self-administered viral swab to collect respiratory specimens. The proposed sensorized swab models utilizing hollow polypropylene tubes possess mechanical compliance, simple construction, and inexpensive components. In detail, the adaptation of the slider-crank mechanism combined with concepts of a deployable telescopic tubular mechanical system is explored through four different oral swab designs. A closed kinematic chain on suitable material to create a developable surface allows the translation of simple two-dimensional motion into more complex multi-dimensional motion. These foldable telescopic straws with multiple kirigami cuts minimize components involved in the system as the characteristics are built directly into the material. Further, it offers a possibility to include soft stretchable sensors for realtime performance monitoring. A variety of features were constructed and tested using the concepts above, including 1) tongue depressor and cough/gag reflex deflector; 2) changing the position and orientation of the oral swab when sample collection is in the process; 3) protective cover for the swabbing bud; 4) a combination of the features mentioned above.

Fully organic compliant dry electrodes self-adhesive to skin for long-term motion-robust epidermal biopotential monitoring.

Wearable dry electrodes are needed for long-term biopotential recordings but are limited by their imperfect compliance with the skin, especially during body movements and sweat secretions, resulting in high interfacial impedance and motion artifacts. Herein, we report an intrinsically conductive polymer dry electrode with excellent self-adhesiveness, stretchability, and conductivity. It shows much lower skin-contact impedance and noise in static and dynamic measurement than the current dry electrodes and standard gel electrodes, enabling to acquire high-quality electrocardiogram (ECG), electromyogram (EMG) and electroencephalogram (EEG) signals in various conditions such as dry and wet skin and during body movement. Hence, this dry electrode can be used for long-term healthcare monitoring in complex daily conditions. We further investigated the capabilities of this electrode in a clinical setting and realized its ability to detect the arrhythmia features of atrial fibrillation accurately, and quantify muscle activity during deep tendon reflex testing and contraction against resistance.