Empathic Validation in Physician–Patient Communication: An Approach to Conveying Empathy for Problems With Uncertain Solutions

Interest in systematic approaches to improving clinical empathy has increased. However, conceptualizations of empathy are inconsistent and difficult to operationalize. Drawing on video recordings of primary care visits with older adults, I describe one particular communication strategy for conveying empathy—empathic validation. Using conversation analysis, I show that the design of empathic validations and the context in which they are delivered are critical to positive patient responses. Effective empathic validations must (a) demonstrate shared understanding and (b) support the patient’s position. Physicians provided empathic validation when there was no medical solution to offer and within this context, for three purposes: (1) normalizing changes in health, (2) acknowledging individual difficulty, and (3) recognizing actions or choices. Empathic validation is a useful approach because it does not rely on patients’ ability to create an “empathic opportunity” and has particular relevance for older adults.

Fascicles split or merge every ~560 microns within the human cervical vagus nerve

Vagus nerve stimulation (VNS) is FDA approved for stroke rehabilitation, epilepsy and depression; however, the underlying vagus functional anatomy underlying the implant is poorly understood. We used microCT to quantify fascicular structure and neuroanatomy within human cervical vagus nerves. Fascicles split or merged every ~560 μm (17.8 ± 6.1 events/cm). The high degree of splitting and merging of fascicles in humans may explain the clinical heterogeneity in patient responses.

Advantages of multi-arm non-randomised sequentially allocated cohort designs for Phase II oncology trials

Background Efficient trial designs are required to prioritise promising drugs within Phase II trials. Adaptive designs are examples of such designs, but their efficiency is reduced if there is a delay in assessing patient responses to treatment. Methods Motivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. The MASTER design recruits patients to one arm at a time, pausing recruitment to an arm when it has recruited the required number for an interim analysis. We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms. Results The parallel multi-arm multi-stage and the MASTER design are much more efficient than separate trials. The MASTER design provides extra efficiency when there is endpoint delay, or recruitment is very quick. Conclusions We recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in non-comparative Phase II trials.

Using exhalation dynamics to evaluate PEEP levels in COVID-19 related ARDS

Background We hypothesized that measured expiratory time constant (TauE) could be a bedside parameter for evaluation of PEEP settings in mechanically ventilated COVID-19 patients during pressure-controlled ventilation (PCV) mode. TauE is an easily measured parameter to assess lung physiology, even in non-homogeneous lungs including COVID-19 ARDS. Methods A prospective study was conducted including consecutively admitted adults (n = 16) with COVID-19 related ARDS requiring mechanical ventilation. Ventilator settings for all patients included: PCV, RR 18/min, constant inspiratory pressure 14 cmH2O, I:E ratio 1:1.5 and FiO2 1.0. Escalating levels of PEEP (0 to 18 cmH2O) were applied and measured TauE and expiratory tidal volume (Vte) recorded. Next, a new parameter, TauE Index (TEI) was calculated (TEI = TauE * Vte) at each PEEP level in prone (n = 29) or supine (n = 24) positions. TEI maps were created to graphically show changes in individual physiology with PEEP. The PEEP setting with the highest TEI corresponded to the highest product of TauE and Vte and was considered the most suitable PEEP. Most suitable PEEP range was calculated as ± 10% from highest TEI. Results Two groups of patterns were observed in the TEI maps, recruitable (R) (75%) and non-recruitable (NR) (25%). In R group, the most suitable PEEP and PEEP range was 9±3 cmH2O and 6-12 cmH2O for prone position and 11±3 cmH2O and 7-13 cmH2O for supine position. In NR group, the most suitable PEEP and PEEP range was 7±3 cmH2O and 0-8 cmH2O for prone position and 4±2 cmH2O and 0-7 cmH2O for supine position, respectively. The R group showed significantly higher suitable PEEP (p<0.01) and PEEP ranges (p<0.01) than NR group. 45% of measurements resulted in most suitable PEEP being significantly different between the positions (p < 0.01). Conclusions Based on TEI mapping, responses to PEEP were easily measured. There was wide variation in patient responses to PEEP that indicate the need for personalized evaluation.

EP.WE.17Surgical Telemedicine Clinics during the Covid-19 Pandemic – Patient-Reported Outcomes Report

Aims The primary aim was to obtain patient feedback about surgical telemedicine clinics. The secondary endpoint was to investigate any factors influencing the patient’s feedback. Methods A retrospective qualitative study was undertaken, during the period between June – September 2020, at Darent Valley Hospital in West Kent. Telephone and online feedback were obtained using a 5 point questionnaire designed to assess their experience and preference for future consultations. Variables such as ‘demographics’, ‘first or follow-up clinic appointment’ and ‘physician-grade’, were analysed for any influence on patients feedback. Results A total of 200 patients responded to the questionnaire (telephone = 133, online = 77). The median age was 67 years (IQR 44 – 79) and male: female ratio 1. About 35.9% were a new referral and 42.7% has had some face-to-face appointment in the hospital before the pandemic. During the period of the study, about 42.7% had more than one telemedicine appointments. About 83.2% were consulted by surgical registrars. A rating from good to excellent for ‘overall experience’, ‘opportunity to express own concern’ and ‘how well the doctor addressed their concerns’ was given at 90%, 93.1% and 89.4%, respectively. About 80.2% felt reassured and 21.7% would prefer telemedicine for future consultations. There was no association between the variables studied and patient responses. Conclusions A high percentage of patients reported satisfactory service provision via telemedicine clinics. A majority of patients felt reassured. However, given the option, the face-to-face clinic would be the prefered option for the majority.

PROMIS Milestones in Patients Undergoing Rotator Cuff Repair (233)

Objectives: Patient Reported Outcome Measurement Information System (PROMIS) has emerged as an effective tool in assessing post-operative outcomes in rotator cuff repair. PROMIS employs computer adaptive testing (CAT) in order to select specific items from a standard question bank based on previous patient responses. In turn, domain-specific PROMIS forms allow optimal tracking of outcomes in specific areas of patient recovery, such as upper extremity function (PROMIS-UE) for rotator cuff repair patients. The objective of this investigation is to analyze the PROMIS-UE CAT question bank to determine the point in recovery at which a patient is able to reach certain milestones and to elucidate the number of days – in increments of 30 (i.e., monthly) – it takes for patients who undergo rotator cuff repair to answer “with some difficulty” or “without any difficulty” for the five most frequently asked questions in the PROMIS-UE CAT questionnaire. Understanding these timepoints will improve clinical monitoring and counseling following surgery and provide standardized measures for appropriate activity progression and restriction. Methods: All patients who underwent rotator cuff repair by one of two sports medicine fellowship-trained orthopedic surgeons between 2/16/17 and 7/13/19 were included in this study. Post-operative PROMIS-UE CAT scores were reviewed with respect to individual item, response, and timing of response (with respect to number of days following surgery using 30-day increments). For each PROMIS-UE CAT item, the following five answer choices were available: “Without any difficulty”, “With a little difficulty”, “With some difficulty”, “With much difficulty”, and “Unable to do”. A task was considered achievable if the patient answered any answer with “Without any difficulty” or “With a little difficulty”. The percentage of patients in each 30-day group who answered with either of these responses was recorded. Chi-square tests were run between the number of days postoperatively the surveys were administered and patient responses to determine whether or not there were statistically significant differences between groups. Results: A total of 1,143 patient responses were included in the final analysis. The five most frequently asked questions in the PROMIS-UE CAT item bank, which were as follows: “Are you able to carry a heavy object (over 10 pounds /5 kg)?” (n=1143), “Are you able to put on and take off a coat or jacket?” (n=932), “Are you able to carry a shopping bag or briefcase?” (n=453), “Are you able to pour liquid from a bottle into a glass?” (n=675), and “Are you able to put on a shirt or blouse?” (n=578). The times at which greater than 50% of respondents answered either “Without any difficulty” or “With a little difficulty” are shown in Table 1. All five questions showed statistically significant associations between number of days postoperatively and patient responses (p<.0005). Conclusions: On average, patients undergoing rotator cuff repair achieved milestones measured by the five most commonly asked questions on the PROMIS-UE CAT by 1-4 months postoperatively. Patients also showed significant improvements in upper extremity function in the same time period. These findings can be utilized in post-operative monitoring, and patients who do not meet these milestones in the appropriate timepoints may require additional supportive care or treatment.

Overview of Idiopathic Normal Pressure Hydrocephalus: Diagnosis and Improvement

Idiopathic normal pressure hydrocephalus (iNPH) is an uncommon yet potentially reversible cause of dementia in the elderly. It is characterized by cognitive deterioration, urinary incontinence, ventriculomegaly (enlarged cerebral ventricles) and gait apraxia. The diagnosis and management of iNPH requires an organized approach, starting with a comprehensive history and neurologic examination, a review of neuroimaging, and an evaluation of diagnosis. It is important to treat comorbidities in patients prior to specific iNPH testing, which includes testing patient responses to temporary CSF removal and assessing CSF hydrodynamics. In carefully selected patients, all physiological and neurological symptoms improved with a ventriculoperitoneal (VP) shunt surgery, which allows for a gradual adjustment in pressure to prevent complications caused by over-drainage.

Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer’s and Parkinson’s Diseases

Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.

A computational model of CAR T-cell immunotherapy predicts leukemia patient responses at remission, resistance, and relapse

Adaptive CD19-targeted CAR (Chimeric Antigen Receptor) T-cell transfer has become a promising treatment for leukemia. Though patient responses vary across different clinical trials, there currently lacks reliable early diagnostic methods to predict patient responses to those novel therapies. Recently, computational models achieve to in silico depict patient responses, with prediction application being limited. We herein established a computational model of CAR T-cell therapy to recapitulate key cellular mechanisms and dynamics during treatment based on a set of clinical data from different CAR T-cell trials, and revealed critical determinants related to patient responses at remission, resistance, and relapse. Furthermore, we performed a clinical trial simulation using virtual patient cohorts generated based on real clinical patient dataset. With input of early-stage CAR T-cell dynamics, our model successfully predicted late responses of various virtual patients compared to clinical observance. In conclusion, our patient-based computational immuno-oncology model may inform clinical treatment and management.