Let's talk about it: an exploration of the comparative use of three different digital platforms to gather patient-reported outcome measures.

BACKGROUND: Patient-reported outcome (PRO) measures provide valuable evidence in clinical trials; however, poor compliance with PRO measures is a notable and long-standing problem, resulting in missing data that potentially impact the interpretation of trial results. Interactive, patient-centric platforms may increase participants' motivation to complete PRO measures over the course of a clinical trial. Thus, the aim of this study was to evaluate and optimize the usability of 3 popular consumer technologies-a traditional app-based interface, a chatbot interface, and a speech-operated interface-that may be used to improve user engagement and compliance with PRO measures. METHODS: Participants aged 18-75 years from the general United States population tested the usability of 3 ePRO platforms: a traditional app-based interface using Datacubed Health Platform (Datacubed), a web-based chatbot interface using the Orbita platform, and a speech-operated Alexa interface using an Alexa Skill called "My Daily Wellness." The usability of these platforms was tested with 2 PRO measures: the EQ-5D-5 L and the SF-12v2 Health Survey (SF-12v2), Daily recall. Using a crossover design, 3 cohorts of participants tested each ePRO platform daily for 1 week. After testing, interviews were conducted regarding the participants' experience with each platform. RESULTS: A total of 24 adults participated in the study. The mean age of participants was 45 years (range, 21-71 years), and half were female (n = 12; 50%). Overall, participants prioritized speed, ease of use, and device portability in selecting their preferred platform. The Datacubed app met these criteria and was the preferred platform among most participants (n = 20; 83%). Participants also suggested various modifications to the platforms, such as programmable notifications, adjustable speed, and additional daily reminders. CONCLUSIONS: These data demonstrate the importance of speed, ease of use, and device portability, features that are currently incorporated in the Datacubed app, in ePRO platforms used in future clinical trials. Additionally, the usability of ePRO platforms may be optimized by adding programmable notifications, adjustable speed, and increased daily reminders. The results of this study may be used to enhance the usability and patient centricity of these platforms to improve user compliance and engagement during clinical trials.

Association Between Hematologic Response and Change in Health-Related Quality of Life Among Patients with Light-Chain (AL) Amyloidosis.

Purpose: The purpose of this secondary data analysis was to examine the association between hematologic response and health-related quality of life (HRQoL) among patients with light-chain (AL) amyloidosis. Patients and Methods: Data for this secondary analysis were collected through a non-interventional, longitudinal, online self-report survey of patients with AL amyloidosis. Patients completed an initial online survey, with follow-up surveys administered 1, 6, 12, 18, and 24 months after completion of the initial survey. The online survey included an assessment of patients' most recent self-reported hematologic response status. Eight domains and 2 summary components of HRQoL were evaluated with the SF-36v2® Health Survey. A series of logistic regression models were used to examine the association between self-reported hematologic response at 24 months (dichotomized as new or maintained complete hematologic response; less than a complete response) and change in HRQoL from baseline to 24 months (dichotomized as meaningful worsening; improvement or preservation). Results: For all measured domains of HRQoL except physical functioning, there was no statistically significant relationship between meaningful worsening in HRQoL and hematologic response status at 24 months. Patients without a complete hematologic response had an odds of experiencing meaningful worsening of HRQoL that was similar to that of patients with a complete hematologic response. Conclusion: Among patients with AL amyloidosis, change in HRQoL was generally not associated with hematologic response. Achieving a complete hematologic response does not necessarily mean that a patient will experience increased or stable HRQoL. When defining treatment success, it is important to recognize that clinical markers such as hematologic response may not fully encapsulate the patient experience.

The Transthyretin Amyloidosis - Quality of Life (ATTR-QOL) Questionnaire: Development of a Conceptual Model and Disease-Specific Patient-Reported Outcome Measure.

Purpose: Patients with transthyretin amyloidosis (ATTR) experience a wide variety of symptoms and impacts on health-related quality of life (HRQoL). However, the lack of an ATTR-specific patient-reported outcome (PRO) measure has made consistent measurement of HRQoL in ATTR challenging. This paper describes the development of a conceptual model and subsequent content for the Transthyretin Amyloidosis - Quality of Life Questionnaire (ATTR-QOL), an ATTR-specific PRO measure. Methods: This was a cross-sectional, non-interventional, US-based study. The study design included three stages: 1) a targeted literature review followed by qualitative data collection with patients and experts; 2) development of a conceptual model and PRO measure; and 3) review of the PRO measure using a modified Delphi method, translatability assessment, and interviews with patients and experts. Revisions were made to the measure after each round of review. Results: Forty-four patients and 29 experts participated in this study. The conceptual model included two primary concepts of interest: symptoms (cardiac, neuropathic-peripheral, neuropathic-autonomic, and other) and impacts (eg, physical, role, and mental/emotional functioning). Seventy-two items were created (32 symptoms; 40 impacts) to align with the model. A recall period of one month was selected based on participant input. Conclusion: The ATTR-QOL was created with significant patient involvement and guidance from a multidisciplinary group of experts. The mix of patient and clinical perspectives helped to ensure a balanced representation of all relevant disease experiences and clinical specialties. With further refinement from psychometric testing, the ATTR-QOL will provide a standard, comprehensive measure for all ATTR-specific research including both clinical trials and clinical practice.

Patient perspectives of bedside teaching in an obstetrics, Gynaecology and neonatology hospital.

BACKGROUND: Osler taught doctors to "have no teaching without a patient for a text, and the best teaching is that taught by the patient himself". Bedside teaching (BST) facilitates clinical practice of skills, teaches empathy, instils confidence and builds on patient-doctor relationships. However, its use has declined dramatically due to concerns regarding privacy and autonomy. Most of the research in this area concentrates on medical student or academic opinion of BST using survey based methods. This qualitative study aimed to explore the patient's experiences and opinions of BST. METHODS: With ethical approval a qualitative study was conducted using semi-structured interviews which were examined using Thematic Analysis. Patients who had participated in a BST tutorial were invited to participate and gave written consent after discussion with a study researcher. RESULTS: Twenty-two patients were interviewed (obstetrics ante-natal [n = 10], obstetrics post-natal [n = 5] and gynaecology [n = 7]) ranging from ages 24-80 yrs. Four major themes were identified, with 11 sub-themes. The major themes included (i) Professional Mannerisms (ii) Privacy and Personal Wellbeing (iii) Quality of Patient Experience of BST and (iv) Clinical Experience and Learning Importance. The reaction of patients toward teaching at the bedside was altruistic and positive, with importance placed on learning. CONCLUSION: This research supports the concept of patient focused learning, and can reassure faculty that patients largely support its continuation as an integral component in education. Future research aims to extend this assessment to other patient groups with the aim of learning from and improving their experience.

Unilateral Lateral Epicondylalgia Shows a Pro-nociceptive Pain Profile: A Case-control Observational Study.

OBJECTIVE: Lateral epicondylalgia (LE, tennis elbow) is characterized by both local tissue pathology and features indicative of secondary hyperalgesia. The aim of this study was to evaluate endogenous pain modulation characteristics in people with chronic LE, and to investigate the relationship between endogenous pain modulation and clinical characteristics. MATERIALS AND METHODS: This case-control observational study included 25 participants with LE of at least 6 weeks' duration and 15 age-matched (±5 y) healthy control participants, who were each evaluated in a single session. Pain and disability were assessed using the patient-rated tennis elbow evaluation and pain-free grip strength. Endogenous pain modulation was assessed using pressure pain threshold, cold pain threshold, conditioned pain modulation (CPM), and temporal summation (TS). RESULTS: The LE group exhibited significantly lower pain-free grip and pressure pain threshold bilaterally compared with the control group. Cold pain threshold was significantly reduced on the affected side compared with the matched control side. There was no significant difference between groups for CPM; however, the LE group exhibited significantly increased facilitation as measured by TS (between-group difference in change score of 9.6 mm on a 0 to 100 mm pain visual analogue scale; 95% confidence intervals, 3.4-15.8 mm). There was no significant correlation between pain modulation and clinical measures of pain and disability. DISCUSSION: LE is characterized by locally increased facilitation of pain, as measured by TS, but this is not associated with severity of pain or disability.

Long-term losses of amygdala corticotropin-releasing factor neurons are associated with behavioural outcomes following neonatal hypoxia-ischemia.

Neuronal losses are observed in the brain after neonatal hypoxia-ischemia (HI) however few studies have examined the effects of HI on specific neuronal phenotypes and their possible contribution to behavioural outcomes. In the present study we examined whether postnatal day 3 (P3) HI alters numbers of corticotropin-releasing factor (CRF) and neuropeptide-Y (NPY) neurons in the paraventricular nucleus of the hypothalamus (PVN), the bed nucleus of the stria terminalis (BNST) and the amygdala, 1 (P10) and 6 (P45) weeks after P3 HI. A significant reduction in the number of CRF-positive neurons in the PVN, central nucleus of the amygdala (CeA) and BNST ipsilateral to the carotid ligation 1 and 6 weeks after P3 HI was observed. There was also a significant reduction in the number of NPY-positive neurons in the PVN, amygdala and BNST ipsilateral to the carotid ligation 1 week after P3 HI. However after 6 weeks, only the number of PVN NPY-positive neurons decreased significantly. At 6 weeks post-insult, the number of CeA CRF-positive neurons was inversely associated with locomotor activity and exploratory behaviour in an open field. In contrast, no significant correlations between neuronal counts and early neurodevelopment tests performed on P10 were observed. Thus after P3 HI persistent losses of CRF- and NPY-positive neurons occur and the loss of CeA CRF neurons may provide a central anatomical mechanism underlying neurobehavioural deficits observed 6 weeks after P3 HI.

Delayed P2X4R expression after hypoxia-ischemia is associated with microglia in the immature rat brain.

In a preterm hypoxia-ischemia model in the post-natal day 3 rat, we characterized how the expression of purine ionotropic P2X(4) receptors change in the brain post-insult. After hypoxia-ischemia, P2X(4) receptor expression increased significantly and was associated with a late increase in ionised calcium binding adapter molecule-1 protein expression indicative of microglia cell activation. Minocycline, a potent inhibitor of microglia, attenuated the hypoxia-ischemia-induced increase in P2X(4) receptor expression. We postulate that P2X(4) receptor-positive microglia may represent a population of secondary injury-induced activated microglia. Future studies will determine whether this population contributes to the progression of injury in the immature brain.

Minocycline: a neuroprotective agent for hypoxic-ischemic brain injury in the neonate?

Minocycline is a second-generation tetracycline and a potential neuroprotective intervention following brain injury. However, despite the recognized beneficial effects of minocycline in a multitude of adult disease states, the clinical application of minocycline in neonates is contentious. Tetracyclines, as a class, are not usually administered to neonates, but there is compelling evidence that minocycline reduces brain injury after neonatal hypoxic-ischemic brain injury. This Review focuses on the evidence for minocycline use in neonates by considering aspects of pharmacology, drug regimens, functional outcomes, and mechanisms of action.

Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens.

An increase in the number of activated microglia in the brain is a key feature of neuroinflammation after a hypoxic-ischemic insult to the preterm neonate and can contribute to white matter injury in the brain. Minocycline is a potent inhibitor of microglia and may have a role as a neuroprotective agent that ameliorates brain injury after hypoxia-ischemia in neonatal animal models. However to date large doses, pre-insult administration and short periods of treatment after hypoxia-ischemia have mostly been investigated in animal models making it difficult to translate minocycline's potential applicability to protect the human preterm neonatal brain exposed to hypoxia-ischemia. We investigated whether repeated doses of minocycline can minimize white matter injury and neuroinflammation one week after hypoxia-ischemia (right carotid artery ligation and 30 min 6% O(2)) in the post-natal day 3 rat pup. Two dosage regimens of minocycline were administered for one week; a high dose of 45 mg/kg 2h after hypoxia-ischemia then 22.5 mg/kg daily or a low dose 22.5 mg/kg 2h after hypoxia-ischemia then 10 mg/kg. Post-natal day 3 hypoxia-ischemia significantly reduced myelin content, numbers of O1- and O4-positive oligodendrocyte progenitor cells and increased activated microglia one week later on post-natal day 10. The low dose minocycline regimen was as effective as the high dose in ameliorating neuroinflammation after post-natal day 3 hypoxia-ischemia. However only the high dose regimen significantly attenuated reductions in O1- and O4-positive oligodendrocyte progenitor cells and myelin content. The low dose only significantly attenuated the reduction in O1-positive oligodendrocyte cell counts. Repeated, daily, post-insult treatment with minocycline abolished neuroinflammation and may provide neuroprotection to white matter for up to one week after hypoxia-ischemia in a rodent preterm model. The present findings suggest the potential clinical relevance of a repeated, daily minocycline treatment strategy, administered after a hypoxia-ischemia insult, as a therapeutic intervention for hypoxia-ischemia-affected preterm neonates.

Selective losses of brainstem catecholamine neurons after hypoxia-ischemia in the immature rat pup.

Hypoxic-ischemic (HI) injury in the preterm neonate incurs numerous functional deficits, however little is known about the neurochemically-defined brain nuclei that may underpin them. Key candidates are the brainstem catecholamine neurons. Using an immature animal model, the postnatal day (P)-3 (P3) rat pup, we investigated the effects of HI on brainstem catecholamine neurons in the locus coeruleus, nucleus tractus solitarius (NTS), and ventrolateral medulla (VLM). On P21, we found that prior P3 HI significantly reduced numbers of catecholaminergic neurons in the locus coeruleus, NTS, and VLM. Only locus coeruleus A6, NTS A2, and VLM A1 noradrenergic neurons, but not NTS C2 and VLM C1 adrenergic neurons, were lost. There was also an associated reduction in dopamine-beta-hydroxylase-positive immunolabeling in the forebrain. These findings suggest neonatal HI can affect specific neurochemically-defined neuronal populations in the brainstem and that noradrenergic neurons are particularly vulnerable to HI injury.