Support for Chronic Pain Management for Breast Cancer Survivors Through Novel Digital Health Ecosystems: Pilot Usability Study of the PainRELife Mobile App.

BACKGROUND: Chronic pain is one of the most common and critical long-term effects of breast cancer. Digital health technologies enhance the management of chronic pain by monitoring physical and psychological health status and supporting pain self-management and patient treatment decisions throughout the clinical pathway. OBJECTIVE: This pilot study aims to evaluate patients' experiences, including usability, with a novel digital integrated health ecosystem for chronic pain named PainRELife. The sample included patients with breast cancer during survivorship. The PainRELife ecosystem comprises a cloud technology platform interconnected with electronic health records and patients' devices to gather integrated health care data. METHODS: We enrolled 25 patients with breast cancer (mean age 47.12 years) experiencing pain. They were instructed to use the PainRELife mobile app for 3 months consecutively. The Mobile Application Rating Scale (MARS) was used to evaluate usability. Furthermore, pain self-efficacy and participation in treatment decisions were evaluated. The study received ethical approval (R1597/21-IEO 1701) from the Ethical Committee of the European Institute of Oncology. RESULTS: The MARS subscale scores were medium to high (range: 3.31-4.18), and the total app quality score was 3.90. Patients with breast cancer reported reduced pain intensity at 3 months, from a mean of 5 at T0 to a mean of 3.72 at T2 (P=.04). The total number of times the app was accessed was positively correlated with pain intensity at 3 months (P=.03). The engagement (P=.03), information (P=.04), and subjective quality (P=.007) subscales were positively correlated with shared decision-making. Furthermore, participants with a lower pain self-efficacy at T2 (mean 40.83) used the mobile app more than participants with a higher pain self-efficacy (mean 48.46; P=.057). CONCLUSIONS: The data collected in this study highlight that digital health technologies, when developed using a patient-driven approach, might be valuable tools for increasing participation in clinical care by patients with breast cancer, permitting them to achieve a series of key clinical outcomes and improving quality of life. Digital integrated health ecosystems might be important tools for improving ongoing monitoring of physical status, psychological burden, and socioeconomic issues during the cancer survivorship trajectory. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/41216.

Usability Testing of a New Digital Integrated Health Ecosystem (PainRELife) for the Clinical Management of Chronic Pain in Patients With Early Breast Cancer: Protocol for a Pilot Study.

BACKGROUND: Chronic pain (CP) and its management are critical issues in the care pathway of patients with breast cancer. Considering the complexity of CP experience in cancer, the international scientific community has advocated identifying cutting-edge approaches for CP management. Recent advances in the field of health technology enable the adoption of a novel approach to care management by developing integrated ecosystems and mobile health apps. OBJECTIVE: The primary end point of this pilot study is to evaluate patients' usability experience at 3 months of a new digital and integrated technological ecosystem, PainRELife, for CP in a sample of patients with breast cancer. The PainRELife ecosystem is composed of 3 main technological assets integrated into a single digital ecosystem: Fast Healthcare Interoperability Resources-based cloud platform (Nu platform) that enables care pathway definition and data collection; a big data infrastructure connected to the Fast Healthcare Interoperability Resources server that analyzes data and implements dynamic dashboards for aggregate data visualization; and an ecosystem of personalized applications for patient-reported outcomes collection, digital delivery of interventions and tailored information, and decision support of patients and caregivers (PainRELife app). METHODS: This is an observational, prospective pilot study. Twenty patients with early breast cancer and chronic pain will be enrolled at the European Institute of Oncology at the Division of Medical Senology and the Division of Pain Therapy and Palliative Care. Each patient will use the PainRELife mobile app for 3 months, during which data extracted from the questionnaires will be sent to the Nu Platform that health care professionals will manage. This pilot study is nested in a large-scale project named "PainRELife," which aims to develop a cloud technology platform to interoperate with institutional systems and patients' devices to collect integrated health care data. The study received approval from the Ethical Committee of the European Cancer Institute in December 2021 (number R1597/21-IEO 1701). RESULTS: The recruitment process started in May 2022 and ended in October 2022. CONCLUSIONS: The new integrated technological ecosystems might be considered an encouraging affordance to enhance a patient-centered approach to managing patients with cancer. This pilot study will inform about which features the health technological ecosystems should have to be used by cancer patients to manage CP. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41216.

Protective Effect of Curcuma Extract in an Ex Vivo Model of Retinal Degeneration via Antioxidant Activity and Targeting the SUMOylation.

Retinal degeneration is the major and principal cause behind many incurable blindness diseases. Several studies indicated the neuroprotective effect of Curcuma longa in eye pathologies, specifically retinopathy. However, the molecular mechanism behind its effect has not been completely elucidated. Using an ex vivo model of retinal degeneration obtained from an ex vivo optic nerve cut (ONC), we demonstrated that Curcuma extract (Cur) exerted a neuroprotective effect. Importantly, Cur was able to modulate apoptosis and MAPK signaling pathway activation and prevent retinal ganglion cell (RGC) loss. Other well-known neuroprotective pharmacological tools, including memantine (Mem), citicoline (Cit), and ginkgolic acid (GA), were used to compare the potential mechanisms of Cur. The antioxidant activity of retinas treated with Cur following optic nerve cut was significantly higher than control, but Cur failed to change the retina glutamate content. Considering the antioxidant effect of Cur and taking advantage of our recent findings on the crosstalk between oxidative stress and post-translational protein modifiers, in particular, small ubiquitin-related modifier (SUMO), we were interested in exploring the effect of Cur on SUMOylation. We found that Cur significantly prevented the increase of protein SUMOylation, confirming our previous in vitro data indicating the cytoprotective effect of curcumin through modulating the oxidative stress and SUMO-JNK axis. Altogether, these results suggest that Curcuma protects the retina from degeneration via antioxidant activity and targets SUMOylation. Therefore, it might be considered for the combination therapy with other neuroprotective agents with different mechanisms in preclinical studies on retinal degeneration.

Retinal ganglion cell loss in an ex vivo mouse model of optic nerve cut is prevented by curcumin treatment.

Retinal ganglion cell (RGC) loss is a pathologic feature common to several retinopathies associated to optic nerve damage, leading to visual loss and blindness. Although several scientific efforts have been spent to understand the molecular and cellular changes occurring in retinal degeneration, an effective therapy to counteract the retinal damage is still not available. Here we show that eyeballs, enucleated with the concomitant optic nerve cut (ONC), when kept in PBS for 24 h showed retinal and optic nerve degeneration. Examining retinas and optic nerves at different time points in a temporal window of 24 h, we found a thinning of some retinal layers especially RGC's layer, observing a powerful RGC loss after 24 h correlated with an apoptotic, MAPKs and degradative pathways dysfunctions. Specifically, we detected a time-dependent increase of Caspase-3, -9 and pro-apoptotic marker levels, associated with a strong reduction of BRN3A and NeuN levels. Importantly, a powerful activation of JNK, c-Jun, and ERK signaling (MAPKs) were observed, correlated with a significant augmented SUMO-1 and UBC9 protein levels. The degradation signaling pathways was also altered, causing a significant decrease of ubiquitination level and an increased LC3B activation. Notably, it was also detected an augmented Tau protein level. Curcumin, a powerful antioxidant natural compound, prevented the alterations of apoptotic cascade, MAPKs, and SUMO-1 pathways and the degradation system, preserving the RGC survival and the retinal layer thickness. This ex vivo retinal degeneration model could be a useful method to study, in a short time window, the effect of neuroprotective tools like curcumin that could represent a potential treatment to contrast retinal cell death.

Omics sciences for systems biology in Alzheimer's disease: State-of-the-art of the evidence.

Alzheimer's disease (AD) is characterized by non-linear, genetic-driven pathophysiological dynamics with high heterogeneity in biological alterations and disease spatial-temporal progression. Human in-vivo and post-mortem studies point out a failure of multi-level biological networks underlying AD pathophysiology, including proteostasis (amyloid-ß and tau), synaptic homeostasis, inflammatory and immune responses, lipid and energy metabolism, oxidative stress. Therefore, a holistic, systems-level approach is needed to fully capture AD multi-faceted pathophysiology. Omics sciences - genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics - embedded in the systems biology (SB) theoretical and computational framework can generate explainable readouts describing the entire biological continuum of a disease. Such path in Neurology is encouraged by the promising results of omics sciences and SB approaches in Oncology, where stage-driven pathway-based therapies have been developed in line with the precision medicine paradigm. Multi-omics data integrated in SB network approaches will help detect and chart AD upstream pathomechanistic alterations and downstream molecular effects occurring in preclinical stages. Finally, integrating omics and neuroimaging data - i.e., neuroimaging-omics - will identify multi-dimensional biological signatures essential to track the clinical-biological trajectories, at the subpopulation or even individual level.

Obstacles against the Marketing of Curcumin as a Drug.

Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.

Integrated care pathways on dementia in Italy: a survey testing the compliance with a national guidance.

Dementias are chronic, degenerative neurological disorders with a complex management that require the cooperation of different healthcare professionals. The Italian Ministry of Health produced the document "Guidance on Integrated Care pathway for People with Dementia" (GICPD) with the specific objective of providing a standardized framework for the definition, development, and implementation of integrated care pathways (ICP) dedicated to people with dementia. We searched all available Italian territorial ICPs. Two raters assessed the retrieved ICPs with a 2-point scale on a 43-item checklist based on the GICPD. Only 5 out of 21 regions and 5 out of 101 local health authorities had an ICP, with most ICPs having a moderate compliance to the GICPD, in particular for the items referring to the development and implementation of the care pathways. A low to moderate inter-rater agreement was observed, mainly due to a lack of standardized models to describe ICPs for dementias. Results suggest that policy- and decision-makers should pay more attention to the GICPD when producing ICPs. The direct communication with clinicians, and the implementation of more precise and appropriate clinical outcomes, could increase the involvement of clinicians, whose participation is crucial to guarantee that ICPs meet needs of patients and their carers.

Fertilizing a Patient Engagement Ecosystem to Innovate Healthcare: Toward the First Italian Consensus Conference on Patient Engagement.

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper.

Meditation training for people with amyotrophic lateral sclerosis and their caregivers.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that is clinically characterized by progressive weakness leading to death by respiratory insufficiency, usually within three years. Although the patient's intellect and personality usually remain unimpaired, as the disease progresses, the patient becomes immobile, develops wasting, and speech becomes impaired, often resulting in social isolation and a high degree of psychological suffering. Mindfulness meditation has proven to be effective technique for reducing distress in many chronic diseases. However, to date, no study has investigated the effect of mindfulness meditation on patients with ALS. DESIGN: A mindfulness meditation training program for ALS patients needs to consider the particularities of ALS symptoms, including the loss of muscular functions and difficulties in respiration, together with the subsequent emotional impairments. With these caveats in mind, a modified protocol, based on original mindfulness meditation interventions, has been created specifically for the ALS population. This article describes the protocol and preliminary results.

Coffee and amyotrophic lateral sclerosis: a possible preventive role.

The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk.

Existential well-being and spirituality of individuals with amyotrophic lateral sclerosis is related to psychological well-being of their caregivers.

Existential well-being (EWB) and spirituality issues are important factors in determining quality of life (QoL) in amyotrophic lateral sclerosis (ALS) patients. No conclusive data among the relation between patient's EWB, their spirituality and caregivers' QoL are available. In the mainframe of a longitudinal study, we performed a cross-sectional analysis aimed to investigate EWB and spirituality issues in sporadic ALS (SALS) patients and the relations with caregivers' psychological features. Thirty-seven SALS patients, together with their caregivers, consecutively recruited at NEuroMuscular Omnicentre, in Milan, were included in this study. EWB and spirituality questions were administrated to patients and caregivers. Caregivers also completed questionnaires about quality of life (MQoL-SI), care burden (ZBI), depression (BDI) and anxiety (STAI). Both EWBs and questions about spirituality of SALS patients showed a positive correlation with MQoL-SI and EWBs in their caregivers. Conversely, SALS patients' EWB and spirituality were negatively correlated with caregivers' STAI, BDI and ZBI scores. In conclusion, existential well-being, as well as spirituality issues, perceived by SALS patients seems to be directly related with quality of life, severity of mood disturbance and burden experienced by their caregivers.