Search

Abstract Background miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls. Methods This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting. Results miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1β, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1β (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles. Conclusions Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation. Trial registration www.clinicaltrials.gov . (NCT05891808).

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score–matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

Abstract Background Regular physical activity helps to reduce weight and improve the general well-being of individuals living with obesity. Chatbots have shown the potential to increase physical activity among their users. We aimed to explore the preferences of individuals living with obesity for the features and functionalities of a modern chatbot based on social media, Artificial intelligence (AI) and other recent and relevant technologies. Methods In this study, we used qualitative methods. Focusing on individuals’ preferences for a chatbot to increase physical activity, we conducted both individual interviews and focus groups with nine adult patients staying at Evjeklinikken, a Norwegian rehabilitation clinic for individuals living with morbid obesity. The interviews were fully transcribed and then analysed inductively using thematic analysis. Results Participants preferred motivational features such as social support, goal setting, physical activity illustrations, monitoring of physical activity behaviour and outcomes, and feedback, prompts and reminders. They also preferred features for connecting and synchronising with smartwatches and training device apps. Participants wanted a chatbot that is easy to use and allows for human assistance when needed. Regarding personalising the chatbot, the participants wanted to choose the language, number of messages, and turn functionalities on and off. Conclusions Co-designing chatbots with potential users is essential to understand their specific needs and preferences. We gained valuable insight into a diverse set of features and functionalities relevant to designing physical activity chatbots for individuals living with obesity. Behaviour change techniques are equally important as personalisation features and the option for synchronising with third-party devices. In future work, we will consider the collected needs in the development of a physical activity chatbot to ensure acceptance and adherence to the digital health intervention.

AbstractObjective To explore Norwegian GPs’ experiences with and perceived suitability of issuing sickness certifications in remote consultations during the COVID-19 pandemic.Design We used a mixed methods research design. An online survey with 301 respondents was combined with qualitative interviews with ten GPs.Setting Norwegian general practice.Results Most GPs agreed it was difficult to assess a patient’s ability to work without physical attendance for a first-time certification in remote consultations. However, extending a certification was considered less problematic. If physical examinations were required, the GPs would ask the patient to come to the office. The most suitable diagnoses for remote certification were respiratory infections and COVID-19-related diagnoses, as well as known chronic and long-term diseases. The GPs emphasized the importance of knowing both the patient and the medical problem. The GP-patient relationship could be affected by remote consultations, and there were mixed views on the impact. Many GPs found it easier to deny a request for a sickness certification in remote consultations. The GPs expressed concern about the societal costs and an increased number of certifications if remote consultations were too easily accessible. The study was conducted during the COVID-19 pandemic, and the findings should be interpreted in that context.Conclusions Our study shows that issuing sickness certifications in remote consultations were viewed to be suitable for COVID-19 related problems, for patients the GP has met before, for the follow-up of known medical problems, and the extension of sickness certifications. Not meeting the patient face-to-face may affect the GP-patient relationship as well as make the GPs’ dual role more challenging.

Objectives To explore patients’ experiences with receiving sick leave certificates via remote consultations during the COVID-19 pandemic and investigate whether there were differences among the types of remote consultation (telephone, video or text).Design A nationwide online patient survey consisting of quantitative data supplemented by qualitative opinions conducted in Norway.Setting Primary care.Participants Patients who received a sick leave certificate via remote consultation in the period from 16 November to 15 December 2020.Results Of the 5429 respondents, 3233 (59.6%) received a sick leave certificate via telephone consultation, 657 (12.1%) via video consultation and 1539 (28.3%) via text-based e-consultation. Most respondents (76.8%) were satisfied. Only 10% of the respondents thought that the doctor would have obtained more information through an office appointment. The majority of the respondents (59.6%) found that they had as much time to explain the problem as at an office appointment. Some patients also thought that it was easier to formulate the problem via a remote consultation (18.2%) and agree with the doctor on the sick leave (10.3%).The users of text-based e-consultations were the most satisfied (79.3%, p

IntroductionArterial blood gas analysis is the gold standard for the assessment of oxygenation, ventilation, and metabolic status in dogs; however, its execution is difficult and painful. Therefore, venous blood gas analysis is used in its replacement for the assessment of the metabolic status, but it is not clear whether it can be used to assess respiratory function, too. This study aimed at: 1) comparing jugular and saphenous pH and partial pressure of carbon dioxide (pCO2) with the correspondent arterial pH and pCO2 (paCO2) in healthy dogs during general anesthesia; 2) clarifying whether the arterial-venous relationship is better expressed in jugular or saphenous blood samples; 3) mathematically transforming venous pCO2 (pvCO2) and evaluating whether the calculated values more accurately agree with paCO2.MethodsNinety dogs were included and randomly divided into three groups: Group 1 - arterial vs jugular; Group 2 - arterial vs saphenous; Group 3 - arterial vs jugular vs saphenous blood gases. Each group counted 30 dogs. Pearson correlations were calculated. Bland-Altman plots were generated to describe the agreement between venous and arterial values; clinical limits for pH and pCO2 set by the authors were, respectively, ± 0.1 and ± 2.5 mmHg. Univariate linear regression was applied for predicting paCO2 from pvCO2.ResultsSaphenous samples showed strong positive correlations with arterial samples for both pCO2 and pH. Pearson ρ values were stronger for pH than for pCO2. Bland-Altman plots showed good agreement between venous and arterial pH, and poor agreement between pvCO2 and paCO2 for both jugular and saphenous samples. Results suggested that saphenous pvCO2 is preferable with respect to jugular as predictor of paCO2. The transformation of saphenous pvCO2 through univariate linear regression produced a model for predicting paCO2; a Bland-Altman plot assessed the transformed pvCO2 agreement with paCO2.DiscussionIn healthy, anesthetized, mechanically ventilated dogs, variations of pH between venous and arterial values are clinically acceptable. Venous and arterial blood gases cannot be interchanged for the evaluation of pCO2. Saphenous pvCO2 is to be preferable to jugular pvCO2 as predictor of paCO2. A formula for the estimation of predicted paCO2 from saphenous pvCO2 is proposed.

IntroductionDespite the positive effects of physical activity (PA) to prevent lifestyle diseases and improve health and well-being, only one-third of Norwegian adults meet the minimum recommendations on PA. Digital interventions to promote PA in inactive adults may improve health and well-being by being available, personalized and adequate. Knowledge on users’ adoption, acceptability and sustainability of digital interventions to promote PA is still limited.ObjectiveTo investigate the adoption, acceptability and sustained use of three digital interventions for promoting PA among inactive adults.DesignA randomized control trial (ONWARDS) with 183 participants assigned to 3 groups and followed up for 18 months. All participants received a wearable activity tracker with the personalized metric Personal Activity Intelligence (PAI) on a mobile app, two groups received additional access to online training and one group had also access to online social support.MethodsA mixed-methods approach was used to address the study objective. Acceptability was evaluated through the System Usability Scale (SUS) (n = 134) at 6 months. Adoption and sustained use were evaluated through a set of questions administered at 12 months (n = 109). Individual interviews were performed at 6 months with a sample of participants (n = 18). Quantitative data were analyzed with descriptive statistics, whereas qualitative data were analyzed using the Framework approach.ResultsPAI was the most successful intervention, with satisfactory usability and positive effects on motivation and behavior change, contributing to high adoption and sustained use. Online social support had a high acceptability and sustained use, but the intervention was not perceived as motivational to increase PA. Online training had low adoption, usability and sustained use. The qualitative interviews identified five main themes: (1) overall approach to physical activity, (2) motivation, (3) barriers to perform PA, (4) effects of PA, and (5) usability and acceptability of the digital interventions.ConclusionPersonalized digital interventions integrating behavior change techniques such as individual feedback and goal setting are more likely to increase acceptability, adoption and sustained use. Future studies should investigate which digital interventions or combinations of different interventions are more successful in promoting PA among inactive adults according to the characteristics and preferences of the users.Trial registrationClinical trial registered at ClinicalTrials.gov: NCT04526444.

Abstract Aims Despite strong recommendations, outpatient cardiac rehabilitation is underused in chronic heart failure (CHF) patients. Possible barriers are frailty, accessibility, and rural living, which may be overcome by telerehabilitation. We designed a randomized, controlled trial to evaluate the feasibility of a 3‐month real‐time, home‐based telerehabilitation, high‐intensity exercise programme for CHF patients who are either unable or unwilling to participate in standard outpatient cardiac rehabilitation and to explore outcomes of self‐efficacy and physical fitness at 3 months post‐intervention. Methods and results CHF patients with reduced (≤40%), mildly reduced (41–49%), or preserved ejection fraction (≥50%) (n = 61) were randomized 1:1 to telerehabilitation or control in a prospective controlled trial. The telerehabilitation group (n = 31) received real‐time, home‐based, high‐intensity exercise for 3 months. Inclusion criteria were (i) ≥18 years, (ii) New York Heart Association class II‐III, stable on optimized medical therapy for >4 weeks, and (iii) N‐terminal pro‐brain natriuretic peptide >300 ng/L. All participants participated in a 2‐day ‘Living with heart failure’ course. No other intervention beyond standard care was provided for controls. Outcome measures were adherence, adverse events, self‐reported outcome measures, the general perceived self‐efficacy scale, peak oxygen uptake (VO2peak) and a 6‐min walk test (6MWT). The mean age was 67.6 (11.3) years, and 18% were women. Most of the telerehabilitation group (80%) was adherent or partly adherent. No adverse events were reported during supervised exercise. Ninety‐six per cent (26/27) reported that they felt safe during real‐time, home‐based telerehabilitation, high‐intensity exercise, and 96% (24/25) reported that, after the home‐based supervised telerehabilitation, they were motivated to participate in further exercise training. More than half the population (15/26) reported minor technical issues with the videoconferencing software. 6MWT distance increased significantly in the telerehabilitation group (19 m, P = 0.02), whereas a significant decrease in VO2peak (−0.72 mL/kg/min, P = 0.03) was observed in the control group. There were no significant differences between the groups in general perceived self‐efficacy scale, VO2peak, and 6MWT distance after intervention or at 3 months post‐intervention. Conclusions Home‐based telerehabilitation was feasible in chronic heart failure patients inaccessible for outpatient cardiac rehabilitation. Most participants were adherent when given more time and felt safe exercising at home under supervision, and no adverse events occurred. The trial suggests that telerehabilitation can increase the use of cardiac rehabilitation, but the clinical benefit of telerehabilitation must be evaluated in larger trials.

Migraine is a common and debilitating neurological disorder characterized by the recurrent attack of pulsating headaches typically localized on one side of the head associated with other disabling symptoms, such as nausea, increased sensitivity to light, sound and smell and mood changes. Various clinical factors, including the excessive use of migraine medication, inadequate acute treatment and stressful events, can contribute to the worsening of the condition, which may evolve to chronic migraine, that is, a headache present on >15 days/month for at least 3 months. Chronic migraine is frequently associated with various comorbidities, including anxiety and mood disorders, particularly depression, which complicate the prognosis, response to treatment and overall clinical outcomes. Emerging research indicates a connection between alterations in the composition of the gut microbiota and mental health conditions, particularly anxiety and depression, which are considered disorders of the gut–brain axis. This underscores the potential of modulating the gut microbiota as a new avenue for managing these conditions. In this context, it is interesting to investigate whether migraine, particularly in its chronic form, exhibits a dysbiosis profile similar to that observed in individuals with anxiety and depression. This could pave the way for interventions aimed at modulating the gut microbiota for treating difficult-to-manage migraines.

The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005 shows potent inhibitory activity in vitro. Here, we assessed the effect of AKU-005 in a migraine animal model based on nitroglycerin (NTG) administration. Male rats were treated with AKU-005 (0.5 mg/kg, i.p.) or vehicle 3 h after receiving NTG (10 mg/kg, i.p.) or NTG vehicle. One hour later, rats were subjected to the open field test followed by the orofacial formalin test. At the end of the test, we collected serum samples for assessing calcitonin gene-related peptide (CGRP) levels as well as meninges, trigeminal ganglia, and brain areas to assess mRNA levels of CGRP and pro-inflammatory cytokines, and endocannabinoid and related lipid levels. AKU-005 reduced NTG-induced hyperalgesia during the orofacial formalin test but did not influence NTG-induced changes in the open field test. It significantly reduced serum levels of CGRP, CGRP, and pro-inflammatory cytokine mRNA levels in the meninges, trigeminal ganglia, and central areas. Surprisingly, AKU-005 caused no change in endocannabinoids and related lipids in the regions evaluated. The present findings suggest that AKU-005 may have anti-migraine effects by reducing CGRP synthesis and release and the associated inflammatory events. This effect, however, does not seem mediated via an interference with the endocannabinoid pathway.

Abstract Cannabidiol (CBD) is the main pharmacologically active phytocannabinoid. CBD exerts an analgesic effect in several pain models, does not have side effects and has low toxicity. The data about CBD mechanisms of action in pain and its therapeutic potential in this area are limited. Here, we tested CBD effects in animal models specific for migraine. We assayed CBD distribution in plasma and in cranial areas related to migraine pain in male Sprague Dawley rats treated chronically (5 days). Successively, we tested CBD activity on the behavioral and biochemical effects induced in the acute and the chronic migraine animal models by nitroglycerin (NTG) administration. In the acute migraine model, rats received CBD (15 mg or 30 mg/kg, i.p) 3 h after NTG (10 mg/kg i.p.) or vehicle injection. In the chronic migraine model, rats were treated with CBD and NTG every other day over nine days with the following doses: CBD 30 mg/kg i.p., NTG 10 mg/kg i.p. We evaluated behavioral parameters with the open field and the orofacial formalin tests. We explored the fatty acid amide hydrolase gene expression, cytokines mRNA and protein levels in selected brain areas and CGRP serum level. CBD levels in the meninges, trigeminal ganglia, cervical spinal cord, medulla pons, and plasma were higher 1 h after the last treatment than after 24 h, suggesting that CBD penetrates but does not accumulate in these tissues. In the acute model, CBD significantly reduced NTG-induced trigeminal hyperalgesia and CGRP and cytokine mRNA levels in peripheral and central sites. In the chronic model, CBD caused a significant decrease in NTG-induced IL-6 protein levels in the medulla–pons, and trigeminal ganglion. It also reduced CGRP serum levels. By contrast, CBD did not modulate TNF-alpha protein levels and fatty acid amide hydrolase (FAAH) gene expression in any of investigated areas. In both experimental conditions, there was no modulation of anxiety, motor/exploratory behavior, or grooming. These findings show that CBD reaches brain areas involved in migraine pain after systemic administration. They also show for the first time that CBD modulates migraine-related nociceptive transmission, likely via a complex signaling mechanism involving different pathways.

BackgroundPatient-accessible electronic health records (PAEHRs) hold promise for empowering patients, but their impact may vary between mental and somatic health care. Medical professionals and ethicists have expressed concerns about the potential challenges of PAEHRs for patients, especially those receiving mental health care. ObjectiveThis study aims to investigate variations in the experiences of online access to electronic health records (EHRs) among persons receiving mental and somatic health care, as well as to understand how these experiences and perceptions vary among those receiving mental health care at different levels of point of care. MethodsUsing Norwegian data from the NORDeHEALTH 2022 Patient Survey, we conducted a cross-sectional descriptive analysis of service use and perceptions of perceived mistakes, omissions, and offensive comments by mental and somatic health care respondents. Content analysis was used to analyze free-text responses to understand how respondents experienced the most serious errors in their EHR. ResultsAmong 9505 survey participants, we identified 2008 mental health care respondents and 7086 somatic health care respondents. A higher percentage of mental health care respondents (1385/2008, 68.97%) reported that using PAEHR increased their trust in health care professionals compared with somatic health care respondents (4251/7086, 59.99%). However, a significantly larger proportion (P

AbstractObjective To explore older patients’ experiences with accessing and using e-consultations to send text-based clinical inquiries to the general practitioner (GP) online.Design Qualitative study based on semi-structured interviews. Results were analysed through a six-phase thematic analysis and interpreted through Levesque’s framework of patient-centred access to health care.Setting General practice in Norway.Subjects Patients aged over 65 years (n = 16) with experience in using e-consultations.Results Respondents considered e-consultations as an integrated part of general practice which helped them achieve better access to health care. We identified four themes describing older patients’ access to and use of e-consultations: 1) the importance of digital health literacy to learn about and use the service – and the fear of losing it, 2) the high availability of the service as the main advantage, due to the perceived unavailability of physical GP services, 3) the importance of voluntary use of e-consultations, 4) the importance of a trusting relationship with the GP.Implications Information about e-consultations and guidelines for suitable use are recommended to ensure equal access to all patients, regardless of their digital health literacy. Availability problems and high work burdens for the GPs could affect the patients’ choice for using e-consultations. If e-consultations are used for triage purposes, caution should be taken to avoid a shift in workload from the health secretary to the GP.Key points of articleThe extended use of e-consultations with the general practitioner has raised concerns that the service may not be accessible and suitable for older patients.For older users, e-consultations can represent a positive addition to physical consultation forms due to the high availability of the service in a general practice setting characterised by long waiting times.Digital health literacy is essential to learn about and use the service. Information about the service and how to use it should be available to all patients to ensure equal access.A trusting relationship with the GP is described as essential for older patients to perceive the outcome of e-consultations as appropriate and safe.

Resistant migraine characterizes those patients who have failed at least three classes of migraine prophylaxis. These difficult-to-treat patients are likely to be characterized by a high prevalence of psychological disturbances. A dysfunction of the endocannabinoid system (ECS), including alteration in the levels of endocannabinoid congeners, may underlie several psychiatric disorders and the pathogenesis of migraines. Here we explored whether the peripheral gene expression of major components of the ECS and the plasma levels of endocannabinoids and related lipids are associated with psychological disorders in resistant migraine. Fifty-one patients (age = 46.0 ± 11.7) with resistant migraine received a comprehensive psychological evaluation according to the DSM-5 criteria. Among the patients, 61% had personality disorders (PD) and 61% had mood disorders (MD). Several associations were found between these psychological disorders and peripheral ECS alterations. Lower plasma levels of palmitoiletanolamide (PEA) were found in the PD group compared with the non-PD group. The MD group was characterized by lower mRNA levels of diacylglycerol lipase α (DAGLα) and CB2 (cannabinoid-2) receptor. The results suggest the existence of peripheral dysfunction in some components of the ECS and an alteration in plasma levels of PEA in patients with resistant migraine and mood or personality disorders.

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

Abstract Aims To investigate the associations of cardiorespiratory fitness with cardiac, vascular, renal and cardiorenal characteristics in chronic heart failure in a telerehabilitation randomized clinical trial. Secondly, to evaluate the associations of cardiorenal syndrome with the effects of exercise. Methods and results Sixty‐nine heart failure patients attended baseline examination, and 61 patients were randomly assigned 1:1 to 3‐month telerehabilitation or control. Data were collected at baseline and 3‐month post‐intervention, including echocardiography and vascular ultrasound, laboratory tests, exercise test with peak oxygen consumption (VO2peak) measurement and 6‐min walk test (6MWT). Baseline VO2peak and 6MWT distance was 0.85 mL*min−1*kg−1 lower and 20 m shorter per 10 mL/min/1.73m2 lower estimated glomerular filtration rate (both P 50% more common compared with those without (all P

Abstract Background The gold standard in canine blood pressure (BP) measurement is the invasive method; however, non‐invasive blood pressure measurement techniques (NIBP) are more commonly used. The lack of small, lightweight, cheap, fast and portable NIBP still remains a point to improve in the emergency setting. Key Findings A human wrist blood pressure (WBP) device was evaluated in comparison with the veterinary high‐definition oscillometry (HDO) in conscious normotensive dogs. Systolic and diastolic BPs were evaluated in two groups of dogs. The bias, the limits of agreement and correlation between variables were calculated. Twenty‐five and 36 dogs were, respectively, included in Study No. 1 (dogs weighting ≥10 kg) and 2 (dogs weighting ≥20 kg). In both studies, correlation between the two devices was moderate. A better agreement was displayed for diastolic pressure and poor precision for both systolic and diastolic pressures measurements (as determined by wide limits of agreement). The WBP method underestimated both the systolic and diastolic BP with respect to the HDO method. The inclusion of bigger dogs (Study No. 2) with limb circumference more like to human limb dimension did not improve the agreement between considered methods. Significance The human WBP monitor considered is not suitable to replace the commonly used veterinary HDO for in‐clinic BP monitoring in normotensive conscious dogs.

Abstract Background Patient accessible electronic health records (PAEHR) hold the potential to increase patient empowerment, especially for patients with complex, long-term or chronic conditions. However, evidence of its benefits for patients who undergo mental health treatment is unclear and inconsistent, and several concerns towards use of PAEHR emerged among health professionals. This study aimed at exploring the impact of PAEHR among mental health professionals in terms of patient-provider relationship, changes in the way of writing in the electronic health records and reasons for denying access to information. Methods In-depth qualitative interviews with health professionals working in two mental health outpatient clinics at Helgelandssykehuset in Northern Norway, one of the first hospitals in Norway to implement the PAEHR in 2015. The interviews were conducted by phone or videoconferencing, audio recorded and transcribed verbatim. Data were analyzed by a multidisciplinary research team using the Framework Method. Results A total of 16 in-depth qualitative interviews were conducted in April and May 2020. The PAEHR implemented in Norway was seen as a tool to increase transparency and improve the patient-provider relationship. The PAEHR was seen to have negative consequences only in limited situations, such as for patients with severe mental conditions, for child protective services when parents access their children’s journal, or for patients with abusive partners. The functionality to deny access to the journal was used rarely. A more common practice for making information not immediately available was to delay the final approval of the notes. The documentation practices changed over the years, but it was not clear to what extent the changes were attributable to the introduction of the PAEHR. Health professionals write their notes keeping in mind that patients might read them, and they try to avoid unclear language, information about third parties, and hypotheses that might create confusion. Conclusions The concerns voiced by mental health professionals regarding the impact of the PAEHR on the patient-provider relationship and practices to deny access to information were not supported by the results of this study. Future research should explore changes in documentation practices by analysing the content of the electronic health records.

Abstract Targeting fatty acid amide hydrolase (FAAH) is a promising therapeutic strategy to combat certain forms of pain, including migraine headache. FAAH inhibitors, such as the O-biphenyl-3-yl carbamate URB597, have been shown to produce anti-hyperalgesic effects in animal models of migraine. The objective of this study was to investigate the behavioral and biochemical effects of compounds ARN14633 and ARN14280, two URB597 analogs with improved solubility and bioavailability, in a migraine-specific rat model in which trigeminal hyperalgesia is induced by nitroglycerin (NTG) administration. ARN14633 (1 mg/kg, i.p.) and ARN14280 (3 mg/kg, i.p.) were administered to adult male Sprague-Dawley rats 3 hours after NTG injection. One hour after the administration of either compound, rats were subjected to the orofacial formalin test. ARN14633 and ARN14280 attenuated NTG-induced nocifensive behavior and reduced transcription of genes encoding neuronal nitric oxide synthase, pain mediators peptides (calcitonin gene-related peptide, substance P) and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and 6) in the trigeminal ganglion, cervical spinal cord and medulla. Finally, both compounds strongly elevated levels of endocannabinoids and/or other FAAH substrates in cervical spinal cord and medulla, and, to a lesser extent, in the trigeminal ganglia. The results indicate that the novel global FAAH inhibitors ARN14633 and ARN14280 elicit significant anti-hyperalgesic effects in a migraine-specific animal model and inhibit the associated peptidergic-inflammatory response. Although the precise mechanism underlying these effects remains to be elucidated, our results support further investigational studies of FAAH blockade as a potential therapeutic strategy to treat migraine conditions.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease.

This retrospective cohort study included one hundred fifty-seven medium and large-size dogs with the aim of evaluating the effect of signalment and echocardiographic features on complications, outcomes and left ventricular modifications before and after patent ductus arteriosus (PDA) closure. The patients were divided in two groups based on the heart remodeling after closure: Group A included dogs that had a reduction in the end-systolic volume index (ESVI) after closure compared to the ESVI measured before; Group B included dogs without a reduction in ESVI after closure. Body weight, minimal ductal diameter (MDD) of PDA, end-diastolic volume index and presence of arrhythmias at presentation were significantly higher in Group B compared to Group A. The shortening fraction and ejection fraction after closure were reduced in both groups, but in Group B there was a major reduction, and the mean values indicated a possible systolic dysfunction. Complications during the procedure and death due to cardiac reasons were greater in Group B compared to Group A. In conclusion, a higher body weight, a larger MDD, a more severe heart enlargement or arrhythmias at presentation increased the risk of developing a worsening structural and functional condition after ductal closure, and this can be associated with perioperative complications and cardiac death.

Cannabinoids are proposed for alleviating neuropathic pain, but their use is limited by cannabimimetic side effects. The inhibition of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the endocannabinoid anandamide, has received attention as an alternative to cannabinoids in the treatment of neuropathic pain. Here, we investigated the effect of URB937, a blood–brain barrier impermeant FAAH inhibitor, on experimentally induced mechanical allodynia in an animal model of trigeminal neuralgia. Male Sprague-Dawley rats were subjected to chronic constriction injury of the infraorbital nerve (IoN-CCI); operated animals were treated sub-chronically with URB937 (1 mg/kg, i.p.) or vehicle before or after trigeminal mechanical allodynia establishment. We also assayed mRNA expression levels of the pain neuropeptide calcitonin gene-related peptide (CGRP) and cytokines in the medulla, cervical spinal cord, and trigeminal ganglion ipsilateral to IoN-CCI using rt-PCR. URB937 treatment prevented the development of mechanical allodynia and IoN-CCI-induced changes in mRNA expression levels of CGRP and cytokines in the evaluated areas. When administered after allodynia development, URB937 prevented IoN-CCI-induced changes in CGRP and cytokine gene expression; this was not associated with a significant abrogation of the mechanical allodynia. These findings suggest that URB937 may counteract, but not reverse, the development of allodynia in trigeminal neuralgia. Further research is needed to elucidate the underlying mechanisms.

BackgroundThe use of video consultations (VCs) in Norwegian general practice rapidly increased during the COVID-19 pandemic. During societal lockdowns, VCs were used for nearly all types of clinical problems, as in-person consultations were kept to a minimum. ObjectiveThis study aimed to explore general practitioners’ (GPs’) experiences of potentials and pitfalls associated with the use of VCs during the first pandemic lockdown. MethodsBetween April 14 and May 3, 2020, all regular Norwegian GPs (N=4858) were invited to answer a web-based survey, which included open-ended questions about their experiences with the advantages and pitfalls of VCs. A total of 2558 free-text answers were provided by 657 of the 1237 GPs who participated in the survey. The material was subjected to reflexive thematic analysis. ResultsFour main themes were identified. First, VCs are described as being particularly convenient, informative, and effective for consultations with previously known patients. Second, strategically planned VCs may facilitate effective tailoring of clinical trajectories that optimize clinical workflow. VCs allow for an initial overview of the problem (triage), follow-up evaluation after an in-person consultation, provision of advice and information concerning test results and discharge notes, extension of sick leaves, and delivery of other medical certificates. VCs may, in certain situations, enhance the GPs’ insight in their patients’ relational and socioeconomical resources and vulnerabilities, and even facilitate relationship-building with patients in need of care who might otherwise be reluctant to seek help. Third, VCs are characterized by a demarcated communication style and the “one problem approach,” which may entail effectiveness in the short run. However, the web-based communication climate implies degradation of valuable nonverbal signals that are more evidently present in in-person consultations. Finally, overreliance on VCs may, in a longer perspective, undermine the establishment and maintenance of relational trust, with a negative impact on the quality of care and patient safety. Compensatory mechanisms include clarifying with the patient what the next step is, answering any questions and giving further advice on treatment if conditions do not improve or there is a need for follow-up. Participation of family members can also be helpful to improve reciprocal understanding and safety. ConclusionsThe findings have relevance for future implementation of VCs and deserve further exploration under less stressful circumstances.

Background Atherosclerosis vulnerability regression has been evidenced mostly in randomized clinical trials with intensive lipid‐lowering therapy. We aimed to demonstrate vulnerability regression in real life, with a comprehensive quantitative method, in patients with asymptomatic mild to moderate carotid atherosclerosis on a secondary prevention program. Methods and Results We conducted a single‐center prospective observational study (MAGNETIC [Magnetic Resonance Imaging as a Gold Standard for Noninvasive Evaluation of Atherosclerotic Involvement of Carotid Arteries]): 260 patients enrolled at a cardiac rehabilitation center were followed for 3 years with serial magnetic resonance imaging. Per section cutoffs (95th/5th percentiles) were derived from a sample of 20 consecutive magnetic resonance imaging scans: (1) lipid‐rich necrotic core: 26% of vessel wall area; (2) intraplaque hemorrhage: 12% of vessel wall area; and (3) fibrous cap: (a) minimum thickness: 0.06 mm, (b) mean thickness: 0.4 mm, (c) projection length: 11 mm. Patients with baseline magnetic resonance imaging of adequate quality (n=247) were classified as high (n=63, 26%), intermediate (n=65, 26%), or low risk (n=119, 48%), if vulnerability criteria were fulfilled in ≥2 contiguous sections, in 1 or multiple noncontiguous sections, or in any section, respectively. Among high‐risk patients, a conversion to any lower‐risk status was found in 11 (17%; P=0.614) at 6 months, in 16 (25%; P=0.197) at 1 year, and in 19 (30%; P=0.009) at 3 years. Among patients showing any degree of carotid plaque vulnerability, 21 (16%; P=0.014) were diagnosed at low risk at 3 years. Conclusions This study demonstrates with a quantitative approach that vulnerability regression is common in real life. A secondary prevention program can promote vulnerability regression in asymptomatic patients in the mid to long term.

Abstract Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rates and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by 61 drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. The test–retest reliability was evaluated using Pearson’s correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software version 12.03.02. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: “attention,” “organization,” and “precision,” with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p = 0.284). In conclusion, despite the small sample size, iKetoCheck is a valid tool for evaluating KDTs’ adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

Abstract Aims In healthy subjects, adrenergic stimulation augments left ventricular (LV) long‐axis shortening and lengthening, and increases left atrial (LA) to LV intracavitary pressure gradients in early diastole. Lower increments are observed in patients with heart failure with preserved ejection fraction (HFpEF). We hypothesized that exercise in HFpEF would further impair passive LV filling in early‐mid diastole, during conduit flow from pulmonary veins. Methods and results Twenty HFpEF patients (67.8 ± 9.8 years; 11 women), diagnosed using 2007 ESC recommendations, underwent ramped semi‐supine bicycle exercise to submaximal target heart rate (∼100 bpm) or symptoms. Seventeen asymptomatic subjects (64.3 ± 8.9 years; 7 women) were controls. Simultaneous LA and LV volumes were measured from pyramidal 3D‐echocardiographic full‐volume datasets acquired from an apical window at baseline and during stress, together with brachial arterial pressure. LA conduit flow was computed from the increase in LV volume from its minimum at end‐systole to the last frame before atrial contraction (onset of the P wave), minus the reduction in LA volume during the same time interval; the difference was integrated and expressed as average flow rate, according to a published formula. The slope of single‐beat preload recruitable stroke work (PRSW) quantified LV inotropic state. 3D LV torsion (rotation of the apex minus rotation of the base divided by LV length) was also measurable, both at rest and during stress, in 10 HFpEF patients and 4 controls. There were divergent responses in conduit flow rate, which increased by 40% during exercise in controls (+17.8 ± 37.3 mL/s) but decreased by 18% in patients with HFpEF (−9.6 ± 42.3 mL/s) (P = 0.046), along with congruent changes (+1.77 ± 1.13°/cm vs. −1.94 ± 2.73°/cm) in apical torsion (P = 0.032). Increments of conduit flow rate and apical torsion during stress correlated with changes in PRSW slope (P = 0.003 and P = 0.006, respectively). Conclusions In HFpEF, conduit flow rate decreases when diastolic dysfunction develops during exercise, in parallel with changes in LV inotropic state and torsion, contributing to impaired stroke volume reserve. Conduit flow is measurable using 3D‐echocardiographic full‐volume atrio‐ventricular datasets, and as a marker of LV relaxation can contribute to the diagnosis of HFpEF.

IntroductionPhysical inactivity is the fourth leading risk factor for global mortality, and inactive adults have a higher risk to develop lifestyle diseases. To date, there is preliminary evidence of the efficacy of fitness technologies and other digital interventions for physical activity (PA) promotion. Intervention studies are needed to test the effectiveness and implementation of innovative PA promotion strategies.Methods and analysisThe ONWARDS study is a hybrid type I effectiveness-implementation randomized control trial aiming at an inactive and presumably high-risk population living in Northern Norway. One hundred and eighty participants will be assigned to 3 groups in a 1:1:1 ratio and participate for 18 months. Participants in group A will be provided an activity tracker with the personalized metric Personal Activity Intelligence (PAI). Participants in group B will be provided with both an activity tracker with the personalized metric PAI and access to online training videos (Les Mills+) to perform home-based training. Participants in group C will be provided an activity tracker with the personalized metric PAI, home-based online training and additional peer support via social media. The primary objective is to test which combination of interventions is more effective in increasing PA levels and sustaining long-term exercise adherence. Secondary objectives include: proportion of participants reaching PA recommendations; exercise adherence; physical fitness; cardiovascular risk; quality of life; perceived competence for exercise; self-efficacy; social support; usability; users' perspectives on implementation outcomes (adoption, acceptability, adherence, sustainability). The study design will allow testing the effectiveness of the interventions while gathering information on implementation in a real-world situation.DiscussionThis study can contribute to reduce disparities in PA levels among inactive adults by promoting PA and long-term adherence. Increased PA might, in turn, result in better prevention of lifestyle diseases. Digital interventions delivered at home can become an alternative to training facilities, making PA accessible and feasible for inactive populations and overcoming known barriers to PA. If effective, such interventions could potentially be offered through national health portals to citizens who do not meet the minimum recommendations on PA or prescribed by general practitioners or specialists.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04526444, Registered 23 April 2021, identifier: NCT04526444.

BackgroundReducing maternal mortality, neonatal mortality and under 5-year mortality are important targets addressed by the United Nations' Sustainable Development Goals. Despite studies reported an improvement in maternal and child health indicators, the progress achieved is not uniform across regions. Due to the increasing availability of mobile phones in low and middle-income countries, mHealth could impact considerably on reducing maternal and child mortality and maximizing women's access to quality care, from the antenatal stage to the post-natal period.MethodsA systematic literature review of mHealth interventions aimed at reducing maternal and child mortality in Sub-Saharan Africa and Southern Asia. Primary outcomes were maternal mortality, neonatal mortality, and under-five mortality. Secondary outcomes were skilled birth attendance, antenatal care (ANC) and post-natal care (PNC) attendance, and vaccination/immunization coverage. We searched for articles published from January 2010 to December 2020 in Embase, Medline and Web of Science. Quantitative comparative studies were included. The protocol was developed according to the PRISMA Checklist and published in PROSPERO [CRD42019109434]. The Quality Assessment Tool for Quantitative Studies was used to assess the quality of the eligible studies.Results23 studies were included in the review, 16 undertaken in Sub-Saharan Africa and 7 in Southern Asia. Most studies used SMS or voice message reminders for education purposes. Only two studies reported outcomes on neonatal mortality, with positive results. None of the studies reported results on maternal mortality or under-five mortality. Outcomes on skilled birth attendance, ANC attendance, PNC attendance, and vaccination coverage were reported in six, six, five, and eleven studies, respectively. Most of these studies showed a positive impact of mHealth interventions on the secondary outcomes.ConclusionSimple mHealth educational interventions based on SMS and voice message reminders are effective at supporting behavior change of pregnant women and training of health workers, thus improving ANC and PNC attendance, vaccination coverage and skilled birth attendance. Higher quality studies addressing the role of mHealth in reducing maternal and child mortality in resource-limited settings are needed, especially in Southern Asia.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019109434, identifier CRD42019109434.

Increased anandamide levels via fatty acid amide hydrolase (FAAH) inhibition can decrease the pronociceptive responses and inflammatory mediators in animal models of migraine. Here, we profile the pharmacological activity of the FAAH inhibitor JZP327A, a chiral 1,3,4-oxadiazol-2(3H)-one compound, in the mediation of spontaneous and nocifensive behaviour in the animal models of migraine based on nitroglycerin (NTG) administration. JZP327A (0.5 mg/kg, i.p.) or vehicle was administered to male rats 3 h after NTG (10 mg/kg, i.p.) or NTG vehicle injection. The rats were then exposed to the open field test and an orofacial formalin test 1 h later. The levels of endocannabinoids and lipid-related substances, and the expression of pain and inflammatory mediators were evaluated in cranial tissues and serum. The findings show that JZP327A did not affect NTG-induced changes in the spontaneous behaviour of rats, while it inhibited NTG-induced hyperalgesia at the orofacial formalin test. Furthermore, JZP327A dramatically decreased the gene expression of calcitonin gene-related peptide (CGRP), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the trigeminal ganglia and medulla-pons, while it did not change endocannabinoids or lipids levels nor CGRP serum levels in the same tissues. These data suggest an anti-hyperalgesic role for JZP327A in the NTG model, which is mediated by the inhibition of the inflammatory cascade of events. This activity does not seem mediated by a change in the levels of endocannabinoids and lipid amides.

Introduction Patients attending psychiatric specialist health services in Northern Norway have since 2015 had the opportunity to access their medical records online. Prior to implementation, there were some concerns in the professional field that patient accessible electronic health records might introduce some challenges. Objectives In this study, we asked psychiatric providers in outpatient psychiatric care about the impact of patients’ online access to documentation practices and whether they felt the access impacted the provider-patient relationship. We also examined whether the providers sought to deny patients’ access to any information. Methods 16 qualitative in-depth interviews were performed with mental health providers working in the specialist services in North Norway. Participants had different professional backgrounds, and included doctors, nurses, psychologists and others. The interviews were audio recorded and transcribed verbatim. The data were qualitatively analyzed by means of the framework method. Results The providers varied in their encouragement of patients’ online access, but few expressed concerns. There had been little specific training on how to optimize the writing of notes to accomodate patients’ online acces, but several pointed out that there had been an increased focus on the importance of adapting the notes to promote understanding. Increased transparency was in general seen positively, but the service might not fit all patient categories. Very few patients were denied access. In most cases, the service could improve the patients’ understanding of the treatment and the provider-patient relationship. Conclusions While some voiced caveats, patients’ online access was in general seen as beneficial to the treatment and the provider-patient relationship. Disclosure No significant relationships.

Objectives: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

Abstract Background Chronic renin-angiotensin-aldosterone system (RAAS) activation in course of heart diseases contributes to cardiac remodeling and heart failure. Myxomatous mitral valve disease (MMVD) is characterized by different stages of severity and trend of RAAS activity during the course of the disease is still uncertain. The urinary aldosterone-to-creatinine ratio (UAldo:C) has been proven to reflect RAAS activation in dogs and might be a useful marker in monitoring therapy and disease progression, but data about this parameter need to be expanded. The objective of this study was to evaluate the UAldo:C in healthy dogs and dogs with naturally occurring MMVD, and to investigate the relationships between this parameter and clinical, echocardiographic and laboratory variables. Results The study population consisted of 149 dogs: 49 healthy and 100 MMVD dogs (45 stage B1, 13 stage B2 and 42 stage C). Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of any stages. Breed, sex and age showed a significant impact on UAldo:C. In particular, Chihuahua and Cavalier King Charles spaniel showed significantly higher UAldo:C than other breeds, as well as intact females than other genders. In stage C dogs, UAldo:C appeared to be increased by spironolactone and was positively associated with furosemide dose (P = 0.024). Aldosterone breakthrough (ABT) appeared to occur in 36% (8/22) of stage C dogs not receiving spironolactone. A significant positive association between UAldo:C and left atrium-to-aortic root ratio (LA/Ao) was found. Conclusions Individual factors such as breed, sex and age appeared to influence UAldo:C, and therapy seemed to add further variability. In the light of these results, comparing the UAldo:C of a single patient with a population-based reference value might lead to wrong interpretations and an individual monitoring should be considered. The prevalence of ABT in the present study (36%) was in line with those previously reported. However, due to the high individual variability of UAldo:C found in the study, even this result should be re-evaluated in the setting of an individual longitudinal approach. The positive association between UAldo:C and LA/Ao supports the mutual relationship between RAAS and cardiac remodeling.

The identification of novel targets to modulate the immune response triggered by cerebral ischemia is crucial to promote the development of effective stroke therapeutics. Since tumour necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, is involved in the regulation of immune and stromal cell functions in acute neurodegeneration, we aimed to characterize its involvement in ischemic stroke. Transient middle cerebral artery occlusion (1 h MCAo, followed by 6 to 48 of reperfusion) in mice resulted in a significant elevation in cerebral TSG-6 protein levels, mainly localized in neurons and myeloid cells of the lesioned hemisphere. These myeloid cells were clearly infiltrating from the blood, strongly suggesting that brain ischemia also affects TSG-6 in the periphery. Accordingly, TSG-6 mRNA expression was elevated in peripheral blood mononuclear cells (PBMCs) from patients 48 h after ischemic stroke onset, and TSG-6 protein expression was higher in the plasma of mice subjected to 1 h MCAo followed by 48 h of reperfusion. Surprisingly, plasma TSG-6 levels were reduced in the acute phase (i.e., within 24 h of reperfusion) when compared to sham-operated mice, supporting the hypothesis of a detrimental role of TSG-6 in the early reperfusion stage. Accordingly, systemic acute administration of recombinant mouse TSG-6 increased brain levels of the M2 marker Ym1, providing a significant reduction in the brain infarct volume and general neurological deficits in mice subjected to transient MCAo. These findings suggest a pivotal role of TSG-6 in ischemic stroke pathobiology and underscore the clinical relevance of further investigating the mechanisms underlying its immunoregulatory role.

In recent years, numerous efforts have been made to identify reliable biomarkers useful in migraine diagnosis and progression or associated with the response to a specific treatment. The purpose of this review is to summarize the alleged diagnostic and therapeutic migraine biomarkers found in biofluids and to discuss their role in the pathogenesis of the disease. We included the most informative data from clinical or preclinical studies, with a particular emphasis on calcitonin gene-related peptide (CGRP), cytokines, endocannabinoids, and other biomolecules, the majority of which are related to the inflammatory aspects and mechanisms of migraine, as well as other actors that play a role in the disease. The potential issues affecting biomarker analysis are also discussed, such as how to deal with bias and confounding data. CGRP and other biological factors associated with the trigeminovascular system may offer intriguing and novel precision medicine opportunities, although the biological stability of the samples used, as well as the effects of the confounding role of age, gender, diet, and metabolic factors should be considered.

Abstract Background Migraine can manifest with an episodic or a chronic pattern in a continuum of disease severity. Multiple factors are associated with the progression of the pattern from episodic to chronic. One of the most consistently reported factors is the overuse of medications (MO) for the acute treatment of migraine attacks. The mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) are elusive. In order to provide insights into these mechanisms, the present study aims to identify possible peripheral biomarkers associated with the two forms of migraine, and with the presence of MO. Methods We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with EM (n = 27) or CM-MO (n = 28). Subjects in the CM-MO group were also tested 2 months after an in-hospital detoxification protocol. Results CGRP, miR-382-5p, and miR-34a-5p levels were significantly higher in CM-MO subjects when compared to EM patients (p = 0.003 for all comparisons). After correcting for age, sex, and disease duration, miRNAs expression was still significantly associated with migraine phenotype (EM vs. CM-MO: p = 0.014 for miR-382-5p, p = 0.038 for miR-34a-5p), while CGRP levels were not (p = 0.115). CGRP plasma levels significantly and positively correlated with miR-382-5p (Spearman’s rho: 0.491, p = 0.001) and miR-34a-5p (Spearman’s rho: 0.303, p =0.025) in the overall population. In the CM-MO group, detoxification significantly decreased CGRP levels and miRNAs expression (p = 0.001). When comparing responders and non-responders to the detoxification, the former group (n = 23) showed significantly higher levels of CGRP at baseline, and significantly lower expression of miR-382-5p after the detoxification. Conclusions Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO. Trial registration The study protocol was registered at www.clinicaltrials.gov ( NCT04473976 ).

Matteo Briguglio,1,* Jacopo Antonino Vitale,1 Roberta Galentino,2 Giuseppe Banfi,1,3 Carlotta Zanaboni Dina,4 Alberto Bona,5 Giancarlo Panzica,6 Mauro Porta,2,* Bernardo Dell’Osso,7–9,* Ira David Glick9,* 1IRCCS Orthopedic Institute Galeazzi, Scientific Direction, Milan, Italy; 2IRCCS Orthopedic Institute Galeazzi, Tourette’s Syndrome and Movement Disorders Centre, Milan, Italy; 3Department of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy; 4TICEA Center, Scientific Direction, Milan, Italy; 5Neurosurgery Department, ICCS Istituto Clinico Città Studi, Milan, Italy; 6Department of Neuroscience, Rita Levi Montalcini, University of Turin, Turin, Italy; 7University of Milan, Department of Clinical and Biomedical Sciences Luigi Sacco, ASST Fatebenefratelli-Sacco, Ospedale Sacco Polo Universitario, Milan, Italy; 8“Aldo Ravelli” Center for Neurotechnology and Brain Therapeutic, University of Milan, Milan, Italy; 9Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA*These authors contributed equally to this workCorrespondence: Matteo BriguglioIRCCS Orthopedic Institute Galeazzi, Scientific Direction, Via Riccardo Galeazzi, 4, Milan 20161, MI, ItalyTel +39 338 6087042Email matteo.briguglio@grupposandonato.itAbstract: Neuropsychiatric disorders stem from gene-environment interaction and their development can be, at least in some cases, prevented by the adoption of healthy and protective lifestyles. Once full blown, neuropsychiatric disorders are prevalent conditions that patients live with a great burden of disability. Indeed, the determinants that increase the affliction of neuropsychiatric disorders are various, with unhealthy lifestyles providing a significant contribution in the interplay between genetic, epigenetic, and environmental factors that ultimately represent the pathophysiological basis of these impairing conditions. On one hand, the adoption of Healthy Eating education, Physical Activity programs, and Sleep hygiene promotion (HEPAS) has the potential to become one of the most suitable interventions to reduce the risk to develop neuropsychiatric disorders, while, on the other hand, its integration with pharmacological and psychological therapies seems to be essential in the overall management of neuropsychiatric disorders in order to reduce the disability and improve the quality of life of affected patients. We present an overview of the current evidence in relation to HEPAS components in the prevention and management of neuropsychiatric disorders and provide suggestions for clinical practice.Keywords: neuropsychiatry, diet, motor activity, sleep, quality of health care

Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges. Rats were treated with ADM_12 (TRPA1 antagonist) and then underwent an orofacial formalin test to assess trigeminal hyperalgesia. mRNA levels of pro- and anti-inflammatory cytokines, calcitonin gene-related peptide (CGRP) and glia cell activation were evaluated in the Medulla oblongata and in the trigeminal ganglia. In the nitroglycerin-treated rats, ADM_12 showed an antihyperalgesic effect in both acute and chronic models, and it counteracted the changes in CGRP and cytokine gene expression. In the acute nitroglycerin model, ADM_12 reduced nitroglycerin-induced increase in microglial and astroglial activation in trigeminal nucleus caudalis area. In the chronic model, we detected a nitroglycerin-induced activation of satellite glial cells in the trigeminal ganglia that was inhibited by ADM_12. These findings show that TRPA1 antagonism reverts experimentally induced hyperalgesia in acute and chronic models of migraine and prevents multiple changes in inflammatory pathways by modulating glial activation.

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited.Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018.Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for

Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology and more specifically in the mechanisms underlying peripheral and central sensitization. Here, we explored the interaction of CGRP with other pain mediators relevant for neuronal sensitization in an animal model of chronic migraine. Male Sprague-Dawley rats were exposed to nitroglycerin (NTG, 5 mg/kg, i.p.) or vehicle co-administered with the CGRP receptor antagonist olcegepant (2 mg/kg i.p.), or its vehicle, every other day over a 9-day period. Twenty-four hours after the last injection of NTG (or vehicle), behavioral test and ex vivo analysis were performed. Olcegepant attenuated NTG-induced trigeminal hyperalgesia in the second phase of the orofacial formalin test. Interestingly, it also reduced gene expression and protein levels of CGRP, pro-inflammatory cytokines, inflammatory-associated miRNAs (miR-155-5p, miR-382-5p, and miR-34a-5p), and transient receptor potential ankyrin channels in the medulla–pons area, cervical spinal cord, and trigeminal ganglia. Similarly, olcegepant reduced the NTG-induced increase in CGRP and inflammatory cytokines in serum. The findings show that the activation of the CGRP pathway in a migraine animal model was associated to the persistent activation of inflammatory pathways, which was paralleled by a condition of hyperalgesia. These molecular events are relevant for informing us about the mechanisms underlying chronic migraine.

Hanne Hoaas,1,2 Paolo Zanaboni,1 Audhild Hjalmarsen,3,4 Bente Morseth,5 Birthe Dinesen,6 Angela T Burge,7–9 Narelle S Cox,7,9 Anne E Holland7–91Norwegian Centre for E-health Research, University Hospital of North Norway, Tromsø, Norway; 2Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; 3Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; 4Department of Pulmonary Medicine, University Hospital of North Norway, Tromsø, Norway; 5School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway; 6Laboratory of Welfare Technologies – Telehealth & Telerehabilitation, SMI, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; 7Discipline of Physiotherapy, La Trobe University, Melbourne, Australia; 8Department of Physiotherapy, Alfred Health, Melbourne, Australia; 9Institute for Breathing and Sleep, Melbourne, AustraliaPurpose: Seasons and weather conditions might influence participation in physical activity and contribute to differences between countries. This study aimed at investigating whether there were differences in physical activity levels between Norwegian, Danish and Australian people with chronic obstructive pulmonary disease (COPD), and establishing if any variations in physical activity were attributable to seasons.Patients and methods: A cross-sectional study where study subjects were people with COPD who participated in two separate clinical trials: the iTrain study (Norway, Denmark, and Australia) and the HomeBase study (Australia). Physical activity was objectively assessed with an activity monitor; variables were total energy expenditure, number of daily steps, awake sedentary time, light, and moderate-to-vigorous intensity physical activity. Differences in physical activity between countries and seasons were compared, with adjustment for disease severity.Results: In total, 168 participants were included from Norway (N=38), Denmark (N=36) and Australia (N=94). After controlling for disease severity, time spent in awake sedentary time was greater in Danish participants compared to the other countries (median 784 minutes/day [660–952] vs 775 minutes/day [626–877] for Norwegians vs 703 minutes/day [613–802] for Australians, P=0.013), whilst time spent in moderate to vigorous physical activity was lower (median 21 minutes/day [4–73] vs 30 minutes/day [7–93] for Norwegians vs 48 minutes/day [19–98] for Australians, P=0.024). Participants walked more during summer (median 3502 [1253–5407] steps/day) than in spring (median 2698 [1613–5207] steps/day), winter (median 2373 [1145–4206] steps/day) and autumn (median 1603 [738–4040] steps/day), regardless of geography. The median difference between summer and other seasons exceeded the minimal clinically important difference of 600 steps/day. However, the differences were not statistically significant (P=0.101).Conclusion: After controlling for disease severity, Danish participants spent more time in an awake sedentary state and less time in moderate to vigorous physical activity than their counterparts in Norway and Australia. People with COPD increased their physical activity in summer compared to other seasons. Weather conditions and seasonal variations may influence outcomes in clinical trials and health registries measuring physical activity over time, irrespective of the interventions delivered, and should be taken into account when interpreting results.Keywords: chronic obstructive pulmonary disease, activity monitoring, population comparison, seasons, weather

BackgroundThe COVID-19 pandemic imposed an acute, sharp rise in the use of video consultations (VCs) by general practitioners (GPs) in Norway. ObjectiveThis study aims to document GPs’ experiences with the large-scale uptake of VCs in the natural experiment context of the pandemic. MethodsA nationwide, cross-sectional online survey was conducted among Norwegian GPs during the pandemic lockdown (April 14-May 3, 2020). Each respondent was asked to evaluate up to 10 VCs. Basic demographic characteristics of the GPs and their practices were collected. The associations between GPs’ perceived suitability of the VCs, the nature of the patients’ main problems, prior knowledge of the patients (relational continuity), and follow-up of previously presented problems (episodic continuity) were explored using descriptive statistics, diagrams, and chi-square tests. ResultsIn total, 1237 GPs (26% of the target group) responded to the survey. Among these, 1000 GPs offered VCs, and 855 GPs evaluated a total of 3484 VCs. Most GPs who offered VCs (1000/1237; 81%) had no experience with VCs before the pandemic. Overall, 51% (1766/3476) of the evaluated VCs were considered to have similar or even better suitability to assess the main reason for contact, compared to face-to-face consultations. In the presence of relational continuity, VCs were considered equal to or better than face-to-face consultations in 57% (1011/1785) of cases, as opposed to 32% (87/274) when the patient was unknown. The suitability rate for follow-up consultations (episodic continuity) was 61% (1165/1919), compared to 35% (544/1556) for new patient problems. Suitability varied considerably across clinical contact reasons. VCs were found most suitable for anxiety and life stress, depression, and administrative purposes, as well as for longstanding or complex problems that normally require multiple follow-up consultations. The GPs estimate that they will conduct about 20% of their consultations by video in a future, nonpandemic setting. ConclusionsOur study of VCs performed in general practice during the pandemic lockdown indicates a clear future role for VCs in nonpandemic settings. The strong and consistent association between continuity of care and GPs’ perceptions of the suitability of VCs is a new and important finding with considerable relevance for future primary health care planning.

Inhibiting the activity of fatty-acid amide hydrolase (FAAH), the enzyme that deactivates the endocannabinoid anandamide, enhances anandamide-mediated signaling and holds promise as a molecular target for the treatment of human pathologies such as anxiety and pain. We have previously shown that the peripherally restricted FAAH inhibitor, URB937, prevents nitroglycerin-induced hyperalgesia – an animal model of migraine - and attenuates the activation of brain areas that are relevant for migraine pain, e.g. trigeminal nucleus caudalis and locus coeruleus. The current study is aimed at profiling the behavioral and biochemical effects of URB937 in animal models of acute and chronic migraine. We evaluated the effects of URB937 in two rat models that capture aspects of acute and chronic migraine, and are based on single or repeated administration of the vasodilating drug, nitroglycerin (NTG). In addition to nocifensive behavior, in trigeminal ganglia and medulla, we measured mRNA levels of neuropeptides and pro-inflammatory cytokines along with tissue levels of anandamide and palmitoylethanolamide (PEA), an endogenous agonist of peroxisome proliferator-activated receptor type-a (PPAR-a), which is also a FAAH substrate. In the acute migraine model, we also investigated the effect of subtype-selective antagonist for cannabinoid receptors 1 and 2 (AM251 and AM630, respectively) on nocifensive behavior and on levels of neuropeptides and pro-inflammatory cytokines. In the acute migraine paradigm, URB937 significantly reduced hyperalgesia in the orofacial formalin test when administered either before or after NTG. This effect was accompanied by an increase in anandamide and PEA levels in target neural tissue, depended upon CB1 receptor activation, and was associated with a decrease in calcitonin gene-related peptide (CGRP), substance P and cytokines TNF-alpha and IL-6 mRNA. Similar effects were observed in the chronic migraine paradigm, where URB937 counteracted NTG-induced trigeminal hyperalgesia and prevented the increase in neuropeptide and cytokine transcription.The results show that peripheral FAAH inhibition by URB937 effectively reduces both acute and chronic NTG-induced trigeminal hyperalgesia, likely via augmented anandamide-mediated CB1 receptor activation. These effects are associated with inhibition of neuropeptidergic and inflammatory pathways.

Objectives To explore patients’ use and experiences with four digital health services implemented in Norway to enable electronic communication between patients and their general practitioner (GP): (1) electronic booking of appointments; (2) electronic prescription renewal; (3) electronic contact with the GP’s office for non-clinical inquiries; and (4) e-consultation for clinical inquiries.Design An online survey consisting of quantitative data supplemented by qualitative information was conducted to explore: (1) characteristics of the users; (2) use; (3) experiences, perceived benefits and satisfaction; and (4) time spent using the digital health services.Setting Primary care.Participants 2043 users of the digital health services answering the survey.Results There was a higher proportion of women, younger adults and digitally active citizens with high education. Electronic booking of appointments was the most used service (66.4%), followed by electronic prescription renewal (54.3%). Most users (80%) could more easily and efficiently book an appointment electronically than by phone. Over 90% of the respondents thought that it was easier to renew a prescription electronically, 76% obtained a better overview of their medications and 46% reported higher compliance. For non-clinical inquiries, most respondents (60%) thought that it was easier to write electronic messages than communicate by phone. For clinical enquiries, many patients agreed that e-consultation could lead to a better followup (72%) and improved quality of treatment (58%). Users were highly satisfied with the services and recommended their use to others. Time saving was the most evident benefit for patients. This was confirmed by the differences in time spent using the digital health services compared with conventional approaches, all found to be statistically significant.Conclusion Citizens using e-consultation and other digital health services with their GP in Norway are satisfied and consider them as useful and efficient alternatives to conventional approaches.

BackgroundDespite the prevalence of mobile health (mHealth) technologies and observations of their impacts on patients’ health, there is still no consensus on how best to evaluate these tools for patient self-management of chronic conditions. Researchers currently do not have guidelines on which qualitative or quantitative factors to measure or how to gather these reliable data. ObjectiveThis study aimed to document the methods and both qualitative and quantitative measures used to assess mHealth apps and systems intended for use by patients for the self-management of chronic noncommunicable diseases. MethodsA scoping review was performed, and PubMed, MEDLINE, Google Scholar, and ProQuest Research Library were searched for literature published in English between January 1, 2015, and January 18, 2019. Search terms included combinations of the description of the intention of the intervention (eg, self-efficacy and self-management) and description of the intervention platform (eg, mobile app and sensor). Article selection was based on whether the intervention described a patient with a chronic noncommunicable disease as the primary user of a tool or system that would always be available for self-management. The extracted data included study design, health conditions, participants, intervention type (app or system), methods used, and measured qualitative and quantitative data. ResultsA total of 31 studies met the eligibility criteria. Studies were classified as either those that evaluated mHealth apps (ie, single devices; n=15) or mHealth systems (ie, more than one tool; n=17), and one study evaluated both apps and systems. App interventions mainly targeted mental health conditions (including Post-Traumatic Stress Disorder), followed by diabetes and cardiovascular and heart diseases; among the 17 studies that described mHealth systems, most involved patients diagnosed with cardiovascular and heart disease, followed by diabetes, respiratory disease, mental health conditions, cancer, and multiple illnesses. The most common evaluation method was collection of usage logs (n=21), followed by standardized questionnaires (n=18) and ad-hoc questionnaires (n=13). The most common measure was app interaction (n=19), followed by usability/feasibility (n=17) and patient-reported health data via the app (n=15). ConclusionsThis review demonstrates that health intervention studies are taking advantage of the additional resources that mHealth technologies provide. As mHealth technologies become more prevalent, the call for evidence includes the impacts on patients’ self-efficacy and engagement, in addition to traditional measures. However, considering the unstructured data forms, diverse use, and various platforms of mHealth, it can be challenging to select the right methods and measures to evaluate mHealth technologies. The inclusion of app usage logs, patient-involved methods, and other approaches to determine the impact of mHealth is an important step forward in health intervention research. We hope that this overview will become a catalogue of the possible ways in which mHealth has been and can be integrated into research practice.

Background: Fatty-acid amide hydrolase (FAAH) is an intracellular serine hydrolase that catalyzes the cleavage of endogenous fatty-acid amides, including the endocannabinoid anandamide (AEA). We previously reported that the peripherally restricted FAAH inhibitor URB937, which selectively increases AEA levels outside the central nervous system, reduces hyperalgesia and c-Fos expression in the trigeminal nucleus caudalis (TNC) and the locus coeruleus in an animal model of migraine based on nitroglycerin (NTG) administration. Aim: To further investigate the relevance of FAAH inhibition in the NTG animal model of migraine by testing the effects of the globally active FAAH inhibitor URB597. Methods: Our experimental approach involved mapping neuronal c-Fos protein expression, measurement of AEA levels in brain areas and in trigeminal ganglia, evaluation of pain-related behavior and quantification of molecular mediators in rats that received URB597 (2 mg/kg i.p.) either before or after NTG administration (10 mg/kg, i.p.). Results: Pre-treatment with URB597 significantly reduced c-Fos immunoreactivity in the TNC and inhibited NTG-induced hyperalgesia in the orofacial formalin test. This behavioral response was associated with a decrease in neuronal nitric oxide synthase, calcitonin gene-related peptide and cytokine gene expression levels in central and peripheral structures. Administration of URB597 after NTG had no such effect. Conclusions: The findings suggest that global FAAH inhibition may offer a therapeutic approach to the prevention, but not the abortive treatment, of migraine attacks. Further studies are needed to elucidate the exact cellular and molecular mechanisms underlying the protective effects of FAAH inhibition.

BackgroundThe electronic health record (EHR) has been fully established in all Norwegian hospitals. Patient-accessible electronic health records (PAEHRs) are available to citizens aged 16 years and older through the national health portal Helsenorge. ObjectiveThis study aimed at understanding how patients use PAEHRs. Three research questions were addressed in order to explore (1) characteristics of users, (2) patients’ use of the service, and (3) patient experience with the service. MethodsWe conducted an online survey of users who had accessed their EHR online at least once through the national health portal. Patients from two of the four health regions in Norway were invited to participate. Quantitative data were supplemented by qualitative information. ResultsA total of 1037 respondents participated in the survey, most of whom used the PAEHR regularly (305/1037, 29.4%) or when necessary (303/1037, 29.2%). Service utilization was associated with self-reported health, age, gender, education, and health care professional background. Patients found the service useful to look up health information (687/778, 88.3%), keep track of their treatment (684/778, 87.9%), prepare for a hospital appointment (498/778, 64.0%), and share documents with their general practitioner (292/778, 37.5%) or family (194/778, 24.9%). Most users found it easy to access their EHR online (965/1037, 93.1%) and did not encounter technical challenges. The vast majority of respondents (643/755, 85.2%) understood the content, despite over half of them acknowledging some difficulties with medical terms or phrases. The overall satisfaction with the service was very high (700/755, 92.7%). Clinical advantages to the patients included enhanced knowledge of their health condition (565/691, 81.8%), easier control over their health status (685/740, 92.6%), better self-care (571/653, 87.4%), greater empowerment (493/674, 73.1%), easier communication with health care providers (493/618, 79.8%), and increased security (655/730, 89.7%). Patients with complex, long-term or chronic conditions seemed to benefit the most. PAEHRs were described as useful, informative, effective, helpful, easy, practical, and safe. ConclusionsPAEHRs in Norway are becoming a mature service and are perceived as useful by patients. Future studies should include experimental designs focused on specific populations or chronic conditions that are more likely to achieve clinically meaningful benefits. Continuous evaluation programs should be conducted to assess implementation and changes of wide-scale routine services over time.