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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.

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.

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.