Search

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.

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.

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

Background and objective: Social media physical activity chatbots use both chatbots and social media platforms for physical activity promotion and, thus, could face privacy and security challenges inherent in both technologies. This study aims to provide an overview of physical activity chatbot interventions delivered via social media platforms, specifically focusing on security and privacy measures. Methods: We conducted a scoping review on this topic across 4 databases: PubMed, PsycINFO, ACM Digital Library, and IEEE Xplore. We extracted and summarised information on the author, population, country of study, social media platform, intervention, data processed (i.e. gathered or stored), and security/privacy measures. Results: Out of 1299 identified articles, 12 were included in the analysis reporting about 9 different chatbots. Although all chatbots applied data processing methods, only a few considered anonymisation. One paper stated compliance with the General Data Protection Regulations. Other studies enforced some verification procedures before chatbot use. Conclusion: Current research fails to adequately report security considerations in social media physical activity chatbot design. However, integration of chatbots into social media platforms seems to be declining, possibly due to security concerns. [ABSTRACT FROM AUTHOR]

To explore Norwegian GPs' experiences with and perceived suitability of issuing sickness certifications in remote consultations during the COVID-19 pandemic. We used a mixed methods research design. An online survey with 301 respondents was combined with qualitative interviews with ten GPs. Norwegian general practice. 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. 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. The GPs perceived issuing sickness certifications in remote consultations as suitable when patient and health problem are known, and when the certification is an extension. Issuing sickness certifications in remote consultations can both harm and strengthen the GP-patient relationship. The GPs were aware of their social responsibility and were concerned that issuing sickness certificates in remote consultations can change their sick-listing practice. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Calcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular system and it is likely related to migraine chronification. Here, we investigated the role of CGRP in an animal model that mimics the chronic migraine condition via repeated and intermittent nitroglycerin (NTG) administration. We also evaluated the modulatory effect of topiramate on this experimental paradigm. Male Sprague-Dawley rats were injected with NTG (5 mg/kg, i.p.) or vehicle, every 2 days over a 9-day period (5 total injections). A group of animals was injected with topiramate (30 mg/kg, i.p.) or saline every day for 9 days. Twenty-four hours after the last administration of NTG or vehicle, animals underwent tail flick test and orofacial Von Frey test. Rats were subsequently sacrificed to evaluate c-Fos and CGRP gene expression in medulla-pons region, cervical spinal cord and trigeminal ganglia. Results NTG administration induced spinal hyperalgesia and orofacial allodynia, together with a significant increase in the expression of CGRP and c-Fos genes in trigeminal ganglia and central areas. Topiramate treatment prevented NTG-induced changes by reversing NTG-induced hyperalgesia and allodynia, and inhibiting CGRP and c-Fos gene expression in all areas evaluated. Conclusions These findings point to the role of CGRP in the processes underlying migraine chronification and suggest a possible interaction with gamma-aminobutyrate (GABA) and glutamate transmission to induce/maintain central sensitization and to contribute to the dysregulation of descending pain system involved in chronic migraine.

Abstract Background Pulmonary rehabilitation is an effective therapeutic intervention for people with chronic respiratory disease. However, fewer than 5% of eligible individuals receive pulmonary rehabilitation on an annual basis, largely due to limited availability of services and difficulties associated with travel and transport. The Rehabilitation Exercise At Home (REAcH) study is an assessor-blinded, multi-centre, randomised controlled equivalence trial designed to compare the efficacy of home-based telerehabilitation and traditional centre-based pulmonary rehabilitation in people with chronic respiratory disease. Methods Participants will undertake an 8-week group-based pulmonary rehabilitation program of twice-weekly supervised exercise training, either in-person at a centre-based pulmonary rehabilitation program or remotely from their home via the Internet. Supervised exercise training sessions will include 30 min of aerobic exercise (cycle and/or walking training). Individualised education and self-management training will be delivered. All participants will be prescribed a home exercise program of walking and strengthening activities. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and 12-months post intervention. The primary outcome is change in dyspnea score as measured by the Chronic Respiratory Questionnaire – dyspnea domain (CRQ-D). Secondary outcomes will evaluate the efficacy of telerehabilitation on 6-min walk distance, endurance cycle time during a constant work rate test, physical activity and quality of life. Adherence to pulmonary rehabilitation between the two models will be compared. A full economic analysis from a societal perspective will be undertaken to determine the cost-effectiveness of telerehabilitation compared to centre-based pulmonary rehabilitation. Discussion Alternative models of pulmonary rehabilitation are required to improve both equity of access and patient-related outcomes. This trial will establish whether telerehabilitation can achieve equivalent improvement in outcomes compared to traditional centre-based pulmonary rehabilitation. If efficacious and cost-effective, the proposed telerehabilitation model is designed to be rapidly deployed into clinical practice. Trial registration Clinical trial registered with the Australian and New Zealand Clinical Trials Register at (ACTRN12616000360415). Registered 21 March 2016.

Abstract Background Norway has a long history of using telemedicine, especially for geographical reasons. Despite the availability of promising telemedicine applications and the implementation of national initiatives and policies, the sustainability and scaling-up of telemedicine in the health system is still far from accomplished. The main objective of this study was to explore and identify the multi-level (micro, meso and macro) factors affecting telemedicine utilization in Norway. Methods We used a mixed methods approach. Data from a national registry were collected to analyze the use of outpatient visits and telemedicine contacts in Norway from 2009 to 2015. Interviews with key stakeholders at national, regional and local level helped complete and contextualize the data analysis and explore the main issues affecting the use of telemedicine by health authorities and hospitals. Relevant national documents were also used to support, contradict, contextualize or clarify information and data. Results Telemedicine use in Norway from 2009 to 2015 remained very low, not exceeding 0.5% of total outpatient activity at regional level and 0.1% at national level. All four regions used telemedicine. Of the 29 hospitals, 24 used it at least once over the 7-year period. Telemedicine was not used regularly everywhere, with some hospitals using it sporadically. Telemedicine was mostly used in selected specialties, including rehabilitation, neurosurgery, skin and venereal diseases. Three major themes affecting implementation and utilization of telemedicine in Norway emerged: (i) governance and strategy; (ii) organizational and professional dimensions; (iii) economic and financial dimensions. For each theme, a number of factors and challenges faced at different health care levels were identified. Conclusions This study allowed shedding light on multi-level and interdependent factors affecting utilization of telemedicine in Norway. The identification of the main implementation and utilization challenges might support decision makers and practitioners in the successful scaling-up of telemedicine. This work provides a knowledge base useful to other countries which intend to implement telemedicine or other digital health services into their healthcare systems.

Introduction: Arterial 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. Methods: Ninety 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. Results: Saphenous samples showed strong positive correlations with arterial samples for both pCO2 and pH. Pearson r 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. Discussion: In 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. [ABSTRACT FROM AUTHOR]

The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals.