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Vestibular symptoms accompanying headache are quite common in migraine patients. Based on the association of vertigo with migraine, vestibular migraine was included in the appendix of the 3rd edition of the International Classification of Headache Disorders as a possible migraine subtype worthy of further investigation. In this post hoc, exploratory analysis, we investigated the occurrence of oculo-vestibular signs (OVSs) during experimentally induced migraine attacks in 24 episodic migraine patients and 19 healthy controls exposed to sublingual nitroglycerin (NTG - 0.9 mg). A comprehensive clinical examination was performed at baseline, at the onset of the migraine-like attack, and immediately before hospital discharge (180 minutes after NTG administration). Three of the 13 migraine patients who developed a spontaneous-like migraine attack during the hospital observation period (23.1%) also developed OVSs during the induction test. Noteworthy, none of the patients with a negative induction test developed OVSs and no OVSs were reported in healthy subjects at any time point. The exploratory nature of our study does not allow to draw definite conclusions on the possible implications of a vestibular dysfunction in migraine pathophysiology. Our results however suggest that NTG administration may lend itself to investigate vestibular dysfunction in migraine, at least in a subset of patients. The present findings represent a starting point for designing future ad hoc and well-powered studies.

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.

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.

Ultrafiltration (UF) is used for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may have the opposite of its intended effect, resulting in acute kidney injury (AKI), oliganuria, and fluid retention. This is a single-center, retrospective review of infants treated with conventional and/or modified UF during CPB surgery. UF volume was indexed to weight. AKI was defined using serum creatinine “Kidney Disease Improving Global Outcome (KDIGO)” criteria. Fluid balance was defined according to: $$ \left[\frac{total\ intake\ (mL)- total\ output\ (mL)}{preoperative\ weight\ (g)}\right]x\ 100 $$ . Peak fluid overload was determined on postoperative day 3. Multivariable logistic regression adjusted for multiple covariates was used to explore associations with UF, AKI, and fluid overload. Five hundred thirty subjects 119.9 mL/kg did not reduce peak fluid overload. Subjects with AKI took longer to reach a negative fluid balance (2 vs. 3 days, p = 0.04). Those with more complex surgery were at highest AKI risk (STAT 3 [25–75 percentile: 3–4] in AKI group versus STAT 3 [25–75 percentile: 2–4] in non-AKI group, p = 0.05). AKI was reduced in subjects undergoing more complex surgery and treated with UF volume < 119.9 mL/kg. Judicious use of UF in more complex congenital cardiac surgery reduces the risk of AKI.

Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating "out-of-hospital" and "hospital" activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The "out-of-hospital" response was analysed in terms of calls, rescues and missions, whereas the "hospital" response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21-March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17-February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21-March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate "Emergency Department-Infective Disease" was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the "out-of-hospital" and "in-hospital" systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future.

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p p p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

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).

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in D-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

Anal fistula is a common acquired anorectal disorder in children. Treatment methods that have been used are associated with inconsistent results and possible serious complications. In 2011 a minimally invasive approach, video-assisted anal fistula treatment (VAAFT) was described for adult patients. The aim of the present study was to assess the first series of pediatric patients treated with VAAFT.All patients who underwent VAAFT between August 2013 and May 2015 were included. Demographics, clinical features, preoperative imaging, surgical details, outcome, and medium-term data were prospectively collected for each patient.Thirteen procedures were performed in nine patients. The male to female ratio was 8:1, and the median age was 9.6 years. Five fistulas were idiopathic, three iatrogenic, and one associated with Crohn's disease. Eight complete VAAFT procedures were performed. The remaining five procedures were either fistuloscopy and cutting seton placement or fistuloscopy and electrocoagulation, both without mucosal sleeve. The median length of surgery was 41 min. The median hospital stay was 24 h, and the median length of follow-up was 10 months. Resolution of the fistula was observed in all patients who underwent a complete VAAFT. In four out of five patients who underwent an incomplete procedure (without mucosal sleeve), the fistula recurred. No incontinence or soiling was reported in the medium term.VAAFT proved to be feasible and safe in children. It also proved to be versatile as it could be applied to fistulas of different etiologies. The key to success seems to be an adequate mucosal sleeve. Older children and adolescents benefit most from VAAFT which is a valid alternative to available surgical procedures.

Objective: To quantify the occurrence of high intracranial pressure (HICP) refractory to conventional medical therapy after traumatic brain injury (TBI) and to describe the use of more aggressive therapies (profound hyperventilation, barbiturates, decompressive craniectomy). Design: Prospective study of 407 consecutive TBI patients Setting: Three neurosurgical intensive care units (ICU). Measurements and results: Intracranial pressure (ICP) was studied during the first week after TBI; 153 patients had at least 1 day of ICP > 20 mmHg. Early surgery was necessary for 221 cases, and standard medical therapy [sedation, mannitol, cerebrospinal fluid (CSF) withdrawal, PaCO2 30-35 mmHg] was used in 135 patients. Reinforced treatment (PaCO2 25-29 mmHg, induced arterial hypertension, muscle relaxants) was used in 179 cases (44%), and second-tier therapies in 80 (20%). Surgical decompression and/or barbiturates were used in 28 of 407 cases (7%). Six-month outcome was recorded in 367 cases using the Glasgow outcome scale (GOS). The outcome was favorable (good recovery or moderate disability) in 195 cases (53%) and unfavorable (all the other categories) in 172 (47%). HICP was associated with worse outcome. Outcome for cases who had received second-tier therapies was significantly worse (43% favorable at 6 months, p = 0.03). Conclusions: HICP is frequent and is associated with worse outcome. ICP was controlled by early surgery and first-tier therapies in the majority of cases. Profound hyperventilation, surgical decompression and barbiturates were used in various combinations in a minority of cases. The indications for surgical decompression and/or barbiturates seem restricted to less than 10% of severe TBI. © 2007 Springer-Verlag.

Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case-control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with β-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients.

With the optimization of transfusional and chelation regimens, beta-thalassemia has changed from a pediatric disease with poor life expectancy into a chronic disease. Bone demineralization is an important cause of morbidity in older patients; the etiology is multifactorial and partially unknown. We examined, cross-sectionally, 111 adult patients with beta-thalassemia major (66 females and 45 males, 32.6 ± 6 years) who were regularly transfused, sufficiently chelated and replaced for endocrine defects. Bone demineralization was detected in 92.7% of patients with different severity according to gender and site: osteopenia was the prominent finding at the femur, osteoporosis at the lumbar spine (p

Background Nowadays, new organisational strategies should be indentified to improve primary care and its link with secondary care in terms of efficacy and timeliness of interventions thus preventing unnecessary hospital accesses and costs saving for the health system. The purpose of this study is to assess the effects of the use of teleconsultation by general practitioners in rural areas. Methods General practitioners were provided with a teleconsultation service from 2006 to 2008 to obtain a second opinion for cardiac, dermatological and diabetic problems. Access, acceptance, organisational impact, effectiveness and economics data were collected. Clinical and access data were systematically entered in a database while acceptance and organisational data were evaluated through ad hoc questionnaires. Results There were 957 teleconsultation contacts which resulted in access to health care services for 812 symptomatic patients living in 30 rural communities. Through the teleconsultation service, 48 general practitioners improved the appropriateness of primary care and the integration with secondary care. In fact, the level of concordance between intentions and consultations for cardiac problems was equal to 9%, in 86% of the cases the service entailed a saving of resources and in 5% of the cases, it improved the timeliness. 95% of the GPs considered the overall quality positively. For a future routine use of this service, trust in specialists, duration and workload of teleconsultations and reimbursement should be taken into account. Conclusions Managerial and policy implications emerged mainly related to the support to GPs in the provision of high quality primary care and decision-making processes in promoting similar services.