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The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in Multiple Sclerosis ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15 min/5 days against MS fatigue. An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions. High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations.

Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.

Background On December 2017 the Italian Parliament approved law n. 219/2017 “Provisions for informed consent and advance directives” regarding challenging legal and bioethical issues related to healthcare decisions and end-of life choices. The law promotes the person’s autonomy as a right and provides for the centrality of the individual in every scenario of health care by mean of three tools: informed consent, shared care planning and advance directives. Few years after the approval of the law, we conducted a survey among physicians working in four health care facilities specific for the care of people suffering from psychiatric disorders, cognitive disorders and dementia located in the North of Italy aiming to investigate their perceived knowledge and training need, attitudes regarding law n. 219/2017 provisions, and practices of implementation of the law. Methods A semi-structured questionnaire was developed on an online platform. The invitation to participate in the survey was sent by email to the potential participants. Information was collected by means of the online platform (Google Forms) which allows to export data in a spreadsheet (Windows Excel) to perform basic statistical analysis (frequency distributions, bar chart representation). Results Twenty-five out of sixty physicians participated in the survey. None of the respondents value their knowledge of the law as very good, 10 good, 13 neither poor nor good, 1 poor and 1 very poor. All the respondents want to learn more about the law (21 yes and 4 absolutely yes). The majority of respondents agrees with the content of the law as a whole (3 absolutely agree, 13 agree), and on each provision. The question on the clarity of the concept of capacity in the law received mixed answers and this impacted on the physicians’ opinion regarding the legitimacy in principle for our groups of patients to realize shared care planning and write advance directives. Thirteen physicians neither introduced the theme of shared care planning nor arranged for shared care planning and the main reason for this was that no patient was in a clinical situation to require it. When shared care planning is realized, a variability in terms of type and number of meetings, mode of tracking and communication is registered. Conclusions Our survey results indicate a need for more clarity regarding the interpretation and implementation of the law in the patient groups under study. There are in particular two related areas that deserve further discussion: (1) the question of whether these patient groups are in principle legitimized by the law to realize shared care planning or write advance directives; (2) the notion of capacity required by the law and how this notion can be declined in real-life situations.

Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration. Sub-threshold and supra-threshold single and ppTMS of the left primary motor cortex were carried out during a multi-channel EEG recording on 8 healthy volunteers; the between-pulse intervals used in the paired pulse trials were 3 (for SICI) and 11ms (for ICF). Motor evoked potentials (MEPs) from the opposite hand were simultaneously recorded. Single and ppTMS induced EEG responses characterized by a sequence of negative deflections peaking at approximately 7, 18, 44, 100 and 280ms alternated with positive peaks at approximately 13, 30, 60 and 190ms post-TMS. Moreover, ppTMS modulated both EEG evoked activity and MEPs. Amplitude variability of EEG responses was correlated with – and therefore might partially explain – amplitude variability of MEPs. EEG-ppTMS is a promising tool to better characterize the neuronal circuits underlying cortical effective connectivity as well as the mechanisms regulating the balance between inhibition and facilitation within the human cortices and the corticospinal pathway.

Parent-mediated intervention is widely used for pre-schoolers with autism spectrum disorder (ASD). Previous studies indicate small-to-moderate effects on social communication skills, but with a wide heterogeneity that requires further research. In this randomized controlled trial (RCT), cooperative parent-mediated therapy (CPMT) an individual parent coaching program for young children with ASD was administered to preschool children with ASD. All children received the same low-intensity psychosocial intervention (LPI) delivered in community settings, to evaluate the potential additional benefit of CPMT. Thirty-four participants with ASD (7 females; 27 males; aged 2, 6, 11 years) and their parents were included in the trial. The primary blinded outcome was social communication skills, assessed using the ADOS-G social communication algorithm score (ADOS-G SC). Secondary outcomes included ASD symptom severity, parent-rated language abilities and emotional/behavioral problems, and self-reported caregiver stress. Evaluations were made at baseline and post-treatment (at 6 months) by an independent multidisciplinary team. Results documented that CPMT showed an additional benefit on LPI with significant improvements of the primary blinded outcome, socio-communication skills, and of some secondary outcomes such as ASD symptom severity, emotional problems and parental stress related to parent–child dysfunctional interaction. No additional benefit was found for language abilities. Findings of our RCT show that CPMT provide an additional significant short-term treatment benefit on ASD core symptoms, when compared with active control group receiving only LPI.

Purpose DSM-5 describe three forms of restrictive and selective eating: Anorexia Nervosa-Restrictive (AN-R), Anorexia Nervosa-Atypical (AN-A), and Avoidant/Restrictive Food Intake Disorder (ARFID). While AN is widely studied, the psychopathological differences among these three diseases are not clear. The aim of this study was to (i) compare the clinical features of AN-R, AN-A, and ARFID, in a clinical sample recruited from a specialized EDs program within a tertiary care children’s Hospital; (ii) identifying three specific symptom profiles, to better understand if restrictive ED share a common psychopathological basis. Methods Data were collected retrospectively. Psychometric assessment included: the Children’s Depression Inventory (CDI), the Multidimensional Anxiety Scale for Children (MASC), the Child Behavior Checklist (CBCL), and the Eating Disorder Inventory-3 (EDI-3). Results A final sample of 346 children and adolescent patients were analyzed: AN-R was the most frequent subtype (55.8%), followed by ARFID (27.2%) and AN-A (17%). Patients with ARFID presented different features from AN-R and AN-A, characterized by lower weight and medical impairment, younger age at onset, and a frequent association with separation anxiety and ADHD symptoms. EDI-3 profiles showed specific different impairment for both AN groups compared to ARFID. However, no differences was detected for items: ‘Interpersonal Insecurity’, “Interoceptive Deficits”, “Emotional Dysregulation”, and “Maturity Fears”. Conclusions Different ED profiles was found for the three groups, but they share the same general psychopathological vulnerability, which could be at the core of EDs in adolescence. Level of evidence III. Evidence obtained from case–control analytic studies.

Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson’s disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P<0.001) and a higher BDNF concentration in patients affected by PD (P=0.045). Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics (P=0.009) and L-DOPA (P<0.001) and significant reductions in patients taking benzodiazepines (P=0.020). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects.

Abstract Context Somatostatin analogs (SSAs) effectively control growth hormone secretion in first- and second-line treatment of acromegaly. Their effect on glucose metabolism is still debated. Objective To address the following questions: (1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin, glycosylated hemoglobin (HbA1c), glucose load (glucose levels after 2-hour oral glucose tolerance test), homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of pancreatic β-cell function (HOMA-β), triglycerides, weight, or body mass index? (2) Do lanreotide and octreotide affect metabolism differently? (3) Does their effect depend on disease control? Design We performed a meta-analysis of prospective interventional trials treating acromegaly with SSAs. Inclusion criteria: all studies reporting glycometabolic outcomes before and after SSAs with a minimum 6-month follow-up. Results The inclusion criteria were met by 47 studies treating 1297 subjects (631 females). SSA treatment effectively lowered fasting plasma insulin [effect size (ES), −6.67 mU/L; 95% confidence interval (CI), −8.38 to −4.95 mU/L; P < 0.001], HOMA-I (ES, −1.57; CI, −2.42 to −0.72; P < 0.001), HOMA-β (ES, −47.45; CI, −73.15 to −21.76; P < 0.001), and triglycerides (ES, −0.37 mmol/L; CI, −0.47 to −0.27 mmol/L; P < 0.001). SSAs worsened glucose levels after a 2-hour oral glucose tolerance test (ES, 0.59 mmol/L; CI, 0.05 to 1.13 mmol/L; P = 0.032), but not FPG. A mild but significant increase in HbA1c (ES, 0.12%; CI, 0.00% to 0.25%; P = 0.044) was found in subjects treated with octreotide. Conclusions SSA treatment in acromegaly patients, while improving disease control, reduces insulin levels, increases after-load glucose, and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting postprandial glucose. The current meta-analysis evaluated the effect of somatostatin analogs treatment on glucose metabolism in acromegaly.

Background There is wide convergence in the positions of scientific societies, patient associations and public bodies regarding the advisability of advance care planning (ACP) in cognitive disorders and dementia to respect the specificity of the person. Nevertheless, planning in advance for dementia represents a unique challenge. In Italy, law n. 219/2017 introduced ACP for the first time at the regulatory level, under the name of shared care planning (SCP). Few surveys on the law implementation have been conducted in Italy, but none have specifically involved patients with cognitive disorders and their caregivers. To contribute filling the gap, we conducted a survey among patients and caregivers attending a memory clinic to investigate what their knowledge, attitudes and experiences were regarding SCP. Methods We developed two semi-structured questionnaires for patients and caregivers organized into the following sections: (i) knowledge of the law; (ii) general attitude on SCP; (iii) experience about SCP; (iv) attitude about realizing a SCP; (v) advance directives. Participation in the survey was offered to consecutive patients discharged from the memory clinic during 26 target weeks and to their caregivers. The interviews were conducted on the occasion of the last scheduled visit to the facility; telephone interview was also provided. Information was collected by means of an online platform (Google Forms). Descriptive and basic inferential analysis was performed by means of SPSS (IBM). The analysis of the open-ended questions was also conducted with the support of the Voyant Tools. Results Sixty-six patient and 65 caregiver interviews were collected. No participant reported that a doctor has ever talked to the patient about SCP. The large majority of patients (85%) and almost all caregivers (95%) agree/absolutely agree with the opportunity for patients to realize SCP. Almost all participants agree/absolutely agree with the usefulness for the patients of indicating a trusted person to act on their behalf (91% patients and 95% caregivers). Forty-three (65%) patients and 48 (74%) caregivers believe it would be good to start SCP with the patient when the time is right. Among them, 20 caregivers and 12 patients believe it is already time to talk about SCP. Conclusions Study results showed patients’ and caregivers’ interest in the SCP process and, at the same time, their mixed attitude when SCP is referred specifically to themselves or their loved ones. This indicates the need to introduce the discourse on SCP into clinical practice while remaining very sensitive to the individual patient’s pace and wishes, including his/her possible refusal to talk about SCP.

Background It has been estimated that the incidence of chronic hepatitis C virus (HCV) will not decline over the next 10 years despite the improved efficacy of antiviral therapy because most patients remain undiagnosed and/or untreated. This study aimed to investigate the opinion of relevant target populations on the practicability, effectiveness and best modalities of the test-and-treat approach in the fight against HCV in Italy. Methods A survey was delivered to patients with HCV from the general population, patients from drug addiction services, hospital physicians and healthcare providers for drug addiction services. Results For both hospital clinicians and SerD HCPs, tolerability is shown as the most important feature of a suitable treatment. Time to treatment (the time from first contact to initiation of treatment) is deemed important to the success of the strategy by all actors. While a tolerable treatment was the main characteristic in a preferred care pathway for general patients, subjects from drug addiction services indicated that a complete Meet–Test–Treat pathway is delivered within the habitual care center as a main preference. This is also important for SerD HCPs who are a strong reference for their patients; hospital clinicians were less aware of the importance of the patient-HCP relationship in this process. Conclusion The health system is bound to implement suitable pathways to facilitate HCV eradication. A Meet–Test–Treat program within the drug addiction services may provide good compliance from subjects mainly concerned with virus transmission.