Reducing the Impact of Headache and Allodynia Score in Chronic Migraine: An Exploratory Analysis from the Real-World Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study.

BACKGROUND: Chronic migraine (CM) is a disabling and hard-to-treat condition, associated with high disability and high cost. Among the preventive treatments, botulinum toxin A (BoNT-a) and monoclonal antibodies against the calcitonin gene-related protein (anti-CGRP mAbs) are the only disease-specific ones. The assessment of the disease burden is complex, and among others, tools such as the allodynia symptoms checklist (ASC-12) and headache impact test (HIT-6) are very useful. This exploratory study analysed the impact of these two therapies on migraine burden. METHODS: The RAMO study was a multicentre, observational, retrospective investigation conducted in two headache centres: the Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan) and the Fondazione Policlinico Campus Bio-Medico (Rome). This study involved patients with chronic migraine treated with mAbs or BoNT-A. We conducted a subgroup exploratory analysis on HIT-6 and ASC-12 scores in the two groups. The Wilcoxon rank-sum test, Fisher's exact test, and ANOVA were performed. RESULTS: Of 126 patients, 36 on mAbs and 90 on BoNT-A had at least one available follow-up. mAbs resulted in a mean reduction of -11.1 and -11.4 points, respectively, in the HIT-6 at 6 and 12 months, while BoNT-A was reduced -3.2 and -3.6 points, respectively; the mAbs arm resulted in mean reductions in ASC-12 at 6 and 12 months of follow-up of -5.2 and -6.0 points, respectively, while BoNT-A showed lesser mean changes of -0.5 and -0.9 points, respectively. The adjusted analysis confirmed our results. CONCLUSIONS: In this exploratory analysis, anti-CGRP mAbs showed superior effectiveness for HIT-6 and ASC12 compared to BoNT-A. Reductions in terms of month headache days (MHD), migraine disability assessment test (MIDAS), and migraine acute medications (MAM) were clinically relevant for both treatments.

The EMPOWER Occupational e-Mental Health Intervention Implementation Checklist to Foster e-Mental Health Interventions in the Workplace: Development Study.

BACKGROUND: Occupational e-mental health (OeMH) interventions significantly reduce the burden of mental health conditions. The successful implementation of OeMH interventions is influenced by many implementation strategies, barriers, and facilitators across contexts, which, however, are not systematically tracked. One of the reasons is that international consensus on documenting and reporting the implementation of OeMH interventions is lacking. There is a need for practical guidance on the key factors influencing the implementation of interventions that organizations should consider. Stakeholder consultations secure a valuable source of information about these key strategies, barriers, and facilitators that are relevant to successful implementation of OeMH interventions. OBJECTIVE: The objective of this study was to develop a brief checklist to guide the implementation of OeMH interventions. METHODS: Based on the results of a recently published systematic review, we drafted a comprehensive checklist with a wide set of strategies, barriers, and facilitators that were identified as relevant for the implementation of OeMH interventions. We then used a 2-stage stakeholder consultation process to refine the draft checklist to a brief and practical checklist comprising key implementation factors. In the first stage, stakeholders evaluated the relevance and feasibility of items on the draft checklist using a web-based survey. The list of items comprised 12 facilitators presented as statements addressing "elements that positively affect implementation" and 17 barriers presented as statements addressing "concerns toward implementation." If a strategy was deemed relevant, respondents were asked to rate it using a 4-point Likert scale ranging from "very difficult to implement" to "very easy to implement." In the second stage, stakeholders were interviewed to elaborate on the most relevant barriers and facilitators shortlisted from the first stage. The interview mostly focused on the relevance and priority of strategies and factors affecting OeMH intervention implementation. In the interview, the stakeholders' responses to the open survey's questions were further explored. The final checklist included strategies ranked as relevant and feasible and the most relevant facilitators and barriers, which were endorsed during either the survey or the interviews. RESULTS: In total, 26 stakeholders completed the web-based survey (response rate=24.8%) and 4 stakeholders participated in individual interviews. The OeMH intervention implementation checklist comprised 28 items, including 9 (32.1%) strategies, 8 (28.6%) barriers, and 11 (39.3%) facilitators. There was widespread agreement between findings from the survey and interviews, the most outstanding exception being the idea of proposing OeMH interventions as benefits for employees. CONCLUSIONS: Through our 2-stage stakeholder consultation, we developed a brief checklist that provides organizations with a guide for the implementation of OeMH interventions. Future research should empirically validate the effectiveness and usefulness of the checklist.

The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study.

BACKGROUND: The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders. METHODS: We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium. RESULTS: A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake. CONCLUSIONS: Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.

Risk and sex-specific trends of dementia and stroke in Italy Compared to European and high-income countries and the world: global implications.

BACKGROUND: Understanding the increasing trends in Italy may inform new prevention strategies and better treatments. We investigated trends and risk factors of dementia, stroke, and ischemic heart disease (IHD) in Italy with the second-oldest population globally, compared to European and high-income countries and the world. METHODS: We analyzed the Global Burden of Disease Study (GBD) 2019 estimates on incidence and burden (i.e., disability and death combined) of the three conditions in both sexes. We also analyzed the burden attributable to 12 modifiable risk factors and their changes during 1990-2019. RESULTS: In 2019, Italy had 186,108 new dementias (123,885 women) and 94,074 new strokes (53,572 women). Women had 98% higher crude dementia and 24% higher crude stroke burdens than men. The average age-standardized new dementia rate was 114.7 per 100,000 women and 88.4 per 100,000 men, both higher than Western Europe, the European Union, high-income countries, and the world. During 1990-2019, this rate increased in both sexes (4%), despite a decline in stroke (- 45%) and IHD (- 17%) in Italy. Dementia burden attributable to tobacco decreased in both sexes (- 12.7%) during 1990-2019, while high blood glucose and high body mass index combined burden increased (25.4%). Stroke and IHD had similar trends. CONCLUSIONS: While decreases in new strokes and IHDs are encouraging, new approaches to their joint prevention are required to reverse the rising dementia trends, especially among women. Life course approaches to promoting holistic brain health should be implemented at the community, national, and international levels before the growing trends become overwhelming.

A comprehensive overview of post-stroke depression treatment options.

Nearly one-third of all stroke patients develop depression at any time after a stroke, and its presence is associated with unfavorable outcomes. This narrative review aims to provide a synopsis of possible pharmacological and non-pharmacological treatment modalities for post-stroke depression (PSD). Several studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors in treating the symptoms of this clinical condition. The treatment of PSD has been recently enhanced by innovative approaches, such as cognitive-behavioral therapy, virtual reality, telehealth, repetitive transcranial magnetic stimulation, and non-conventional therapies, which might improve depression treatment in stroke survivors. Future high-quality randomized controlled trials are necessary to confirm this hypothesis.

The World Health Organization Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders and the headache revolution: from headache burden to a global action plan for headache disorders.

The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.

An observational, cross-sectional and monocentric study assessing psychological and cognitive features as main predictors of psychological well-being in stroke survivors.

Well-being is a relevant outcome after stroke, potentially impacted by mental health difficulties. We addressed the psychological and cognitive predictors of psychological well-being in a sample of 122 stroke survivors (75 males, 97 with ischemic stroke; mean age 64.1, mean NIHSS 2.9, mean distance from the acute event 5.1 years) admitted to the 'Carlo Besta' Neurological Institute. Trait anxiety (ß = -0.257), state anxiety (ß = -0.208) and symptoms of depression (ß = -0.484) significantly predicted well-being variation (Adj. R2 = 0.687). These potentially modifiable factors are promising targets for interventions to reduce the burden of illness and enhance the recovery process.

Rethinking headache as a global public health case model for reaching the SDG 3 HEALTH by 2030.

The 2030 Agenda for Sustainable Development sets out, through 17 Sustainable Development Goals (SDGs), a path for the prosperity of people and the planet. SDG 3 in particular aims to ensure healthy lives and promote well-being for all at all ages and includes several targets to enhance health. This review presents a "headache-tailored" perspective on how to achieve SDG 3 by focusing on six specific actions: targeting chronic headaches; reducing the overuse of acute pain-relieving medications; promoting the education of healthcare professionals; granting access to medication in low- and middle-income countries (LMIC); implementing training and educational opportunities for healthcare professionals in low and middle income countries; building a global alliance against headache disorders. Addressing the burden of headache disorders directly impacts on populations' health, as well as on the possibility to improve the productivity of people aged below 50, women in particular. Our analysis pointed out several elements, and included: moving forward from frequency-based parameters to define headache severity; recognizing and managing comorbid diseases and risk factors; implementing a disease management multi-modal management model that incorporates pharmacological and non-pharmacological treatments; early recognizing and managing the overuse of acute pain-relieving medications; promoting undergraduate, postgraduate, and continuing medical education of healthcare professionals with specific training on headache; and promoting a culture that favors the recognition of headaches as diseases with a neurobiological basis, where this is not yet recognized. Making headache care more sustainable is an achievable objective, which will require multi-stakeholder collaborations across all sectors of society, both health-related and not health-related. Robust investments will be needed; however, considering the high prevalence of headache disorders and the associated disability, these investments will surely improve multiple health outcomes and lift development and well-being globally.

Surgical Complexity and Complications: The Need for a Common Language.

BACKGROUND: Quality measurement and outcome assessment have recently caught an attention of the neurosurgical community, but lack of standardized definitions and methodology significantly complicates these tasks. OBJECTIVE: To identify a uniform definition of neurosurgical complications, to classify them according to etiology, and to evaluate them comprehensively in cases of intracranial tumor removal in order to establish a new, easy, and practical grading system capable of predicting the risk of postoperative clinical worsening of the patient condition. METHODS: A retrospective analysis was conducted on all elective surgeries directed at removal of intracranial tumor in the authors' institution during 2-year study period. All sociodemographic, clinical, and surgical factors were extracted from prospectively compiled comprehensive patient registry. Data on all complications, defined as any deviation from the ideal postoperative course occurring within 30 days of the procedure, were collected with consideration of the required treatment and etiology. A logistic regression model was created for identification of independent factors associated with worsening of the Karnofsky Performance Scale (KPS) score at discharge after surgery in comparison with preoperative period. For each identified statistically significant independent predictor of the postoperative worsening, corresponding score was defined, and grading system, subsequently named Milan Complexity Scale (MCS), was formed. RESULTS: Overall, 746 cases of surgeries for removal of intracranial tumor were analyzed. Postoperative complications of any kind were observed in 311 patients (41.7%). In 223 cases (29.9%), worsening of the KPS score at the time of discharge in comparison with preoperative period was noted. It was independently associated with 5 predictive factors-major brain vessel manipulation, surgery in the posterior fossa, cranial nerve manipulation, surgery in the eloquent area, tumor size >4 cm-which comprised MCS with a range of the total score from 0 to 8 (higher score indicates more complex clinical situations). Patients who demonstrated KPS worsening after surgery had significantly higher total MCS scores in comparison with individuals whose clinical status at discharge was improved or unchanged (3.24 ± 1.55 versus 1.47 ± 1.58; P < 0.001). CONCLUSION: It is reasonable to define neurosurgical complication as any deviation from the ideal postoperative course occurring within 30 days of the procedure. Suggested MCS allows for standardized assessment of surgical complexity before intervention and for estimating the risk of clinical worsening after removal of intracranial tumor. Collection of data on surgical complexity, occurrence of complications, and postoperative outcomes, using standardized prospectively maintained comprehensive patient registries seems very important for quality measurement and should be attained in all neurosurgical centers.

The perception of disability in cerebral palsy: a cross-sectional study using the WHODAS 2.0.

This observational study aims to describe the level of perceived disability in Cerebral Palsy (CP). We described the perception of adults by using the interviewer-administered version of the WHO disability assessment schedule (WHODAS 2.0). In case of intellectual disability (ID), the proxy-administered version was used, and a caregiver was asked to report the difficulties experienced by the patient; 199 patients were enrolled. The level of perceived disability was higher when referred to patients with ID (proxy report) than when referred to patients without ID (p < .001). For all patients, the level of perceived disability varied depending on the severity and the localization of motor impairment (both p < .001). No differences were observed based on the type of motor impairment. The perceived disability was correlated with age only for patients with no ID (p < .05). The WHODAS 2.0 may be a useful tool to explore the perception of disability in CP.

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

The Be-Home Kids Program: An Integrated Approach for Delivering Behavioral Therapies to Adolescents with Episodic and Chronic Migraine.

Migraine disorders are common in populations of children and adolescents. There are different pharmacological treatments for migraine in young patients, but none have specific indications, and doubts about their efficacy exist. The feasibility and effectiveness of behavioral approaches have already been documented in clinical experiences, and they are generally associated with fewer or no unpleasant effects. Among them, mindfulness practice offers a suitable alternative to other adolescent treatments. We present the results of a pilot study, the Be-Home Kids program, performed during the COVID-19 emergency. It was delivered by web and included education on drug use, lifestyle issues, and six sessions of mindfulness-based behavioral practice. We assessed headache frequency, medication intake, and other psychological variables and followed twenty-one adolescents with chronic or high-frequency episodic migraine without aura for 12 months. Results indicated an overall clinical improvement, particularly a 64% reduction in headache frequency over 12 months. In conclusion, our results indicate that a combined treatment which includes patients' education and six sessions of mindfulness-based practice delivered over the web, can be of great support in reducing headache frequency, medication intake, and the associated psychological burden disability in adolescent migraine patients.

Quantification of retinal ganglion cell loss in patients with homonymous visual field defect due to stroke.

BACKGROUND: To quantify the degree of ganglion cell degeneration through spectral domain optical coherence tomography (SD-OCT) in adult patients with post-stroke homonymous visual field defect. METHODS: Fifty patients with acquired visual field defect due to stroke (mean age = 61 years) and thirty healthy controls (mean age = 58 years) were included. Mean deviation (MD) and pattern standard deviation (PSD), average peripapillary retinal nerve fibre layer thickness (pRNLF-AVG), average ganglion cell complex thickness (GCC-AVG), global loss volume (GLV) and focal loss volume (FLV) were measured. Patients were divided according to the damaged vascular territories (occipital vs. parieto-occipital) and stroke type (ischaemic vs. haemorrhagic). Group analysis was conducted with ANOVA and multiple regressions. RESULTS: pRNFL-AVG was significantly decreased among patients with lesions in parieto-occipital territories compared to controls and to patients with lesions in occipital territories (p = .04), with no differences with respect to stroke type. GCC-AVG, GLV and FLV differed in stroke patients and controls, regardless of stroke type and involved vascular territories. Age and elapsed time from stroke had a significant effect on pRNFL-AVG and GCC-AVG (p < .01), but not on MD and PSD. CONCLUSIONS: Reduction of SD-OCT parameters occurs following both ischaemic and haemorrhagic occipital stroke, but it is larger when the injury extends to parietal territories and increases as time since stroke increases. The size of visual field defect is unrelated to SD-OCT measurements. Macular GCC thinning appeared to be more sensitive than pRNFL in detecting retrograde retinal ganglion cell degeneration and its retinotopic pattern in stroke.

Electrophysiological and Neuropsychological Indices of Cognitive Dysfunction in Patients with Chronic Insomnia and Severe Benzodiazepine Use Disorder.

Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.

A Single-Group Study on the Effect of OnabotulinumtoxinA in Patients with Chronic Migraine Associated with Medication Overuse Headache: Pain Catastrophizing Plays a Role.

Pain catastrophizing and cutaneous allodynia are commonly altered in patients with chronic migraine associated with medication overuse headache (CM-MOH) and tend to improve in parallel with clinical improvement. The relation between pain catastrophizing and cutaneous allodynia is poorly understood in patients with CM-MOH receiving OnabotulinumtoxinA therapy. In this single-arm open-label longitudinal observational study, patients with CM-MOH were assigned to structured withdrawal and then administered OnabotulinumtoxinA (5 sessions on a three-month basis, 195 UI per 31 sites). Headache frequency, medication intake, disability, impact, cutaneous allodynia and pain catastrophizing were evaluated with specific questionnaires. In total, 96 patients were enrolled and 79 completed the 12-month follow-up. With the exclusion of cutaneous allodynia and the magnification subscale of the pain catastrophizing questionnaire, all variables showed significant improvement by the sixth month, which was maintained at 12 months. Reduction of pain catastrophizing, and particularly of its helplessness subscale, was a significant predictor of reduction in headache frequency and medication intake. Pain catastrophizing is often implicated in the clinical improvement in patients with CM-MOH receiving behavioral treatments, but, in this study, also showed a role in patients receiving OnabotulinumtoxinA; combining OnabotulinumtoxinA and behavioral treatments specifically addressing pain catastrophizing might further enhance patients' clinical outcome.

Lessons Learned from the Lessons Learned in Public Health during the First Years of COVID-19 Pandemic.

(1) Objectives: to investigate the main lessons learned from the public health (PH) response to COVID-19, using the global perspective endorsed by the WHO pillars, and understand what countries have learned from their practical actions. (2) Methods: we searched for articles in PubMed and CINAHL from 1 January 2020 to 31 January 2022. 455 articles were included. Inclusion criteria were PH themes and lessons learned from the COVID-19 pandemic. One hundred and forty-four articles were finally included in a detailed scoping review. (3) Findings: 78 lessons learned were available, cited 928 times in the 144 articles. Our review highlighted 5 main lessons learned among the WHO regions: need for continuous coordination between PH institutions and organisations (1); importance of assessment and evaluation of risk factors for the diffusion of COVID-19, identifying vulnerable populations (2); establishment of evaluation systems to assess the impact of planned PH measures (3); extensive application of digital technologies, telecommunications and electronic health records (4); need for periodic scientific reviews to provide regular updates on the most effective PH management strategies (5). (4) Conclusion: lessons found in this review could be essential for the future, providing recommendations for an increasingly flexible, fast and efficient PH response to a healthcare emergency such as the COVID-19 pandemic.

Psychosocial factors as main predictors of quality of life 5 years after stroke: a cross-sectional study from a third-level Italian center.

Stroke causes a significant reduction in health-related quality of life (HRQoL), and studies addressing its predictors often rely on models with few variables. This study aimed to assess the degree to which health status, health habits, and features of the environment predict HRQoL in stroke survivors with stable clinical condition. WHO Quality of Life questionnaire for old-Age subjects (WHOQOL-AGE) was used to assess HRQoL. We ran a multivariable linear regression to predict WHOQOL-AGE variation, entering measures of health state, bad habits, healthy behaviors, physical environment features, and social support. Patients were stroke survivors with a stable clinical condition, distance from acute event of more than 6 months, and National Institutes of Health Stroke Scale (NIHSS) of 10 or less. A total of 122 participants (47 females, 97 with ischemic stroke) were enrolled, the mean age was 64.1, mean NIHSS 2.9, and mean distance from the acute event was 5.1 years. State anxiety (ß = -0.202), trait anxiety (ß = -0.232), depression (ß = -0.255), social support (ß = 0.247), and functional independence (ß = -0.210) predicted WHOQOL-AGE variation (Adj. R2 = 0.549). Our results show that psychological symptoms, reduced social network, and functional dependence together have a negative impact on HRQoL. These elements, which are partly stroke-specific, should be taken into account in the recovery process to enhance patients' health outcomes.

Clonazepam for the management of sleep disorders.

BACKGROUND: The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals. METHODS: A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index. RESULTS: A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis. DISCUSSION AND CONCLUSIONS: Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.