Search

Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Background and purpose Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. Methods A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. Results The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. Conclusions This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Background Recurrent strokes occur in 25% of the cases during the first 5 years after the initial event. Each recur- rent stroke increases the risk for severe disability and mortality. Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rtPA) is one of the therapeutic options when secondary prevention is not efficient and recurrent stroke occurs. Aim Aim of this paper is to present the first ever case of repeated IVT with rtPA in a female patient with recurrent stroke, hospitalized at the Department for Urgent Neurology, University Clinic of Neurology in Skopje, North Macedonia with a review from the literature. Case presentation A 59 years old female patient was admitted due to acute onset of motor and sensory dysphasia and right-sided hemiplegia. The symptoms occurred 1,5 hours before admission. Urgent computed tomography (CT) of the brain showed chronic cerebral infarction in the left and parietal regions, which causing traction of the left lateral ventricle. The patient experienced her first ischemic stroke 2,5 years ago and she was treated with IVT at the time. At the second hospital admission, the patient was conscious, with vital signs and urgent laboratory parameters within normal range. NIHSS score was 13 and a decision for IVT treatment was made. During the application of rtPA, her vital parameters were stable and no side effects were observed. Neurological status of the patient also improved, with NIHSS of 7 at the end of the IVT treatment. Control CT scan performed 24 hours after was without any new lesions. The patient was discharged in a stable condition, with a NIHSS of 4 and mRS of 3. Conclusion Repeated IVT in recurrent stroke is feasible and safe in carefully selected patients. Assessment of risk factors and neuroimaging are crucial when deciding on repeated IVT., Uvod Recidivi moždanih udara javljaju se u 25% slučajeva tijekom prvih 5 godina nakon inicijalnog događaja. Svaki ponovljeni moždani udar povećava rizik za težu onesposobljenost i smrtnost. Intravenska tromboliza (IVT) s rekombinantnim tkivnim aktivatorom plazminogena (rtPA) jedna je od terapijskih mogućnosti u slučajevima kada sekundarna prevencija moždanog udara nije učinkovita te nastupi recidiv moždanog udara. Prikaz slučaja Predstavljamo prvi slučaj na našoj klinici s recidivom moždanim udarom liječenim ponovljenim IVT. 59-godišnja pacijentica primljena je zbog akutne pojave senzomotore disfazije i desne hemiplegije. Simptomi su se javili 1,5 sata prije prijema u bolnicu. Hitna kompjuterizirana tomografija (CT) mozga nije pokazala nove lezije, dok su se prikazale malacijske lezije u lijevoj frontalnoj i parijetalnoj regiji uzrokujući retraktilne promjene na lijevu lateralnu moždanu klijetku. Pacijentica je prvi ishemijski moždani udar doživjela prije 2,5 godine i tada je liječena IVT-om. Pri ovom prijemu u bolnicu, paci- jentica je bila pri svijesti, s vitalnim znakovima i hitnim laboratorijskim parametrima unutar normal- nih granica. NIHSS rezultat je bio 13 i donesena je odluka o IVT liječenju. Tijekom primjene rtPA, vitalni su joj parametri bili stabilni i nisu primijećene nuspojave. Neurološki status pacijenta također se poboljšao na NIHSS od 7 na kraju IVT-a. Kontrolno CT snimnanje mozga nakon 24 sata nije poka- zalo novih lezija. Pacijentica je otpušten u stabilnom stanju, s NIHSS 4 i mRS 3. Zaključak Ponovljeni IVT kod ponovljenog moždanog udara izvediv je i siguran kod pažljivo odabranih bole- snika. Procjena čimbenika rizika i nalaz neuoslikovnih metoda prikaza mozga presudni su pri odluci o ponovljenoj primjeni IVT-a.

Background To date, the scientific literature on socioeconomic correlates and determinants of physical activity behaviours has been dispersed throughout a number of systematic reviews, often focusing on one factor (e.g. education or parental income) in one specific age group (e.g. pre-school children or adults). The aim of this umbrella review is to provide a comprehensive and systematic overview of the scientific literature from previously conducted research by summarising and synthesising the importance and strength of the evidence related to socioeconomic correlates and determinants of PA behaviours across the life course. Methods Medline, Embase, ISI Web of Science, Scopus and SPORTDiscus were searched for systematic literature reviews and meta-analyses of observational studies investigating the association between socioeconomic determinants of PA and PA itself (from January 2004 to September 2017). Data extraction evaluated the importance of determinants, strength of evidence, and methodological quality of the selected papers. The full protocol is available from PROSPERO (PROSPERO2014:CRD42015010616). Results Nineteen reviews were included. Moderate methodological quality emerged. For adults, convincing evidence supports a relationship between PA and socioeconomic status (SES), especially in relation to leisure time (positive relationship) and occupational PA (negative relationship). Conversely, no association between PA and SES or parental SES was found for pre-school, school-aged children and adolescents. Conclusions Available evidence on the socioeconomic determinants of PA behaviour across the life course is probable (shows fairly consistent associations) at best. While some evidence is available for adults, less was available for youth. This is mainly due to a limited quantity of primary studies, weak research designs and lack of accuracy in the PA and SES assessment methods employed. Further PA domain specific studies using longitudinal design and clear m

Background: Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective: To identify the physical environmental determinants that influence PA across the life course. Methods: An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that investigated the association between physical determinants and physical activity outcomes, were eligible for inclusion. The extracted data were assessed on the importance of determinants, strength of evidence and methodological quality. Results: The literature search identified 28 SLRs and 3 MAs on 67 physical environmental characteristics potentially related to physical activity that were eligible for inclusion. Among preschool children, a positive association was reported between availability of backyard space and outdoor toys/equipment in the home and overall physical activity. The availability of physical activity programs and equipment within schools, and neighbourhood features such as pedestrian and cyclist safety structure were positively associated with physical activity in children and adolescents. Negative street characteristics, for example, lack of sidewalks and streetlights, were negatively associated with physical activity in adults. Inconsistent associations were reported for the majority of reviewed determinants in adults. Conclusion: This umbrella SLR provided a comprehensive overview of the physical environment determinants of physical activity across the life course and has highlighted, particularly amongst youth, a number of key d

Low levels of physical activity (PA) are reported to contribute to the occurrence of non-communicable diseases over the life course. Although psychological factors have been identified as an important category concerning PA behavior, knowledge on psychological determinants of PA is still inconclusive. Therefore, the aim of this umbrella systematic literature review (SLR) was to summarize and synthesize the scientific evidence on psychological determinants of PA behavior across the life course. A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January 2004 to April 2016. SLRs and meta-analyses (MAs) of observational studies investigating the association of psychological variables and PA were considered eligible. Extracted data were evaluated based on importance of determinants, strength of evidence, and methodological quality. The full protocol is available from PROSPERO (Record ID: CRD42015010616). Twenty reviews (14 SLRs and 6 MAs), mostly of moderate methodological quality, were found eligible. Convincing evidence was found for self-efficacy (positive association with PA) in children and adolescents, and stress (negative association with PA) regardless of age. Most of the evidence revealing an association between psychological determinants and PA is probable and limited, mainly due to differences in the definition of PA and of psychological determinants across reviews. Thus, scholars are urged to reach a consensus on clear definitions of relevant psychological determinants of PA, subsuming cultural biases and allowing the possibility to obtain clear interpretations and generalizability of findings. Finally, most psychological determinants should be considered within a larger framework of other multi-level determinants that may interact or mediate some of the effects.

Background: Low levels of physical activity (PA) are a global concern and increasing PA engagement is becoming a priority in current public health policies. Despite the large number of studies and reviews available, the evidence regarding the behavioral determinants of PA is still inconclusive. Thus, the aim of this umbrella systematic literature review (SLR) was to summarize the evidence on the behavioral determinants of PA across the life course. Methods: A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January, 2004 to April, 2016. SLRs and meta-analyses (MAs) of observational studies that investigated the behavioral determinants of PA were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42015010616). Results: Seventeen reviews on 35 behavioral determinants of PA were eligible for this umbrella SLR. Regardless of age, the most investigated determinants were those related with 'screen use' and 'smoking'. For youth, probable positive evidence emerged for 'previous PA' and 'independent mobility and active transport' among children and adolescents. For the adult population, 'transition to university' and 'pregnancy/having a child' showed probable negative associations. Conclusions: Although the majority of the evidence was limited and most of the determinants were not associated with PA, this umbrella SLR provided a comprehensive overview of the associations between behavioral determinants and PA. Youth should be physically active in the early years and increase active transportation to/from school, independent mobility, and 'free-range activities' without adult supervision, whilst adult PA behaviors are mostly influenced by the life events. Finally, more research is needed that in

peer-reviewed, Background: Despite the large number of studies and reviews available, the evidence regarding the biological determinants of physical activity (PA) is inconclusive. In this umbrella review, we summarized the current evidence on the biological determinants of PA across the life course, by pooling the results of the available systematic literature reviews (SLRs) and meta-analyses (MAs). Methods: We conducted an online search on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases up to January 2018. SLRs and MAs of observational studies that investigated the association between biological determinants of PA and having PA as outcome were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. Results: We identified 19 reviews of which most were of moderate methodological quality. Determinants that were studied most frequently among all ages and demonstrated evidence suggesting a positive association to PA were younger age, being male, higher health status, and higher physical fitness levels. Among adults, normal birth weight was found to be positively associated to PA with convincing strength of evidence, while findings among adolescents were inconsistent and with limited strength of evidence. Conclusions: Different social or behavioral factors may contribute to the decrease of PA with age and among females versus males, and creating programmes targeted at diverse ages, female population, and adults with abnormal birth weight is recommended. Future studies should use prospective study designs, standardized definitions of PA, and objective measurement methods of PA assessment.

peer-reviewed, Low levels of physical activity (PA) are reported to contribute to the occurrence of non-communicable diseases over the life course. Although psychological factors have been identified as an important category concerning PA behavior, knowledge on psychological determinants of PA is still inconclusive. Therefore, the aim of this umbrella systematic literature review (SLR) was to summarize and synthesize the scientific evidence on psychological determinants of PA behavior across the life course. A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January 2004 to April 2016. SLRs and meta-analyses (MAs) of observational studies investigating the association of psychological variables and PA were considered eligible. Extracted data were evaluated based on importance of determinants, strength of evidence, and methodological quality. The full protocol is available from PROSPERO (Record ID: CRD42015010616). Twenty reviews (14 SLRs and 6 MAs), mostly of moderate methodological quality, were found eligible. Convincing evidence was found for self-efficacy (positive association with PA) in children and adolescents, and stress (negative association with PA) regardless of age. Most of the evidence revealing an association between psychological determinants and PA is probable and limited, mainly due to differences in the definition of PA and of psychological determinants across reviews. Thus, scholars are urged to reach a consensus on clear definitions of relevant psychological determinants of PA, subsuming cultural biases and allowing the possibility to obtain clear interpretations and generalizability of findings. Finally, most psychological determinants should be considered within a larger framework of other multi-level determinants that may interact or mediate some of the effects.

peer-reviewed, Background To date, the scientific literature on socioeconomic correlates and determinants of physical activity behaviours has been dispersed throughout a number of systematic reviews, often focusing on one factor (e.g. education or parental income) in one specific age group (e.g. pre-school children or adults). The aim of this umbrella review is to provide a comprehensive and systematic overview of the scientific literature from previously conducted research by summarising and synthesising the importance and strength of the evidence related to socioeconomic correlates and determinants of PA behaviours across the life course. Methods Medline, Embase, ISI Web of Science, Scopus and SPORTDiscus were searched for systematic literature reviews and meta-analyses of observational studies investigating the association between socioeconomic determinants of PA and PA itself (from January 2004 to September 2017). Data extraction evaluated the importance of determinants, strength of evidence, and methodological quality of the selected papers. The full protocol is available from PROSPERO (PROSPERO2014:CRD42015010616). Results Nineteen reviews were included. Moderate methodological quality emerged. For adults, convincing evidence supports a relationship between PA and socioeconomic status (SES), especially in relation to leisure time (positive relationship) and occupational PA (negative relationship). Conversely, no association between PA and SES or parental SES was found for pre-school, school-aged children and adolescents. Conclusions Available evidence on the socioeconomic determinants of PA behaviour across the life course is probable (shows fairly consistent associations) at best. While some evidence is available for adults, less was available for youth. This is mainly due to a limited quantity of primary studies, weak research designs and lack of accuracy in the PA and SES assessment methods employed. Further PA domain specific studies using longitudinal design and clear m

peer-reviewed, Background: Low levels of physical activity (PA) are a global concern and increasing PA engagement is becoming a priority in current public health policies. Despite the large number of studies and reviews available, the evidence regarding the behavioral determinants of PA is still inconclusive. Thus, the aim of this umbrella systematic literature review (SLR) was to summarize the evidence on the behavioral determinants of PA across the life course. Methods: A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORT Discus databases. The search was limited to studies published in English from January, 2004 to April, 2016. SLRs and meta-analyses (MAs) of observational studies that investigated the behavioral determinants of PA were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42015010616). Results: Seventeen reviews on 35 behavioral determinants of PA were eligible for this umbrella SLR. Regardless of age, the most investigated determinants were those related with ‘screen use’ and ‘smoking’. For youth, probable positive evidence emerged for ‘previous PA’ and ‘independent mobility and active transport’ among children and adolescents. For the adult population, ‘transition to university’ and ‘pregnancy/having a child’ showed probable negative associations. Conclusions: Although the majority of the evidence was limited and most of the determinants were not associated with PA, this umbrella SLR provided a comprehensive overview of the associations between behavioural determinants and PA. Youth should be physically active in the early years and increase active transportation to/from school, independent mobility, and ‘free-range activities’ without adult supervision, whilst adult PA behaviors are mostly influenced by the life events. Finally, more research is needed that

peer-reviewed, Objective: Regular physical activity (PA) reduces the risk of disease and premature death. Knowing factors associated with PA might help reducing the disease and economic burden caused by low activity. Studies suggest that socio-cultural factors may affect PA, but systematic overviews of findings across the life course are scarce. This umbrella systematic literature review (SLR) summarizes and evaluates available evidence on socio-cultural determinants of PA in children, adolescents, and adults. Methods: This manuscript was drafted following the recommendations of the ‘Preferred Reporting Items for Systematic reviews and Meta-Analyses’ (PRISMA) checklist. The MEDLINE, Web of Science, Scopus, and SPORTDiscus databases were searched for SLRs and meta-analyses (MAs) on observational studies published in English that assessed PA determinants between January 2004 and April 2016. The methodological quality was assessed and relevant information on socio-cultural determinants and any associations with PA was extracted. The available evidence was evaluated based on the importance of potential determinants and the strength of the evidence. Results: Twenty SLRs and three MAs encompassing 657 eligible primary studies investigated potential socio-cultural PA determinants, with predominantly moderate methodological quality. Twenty-nine potential PA determinants were identified that were primarily assessed in children and adolescents and investigated the micro-environmental home/household level. We found probable evidence that receiving encouragement from significant others and having a companion for PA were associated with higher PA in children and adolescents, and that parental marital status (living with partner) and experiencing parental modeling were not associated with PA in children. Evidence for the other potential determinants was limited, suggestive, or non-conclusive. In adults, quantitative and conclusive data were scarce. Conclusions: A substantial number of SLRs and

peer-reviewed, Despite the large number of studies and reviews available, the evidence regarding the policy determinants of physical activity (PA) is inconclusive. This umbrella systematic literature review (SLR) summarizes the current evidence on the policy determinants of PA across the life course, by pooling the results of the available SLRs and meta-analyses (MAs). Methods: A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus and SPORTDiscus databases up to April 2016. SLRs and MAs of observational studies investigating the association between policy determinants of PA and having PA as outcome were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence and the methodological quality. Results: Fourteen reviews on 27 policy determinants of PA were eligible for this umbrella SLR. The majority of the reviews were of moderate quality. Among children, a clear association between time spent outdoors and PA emerged. Among adults, working hours were negatively associated with PA, though evidence was limited. At the population level, community- and street-scale urban design and land use policies were found to positively support PA levels, but levels of evidences were low. Conclusions: With this umbrella SLR the policy determinants of PA at individual-level and population-level have been summarized and assessed. None of the investigated policy determinants had a convincing level of evidence, and very few had a probable level of evidence. Further research is needed, preferably by using prospective study designs, standardized definitions of PA and objective measurement of PA.

peer-reviewed, Background Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective To identify the physical environmental determinants that influence PA across the life course. Methods An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that investigated the association between physical determinants and physical activity outcomes, were eligible for inclusion. The extracted data were assessed on the importance of determinants, strength of evidence and methodological quality. Results The literature search identified 28 SLRs and 3 MAs on 67 physical environmental characteristics potentially related to physical activity that were eligible for inclusion. Among preschool children, a positive association was reported between availability of backyard space and outdoor toys/equipment in the home and overall physical activity. The availability of physical activity programs and equipment within schools, and neighbourhood features such as pedestrian and cyclist safety structure were positively associated with physical activity in children and adolescents. Negative street characteristics, for example, lack of sidewalks and streetlights, were negatively associated with physical activity in adults. Inconsistent associations were reported for the majority of reviewed determinants in adults. Conclusion This umbrella SLR provided a comprehensive overview of the physical environment determinants of physical activity across the life course and has highlighted, particularly amongst youth, a number of key determ