The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated.
The aim of this study was to map and assess the evidence on MS occurrence after drug ...exposure, in order to identify possible signals of causal association.
A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies.
After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results.
A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes.
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring complex diagnostic and therapeutic management. Treatment with Disease Modifying Drugs (DMDs) is aimed ...at reducing relapse rate and disease disability. Few real-world, population-based data are available on the impact of adherence on relapse rate. The objective of this study was to assess the impact of adherence to DMDs on relapses in a real-world Italian setting.
Population-based cohort study. People with MS (PwMS) older than 18 years and residing in the Emilia-Romagna region, Northern Italy, were identified through administrative databases using a validated algorithm. A Cox regression model with a time-varying exposure was performed to assess the association between level of adherence to DMDs and relapses over a 5-year period.
A total of 2,528 PwMS receiving a first prescription of DMDs between 2015 and 2019 were included (average age of 42, two-thirds female). Highly adherent PwMS had a 25 % lower hazard of experiencing moderate or severe relapses than non-adherent PwMS (Hazard Ratio 0.75, 95 % CI 0.58 to 0.98), after adjusting for age and sex. Several sensitivity analyses supported the main result.
The results of our study support the hypothesis that a high level of DMD adherence in MS is associated with a lower risk of moderate or severe relapse. Therefore, choosing the DMD with which to start drug treatment and recommending adherence to treatment appear to be crucial aspects involving both physicians and patients.
Objectives
Sleep‐wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient ...training during their residency, the Young European Sleep Neurologist Association (YESNA) of the European Academy of Neurology (EAN) performed a survey on postgraduate sleep education.
Methods
A 16‐item questionnaire was developed and distributed among neurologists and residents across European countries. Questions assessed demographic, training and learning preferences in sleep disorders, as well as a self‐evaluation of knowledge based on five basic multiple‐choice questions (MCQs) on sleep‐wake disorders.
Results
The questionnaire was completed by 568 participants from 20 European countries. The mean age of participants was 31.9 years (SD 7.4 years) and was composed mostly of residents (73%). Three‐quarters of the participants reported undergraduate training in sleep medicine, while fewer than 60% did not receive any training on sleep disorders during their residencies. Almost half of the participants (45%) did not feel prepared to treat neurological patients with sleep problems. Only one‐third of the participants correctly answered at least three MCQs. Notably, 80% of participants favoured more education on sleep‐wake disorders during the neurology residency.
Conclusions
Education and knowledge on disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. The results of our study may be useful for improving the European neurology curriculum and other postgraduate educational programmes.
Sleep‐wake disorders are common in the general population and in most neurological disorders but often poorly recognised. Education and knowledge on sleep‐wake disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. Our study results may be useful to improve the European Neurology curriculum and other postgraduate educational programs.
Abstract We evaluated several commonly used screening instruments for the detection of mood disorders, anxiety disorders, and attention-deficit hyperactivity disorder (ADHD). These were compared to a ...criterion-based standardized questionnaire, the Diagnostic Interview Survey (DIS)-IV, designed to make DSM-IV-TR diagnoses in the community-based study of childhood-onset epilepsy. The DIS-IV was administered to young adult cases with epilepsy at a 15-year follow-up assessment and compared to symptom screens administered at the same visit, and at a previous 9-year assessment. Among cases, the specificity of the DIS-IV ranged from 0.77 to 0.99 and the predictive value of a negative psychiatric diagnosis was similarly high. Sensitivity was lower, ranging from 0 to 0.77, with correspondingly low predictive value of a positive diagnosis. Symptom-based instruments assess current symptom burden and are useful for determining associations with ongoing seizures or quality of life. Criterion-based standardized interviews, such as the DIS-IV, provide psychiatric diagnoses over the lifetime, which is most useful in studies of epilepsy genetics and studies of comorbidities and prognosis of epilepsy.
Objectives: Mortality data have been used as a proxy for amyotrophic lateral sclerosis (ALS) incidence. However, the accuracy of death certificates (DCs) needs to be validated. This study aims to ...assess the accuracy of DCs in the identification of ALS cases. Methods: This is a retrospective population-based validation study. DC information, provided by the "Centre d'épidémiologie sur les causes médicales de décès", including ICD10 codes for specific cause of death for patients recorded in the French register of ALS cases in the Limousin region (FRALim) and deceased between 2000 and 2011, was assessed. The FRALim register was used as gold standard. Results: In the study period, DCs were available for 197 patients diagnosed with ALS, of whom 185 (93.9%) were correctly identified with an ICD10 code (G12.2) corresponding to ALS. The overall sensitivity was 93.9% (95% CI 89.6-96.8) and the positive predictive value (PPV) was 64.9 (59.1-70.4), with higher values in the period 2004-2011 (75.0-78.9). Stratification for sex, age, and year at death did not show difference in accuracy, except a lower PPV during the first years of observation. Conclusions: DCs identifying subjects with a diagnosis of ALS in the Limousin region, France showed an overall good sensitivity and moderate PPV. The absence of ALS diagnosis as the main and underlying cause of death on DCs highlights the need to use DC in combination with other administrative data to create algorithms with higher accuracy performances.
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
We will perform a network meta‐analysis to assess the relative effectiveness and safety of immunomodulatory and ...immunosuppressive treatments for people with multiple sclerosis in progressive forms of the condition.
Depression is more frequently associated with akinetic-rigid/postural instability gait difficulty subtypes of Parkinson's disease than with tremor-dominant subtype.
The aim of the study is to ...investigate the frequency of exposure to antidepressant drugs, as proxy of depression, before motor onset according to Parkinson's disease subtypes.
Based on a historical cohort design, the exposure to antidepressant drugs before Parkinson's disease motor onset was obtained from the drug prescription database and assessed in the resident population of the Local Healthcare Trust of Bologna (443,117 subjects older than 35 years). Diagnosis of Parkinson's disease and subtype (tremor dominant, non-tremor dominant) at onset were recorded by neurologists and obtained from the “ParkLink Bologna” record linkage system. Exposure to antidepressants was compared both to the general population and between the two subtypes.
From 2006 to 2018, 198 patients had a tremor dominant subtype at onset whereas 450 did not. Comparison with the general population for antidepressant exposure showed an adjusted hazard ratio of 0.86 (95% CI 0.44–1.70) for the tremor dominant subtype and 1.66 (1.16–2.39) for the non-tremor dominant subtype. Comparison of non-tremor dominant with tremor dominant subtypes showed an adjusted odds ratio of 1.86 (1.05–3.95) for antidepressant exposure.
In our study, non-tremor dominant Parkinson's disease at onset was significantly associated with exposure to antidepressants in comparison to the general population and in comparison with the tremor dominant subtype. These results support the hypothesis of different biological substrates for different Parkinson's disease subtypes even before motor onset.
•Depression is more frequent in the non-tremor Parkinson's disease subtype.•Whether depression before motor onset varies in PD subtypes is unknown.•We found an association with premotor antidepressants use and non-tremor subtype.•Our results support different pathophysiology for Parkinson's disease subtypes.
The patterns of long term risk of SARS-CoV-2 infection, hospitalization for COVID-19 and related death are uncertain in people with Parkinson's disease (PD) or parkinsonism (PS). The aim of the study ...was to quantify these risks compared to a control population cohort, during the period March 2020-May 2021, in Bologna, northern Italy.
ParkLink Bologna cohort (759 PD; 192 PS) and controls (9,226) anonymously matched (ratio 1:10) for sex, age, district, comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March-May 2020 and October 2020-May 2021).
Adjusted hazard ratio of SARS-CoV-2 infection was 1.3 (95% CI 1.04-1.7) in PD and 1.9 (1.3-2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID-19 was 1.1 (95% CI 0.8-1.7) in PD and 1.8 (95% CI 0.97-3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30-day mortality risk after hospitalization was higher (p=0.048) in PS (58%) than in PD (19%) and controls (26%).
Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS-CoV-2 infection throughout the first 15 months of the pandemic. COVID-19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.
•International stakeholders identified an evidence-based “gap-map” in MS care.•A survey was translated into 12 languages and disseminated via MS web channels.•Over 1000 people provided input into ...prioritizing topics.•This multi stakeholder priority setting exercise offers a worldwide perspective.•Among the five most urgent research questions is the role of MRI in predicting disease progression.
Eliciting the research priorities of people affected by a condition, carers and health care professionals can increase research value and reduce research waste. The Cochrane Multiple Sclerosis and Rare Disease of CNS Group, in collaboration with the Cochrane Neurological Sciences Field, launched a priority setting exercise with the aim of prioritizing pressing questions to ensure that future systematic reviews are as useful as possible to the people who need them, in all countries, regardless of their economic status.
Sixteen high priority questions on different aspects of MS were developed by members of a multi-stakeholder priority setting Steering Group (SG). In an anonymous online survey translated into 12 languages researchers, clinicians, people with MS (PwMS) and carers were asked to identify and rank, 5 out of 16 questions as high priority and to provide an explanation for their choice. An additional free-text priority research topic suggestion was allowed.
The survey was accessible through MS advocacy associations’ social media and Cochrane web pages from October 20, 2020 to February 6, 2021. 1.190 responses (86.73% of all web contacts) were evaluable and included in the analysis. Responses came from 55 countries worldwide, 7 of which provided >75% of respondents and 95% of which were high and upper-middle income countries. 58.8% of respondents live in the EU, 23% in the Americas, 8.9% in the Western Pacific, 2.8% in the Eastern Mediterranean and 0.3% in South Eastern Asia. About 75% of the respondents were PwMS. The five research questions to be answered with the highest priority were: Question (Q)1 “Does MRI help predict disability worsening of PwMS?” (19.9%), Q5 “What are the benefits and harms of treating PwMS with one disease-modifying drug compared to another?” (19.3%), Q3 “Does multidisciplinary care by teams of different social and health professionals improve health outcomes and experiences for PwMS?” (11.9%), Q16 “Does psychological health affect disease progression in PwMS?” (9.2%) and Q10 “What are the benefits and harms of exercise for PwMS?” (7.2%). The multivariable logistic regression analysis indicated a significant influence of geographic area and income level on the ranking of Q1 and a marginal for Q16 as top a priority after accounting for the effect of all other predictors. Approximately 50% of the respondents indicated that they had an important additional suggestion to be considered.
This international collaborative initiative in the field of MS offers a worldwide perspective on the research questions perceived as pivotal by a geographically representative sample of multiple stakeholders in the field of MS. The results of the survey could guide the prioritization of research on pharmacological and non-pharmacological interventions which could be meaningful and useful for PwMS and carers, avoiding the duplication of efforts and research waste. High quality systematic reviews elicited by priority setting exercises may offer the best available evidence and inform decisions by healthcare providers and policy-makers which can be adapted to the different realities around the world.
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