Early-life factors are reported to modulate the risk of developing multiple sclerosis (MS) among adults. The association between exposure to breastfeeding and the risk of MS is debated. We aimed to ...disclose whether past exposure to breastfeeding and its duration are associated with the risk of developing MS.
We used a cohort design linking prospectively collected information on breastfeeding from the Cohort of Norway community-based surveys on health status (CONOR) with the Norwegian MS Registry and the population-based Medical Birth Registry of Norway that includes information on all births in Norway since 1967. MS clinical onset was collected throughout 2016. A total of 95 891 offspring born between 1922 and 1986 to mothers participating in CONOR were included. We identified 215 offspring within this cohort who developed adult-onset MS. Associations between breastfeeding and MS risk were estimated as hazard ratios using Cox proportional hazard models adjusting for maternal factors including education.
We found no association between having been breastfed for ≥4 months and MS risk, also after adjusting for various maternal factors (hazard ratio = 0.90; 95% confidence interval 0.68-1.19). The estimates did not change for different durations of breastfeeding. The results were similar when adjusting for other perinatal factors.
Our study could not confirm previous findings of an association between breastfeeding and risk of MS. Breastfeeding information was less likely to be biased by knowledge of disease compared with case-control studies.
Abstract Introduction: Chronic kidney disease and hemodialysis normally have an impact on the functioning. Objective: To validate the Brazilian version of the World Health Organization Disability ...Assessment Schedule 2.0 in individuals with chronic kidney disease on hemodialysis treatment. Methods: The 36-item version was applied to interview 51 individuals with chronic kidney disease undergoing dialysis treatment. To ascertain the instrument’s applicability, its internal consistency and test-retest stability were studied. To check the validity, a convergent/divergent analysis was performed. Results: The participants answered the questions on the main instrument at two timepoints and on the World Health Organization Quality of Life Abbreviated instrument and the Kidney Disease Quality of Life - Short FormTM 1.3 once each. Cronbach’s α coefficient was appropriate in all domains except the “Getting along” domain. The test-retest coefficients were above the recommended value (> 0.70). Convergent and divergent validity analysis also showed consistent results by correlation coefficient assessment. Conclusion: The instrument is valid and reliable. This study supports the use of the questionnaire by presenting its appropriate psychometric properties. We suggest that some care should be taken specifically in the sexual questions of the “Getting along” domain.
Resumo Introdução: A doença renal crônica e a hemodiálise normalmente têm um impacto na funcionalidade. Objetivo: Validar a versão brasileira do World Health Organization Disability Assessment Schedule - WHODAS 2.0 em indivíduos com doença renal crônica em tratamento de hemodiálise. Métodos: A versão de 36 itens foi aplicada por entrevista em 51 indivíduos com doença renal crônica submetidos a tratamento de hemodiálise. Para verificar a aplicabilidade do instrumento, sua consistência interna e estabilidade teste-reteste foram estudadas. Para verificar a validade, a análise convergente/divergente foi realizada. Resultados: Os participantes responderam às perguntas do instrumento principal em dois momentos distintos no tempo, e do instrumento abreviado sobre Qualidade de Vida da Organização Mundial de Saúde e do questionário Qualidade de Vida com Doença Renal - Short FormTM 1.3 uma vez cada u m. O coeficiente α de Cronbach foi apropriado em todos os domínios, exceto o domínio “Relações Interpessoais”. Os coeficientes teste-reteste estavam acima do valor recomendado (> 0,70). A análise de validade convergente e divergente também mostrou resultados consistentes pela avaliação dos coeficientes de correlação. Conclusão: O instrumento é válido e confiável. Este estudo apoia o uso do instrumento pela apresentação das suas propriedades psicométricas apropriadas. Sugerimos que alguns cuidados devem ser tomados especificamente nas questões sobre relações sexuais.
Resumen Introducción: La enfermedad renal crónica y la hemodiálisis normalmente tienen un impacto en el funcionamiento. Propósito: Validar la versión brasileña del World Health Organization Disability Assessment Schedule - WHODAS 2.0 en individuos con enfermedad renal crónica en tratamiento de hemodiálisis. Métodos: La versión de 36 ítems se aplicó a 51 personas con enfermedad renal crónica sometidas a tratamiento de diálisis. Para determinar la aplicabilidad del instrumento, se estudió su consistencia interna y estabilidad test-retest. Para verificar la validez, se realizó el análisis convergente / divergente. Resultados: Los participantes respondieron las preguntas sobre el instrumento principal en dos puntos de tiempo y sobre el instrumento abreviado de calidad de vida de la Organización Mundial de la Salud y la calidad de vida de la enfermedad renal-Short FormTM 1.3 una vez. El coeficiente alpha de Cronbach fue apropiado en todos los dominios, excepto en el dominio “Getting along”. Los coeficientes de prueba-reprueba estaban por encima del valor recomendado (>0,70). El análisis de validez convergente y divergente también mostró resultados consistentes por la evaluación del coeficiente de correlación. Conclusión: El instrumento es válido y confiable. Este estudio apoya el uso del instrumento por presentación de sus las propiedades psicométricas apropiadas. Sugerimos que se tenga algo de cuidado específicamente en las cuestiones sexuales del dominio de la apropiación.
Azathioprine for people with multiple sclerosis Nonino, Francesco; Baldin, Elisa; Ridley, Ben ...
Cochrane database of systematic reviews,
07/2021, Letnik:
2021, Številka:
7
Journal Article
Recenzirano
Odprti dostop
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
The objectives of the review are to estimate the benefits and harms of:
azathioprine (AZA) compared with ...placebo or other disease ‐modifying treatments (DMTs) as first‐choice treatment for relapsing forms of multiple sclerosis (MS);
AZA compared with placebo or other DMTs for relapsing forms of MS when switching from another DMT;
AZA compared with placebo or other DMTs as first‐choice treatment for progressive forms of MS; and
AZA compared with placebo or other DMTs for progressive forms of MS when switching from another DMT.
Background
Different therapeutic strategies are available for the treatment of people with relapsing‐remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological ...agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear.
This is an update of a Cochrane review published in 2015.
Objectives
To compare the efficacy and safety, through network meta‐analysis, of interferon beta‐1b, interferon beta‐1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta‐1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1‐a and beta 1‐b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS.
Search methods
CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top‐up search was conducted on 8 August 2022.
Selection criteria
Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS.
Data collection and analysis
Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta‐analysis. Certainty of the evidence was assessed by the GRADE approach.
Main results
We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo‐controlled.
Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk).
Placebo was used as the common comparator for network analysis.
Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high‐certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate‐certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate‐certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate‐certainty evidence) probably result in a large reduction of people with relapses at 12 months.
Relapses over 24 months: data were reported in 28 studies (19,869 participants). Cladribine (RR 0.53, 95% CI 0.44 to 0.64; high‐certainty evidence), alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68; high‐certainty evidence) and natalizumab (RR 0.56, 95% CI 0.48 to 0.65; high‐certainty evidence) result in a large decrease of people with relapses at 24 months. Fingolimod (RR 0.54, 95% CI 0.48 to 0.60; moderate‐certainty evidence), dimethyl fumarate (RR 0.62, 95% CI 0.55 to 0.70; moderate‐certainty evidence), and ponesimod (RR 0.58, 95% CI 0.48 to 0.70; moderate‐certainty evidence) probably result in a large decrease of people with relapses at 24 months. Glatiramer acetate (RR 0.84, 95%, CI 0.76 to 0.93; moderate‐certainty evidence) and interferon beta‐1a (Avonex, Rebif) (RR 0.84, 95% CI 0.78 to 0.91; moderate‐certainty evidence) probably moderately decrease people with relapses at 24 months.
Relapses over 36 months findings were available from five studies (3087 participants). None of the treatments assessed showed moderate‐ or high‐certainty evidence compared to placebo.
Disability worsening over 24 months was assessed in 31 studies (24,303 participants). Natalizumab probably results in a large reduction of disability worsening (RR 0.59, 95% CI 0.46 to 0.75; moderate‐certainty evidence) at 24 months.
Disability worsening over 36 months was assessed in three studies (2684 participants) but none of the studies used placebo as the comparator.
Treatment discontinuation due to adverse events data were available from 43 studies (35,410 participants). Alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (OR 0.39, 95% CI 0.19 to 0.79; moderate‐certainty evidence). Daclizumab (OR 2.55, 95% CI 1.40 to 4.63; moderate‐certainty evidence), fingolimod (OR 1.84, 95% CI 1.31 to 2.57; moderate‐certainty evidence), teriflunomide (OR 1.82, 95% CI 1.19 to 2.79; moderate‐certainty evidence), interferon beta‐1a (OR 1.48, 95% CI 0.99 to 2.20; moderate‐certainty evidence), laquinimod (OR 1.49, 95 % CI 1.00 to 2.15; moderate‐certainty evidence), natalizumab (OR 1.57, 95% CI 0.81 to 3.05), and glatiramer acetate (OR 1.48, 95% CI 1.01 to 2.14; moderate‐certainty evidence) probably result in a slight increase in the number of people who discontinue treatment due to adverse events.
Serious adverse events (SAEs) were reported in 35 studies (33,998 participants). There was probably a trivial reduction in SAEs amongst people with RRMS treated with interferon beta‐1b as compared to placebo (OR 0.92, 95% CI 0.55 to 1.54; moderate‐certainty evidence).
Authors' conclusions
We are highly confident that, compared to placebo, two‐year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two‐year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta‐1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta‐1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower.
Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow‐up of at least three years, and assess other patient‐relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.
Summary
Objective
The literature is sparse on the complex interrelationships between stressors, depression, anxiety disorders, and epilepsy. We hypothesized that a relationship exists between stress ...and epilepsy. We evaluated whether markers of stress are associated with seizure recurrence in a low income community‐based cohort of adults with single unprovoked seizure or newly diagnosed epilepsy.
Methods
We ascertained adult residents of Northern Manhattan and Harlem, New York City, with a first unprovoked seizure or newly diagnosed epilepsy, between December 2010 and January 2013. At enrollment, we collected information about seizure phenomenology, demographics, clinical information, and measures of stress (environmental stress, stressful life events, facets of allostatic load—i.e., the cumulative effect of adaptation to stress, psychiatric disorders, and low collective efficacy). Collective efficacy assesses neighborhood characteristics and incorporates social cohesion and informal social control. All subjects were followed for 2 years for further seizures. Cox proportional hazard regression models were used to estimate the hazard ratios of seizure recurrence during the 2 years of follow‐up.
Results
We identified 52 subjects (64.2%) with a single unprovoked seizure and 29 (35.9%) with newly diagnosed epilepsy. Seizure recurrence was recorded in 38.5% (N = 20) of subjects with a single unprovoked seizure and in 69% of those with epilepsy (N = 20) (p = 0.01). In the overall sample, the hazard of seizure recurrence was increased by lifetime generalized anxiety disorder (3.0‐fold) and by low collective efficacy (2.7‐fold). In a second model, the hazard was increased by lifetime mood disorder (2.1‐fold) and low collective efficacy (2.5‐fold).
Significance
Markers of stress (i.e., low collective efficacy, lifetime mood disorder, and lifetime generalized anxiety disorder) were associated with an increased risk for seizure recurrence in adults with a single unprovoked seizure or newly diagnosed epilepsy. Stress‐reducing interventions, such as mindfulness, may be a useful, safe, and inexpensive adjunctive treatment for epilepsy.
Caesarean section (CS) may affect the risk of developing multiple sclerosis (MS) in the offspring, possibly through changes in gut microbiota composition, but findings from previous studies are ...inconsistent. We investigated whether birth by CS was associated with the risk of adult-onset MS.
We conducted a prospective population-based cohort study, including all individuals born in Norway between 1967 and 2003, using the Medical Birth Registry of Norway linked with the Norwegian Multiple Sclerosis Registry and Biobank. The follow-up was until 2021. We used multivariable Cox models to estimate HRs for MS risk with 95% CIs.
Among 2 046 637 individuals in the cohort, 4954 MS cases were identified. Being born by CS was associated with a modest increase in MS risk (HR=1.18, 95% CI 1.05 to 1.32). In the sibling-matched analysis, we found no association between CS and MS risk. We found an interaction between CS and gestational age (p=0.03): CS was associated with an increased risk of MS in individuals born preterm (HR=1.62, 95% CI 1.18 to 2.24), whereas there was no association in individuals born at term (HR=1.13, 95% CI 0.99 to 1.27). In a subgroup analysis of individuals born in 1988 and onwards, emergency CS was related to an elevated MS risk (HR=1.40, 95% CI 1.07 to 1.83), whereas planned CS was not (HR: 1.10, 95% CI 0.77 to 1.58).
CS was associated with a modestly higher risk of developing MS. However, the stronger associations seen in subgroups who likely experienced a more complicated pregnancy/delivery may point to confounding underlying these associations.
Summary
Background and aim
Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence‐based guidelines ...for the management of narcolepsy in both adults and children.
Methods
The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU‐NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.
Results
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults—scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults—SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children—scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children—SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient’s symptoms, comorbidities, tolerance and risk of potential drug interactions.
Conclusion
The management of narcolepsy involves non‐pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Management of narcolepsy involves both non‐pharmacological and pharmacological approaches. An increasing number of symptomatic treatment options for adults and children is available.
Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and ...real-life feasibility of patient self-collected capillary VAMS for TDM of antiseizure medication (ASMs), using plasma ASMs concentrations from venous blood as a reference standard. Nurses collected venous and capillary blood samples using VAMS. Afterward, persons with epilepsy (PWE) performed VAMS sampling by themselves. All samples were analyzed by UHPLC-MS/MS. We performed a cross-validation study, comparing ASMs concentrations obtained by VAMS nurses and patients’ self-collected versus plasma through Bland-Altman analysis and Passing-Bablok regression. We enrolled 301 PWE (M: F 42.5%:57.5%; mean age 44±16 years), treated with 13 ASMs, providing a total of 464 measurements. Statistical analysis comparing VAMS self-collected versus plasma ASMs concentrations showed a bias close to zero and slope and intercept values indicating a good agreement for CBZ, LCS, LEV, LTG, OXC, PB, and PHT, while a systematic difference between the two methods was found for VPA, PMP, TPM and ZNS. This is the first study showing the reliability and feasibility of the real-world application of PWE self-collected VAMS for most of the ASMs considered, giving a promising basis for at-home VAMS applications.
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•Real-life data on using VAMS for antiseizure medication (ASMs) are lacking.•Cross-validation investigated reliability and feasibility of VAMS vs venous blood.•VAMS showed good accuracy and reliability for CBZ, LCS, LEV, LTG, OXC, PB, and PHT.•Comparison between self and nurse-collected VAMS demonstrates good correlation.•VAMS was demonstrated as a promising tool for future TDM at-home applications.
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