Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1:a multicentre, single-blind, randomised trial

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI −0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (−2·02, −4·02 to −0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Funding: The European Union Seventh Framework Programme

Radon dose conversion coefficients and their use in the Nordic countries : Nordic-Nat Report 03/2024

The dose conversion coefficients for radon published by the ICRP in 2018 caused some puzzlement among many radiation protection authorities, as doses for the same radon exposure would be twice as high, and in some cases even higher. This may lead to an increased number of workplaces being considered as a planned exposure situations and requiring a safety license under the EU-BSS directive. Furthermore, the credibility of the authority may suffer in the eyes of those workplaces with elevated radon levels if a concentration level previously considered safe enough is no longer acceptable. A further complication factor is that the ICRP and UNSCEAR each have their own, different dose conversion coefficients. The problem is not confined to workplaces. Radiation protection authorities often publish dose pie charts of the mean effective doses received by the public annually. In these, radon typically accounts for a large proportion, but with the latest dose conversion coefficients from the ICRP, radon can account for the majority of the total dose. At the same time, the effective dose to the population can almost double. How should this change in effective dose be explained to the public and the media? This report emphasizes that the effective dose is not a measure of risk, but a tool used in radiation protection work to monitor compliance with dose limits or dose constraints when radiation exposure comes from different sources. In addition, the effective dose is a useful tool for optimizing radiation protection in order to target measures to reduce radiation exposure in a cost-effective way. It should also be noted that in the case of radon, there is an exposure-response relationship for long-term exposure to different radon concentrations (time integral of radon concentration) and risk of lung cancer. Therefore, it is not necessary to make a risk assessment based on effective dose, but to use data directly from epidemiological studies. It is also emphasized that in the case of radon exposure, smoking is particularly important in assessing the risk to an individual, so that the effective dose is a particularly poor tool for assessing the health risk due to radon exposure to an individual. This report summarises the current approaches in Finland, Sweden and Norway for estimating the effective dose from indoor radon in workplaces and dwellings, and for radon in drinking water. So far, Denmark and Iceland have not had the need for dose assessment for radon exposure and are therefore not covered in this report. For occupational exposure to radon in indoor air, the working group recommends that all Nordic countries, including non-EU member states, adopt the effective dose assessment method outlined in ICRP 137 from the radiation protection point of view. The current monitoring practices and reference values specified in existing Finnish, Swedish and Norwegian legislation allow for the application of the dose conversion coefficient from ICRP 137 with minimal impact. For managing radon exposure in the home, effective doses are not recommended. Instead focus should remain on radon activity concentration, as risk assessment for radon exposure is based on epidemiological evidence. If a "dose pie chart" is published to compare different sources of radiation, it is essential to highlight the three points outlined in the previous paragraph. In addition, the caption should clearly state that the risk assessment for radon is not based on the effective dose. For ingested radon, the working group recommends that the latest ICRP dose conversion coefficients, based on recent scientific findings, be used in the future

Alternativas de cuidado para evitar la mortalidad neonatal

La mortalidad neonatal es uno de los principales problemas de salud pública en todo el mundo ante los que cada año se han venido incrementando la implementación de intervenciones con la intención de mejorar tanto la salud del recién nacido como la reducción de los índices de mortalidad neonatal. En 2017, las cifras de neonatos fallecidos en su primer mes de vida era de 2,5 millones y la inmensa mayoría de las defunciones de recién nacidos se producen en países de ingresos bajos y medianos. El objetivo fundamental de la presente investigación consiste en revisar y plasmar los cuidados alternativos para evitar la mortalidad neonatal, referida a la madre durante el proceso de embarazo, específicamente la meditación y la relajación y la nutrición natural. El diseño de investigación que se llevó a cabo es de tipo documental o bibliográfico. En el embarazo y parto, la meditación es usada con la finalidad de disminuir la ansiedad, además del dolor y el nerviosismo que representa cada etapa. Una alimentación equilibrada como práctica de la naturopatía donde se recomienden alimentos y preparaciones naturales, garantizan mayores probabilidades de salud para la madre embarazada y la prevención de complicaciones relacionadas con la mortalidad neonatal tales como: la prematuridad, el bajo peso al nacer, y otras complicaciones fetales. Por último, es importante que las mujeres embarazadas no tomen ningún producto alternativo o realicen alguna práctica natural sin consultar a su médico con antelación. Asimismo, es fundamental que en el caso de optar por este tipo de cuidados naturales se acuda a personal capacitado y con experiencia reconocida en el área

Overview of radon management in the Nordic countries : Nordic-Nat Report 01- 2024.

The aim of this document has been to make an overview of radon management and have a closer look at the similarities and differences between the Nordic countries in this matter. The document is not exhaustive but will be useful for the Nordic co-operation and serves as a basis for further discussions and work to achieve our goals given in the mandate of the Nordic-Nat group. When comparing typical radon activity concentrations e.g. in dwellings, drinking water, etc. it can be seen that the challenges are relatively similar in Finland, Norway and Sweden. Denmark has a less widespread problem, and the radon activity concentrations are generally lower, but the problem is definitely present. In Iceland several national surveys have shown that the radon activity concentrations both in indoor air and drinking water are overall very low. However, comparisons between surveys or individually measured buildings in the different countries must be made with caution. That is one of the reasons that this document will be very useful. For instance, this study has shown that the measurement procedures vary between the Nordic countries. One example is that the seasonal correction factor varies between 0.75 and 1 (no correction). Further, the reference level in Denmark and Sweden refers to an average of measurements in the dwelling, while in Norway it refers to each single living- and bedroom. In Finland, the radon activity concentration in dwellings was reported as the average of the measurement results according to the housing health guidelines until 2016. At that time, the application guide for housing health legislation was updated, in which radon was no longer mentioned. In practice, the outdated guideline has still been in use. The reference level for existing dwellings and premises where the public have access varies between 100 and 300 Bq/m3 and limit/reference values in new buildings between 100 and 200 Bq/m3. Norway differs from the other countries in having a two-part system of reference values. Further, there are differences between the countries in how long the limit/reference values given in the national building regulations for a new building apply. In Denmark it applies as long as the building exists, and consequently all buildings constructed according to the provisions in Building Regulations 2010 or later are subject to the limit value of 100 Bq/m3. In Finland, the reference value for new buildings is usually valid for 10 years after completion. In Norway the regulations apply until the certificate of completion is issued, but with a general warranty period of 5 years. In Sweden, the requirement must be met in such a way that with normal maintenance the requirement can be assumed to continue to be met for an economically reasonable lifetime of the building, in accordance with 8 chapter, 5 section 2 item in the Planning and Building Act (SFS, 2010:900). Should the requirement become stricter in the future for new buildings, you cannot be obliged to upgrade the building. In addition to the limit value, solutions for preventive measures in new buildings are mandatory and specifically mentioned in the regulation in Norway. In Denmark, Finland and Sweden, the limit/reference values are given in the regulations, and guidance material is provided on how to fulfil the regulatory limit values by means of preventive measures. In Sweden, the national grants for radon remediation in dwellings that were offered by the authorities in two periodes, 1988-2015 and 2018-2021 have been discontinued. The general tax deduction for craftsman services in private dwellings still exists. Similar general tax deductions are offered in Finland. In Denmark the tax deduction option for costs related to radon mitigation measures in existing dwellings, was abolished in April 2022. In Norway no grants or tax deductions are offered. 6 Denmark, Finland and Sweden all have reference levels and/or limit values for workplaces stated in national regulations. In Norway the workplace is regulated in general terms in the regulations and reference values are given in guidance material. When it comes to drinking water the recommendations and requirements also differ between the countries. For waterworks the quality requirements of radon activity concentration are either 100 or 1000 Bq/L. The countries with the highest quality requirements levels have a quality target value of 100 or 300 Bq/L. For private wells there are no requirements, but the quality recommendations vary between 500 and 1000 Bq/L. Finland, Denmark and Sweden have implemented reference levels for doses caused by gamma radiation in new buildings and building materials in the national regulations. In Norway gamma radiation in buildings and building material is not regulated

Structural white matter networks in myotonic dystrophy type 1

The myriad of neuropsychiatric manifestations reported in myotonic dystrophy type 1 may have its origin in alterations of complex brain network interactions at the structural level. In this study, we tested the hypothesis that altered white matter microstructural integrity and network organisation were present in a cohort of individuals with DM1 compared to unaffected controls, which was expected to be associated with CNS related disease manifestations of DM1. We performed a cross-sectional neuropsychological assessment and brain MRI in 25 myotonic dystrophy type 1 (DM1) patients and 26 age, sex and educational level matched unaffected controls. Patients were recruited from the Dutch cohort of the OPTIMISTIC study, a concluded trial which had included ambulant, genetically confirmed DM1 patients who were severely fatigued. We applied graph theoretical analysis on structural networks derived from diffusion tensor imaging (DTI) data and deterministic tractography to determine global and local network properties and performed group-wise comparisons. Furthermore, we analysed the following variables from structural MRI imaging: semi-quantitative white matter hyperintensity load and white matter tract integrity using tract-based spatial statistics (TBSS). Structural white matter networks in DM1 were characterised by reduced global efficiency, local efficiency and strength, while the network density was compatible to controls. Other findings included increased white matter hyperintensity load, and diffuse alterations of white matter microstructure in projection, association and commissural fibres. DTI and network measures were associated (partial correlations coefficients ranging from 0.46 to 0.55) with attention (d2 Test), motor skill (Purdue Pegboard test) and visual-constructional ability and memory (copy subtest of the Rey-Osterrieth Complex Figure Test). DTI and network measures were not associated with clinical measures of fatigue (checklist individual strength, fatigue subscale) or apathy (apathy evaluation scale - clinician version). In conclusion, our study supports the view of brain involvement in DM1 as a complex network disorder, characterised by white matter network alterations that may have relevant neuropsychological correlations. This work was supported by the European Community's Seventh Framework Programme (FP7/2007-2013; grant agreement n degrees 305,697) and the Marigold Foundation

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI −0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (−2·02, −4·02 to −0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Funding: The European Union Seventh Framework Programme