Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

Background The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear. Objective Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years. Methods 85 patients, originally enrolled in a multicentre, randomised trial of ω−3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer. Results Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (β=−0.399, p=0.040) and deep (β=−0.556, p=0.010) GM volume, lower mean cortical thickness (β=−0.581, p=0.010) and higher T2 lesion count (β=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (β=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression. Conclusion Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.publishedVersio

The economic impacts of UK fiscal policies and their spillover effects on the energy system

The energy system and the economy are inextricably intertwined. Whilst this interdependence is, of course, widely recognized, it has not featured prominently in assessing the likely impact of economic policies. In principle, fiscal policies are likely to have an influence on key elements of the energy system, the neglect of which may lead to inefficiencies in the design of appropriate energy and economic policies. The importance of this in practice depends on the strength of the spillover effects from fiscal policy instruments to energy policy goals. This is the focus of this chapter. We employ a multi-sectoral computable general equilibrium approach for the United Kingdom that allows us to track the impact of key fiscal policy interventions on goals of economic and energy policies. We explore whether it is possible to stimulate the economy through fiscal policy without generating an adverse impact on the energy system. Overall, our results suggest that it is unlikely that an increase in current public spending or a fall in the income tax rate will generate a simultaneous increase in GDP and fall in emissions in the United Kingdom context. Nonetheless, there are undoubted differential spillover effects on key components of the energy system from tax and public spending interventions that may prove capable of being exploited through the coordination of fiscal and energy policies. Even if it seems doubtful that fiscal policies would be formulated with a view to improved coordination with energy policies, policymakers can benefit from knowledge of the likely direction and scale of fiscal spillover effects to key elements of the energy system, since this reveals, for example, the extent of any energy policy adjustment that would be required to maintain a given level of emissions

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis

High BMI is associated with low ALS risk: A population-based study

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. Abstract Objective To investigate the temporal relationship among prediagnostic body mass index (BMI), weight change, and risk of amyotrophic lateral sclerosis (ALS). Methods From the compulsory Norwegian tuberculosis screening program, we collected objectively measured BMI from 85% of all citizens (near 1.5 million) between 20 and 70 years of age living in 18 of 19 Norwegian counties between 1963 and 1975. For those who participated in later health surveys, we collected further information on weight change, lifestyle, and health. We identified ALS cases until September 2017 through national registries of diagnoses at death and at encounters with the specialist health service. Both Cox hazard models and flexible parametric survival models were fitted to address our research question. Results We identified 2,968 ALS cases during a mean of 33 (maximum 54) years follow-up. High prediagnostic BMI was associated with low subsequent ALS risk across the typical ALS ages in both sexes. Overall, hazard ratio (HR) for ALS per 5-unit increase in prediagnostic BMI was 0.83 (95% confidence interval [CI] 0.79–0.88). After an initial increase during the first 10 years, it decreased almost linearly throughout the observation period and was 0.69 (95% CI 0.62–0.77) after 50 years. Those in the quartile with highest weight gain had lower ALS risk than those in the lowest quartile (HR 0.63, 95% CI 0.44–0.89). Conclusion High BMI and weight gain are associated with low ALS risk several decades later. The strength of the association between BMI and ALS risk increases up to 50 years after BMI measurement

High BMI is associated with low ALS risk: A population-based study

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. Abstract Objective To investigate the temporal relationship among prediagnostic body mass index (BMI), weight change, and risk of amyotrophic lateral sclerosis (ALS). Methods From the compulsory Norwegian tuberculosis screening program, we collected objectively measured BMI from 85% of all citizens (near 1.5 million) between 20 and 70 years of age living in 18 of 19 Norwegian counties between 1963 and 1975. For those who participated in later health surveys, we collected further information on weight change, lifestyle, and health. We identified ALS cases until September 2017 through national registries of diagnoses at death and at encounters with the specialist health service. Both Cox hazard models and flexible parametric survival models were fitted to address our research question. Results We identified 2,968 ALS cases during a mean of 33 (maximum 54) years follow-up. High prediagnostic BMI was associated with low subsequent ALS risk across the typical ALS ages in both sexes. Overall, hazard ratio (HR) for ALS per 5-unit increase in prediagnostic BMI was 0.83 (95% confidence interval [CI] 0.79–0.88). After an initial increase during the first 10 years, it decreased almost linearly throughout the observation period and was 0.69 (95% CI 0.62–0.77) after 50 years. Those in the quartile with highest weight gain had lower ALS risk than those in the lowest quartile (HR 0.63, 95% CI 0.44–0.89). Conclusion High BMI and weight gain are associated with low ALS risk several decades later. The strength of the association between BMI and ALS risk increases up to 50 years after BMI measurement

Vitamin D supplementation and neurofilament light chain in multiple sclerosis

OBJECTIVES: The effect of vitamin D supplementation on the disease course of multiple sclerosis (MS) is not established. Neurofilament light chain (NFL) is a sensitive marker of axonal degeneration. The aim of this study was to establish whether high-dose vitamin D supplementation reduces serum levels of NFL. MATERIALS AND METHODS: We have performed a 96 weeks placebo-controlled randomized study of weekly supplementation with 20.000 IU vitamin D3 in 71 patients with relapsing remitting MS (RRMS). Serum levels of NFL were measured at baseline, week 48 and week 96 with a single molecule (Simoa) assay in 69 of these patients. RESULTS: Serum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group. Compared to placebo, vitamin D supplementation had no overall effect on the change in serum levels of NFL from baseline (p=0.93 at week 48 and p=0.56 at week 96). In the subgroup of patients not receiving disease-modifying therapy, NFL decreased by 30.9% to week 48 and 32.6% to week 96 from baseline in the vitamin D group as compared to the placebo group (p=0.06 for both time points). CONCLUSION: With a possible exception for patients not treated with disease-modifying drugs, weekly supplementation with 20.000 IU vitamin D3 did not affect NFL levels in these RRMS patients. This article is protected by copyright. All rights reserved