The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use

Risks for Central Nervous System Diseases among Mobile Phone Subscribers: A Danish Retrospective Cohort Study

The aim of this study was to investigate a possible link between cellular telephone use and risks for various diseases of the central nervous system (CNS). We conducted a large nationwide cohort study of 420 095 persons whose first cellular telephone subscription was between 1982 and 1995, who were followed through 2003 for hospital contacts for a diagnosis of a CNS disorder. Standardized hospitalization ratios (SHRs) were derived by dividing the number of hospital contacts in the cohort by the number expected in the Danish population. The SHRs were increased by 10–20% for migraine and vertigo. No associations were seen for amyotrophic lateral sclerosis, multiple sclerosis or epilepsy in women. SHRs decreased by 30–40% were observed for dementia (Alzheimer disease, vascular and other dementia), Parkinson disease and epilepsy among men. In analyses restricted to subscribers of 10 years or more, the SHRs remained similarly increased for migraine and vertigo and similarly decreased for Alzheimer disease and other dementia and epilepsy (in men); the other SHRs were close to unity. In conclusion, the excesses of migraine and vertigo observed in this first study on cellular telephones and CNS disease deserve further attention. An interplay of a healthy cohort effect and reversed causation bias due to prodromal symptoms impedes detection of a possible association with dementia and Parkinson disease. Identification of the factors that result in a healthy cohort might be of interest for elucidation of the etiology of these diseases

Mobile Phones and Multiple Sclerosis – A Nationwide Cohort Study in Denmark

We investigated the risk of, prognosis of and symptoms of multiple sclerosis (MS) among all Danish residents who owned a mobile phone subscription before 1996. Using the Danish Multiple Sclerosis Registry and Civil Registration System, study subjects were followed up for MS through 2004. Poisson models were used to calculate incidence rate ratios (IRR, age range: 18–64 years) and mortality rate ratios (MRR, age range: 18+) and to compare presenting symptoms among subscribers and all non-subscribers. A total of 405 971 subscription holders accrued four million years of follow up, with men accounting for 86% of the observation time. Among subscription holding men, the IRR of MS was close to unity, overall as well as 13+ years after first subscription (IRR 1.02, 95% CI: 0.48–2.16). Among women, the IRR was 3.43 (95% CI: 0.86–13.72) 13+ years after first subscription, however, based on only two cases. Presenting symptoms of MS differed between subscribers and non-subscribers (p = 0.03), with slightly increased risk of diplopia in both genders (IRR: 1.38, 95% CI: 1.02–1.86), an increased risk of fatigue among women (IRR: 3.02, 95% CI: 1.45–6.28), and of optic neuritis among men (IRR: 1.38, 95% CI: 1.03–1.86). Overall the MRR was close to one (MRR: 0.91, 95%CI 0.70–1.19) among MS-patients with a subscription and although we observed some increased MRR estimates among women, these were based on small numbers. In conclusion, we found little evidence for a pronounced association between mobile phone use and risk of MS or mortality rate among MS patients. Symptoms of MS differed between subscribers and nonsubscribers for symptoms previously suggested to be associated with mobile phone use. This deserves further attention, as does the increased long-term risk of MS among female subscribers, although small numbers and lack of consistency between genders prevent causal interpretation

Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (,0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned

Distance to high-voltage power lines and risk of childhood leukemia:An analysis of confounding by and interaction with other potential risk factors

We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73). We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial

Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/ critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute diference and 95% CI −0.1% [−8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (−3.2% [−9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a signifcant interac‑ tion between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated partici‑ pants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to con‑ clude on a potential survival beneft of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these fnd‑ ings warrant further investigation in other trials and real-world studies

Influence of obesity-related risk factors in the aetiology of glioma

BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma