No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine

Objective: To compare the cancer risk of cladribine and other disease-modifying drugs (DMDs) in trials of people with relapsing multiple sclerosis (pwRMS). Methods: Meta-analysis of phase III trials of licensed DMDs for pwRMS and a phase III trial of cladribine (CLARITY). Cancer rates were compared using Fisher exact test. Results: Eleven trials were included. Investigated treatments included cladribine, dimethyl fumarate, fingolimod, teriflunomide, natalizumab, alemtuzumab, and glatiramer acetate. The cancer rate in the CLARITY treatment group (0.34%) was not increased compared to all other treatment groups, whether including placebo-controlled trials only (0.6%, p = 0.4631) or all trials, i.e., including those with an active comparator arm (0.67%, p = 0.3669). No cancer was reported in the CLARITY placebo group, whereas the combined cancer rate of all other placebo groups was 1.19% (p = 0.0159). The cancer rate of zero in the CLARITY placebo group was also lower than that in the phase III trial of cladribine in people with clinically isolated syndrome (ORACLE MS, 2.91%, p = 0.0012). In fact, no difference was detected between cancer rates in the treatment groups of CLARITY (0.34%) and ORACLE MS (0.49%) (p = 0.6546). Conclusions: Our study does not support an increased cancer risk from cladribine in the doses used in CLARITY and ORACLE MS, which previously contributed to refusal of market authorization of cladribine in Europe. Longer-term follow-up is required to assess the safety profile of cladribine, as well as currently licensed DMDs, to definitively assess cancer risk

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

High reprint orders in medical journals and pharmaceutical industry funding: case-control study.

OBJECTIVES: To assess the extent to which funding and study design are associated with high reprint orders. DESIGN: Case-control study. SETTING: Top articles by size of reprint orders in seven journals, 2002-09. PARTICIPANTS: Lancet, Lancet Neurology, Lancet Oncology (Lancet Group), BMJ, Gut, Heart, and Journal of Neurology, Neurosurgery and Psychiatry (BMJ Group) matched to contemporaneous articles not in the list of high reprint orders. MAIN OUTCOME MEASURES: Funding and design of randomised controlled trials or other study designs. RESULTS: Median reprint orders for the seven journals ranged from 3000 to 126,350. Papers with high reprint orders were more likely to be funded by the pharmaceutical industry than were control papers (industry funding versus other or none: odds ratio 8.64, 95% confidence interval 5.09 to 14.68, and mixed funding versus other or none: 3.72, 2.43 to 5.70). CONCLUSIONS: Funding by the pharmaceutical industry is associated with high numbers of reprint orders

CANCER RISK IN MULTIPLE SCLEROSIS PATIENTS TAKING CLADRIBINE

J Neurol Neurosurg Psychiatry 2014;85(10):A1–A5

Value of Emergent Neurovascular Imaging for Seat Belt Injury : A Multi-institutional Study

BACKGROUND AND PURPOSE: Screening for blunt cerebrovascular injury in patients after motor vehicle collision (MVC) solely based on the presence of cervical seat belt sign has been debated in the literature without consensus. Our aim was to assess the value of emergent neurovascular imaging in patients after an MVC who present with a seat belt sign through a large-scale multi-institutional study. MATERIALS AND METHODS: The electronic medical records of patients admitted to the emergency department with CTA/MRAs performed with an indication of seat belt injury of the neck were retrospectively reviewed at 5 participating institutions. Logistic regression analysis was used to determine the association among age, sex, and additional trauma-related findings with blunt cerebrovascular injury. RESULTS: Five hundred thirty-five adult and 32 pediatric patients from June 2003 until March 2020 were identified. CTA findings were positive in 12/567 (2.1%) patients for the presence of blunt cerebrovascular injury of the vertebral ( CONCLUSIONS: The risk of vascular injury in the presence of the cervical seat belt sign is small, and most patients diagnosed with blunt cerebrovascular injury have other associated findings. Therefore, CTA based solely on this sign has limited value (3/567 =  a 0.5% positivity rate). We suggest that in the absence of other clinical findings, the seat belt sign does not independently justify neck CTA in patients after trauma

Gender identity disorders and multiple sclerosis risk: a national record-linkage study

The building of the linked datasets, and the development of the analytical software used to study disease associations, was funded by the English National Institute for Health Research. This study had no specific funding. The funder had no role in study design, data collection, data analysis, data interpretation, writing of the report or for the decision to submit for publication. The views expressed in the paper do not necessarily reflect those of the funding body. K.S. has been supported by a Higher Education Funding Council for England Clinical Senior Lectureship Award

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65–1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016–19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: −0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses