Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Regional differences in awareness and attitudes regarding genetic testing for disease risk and ancestry

Little is known about the lay public’s awareness and attitudes concerning genetic testing and what factors influence their perspectives. The existing literature focuses mainly on ethnic and socioeconomic differences; however, here we focus on how awareness and attitudes regarding genetic testing differ by geographical regions in the US. We compared awareness and attitudes concerning genetic testing for disease risk and ancestry among 452 adults (41% Black and 67% female) in four major US cities, Norman, OK; Cincinnati, OH; Harlem, NY; and Washington, DC; prior to their participation in genetic ancestry testing. The OK participants reported more detail about their personal ancestries (p = 0.02) and valued ancestry testing over disease testing more than all other sites (p < 0.01). The NY participants were more likely than other sites to seek genetic testing for disease (p = 0.01) and to see benefit in finding out more about one’s ancestry (p = 0.02), while the DC participants reported reading and hearing more about genetic testing for African ancestry than all other sites (p < 0.01). These site differences were not better accounted for by sex, age, education, self-reported ethnicity, religion, or previous experience with genetic testing/counseling. Regional differences in awareness and attitudes transcend traditional demographic predictors, such as ethnicity, age and education. Local sociocultural factors, more than ethnicity and socioeconomic status, may influence the public’s awareness and belief systems, particularly with respect to genetics

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Probabilistic thinking and health risks: An editorial

This special issue is the third in a four-part series, Health Care Through the ‘Lens of Risk', which focus on risk categorisation, valuing, expecting and time-framing respectively, and published or to be published in 2012 and 2013. The present editorial introduces the issue of probabilistic thinking about health in relation to an interview-based article and five substantial research articles, with further articles to appear subsequently in an annex in the next issue of Health, Risk & Society

"Research you cannot talk about": a personal account of researching sudden, unexpected child death

This article takes as its starting point the author’s personal experience of sudden, unexpected child death and the impetus this provided for research exploring the topic. The article charts the isolation which parents may experience following a sudden, unexpected child death and situates this within a cultural taboo around dying. The author further discusses her involvement as a researcher combining personal experience and academic study in a way which formed potentially “dangerous knowledge.” The article concludes with a discussion of how certain forms of knowledge may become segregated from research and provides ways forward from this

Introducing DuPont Exirel™ and Verimark™ new insect control products for pest management and optimizing yield in Florida citrus

DuPont™ Exirel™ and Verimark™ insect control contain DuPont™ Cyazypyr™ insecticide, the second active ingredient from the anthranilic diamide class of chemistry, and the first to control a cross-spectrum of insect pests including Lepidoptera, Dipteran leafminers, fruit flies, beetles, whiteflies, thrips, aphids, leafhoppers, psyllids and weevils, while conserving key predators and parasitoids.&nbsp; Exirel™ and Verimark™ deliver a novel mode of action that impacts insect behavior by impairing muscle function.&nbsp; Intoxicated insects stop feeding rapidly, resulting in excellent plant protection.&nbsp; Exirel™ is designed for foliar applications to optimize leaf penetration and spray coverage.&nbsp; Exirel™ applied at the major flush periods provides excellent protection against Asian citrus psyllid adult and nymphs and citrus leafminer for extended periods, generally 3-4 weeks

Introducing DuPont Exirel™ and Verimark™ new insect control products for pest management and optimizing yield in Florida citrus

DuPont™ Exirel™ and Verimark™ insect control contain DuPont™ Cyazypyr™ insecticide, the second active ingredient from the anthranilic diamide class of chemistry, and the first to control a cross-spectrum of insect pests including Lepidoptera, Dipteran leafminers, fruit flies, beetles, whiteflies, thrips, aphids, leafhoppers, psyllids and weevils, while conserving key predators and parasitoids.&nbsp; Exirel™ and Verimark™ deliver a novel mode of action that impacts insect behavior by impairing muscle function.&nbsp; Intoxicated insects stop feeding rapidly, resulting in excellent plant protection.&nbsp; Exirel™ is designed for foliar applications to optimize leaf penetration and spray coverage.&nbsp; Exirel™ applied at the major flush periods provides excellent protection against Asian citrus psyllid adult and nymphs and citrus leafminer for extended periods, generally 3-4 weeks