Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial

ObjectivesPreclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression.DesignRandomized double-blind placebo-controlled delayed-start study.Setting and ParticipantPatients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035).MethodsThe primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog) and other assessment scales.ResultsThere was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference ?4.4%, 90% CI –16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) ?1.0, 95% CI –3.3 to 1.3] and M12 (MD –2.35, 95% CI –5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences.Conclusions and ImplicationsThis study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.     

基于正交试验的肾造瘘管固定方案研究

目的 探讨基于正交试验的肾造瘘管不同固定方案的比较效果。方法 将14Fr硅胶肾造瘘管固定在聚乙烯展板和拉力显示器上，以固定材料、固定方法、面积为3个影响因素，每个因素3个水平，每组进行3次试验再求平均值作为最后拉力值F，共进行9个固定方案共27次试验。利用L9（33）正交试验矩阵研究不同材料（医用橡皮膏、医用透气胶带、医用无纺布胶带）、固定方法（交叉固定法、“工”字固定法和改良“工”字固定法）及面积(16 cm2、24 cm2、32 cm2）对肾造瘘管固定强度的影响。结果 正交试验所选的3种影响因素中，对拉力值影响显著性排序为：材料＞方法＞面积；3种固定材料中，医用橡皮膏固定强度最大。结论 肾造瘘管固定方案中，最佳固定组合为以医用橡皮膏结合改良“工”字法固定，可为临床管道固定方案的选择提供参考。     

MR-safety in clinical practice at 7T: Evaluation of a multistep screening process in 1819 subjects

IntroductionMR facilities must implement and maintain adequate screening and safety procedures to ensure safety during MR examinations. The aim of this study was to evaluate a multi-step MR safety screening process used at a 7T facility regarding incidence of different types of safety risks detected during the safety procedure.MethodsSubjects scheduled for an MR examination and having entered the 7T facility during 2016–2019 underwent a pre-defined multi-step MR safety screening process. Screening documentation of 1819 included subjects was reviewed, and risks identified during the different screening steps were compiled. These data were also related to documented decisions made by a 7T MR safety committee and reported MR safety incidents.ResultsPassive or active implants (n = 315) were identified in a screening form and/or an additional documented interview in 305 subjects. Additional information not previously self-reported by the subject, regarding implants necessitating safety decisions performed by the staff was revealed in the documented interview in 102 subjects (106 items). In total, the 7T MR safety committee documented a decision in 36 (2%) of the included subjects. All of these subjects were finally cleared for scanning.ConclusionA multi-step screening process allows a thorough MR screening of subjects, avoiding safety incidents. Different steps in the process allow awareness to rise and items to be detected that were missed in earlier steps.Implications for practiceSafety questions posed at a single timepoint during an MR screening process might not reveal all safety risks. Repetition and rephrasing of screening questions leads to increased detection of safety risks. This could be effectively mitigated by a multi-step screening process. A multi-disciplinary safety committee is efficient at short notice responding to unexpected safety issues.     

Evaluating a Food Pantry–Based Intervention to Improve Food Security,Dietary Intake,and Quality in Midwestern Food Pantries

BackgroundVoices for Food was a longitudinal community, food pantry–based intervention informed by the social ecological model, and designed to improve food security, dietary intake, and quality among clients, which was carried out in 24 rural food pantries across 6 Midwestern states.ObjectiveOur objective was to evaluate changes in adult food security, dietary intake, and quality from baseline (2014) to follow-up (2016), and to assess the role of adult food security on dietary outcomes.DesignA multistate, longitudinal, quasi-experimental intervention with matched treatment and comparison design was used to evaluate treatment vs comparison group changes over time and changes in both groups over time.Participants/settingAdult food pantry clients (n = 617) completed a demographic food security survey, and up to three 24-hour dietary recalls at baseline (n = 590) and follow-up (n = 160).InterventionCommunity coaching served as the experimental component, which only “treatment” communities received, and a food council guide and food pantry toolkit were provided to both “treatment” and matched “comparison” communities.Main outcome measuresChange in adult food security status, mean usual intakes of nutrients and food groups, and Healthy Eating Index-2010 scores were the main outcome measures.Statistical analyses performedLinear mixed models estimated changes in outcomes by intervention group and by adult food security status over time.ResultsImprovements in adult food security score (–0.7 ± 0.3; P = .01), Healthy Eating Index-2010 total score (4.2 ± 1.1; P < .0001), and empty calories component score (3.4 ± 0.5; P <.0001) from baseline to follow-up were observed in treatment and comparison groups, but no statistically significant changes were found for adult food security status, dietary quality, and usual intakes of nutrients and food groups between the 2 groups over time. The intervention effect on dietary quality and usual intake changes over time by adult food security status were also not observed.ConclusionsFood pantry clients in treatment and comparison groups had higher food security and dietary quality at the follow-up evaluation of the Voices for Food intervention trial compared with baseline, despite the lack of difference among the groups as a result of the experimental coaching component.     

Fourteen years of the Pregnancy Registry on maternal immunisation with a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine

BackgroundGSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy.MethodsVoluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated.ResultsFrom May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry.ConclusionsData currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.     

Maternal influenza vaccination and child mortality: Longitudinal,population-based linked cohort study

Influenza vaccination is recommended to protect mothers and their infants from influenza. Few studies have evaluated the association between maternal influenza vaccination and child mortality. We aimed to evaluate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and mortality among young children. This longitudinal, population-based cohort study included 191,247 maternal-child pairs in Western Australia between April 2012 and December 2017. Maternal vaccine information was obtained from a state-wide antenatal vaccination database. Mortality was defined as a record of a death registration. We used Cox proportional hazard models, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio of child mortality associated with in utero exposure to seasonal IIV. This study found no association between in utero exposure to seasonal IIV and mortality through age five years.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

Estimated Reductions in Added Sugar Intake among US Children and Youth in Response to Sugar Reduction Targets

BackgroundIn 2021, the National Salt and Sugar Reduction Initiative (NSSRI) released voluntary sugar reduction targets for packaged foods and drinks in the United States.ObjectiveThe objectives of this study were to describe trends in added sugar intake from NSSRI foods and beverages among children and youth and estimate possible reductions if industry were to meet the targets.DesignThis study consisted of cross-sectional and trend analyses of demographic and 24-hour dietary recall data from eight survey cycles (2003-2004 to 2017-2018) of the National Health and Nutrition Examination Survey.Participants/settingThe study sample included 23,248 children and youth (aged 2 to 19 years).Main outcome measuresThe main outcome measure was the percent of daily calories from added sugar for foods and beverages in NSSRI categories.Statistical analyses performedFoods and beverages reported by participants were mapped to one of the NSSRI’s categories or coded as a non-NSSRI item. Trends over time in added sugar intake were assessed using regression models. To assess possible reductions in added sugar intake if industry were to meet the targets, sales-weighted mean percent reductions for 2023 and 2026 targets were applied to NSSRI items in the 2017-2018 National Health and Nutrition Examination Suvey data. Results were examined overall and by demographic characteristics.ResultsFrom 2003-2004 to 2017-2018, added sugar intake from NSSRI foods and beverages declined, but consumption remained high. During 2017-2018, NSSRI categories accounted for 70% of US child and youth added sugar intake. If industry met the NSSRI targets, US children and youth would consume 7% (2023 targets) to 21% (2026 targets) less added sugar.ConclusionsAlthough added sugar intake from NSSRI foods and drinks has declined over the past decade, added sugar intake from all sources remains high and consumption of added sugar from certain NSSRI categories has remained steady over time. If met, the NSSRI targets are expected to result in meaningful reductions in added sugar intake for US children and youth.