ASPREE-D: Aspirin for the prevention of depression in the elderly

Copyright © International Psychogeriatric Association 2016. Background:: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. Method:: ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. Results:: This paper presents the rationale for the study and presents a summary of the study design. Conclusions:: ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression

Prediction of disability-free survival in healthy older people

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583)

Behavioural characteristics, prevalence of Chlamydia trachomatis and antibiotic susceptibility of Neisseria gonorrhoeae in men with urethral discharge in Thyolo, Malawi.

A study was carried out in 2000/2001 in a rural district of Malawi among men presenting with urethral discharge, in order to (a) describe their health-seeking and sexual behaviour, (b) determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis, and (c) verify the antibiotic susceptibility of N. gonorrhoeae. A total of 114 patients were entered into the study; 61% reported having taken some form of medication before coming to the sexually transmitted infections clinic. The most frequent alternative source of care was traditional healers. Sixty-eight (60%) patients reported sexual encounters during the symptomatic period, the majority (84%) not using condoms. Using ligase chain reaction on urine, N. gonorrhoeae was detected in 91 (80%) and C. trachomatis in 2 (2%) urine specimens. Forty five of 47 N. gonorrhoeae isolates produced penicillinase, 89% showing multi-antimicrobial resistance. This study emphasizes the need to integrate alternative care providers and particularly traditional healers in control activities, and to encourage their role in promoting safer sexual behaviour. In patients presenting with urethral discharge in our rural setting, C. trachomatis was not found to be a major pathogen. Antimicrobial susceptibility surveillance of N. gonorrhoeae is essential in order to prevent treatment failures and control the spread of resistant strains

Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.

In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out in 1999 and 2001 to determine (i) whether faecal Escherichia coli resistance to co-trimoxazole in TB patients changed with time, and (ii) whether the resistance pattern was different in HIV-positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E. coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone) it was 62% (P < 0.001). The study shows a significant increase of E. coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E. coli and the Salmonella species, these findings could herald limitations on the short- and long-term benefits to be expected from the use of co-trimoxazole prophylaxis in preventing non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in Malawi

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants

Baseline Characteristics of Participants in the ASPREE (Aspirin in Reducing Events in the Elderly) Study

This is a correction to: The Journals of Gerontology: Series A, Volume 72, Issue 11, November 2017, Pages 1586–1593, https://doi.org/10.1093/gerona/glw342 In the article “Baseline Characteristics of Participants in the ASPREE (ASPirin in Reducing Events in the Elderly) Study”, values for CES-D-10 score 8+ in Table 3 were incorrect. The original data were for scores of >8 for the CES-D-10. The correct data for CES-D-10 scores of 8+, as numbers and percentages, are 1077 (10%) for 65–74 years, 724 (10%) for 75–84 years, 78 (11%) for (85+ years) and 1879 (10%) for Overall

Industrial House Building : An analysis of the constraints and opportunities in modular house building

Syftet med denna rapport är att undersöka och analysera vad det finns för begränsningar och möjligheter med en industriell byggprocess där det byggs med moduler. Den syftar även till att undersöka relationerna mellan en projektör, entreprenör och leverantör i en industriell byggförsörjningskedja och hur dessa relationer kan utvecklas.I dagens Sverige är bostäder ett stort problem då det inte finns tillräckligt för att täcka dagens behov. För att bemöta detta behov har det blivit allt mer vanligt med en industriell byggprocess där stora delar av byggnaden tillverkas som moduler i fabrik. Med modul menas en del eller komponent av ett byggnadsverk som tillsammans med andra moduler går att montera ihop till en byggnad. Inom industriellt byggande benämns utformningen av moduler som en begränsning. I och med att aktörer behöver följa regler gällande mått blir det mindre möjligheter för att ha större öppna ytor i bostaden. Det behövs också en viss standardisering i produktionen vilket leder till mindre flexibilitet och eventuellt inte lika god estetik som ett traditionellt bygge. Det är därför viktigt för aktörerna att hitta den typ av kund och marknad som är mest lämplig för modulbyggnation. Vid montering av moduler på byggarbetsplatsen kan det uppstå problem, särskilt gällande gränssnittet. Det är därför viktigt att denna del har någon form av standardisering samt att alla inblandade aktörer får ta del av projekteringen och påverka modulen i tidigt skede. På så sätt kan det bli mindre risk för att fel uppstår längre fram i processen. Vid en industriell byggprocess skapas möjligheten till att göra stora effektiviseringar och optimeringar i produktionen. Av den anledning är det nödvändigt att tillämpa någon typ av förbättringsarbete så som exempelvis Lean och Plan-Do-Check-Act-cykeln. Dock bör det beaktas att alla verktyg inte passar alla verksamheter och av den anledningen bör varje verktyg optimeras för den specifika verksamheten som det ska tillämpas i. För effektiviseringar i en industriell byggprocess är Byggnadsinformationsmodellering (BIM) ett bra verktyg som går att tillämpa. Med hjälp av BIM kan inblandade aktörer ta del av samma digitala modell från tidigt skede i projekteringen till förvaltningen. Då alla aktörer tar del av samma information skapas det bättre relationer och mindre missuppfattningar.The purpose of this report is to investigate and analyze what constraints and opportunities that exist within an industrial building process based on modules. It also aims to investigating the relationships between a projector, contractor and supplier in an industrial building supply chain and how these can be developed. In Sweden today, housing is a major problem as there is not enough houses to meet the people’s need. To meet this need, it has become increasingly common with an industrial housing process, where large parts of the building are manufactured as modules in a factory. Module is described as a component of a building that together with other modules can be assembled to a complete building. Within an industrial building process, the design of the modules is referred as a limitation. As the actors need to follow the rules regarding measurements, there will be fewer opportunities for having larger open spaces in the buildings. There is also a need for some standardization in the production process, which leads to less flexibility and possibly not as good aesthetics as a traditional building; therefore it is important to focus on what kind of customer and market that is the most suitable for modular construction. When assembling modules at a construction site problems may occur, especially regarding the interface. It is therefore important that the process has some kind of standardization and that all involved actors may participate and influence the module at the early stages of the building process. If this is executed in a good way the risk of errors in the building process is reduced. In an industrial building process, the possibility of making major optimizations and efficiency improvements is created. For this reason, it is necessary to apply some kind of improvement work, such as Lean and the Plan-Do-Check-Act-Cycle. Thus, it should be borne in mind that all tools do not suit all activities, and for this reason each tool should be optimized for the specific activity. For efficiency improvements in an industrial building process, Building Information Model (BIM) is a good tool that can be applied. When using BIM, different actors can share the same digital model from the early stages of design to management of the building. When all actors share the same information, better relationships and fewer misconceptions are created