Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis

Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results. Methods We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups. Results There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was-4.61 mm Hg (95% CI-6.07 to-3.14) and of diastolic blood pressure (DBP) was-1.61 mm Hg (95% CI-2.42 to-0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a-1.53 mm Hg (95% CI-3.02 to-0.03, p=0.045) greater reduction in SBP and a-0.95 mm Hg (95% CI-1.78 to-0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94). Conclusions The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide. Trial registration number CRD42020161077

Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors

BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins). IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. CONCLUSION: Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents

Challenges in microbial ecology: building predictive understanding of community function and dynamics.

The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited. Building predictive models that link MC composition to function is a key emerging challenge in microbial ecology. Here, we argue that addressing this challenge requires close coordination of experimental data collection and method development with mathematical model building. We discuss specific examples where model-experiment integration has already resulted in important insights into MC function and structure. We also highlight key research questions that still demand better integration of experiments and models. We argue that such integration is needed to achieve significant progress in our understanding of MC dynamics and function, and we make specific practical suggestions as to how this could be achieved

Cephalopods in neuroscience: regulations, research and the 3Rs

Cephalopods have been utilised in neurosci- ence research for more than 100 years particularly because of their phenotypic plasticity, complex and centralised nervous system, tractability for studies of learning and cellular mechanisms of memory (e.g. long-term potentia- tion) and anatomical features facilitating physiological studies (e.g. squid giant axon and synapse). On 1 January 2013, research using any of the about 700 extant species of ‘‘live cephalopods’’ became regulated within the European Union by Directive 2010/63/EU on the ‘‘Protection of Animals used for Scientific Purposes’’, giving cephalopods the same EU legal protection as previously afforded only to vertebrates. The Directive has a number of implications, particularly for neuroscience research. These include: (1) projects will need justification, authorisation from local competent authorities, and be subject to review including a harm-benefit assessment and adherence to the 3Rs princi- ples (Replacement, Refinement and Reduction). (2) To support project evaluation and compliance with the new EU law, guidelines specific to cephalopods will need to be developed, covering capture, transport, handling, housing, care, maintenance, health monitoring, humane anaesthesia, analgesia and euthanasia. (3) Objective criteria need to be developed to identify signs of pain, suffering, distress and lasting harm particularly in the context of their induction by an experimental procedure. Despite diversity of views existing on some of these topics, this paper reviews the above topics and describes the approaches being taken by the cephalopod research community (represented by the authorship) to produce ‘‘guidelines’’ and the potential contribution of neuroscience research to cephalopod welfare

A list of mosquito species of the Brazilian State of Pernambuco, including the first report of Haemagogus janthinomys (Diptera: Culicidae), yellow fever vector and 14 other species (Diptera: Culicidae) Lista de espécies de mosquitos do Estado de Pernambuco e primeiro relato de Haemagogus janthinomys (Diptera: Culicidae) vetor de febre amarela silvestre e outras 14 espécies (Diptera: Culicidae)

INTRODUCTION: Besides mosquito species adapted to urban environments (Culex quinquefasciatus, Aedes aegypti and Aedes albopictus), only 15 species of Anopheles had been recorded in the State of Pernambuco. METHODS: Human-landing mosquitoes were collected in Dois Irmãos Park, in Recife. RESULTS: The first report for the state of Haemagogus janthinomys, an important vector of yellow fever virus, and 14 other species, including Trichoprosopon lampropus, a first reported for Brazil. CONCLUSIONS: The mosquito fauna in the area is diversified and has potential medical and veterinary importance.<br>INTRODUÇÃO: Além de mosquitos adaptados ao ambiente urbano (Culex quinquefasciatus, Aedes aegypti e Ae. albopictus), apenas 15 espécies de Anopheles haviam sido relatadas no Estado de Pernambuco. MÉTODOS: Mosquitos que pousavam em humanos no Parque Dois Irmãos, em Recife foram coletados. RESULTADOS: Haemagogus janthinomys, importante vetor de vírus de febre amarela, e outras 14 espécies são relatadas pela primeira vez no estado, incluindo Trichoprosopon lampropus, relatado pela primeira vez no Brasil. CONCLUSÕES: A fauna de mosquitos na área é muito diversificada e tem potencial importância médica e veterinária