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Objectives The Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia.Design A decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process.Setting Conducted with participants online in the state of New South Wales, Australia.Participants Participants were aged 50–70 years with moderately elevated BP (systolic >120 and 80 and

Background The urgency of the climate crisis requires attention from biomedical research, not least clinical trials which can involve significant greenhouse gas emissions. The Low Carbon Clinical Trials Working Group set out a strategy to reduce the emissions of clinical trials, starting with the development of a method to measure their carbon footprint (CO2e).Methods As a first step, we developed a process map defining clinical trial core activities. Corresponding emission factors were sourced to convert activity data into greenhouse gas emissions. The subsequent method was applied to two Cancer Research UK (CRUK)-funded trials (the international randomised sarcoma trial CASPS (ISRCTN63733470) and the UK cohort-based breast cancer trial PRIMETIME (ISRCTN41579286)). A guidance document defining the scope, method and assumptions was written to allow application to any publicly funded/investigator initiated clinical trial.Results Trial specific activities over and above routine care were grouped into 10 modules covering trial set up, conduct and closure. We identified emission factors for all trial activities within both trials and used them to estimate their total carbon footprint. The carbon footprint of CASPS, an international phase 2 trial of an investigational medicinal product with 47 participants, was 72 tonnes CO2e, largely attributable to clinical trials unit emissions and staff travel. PRIMETIME, a UK-based phase 3 non-investigational medicinal product trial with 1962 patients, produced 89 tonnes CO2e, largely attributable to trial-specific in-person participant assessments.Conclusion We have developed a method and guidance that trialists can use to determine the carbon footprint of clinical trials. The guidance can be used to identify carbon hotspots where alternative approaches to trial design and conduct could reduce a trial footprint, and where methodology research is required to investigate the potential impact of interventions taken to reduce carbon emissions. We will continue to refine the guidance to increase the potential application and improve usability.

Introduction China has recently introduced a range of e-cigarette control policies with a focus on addressing an increase in youth vaping. This study aimed to investigate a wide range of e-cigarette-related attitudes and behaviors in a national sample of Chinese adolescents and young adults to obtain insights into their exposure to, experiences with, and attitudes to e-cigarettes on the cusp of new regulations coming into force. Methods An online survey was administered to a sample of 1062 adolescents and young adults (aged 15–30 years) in China in November–December 2021. Quotas were applied to achieve an approximately equal gender split, representation across age sub-groups (15–17, 18–20, 21–23, 24–26, and 27–30 years), and approximately two-thirds representing low- and middle-income groups. Adjusted odds ratios (AORs) were also calculated. Results Just under half (47%) reported no knowledge of e-cigarettes and/or vaping. One in five reported ever using e-cigarettes (‘even once or twice’), 8% reported being current users, and 3% reported being daily users. Around twothirds of those who had heard of e-cigarettes/vaping had friends who vaped and had seen e-cigarette advertising. Fruit flavors were most popular, and the most frequently nominated reasons for vaping were to cut down on cigarette smoking and because a friend used them. The factors positively associated with ever use of e-cigarettes were current tobacco smoking (AOR=68.26) or previous tobacco smoking (AOR=39.15) and having friends who vape (AOR=1.76). Perceptions of addictiveness were negatively associated with ever use (AOR=0.47). Strong support was evident for most assessed e-cigarette control policies. Conclusions The results indicate that young people in China have been able to access and use e-cigarettes, although rates of regular use are low. Generally, high levels of expressed support for a range of e-cigarette control policies among members of this age group suggest the new regulatory environment is consistent with their policy preferences.

Abstract Background Multimorbidity (the presence of two or more chronic conditions) is common amongst people with chronic kidney disease, but it is unclear which conditions cluster together and if this changes as kidney function declines. We explored which clusters of conditions are associated with different estimated glomerular filtration rates (eGFRs) and studied associations between these clusters and adverse outcomes. Methods Two population-based cohort studies were used: the Stockholm Creatinine Measurements project (SCREAM, Sweden, 2006–2018) and the Secure Anonymised Information Linkage Databank (SAIL, Wales, 2006–2021). We studied participants in SCREAM (404,681 adults) and SAIL (533,362) whose eGFR declined lower than thresholds (90, 75, 60, 45, 30 and 15 mL/min/1.73m2). Clusters based on 27 chronic conditions were identified. We described the most common chronic condition(s) in each cluster and studied their association with adverse outcomes using Cox proportional hazards models (all-cause mortality (ACM) and major adverse cardiovascular events (MACE)). Results Chronic conditions became more common and clustered differently across lower eGFR categories. At eGFR 90, 75, and 60 mL/min/1.73m2, most participants were in large clusters with no prominent conditions. At eGFR 15 and 30 mL/min/1.73m2, clusters involving cardiovascular conditions were larger and were at the highest risk of adverse outcomes. At eGFR 30 mL/min/1.73m2, in the heart failure, peripheral vascular disease and diabetes cluster in SCREAM, ACM hazard ratio (HR) is 2.66 (95% confidence interval (CI) 2.31–3.07) and MACE HR is 4.18 (CI 3.65–4.78); in the heart failure and atrial fibrillation cluster in SAIL, ACM HR is 2.23 (CI 2.04 to 2.44) and MACE HR is 3.43 (CI 3.22–3.64). Chronic pain and depression were common and associated with adverse outcomes when combined with physical conditions. At eGFR 30 mL/min/1.73m2, in the chronic pain, heart failure and myocardial infarction cluster in SCREAM, ACM HR is 2.00 (CI 1.62–2.46) and MACE HR is 4.09 (CI 3.39–4.93); in the depression, chronic pain and stroke cluster in SAIL, ACM HR is 1.38 (CI 1.18–1.61) and MACE HR is 1.58 (CI 1.42–1.76). Conclusions Patterns of multimorbidity and corresponding risk of adverse outcomes varied with declining eGFR. While diabetes and cardiovascular disease are known high-risk conditions, chronic pain and depression emerged as important conditions and associated with adverse outcomes when combined with physical conditions.

Abstract Background Prehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2). Methods RIGHT-2 was a prospective, multicentre, paramedic-delivered, ambulance-based, sham-controlled, participant-and outcome-blinded, randomised-controlled trial of transdermal glyceryl trinitrate (GTN) in adults with ultra-acute presumed stroke in the UK. Final diagnosis (intracerebral haemorrhage, ischaemic stroke, transient ischaemic attack, mimic) was determined by the hospital investigator. This pre-specified subgroup analysis assessed the safety and efficacy of transdermal GTN (5 mg daily for 4 days) versus sham patch among stroke mimic patients. The primary outcome was the 7-level modified Rankin Scale (mRS) at 90 days. Results Among 1149 participants in RIGHT-2, 297 (26%) had a final diagnosis of mimic (GTN 134, sham 163). The mimic group were younger, mean age 67 (SD: 18) vs 75 (SD: 13) years, had a longer interval from symptom onset to randomisation, median 75 [95% CI: 47,126] vs 70 [95% CI:45,108] minutes, less atrial fibrillation and a lower systolic blood pressure and Face-Arm-Speech-Time tool score than the stroke group. The three most common mimic diagnoses were seizure (17%), migraine or primary headache disorder (17%) and functional disorders (14%). At 90 days, the GTN group had a better mRS score as compared to the sham group (adjusted common odds ratio 0.54; 95% confidence intervals 0.34, 0.85; p = 0.008), a difference that persisted at 365 days. There was no difference in the proportion of patients who died in hospital, were discharged to a residential care facility, or suffered a serious adverse event. Conclusions One-quarter of patients suspected by paramedics to have an ultra-acute stroke were subsequently diagnosed with a non-stroke condition. GTN was associated with unexplained improved functional outcome observed at 90 days and one year, a finding that may represent an undetected baseline imbalance, chance, or real efficacy. GTN was not associated with harm. Trial registration This trial is registered with International Standard Randomised Controlled Trials Number ISRCTN 26986053 .

Uncertainties about the efficacy of influenza vaccination for populations with heart failure (HF) in preventing cardiovascular outcomes, as well as lack of effective vaccination strategies, may contribute to low vaccine coverage rate (VCR) in China and globally. We assessed the feasibility of a strategy to promote influenza vaccines in patients hospitalized with acute HF in China and to inform the design of a hybrid effectiveness-implementation cluster randomized trial to evaluate this strategy on mortality and hospital re-admission. We conducted a cluster randomized pilot trial involving 11 hospitals in Henan Province in China, with mixed-methods evaluation between December 2020 and April 2021. A process evaluation involved interviews with 51 key informants (patients, health professionals, policy makers). The intervention included education about influenza vaccination and availability of free vaccines administered prior to hospital discharge for HF patients, while usual care included attending community-based points of vaccination (PoV) for screening and vaccination. Implementation outcomes focused on reach, fidelity, adoption, and acceptability. Recruitment rates were assessed for trial feasibility. Effectiveness outcomes were influenza VCR, HF-specific rehospitalizations and mortality at 90 days. A total of 518 HF patients were recruited from 7 intervention and 4 usual care hospitals (mean of 45 participants per hospital per month). VCR was 89.9% (311/346, 86.1-92.8%) in the intervention group and 0.6% (1/172, 0.0-3.7%) in the control group. The process evaluation demonstrated reach to patients with lower socioeconomic and education status. There was good fidelity of the intervention components, with education and PoV set up processes being adapted to local hospital workflow and workforce capacity. Intervention was acceptable and adopted by patients and health professionals. However, outside of a trial setting, concerns were raised around vaccination reimbursement costs, workforce accountability and capacity. The intervention strategy appears feasible and acceptable for improving VCR in HF patients at county-level hospitals in China. Trial registration: This pilot trial is registered with the acronym PANDA II Pilot (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2000039081).

Abstract Objectives We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke. Methods We performed a systematic literature search across MEDLINE and Embase, from January 1, 2015, to February 17, 2022, to identify studies reporting antithrombotic medications (anticoagulants and antiplatelets) post stroke. Two people independently identified reports to include, extracted data, and assessed the quality of included studies according to the Newcastle–Ottawa scale. Where possible, data were pooled using random‐effects meta‐analysis. Results We included 453,625 stroke patients from 46 studies. The pooled proportion of prescribed antiplatelets and anticoagulants among patients with atrial fibrillation (AF) was 62% (95% CI: 57%–68%), and 68% (95% CI: 58%–79%), respectively. The pooled proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications from four studies was 67% (95% CI: 41%–93%). It was reported that 11% (95% CI: 2%–19%) of patients did not receive antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%–89%), 71% (95% CI: 57%–84%), and 73% (95% CI: 59%–86%), respectively. Conclusion In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993?2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23% (95% confidence interval [CI]: 22%?25%) in women and 17% (15%?18%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2???9.1, years) being older than men (76.5???9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01?1.51; 5-year 1.12; 1.03?1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97?1.22; 5-year 0.98; 0.84?1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95% CI: 0.89?0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

Abstract Background Cerebrovascular disease (CVD) survivors are at a high risk of recurrent stroke. Although it is thought that survivors with higher risk of stroke respond better to stroke onset, to date, no study has been able to demonstrate that. Thus, we investigated whether the intent to call emergency medical services (EMS) increased with recurrent stroke risk among CVD survivors. Methods A cross-sectional community-based survey was conducted from January 2017 to May 2017, including 187,723 adults (age ≥ 40 years) across 69 administrative areas in China. A CVD survivor population of 6290 was analyzed. According to the stroke risk score based on Essen Stroke Risk Score, CVD survivors were divided into three subgroups: low (0), middle (1–3) and high (4–7) recurrent risk groups. Multivariable logistic regression models were used to identify the association between the stroke risk and stroke recognition, as well as stroke risk and EMS calling. Results The estimated stroke recognition rate in CVD survivors with low, middle, and high risk was 89.0% (503/565), 85.2% (3841/4509), and 82.5% (1001/1213), respectively, while the rate of calling EMS was 66.7% (377/565), 64.3% (2897/4509), and 69.3% (840/1213), respectively. The CVD survivors’ knowledge of recognizing stroke and intent to call EMS did not improve with recurrent stroke risk, even after adjustment for multiple socio-demographic factors. Conclusions Despite being at a higher risk of recurrent stroke, Chinese CVD survivors showed poor knowledge of stroke, and their intent to call EMS did not increase with recurrent stroke risk. Enhanced and stroke risk-orientated education on stroke recognition and proper response is needed for all CVD survivors.

The most common configuration of the mandibular first molar is the presence of two roots and three root canals. The objective of this work is to present two rare anatomic configurations with six root canals on two mandibular left first molars diagnosed during endodontic therapy. Root canal therapy was performed using a dental operating microscope. Ultrasonic troughing in the grooves in between the mesial root canals and in between the distal root canals was able to show the middle root canals. Large samples population characterization researches and systematic reviews were unable to detect a single case of six root canals configuration in a mandibular first molar in their investigations. Although it is a rare configuration, a six root canal configuration is possible to be found in the mandibular first molar. Three different pulp chamber configurations are possible to be found. Two or three roots may be present and the root configuration more common in the mesial root is the Type 8 and Type 12 for the distal root. Some concepts about the required technique to approach these cases are also debated.

We present the detection of 661 known pulsars observed with the Australian SKA Pathfinder (ASKAP) telescope at 888 MHz as part of the Rapid ASKAP Continuum Survey (RACS). Detections were made through astrometric coincidence and we estimate the false alarm rate of our sample to be ∼0.5%. Using archival data at 400 and 1400 MHz, we estimate the power-law spectral indices for the pulsars in our sample and find that the mean spectral index is −1.78 ± 0.6. However, we also find that a single power law is inadequate for modeling all the observed spectra. With the addition of flux densities between 150 MHz and 3 GHz from various imaging surveys, we find that up to 40% of our sample show deviations from a simple power-law model. Using Stokes V measurements from the RACS data, we measured the circular polarization fraction for 9% of our sample and find that the mean polarization fraction is ∼10% (consistent between detections and upper limits). Using the dispersion-measure-derived distance, we estimate the pseudo-luminosity of the pulsars and do not find any strong evidence for a correlation with the pulsars’ intrinsic properties.

Abstract Background As health behavior varies with increasing age, we aimed to examine the potential barriers in calling emergency medical services (EMS) after recognizing a stroke among 40–74- and 75–99-year-old adults. Methods Data were obtained from a cross-sectional community-based study (FAST-RIGHT) that was conducted from January 2017 to May 2017 and involved adults (age ≥ 40 years) across 69 administrative areas in China. A subgroup of residents (153675) who recognized stroke symptoms was analyzed. Multivariable logistic regression models were performed in the 40–74 and 75–99 age groups, separately, to determine the factors associated with wait-and-see behaviors at the onset of a stroke. Results In the 40–74 and 75–99 age groups, the rates of participants who chose “Self-observation at home” were 3.0% (3912) and 3.5% (738), respectively; the rates of “Wait for family, then go to hospital” were 31.7% (42071) and 33.1% (6957), respectively. Rural residence, living with one’s spouse, low income (

Abstract Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega‐3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non‐steroidal anti‐inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti‐hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

Background The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China.Methods A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020.Results A total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction >50%) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3%; 36.5%, 22.1% and 22.6%; and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p50%), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3%; 44.2%, 39.4%; and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all p

Objective This study comprehensively estimated the excess cardiovascular disease (CVD) mortality attributable to influenza in an older (age ≥65 years) population.Design Ecological study.Setting Aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data in Beijing, China.Main outcome measure Excess overall CVD, and separately for ischaemic heart disease (IHD), ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature.Results CVD (risk ratio (RR) 1.02, 95% CI 1.01, 1.02), IHD (RR 1.01, 95% CI 1.01, 1.02), ischaemic stroke (RR=1.03, 95% CI 1.02, 1.04), but not haemorrhagic stroke (RR=1.00, 95% CI 0.99, 1.01) mortality, were significantly associated with every 10% increase in influenza activity. An increase in circulating A(H1N1)09pdm, A(H3N2) and B type virus were all significantly associated with CVD and ischaemic stroke mortality, but only A(H3N2) and B type virus with IHD mortality. The strongest increase in disease mortality was in the same week as the increase in influenza activity. Annual excess CVD mortality rate attributable to influenza ranged from 54 to 96 per 100 000 population. The 3%–6% CVD mortality attributable to influenza activity was related to an annual excess of 916–1640 CVD deaths in Beijing, China.Conclusions Influenza activity has moderate to strong associations with CVD, IHD and ischaemic stroke mortality in older adults in China. Promoting influenza vaccination could have major health benefit in this population.Background Influenza may trigger serious CVD events. An estimation of excess CVD mortality attributable to influenza has particular relevance in China where vaccination is low and CVD burden is high.Methods This study analysed data at the population level (age ≥65 years) using linked aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data during 2011 to 2018. Quasi-Poisson regression models were used to estimate the excess overall CVD, and separately for IHD, ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature. Analyses were also undertaken for influenza subtypes (A(H1N1)09pdm, A(H3N2) and B viruses), and mortality risk with time lags of 1–5 weeks following influenza activity in the current week.

Background: Ischaemic stroke is reportedly preceded by transient ischaemic attack (TIA) in 15–30% of all cases. The risk of stroke following TIA is highest in the presence of unstable atherosclerotic plaques in large arteries. The recent population-based Adelaide Stroke Incidence Study describes a population with a low proportion (16%) of stroke attributable to large artery atherosclerosis (LAA). We hypothesized that this population-based ischaemic stroke cohort would have a lower rate of preceding TIA than previously reported. Methods: This paper is a prospective ascertainment of all suspected TIAs and strokes in a 12-month period from 2009 to 2010. Ischaemic stroke pathogenesis was classified by the TOAST criteria. Details of preceding TIA events were scrutinised. Results: In this 12-month period, 318 stroke events in 301 individuals were recorded. Of the total 258 ischaemic strokes, 16% (95% confidence interval [CI] 12–22) were from LAA. Of 258 ischaemic stroke patients, only 11 (4%; 95% CI 2–7) reported symptoms in the preceding 90 days consistent with TIA. Nine (82%) sought medical attention. The median ABCD2 score in this group was 4.5 (IQR: 3–7), and the median time of event prior to stroke was 20 days (IQR: 4–32). Conclusion: In our population-based cohort, rates of TIA preceding ischaemic stroke were much lower than previously reported, probably reflective of effective secondary prevention (active TIA clinics) and primary prevention (limiting LAA prevalence). In our population, further enhancements in TIA care will be of limited yield.

Abstract Background Populations of the earthworm, Lumbricus rubellus, are commonly found across highly contaminated former mine sites and are considered to have under-gone selection for mitigating metal toxicity. Comparison of adapted populations with those found on less contaminated soils can provide insights into ecological processes that demonstrate the long-term effects of soil contamination. Contemporary sequencing methods allow for portrayal of demographic inferences and highlight genetic variation indicative of selection at specific genes. Furthermore, the occurrence of L. rubellus lineages across the UK allows for inferences of mechanisms associated with drivers of speciation and local adaptation. Results Using RADseq, we were able to define population structure between the two lineages through the use of draft genomes for each, demonstrating an absence of admixture between lineages and that populations over extensive geographic distances form discrete populations. Between the two British lineages, we were able to provide evidence for selection near to genes associated with epigenetic and morphological functions, as well as near a gene encoding a pheromone. Earthworms inhabiting highly contaminated soils bare close genomic resemblance to those from proximal control soils. We were able to define a number of SNPs that largely segregate populations and are indicative of genes that are likely under selection for managing metal toxicity. This includes calcium and phosphate-handling mechanisms linked to lead and arsenic contaminants, respectively, while we also observed evidence for glutathione-related mechanisms, including metallothionein, across multiple populations. Population genomic end points demonstrate no consistent reduction in nucleotide diversity, or increase in inbreeding coefficient, relative to history of exposure. Conclusions Though we can clearly define lineage membership using genomic markers, as well as population structure between geographic localities, it is difficult to resolve markers that segregate entirely between populations in response to soil metal concentrations. This may represent a highly variable series of traits in response to the heterogenous nature of the soil environment, but ultimately demonstrates the maintenance of lineage-specific genetic variation among local populations. L. rubellus appears to provide an exemplary system for exploring drivers for speciation, with a continuum of lineages coexisting across continental Europe, while distinct lineages exist in isolation throughout the UK.

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2–4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.

BACKGROUND:Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes. METHODS AND FINDINGS:We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06-1.09; P < 0.001), PTB (1.02; 1.01-1.03; P < 0.001), macrosomia (1.07; 1.06-1.08; P < 0.001), SGA (1.06; 1.02-1.10; P = 0.007), and perinatal infant death (1.08; 1.03-1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07-1.15; P < 0.001), 1.17 (1.14-1.20; P < 0.001), 1.13 (1.09-1.16; P < 0.001), 1.17 (1.04-1.32; P = 0.008), and 1.59 (1.44-1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15-1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend

Abstract Objectives Patients with a history of cardiovascular surgery are at risk of stroke, and immediately calling emergency medical services (EMS) after stroke onset is crucial to receiving effective reperfusion therapy. We aimed to determine the effect of a history of cardiovascular surgery on patients' ability to recognize stroke and intent to call EMS. Methods We performed a cross‐sectional community‐based study from January 2017 to May 2017. A total population of 186,167 individuals, recruited from 69 administrative areas across China, was analyzed. Different multivariable logistic regression models were performed to identify the associations between cardiovascular surgical history and stroke recognition or intent to call EMS, respectively. Results 0.1% of the total population had a history of cardiovascular surgery. In the surgery group, the estimated stroke recognition rate (SRR) and correct action rate (CAR) were 84.9% and 74.7%, respectively. The prevalence of cardiovascular risk factors was significantly higher in the surgery group. Cardiovascular surgical history was not associated with recognition of stroke across different models. The surgery group was more likely to call EMS, but the difference was not significant after full adjustment (OR: 1.40, 95% CI: 0.99–1.98, p = .0572). Conclusions Cardiovascular surgical history does not influence patients' likelihood of calling EMS more often at stroke onset. Patients receiving cardiovascular surgeries should be counseled regarding stroke recognition, proper response to stroke, and the importance of controlling risk factors.

Introduction: Our goal was to evaluate the feasibility and effectiveness of using telesimulation to deliver an emergency medical services (EMS) course on mass casualty incident (MCI) training to healthcare providers overseas. Methods: We conducted a feasibility study to establish the process for successful delivery of educational content to learners overseas via telesimulation over a five-month period. Participants were registrants in an EMS course on MCI triage broadcast from University of California, Irvine Medical Simulation Center. The intervention was a Simple Triage and Rapid Treatment (START) course. The primary outcome was successful implementation of the course via telesimulation. The secondary outcome was an assessment of participant thoughts, feelings, and attitudes via a qualitative survey. We also sought to obtain quantitative data that would allow for the assessment of triage accuracy. Descriptive statistics were used to express the percentage of participants with favorable responses to survey questions. Results: All 32 participants enrolled in the course provided a favorable response to all questions on the survey regarding their thoughts, feelings, and attitudes toward learning via telesimulation with wearable/mobile technology. Key barriers and challenges identified included dependability of Internet connection, choosing appropriate software platforms to deliver content, and intercontinental time difference considerations. The protocol detailed in this study demonstrated the successful implementation and feasibility of providing education and training to learners at an off-site location. Conclusion: In this feasibility study, we were able to demonstrate the successful implementation of an intercontinental MCI triage course using telesimulation and wearable/mobile technology. Healthcare providers expressed a positive favorability toward learning MCI triage via telesimulation. We were also able to establish a process to obtain quantitative data that would allow for the calculation of triage accuracy for further experimental study designs.

In arable cropping systems, reduced or conservation tillage practices are linked with improved soil quality, C retention and higher microbial biomass, but most long-term studies rarely focus on depths greater than 15 cm nor allow comparison of microbial community responses to agricultural practices. We investigated microbial community structure in a long-term field trial (12-years, Lincoln, New Zealand) established in a silt-loam soil over four depth ranges down to 30 cm. Our objectives were to investigate the degree of homogenisation of soil biological and chemical properties with depth, and to determine the main drivers of microbial community response to tillage. We hypothesised that soil microbiological responses would depend on tillage depth, observed by a homogenisation of microbial community composition within the tilled zone. Tillage treatments were mouldboard plough and disc harrow, impacting soil to ∼20 and ∼10 cm depth, respectively. These treatments were compared to a no-tillage treatment and two control treatments, both permanent pasture and permanent fallow. Bacterial and fungal communities collected from the site were not impacted by the spatial location of sampling across the study area but were affected by physicochemical changes associated with tillage induced soil homogenisation and plant presence. Tillage treatment effects on both species richness and composition were more evident for bacterial communities than fungal communities, and were greater at depths

BackgroundExamination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Methods and ResultsProspective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke). ConclusionsDetailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Registration number: NCT00359424.

Introduction: The accurate diagnosis of elevated intracranial pressure (eICP) in the emergent setting is a critical determination that presents significant challenges. Several studies show correlation of sonographic optic nerve sheath diameter (ONSD) to eICP, while others show high inter-observer variability or marginal performance with less experienced sonographers. The objective of our study is to assess the ability of bedside ultrasound measurement of ONSD to identify the presence of eICP when performed by a single experienced sonographer. We hypothesize that ONSD measurement is sensitive and specific for detecting eICP and can be correlated with values obtained by external ventricular device (EVD). Methods: This was a prospective blinded observational study conducted in a neurocritical care unit of a level 1 trauma center. ONSD measurement was performed on a convenience sample of 27 adult patients who required placement of an invasive intracranial monitor as part of their clinical care. One certified sonographer/physician performed all ultrasounds within 24 hours of placement of EVD. The sonographer was blinded to the ICP recorded by invasive monitor at the time of the scan. A mean ONSD value of ≥5.2 mm was taken as positive. Results: The sonographer performed 27 ocular ultrasounds on individual patients. Six (22%) of these patients had eICP (EVD measurement of >20 mmHg). Spearman rank correlation coefficient of ONSD and ICP was 0.408 (p=0.03), demonstrating a moderate positive correlation. A ROC curve was created to determine the optimal cut off value to distinguish an eICP greater than 20 mmHg. The area under the receiver operator characteristic curve was 0.8712 (95% confidence interval [CI]=0.67 to 0.96). ONSD ≥5.2 mm was a good predictor of eICP (>20 mmHg) with a sensitivity of 83.3% (95% CI=35.9% to 99.6%) and specificity of 100% (95% CI=84.6% to 100%). Conclusion: While the study suggests ONSD measurements performed by a single skilled operator may be both sensitive and specific for detecting eICP, confirmation in a much larger sample is needed. Ocular ultrasound may provide additional non-invasive means of assessing eICP . [West J Emerg Med. 2014;15(2):217–220.]

We evaluated the effectiveness of text messaging versus email, as a delivery method to enhance knowledge retention of emergency medicine (EM) content in EM residents. We performed a multi-centered, prospective, randomized study consisting of postgraduate year (PGY) 1 to PGY 3 & 4 residents in three United States EM residency programs in 2014. Fifty eight residents were randomized into one delivery group: text message or email. Participants completed a 40 question pre- and post-intervention exam. Primary outcomes were the means of pre- and post-intervention exam score differences. Data were analyzed using descriptive statistics, paired t-test, and multiple linear regressions. No significant difference was found between the primary outcomes of the two groups (P=0.51). PGY 2 status had a significant negative effect (P=0.01) on predicted exam score difference. Neither delivery method enhanced resident knowledge retention. Further research on implementation of mobile technology in residency education is required.

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

The most common configuration of the mandibular first molar is the presence of two roots and three root canals. The objective of this work is to present two rare anatomic configurations with six root canals on two mandibular left first molars diagnosed during endodontic therapy. Root canal therapy was performed using a dental operating microscope. Ultrasonic troughing in the grooves in between the mesial root canals and in between the distal root canals was able to show the middle root canals. Large samples population characterization researches and systematic reviews were unable to detect a single case of six root canals configuration in a mandibular first molar in their investigations. Although it is a rare configuration, a six root canal configuration is possible to be found in the mandibular first molar. Three different pulp chamber configurations are possible to be found. Two or three roots may be present and the root configuration more common in the mesial root is the Type 8 and Type 12 for the distal root. Some concepts about the required technique to approach these cases are also debated.

Insufficient data exist on population-based trends in morbidity and mortality to determine the success of prevention strategies and improvements in health care delivery in stroke. The aim of this study was to determine trends in incidence and outcome (1-year mortality, 28-day case-fatality) in relation to management and risk factors for stroke in the multi-ethnic population of Auckland, New Zealand (NZ) over 30-years.Four stroke incidence population-based register studies were undertaken in adult residents (aged ≥15 years) of Auckland NZ in 1981-1982, 1991-1992, 2002-2003 and 2011-2012. All used standard World Health Organization (WHO) diagnostic criteria and multiple overlapping sources of case-ascertainment for hospitalised and non-hospitalised, fatal and non-fatal, new stroke events. Ethnicity was consistently self-identified into four major groups. Crude and age-adjusted (WHO world population standard) annual incidence and mortality with corresponding 95% confidence intervals (CI) were calculated per 100,000 people, assuming a Poisson distribution.5400 new stroke patients were registered in four 12 month recruitment phases over the 30-year study period; 79% were NZ/European, 6% Māori, 8% Pacific people, and 7% were of Asian or other origin. Overall stroke incidence and 1-year mortality decreased by 23% (95% CI 5%-31%) and 62% (95% CI 36%-86%), respectively, from 1981 to 2012. Whilst stroke incidence and mortality declined across all groups in NZ from 1991, Māori and Pacific groups had the slowest rate of decline and continue to experience stroke at a significantly younger age (mean ages 60 and 62 years, respectively) compared with NZ/Europeans (mean age 75 years). There was also a decline in 28-day stroke case fatality (overall by 14%, 95% CI 11%-17%) across all ethnic groups from 1981 to 2012. However, there were significant increases in the frequencies of pre-morbid hypertension, myocardial infarction, and diabetes mellitus, but a reduction in frequency of current smoking among stroke patients.In this unique temporal series of studies spanning 30 years, stroke incidence, early case-fatality and 1-year mortality have declined, but ethnic disparities in risk and outcome for stroke persisted suggesting that primary stroke prevention remains crucial to reducing the burden of this disease.

Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov NCT00145925).The ADVANCE trial was a multicentre, 2 × 2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85%) with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8% (-1 to 15%) based on the investigator-reported events and 9% (0 to 17%) based on the EPAC-based events (P for homogeneity = 0.70). The corresponding findings for the glucose comparison were 8% (1 to 15%) and 10% (2% to 18%) (P for homogeneity = 0.60). The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6).The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment.

The highly polyphagous Old World cotton bollworm Helicoverpa armigera is a quarantine agricultural pest for the American continents. Historically H. armigera is thought to have colonised the American continents around 1.5 to 2 million years ago, leading to the current H. zea populations on the American continents. The relatively recent species divergence history is evident in mating compatibility between H. zea and H. armigera under laboratory conditions. Despite periodic interceptions of H. armigera into North America, this pest species is not believed to have successfully established significant populations on either continent. In this study, we provide molecular evidence via mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) partial gene sequences for the successful recent incursion of H. armigera into the New World, with individuals being detected at two sites (Primavera do Leste, Pedra Preta) within the State of Mato Grosso in Brazil. The mtDNA COI and Cyt b haplotypes detected in the Brazilian H. armigera individuals are common throughout the Old World, thus precluding identification of the founder populations. Combining the two partial mtDNA gene sequences showed that at least two matrilines are present in Brazil, while the inclusion of three nuclear DNA Exon-Primed Intron-Crossing (EPIC) markers identified a further two possible matrilines in our samples. The economic, biosecurity, resistance management, ecological and evolutionary implications of this incursion are discussed in relation to the current agricultural practices in the Americas.

Little is known about the strategies people use to effectively hide objects from others, or to search for objects others have hidden. The present research extends a recent investigation of people's hiding and searching strategies in a simple room with 9 cache location. In the present studies, people hid and searched for three objects under more than 70 floor tiles in complex real and virtual rooms. Experiment 1 replicated several finding of Talbot et al within the more complex real and virtual environments. Specifically, people traveled further from origin and selected more dispersed locations when hiding than when searching. Experiments 2 and 3 showed that: 1) people were attracted to an area of darkness when searching and avoided locations close to a window when hiding, 2) when search attempts were limited to three choices, people searched farther from origin and dispersed their locations more when hiding than when searching, and 3) informing people that they would need to recover their hidden objects altered their hiding behavior and increased recovery accuracy. Across all experiments, consistencies in location preferences emerged, with more preference for the middle of the room during hiding and more preference for corners of the room during searching. Even though the same people participated in both the hiding and searching tasks, it appears that people use different strategies to select hiding places than to search for objects hidden by others.