Tag: pubmed

Neurology. 2021 Aug 4:10.1212/WNL.0000000000012482. doi: 10.1212/WNL.0000000000012482. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association between midlife plasma amyloid-beta (Aβ_1-42, Aβ_1-40, Aβ₄₂:Aβ₄₀) and risk of MCI and dementia.

METHODS: Plasma Aβ₄₂ and Aβ₄₀ were retrospectively measured using a fluorimetric bead-based immunoassay in a subsample of the Atherosclerosis Risk in Communities cohort study. We investigated the relationship of plasma Aβ₄₂, Aβ₄₀, and Aβ₄₂:Aβ₄₀ ratio measured in midlife, late-life, and the change from midlife to late-life, to risk of MCI, dementia, and combined MCI/dementia outcomes in late-life (from 2011-19). We used multinomial logistic regressions estimating relative risk ratios (RRR) of these cognitive outcomes vs cognitively normal adjusted for age, sex, education, site-race, APOE, hypertension, diabetes, and body mass index.

RESULTS: A total of 2284 participants were included (midlife mean age=59.2±5.2, 57% female, 22% Black). Each doubling of midlife Aβ₄₂:Aβ₄₀ was associated with 37% lower risk of MCI/dementia (RRR=0.63, 95% CI: 0.46, 0.87), but only up to approximately the median (spline model threshold 0.20). Every standard deviation increase in plasma Aβ₄₂ (10 pg/mL) was associated with 13% lower risk of MCI/dementia (RRR=0.87, 95% CI: 0.77, 0.98), whereas every standard deviation increase in plasma Aβ₄₀ (67 pg/mL) was associated with 15% higher risk of MCI/dementia (RRR=1.15, 95% CI: 1.01, 1.29). Associations were comparable, but slightly weaker statistically, when repeating models using late-life plasma Aβ predictors. Aβ₄₂ and Aβ₄₀ increased from midlife to late-life, but changes were not associated with cognitive outcomes.

CONCLUSION: Midlife measurement of plasma Aβ may have utility as a blood-based biomarker indicative of risk for future cognitive impairment.

PMID:34349010 | DOI:10.1212/WNL.0000000000012482

Open Heart. 2021 Aug;8(2):e001653. doi: 10.1136/openhrt-2021-001653.

ABSTRACT

BACKGROUND: The clinical effectiveness of ablating non-paroxysmal atrial fibrillation (non-PAF) relies on proper patient selection. We developed and validated a scoring system to predict non-PAF ablation outcomes.

METHODS: Data on 416 non-PAF ablations were analysed using binary logistic regression at a London centre. Identified preprocedural variables, which independently predicted freedom from atrial tachyarrhythmia. Twenty-one possible predictive variables and a model with c-statistic 0.751-explained outcome variation in London at mean follow-up 12±3 months. An additive point score (range 0-9) was developed-the FLAME score: female=1; long-lasting persistent atrial fibrillation=1; left atrial diameter in mm: 40 to <45 = 1, 45 to <50 = 2, 50 to <55=3, ≥55 =4; mitral regurgitation (MR) mild to moderate=1; extreme comorbidity=2. Extreme comorbidities include severe MR, moderate mitral stenosis, mitral replacement, hypertrophic cardiomyopathy or congenital heart disease.

RESULTS: The FLAME score was applied to data (882 non-PAF ablations) at a Californian centre, and predicted the outcome of both single (p<0.0001) and multiple (p<0.0001) procedures. For first ablation (follow-up 2.1 years (median, IQR 1.0-4.1)), FLAME score: 0-1 predicts 62% success, 2-4 44% and ≥5 29% (P_trend <0.0001). After the final ablation (mean procedures: 1.4±0.6, follow-up 1.8 years (median, IQR 0.8-3.6)), FLAME score: 0-1 predicts 81% success, 2-4 65% and ≥5 44% (P_trend <0.0001).

CONCLUSIONS: FLAME score is easily calculated, derived in London, and predicted single and multiple procedural outcomes for non-PAF ablations in California. In patients with a high score, even multiple procedures are usually ineffective.

PMID:34348972 | DOI:10.1136/openhrt-2021-001653

Postgrad Med J. 2021 Aug 4:postgradmedj-2021-140861. doi: 10.1136/postgradmedj-2021-140861. Online ahead of print.

NO ABSTRACT

PMID:34348989 | DOI:10.1136/postgradmedj-2021-140861

BMJ Open. 2021 Aug 4;11(8):e046195. doi: 10.1136/bmjopen-2020-046195.

ABSTRACT

OBJECTIVE: The aim of this study was to estimate 10-year cardiovascular disease (CVD) risk among Bangladeshi rural community residents, using the 2014 WHO/International Society of Hypertension (WHO/ISH) risk prediction charts.

STUDY DESIGN: Cross-sectional population-based study done by local community healthcare workers engaging the lowest level facilities of the primary healthcare system.

SETTING AND PARTICIPANTS: A total of 1545 rural adults aged ≥40 years of Debhata upazila of Satkhira district of Bangladesh participated in this survey done in 2015. The community health workers collected data on age, smoking, blood pressure, blood glucose and treatment history of diabetes and hypertension.

PRIMARY OUTCOME MEASURES: We estimated total 10-year CVD risk using the WHO/ISH South East Asia Region-D charts without cholesterol and categorised the risk into low (<10%), moderate (10%-19.9%), high (20%-29.9%) and very high (≥30%).

RESULTS: The participants’ mean age (±SD) was 53.9±11.6 years. Overall, the 10-year CVD risks (%, 95% CI) were as follows: low risk (81.6%, 95% CI 78.4% to 84.6%), moderate risk (9.9%, 95% CI 7.4% to 12.1%), high risk (5.8%, 95% CI 4.4% to 7.2%) and very high risk (2.8%, 95% CI 1.5% to 4.1%). In women, moderate to very high risks were higher (moderate 12.1%, high 6.1% and very high 3.7%) compared with men (moderate 7.5%, high 5.5% and very high 1.9%) but none of these were statistically significant. The age-standardised prevalence of very high risk increased from 2.9% (0.7%-5.2%) to 8.5% (5%-12%) when those with anti-hypertensive medication having controlled blood pressure (<140/90 mm Hg) added.

CONCLUSION: The very high-risk estimates could be used for planning resource for CVD prevention programme at upazila level. There is a need for a national level study, covering diversities of rural areas, to contribute to national planning of CVD prevention.

PMID:34348948 | DOI:10.1136/bmjopen-2020-046195

BMJ Open. 2021 Aug 4;11(8):e049675. doi: 10.1136/bmjopen-2021-049675.

ABSTRACT

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands.

METHODS: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV₁), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively.

RESULTS: Treatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer’s incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries.

CONCLUSIONS: Based on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.

PMID:34348953 | DOI:10.1136/bmjopen-2021-049675

Neurol Neuroimmunol Neuroinflamm. 2021 Aug 4;8(5):e1051. doi: 10.1212/NXI.0000000000001051. Print 2021 Sep.

ABSTRACT

OBJECTIVE: To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).

METHODS: We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing-remitting MS with a median (interquartile range) follow-up of 23.9 (23.3-24.7) months. Patients were grouped into those with abnormal or normal sNfL levels, defined as sNfL ≥/<80th percentile of age-corrected reference values. Likewise, patients were grouped by a median split into those with thin or thick ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer, and inner nuclear layer in nonoptic neuritis eyes. Outcome parameters were violation of no evidence of disease activity (NEDA-3) criteria or its components.

RESULTS: Patients with abnormal baseline sNfL had a higher risk of violating NEDA-3 (hazard ratio [HR] 2.28, 95% CI 1.27-4.09, p = 0.006) and developing a new brain lesion (HR 2.47, 95% CI 1.30-4.69, p = 0.006), but not for a new relapse (HR 2.21, 95% CI 0.97-5.03, p = 0.058). Patients with both abnormal sNfL and thin GCIP had an even higher risk for NEDA-3 violation (HR 3.61, 95% CI 1.77-7.36, p = 4.2e^-4), new brain lesion (HR 3.19, 95% CI 1.51-6.76, p = 0.002), and new relapse (HR 5.38, 95% CI 1.61-17.98, p = 0.006) than patients with abnormal sNfL alone.

CONCLUSIONS: In patients with early MS, the presence of both abnormal sNfL and thin GCIP is a stronger risk factor for future disease activity than the presence of each parameter alone.

PMID:34348969 | DOI:10.1212/NXI.0000000000001051

Cancer Prev Res (Phila). 2021 Aug 4:canprevres.0141.2021. doi: 10.1158/1940-6207.CAPR-21-0141. Online ahead of print.

ABSTRACT

Without preventive interventions, women with germline pathogenic variants in BRCA1 or BRCA2 have high lifetime risks for breast cancer (BC) and tubo-ovarian cancer. The increased risk for BC starts at a considerably younger age than that for tubo-ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is effective in reducing tubo-ovarian cancer risk for BRCA1 and BRCA2 mutation carriers, but whether it reduces BC risk is less clear. All studies of rrBSO and BC risk are observational in nature, and subject to various forms of bias and confounding, thus limiting conclusions that can be drawn about causation. Early studies supported a statistically significant protective association for rrBSO on BC risk, which is reflected by several international guidelines that recommend consideration of pre-menopausal rrBSO for BC risk reduction. However, these historical studies were hampered by the presence of several important biases, including immortal person-time bias, confounding by indication, informative censoring, and confounding by other risk factors, which may have led to over-estimation of any protective benefit. Contemporary studies, specifically designed to reduce some of these biases, have yielded contradictory results. Taken together, there is no clear and consistent evidence for a role of pre-menopausal rrBSO in reducing BC risk in BRCA1 or BRCA2 mutation carriers.

PMID:34348913 | DOI:10.1158/1940-6207.CAPR-21-0141

Br J Sports Med. 2021 Aug 4:bjsports-2021-104256. doi: 10.1136/bjsports-2021-104256. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the incidence, clinical correlates and exposure risk of medical encounters during community-based physical activity events in the UK.

METHODS: An analysis of medical data from weekly, community-based physical activity events (parkrun) at 702 UK locations over a 6-year period (29 476 294 participations between 2014 and 2019) was conducted in order to define the incidence and clinical correlates of serious life-threatening, non-life-threatening and fatal medical encounters.

RESULTS: 84 serious life-threatening encounters (overall incidence rate=0.26/100 000 participations) occurred including 18 fatalities (0.056/100 000 participations). Statistical modelling revealed that the probabilities of serious life-threatening encounters were exceptionally low, however, male sex, increasing age, slower personal best parkrun time and less prior running engagement/experience (average number of runs per year and number of years as a parkrun participant) were associated with increased probability of serious life-threatening encounters. These were largely accounted for by cardiac arrest (48/84, 57%) and acute coronary syndromes (20/84, 24%). Non-life-threatening medical encounters were mainly attributed to tripping or falling, with a reported incidence of 39.2/100 000 participations.

CONCLUSIONS: Serious life-threatening and fatal medical encounters associated with parkrun participation are extremely rare. In the context of a global public health crisis due to inactivity, this finding underscores the safety and corollary public health value of community running/walking events as a strategy to promote physical activity.

PMID:34348921 | DOI:10.1136/bjsports-2021-104256

Sci Adv. 2021 Aug 4;7(32):eabd2605. doi: 10.1126/sciadv.abd2605. Print 2021 Aug.

ABSTRACT

The study of RNA modifications in large clinical cohorts can reveal relationships between the epitranscriptome and human diseases, although this is especially challenging. We developed ModTect (https://github.com/ktan8/ModTect), a statistical framework to identify RNA modifications de novo by standard RNA-sequencing with deletion and mis-incorporation signals. We show that ModTect can identify both known (N ¹-methyladenosine) and previously unknown types of mRNA modifications (N ²,N ²-dimethylguanosine) at nucleotide-resolution. Applying ModTect to 11,371 patient samples and 934 cell lines across 33 cancer types, we show that the epitranscriptome was dysregulated in patients across multiple cancer types and was additionally associated with cancer progression and survival outcomes. Some types of RNA modification were also more disrupted than others in patients with cancer. Moreover, RNA modifications contribute to multiple types of RNA-DNA sequence differences, which unexpectedly escape detection by Sanger sequencing. ModTect can thus be used to discover associations between RNA modifications and clinical outcomes in patient cohorts.

PMID:34348892 | DOI:10.1126/sciadv.abd2605

Sci Adv. 2021 Aug 4;7(32):eabg5882. doi: 10.1126/sciadv.abg5882. Print 2021 Aug.

ABSTRACT

Cement is the most produced material in the world. A major player in greenhouse gas emissions, it is the main binding agent in concrete, providing a cohesive strength that rapidly increases during setting. Understanding how such cohesion emerges is a major obstacle to advances in cement science and technology. Here, we combine computational statistical mechanics and theory to demonstrate how cement cohesion arises from the organization of interlocked ions and water, progressively confined in nanoslits between charged surfaces of calcium-silicate-hydrates. Because of the water/ions interlocking, dielectric screening is drastically reduced and ionic correlations are proven notably stronger than previously thought, dictating the evolution of nanoscale interactions during cement hydration. By developing a quantitative analytical prediction of cement cohesion based on Coulombic forces, we reconcile a fundamental understanding of cement hydration with the fully atomistic description of the solid cement paste and open new paths for scientific design of construction materials.

PMID:34348896 | DOI:10.1126/sciadv.abg5882