Peak Expiratory Flow and the Risk of Injurious Falls in Older Adults: The Role of Physical and Cognitive Deficits

ObjectivesPrevious studies showed that peak expiratory flow (PEF) is associated with health-related outcomes in advanced age, but the extent to which it may be related to falls risk remains unclear. We aimed to detect the association between PEF and injurious falls in older adults and to explore the role of cognitive and physical deficits in this association.DesignProspective study with a 6-year follow-up.Setting and ParticipantsThe study involves 2234 community-dwelling older adults with no history of pulmonary disease.MethodsFor each study participant, we assessed the PEF at baseline, expressed as standardized residual (SR) percentile and derived from the normalization of residuals between the measured and predicted PEF values (based on individual age, sex, and body height); incident injurious falls over 6 years, from Hospital Discharge Diagnosis; and physical and cognitive functioning at the baseline and at 3- and 6-year follow-ups by evaluating walking speed, balance, chair stand, and Mini-Mental State Examination, respectively.ResultsOver the follow-up, 232 individuals experienced injurious falls. Cox models indicated 7% higher risk of falls per each 10th reduction in PEF SR-percentile. The risk of injurious falls increased by more than twice for those who had PEF SR-percentile <10th as for values of 80th-100th (hazard ratio = 2.31, 95% confidence interval: 1.41-3.76). Physical deficits mediated 63% of the total effect of PEF on falls risk.Conclusions and ImplicationsOur findings suggest that low PEF is associated with higher risk of injurious falls in older adults, and most of this association is explained by balance or muscular strength deficits.     

Contrast circulation in adult fontan patients using MR Time Resolved Angiography: Application for CT pulmonary angiography

BackgroundWhen patients with Fontan circulation require a computed tomographic pulmonary angiogram (CTPA), there are significant challenges in achieving adequate contrast opacification due to the altered anatomical connections. This study used Time Resolved Angiography with Interleaved Stochastic Trajectories (TWIST) Magnetic Resonance Angiography (MRA) to examine contrast circulation in a cohort of patients with Fontan circulation who were having routine MRI follow up to inform the contrast timing of any subsequent CT.MethodsThis is a single centre, cross-sectional, observational, retrospective study. The time to peak (TTP) signal intensity from the MRA was recorded using regions of interest on the aorta, pulmonary arteries, cavae and Fontan conduit. Patients were grouped by ejection fraction, global longitudinal strain, indexed stroke volume and cardiac index to examine if these cardiac performance parameters affected the mean TTP. Statistical analysis was performed to find the mean TTP for each of the vessels, which was consequently compared between the different cardiac performance parameters.Results35 patients were included in the study. Mean TTP contrast enhancement was 31s in the thoracic aorta, 46s in the right pulmonary artery, 41s in the left pulmonary artery and 55s in the Fontan conduit. Cardiac performance shows no statistically significant relationship to the peak contrast enhancement whether measured by ejection fraction, global longitudinal strain, stroke volume index or cardiac index.ConclusionThe mean optimal timing for a single-phase examination of the Fontan circulation, following an upper limb injection, was 55 s following start of contrast injection irrespective of cardiac performance. In TWIST MRA, the IV bolus is 4–5 s duration. A longer bolus is required for CTA, around 20s, suggesting an additional delay will be required. We propose that an optimal single phase CTPA to be protocolled at 70 s following the start of contrast injection, assuming adequate iodinated contrast dose.     

A Two-Dimensional Second Order Conservative Front-Tracking Method with an Original Marker Advection Approach Based on Jump Relations

A two-dimensional front-tracking method is developed for handling complex shape interfaces satisfying the volume conservation. In order to validate the proposed front-tracking method, a complete convergence study is carried out on several analytical test cases for which the interface is widely stretched and deformed. Comparisons to different existing approaches show that our front-tracking method is second order accurate in space with lower errors than existing interface tracking techniques of the literature.We also propose an original marker advection method which takes into account the jump relations valid at interface in order to deal with the contrast of physical properties encountered in two-phase flow simulations. The conservative front-tracking method computed in this work is shown to be able to describe interfaces with high accuracy even for poorly resolved Eulerian grids.     

利用交叉滞后通径分析研究血压与肾小球滤过率之间的时间因果关系

目的了解血压(blood pressure,BP)与肾小球滤过率(estimated glomerular filtration rate,eGFR)之间的因果关系。方法于2013年1-8月在辽宁省大洼、彰武和辽阳县农村地区采用多阶段随机整群抽样方法建立了心血管疾病研究队列,并于2015年8月-2016年1月对其中6893名35岁及以上农村居民进行随访调查。采用交叉滞后通径分析模型描述BP与eGFR在高血压和非高血压人群中的因果关系。结果 6893名农村居民(女性占52.3%;平均年龄52.39±10.10岁)的平均随访时间为(28.74±3.47)个月。对于高血压患者,eGFR与收缩压(systolic BP,SBP)相互影响,但eGFR先于SBP发生变化[eGFR→SBP的路径系数ρ1=-0.112,P<0.001;SBP→eGFR的路径系数ρ2=-0.070,P<0.001;ρ1 vs ρ2,P=0.044];eGFR单向影响舒张压(diastolic BP,DBP)。对于非高血压人群,eGFR与SBP相互影响,无先后之分;eGFR与DBP不相互影响。结论农村高血压患者eGFR和血压是相互作用的,且仅存在eGFR升高先于SBP升高。农村非高血压人群eGFR和SBP是相互作用的,且没有先后顺序之分,eGFR和DBP之间无因果关系。     

Differentiation between Streptococcus pneumoniae and other viridans group streptococci by matrix-assisted laser desorption/ionization time of flight mass spectrometry

ObjectivesMatrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is becoming the method of choice for bacterial identification. However, correct identification by MALDI-TOF of closely related microorganisms such as viridans streptococci is still cumbersome, especially in the identification of S. pneumoniae. By making use of additional spectra peaks for S. pneumoniae and other viridans group streptococci (VGS). We re-identified viridans streptococci that had been identified and characterized by molecular and phenotypic techniques by MALDI-TOF.MethodsVGS isolates (n = 579), 496 S. pneumoniae and 83 non-S. pneumoniae were analysed using MALDI-TOF MS and the sensitivity and specificity of MALDI-TOF MS was assessed. Hereafter, mass spectra analysis was performed. Presumptive identification of proteins represented by discriminatory peaks was performed by molecular weight matching and the corresponding nucleotides sequences against different protein databases.ResultsUsing the Bruker reference library, 495 of 496 S. pneumoniae isolates were identified as S. pneumoniae and one isolate was identified as non-S. pneumoniae. Of the 83 non-S. pneumoniae isolates, 37 were correctly identified as non-S. pneumoniae, and 46 isolates as S. pneumoniae. The sensitivity of the MALDI-TOF MS was 99.8% (95% confidence interval (CI) 98.9–100) and the specificity was 44.6% (95% CI 33.7–55.9). Eight spectra peaks were mostly present in one category (S. pneumoniae or other VGS) and absent in the other category and inversely. Two spectra peaks of these (m/z 3420 and 3436) were selected by logistic regression to generate three identification profiles. These profiles could differentiate between S. pneumoniae and other VGS with high sensitivity and specificity (99.4% and 98.8%, respectively).ConclusionsSpectral peaks analysis based identification is a powerful tool to differentiate S. pneumoniae from other VGS species with high specificity and sensitivity and is a useful method for pneumococcal identification in carriage studies. More research is needed to further confirm our findings. Extrapolation of these results to clinical strains need to be deeply investigated.     

Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: A randomized controlled trial

Resistant hypertension (RHT) is associated with obstructive sleep apnea (OSA) and increased aortic stiffness, measured by carotid‐femoral pulse wave velocity (cf‐PWV). We aimed to evaluate in a randomized controlled trial, the effect of Continuous positive airway pressure (CPAP) treatment on cf‐PWV in comparison with a control group in patients with RHT and moderate‐severe OSA. One‐hundred and sixteen patients were randomized to 6‐month CPAP treatment (56 patients) or no therapy (60 patients), while keeping their antihypertensive treatment unchanged. Carotid‐femoral pulse wave velocity was performed at the beginning and end of the 6‐month period. Intention‐to‐treat intergroup differences in cf‐PWV changes were assessed by a generalized mixed‐effects model with the allocation group as a fixed factor and adjusted for age, sex, changes in mean arterial pressure and the baseline cf‐PWV values. Subgroup sensitivity analyses were performed, excluding patients with low CPAP adherence and low cf‐PWV at baseline. CPAP and control groups had similar clinic‐laboratorial characteristics. Patients had a mean cf‐PWV of 9.4 ± 1.6 m/s and 33% presented cf‐PWV > 10 m/s. During treatment, the control group had a mean increase in cf‐PWV of +0.43 m/s (95% confidence interval [CI], +0.14 to +0.73 m/s; p = .005), whereas the CPAP group had a mean increase of +0.03 m/s (95% CI, ?0.33 to +0.39 m/s; p = .87), resulting in a mean difference in changes between CPAP and control of ?0.40 m/s (95% CI, ?0.82 to +0.02 m/s; p = .059). Subgroup analyses did not change the results. In conclusion, a 6‐month CPAP treatment did not reduce aortic stiffness, measured by cf‐PWV, in patients with RHT and moderate/severe OSA, but treatment may prevent its progression, in contrast to no‐CPAP therapy.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Adolescent cardiometabolic risk scores: A scoping review

AimsClustering of cardiometabolic risk factors (CMRFs) indicates cardiometabolic risk (CMR), a key driver of cardiovascular disease. Early detection and treatment of CMR are important to decrease this risk. To facilitate the identification of individuals at risk, CMRFs are commonly combined into a CMR Score. This scoping review aims to identify CMRFs and methods used to calculate adolescent CMR Scores.Data synthesisSystematic searches were executed in Child Development and Adolescent Studies, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCO CINAHL, Scopus Elsevier, Cochrane CENTRAL, and Nursing and Allied Health. No limits were placed on publication date or geographic location. Studies were included if participants were 10–19 years and the study reported CMRFs in a composite score. Key extracted information included participant characteristics, CMRFs comprising the scores, and methods of score calculation. CMRFs were categorized and data were reported as frequencies. This study identified 170 studies representing 189 CMR Scores. The most common CMRF categories were related to lipids, blood pressure, and adiposity. The most frequent CMRFs were triglyceride z-score, systolic blood pressure z-score, and inverse high-density lipoproteins z-score. Scores were mostly calculated by summing CMRF z-scores without weighting.ConclusionsThe range of CMRFs and Scores identified in adolescent CMR literature limits their use and interpretation. Published CMR Scores commonly contain two main limitations: (a) use of an internal cohort as the z-score reference population, and (b) Scores relying on adiposity measures. We highlight the need for a standard set of CMRFs and a consensus for a CMR Score for adolescents.     

Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques

ObjectiveTo determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans.MethodsA collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1–5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time.ResultsCompound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve.ConclusionsThe conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test.SignificanceWe provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.