Composite Risk Score Research Articles

Development of a Novel Clinical and Radiologic Risk Score to Predict Septic Complications After Urinary Decompression in Patients with Obstructive Uropathy.

Background: Well-defined clinical predictors of sepsis after upper tract drainage for obstructive uropathy are lacking. The study aim is to develop a data-driven score to predict risk of sepsis after decompression of the upper urinary tract. Materials and Methods: Complete clinical and radiologic data from 271 patients entering the emergency department for obstructive uropathy and submitted to stent/nephrostomy tube decompression were evaluated. The Charlson Comorbidity Index (CCI) was used to score comorbidities. The definition of sepsis was an increase in ≥2 Sequential Organ Failure Assessment points (or a postoperative persistently elevated score +1 additional increase) and documented blood or urine cultures. Descriptive statistics and stepwise multivariable logistic regression modeling with receiver operating characteristic analysis were performed to obtain a composite risk score to predict the risk of sepsis after surgery. This study was approved by our local Ethics Commitee (Prot. 25508). Results: Fifty-five (20.3%) patients developed sepsis. At multivariable analysis, CCI ≥2 (odds ratio [OR] 3.10; 95% confidence interval [CI] 1.36-7.04), maximum body temperature ≥38°C (OR 4.35; 95% CI 1.89-9.44), grade III-IV hydronephrosis (OR 2.37; 95% CI 1.10-4.98), HU of the dilated collecting system ≥7.0 (OR 4.47; 95% CI 2.03-9.81), white blood cells ≥15 × 103/mmc (OR 2.77; 95% CI 1.24-6.19), and C-reactive protein ≥10 (OR 3.27; 95% CI 1.41-7.56) were independently associated with sepsis. The positive predictive value of a true sepsis increased incrementally as a function of number of positive variables, ranging from 1.6% to 100.0% among patients with 1 and 6 positive variables, respectively. Conclusion: Our risk score identifies accurately patients with an increased risk of sepsis after urinary decompression for obstructive uropathy, hence improving clinical management.

Classification Schemes of COVID-19 High Risk Areas and Resulting Policies: A Rapid Review

The COVID-19 pandemic has posed a significant global health threat since January 2020. Policies to reduce human mobility have been recognized to effectively control the spread of COVID-19; although the relationship between mobility, policy implementation, and virus spread remains contentious, with no clear pattern for how countries classify each other, and determine the destinations to- and from which to restrict travel. In this rapid review, we identified country classification schemes for high-risk COVID-19 areas and associated policies which mirrored the dynamic situation in 2020, with the aim of identifying any patterns that could indicate the effectiveness of such policies. We searched academic databases, including PubMed, Scopus, medRxiv, Google Scholar, and EMBASE. We also consulted web pages of the relevant government institutions in all countries. This rapid review's searches were conducted between October 2020 and December 2021. Web scraping of policy documents yielded additional 43 country reports on high-risk area classification schemes. In 43 countries from which relevant reports were identified, six issued domestic classification schemes. International classification schemes were issued by the remaining 38 countries, and these mainly used case incidence per 100,000 inhabitants as key indicator. The case incidence cut-off also varied across the countries, ranging from 20 cases per 100,000 inhabitants in the past 7 days to more than 100 cases per 100,000 inhabitants in the past 28 days. The criteria used for defining high-risk areas varied across countries, including case count, positivity rate, composite risk scores, community transmission and satisfactory laboratory testing. Countries either used case incidence in the past 7, 14 or 28 days. The resulting policies included restrictions on internal movement and international travel. The quarantine policies can be summarized into three categories: (1) 14 days self-isolation, (2) 10 days self-isolation and (3) 14 days compulsory isolation.

POS-189 Added Value of KidneyIntelXTM for Predicting Future Kidney Function Decline Compare to Historical eGFR Trajectories

Enrollment into clinical trials for kidney disease based on high albuminuria or low eGFR have not always yielded desired event rates. Recent data suggests that pre-trial eGFR slope may be a better tool to select trial participants. Few studies have attempted to estimate the improvement in prediction with biomarkers or a composite risk score beyond historical eGFR readings. KidneyIntelXTMis a composite risk score for DKD progression that incorporates static clinical variables and 3 plasma biomarkers.

POS-322 Association of Changes in Modifiable Factors with Changes in KidneyIntelXTM Scores in the CANVAS Participants with Prevalent Diabetic Kidney Disease

KidneyIntelXTMis a composite risk score for DKD progression that incorporates clinical variables and 3 plasma biomarkers. We have previously shown that changes in KidneyIntelX are informative as a time-updated prognostic risk assessment in the CANVAS trial cohort. The associations between changes in common clinical treatment targets with early changes in the composite kidney health, as measured by KidneyIntelX, have not been explored heretofore.

Clinical Utility of KidneyIntelX in Early Stages of Diabetic Kidney Disease in the CANVAS Trial

Introduction: KidneyIntelX is a composite risk score, incorporating biomarkers and clinical variables for predicting progression of diabetic kidney disease (DKD). The utility of this score in the context of sodium glucose co-transporter 2 inhibitors and how changes in the risk score associate with future kidney outcomes are unknown. Methods: We measured soluble tumor necrosis factor receptor (TNFR)-1, soluble TNFR-2, and kidney injury molecule 1 on banked samples from CANagliflozin cardioVascular Assessment Study (CANVAS) trial participants with baseline DKD (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m² or urine albumin-to-creatinine ratio [UACR] ≥30 mg/g) and generated KidneyIntelX risk scores at baseline and years 1, 3, and 6. We assessed the association of baseline and changes in KidneyIntelX with subsequent DKD progression (composite outcome of an eGFR decline of ≥5 mL/min/year [using the 6-week eGFR as the baseline in the canagliflozin group], ≥40% sustained decline in the eGFR, or kidney failure). Results: We included 1,325 CANVAS participants with concurrent DKD and available baseline plasma samples (mean eGFR 65 mL/min/1.73 m² and median UACR 56 mg/g). During a mean follow-up of 5.6 years, 131 participants (9.9%) experienced the composite kidney outcome. Using risk cutoffs from prior validation studies, KidneyIntelX stratified patients to low- (42%), intermediate- (44%), and high-risk (15%) strata with cumulative incidence for the outcome of 3%, 11%, and 26% (risk ratio 8.4; 95% confidence interval [CI]: 5.0, 14.2) for the high-risk versus low-risk groups. The differences in eGFR slopes for canagliflozin versus placebo were 0.66, 1.52, and 2.16 mL/min/1.73 m² in low, intermediate, and high KidneyIntelX risk strata, respectively. KidneyIntelX risk scores declined by 5.4% (95% CI: −6.9, −3.9) in the canagliflozin arm at year 1 versus an increase of 6.3% (95% CI: 3.8, 8.7) in the placebo arm (p < 0.001). Changes in the KidneyIntelX score at year 1 were associated with future risk of the composite outcome (odds ratio per 10 unit decrease 0.80; 95% CI: 0.77, 0.83; p < 0.001) after accounting for the treatment arm, without evidence of effect modification by the baseline KidneyIntelX risk stratum or by the treatment arm. Conclusions: KidneyIntelX successfully risk-stratified a large multinational external cohort for progression of DKD, and greater numerical differences in the eGFR slope for canagliflozin versus placebo were observed in those with higher baseline KidneyIntelX scores. Canagliflozin treatment reduced KidneyIntelX risk scores over time and changes in the KidneyIntelX score from baseline to 1 year associated with future risk of DKD progression, independent of the baseline risk score and treatment arm.

Subjective social status and cardiometabolic risk markers in young adults

BackgroundLow subjective social status (SSS), the perceived status in the social hierarchy, is associated with cardiometabolic risk in middle-aged and older adults. However, most studies are cross-sectional and very little is known about the association in adolescence and young adulthood. The aims of this study were; a) to prospectively investigate the association between SSS at ages 15 and 28 and cardiometabolic risk at age 28–30 and b) to examine if such an association was independent of smoking, physical activity and objective measures of social position. MethodsThe study used questionnaire information at ages 15 and 28 from the West Jutland Cohort Study (N = 3681), health measurements from a sub-sample of the cohort (N = 264, age 28–30, 50% women) and information from population-based national registers. The independent variable was a measure of SSS evaluated by a 10-rung ladder scale and dichotomized at the 25th percentile of data from the cohort study population. The outcome measure was a composite score of cardiometabolic risk including measures of lipids, inflammation, blood pressure and glucose-metabolism. Co-variates included smoking, physical activity, childhood and adulthood socioeconomic position. Sex-stratified linear regression analyses were performed to evaluate the associations between SSS and cardiometabolic risk. ResultsIn both sexes, low SSS at age 28, but not at age 15, was significantly associated with increased cardiometabolic risk at age 28–30. Neither smoking, physical activity, childhood or adulthood objective socioeconomic position fully explained the associations. ConclusionIn young adulthood, SSS was inversely related to cardiometabolic risk after accounting for smoking, physical activity and objective measures of socioeconomic position. These findings suggest that SSS could play a role in the social disparities in cardiometabolic risk in addition to traditional measures of socioeconomic position.

Genome-wide pleiotropy analysis identifies novel blood pressure variants and improves its polygenic risk scores.

Systolic and diastolic blood pressure (S/DBP) are highly correlated modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and horizontal pleiotropy analysis of S/DBP summary statistics from the UK Biobank (UKB)‐International Consortium for Blood Pressure (ICBP) (UKB‐ICBP) BP genome‐wide association study and construct a composite genetic risk score (GRS) by including pleiotropic variants. The composite GRS captures greater (1.11–3.26 fold) heritability for BP traits and increases (1.09‐ and 2.01‐fold) Nagelkerke's R 2 for hypertension and CVD. We replicated 118 novel BP horizontal pleiotropic variants including 18 novel BP loci using summary statistics from the Million Veteran Program (MVP) study. An additional 219 novel BP signals and 40 novel loci were identified after a meta‐analysis of the UKB‐ICBP and MVP summary statistics but without further independent replication. Our study provides further insight into BP regulation and provides a novel way to construct a GRS by including pleiotropic variants for other complex diseases.

A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings

BackgroundThe use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources.MethodsA GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts where Plasmodium falciparum transmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions.ResultsA case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as ‘extremely high’ or ‘high’ priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions.ConclusionThe authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

MiRNA expression deregulation correlates with the Oncotype DX® DCIS score

BackgroundCurrent clinical criteria do not discriminate well between women who will or those who will not develop ipsilateral invasive breast cancer (IBC), or a DCIS recurrence after a ductal carcinoma in situ (DCIS) diagnosis. The 12-gene Oncotype DX® DCIS assay (RT qPCR gene-based scoring system) was established and shown to predict the risk of subsequent ipsilateral IBC or DCIS recurrence. Recent studies have shown that microRNA (miRNA) expression deregulation can contribute to the development of IBC, but very few have evaluated miRNA deregulation in DCIS lesions. In this study, we sought to determine whether specific miRNA expression changes may correlate with Oncotype DX® DCIS scores.MethodsFor this study, we used archived formalin-fixed, paraffin-embedded (FFPE) specimens from 41 women diagnosed with DCIS between 2012 and 2018. The DCIS lesions were stratified into low (n = 26), intermediate (n = 10), and high (n = 5) risk score groups using the Oncotype DX® DCIS assay. Total RNA was extracted from DCIS lesions by macro-dissection of unstained FFPE sections, and next-generation small-RNA sequencing was performed. We evaluated the correlation between miRNA expression data and Oncotype score, as well as patient age. RT-qPCR validations were performed to validate the topmost differentially expressed miRNAs identified between the different risk score groups.ResultsMiRNA sequencing of 32 FFPE DCIS specimens from the three different risk group scores identified a correlation between expression deregulation of 17 miRNAs and Oncotype scores. Our analyses also revealed a correlation between the expression deregulation of 9 miRNAs and the patient’s age. Based on these results, a total of 15 miRNAs were selected for RT-qPCR validation. Of these, miR-190b (p = 0.043), miR-135a (p = 0.05), miR-205 (p = 0.00056), miR-30c (p = 0.011), and miR-744 (p = 0.038) showed a decreased expression in the intermediate/high Oncotype group when compared to the low-risk score group. A composite risk score was established using these 5 miRNAs and indicated a significant association between miRNA expression deregulation and the Oncotype DX® DCIS Score (p < 0.0021), between high/intermediate and low risk groups.ConclusionsOur analyses identified a subset of 5 miRNAs able to discriminate between Oncotype DX® DCIS score subgroups. Together, our data suggest that miRNA expression analysis may add value to the predictive and prognostic evaluation of DCIS lesions.

Disentangling brain heterogeneity via semi‐supervised deep‐learning and MRI: Application to dimensional representations of Alzheimer’s disease

AbstractBackgroundHeterogeneity of neurodegenerative diseases, including Alzheimer’s disease (AD), has hampered precision diagnosis and prognosis. Machine learning methods are able to dissect neuroanatomical heterogeneity and enable identification of disease subtypes via their imaging signatures.MethodWe apply a novel semi‐supervised deep‐learning clustering method to derive dimensions of neurodegeneration, and investigate longitudinal paths in this dimensional system. Analyses used structural MRIs (from the Alzheimer’s Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging; total 2,832 participants; 8,146 scans) including controls and patients with Mild Cognitive Impairment (MCI) and AD.ResultSmile‐GAN identified 4 neurodegenerative patterns/axes (Figure 1): P1, normal anatomy; P2, mild/diffuse atrophy; P3, focal medial temporal atrophy; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1→P2→P4 and P1→P3→P4. Clinically, P2 participants showed worse performance in executive function than P3 participants (median ADNI‐EF= ‐0.29 vs. ‐0.1, with p=0.038) but had better memory (ADNI‐MEM= ‐0.13 vs. ‐0.39, with p=0.003) (Figure 2). Progression to P4 occurred more rapidly from P3 than P2, with median survival time to progression of 4.5 years and 3.2 years for P2 and P3 MCI/Dementia participants, respectively. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration, with high accuracy for determining whether P1 participants would progress and whether they would progress to P2 or P3 (Cox‐proportional‐hazard model average concordance index (CI) on the validation set of 0.8±0.02). Pattern expression offered better performance (CI=0.72±0.02) in predicting clinical conversion from MCI to Dementia compared to amyloid/tau (CI=0.69±0.02), with all three together showing modest improvement over pattern performance (CI=0.76±0.02). A composite risk score comprised of pattern probabilities, Abeta, pTau, presence of APOE E4, and ADAS‐cog score was able to predict survival time with an average concordance index, 0.78±0.02 on randomly split validation sets. (Figure 3).ConclusionFour reproducible volumetric patterns, and 2 major longitudinal pathways were revealed using deep learning, which can be determined on an individual patient basis and has implications for rate of future decline. These pattern‐based biomarkers can enrich the N‐dimension of the A/T/N framework which may inform on clinical trial enrollment and monitoring outcomes in a more personalized manner.

Analytical validation of a multi-biomarker algorithmic test for prediction of progressive kidney function decline in patients with early-stage kidney disease

BackgroundThe KidneyIntelX™ test applies a machine learning algorithm that incorporates plasma biomarkers and clinical variables to produce a composite risk score to predict a progressive decline in kidney function in patients with type 2 diabetes (T2D) and early-stage chronic kidney disease (CKD). The following studies describe the analytical validation of the KidneyIntelX assay including impact of observed methodologic variability on the composite risk score.MethodsAnalytical performance studies of sensitivity, precision, and linearity were performed on three biomarkers assayed in multiplexed format: kidney injury molecule-1 (KIM-1), soluble tumor necrosis factor receptor-1 (sTNFR-1) and soluble tumor necrosis factor receptor-2 (sTNFR-2) based on Clinical Laboratory Standards Institute (CLSI) guidelines. Analytical variability across twenty (20) experiments across multiple days, operators, and reagent lots was assessed to examine the impact on the reproducibility of the composite risk score. Analysis of cross-reactivity and interfering substances was also performed.ResultsAssays for KIM-1, sTNFR-1 and sTNFR-2 demonstrated acceptable sensitivity. Mean within-laboratory imprecision coefficient of variation (CV) was established as less than 9% across all assays in a multi-lot study. The linear range of the assays was determined as 12–5807 pg/mL, 969–23,806 pg/mL and 4256–68,087 pg/mL for KIM-1, sTNFR-1 and sTNFR-2, respectively. The average risk score CV% was less than 5%, with 98% concordance observed for assignment of risk categories. Cross-reactivity between critical assay components in a multiplexed format did not exceed 1.1%.ConclusionsThe set of analytical validation studies demonstrated robust analytical performance across all three biomarkers contributing to the KidneyIntelX risk score, meeting or exceeding specifications established during characterization studies. Notably, reproducibility of the composite risk score demonstrated that expected analytical laboratory variation did not impact the assigned risk category, and therefore, the clinical validity of the reported results.

Molecular genetics of β-thalassemia: A narrative review.

β-thalassemia is a hereditary hematological disease caused by over 350 mutations in the β-globin gene (HBB). Identifying the genetic variants affecting fetal hemoglobin (HbF) production combined with the α-globin genotype provides some prediction of disease severity for β-thalassemia. However, the generation of an additive composite genetic risk score predicts prognosis, and guide management requires a larger panel of genetic modifiers yet to be discovered.Presently, using data from prior clinical trials guides the design of further research and academic studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene therapy approaches.Genetic studies have successfully characterized the causal variants and pathways involved in HbF regulation, providing novel therapeutic targets for HbF reactivation. In addition to these HBB mutation-independent strategies involving HbF synthesis de-repression, the expanding genome editing toolkit provides increased accuracy to HBB mutation-specific strategies encompassing adult hemoglobin restoration for personalized treatment of hemoglobinopathies. Allogeneic hematopoietic stem cell transplantation was, until very recently, the curative option available for patients with transfusion-dependent β-thalassemia. Gene therapy currently represents a novel therapeutic promise after many years of extensive preclinical research to optimize gene transfer protocols.We summarize the current state of developments in the molecular genetics of β-thalassemia over the last decade, including the mechanisms associated with ineffective erythropoiesis, which have also provided valid therapeutic targets, some of which have been shown as a proof-of-concept.

Using Clinical and Echocardiographic Characteristics to Characterize the Risk of Ischemic Stroke in Patients with COVID-19

BackgroundCOVID-19 has been associated with an increased incidence of ischemic stroke. The use echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19 has not been explored. MethodsWe conducted a retrospective study of 368 patients hospitalized between 3/1/2020 and 5/31/2020 who had laboratory-confirmed infection with SARS-CoV-2 and underwent transthoracic echocardiography during hospitalization. Patients were categorized according to the presence of ischemic stroke on cerebrovascular imaging following echocardiography. Ischemic stroke was identified in 49 patients (13.3%). We characterized the risk of ischemic stroke using a novel composite risk score of clinical and echocardiographic variables: age <55, systolic blood pressure >140 mmHg, anticoagulation prior to admission, left atrial dilation and left ventricular thrombus. ResultsPatients with ischemic stroke had no difference in biomarkers of inflammation and hypercoagulability compared to those without ischemic stroke. Patients with ischemic stroke had significantly more left atrial dilation and left ventricular thrombus (48.3% vs 27.9%, p = 0.04; 4.2% vs 0.7%, p = 0.03). The unadjusted odds ratio of the composite novel COVID-19 Ischemic Stroke Risk Score for the likelihood of ischemic stroke was 4.1 (95% confidence interval 1.4-16.1). The AUC for the risk score was 0.70. ConclusionsThe COVID-19 Ischemic Stroke Risk Score utilizes clinical and echocardiographic parameters to robustly estimate the risk of ischemic stroke in patients hospitalized with COVID-19 and supports the use of echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19.

Primary Care's Effects on Costs in the US Veterans Health Administration, 2016-2019: an Observational Cohort Study.

Enhancing primary care is a promising strategy for improving the efficiency of health care. Previous studies of primary care's effects on health expenditures have mostly relied on ecological analyses comparing region-wide expenditures rather than spending for individual patients. To compare overall medical expenditures for individual patients enrolled vs. those not enrolled in primary care in the Veterans Health Administration (VHA). Cohort study with stratification for clinical risk and multivariable linear regression models adjusted for clinical and demographic confounders of expenditures. In total, 6,009,973 VHA patients in fiscal year (FY) 2019-5,410,034 enrolled with a primary care provider (PCP) and 599,939 without a PCP-and similar numbers in FYs 2016-2018. Total annual cost per patient to the VHA (including VHA payments to non-VHA providers) stratified by a composite health risk score previously shown to predict VHA expenditures, and multivariate models additionally adjusted for VHA regional differences, patients' demographic characteristics, non-VHA insurance coverage, and driving time to the nearest VHA facility. Sensitivity analyses explored different modeling strategies and risk adjusters, as well as the inclusion of expenditures by the Medicare program that covers virtually all elderly VHA patients for care not paid for by the VHA. Within each health-risk decile, non-PCP patients had higher outpatient, inpatient, and total costs than those with a PCP. After adjustment for health risk and other factors, lack of a PCP was associated 27.4% higher VHA expenditures, $3274 per patient annually (p < .0001). Sensitivity analyses using different risk adjusters and including Medicare's spending for VHA patients yielded similar results. In the VHA system, primary care is associated with substantial cost savings. Investments in primary care in other settings might also be cost-effective.

Political risks and financial markets: emerging vs developed economies

PurposeThe authors provide a comparative analysis between emerging and developed financial markets in terms of the effects of political risks on stock market returns and volatility. The authors also examine whether this impact depends on the nature of political risks. Therefore, this study aims to detect which financial markets are the most profitable and the riskiest in terms of political risks.Design/methodology/approachThe authors investigate the impact of political risks on the excess stock market return and its conditional volatility using the generalized ARCH model for a sample of 46 developed and emerging markets over a period ranging from 1995 to 2019. In order to test how the nature of political risks affects equity excess returns and volatility differently in different markets, the authors employ (1) a composite political risk score, (2) the four subgroups of political risks as defined by Bekaert et al. (2005, 2014) and (3) the individual dimensions of political risks.FindingsThe findings indicate that the composite political risk is priced into both stock markets. The effect of political risks is positive for excess returns and negative for volatility. The authors show that the political risk leads to more volatility in developed markets. Nevertheless, the effect of individual components varies according to the market category.Practical implicationsThe authors provide a framework for predicting market returns and volatility using changes in the political risk of the country. The findings help investors make investment decisions based on the political decisions of governments. In other words, investors should consider political uncertainty when determining their expected earnings.Originality/valueThe authors engage monthly panel data methodology in terms of the political risk stock market relationship. In addition, the authors consider recent and very long data covering the period 1995–2019. Furthermore, this study combines three various political risk measures, and both equity returns and volatility.

The Italian dementia with lewy bodies study group (DLB-SINDEM): A multicenter survey on the accuracy and the prevalence of DLB diagnosis

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia. However, clinical diagnosis can be challenging. Two toolkits have been deverloped to aid the clinical diagnosis of DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). The aim of the present study is to evaluate the diagnostic accuracy of these two questionnaires, as well as their capacity to enhance application and interpretation of the Consensus Criteria.

Estimating the global risk of anthropogenic climate change

The three recent Special Reports of the IPCC provide an opportunity to understand overarching climate risk, as they cover a wide diversity of risks to natural and human systems. Here we develop a scoring system to translate qualitative IPCC risk assessments into risk scores that, when aggregated, describe global risk from climate change. By the end of this century, global climate risk will increase substantially with greenhouse gas emissions compared to today (composite risk score increase of two- and fourfold under RCP2.6 and RCP8.5, respectively). Comparison of risk levels under +1.5 °C and +2 °C suggests that every additional 0.5 °C of global warming will contribute to higher risk globally (by about a third). Societal adaptation has the potential to decrease global climate risk substantially (by about half) under all RCPs, but cannot fully prevent residual risks from increasing (by one-third under RCP2.6 and doubling under RCP8.5, compared to today).

Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults.

Twilight and low luminance levels are visually challenging environments for the elderly, especially when driving at night. Carotenoid rich diets are known to increase macular pigment optical density (MPOD), which in turn leads to an improvement in visual function. It is not known whether augmenting MPOD can lead to a decrease in vision related night driving difficulties. Additionally, it is unknown if carotenoid supplementation provides additional measurable benefits to one’s useful field of view (UFOV) along with a decreased composite crash risk score. The aim of the study was to evaluate changes in night vision function and UFOV in individuals that took carotenoid vitamin supplements for a six-month period compared to a placebo group. Methods: A prospective, randomized, double-blind, six-month trial of a 14 mg zeaxanthin/7 mg lutein-based supplement was carried out. Participants were randomized into active or placebo group (approx 2:1). Results: n = 33 participants (26 males/7 females) participated with 93% capsule intake compliance in the supplemented group (n = 24) and placebo group (n = 9). MPOD (mean/standard error SE) in the active group increased in the Right eye from 0.35 density units (du)/0.04 SE to 0.41 du/0.05 SE; p < 0.001 and in the Left eye from 0.35 du/0.05 SE to 0.37 du, p > 0.05). The supplemented group showed significant improvements in contrast sensitivity with glare in both eyes with improvements in LogMAR scores of 0.147 and 0.149, respectively (p = 0.02 and 0.01, respectively), monocularly tested glare recovery time improved 2.76 and 2.54 s, respectively, (p = 0.008 and p = 0.02), and we also noted a decreased preferred luminance required to complete visual tasks (p = 0.02 and 0.03). Improvements in UFOV scores of divided attention (p < 0.001) and improved composite crash risk score (p = 0.004) were seen in the supplemented group. The placebo group remained unchanged. Conclusions: The NVC demonstrates that augmenting MPOD in individuals with difficulty in night vision showed measurable benefits in numerous visual functions that are important for night vision driving in this small sample RCT. Additionally, we observed an improvement in UFOV divided attention test scores and decreased composite risk scores.

PD29-05 WHICH INFERTILE MEN WITH NORMAL SEMEN ANALYSIS DESERVE A SECOND SEMEN ANALYSIS IN THE REAL-LIFE SETTING?

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II (PD29)1 Sep 2021PD29-05 WHICH INFERTILE MEN WITH NORMAL SEMEN ANALYSIS DESERVE A SECOND SEMEN ANALYSIS IN THE REAL-LIFE SETTING? Luca Boeri, Paolo Capogrosso, Edoardo Pozzi, Luigi Candela, Federico Belladelli, Walter Cazzaniga, Giuseppe Fallara, Daniele Cignoli, Nicolò Schifano, Eugenio Ventimiglia, Gianmarco Colandrea, Massimo Alfano, Costantino Abbate, Francesco Montorsi, and Andrea Salonia Luca BoeriLuca Boeri More articles by this author , Paolo CapogrossoPaolo Capogrosso More articles by this author , Edoardo PozziEdoardo Pozzi More articles by this author , Luigi CandelaLuigi Candela More articles by this author , Federico BelladelliFederico Belladelli More articles by this author , Walter CazzanigaWalter Cazzaniga More articles by this author , Giuseppe FallaraGiuseppe Fallara More articles by this author , Daniele CignoliDaniele Cignoli More articles by this author , Nicolò SchifanoNicolò Schifano More articles by this author , Eugenio VentimigliaEugenio Ventimiglia More articles by this author , Gianmarco ColandreaGianmarco Colandrea More articles by this author , Massimo AlfanoMassimo Alfano More articles by this author , Costantino AbbateCostantino Abbate More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Andrea SaloniaAndrea Salonia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002030.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current EAU Guidelines suggest that during the diagnostic work-up of an infertile man one semen analysis is sufficient in the case of normality as for WHO criteria. Conversely, a second test is recommended when the first one is abnormal. We aimed to investigate the rate and the clinical characteristics of infertile men with abnormal sperm parameters at a second test, after a normal first semen analysis. METHODS: Complete demographic, clinical and laboratory data from 1358 consecutive primary infertile men (defined according to the WHO definition) were considered. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones were measured in every patient. Patients underwent two consecutive semen analyses at the same laboratory (following 2010 WHO reference criteria). Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. ROC curves were used to create a composite risk score for pathological sperm parameters at a second test. RESULTS: At first analysis, 212 (15.6%) infertile men had normal semen parameters. Of 212, 87 (41.0%) had a second normal semen analysis, while 80 (37.7%), 35 (16.5%) and 10 (4.7%) men showed 1, 2 and 3 pathological parameters at a second test. Men with a pathological second semen analysis had higher CCI, smaller testicular volume and higher FSH values (all p<0.01) than those with normal second test. Sperm concentration was also lower, 34 (23-57) vs. 62 (35-94) (p<0.01). At multivariable logistic regression analysis, smaller testicular volume (OR 0.9, p=0.03), FSH (OR 1.2, p<0.01), and lower sperm concentration (OR 0.9, p<0.01) were associated with pathological second semen analyses, after accounting for age and CCI. ROC curves showed that testicular volume <15 ml, FSH values >6 mUI/ml and sperm concentration <40 mil/ml had good predictive ability for pathologic second sperm anlysis (all AUC >0.8). Considering 1-point for each of the previous variables, the chances of a pathological second analysis increased from 38.8% to 74.6%, 77.3% and 100% among patients with risk scores of 0, 1, 2 and 3, respectively. CONCLUSIONS: Approximately 60% of infertile men with a first normal semen analysis had a pathological second test. Predictors for pathological second test were small testicular volumes, high FSH, and low sperm concentration at first analysis. A risk score based on these parameters could be useful to identify infertile men with a first normal semen analysis that deserve a second test. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e528-e528 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luca Boeri More articles by this author Paolo Capogrosso More articles by this author Edoardo Pozzi More articles by this author Luigi Candela More articles by this author Federico Belladelli More articles by this author Walter Cazzaniga More articles by this author Giuseppe Fallara More articles by this author Daniele Cignoli More articles by this author Nicolò Schifano More articles by this author Eugenio Ventimiglia More articles by this author Gianmarco Colandrea More articles by this author Massimo Alfano More articles by this author Costantino Abbate More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Expand All Advertisement Loading ...

Reward‐ and threat‐related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil

Neuroimaging studies on adolescents at risk for depression have relied on a single risk factor and focused on adolescents in high-income countries. Using a composite risk score, this study aims to examine neural activity and connectivity associated with risk and presence of depression in adolescents in Brazil. Depression risk was defined with the Identifying Depression Early in Adolescence Risk Score (IDEA-RS), calculated using a prognostic model that included 11 socio-demographic risk factors. Adolescents recruited from schools in Porto Alegre were classified into a low-risk (i.e., low IDEA-RS and no lifetime depression), high-risk (i.e., high IDEA-RS and no lifetime depression), or clinically depressed group (i.e., high IDEA-RS and depression diagnosis). One hundred fifty adolescents underwent a functional MRI scan while completing a reward-related gambling and a threat-related face-matching task. We compared group differences in activity and connectivity of the ventral striatum (VS) and amygdala during the gambling and face-matching tasks, respectively, and group differences in whole-brain neural activity. Although there was no group difference in reward-related VS or threat-related amygdala activity, the depressed group showed elevated VS activity to punishment relative to high-risk adolescents. The whole-brain analysis found reduced reward-related activity in the lateral prefrontal cortex of patients and high-risk adolescents compared with low-risk adolescents. Compared with low-risk adolescents, high-risk and depressed adolescents showed reduced threat-related left amygdala connectivity with thalamus, superior temporal gyrus, inferior parietal gyrus, precentral gyrus, and supplementary motor area. We identified neural correlates associated with risk and presence of depression in a well-characterized sample of adolescents. These findings enhance knowledge of the neurobiological underpinnings of risk and presence of depression in Brazil. Future longitudinal studies are needed to examine whether the observed neural patterns of high-risk adolescents predict the development of depression.