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

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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). <b><i>Results:</i></b> 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 (<i>p</i> &#x3c; 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; <i>p</i> &#x3c; 0.001) after accounting for the treatment arm, without evidence of effect modification by the baseline KidneyIntelX risk stratum or by the treatment arm. <b><i>Conclusions:</i></b> 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.

Dhaka Sitting on a Plastic Bomb: Issues and Concerns around Waste Governance, Water Quality, and Public Health

Plastic, an offer of modernity, has become one of the essential parts of our everyday life. However, it is presenting a massive threat in altered forms, to our health and environment. Plastic does not only pollute the surface environment, freshwater, and marine ecosystems, but toxic elements released from plastics also percolate down the surface and contaminate groundwater, which we often use as ‘safe’ drinking water. This probable future risk is deeply rooted in the entire governance infrastructure of plastic waste which could potentially lead to contamination of groundwater. Thus, a state-sponsored ‘safe drinking water’ initiative could contrarily produce a ‘risk society’. A recent study finds 81% of tap water samples collected worldwide contained plastic pollutants, which means that annually we may be ingesting between 3000 and 4000 microparticles of plastic from tap water. Based on review, ethnographic observations and interviews, and lived experience in a plastic-wrapped city (Dhaka), this paper sheds light on the complex interface of plastic, water, and public health, on the relevance of Beck’s ‘risk society’ to understand this complexity, and on replicating the idea of ‘risk society’ in the case of Bangladesh. Through understanding the plastic–groundwater–waste management nexus, this paper highlights and advocates for a new strategy of plastic governance in modern states.

Short-term Projections based on Early Omicron Variant Dynamics in England.

Throughout the ongoing COVID-19 pandemic, the worldwide transmission and replication of SARS- COV-2, the causative agent of COVID-19 disease, has resulted in the opportunity for multiple mutations to occur that may alter the virus transmission characteristics, the effectiveness of vaccines and the severity of disease upon infection. The Omicron variant (B.1.1.529) was first reported to the WHO by South Africa on 24 November 2021 and was declared a variant of concern by the WHO on 26 November 2021. The variant was first detected in the UK on 27 November 2021 and has since been reported in a number of countries globally where it is frequently associated with rapid increase in cases. Here we present analyses of UK data showing the earliest signatures of the Omicron variant and mathematical modelling that uses the UK data to simulate the potential impact of this variant in the UK. In order to account for the uncertainty in transmission advantage, vaccine escape and severity at the time of writing, we carry out a sensitivity analysis to assess the impact of these variant characteristics on future risk.

Low weight at birth can be an indicative in childhood as a marker of metabolic syndrome and hypertension

As low weight at birth can be a marker for future risk factors for cardiovascular diseases, public school children who had this positive history were studied S to nutritional status, lipids, glucose, uric acid, blood pressure and socioeconomic conditions. The main interest of the investigation is to find statistically significant correlations among data collected from young public school children from a city outside of the capital of Sao Paulo in Brazil. Results: risk factors for metabolic syndrome presented higher impact considering blood pressure and socioeconomic conditions, calling for better prenatal care and surveillance plus intervention in the low weight at birth children.

Intracranial Internal Carotid Artery Calcification Is Not Predictive of Future Cognitive Decline

BackgroundIntracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICA calcification for future risk of dementia and compared the results with conventional imaging biomarkers of dementia.MethodsIn a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICA calcification was quantified on baseline CT scans using the Agatson calcium score. The ability of baseline ICA calcification to discriminate between a control group (participants who maintained a Clinical Dementia Rating (CDR™) score of zero over all follow-up visits) and a converter group (participants who had a baseline CDR of zero but received a persistent CDR>0 at any follow-up visit) was evaluated along with the predictive value of baseline ICA calcification for longitudinal clinical and imaging biomarkers. ResultsBaseline ICA calcium score could not distinguish participants who converted to CDR>0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICA calcification increased with age, male sex, and higher WMH volumes at baseline visit. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICA calcification was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume.ConclusionsIn elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICA calcification is not directly associated with a future risk of dementia, cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

Parole as resentencing: Exploring the punitive accounts of parole decision-making through the comparative case study of Israel

Parole boards have traditionally assessed prisoners’ future risk and rehabilitation prospects in deciding on early release from prison. However, parole boards may do more. In some systems, they may deny parole applications for punitive reasons, thus acting as a resentencing authority. This study conducted a qualitative analysis of the punitive discourses of parole decision-making, with Israel as a comparative case study. Through interviews with 20 chairpersons of Israeli Parole Boards, we found three themes of punitive parole decision-making: (a) preserving public confidence in the criminal justice system; (b) preserving penal proportionality; and (c) re-censuring an especially depraved moral character. The findings suggested that parole boards’ punitive discretion is multidimensional and complex. Such punitive discretion may be openly implemented, it may be cloaked as risk assessment, or decided without formal recognition. The findings further indicated that resentencing through discretionary parole may not only conflict with rehabilitation and risk aims, but may also raise challenges for retributive and deterrent penal policy. Implications for comparative parole policy are discussed.