Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Essentiality of dietary cholesterol and its interactions with phospholipid in juvenile slipper lobster (Thenus australiensis).

This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g, mean ± SD, CV = 0.16), and to explore the potential for interactions between dietary cholesterol and phospholipid. An 8-week experiment was conducted using six experimental feeds containing three supplemental cholesterol concentrations (0, 0.2 and 0.4% dry matter) at two supplemental phospholipid concentrations (0% and 1.0% dry matter). Dietary cholesterol concentrations of ≥ 0.2% resulted in up to threefold greater weight gain compared to 0% dietary cholesterol, but without any significant main or interactive dietary phospholipid effect. An interaction was observed for lobster survival with lowest survival (46%) recorded for combined 0% cholesterol and 0% phospholipid compared to every other treatment (71-100%). However, all surviving lobsters at 0% dietary cholesterol, regardless of dietary phospholipid level, were in poor nutritional condition. Apparent feed intake (AFI) was significantly higher at dietary cholesterol ≥ 0.2% but was lower for each corresponding dietary cholesterol level at 1% dietary phospholipid. This implied that the feed conversion ratio was improved with supplemental phospholipid. In conclusion, this study confirms the essential nature of dietary cholesterol and that dietary phospholipid can provide additional benefits.

Bulk Nanostructure of Mixtures of Choline Arginate, Choline Lysinate, and Water.

Neutron diffraction with empirical potential structure refinement was used to investigate the bulk liquid nanostructure of mixtures of choline arginate (Ch[Arg]), choline lysinate (Ch[Lys]), and water at mole ratios of 1Ch[Arg]:1Ch[Lys]:6H2O (balanced), 1Ch[Arg]:1Ch[Lys]:20H2O (balanced dilute), 3Ch[Arg]:1Ch[Lys]:12H2O (Arg- rich), and 1Ch[Arg]:3Ch[Lys]:12H2O (Lys- rich). The Arg- and Lys- anions tend not to associate due to electrostatic repulsion between charge groups and weak anion-anion attractions. This means that the local ion structures around the anions in these mixtures resemble the parent single-component systems. The bulk liquid nanostructure varies with the Arg-:Lys- ratio. In the Lys--rich mixture (1Ch[Arg]:3Ch[Lys]:12H2O), Lys- side chains cluster into a continuous apolar domain separated from a charged domain of polar groups. In the balanced mixture (1Ch[Arg]:1Ch[Lys]:6H2O), Lys- side chains form discrete apolar aggregates within a continuous polar domain of Arg-, Ch+, and water, and in the Arg--rich mixture (3Ch[Arg]:1Ch[Lys]:12H2O), the distribution of Lys- and Arg- is nearly homogeneous. Finally, in the balance dilute system (1Ch[Arg]:1Ch[Lys]:20H2O), a percolating water domain forms.

Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.

Periventricular nodular heterotopia in patients with a prenatal diagnosis of myelomeningocele/myeloschisis: associations with seizures and neurodevelopmental outcomes during early childhood.

PURPOSE: Historically, the presence of gray matter heterotopia was a concern for adverse postnatal neurocognitive status in patients undergoing fetal closure of open spinal dysraphism. The purpose of this study was to evaluate neurodevelopmental outcomes and the onset of seizures during early childhood in patients with a prenatal diagnosis of myelomeningocele/myeloschisis (MMC) and periventricular nodular heterotopia (PVNH). METHODS: All patients evaluated at the Center for Fetal Diagnosis and Treatment with a diagnosis of MMC between June 2016 to March 2023 were identified. PVNH was determined from prenatal and/or postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III or IV) were used for neurodevelopmental assessments. Patients were screened for seizures/epilepsy. RESULTS: Of 497 patients evaluated with a prenatal diagnosis of MMC, 99 were found to have PVNH on prenatal MRI, of which 35 had confirmed PVNH on postnatal imaging. From the 497 patients, 398 initially did not exhibit heterotopia on prenatal MRI, but 47 of these then had confirmed postnatal PVNH. The presence of PVNH was not a significant risk factor for postnatal seizures in early childhood. The average neurodevelopmental scores were not significantly different among heterotopia groups for cognitive, language, and motor domains. CONCLUSION: The presence of PVNH in patients with a prenatal diagnosis of MMC does not indicate an increased risk for neurodevelopmental delay at 1 year of age. We did not demonstrate an association with seizures/epilepsy. These findings can aid clinicians in prenatal consultation regarding fetal repair of open spinal dysraphism. Long-term follow-up is required to discern the true association between PVNH seen on prenatal imaging and postnatal seizures/epilepsy and neurodevelopmental outcomes.

Safety Of The Pcsk9 Inhibitor Alirocumab: insights From 47,296 Patient-Years Of Observation.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared to that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection-site reactions. Further, the safety of alirocumab compared to placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Increasing the impact of vertebrate scientific collections through 3D imaging: The openVertebrate (oVert) Thematic Collections Network.

The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate (oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Nanostructure and Dynamics of Aprotic Ionic Liquids at Graphite Electrodes as a Function of Potential.

Atomic force microscope (AFM) videos reveal the near-surface nanostructure and dynamics of the ionic liquids (ILs) 1-butyl-3-methylimidazolium dicyanamide (BMIM DCA) and 1-hexyl-3-methylimidazolium dicyanamide (HMIM DCA) above highly oriented pyrolytic graphite (HOPG) electrodes as a function of surface potential. Molecular dynamics (MD) simulations reveal the molecular-level composition of the nanostructures. In combination, AFM and MD show that the near-surface aggregates form via solvophobic association of the cation alkyl chains at the electrode interface. The diffusion coefficients of interfacial nanostructures are ≈0.01 nm2 s-1 and vary with the cation alkyl chain length and the surface potential. For each IL, the nanostructure diffusion coefficients are similar at open-circuit potential (OCP) and OCP + 1V, but BMIM DCA moves about twice as fast as HMIM DCA. At negative potentials, the diffusion coefficient decreases for BMIM DCA and increases for HMIM DCA. When the surface potential is switched from negative to positive, a sudden change in the direction of the nanostructure motion is observed for both BMIM DCA and HMIM DCA. No transient dynamics are noted following other potential jumps. This study provides a new fundamental understanding regarding the dynamics of electrochemically stable ILs at electrodes vital for the rational development of IL-based electrochemical devices.

Algorithm Training and Testing for a Nonendoscopic Barrett's Esophagus Detection Test in Prospective Multicenter Cohorts.

BACKGROUND & AIMS: Endoscopic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. METHODS: Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. RESULTS: Training (N = 352) and test (N = 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%-94%) at 90% (79%-98%) specificity and 88% (78%-94%) sensitivity at 84% (70%-93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. CONCLUSIONS: A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.).

Coronary stent migration to aorta with successful recovery during aortobifemoral bypass.

We present with full and proper consent of the patient, the case of a 64-year-old man with severe peripheral arterial disease and a known chronic infrarenal aortic occlusion causing severe short-distance claudication. Preoperative computed tomography angiography was significant for a new "cylindrical" calcified lesion. During the elective surgery, the lesion was confirmed to be a coronary stent. The coronary stent was confirmed to be from the patient's prior percutaneous coronary intervention to the left anterior descending artery 1 year prior. The stent was removed without complications by the surgical team. To the best of our knowledge, this is the first such case to be described in current literature. This patient is currently alive, and a revision of his left anterior descending artery intervention was found to be unwarranted on repeat coronary angiography.

Recurrence After Atrial Fibrillation Ablation and Investigational Biomarkers of Cardiac Remodeling.

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

What Predicts Graduate Public Health Student Success? Evidence for Admission Committees in a Post-Affirmative Action Landscape.

OBJECTIVE: A severe staff shortage and a dearth of professionals from underrepresented backgrounds in the public health workforce are contributing to poor health outcomes in the United States. Schools and programs can mitigate these problems by admitting more graduate public health students overall and from underrepresented backgrounds. We identified predictors of foundational graduate public health course grades and graduate grade point average (GPA), sharing evidence to remove application factors that are admission barriers and do not predict student outcomes. METHODS: We conducted a linear regression analysis on demographic and academic factors from 564 graduate public health applications for students at the University at Buffalo who received their degree from January 1, 2016, to February 1, 2021, analyzing age, race and ethnicity, sex, income, undergraduate degree, verbal and quantitative Graduate Record Examination (GRE) percentiles, and undergraduate GPA. Outcomes were grades in foundational public health courses and cumulative graduate GPA. RESULTS: Undergraduate GPA was the best predictor of graduate public health student success, explaining nearly 7% of foundational public health course grades and 29% of graduate GPA. Higher undergraduate GPA contributed to higher course grades and graduate GPA. GRE scores explained <1% of student outcomes. CONCLUSIONS: Our findings add to the growing body of research showing that standardized test scores may not predict graduate student outcomes and provide further evidence for the field of public health to consider removing this admission barrier. By doing so, institutions could admit more students to graduate public health programs who can bring needed skills to the market, further diversifying the workforce and public health faculty, to better meet population health needs.

Improving asthma outcomes: Clinicians' perspectives on peripheral airways.

Disease of the peripheral (or small) airways is fundamental in asthma, being closely related to symptoms (or lack of control of them), airway hyperresponsiveness, spirometric abnormalities, risk of loss of control, or exacerbations and inflammation. Current technology now allows routine measurement of peripheral airway function. Having a working concept of peripheral airways disease in asthma is arguably very useful to clinicians and beneficial to patients because it allows a more comprehensive assessment of asthma severity (rather than just symptoms alone, which is the norm), tracking of progress or deterioration, and assessing response to treatment. Oscillometry is a sensitive way to monitor the peripheral airways, whereas multiple breath nitrogen washout parameters are excellent measures of future risk. In the longer term, physiologic measurements will be crucial in research to define causes and find new disease-modifying treatments.

Natural attenuation of sulfonamides and metabolites in contaminated groundwater - Review, advantages and challenges of current documentation techniques.

Sulfonamides are applied worldwide as antibiotics. They are emerging contaminants of concern, as their presence in the environment may lead to the spread of antibiotic resistance genes. Sulfonamides are present in groundwater systems, which suggest their persistence under certain conditions, highlighting the importance of understanding natural attenuation processes in groundwater. Biodegradation is an essential process, as degradation of sulfonamides reduces the risk of antibiotic resistance spreading. In this review, natural attenuation, and in particular assessment of biodegradation, is evaluated for sulfonamides in groundwater systems. The current knowledge level on biodegradation is reviewed, and a scientific foundation is built based on sulfonamide degradation processes, pathways, metabolites and toxicity. An overview of bacterial species and related metabolites is provided. The main research effort has focused on aerobic conditions while investigations under anaerobic conditions are lacking. The level of implementation in research is laboratory scale; here we strived to bridge towards field application and assessment, by assessing approaches commonly used in monitored natural attenuation. Methods to document contaminant mass loss are assessed to be applicable for sulfonamides, while the approach is limited by a lack of reference standards for metabolites. Furthermore, additional information is required on relevant metabolites in order to improve risk assessments. Based on the current knowledge on biodegradation, it is suggested to use the presence of substituent-containing metabolites from breakage of the sulfonamide bridge as specific indicators of degradation. Microbial approaches are currently available for assessment of microbial community's capacities, however, more knowledge is required on indigenous bacteria capable of degrading sulfonamides and on the impact of environmental conditions on biodegradation. Compound specific stable isotope analysis shows great potential as an additional in situ method, but further developments are required to analyse for sulfonamides at environmentally relevant levels. Finally, in a monitored natural attenuation scheme it is assessed that approaches are available that can uncover some processes related to the fate of sulfonamides in groundwater systems. Nevertheless, there are still unknowns related to relevant bacteria and metabolites for risk assessment as well as the effect of environmental settings such as redox conditions. Alongside, uncovering the fate of sulfonamides in future research, the applicability of the natural attenuation documentation approaches will advance, and provide a step towards in situ remedial concepts for the frequently detected sulfonamides.

Can ChatGPT Answer Patient Questions Regarding Total Knee Arthroplasty?

The internet has introduced many resources frequently accessed by patients prior to orthopaedic visits. Recently, Chat Generative Pre-Trained Transformer, an artificial intelligence-based chat application, has become publicly and freely available. The interface uses deep learning technology to mimic human interaction and provide convincing answers to questions posed by users. With its rapidly expanding usership, it is reasonable to assume that patients will soon use this technology for preoperative education. Therefore, we sought to determine the accuracy of answers to frequently asked questions (FAQs) pertaining to total knee arthroplasty (TKA).Ten FAQs were posed to the chatbot during a single online interaction with no follow-up questions or repetition. All 10 FAQs were analyzed for accuracy using an evidence-based approach. Answers were then rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification."Of the 10 answers given by the chatbot, none received an "unsatisfactory" rating with the majority either requiring minimal (5) or moderate (4) clarification. While many answers required nuanced clarification, overall, answers tended to be unbiased and evidence-based, even when presented with controversial subjects.The chatbot does an excellent job of providing basic, evidence-based answers to patient FAQs prior to TKA. These data were presented in a manner that will be easily comprehendible by most patients and may serve as a useful clinical adjunct in the future.

Estimating potential cardiovascular health benefits of improved population level control of LDL cholesterol through a twice-yearly siRNA-based approach: A simulation study of a health-system level intervention.

BACKGROUND AND AIMS: Inclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation. METHODS: For each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90-540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo. RESULTS: Mean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9% versus 24.6%, respectively. Placebo-corrected time-adjusted absolute reduction in LDL-C with inclisiran was -1.32 mmol/L (95% CI -1.37 to -1.26; p < 0.001), which predicted a 10-year cardiovascular risk of 18.1% with inclisiran versus 24.7% with placebo (absolute difference [95% CI], -6.99% [-7.33 to -6.66]; p < 0.001) NNT 15. Extrapolating to 500,000 inclisiran-treated individuals, the model predicted large population shifts towards lower quintiles of risk with fewer remaining in high-risk categories; 3350 to 471 (≥80% risk), 11,793 to 3332 (60-<80% risk), 52,142 to 22,665 (40-<60% risk), 197,752 to 141,014 (20-<40% risk), and more moving into the lowest risk category (<20%) from 234,963 to 332,518. CONCLUSIONS: Meaningful gains in population health might be achieved over 10 years by implementing at-scale approaches capable of providing substantial and sustained reductions in LDL-C beyond those achievable with statins.