Estimates Of Populations Research Articles

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.

Comparing written exposure therapy delivered via telehealth to trauma-focused expressive writing in undergraduates: A proof-of-concept trial.

The literature demonstrates that posttraumatic stress disorder (PTSD) rates are estimated to be higher on college campuses compared to lifetime estimates in the general population. Written exposure therapy (WET) is a promising brief intervention for posttraumatic stress symptoms (PTSS) with a growing literature of evidence suggesting efficacy, lower drop-out rates compared to other evidence-based protocols, and long-term treatment gains. This proof-of-concept study examined the efficacy of WET delivered via telehealth compared to expressive writing (EW), the protocol from which WET was derived. The sample included non-treatment-seeking trauma-exposed undergraduate students (N = 33) with elevated PTSS. The results suggest that both WET, g = 1.26, and EW, g = 0.61, were associated with within-person decreases in PTSS. However, reliable change indices indicated that a significantly larger proportion of individuals in the WET condition (61.5%) demonstrated reliable symptom improvement compared to those who received EW (20.0%), g = 0.91. Contrary to our hypotheses, the WET and EW groups did not differ on reliable slopes of change; however, between-group effects were underpowered and should be interpreted with caution. These findings offer preliminary support for WET delivered via telehealth, including for individuals with subthreshold PTSS.

Dietary intake of acrylamide in the Norwegian EuroMix biomonitoring study: Comparing probabilistic dietary estimates with haemoglobin adduct measurements.

Acrylamide is a probable human carcinogen with widespread exposure via food. The present study compared acrylamide intake measurements obtained from haemoglobin adduct levels and self-registered dietary consumption data in a group of 144 Norwegian healthy adults. Acrylamide adducts to N-terminal valine in haemoglobin were measured and used to estimate the intake via the internal dose approach which showed a median (interquartile range) of 0.24 (0.19-0.30) μg/kg bw/day. Data from weighed food records and food frequency questionnaires from the same individuals were used for probabilistic modelling of the intake of acrylamide. The median acrylamide intake was calculated to be 0.26 (0.16-0.39) and 0.30 (0.23-0.39) μg/kg bw/day, respectively from the two sources of self-registered dietary consumption data. Overall, a relatively good agreement was observed between the methods in pairwise comparison in Bland-Altman plots, with the methods disagreeing with 7% or less of the values. The intake estimates obtained with the two dietary consumption methods and one biomarker method are in line with earlier dietary estimates in the Norwegian population. The Margin of Exposure indicate a possible health risk concern from dietary acrylamide. This is the first study with a comparison in the same individuals of acrylamide intake estimates obtained with these methods.

Analysis of the impact of COVID-19 pandemic and response on routine childhood vaccination coverage and equity in Northern Nigeria: a mixed methods study

BackgroundBased on 2021 data, Nigeria had the second largest number of zero-dose children globally estimated at over 2.25 million, concentrated in the northern part of the country due to factors...

Adverse childhood experiences: a meta-analysis of prevalence and moderators among half a million adults in 206 studies.

Exposure to adverse childhood experiences (ACEs), including maltreatment and family dysfunction, is a major contributor to the global burden of diseaseand disability. With a large body of international literature on ACEs having emerged over the past 25 years, it is timely to now synthetize the availableevidence to estimate the global prevalence of ACEs and, through a series of moderator analyses, determine which populations are at higher risk. We searched studies published between January 1, 1998 and August 5, 2021 in Medline, PsycINFO and Embase. Study inclusion criteria were using the 8- or 10-item ACE Questionnaire (±2 items), reporting the prevalence of ACEs in population samples of adults, and being published in English. The review protocol was registered with PROSPERO (CRD42022348429). In total, 206 studies (208 sample estimates) from 22 countries, with 546,458 adult participants, were included. The pooled prevalence of the five levels of ACEs was: 39.9% (95% CI: 29.8-49.2) for no ACE; 22.4% (95% CI: 14.1-30.6) for one ACE; 13.0% (95% CI: 6.5-19.8) for two ACEs; 8.7% (95% CI: 3.4-14.5) for three ACEs, and 16.1% (95% CI: 8.9-23.5) for four or more ACEs. In subsequent moderation analyses, there was strong evidence that the prevalence of 4+ ACEs was higher in populations with a history of a mental health condition (47.5%; 95% CI: 34.4-60.7) and with substance abuse or addiction (55.2%; 95% CI: 45.5-64.8), as well as in individuals from low-income households (40.5%; 95% CI: 32.9-48.4) and unhoused individuals (59.7%; 95% CI: 56.8-62.4). There was also good evidence that the prevalence of 4+ ACEs was larger in minoritized racial/ethnic groups, particularly when comparing study estimates in populations identifying as Indigenous/Native American (40.8%; 95% CI: 23.1-59.8) to those identifying as White (12.1%; 95% CI: 10.2-14.2) and Asian (5.6%; 95% CI: 2.4-10.2). Thus, ACEs are common in the general population, but there are disparities in their prevalence. They are among the principal antecedent threats to individual well-being and, as such, constitute a pressing socialissue globally. Both prevention strategies and downstream interventions are needed to reduce the prevalence and mitigate the severity of the effects of ACEs and thereby reduce their deleterious health consequences on future generations.

Point estimation and related classification problems for several Lindley populations with application using COVID-19 data

ABSTRACT The problems of point estimation and classification under the assumption that the training data follow a Lindley distribution are considered. Bayes estimators are derived for the parameter of the Lindley distribution applying the Markov chain Monte Carlo (MCMC), and Tierney and Kadane's [Tierney and Kadane, Accurate approximations for posterior moments and marginal densities, J. Amer. Statist. Assoc. 81 (1986), pp. 82–86] methods. In the sequel, we prove that the Bayes estimators using Tierney and Kadane's approximation and Lindley's approximation both converge to the maximum likelihood estimator (MLE), as n → ∞ , where n is the sample size. The performances of all the proposed estimators are compared with some of the existing ones using bias and mean squared error (MSE), numerically. It has been noticed from our simulation study that the proposed estimators perform better than some of the existing ones. Applying these estimators, we construct several plug-in type classification rules and a rule that uses the likelihood accordance function. The performances of each of the rules are numerically evaluated using the expected probability of misclassification (EPM). Two real-life examples related to COVID-19 disease are considered for illustrative purposes.

Relationships of walking activity with depressed mood and suicidal ideation among the middle-aged Korean population: a nationwide cross-sectional study.

The suicide rate of middle-aged adults has increased rapidly, which is a significant public health concern. A depressed mood and suicidal ideation are significant risk factors for suicide, and non-pharmacological interventions such as exercise therapy have been suggested as potential treatments. Walking is a feasible and accessible form of exercise therapy for middle-aged adults. We conducted a study based on the Seventh Korea National Health and Nutrition Examination Survey (2016-2018) data of 6,886 general middle-aged adults in South Korea to investigate the relationships of walking exercise with depressed mood and suicidal ideation. Multiple logistic regression analysis was used to adjust for confounding variables. Sampling weights were applied to obtain estimates for the general Korean population. Participants who walked ≥5 days per week had a significantly lower odds ratio (OR) for depressed mood [OR = 0.625, 95% confidence interval (CI): 0.424-0.921, p = 0.018] and suicidal ideation (OR = 0.252, 95% CI: 0.125-0.507, p < 0.001) compared to those who never walked, regardless of the duration of exercise. The same results were obtained for males after stratifying the data by sex and suicidal ideation was associated with walking in females. Regular walking exercise was associated with diminished mental health problems in middle-aged adults. Light walks may serve as a useful starting point for patients with serious mental health issues, such as suicidal ideation.

Impact of COVID-19 on subnational variations in life expectancy and life disparity at birth in India: evidence from NFHS and SRS data

BackgroundMeasuring life expectancy and life disparity can assist in comprehending how the COVID-19 pandemic has affected the mortality estimates in the Indian population. The present study aims to study the life expectancy and life disparity at birth at the national and subnational levels before and during the COVID-19 pandemic using the NFHS and SRS data.MethodsThe measures Life expectancy at birth ({e}_{0}) and Life disparity at birth ({e}_{0}^{dagger}) were computed for the non-pandemic and pandemic years from NFHS (2015–16), SRS (2015) and NFHS (2019–21), SRS (2020) respectively at the national and Subnational level in India. Using NFHS data for the 36 states and SRS data for the 22 states, the study calculates {e}_{0} and {e}_{0}^{dagger} by total, male and female population.ResultsThe {e}_{0} for male and female decline from 64.3 years and 69.2 years in 2015–16 to 62.9 years and 68.9 years in 2019–21. The {e}_{0} shows a drop of approximately 1.4 years for males and 0.3 years for females in the pandemic year 2019–21 when compared to the non-pandemic year 2015–16. At the subnational level {e}_{0} shows a decline for 22 states in person, 23 states in males and 21 states in females in the pandemic year 2019–21 as compared to the non-pandemic years 2015–16. The {e}_{0}^{dagger} shows a increase for 21 states in person, 24 states in females and 17 states in males in the pandemic year than non-pandemic year. The findings shows a significant losses in {e}_{0} and gains in {e}_{0}^{dagger} for males than females in the pandemic year as compared to the non-pandemic year at the subnational level in India.ConclusionsCOVID-19 pandemic has decreased {e}_{0} and increased {e}_{0}^{dagger} in the pandemic year 2019–21 at the national and subnational level in India. COVID-19 had a significant impact on the age pattern of mortality for many states and male, female population and delayed the mortality transition in India.

A new system for cuffless blood pressure measurement

High blood pressure (HBP) increases the risk of cardiovascular, brain, and renal diseases which can lead to severe illness and death. Due to the variability of BP values at different times during the day, continuous BP measurement would allow more effective early diagnosis of elevated blood pressure, and aid in the management of treatment. Various techniques have been proposed for cuffless BP measurement, often relying on the estimation of pulse transit time (PTT) to infer BP. However, challenges such as computational complexity and limited availability of BP monitoring sensors hinder the reliable and widespread implementation of continuous BP measurement. The proposed wristwatch-based system uses speech sounds together with photoplethysmogram (PPG) and electrocardiogram (ECG) signals, and uses a mathematical model which estimates the systolic BP (SBP) and diastolic BP (DBP) from these inputs.We have obtained Pearson correlation coefficient (PCC)s of 0.6094 for systolic BP and 0.6001 for diastolic BP in these experiments. The mean average errors (MAE) obtained are 8.06 mmHg for systolic BP and 7.48 mmHg for diastolic BP, respectively. This study provides meaningful results based on experimental outputs, demonstrating the feasibility of using speech signals in conjunction with PPG and ECG signals for BP estimation. The simplicity of our mathematical model enables efficient and practical implementation in real-time BP monitoring. As a pilot study, our work establishes a foundation for further research, emphasizing the need for enhancing accuracy and reliability, expanding the dataset, and exploring additional physiological parameters to advance continuous BP estimation.Our findings advance the development of cuffless BP monitoring, and address the computational complexity and real-time processing requirements. Future studies should build upon our work to refine and optimize the proposed approach, ultimately leading to improved continuous BP estimation in diverse populations.

Saturn’s ancient regular satellites

Are Saturn’s regular satellites young or old? And how old are Enceladus’ cratered plains? To answer these questions we computed model surface ages of the most heavily cratered terrains on Saturn’s regular icy satellites using new high-resolution outer Solar System evolution simulations, and coupled with improved estimates of the trans-Neptunian objects populations. The output of the simulations allowed us to construct a model impact chronology onto Saturn which automatically applies to its regular satellites. We used crater densities and our impact chronology onto Saturn to construct model impact-crater isochrons, i.e., the scaling of the satellite crater production function with time. The surface ages derived for the cratered plains on Mimas, Enceladus, Tethys, Dione and Rhea range from 4.1 Ga to 4.4 Ga, with the surfaces of Mimas and Enceladus roughly 200 Myr younger than those of the outer three satellites. Uncertainties in these ages are less than 300 Myr. The calculated model surface ages of these satellites are consistent over as much as two orders of magnitude in the observed crater diameter. The similarity of the crater production function amongst all satellites suggests that they were bombarded by a single impactor source. This work supports the idea that Saturn’s regular satellites are ancient, and has implications for their formation and their tidal evolution.

Density estimation for an island population of raccoon dogs in Japan using fecal DNA

Estimation of the population size is essential for understanding population dynamics. Estimating animal density using multiple methods and/or multiple attempts is required for accurate estimations. Raccoon dog Nyctereutes procyonoides is native to East Asia, including Japan, and has become an invasive species in Europe. Information on raccoon dog density in their native range is important to understand their invasion; however, relatively few studies have been conducted on raccoon dog density in their native range. In this study, we extracted DNA from fecal samples of raccoon dogs inhabiting a small island in Japan and conducted density estimation over two periods using DNA capture‐recapture methods: CAPWIRE and SECR. We also investigated sex ratio using genetic sex identification. Density estimates using SECR were approximately threefold different between the two study periods: 17.2 individuals per km2 in 2018 and 49.0 individuals per km2 in 2020. In contrast, estimates using CAPWIRE were relatively stable: 21.7 individuals per km2 in 2018 and 24.3 individuals per km2 in 2020. A drastic increase or decrease is not expected during the study period, and thus, density estimates using CAPWIRE are more reasonable than those using SECR. The small number of samples per individual might result in low accuracy of density estimates by SECR. The density estimated by CAPWIRE was similar to that in the main island in Japan and higher than that in Europe. Feeding competition with other omnivorous carnivores and/or predation risk by wolves might maintain the low density in Europe. The sex ratio of raccoon dogs was 1:1, which was similar to the values in invasive raccoon dogs and other canids. Further genetic census, including sex identification in various landscapes in their native and invasive range, will enable us to understand not only the ecology of raccoon dogs but also their adaptations to their invading areas.

Extended Use of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) 52 mg: A Population Pharmacokinetic Approach to Estimate In Vivo Levonorgestrel Release Rates and Systemic Exposure Including Comparison With Two Other LNG-IUSs

ABSTRACT With over 30 years of use, levonorgestrel-releasing intrauterine systems (LNG-IUSs) have proven to be highly effective methods of contraceptives. The active ingredient in LNG-IUS, levonorgestrel (LNG), is released directly into the uterine cavity, which causes suppression of endometrial maturation and thickened cervical mucus. A variety of LNG-IUS options exhibit well-established safety profiles and efficacy, providing anywhere between 2 and 18 times lower systemic exposure when compared with LNG-containing pills or implants. Patient-centered decision-making regarding product choice may be encouraged through standardized comparisons of LNG release and exposure during the time of their respective usage periods. Evaluation of the efficacy, safety, and PK of extended Mirena use from beyond 5 years to the conclusion of 8 years was designed in the Mirena Extension Trial (MET), thereby facilitating comparisons with LNG-IUS 19.5 mg and LNG-IUS 13.5 mg. Using validated liquid chromatography-tandem mass spectrometry methods and SHBG concentrations, the authors determined concentrations of plasma LNG levels. Dichloromethane was used for extracting residual LNG from the elastomer material from removed IUS devices, which was then quantified via liquid chromatography and external calibration on a reversed-phase column. Although previous models used measured LNG and SHBG (serum) concentrations, the population pharmacokinetics (popPK) allows for a uniform method of comparison among different pharmacologic studies. The popPK approach allows for a reliable estimates of in vivo LNG exposure and release during the entirety of the 8-year use period. The MET enrolled premenopausal women aged 18–35 years for a multicenter, single-arm study regarding patients who had used LNG-IUS 52 mg for the last 4.5–5 years for up to 8 years. The study took place from December 22, 2016 to May 28, 2021 throughout 54 US centers, with the primary outcome of contraceptive efficacy and failure rate. Participants each provided written, informed consent. Study strengths of the popPK approach included its robust methodology, its ability to provide in vivo release rate estimates, a stepwise demo of model suitability from use years 6 to 8, model-based estimation of unbound LNG, and the ability to provide estimates for both population and individual PK profiles from sparse available sampling. Limitations include the possibility of findings being group effects possibly inapplicable to all LNG-IUS users. In addition, the data fail to provide local endometrial and cervical LNG concentrations due to the systemic nature of the LNG exposure. Finally, the popPK Mondale should not be used for theoretical question addressing (such as creating rate release estimates outside of available data sets). In conclusion, a broad data set indicates that reliable LNG exposure is delivered by 8-year popPK and release models for up to 7 years of LNG-IUs 52 mg use. Efficacy is data-supported for 6–8 years of use, with constant LNG release throughout this time frame. Systemic LNG exposure from LNG-IUD 52 mg proved both comparable to other LNG-IUS devices and significantly lower than oral and implanted LNG-containing contraceptives.

Parasite exchange and hybridisation at a wild-feral-domestic interface

Interactions between wild, feral, and domestic animals are of economic and conservation significance. The pigeon Columba livia is a synanthropic species in a feral form, but it also includes the rare Rock Dove. Columba livia is an important player at the wild-domestic interface, acting as a carrier of avian diseases, and the feral form threatens Rock Doves with extinction via hybridisation. Despite its abundance, little is known about drivers of disease prevalence in C. livia, or how disease and hybridisation represent synergistic threats to Rock Doves. We focused on infection by the parasite Trichomonas, first collating prevalence estimates in domestic and free-living populations from relevant studies of C. livia. Second, we characterised variation in the diversity and prevalence of Trichomonas among three C. livia populations in the United Kingdom: a feral, a Rock Dove, and a feral-wild hybrid population. Across multiple continents, free-living pigeons had lower Trichomonas infection than captive conspecifics, but the effect was weak. Environmental factors which could impact Trichomonas infection status did not explain variation in infection among populations. Among the British populations, strain diversity varied, and there was lower parasite prevalence in Rock Doves than feral pigeons. Individual infection status was not explained by the available covariates, including hybrid score and site. The drivers of Trichomonas prevalence are unclear, perhaps due to idiosyncratic local-scale drivers. However, given the population-level variation in both infection prevalence and introgressive hybridisation, the potential combined effects could accelerate the extinction of the Rock Dove. Further study of the synergistic effects of multiple types of biotic interactions at the wild-feral-domestic interface is warranted, especially where vagile, globally distributed and superabundant animals are involved.

Eastern High Arctic–Baffin Bay beluga whale (Delphinapterus leucas) estuary abundance and use from space

IntroductionThe Eastern High Arctic–Baffin Bay (EHA-BB) beluga whale (Delphinapterus leucas) population spends summer in estuaries around Somerset Island, Nunavut, Canada. A single abundance estimate from 1996 suggests an abundance &amp;gt;21,000 beluga whales; however, more information on abundance and distribution is needed to ensure effective management of this population, especially in estuaries where previous surveys provided minimal coverage. To assess the feasibility of using Very High Resolution (VHR) satellite imagery to obtain estuary abundance estimates for this beluga population, we evaluated a citizen science crowd counting initiative that was designed to monitor remote beluga whale populations and their estuary use.MethodsIn July and August 2020 the WorldView 2 and 3, and GeoEye 1 satellites were tasked to collect VHR imagery (30–41 cm) of estuaries previously known to be used by Eastern High Arctic–Baffin Bay beluga whales. The objectives were to obtain an estuary abundance estimate for this population from satellite imagery, and to evaluate the effectiveness of having imagery annotated using a crowd-source platform. Almost 3,800 km2of ocean imagery was analyzed using Maxar’s Geospatial Human Imagery Verification Effort (GeoHIVE) Crowdsourcing platform. Expert readers then manually compared counts to those performed by crowd-counters to determine variance in observer counts.Results and DiscussionThe estuary abundance estimate from 11 core estuaries was 12,128 (CV 36.76%, 95% confidence interval 6,036–24,368) beluga whales. This represents an estuary abundance estimate only, as the greater Peel Sound and Prince Regent Inlet areas were not photographed. The estuaries with the largest abundance of beluga whales were Creswell Bay, Maxwell Bay, and Prince Whales Island, with over 2,000 crowd-counted whales in each estuary. Although VHR imagery has potential to assist with surveying and monitoring marine mammals, for larger estuaries it was not always possible to photograph the entire area in a single day, and cloud cover was an issue for sections of most images. This work will assist with planning large-scale aerial surveys for monitoring beluga whale populations, identifying high-use areas and important beluga habitat, and highlights the utility of using VHR imagery to enhance our understanding of estuary abundance and distribution of Arctic whales.

Estimates of diagnosed dementia prevalence and incidence among diverse beneficiaries in traditional Medicare and Medicare Advantage.

Approximately half of Medicare beneficiaries are enrolled in Medicare Advantage (MA), a private plan alternative to traditional Medicare (TM). Yet little is known about diagnosed dementia rates among MA enrollees, limiting population estimates. All (100%) claims of Medicare beneficiaries using encounter data for MA and claims for TM for the years 2015 to 2018 were used to quantify diagnosed dementia prevalence and incidence rates in MA, compare rates to TM, and provide estimates for the entire Medicare population and for different racial/ethnic populations. In 2017, dementia incidence and prevalence among MA beneficiaries were 2.54% (95% confidence interval [CI]: 2.53 to 2.55) and 7.04% (95% CI: 7.03 to 7.06). Comparison to TM adjusted for sociodemographic and health differences among beneficiaries in MA and TM; the prevalence of diagnosed dementia among beneficiaries in MA was lower (7.1%; 95% CI: 7.12 to 7.13) than in TM (8.7%; 95% CI: 8.71 to 8.72). The diagnosed dementia incidence rate was also lower in MA (2.50%; 95% CI: 2.50 to 2.50) compared to TM (2.99%; 95% CI: 2.99 to 2.99). There were lower rates in MA compared to TM for men and women and White, Black, Hispanic, Asian, American Indian/Alaska Native persons. Diagnosed dementia prevalence and incidence for the entire Medicare population was 7.9% (95% CI: 7.91 to 7.93) and 2.8% (95% CI: 2.77 to 2.78). Lower diagnosed dementia rates in MA compared to TM may exacerbate racial/ethnic disparities in diagnosed dementia. Rates tracked over time will provide understanding of the impact on dementia diagnosis of 2020 MA risk adjustment for dementia.

Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging

ObjectiveAs thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed. MethodsWe determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual. ResultsOne hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 μg/kg (1.35 μg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 μg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 μg/kg vs 1.14 μg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 μg/kg IBW; P = .41) compared with those with a body mass index of <30. ConclusionThyroid hormone dose per body weight estimates for replacement in older adults (1.09 μg/kg ABW or 1.35 μg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.

Robust sample weighting to facilitate individualized treatment rule learning for a target population

Summary Learning individualized treatment rules is an important topic in precision medicine. Current literature mainly focuses on deriving individualized treatment rules from a single source population. We consider the observational data setting when the source population differs from a target population of interest. Compared with causal generalization for the average treatment effect that is a scalar quantity, individualized treatment rule generalization poses new challenges due to the need to model and generalize the rules based on a prespecified class of functions that may not contain the unrestricted true optimal individualized treatment rule. The aim of this paper is to develop a weighting framework to mitigate the impact of such misspecification, and thus facilitate the generalizability of optimal individualized treatment rules from a source population to a target population. Our method seeks covariate balance over a nonparametric function class characterized by a reproducing kernel Hilbert space and can improve many individualized treatment rule learning methods that rely on weights. We show that the proposed method encompasses importance weights and overlap weights as two extreme cases, allowing for a better bias-variance trade-off in between. Numerical examples demonstrate that the use of our weighting method can greatly improve individualized treatment rule estimation for the target population compared with other weighting methods.

#6737 ESTIMATED GLOMERULAR FILTRATION RATE BY FIVE DIFFERING MEASURES, RACE, GENETIC RISK AND PREDICTION OF CARDIOVASCULAR DISEASE AND MORTALITY

Abstract Background and Aims Estimated glomerular filtration rate (eGFR), a significant measurement of chronic kidney disease (CKD), is associated with adverse health outcomes in the general population but whether its utility differs by race and genetic risk remains unclear. The current study aims to investigate the performance of CKD staging and risk prediction in cardiovascular disease and mortality based on five eGFR measures among people of different ethnic groups and genetic background. Method In this prospective cohort study, we included 431,126 participants from the UK Biobank, deriving hazard ratios and 95% confidence intervals from multivariable adjusted Cox proportional hazards models. C statistic and net reclassification improvement (NRI) were utilized for comparing the predictive benefit of eGFR measures when added to the traditional cardiovascular risk factors. Results Over a median of 13.4 (IQR 12.7-14.9) years of follow-up, 27,757 (6.4%) participants died from any cause, of which 3272 (0.8%) died primarily from CVD. 39,522 (9.2%) incident composite CVD hospitalization and 911 (0.2%) ESRD occurred. Two new eGFR equations refitted without race provided lower estimates in Black population but higher in other ethnic backgrounds than the corresponding old ones. The relative risk of adverse outcomes was generally greater in Blacks and participants with low genetic susceptibility to impaired kidney function. The superiority of cystatin C-based eGFR measures in risk prediction did not differ by race and genetic risk. Conclusion Eliminating the use of racial categories in eGFR calculation help enhance the access to specialist care and intervention at the early stage of CKD for Black population. Cystatin C-based eGFR measures can be extensively used in risk assessment in clinical practice.

#4028 INSIDE CKD: PROJECTING THE POPULATION LEVEL CLINICAL BURDEN OF CHRONIC KIDNEY DISEASE ACCORDING TO URINE ALBUMIN-TO-CREATININE RATIO CATEGORIES

Abstract Background and Aims Chronic kidney disease (CKD) and its associated complications constitute a major challenge for healthcare systems worldwide. Albuminuria, measured as albumin-to-creatinine ratio (uACR), is a critical marker of glomerular injury and endothelial dysfunction. Elevated uACR is an independent predictor of CKD progression and cardio-renal mortality [1,2]. However, there is a paucity of data translating the burden of CKD at the population level according to uACR categories, in order to promote evidence-based policies. This study aims to assess the future epidemiological and financial burden of CKD using the Inside CKD microsimulation [3]. Specifically, we report CKD population level projections for cardio-renal complications, progression to end stage kidney disease (ESKD), and death due to any cause according to uACR categories. Method The Inside CKD microsimulation was used to simulate virtual individuals from 28 countries and regions. Individuals were assigned baseline characteristics such as age or sex based on national statistics, and estimated glomerular filtration rate (eGFR), uACR, CKD stage, and cardio-renal complications based on data from national health surveys or epidemiological studies. The following cardio-renal complications were projected between 2022 and 2027 according to uACR categories (normo-, micro-, macro-albuminuria): myocardial infarction (MI), stroke, heart failure (HF), CKD transition from stage 3 to 4 and from 4 to 5 (defined as a change in either eGFR or uACR category), and death due to any cause. Results Projected estimates for the total CKD population (all stages) with macro-albuminuria varied by country and region for 2023 (mean = 9.8%, range = 1.6% – 40.2%). The lowest percentages of macro-albuminuria (&amp;lt; 5%) were in Romania, Belgium, and the UK, compared to the highest (≥ 27%) in Brazil, Philippines and Mexico. Macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per person basis, but according to these estimates only a small proportion of the population have macro-albuminuria. Hence, the predominant CKD population with normo- or micro-albuminuria would be expected to account for most of the clinical burden. Accordingly, most of the cardio-renal incident events projected to occur by 2027 will be in the population with normo- or micro-albuminuria in all countries and regions (Figure 1): MI (97.9%), stroke (96.5%), HF (98.0%), the transition from CKD stage 3 to 4 (94.9%) and from stage 4 to 5 (97.5%), and death due to any cause (95.6%) (percentages represent mean and included the combined normo- and micro-albuminuria populations). Conclusion Although, macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per patient basis, the total CKD population should be considered with regards to the clinical burden in absolute terms. The Inside CKD microsimulation supports early intervention in the total CKD population, including individuals with normo- or micro-albuminuria, to reduce cardio-renal outcomes, delay progression to ESKD, and therefore the requirement for costly interventions, including heart related hospitalisations, transplantation and dialysis.

MSR31 Applying Multi-Level Network Meta-Regression (ML-NMR) to a Case Study in Triple-Class Exposed (TCE) Relapsed/Refractory Multiple Myeloma (RRMM)

BACKGROUND: ML-NMR provides a framework for defining an individual-level regression model, which is integrated over aggregate populations to form an aggregate-level model. ML-NMR avoids aggregation bias and produces estimates in any target population. ML-NMR has been published and applied to binary outcomes, but not time-to-event outcomes.