Burden Of Disease Research Articles

#1432 Prevalence, risks and treatment of incident chronic kidney disease stage 3-4: an observational study in Finland between 2016-2022

Abstract Background and Aims The rising burden of chronic kidney disease (CKD) calls for early detection and targeted interventions. Kidney-protective treatments (renin–angiotensin system inhibitors [RASis] and sodium-glucose co-transporter-2 inhibitors [SGLT2is]) can delay chronic kidney disease (CKD) progression, cardiovascular events and death. However, contemporary differences between CKD patients with and without type 2 diabetes (T2D) is limited. This study aimed to describe the prevalence, patient characteristics, the use of kidney protective treatments (RASi or SGLT2i) and event risks among patients with incident stage 3-4 CKD in Finland. Method We used comprehensive real-world clinical data from electronic health records from primary and hospital care in five municipalities in Finland between 1st January 2016 to 31st December 2022 to identify stage 3-4 CKD patients aged ≥18 years, defined as having either one estimated glomerular filtration rate (eGFR) measurement between 15 to 60 ml/min/1.73 m2 followed by a second one ≥90 days apart, or a registered CKD diagnosis. Two cohorts from primary care were identified: a prevalent cohort indexed at a fixed date, 1st Jan 2022 and an incident cohort indexed at the date of new CKD. The incident CKD patients were followed from CKD incident index date until death, emigration, or end of study on 31 December 2022. Analyses were also stratified by CKD patients with T2D and non-diabetes (T1D and gestational diabetes excluded), respectively. Risks were estimated as event rates per 1000 patient-years. The proportion of patients on/off treatment were estimates as a function of time and divided into pre- vs. post-index. Results In 2022 the prevalent cohort of 16,380 CKD stage 3-4 patients, represented a prevalence of 6.2% in the total background population of 263,383 individuals. The 12,129 incident Stage 3-4 CKD patients had a median eGFR of 55 ml/min/1.73 m2, similar in both non-T2D and T2D. Most patients were non-T2D; 73% (n = 8859). At index, 1.7% had a CKD diagnosis, lower in non-T2D (1.0%) vs T2D (3.5%) patients. The use of urine albumin creatinine ratio (UACR) was generally very low (21% had a measurement), 9% in the non-T2D and 53% in the T2D patients. Non-T2D, compared to T2D patients, were similar in age (76 vs 75 years) and had slightly less comorbidities like HF (12% vs 18%), myocardial infarction (9% vs 14%), stroke (15% vs 16%), atrial fibrillation (21% vs 25%) and less treated with statins (38% vs 64%). During follow-up, 10% had died within 1-year (97 deaths per 1000 patient years), similar in non-T2D (95 deaths per 1000 patient years) and T2D patients (104 deaths per 1000 patient years). One year risk of any hospitalization was also high, 49% and 64%, respectively. The use of kidney-protective treatments (renin angiotensin system inhibitor [RASi] or SGLT2i) at index (date of incident CKD) was lower in patients without T2D (47%) compared to those with T2D (69%). No change was observed in their use in the 12 months after incident CKD (Fig.). Finally, when studying the proportion of all non-T2D patients receiving SGLT2i after approval for CKD treatment, less than 1% of all CKD patients in the study group were treated with SGLT2i on 31st December 2022. Conclusion This study shows that CKD stage 3-4 is highly prevalent in Finland. Newly detected CKD stage 3-4 patients were little diagnosed and the use of UACR was low, especially among those who were non-diabetic. More than 2 out of 3 CKD patients were non-diabetic. Importantly, these non-diabetic CKD patients had similarly high disease burden, similar high risk of dying and had less kidney/cardiovascular prevention compared to those with T2D. The high mortality risks, substantial kidney-protective treatment inertia and UACR underutilization in stage 3-4 CKD patients all call for an urgent need for improved awareness and risk management, especially in the larger group of non-T2D.

#1212 Trends in real-world lipid lowering therapy use among adult patients with chronic kidney disease: 5-year single center experience in the Philippines

Abstract Background and Aims Patients with chronic kidney disease (CKD) carry an extremely high burden for atherosclerotic cardiovascular disease (ASCVD), which worsens as CKD progresses. Several international guidelines, including the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, have recommended the use of lipid-lowering therapy (LLT) in this high-risk population. To evaluate the implementation of these recommendations in real-world practice, we assessed patterns of dyslipidemia management among patients with CKD. Specific objectives include describing the prevalence and intensity of LLT prescription [stratified by estimated glomerular filtration rate (GFR) and whether requiring renal replacement therapy or not] as well as adherence to guideline recommendations on LLT use. Method We conducted a single-center, cross-sectional study covering the period of January 2019 to December 2023. A review of inpatient and outpatient medical records of the Department of Medicine, University of the Philippine—Philippine General Hospital was done. Eligible patients were at least 18 years of age, and diagnosed with CKD. Exclusion criteria included having a concomitant diagnosis of Acute Kidney Injury, and being pregnant or breastfeeding at any point in the study period. Sociodemographic, clinical, and laboratory data were based off the latest entry in each patient's medical record. No clinical data were collected beyond those that were available on the records. Classification of statin intensity was based on the 2019 American Heart Association/American College of Cardiology Guidelines on the Management of Blood Cholesterol as well as the 2020 Philippine Clinical Practice Guidelines on the Management of Dyslipidemia. All analyses were descriptive and done using STATA 18. Categorical variables were summarized as frequencies and percentages. Continuous variables were reported as measures of central tendency [i.e. mean (SD) or median (IQR), as appropriate]. Results Of the 3845 patients included in the study, 2922 (76%) were prescribed LLT. The most common LLT were statins (92%), followed by statin/ezetimibe combinations (6%), then statin/fibrate combinations (2%). None were prescribed PCKS9 inhibitors, niacin, omega-3 fatty acids, or bile acid sequestrants. Among non-dialytic patients, the distribution of LLT use was as follows: a) eGFR ≥ 60 ml/min/1.73 m2: 40% (173/431) b) eGFR 30-60 ml/min/1.73 m2: 76% (1198/1576) c) eGFR <30 ml/min/1.73 m2: 84% (1551/1838). Among dialytic patients, 68% (601/884) were already on LLT prior to initiation of dialysis while 35% (283/884) were started on LLT after dialysis initiation. Notably, 89% (786/884) of these dialytic patients were still on moderate-to-high-intensity statin doses. Based on recommendations from the 2013 KDIGO guidelines, only 78% (2610/3334) of eligible patients were prescribed on LLT, while 61% (312/511) of ineligible patients were prescribed on LLT. Similar rates of adherence were seen to other international guideline recommendations on the management of dyslipidemia in CKD (e.g. 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol, 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemias, 2020 Clinical Practice Guidelines for the management of dyslipidemia in the Philippines). Conclusion Real-world LLT use among CKD patients remains high, even at lower eGFRs. More importantly, a large proportion of patients remain under- and over-treated, highlighting significant gaps between guideline recommendations and real-world clinical practice. Further investigation regarding the underlying reasons for these practice variations is necessary to improve quality of care, and safely reduce the burden of dyslipidemia and ASCVD among CKD patients.

#2617 Impact of CKD screening in high‑risk populations and guideline-directed therapy on RRT, CV events, and mortality in Europe: an IMPACT CKD analysis

Abstract Background and Aims Despite the rising and substantial burden of chronic kidney disease (CKD), there is a lack of recognition of CKD as a health priority in Europe. This contributes to underdiagnosis of CKD despite the potential for early detection and effective intervention to delay progression to late-stages (associated with costly and resource-intensive renal replacement therapy [RRT; i.e., dialysis and transplantation]). Further, diagnosed patients are undertreated when compared to current and upcoming CKD guidelines, leading to increased risk for progression to RRT and cardiovascular (CV) or other events. Early detection and intervention in high-risk populations, such as those with diabetes mellitus (DM) and hypertension (HTN) have shown cost-effectiveness; however, the broader implications of these strategies on CKD progression and clinical outcomes in a European context remains underexplored. Our study aims to illustrate the clinical benefit of targeted screening followed by an optimal compliance to guideline-directed treatment use to provide insight into potential CKD policies across Europe. Method Four country populations (Germany, Netherlands, Spain, United Kingdom [UK]) were simulated for 10-years (baseline: 2022; simulated years: 2023-2032) using the validated IMPACT CKD model to compare two scenarios: targeted screening for people with DM and/or HTN followed by 90% compliance to guideline-directed therapy versus current practice (i.e., underdiagnosis without screening and low treatment rates). Annual targeted screening was modelled using estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing. Initiation of therapies for people with diagnosed CKD was based on Kidney Disease Improving Global Outcomes guidelines. A 90% compliance to guideline-directed therapies was assumed to approximate maximum clinical benefit. Current practice was modelled based on the observed diagnosed rate without screening and the observed treatment rate in each country. The incremental population initiated on recommended therapies were modelled to experience a multiplicative treatment effect on GFR decline, CV events, and acute kidney injury (AKI) events. The model projected CKD and RRT prevalence, incidence of CV and AKI events with results shown for year 10 (2032), as well as cumulative all-cause mortality over the simulated 10-years. Results Results compare the high-risk population screening followed by guideline-directed treatment scenario to continuation of current practices for the four countries (Fig. 1). The identification of undiagnosed CKD, as well as lower rates of progression due to guideline-directed treatment was associated with a small rise in the number of total CKD patients, with increases in stage 1-2 by 3.5% to 5.0%, and stage 3-5 by 0.2% to 1.2%. There was a reduction in the number of undiagnosed CKD stage 1-2 patients by 49.2% to 71.6%, and stage 3-5 by 60.2% to 69.8%. The largest reductions were predicted for CV events (44.6% to 49.1%) followed by dialysis (22.6% to 41.9%). The strategy resulted in a decrease in cumulative 10-year all-cause mortality between 4.5% to 9.1% in CKD patients. Conclusion The study predicted significant clinical benefits from targeted CKD screening followed by guideline-directed interventions across all four European countries. Notably, this approach was forecasted to reduce undiagnosed CKD cases, dialysis, CV events, and mortality. These findings underscore the potential of acting earlier on CKD to mitigate the future CKD burden.

#2365 Spectrum and prevalence of renal pathologies: a retrospective analysis of biopsy data from a tertiary care center in India

Abstract Background and Aims Renal biopsy remains a cornerstone in diagnosing various nephropathies, providing vital insights into disease etiology and guiding therapeutic strategies. In India, where the burden of renal diseases is on the rise, characterizing the spectrum of renal pathologies through biopsy can significantly influence clinical outcomes. Despite increasing global data on kidney diseases, regional variations exist, and localized data from tertiary care centers in India are sparse. The primary objective of this study was to delineate the spectrum of renal diseases diagnosed via biopsy at a tertiary care center in New Delhi, India, over a seven-year period. Method This retrospective study analyzed records from a tertiary care center in New Delhi, India, from 2015 to 2022. Data were extracted from paper-based records and electronic medical records (EMR). The study included patients who underwent native kidney biopsy during this period. Graft biopsies and biopsies with inadequate samples were excluded. Biopsies were evaluated by nephropathologists, and diagnoses were categorized based on standardized criteria. Results Between 2015 and 2022, 1,174 renal biopsies were analyzed from patients aged 1.3 to 82 years, with an average age of 40.5 years, showing a male predominance (60%). Chronic Interstitial Nephritis was the most prevalent diagnosis at 14.58%, followed by Diffuse Global Glomerulosclerosis at 13.13%, and IgA Nephropathy at 12.77% (Table 1). In IgA Nephropathy patients (n = 141), the majority exhibited microhematuria (53.9%) and subnephrotic proteinuria (56.02%), while 24.82% presented with nephrotic range proteinuria. Lupus Nephritis was the most common secondary glomerular disease (6.34%). Within the Lupus Nephritis subgroup (n = 70), Class IV (34.29%) and Class V (24.28%) were the most observed classes, with a notable presence of combined Class III+V (10%) and Class IV+V (8.57%). Within the cohort, the most common primary glomerulonephritis diagnosed in the age group of 18-30 years was IgA Nephropathy. For the 30-60 years demographic, Membranous nephropathy was most frequently identified, while in those older than 60 years, Diabetic Glomerulosclerosis was predominant. In cases presenting with hematuria (n = 417), IgA Nephropathy was identified in 17.74%. Among those with rapidly progressive renal failure (n = 79), Pauci immune GN accounted for 46.83% of diagnoses, followed by IgA Nephropathy at 15.18%. For patients with nephrotic range proteinuria (n = 139), IgA Nephropathy, Membranous nephropathy, and FSGS were leading diagnoses, each accounting for 12.94%, 12.23%, and 12.23% respectively. Conclusion The analysis revealed IgA Nephropathy as the most common histopathological finding in renal biopsies. The primary indication for biopsy is nephrotic range proteinuria. In this category, IgA Nephropathy is also the most prevalent diagnosis. For patients with rapidly progressive renal failure, Pauci immune GN is the most frequent finding. Additionally, IgA Nephropathy is the leading cause in patients presenting with hematuria. Lupus Nephritis is the most common secondary glomerular disease with class IV being the most common biopsy finding. The study underscores the necessity for continued surveillance of renal pathology trends to inform healthcare strategies in India.

#2155 Evaluating the health-related quality of life of patients undergoing haemodialysis: highlights from a multicentric nationwide study

Abstract Background and Aims Haemodialysis (HD) represents the most common renal replacement therapy for end-stage renal disease worldwide. Despite recent advances in HD the health-related quality of life (HRQoL) should be monitored in conjunction with clinical variables to optimize a comprehensive treatment. Method From June to July 2022, all patients from 47 clinics were included. Among other key relevant clinical variables, HRQoL was assessed by using the Kidney Disease Quality of Life Short Form (KDQOL-SF™ 1.3).It`s generic part is summarised in the physical component summary (PCS) and mental component summary (MCS). The specific part evaluates 11 domains: symptom/problem list; effects of kidney disease on daily life; burden of kidney disease; work status; cognitive function; quality of social interactions; sexual function; sleep; social support; dialysis staff encouragement; and patient satisfaction. All scores range from 0 (worst) to 100 (best). To ensure comparability of results, mean ± SD values are outlined, even though non-parametric tests were used to test associations. Results A total of 3,595 patients (67.3% male) completed the KDQOL (out of 4259 HD patients treated during study period). Most of them (67.18%) were over 60yo of age, and 65.67% had a severe comorbidity index score. In addition, 50.54% had a native AV fistula and only 3.92% were incident HD. PCS scores reported were higher in over 75yo (47.68 ± 10.63) rather than normative population (40.16 ± 11.62), indicating an overall good physical function. However, MCS values (33.17 ± 9.36) were indicative of substantial impact. Gender differences were noted across almost all disease-specific and generic domains (all p < 0.05). Severe comorbidity scores were associated with lower scores in certain renal specific domains and MCS. Finally, incident HD patients reported lower satisfaction and poorer perceived overall health (p-values = 0.001). Conclusion Although PCS scores reported were reasonable, a remarkable impact on mental health was found. Moreover, a differential impact of patient's HRQoL was captured based on gender and other variables highlighting the need of individualised evaluation and management of HD patients.

#1479 Single nucleus RNA-sequencing indicates functional heterogeneity of renal endothelial cells in chronic kidney disease

Abstract Background and Aims The burden of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) remains very high. Endothelial cell (EC) dysfunction is an important key player in the initiation and progression of both pathologies. More importantly, endothelial dysfunction occurs early in both disease courses and is potentially reversible, making it a promising target for effective preventive strategies. Recently, accumulating single-cell RNA sequencing-based evidence has highlighted EC heterogeneity in different pathophysiological contexts. However, while biological processes such as systemic inflammation, oxidative stress fibrosis are being defined as comm EC in CKD and CVD, a comprehensive understanding of at single-cell resolution is lacking. Here, we characterized renal EC subpopulations by single-nucleus RNA sequencing (snRNA-seq) to investigate alterations in CKD patients healthy controls and identify potential drivers of EC dysfunction in CKD. Method Droplet-based snRNA-seq (10X Genomics Chromium) was performed on cryopreserved kidney biopsy cores from 6 human patients with CKD (eGFR < 45 mL/min/1.73 m2) and 3 healthy controls. CKD patients included 2 patients with primary focal segmental glomerulosclerosis (FSGS) and 4 with secondary/maladaptive FSGS (2 patients with diabetes mellitus, 2 female patients in total); all patients had a Framingham 10-year cardiovascular risk score > 20, but no established CVD. Healthy control samples were pre-perfusion biopsies from patients undergoing living kidney donation (including 2 female patients). EC subclusters were annotated based on the expression of canonical EC marker genes. Differential gene expression analysis for patient samples vs. controls included all ECs and DEGs were filtered for log2FC > 0.25 or < −0.25 and adjusted P-value of < .05. Gene set enrichment analysis (GSEA) on the identified DEGs was performed using GO terms. Results A total of 4 081 ECs were present in the dataset, consisting of 5 EC subtypes in both the patient and control cohorts (Panel A). DEGs in CKD patients vs. controls included upregulated genes related to organogenesis and cell differentiation (MEF2C, MEIS2), vascular development (FLRT2), and angiogenesis regulators (VEGFC, PRCP, HDAC9) (Panel B). Notably, VEGFC and FLRT2, are involved in directing EC motility and vascular patterning. In accordance, GSEA showed enrichment for GO biological processes related to vascular endothelial growth factor signaling pathway, endothelial cell differentiation, endothelial development, regulation of angiogenesis, and endothelial cell migration (Panel C). This suggests a potential link between these genes and aberrant angiogenesis, analogous to previous findings in diabetic nephropathy. Some but not all of these changes were also reported for renal ECs of early diabetic nephropathy patients. Of note, the majority of patients studied in our cohort were non-diabetic, warranting further investigation into renal endothelial cell transcriptional alterations that are general to renal disease or specific to particular renal conditions such as diabetic nephropathy. Differential gene expression and GSEA analysis of the EC subclusters in CKD indicated involvement of the peritubular capillary and ascending vasa recta ECs in EC migration / angiogenesis-related responses, overlapping with the overall analysis described above. Glomerular capillary ECs showed upregulation of immune-related genes and processes, reflecting the inflammatory status of the kidney disease. Conclusion snRNA-seq analysis revealed heterogeneity and subtype-specific gene expression alterations of renal ECs from CKD patients compared to healthy controls. Differential functions include enhanced angiogenic (potentially compensatory) and immune-related responses. These findings suggest that specific biological functions may direct different roles of the renal EC subtypes in CKD and will be further validated for their cluster-specificity and for their therapeutic relevance.

#1353 Apathy and fatigue in patients treated with haemodialysis and peritoneal dialysis

Abstract Background and Aims Apathy is a distinct syndrome manifesting with a loss of interest in social or emotional situations, lack of sense of purpose, low energy levels and detachment from life and personal events. Previous studies showed that apathy is associated with vascular impairment and consequent cognitive dysfunction, reduced quality of life and increased hospitalization, institutionalization, healthcare costs and death. So far there has been little research on the prevalence of apathy among dialysis patients although this population could be considered at risk for this condition due to increasing age, and disease and treatment burden. Fatigue is also common in dialyzed patients and impacts daily living, impairs the quality of life, increases the risk of cardiovascular events and negatively influences survival. This study aimed to explore the link between apathy and fatigue among hemodialysis (HD) and peritoneal dialysis (PD) patients. Method We conducted a cross-sectional cohort study which included 75 HD (57.3% male, median age 64 years) and 62 PD patients (48.4% male, median age 61 years) from two dialysis centres. Apathy status was assessed by the Apathy Evaluation Scale (AES) by Starkstein. Fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT) scale. AES score of 14 and higher denotes the presence of apathy, while a FACIT score of less than 30 indicates severe fatigue. Demographic, clinical and laboratory data were obtained by a focused questionnaire and from electronic medical records. Data were analyzed with T-test, Hi-square, ANOVA and Pearson correlation as applicable. Results HD patients were significantly longer on dialysis than PD patients (p=0.046). Apathy was more frequent among PD patients compared to the HD group (64.5% vs 48%), but the difference was not statistically significant (p = 0.053). Severe fatigue was more frequent in the HD group (33.8% vs 27.4%), but the difference was not statistically significant (p = 0.424). Elderly patients had a higher prevalence of apathy in both HD (70.3% vs 29.7%, p<0.001) and PD groups (84.2% vs 16.3%, p = 0.008), and a significantly higher prevalence of severe fatigue in the HD group (68% vs 32%, p = 0.017). Among HD patients higher education level was significantly associated with higher FACIT and lower apathy scores (p = 0.002 and p = 0.001 respectively). HD patients taking psychotropic medication had significantly lower FACIT (27.2±13.5 vs 35.0 ± 11.9, p = 0.03). Also, the presence of apathy was significantly associated with lower hemoglobin levels (101.7±9.7 vs 110.3±11.2, p = 0.001), red blood cells count (3.2±0.2 vs 3.5±0.6, p = 0.004), lower serum creatinine (900.0±149.1 vs 1001.5±266.4, p = 0.047) and lower Kt/V (1.35±0.22 vs 1.49±0.24, p = 0.008) in the HD group, while PD patients with severe fatigue had significantly higher creatinine levels (796.7±176.9 vs 646.4±200.0, p = 0.009). Gender, dialysis vintage, primary renal disease, and comorbidities were not significantly associated with either apathy or fatigue in either group of patients. Apathy and fatigue were significantly correlated in both the HD (p = 0.04) and the PD (p = 0.001) groups. Conclusion Apathy is a highly prevalent and often overlooked condition among dialyzed patients regardless of dialysis modality. Longitudinal studies should explore whether apathy is a causative factor for fatigue in these populations.

Trends in environmental risk and child health research: A bibliometric study, 1990–2022

BackgroundWorldwide, climate change has significantly contributed to the global burden of disease. Children are among the most vulnerable groups of population bearing the brunt of climate change. To explore the development of research on environmental risk and child health, a bibliometric analysis was conducted encompassing literature from 1990 to 2022. MethodsThe study draws upon 6816 published articles related to environmental risk and child health, sourced from the Scopus database spanning the period from 1990 to 2022. The research encompasses several key analyses: trend analysis, country and journal contribution, author contribution using the Bibliometrix R package and co-occurrence analysis was performed using VOSviewer. ResultsThe study highlights the major contributions of the USA and China. The USA leads in both Single Country Publications and Multiple Country Publications. The International Journal of Environmental Research and Public Health stands out as the primary source, with the highest number of documents in this field. Co-occurrence analysis revealed common clusters of words like children, child health, mental health, adolescence, and physical activity. The keyword network map highlighted climate change, social determinants of health, and resilience as the most emerging research topics. ConclusionsThe study highlights the crucial role of environmental factors in influencing child health. The geographical disparities in research output suggest a need for broader research engagement globally, particularly from developing countries, to better address and mitigate the adverse effects of environmental exposures on children's health worldwide.

#985 Disease outcomes of chronic kidney disease: a Phenome-wide association study

Abstract Background and Aims Chronic kidney disease (CKD) is one of the prevalent diseases worldwide leading to increasing global disease burden, however, comprehensive studies of the subsequently developed disease outcomes are lacking. We aimed to explore the associations between CKD and a broad range of following disease conditions. Method Polygenic risk score (PRS) of 347308 white participants in UK Biobank were calculated using PLINK1.9 software with summing of risk alleles weighted by the effect sizes of. Genome-wide association study (GWAS) summary statistical data of CKD from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phecodes = 7.52 × 10−5) to correct for multiple testing. Results Totally, 261,254 SNPs (pruned by r2 < 0.1 within the 250 kb region, P < 0.4) from base data were retained for PRS calculation. Our PheWas identified that one standard deviation (SD) increase in the PRS of CKD significantly associated with chronic renal failure (OR = 1.16, 95% CI: 1.14-1.18, P = 2.01 × 10−66), essential (primary) hypertension (OR = 1.05, 95% CI: 1.04-1.06, P = 2.12 × 10−29), hypertensive renal disease (OR = 1.22, 95% CI: 1.16-1.29, P = 3.81 × 10−14), gout (OR = 1.09, 95% CI: 1.07-1.12, P = 6.57 × 10−13), intestinal malabsorption (OR = 1.12, 95% CI: 1.08-1.16, P = 6.71 × 10−9), acute renal failure (OR = 1.05, 95% CI: 1.03-1.07, P = 2.08 × 10−8), disorders of lipoprotein metabolism and other lipidaemias (OR = 1.03, 95% CI: 1.01-1.04, P = 9.11 × 10−7), non-insulin-dependent diabetes mellitus (OR = 1.03, 95% CI: 1.02-1.04, P = 3.11 × 10−6), obesity (OR = 1.03, 95% CI: 1.02-1.05, P = 3.13 × 10−6), unspecified renal failure (OR = 1.11, 95% CI: 1.06-1.16, P = 1.18 × 10−5), chronic ischaemic heart disease (OR = 1.03, 95% CI: 1.01-1.04, P = 1.52 × 10−5). Conclusion Increased risk of CKD significantly associated with a series of subsequent conditions, providing evidence for prevention of following diseases in patients with CKD.

Regional and temporal variations in COVID-19 cases and deaths in Ethiopia: Lessons learned from the COVID-19 enhanced surveillance and response.

The COVID-19 pandemic is one of the most devastating public health emergencies of international concern to have occurred in the past century. To ensure a safe, scalable, and sustainable response, it is imperative to understand the burden of disease, epidemiological trends, and responses to activities that have already been implemented. We aimed to analyze how COVID-19 tests, cases, and deaths varied by time and region in the general population and healthcare workers (HCWs) in Ethiopia. COVID-19 data were captured between October 01, 2021, and September 30, 2022, in 64 systematically selected health facilities throughout Ethiopia. The number of health facilities included in the study was proportionally allocated to the regional states of Ethiopia. Data were captured by standardized tools and formats. Analysis of COVID-19 testing performed, cases detected, and deaths registered by region and time was carried out. We analyzed 215,024 individuals' data that were captured through COVID-19 surveillance in Ethiopia. Of the 215,024 total tests, 18,964 COVID-19 cases (8.8%, 95% CI: 8.7%- 9.0%) were identified and 534 (2.8%, 95% CI: 2.6%- 3.1%) were deceased. The positivity rate ranged from 1% in the Afar region to 15% in the Sidama region. Eight (1.2%, 95% CI: 0.4%- 2.0%) HCWs died out of 664 infected HCWs, of which 81.5% were from Addis Ababa. Three waves of outbreaks were detected during the analysis period, with the highest positivity rate of 35% during the Omicron period and the highest rate of ICU beds and mechanical ventilators (38%) occupied by COVID-19 patients during the Delta period. The temporal and regional variations in COVID-19 cases and deaths in Ethiopia underscore the need for concerted efforts to address the disparities in the COVID-19 surveillance and response system. These lessons should be critically considered during the integration of the COVID-19 surveillance system into the routine surveillance system.

Brain health index as a predictor of possible vascular dementia in the Mexican health and aging study 2012-2015.

To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

#1151 The prevalence and disease burden of CKD associated pruritus in Danish dialysis patients and current treatment practices—preliminary results

Abstract Background and Aims Chronic kidney disease associated pruritus (CKD-aP) is rarely assessed by health care providers and potentially under-reported by patients despite the potential negative impact on health-related quality of life (HRQoL). Our aim was to investigate the prevalence of CKD-aP in a large cohort of Danish dialysis patients based on validated patient-reported outcome (PRO) instruments. A secondary aim was to investigate CKD-aP awareness among renal physicians including current treatment practices. Method The study was designed as a non-interventional, cross-sectional multicentre study. Chronic dialysis patients from four different regions in Denmark were invited to participate. CKD-aP was assessed with a one-page questionnaire containing Danish versions of two validated PRO instruments. The worst itch numeric rating scale (WI-NRS) was used for itch severity within the previous 24 hours (ranging from 0-10 with CKD-aP defined as WI-NRS score &amp;gt;4 which equals moderate to severe CKD-aP). The 5-D itch scale was used as a multidimensional measure of itching and HRQoL. The five dimensions of the 5-D itch scale (degree, duration, direction, disability, and distribution) were summed together to obtain total score ranging from 5 (no pruritus) to 25 (most severe). CKD-aP awareness and treatment practices among doctors and nurses were investigated with a simple self-invented questionnaire. Results We recruited 500 chronic dialysis patients of which 87% were treated with in-center haemodialysis (HD), 10% with peritoneal dialysis (PD) and 3% with home HD (HHD). Mean age ± SD was 65 ± 14 years and 64% were males. Fig. 1 shows WI-NRS and total 5-D itch score distribution according to dialysis modality. CKD-aP prevalence (based on WI-NRS score &amp;gt;4) was 19% (all patients regardless of dialysis modality) but tended to be higher among PD patients (29%) in comparison with HD (18%) and HHD (23%) as shown in Fig. 1. Odds ratio (OR) with logistic regression for CKD-aP based on WI-NRS score as a binary dependent variable (≤4 or &amp;gt;4) and dialysis modality yielded: OR (PD vs. HD): 1.83 (0.96-3.49) and OR (HHD vs. HD): 1.35 (0.36-5.03). No pruritus (WI-NRS score = 0) was found in 61% of patients and 20% had mild pruritus (WI-NRS score ≤4). WI-NRS score correlated significantly with total 5-D itch score (Spearman's rank correlation coefficient (all patients): ρ = 0.80; P &amp;lt; .001). Median total 5-D itch score (IQR) was 5 (5-10) based on all patients regardless of dialysis modality. Itch intensity over the past 2 weeks was rated moderate to unbearable by 23% and not present in 54% of patients. Itch duration was less than 6 hours in 91% of patients and 29% of patients had no change in itching over the past 2 weeks. Overall, the impact of CKD-aP on daily activities (leisure/social, housework/errands and work/school) was minimal in most patients but sleep disability (score &amp;gt;1) was found in 18%. Sleep disability was significantly associated with higher WI-NRS score. Perceived CKD-aP prevalence (based on 28 questionnaires) was 20-40% according to most physicians (54%), 25% estimated it to be lower and 21% expected it to be higher. Topical therapy with fatty cream was the preferred treatment by most physicians followed by increased dialysis and non-sedating antihistamines. Conclusion Roughly one out of five patients on chronic dialysis treatment suffers from moderate to severe CKD-aP. HRQoL is negatively affected by CKD-aP primarily manifested as sleep disturbance. Most physicians tend to overestimate CKD-aP prevalence and prescribe fatty cream as their preferred treatment.

Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.MethodsWe conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs.ResultsHere, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098).ConclusionsBased on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.

Polycystic ovary syndrome (PCOS) presents as a multimorbid condition by age 50-birth cohort linkage to national register data.

This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort. Population-based longitudinal cohort study. Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1 556) in the Northern Finland Birth Cohort 1966. National register data on diagnosed diseases (ICD-8-10) and medication use (ATC) until the age of 50. Women with PCOS had a 26% higher risk for any registered diagnosis (RR: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared to non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, e.g., endocrine, metabolic, nervous system, musculoskeletal and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a BMI ≥ 25gk/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI <25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, e.g., medications related to the alimentary tract and metabolism, the cardiovascular system, genito-urinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems. Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.

#1030 Addressing the unmet need of patient reported outcomes in ANCA associated vasculitis, in routine clinical practice

Abstract Background and Aims ANCA associated vasculitis (AAV) is associated with increased morbidity. Recent years has seen improvement in clinical outcomes yet little work has been done to better understand the patient's role within this condition. Patient reported outcome measures (PROMs) are increasingly standard in clinical research outcomes, as well as an overall indicator for good quality patient care. With the exception of Robson et al AAV-PRO [1], little research has been done to develop validated disease specific tools for patients living with AAV. We aim to develop a disease specific tool that can be used in clinical practice to aid patients and clinicians in understanding and track changes in health-related quality of life (HRQoL) over time. Method AAV patients from a single centre were invited to take part in focus groups conducted using a semi-structured topic guide. Participants were asked to discuss topics relating to four broad areas; 1) the effects of AAV on everyday life and living, 2) the effects of treatment on everyday life and living, 3) the role of patients in health management and the patient experience 4) a review of existing generic and disease specific PROM tools (SF-36 and AAV-PRO). Audio transcript of each focus group was transcribed verbatim and data was analysed using a combination of inductive and deductive framework analysis [2]. Results Twenty-eight patients with AAV were invited to participate, 19 attended one of three, 2.5 hour focus groups, 2 patients failed to attend, 4 declined and 3 were unavailable. The mean age of participants was 66.6 +9.4 years and there was a near equal male to female split (10:9). The median time from diagnosis as 7.4 years. Three participants had active or newly diagnosed AAV with BVAS scores of &amp;gt;10. Five participants had previously required dialysis with 1 receiving a renal transplant. All participants received glucocorticoid and immunosuppressive therapy (cyclophosphamide and or Rituximab), 15 (78.9%) were still receiving immunotherapy. Full analysis of the qualitative data is being undertaken. Preliminary findings outlined what was most important to participants when considering HRQoL. Areas acknowledged included; self-identity, social roles e.g. fulfilling caring responsibilities, fears of relapse and disease and treatment burden. Fifty-six deductive and inductive codes were identified which have been further categorised. Participants felt existing tools lacked consideration of some key issues. Scoring systems were considered to be negativity worded e.g. mild, moderate, severe, with the term ‘none’ being the only positive option. Participants reported that existing tools overlooked positive factors which impact HRQoL, such as symptom validation, close clinician monitoring and improvement with treatment. Limitations were noted when trying to address transient or inconsistent symptoms and difficulty separating vasculitis from other health conditions when answering questions. Participants expressed a preference for using a PROM as part of their clinical care and felt that completing it prior to clinic would be most helpful and facilitate discussions with healthcare professionals. The use of an electronic-PROM was widely supported and would support clinicians and patients to monitor changes over time. Conclusion The AAV-PRO represents a significant advancement over generic tools such as the SF-36, however, existing PROMs are not without limitations and are primarily used in research practices. Our study revealed that patients desire active participation in HRQoL discussions and further work to incorporate this into the clinic setting is needed. We are continuing to develop a PROM tool that can be used to assess patients HRQoL in relation to their AAV in the outpatient setting. We believe this will allow a deeper understanding of the disease burden and could support a comprehensive, patient-centred approach to decision-making, offering new insights and identifying the need for supportive care. On a broader scale, these insights can be utilized to compare treatments, shed light on inequalities and facilitate enhancements in services.

Factors associated with the enrollment of commercial medical insurance in China: Results from China General Social Survey.

The Chinese government has been promoting commercial medical insurance (CMI) in recent decades as it plays an increasingly important role in addressing disease burden, health inequities, and other healthcare challenges. However, compared with developed countries, the CMI is still less fledged with low coverage. This study aims to explore the factors associated with enrollment in CMI, with regards to explicit characteristics (including sociodemographic characteristics and family economic status), latent characteristics (including social security status), and the global incentive compatibility index (including health status), to inform the design of CMI to improve its coverage in China. Based on the principal-agent model, we summarized and classified the factors associated with the enrollment in CMI, and then analyzed the data generated from the Chinese General Social Survey in 2015,2018 and 2021 respectively. A comparison of factors regarding sociodemographic characteristics, family economic status, social security status, and health status was conducted between individuals enrolled and unenrolled in CMI using Mann-Whitney U test and Chi-square test. Binary logistic regression analysis was used to explore factors influencing the enrollment status of CMI. Of all individuals, the proportion of enrolled individuals shows an increasing trend year by year, with 8.7%,11.8% and 14.1% enrolled in CMI in 2015,2018 and 2021, respectively. The binary regression analysis further suggested that the factors associated with the enrollment in CMI were consistent in 2015,2018 and 2021.We found that individuals divorced, obese, who had a higher level of education, had non-agricultural household registration, perceived themselves as the upper social status, conducted daily exercise, had more family houses, had a car, had investment activities, or did not have basic health insurance were more likely to be enrolled in CMI. We identified multidimensional factors associated with the enrollment of CMI, which help inform the government and insurance industry to improve the coverage of CMI.

#1357 Regional and national hospitalization burden of lupus nephritis and systemic lupus erythematous in Spain

Abstract Background and Aims The regional epidemiology of Systemic lupus erythematosus (SLE) and lupus nephritis (LN) within the same country is poorly understood. Being a rare disease, its severity may be influenced by local expertise and treatment protocols, especially when healthcare systems are fragmented, like in Spain (17 different healthcare systems in 17 Autonomous Community (AACC), population range 319.796 to 8.472.407), resulting in potentially different levels of expertise in regional referral centers. Additional heterogeneity may derive from different specialists (rheumatology, internal medicine, nephrology) caring for SLE and LN. We aim to investigate the disease burden of SLE and LN in Spain and its AACC between 2019 and 2021, and to characterize factors that may influence this burden. Method The primary diagnostic data and average cost of SLE and NL hospitalization were extracted from the Minimum Basic Data Set (MBDS, Ministry of Health) that contains data from private and public hospitals. Sociodemographic data were obtained from the National Statistics Institute. Results From 2019 to 2021, there were 872 LN and 3612 SLE nationwide hospitalizations. Over 60% occurred in Andalucia, Catalonia, and Madrid, which account for 48% of Spanish population. Nationwide, the incidence of LN and SLE hospitalization was 1.44 and 4.59 per 100 000, respectively. However, regional variability was large, with a 3.7-fold difference for LN and a 7.3-fold difference for SLE between Madrid and Valencia, 2 of the more populated AACC. The median LN/SLE hospitalization ratio was 0.33. Relative risk for hospitalization, compared to the national mean, ranged in AACC from 0.37 (Baleares) to 2.55 (La Rioja) for LN and from 0.22 (Baleares) to 3.67 (Ceuta and Melilla) for SLE (Fig. 1A). Heterogeneity was larger at the provincial level where 10/50 provinces had significantly higher or lower relative risk than the national mean (Fig. 1B). The length of SLE/LN hospitalizations was very variable across specialties and AACC. There was a trend for shorter duration in Nephrology and longer in Internal Medicine for both LN and SLE. Nephrology was mainly responsible (76%) for LN hospitalization, with regional differences. For SLE hospitalization, Nephrology was also most commonly in charge. Heterogeneity was larger at the province level within the same AACC. The average All-Patient-Related (APR) cost per LN and SLE hospitalization episodes was €5254 and €4376, respectively, with significant geographical variability. Total annual hospitalization costs varied significantly among AACC, ranging from €8683 (Ceuta and Melilla) to €682512 (Catalonia) for LN and from €68361 (Ceuta and Melilla) to €2229456 (Madrid) for SLE. Adjusted per million population, total LN hospitalization cost ranged from €27920 (Baleares) to €179248 (La Rioja), and SLE cost from €91563 (Baleares) to €399693 (Ceuta and Melilla). When adjusted by €1000 of average household net income, the budget burden of LN hospitalization was highest in La Rioja (€5812 per €1000 of average household net income) and lowest in Baleares (€809 per €1000), while for SLE was highest in Murcia (€11186 per €1000) and lowest in Baleares (€2652 per €1000) (Fig. 2A,B). Conclusion In conclusion, the burden of LN and SLE hospitalization is heterogeneous across and within Spanish AACC, with large regional differences in the distribution of cases, costs and specialists who care for these patients. The analysis of these differences may contribute to benchmarking of best practices, decreasing clinical practice heterogeneity, optimizing care for SLE and LN and improving outcomes.

Adipose tissue as a linchpin of organismal ageing.

Ageing is a conserved biological process, modulated by intrinsic and extrinsic factors, that leads to changes in life expectancy. In humans, ageing is characterized by greatly increased prevalence of cardiometabolic disease, type 2 diabetes and disorders associated with impaired immune surveillance. Adipose tissue displays species-conserved, temporal changes with ageing, including redistribution from peripheral to central depots, loss of thermogenic capacity and expansion within the bone marrow. Adipose tissue is localized to discrete depots, and also diffusely distributed within multiple organs and tissues in direct proximity to specialized cells. Thus, through their potent endocrine properties, adipocytes are capable of modulating tissue and organ function throughout the body. In addition to adipocytes, multipotent progenitor/stem cells in adipose tissue play a crucial role in maintenance and repair of tissues throughout the lifetime. Adipose tissue may therefore be a central driver for organismal ageing and age-associated diseases. Here we review the features of adipose tissue during ageing, and discuss potential mechanisms by which these changes affect whole-body metabolism, immunity and longevity. We also explore the potential of adipose tissue-targeted therapies to ameliorate age-associated disease burdens.

Anxiety, depression and distress outcomes from the Health4Life intervention for adolescent mental health: a cluster-randomized controlled trial

AbstractMental disorders are a leading cause of disease burden worldwide. As onset typically occurs in adolescence, prevention during this period is critical. The Health4Life-school-based multiple health behavior change (MHBC) intervention targets six lifestyle risk factors: diet, sleep, physical activity, screentime, alcohol use and smoking. Health4Life has been evaluated in a cluster-randomized controlled trial in 71 Australian schools (6,639 grade seven students). This study presents intervention effects on secondary outcomes of depressive, anxiety and psychological distress symptoms. Generalized linear mixed-effect analyses of data from baseline, post-intervention (7 weeks), 12 months and 24 months showed that the Health4Life intervention was no more effective than an active control in reducing depressive, anxiety or psychological distress symptoms at a 24 or 12 month follow-up; however, there were short-term benefits for psychological distress and depressive symptoms immediately post-intervention. This study offers new evidence that multiple health behavior change interventions may improve adolescent mental health, but future research should explore methods to address anxiety and sustain effects over the longer term. A priori ANZCTR trial registration: ACTRN12619000431123.