Significant Excess Risk Research Articles

Unraveling the paradox: the impact of one or more traditional risk factors on short-term mortality following acute coronary syndromes.

Abstract Background It has been recently suggested that individuals without exposure to any standardized modifiable risk factors may have an increased risk of all-cause mortality from acute coronary syndromes (ACS) compared with their counterparts with one or more risk factors, including diabetes. Purpose To estimate the individual contribution of the four traditional risk factors to the risk of adverse outcomes from first ACS. Methods We analyzed data from 70,953 Caucasian patients presenting with first ACS, but without prior coronary heart disease in the International Survey of Acute Coronary Syndromes (ISACS) Archives registry network from October 2005 to January 2021. The primary outcome was all-cause mortality within 30 days after hospital admission. We calculated sex-specific risk ratios (RRs) stratifying traditional risk factors, current smoking, diabetes, hypercholesterolemia and hypertension into mutually exclusive categories using a balancing strategy by inverse probability weighting. Results Compared with patients presenting without risk factors, those with diabetes had significantly higher 30-day mortality in both women (RR, 1.29; 95% CI, 1.06-1.57) and men (RR, 1.40; 95% CI, 1.16-1.69). By contrast, patients who were current smokers or presented with a history of hypercholesterolemia or hypertension had significantly lower 30-day mortality than patients with no risk factors with RRs ranging from 0.53; 95% CI 0.42–0.67 in women who were smokers to 0.46; 95% CI 0.37–0.59 in men with hypercholesterolemia. The impact of diabetes on mortality was obscured in patients who concomitantly presented with diabetes and one more traditional risk factor. The RRs in combination with current smoking were 1.39; 95% CI 0.92 -2.09 in women and 0.89; 95% CI 0.68 -1.17 in men; with hypercholesterolemia: 0.91; 95% CI 0.66 -1.25 in women and 0.75; 95% CI 0.53–1.06 in men; with hypertension: 1.14; 95% CI 0.99–1.32 in women and 1.12; 95% CI 0.96–1.31 in men. Conclusions Diabetes confers a significant independent excess mortality risk at 30 days following ACS. Dilution bias in this setting refers to the weakening of the observed effect of diabetes because of the inclusion of "one more" risk factor with lower risk profile. Potential misinterpretation of the relationship between diabetes and death from ACS may negatively affect healthcare organization

Genomic ascertainment of CHEK2-related cancer predisposition.

There is clear evidence that deleterious germline variants in CHEK2 increases risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Genomic ascertainment was used to quantify cancer risk in CHEK2 germline pathogenic variant heterozygotes. Germline CHEK2 variants were extracted from two exome-sequenced biobanks linked to the electronic health record: UK Biobank (n= 469,765) and Geisinger MyCode (n=170,503). Variants were classified as per American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) criteria. Heterozygotes harbored a CHEK2 pathogenic/likely pathogenic (P/LP) variant; controls harbored benign/likely benign CHEK2 variation or wildtype CHEK2. Tumor phenotype and demographic data were retrieved; to adjust for relatedness, association analysis was performed with SAIGE-GENE+ with Bonferroni correction. In CHEK2 heterozygotes in both MyCode and UK Biobank, there was a significant excess risk of all cancers tested, including breast cancer (C50; OR=1.54 and 1.84, respectively), male genital organ cancer (C60-C63; OR=1.61 and 1.77 respectively), urinary tract cancer (C64-C68; OR=1.56 and 1.75, respectively) and lymphoid, hematopoietic, and related tissue cancer (C81-C96; OR=1.42 and 2.11, respectively). Compared to controls, age-dependent cancer penetrance in CHEK2 heterozygotes was significantly younger in both cohorts; no significant difference was observed between the penetrance of truncating and missense variants for cancer in either cohort. Overall survival was significantly decreased in CHEK2 heterozygotes in UK Biobank but there was no statistical difference in MyCode. Using genomic ascertainment in two population-scale cohorts, this investigation quantified the prevalence, penetrance, cancer phenotype and survival in CHEK2 heterozygotes. Tailored treatment options and surveillance strategies to manage those risks are warranted.

Exposure to second-hand smoke and breast cancer risk in non-smoking women: a comprehensive systematic review and meta-analysis.

Through the use of an innovative method to identify original publications, we conducted ameta-analysis of all epidemiological studies evaluating the association between second-hand smoke (SHS) exposure and breast cancer risk among female non-smokers published in English up to October 2022. Pooled relative risks (RR) were obtained through the use of random-effects models. Dose-response relationships were derived using log-linear functions. Out of 73 identified eligible studies, 63 original articles were included in the meta-analysis. The pooled RR for breast cancer for overall exposure to SHS was 1.24 (95% confidence interval, CI, 1.15-1.34, number of articles, n = 52). Regarding the setting of exposure, RRs were 1.17 (95% CI 1.08-1.27, n = 37) for SHS exposure at home, 1.03 (95% CI 0.98-1.08, n = 15) at the workplace, 1.24 (95% CI 1.11-1.37, n = 16) at home or workplace, and 1.45 (95% CI 1.16-1.80, n = 13) for non-specified settings. The risk of breast cancer increased linearly with higher duration (RR 1.29;95% CI 1.04-1.59 for 40 years of SHS exposure, n = 12), intensity (RR 1.38;95% CI 1.14-1.67 for 20 cigarettes of SHS exposure per day, n = 6), and pack-years (RR 1.50;95% CI 0.92-2.45 for 40 SHS pack-years, n = 6) of SHS exposure. This meta-analysis shows a statistically significant excess risk of breast cancer in women exposed to SHS.

Excess long-term risk of adverse outcomes in heart failure patients with high and low levels of NT-proBNP: A 7-year follow-up study (NorthStar Trial)

BackgroundThis study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide). MethodsPatients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as </≥ 600 pg/ml in patients with sinus rhythm and </≥ 900 pg/ml in patients with AF. The primary composite endpoint was a 7-year risk of cardiovascular death or HF admission. ResultsIn the HFrEF cohort, 704 patients had high NT-proBNP (median age, 73; mean left ventricular ejection fraction (LVEF), 33%). 416 patients had low NT-proBNP (median age, 65; LVEF, 30%). Patients from both groups were in NYHA class I-III. The primary endpoint occurred in 531 patients (75.4%) with HFrEF and elevated NT-proBNP, and 748 controls (21.3%) (risk difference, 54.2%; 95% confidence interval (CI) 50.7–57.6%). In comparison, it occurred in 199 patients (47.9%) with HFrEF and without elevated NT-proBNP, and 185 controls (8,9%) (risk difference, 38.9%; 95% CI 34.0–43.9%). Risk differences for all secondary endpoints were significant, except for overall mortality in the low NT-proBNP group (risk difference, 3.8%; 95% CI, −0.4–8.0%). ConclusionThis study identified a significant excess risk in patients with HFrEF across various endpoints, which persisted after stratification into high and low levels of NT-proBNP.

Effects of Coexposure to Air Pollution from Vegetation Fires and Extreme Heat on Mortality in Upper Northern Thailand.

Background: understanding the effects of coexposure to compound extreme events, such as air pollution and extreme heat, is important for reducing current and future health burdens. This study investigated the independent and synergistic effects of exposure to air pollution from vegetation fires and extreme heat on all-cause mortality in Upper Northern Thailand. Methods: we used a time-stratified case-crossover study design with a conditional quasi-Poisson model to examine the association between mortality and coexposure to air pollution due to vegetation fire events (fire-PM2.5) and extreme heat. Extreme heat days were defined using the 90th and 99th percentile thresholds for daily maximum temperature. Results: we observed a significant positive excess risk of mortality due to independent exposure to fire-PM2.5 and extreme heat, but not an interactive effect. All-cause mortality risk increased by 0.9% (95% confidence interval (CI): 0.1, 1.8) for each 10 μg/m3 increase in fire-PM2.5 on the same day and by 12.8% (95% CI: 10.5, 15.1) on extreme heat days (90th percentile) relative to nonextreme heat days. Conclusion: this study showed that exposure to PM2.5 from vegetation fires and extreme heat independently increased all-cause mortality risk in UNT. However, there was no evidence of a synergistic effect of these events.

Assessing the impact of type 2 diabetes on mortality and life expectancy according to the number of risk factor targets achieved: an observational study

BackgroundType 2 diabetes (T2D) is associated with an increased risk of premature death. Whether multifactorial risk factor modification could attenuate T2D-related excess risk of death is unclear. We aimed to examine the association of risk factor target achievement with mortality and life expectancy among patients with T2D, compared with individuals without diabetes.MethodsIn this longitudinal cohort study, we included 316 995 participants (14 162 with T2D and 302 833 without T2D) free from cardiovascular disease (CVD) or cancer at baseline between 2006 and 2010 from the UK Biobank. Participants with T2D were categorised according to the number of risk factors within target range (non-smoking, being physically active, healthy diet, guideline-recommended levels of glycated haemoglobin, body mass index, blood pressure, and total cholesterol). Survival models were applied to calculate hazard ratios (HRs) for mortality and predict life expectancy differences.ResultsOver a median follow-up of 13.8 (IQR 13.1–14.4) years, deaths occurred among 2105 (14.9%) participants with T2D and 18 505 (6.1%) participants without T2D. Compared with participants without T2D (death rate per 1000 person-years 4.51 [95% CI 4.44 to 4.57]), the risk of all-cause mortality among those with T2D decreased stepwise with an increasing number of risk factors within target range (0–1 risk factor target achieved: absolute rate difference per 1000 person-years 7.34 [4.91 to 9.78], HR 2.70 [2.25 to 3.25]; 6–7 risk factors target achieved: absolute rate difference per 1000 person-years 0.68 [-0.62 to 1.99], HR 1.16 [0.93 to 1.43]). A similar pattern was observed for CVD and cancer mortality. The association between risk factors target achievement and all-cause mortality was more prominent among participants younger than 60 years than those 60 years or older (P for interaction = 0.012). At age 50 years, participants with T2D who had 0–1 and 6–7 risk factors within target range had an average 7.67 (95% CI 6.15 to 9.19) and 0.99 (-0.59 to 2.56) reduced years of life expectancy, respectively, compared with those without T2D.ConclusionsIndividuals with T2D who achieved multiple risk factor targets had no significant excess mortality risk or reduction in life expectancy than those without diabetes. Early interventions aiming to promote risk factor modification could translate into improved long-term survival for patients with T2D.

Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)

according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. adherence to colorectal and breast cancer screenings. during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Long-term ozone exposure and all-cause mortality: Cohort evidence in China and global heterogeneity by region

BackgroundCohort evidence linking long-term ozone (O3) exposure to mortality remained largely mixed worldwide and was extensively deficient in densely-populated Asia. This study aimed to assess the long-term effects of O3 exposure on all-cause mortality among Chinese adults, as well as to examine potential regional heterogeneity across the globe. MethodsA national dynamic cohort of 42153 adults aged 16+ years were recruited from 25 provinces across Chinese mainland and followed up during 2010–2018. Annual warm-season (April–September) O3 and year-round co-pollutants (i.e., nitrogen dioxide [NO2] and fine particulate matter [PM2.5]) were simulated through validated spatial-temporal prediction models and were assigned to each enrollee in each calendar year. Cox proportional hazards models with time-varying exposures were employed to assess the O3-mortality association. Concentration-response (C-R) curves were fitted by natural cubic spline function to investigate the potential nonlinear association. Both single-pollutant model and co-pollutant models additionally adjusting for PM2.5 and/or NO2 were employed to examine the robustness of the estimated association. The random-effect meta-analysis was adopted to pool effect estimates from the current and prior population-based cohorts (n = 29), and pooled C-R curves were fitted through the meta-smoothing approach by regions. ResultsThe study population comprised of 42153 participants who contributed 258921.5 person-years at risk (median 6.4 years), of whom 2382 death events occurred during study period. Participants were exposed to an annual average of 51.4 ppb (range: 22.7−74.4 ppb) of warm-season O3 concentration. In the single-pollutant model, a significantly increased hazard ratio (HR) of 1.098 (95% confidence interval [CI]: 1.023−1.179) was associated with a 10-ppb rise in O3 exposure. Associations remained robust to additional adjustments of co-pollutants, with HRs of 1.099 (95% CI: 1.023−1.180) in bi-pollutant model (+PM2.5) and 1.093 (95% CI: 1.018−1.174) in tri-pollutant model (+PM2.5+NO2), respectively. A J-shaped C-R relationship was identified among Chinese general population, suggesting significant excess mortality risk at high ozone exposure only. The combined C-R curves from Asia (n = 4) and North America (n = 17) demonstrated an overall increased risk of all-cause mortality with O3 exposure, with pooled HRs of 1.124 (95% CI: 0.966−1.307) and 1.023 (95% CI: 1.007−1.039) per 10-ppb rise, respectively. Conversely, an opposite association was observed in Europe (n = 8, HR: 0.914 [95% CI: 0.860−0.972]), suggesting significant heterogeneity across regions (P < 0.01). ConclusionsThis study provided national evidence that high O3 exposure may curtail long-term survival of Chinese general population. Great between-region heterogeneity of pooled O3-mortality was identified across North America, Europe, and Asia.

Measuring substance use disorder (SUD) in commercial and Medicaid insured patients with cancer in Washington state.

177 Background: Studies have shown that SUDs not only impact cancer risk, treatment, and survivorship but also increase ED and hospital use. We sought to characterize SUD within Medicaid enrollees diagnosed with cancer in Washington state, hypothesizing thatMedicaid enrollees were more likely to be diagnosed with SUDs than commercial enrollees, and that patients with an SUD experienced higher rates of emergency department (ED) visits or inpatient (IP) stays during initial cancer treatment. Methods: We linked Washington State cancer registry records with claims data from two large commercial insurers and Medicaid. Eligibility criteria included patients under 65 diagnosed with a solid tumor between 2013-2021 who started systemic therapy within 6 months of diagnosis. SUD diagnoses were identified using codes from CMS’s hierarchical condition category for SUD in the 6 months following diagnosis. Chi-square tests were used to compare demographic characteristics of those with and without a SUD diagnosis. Multivariate logistic regressions were used to evaluate the association between SUD and likelihood of at least one ED visit or IP stay, after controlling for payer, sex, race, ethnicity, age, marital status, stage, cancer group, area deprivation index, and diagnosis year. Results: Among the 10,709 patients (6,680 Commercial, 3,718 Medicaid, 311 Multiple) who received systemic therapy, 7.2% had a SUD diagnosis. SUD patients were less likely to be Asian and more likely to be male, living without a partner, diagnosed at a later cancer stage, and living in more deprived areas. Medicaid patients had significantly higher rates of SUD than commercial-insured patients (14.3% vs 3.3%). Overall, 46.6% of cancer patients had an ED visit or IP stay. Patients with SUD had greater use of ED or IP visits than patients without SUD (70.1% and 44.8%, respectively). In the first 6 months of systemic therapy patients with SUD were significantly more likely to visit the ED or be admitted to IP (OR 2.12, 95% CI 1.79 - 2.50) than cancer patients without SUD. Conclusions: More than 1 in 7 Medicaid cancer patients in WA state has an identified SUD. SUD is associated with significant excess risk for ED/IP admissions during treatment. Accurate identification of SUD in patients is necessary prior to strategies aimed at mitigation of unplanned ED visits and hospitalizations during cancer care. Further research is needed on interventions that effectively reduce the risk during treatment.[Table: see text]

Is the clinical phenotype impact the prognosis in dementia with Lewy bodies?

IntroductionThe first predominant clinical symptoms of dementia with Lewy bodies (DLB) are highly variable; however, the prognosis based on initial predominant symptoms remains poorly understood.MethodsMulticenter retrospective study in 4 French expert neurological centers. Patients were categorized in 3 groups according to their first more predominant symptoms: cognitive, psychiatric, or motor.ResultsAnalysis of 310 DLB patients. The mean age was 73.5 years old (SD 7.5) including 32.3% of women. The mean follow-up was 7.25 years (SD 3.6). We observed that the full clinical picture was more frequent in the motor group than in the cognitive group (p = 0.01); male gender and age at onset were associated with a significant excess risk of instantaneous mortality (p = 0.01).ConclusionInitial symptoms may affect the clinical course of patients, but no significant difference in mortality was observed.

Progression of non-alcoholic fatty liver disease and long-term outcomes: A nationwide paired liver biopsy cohort study

More data are needed regarding the long-term impact of the histological progression of non-alcoholic fatty liver disease (NAFLD) on long-term outcomes, including end-stage liver disease (ESLD) and mortality. We included Swedish adults with biopsy-confirmed non-cirrhotic NAFLD and ≥2 liver biopsies >6 months apart (1969-2017; n= 718). NAFLD was categorized at initial biopsy as simple steatosis, non-fibrotic steatohepatitis (NASH), or non-cirrhotic fibrosis. NAFLD progression was defined by histological changes between biopsies (i.e. incident NASH, incident fibrosis, fibrosis progression, cirrhosis). Using Cox regression, we estimated multivariable adjusted hazard ratios (aHRs) and 95% CIs for incident ESLD (i.e. hospitalization for decompensated cirrhosis, hepatocellular carcinoma or liver transplantation) and mortality, according to NAFLD progression vs. stable/regressed disease. At initial biopsy, 497 patients (69.2%) had simple steatosis, 90 (12.5%) had non-fibrotic NASH, and 131 (18.2%) had non-cirrhotic fibrosis. Over a median of 3.4 years between biopsies, 30.4% (218/718) experienced NAFLD progression, including 12.5% (62/497) with incident non-fibrotic NASH, 24.0% (141/587) with incident fibrosis, and 5.6% (40/718) with cirrhosis. Compared to stable/regressed disease, NAFLD progression was associated with significantly higher rates of developing incident ESLD (23.8 vs. 11.4/1,000 person-years [PY]; difference= 12.4/1,000 PY; aHR 1.65, 95% CI 1.17-2.32). While the highest ESLD incidence occurred with progression to cirrhosis (difference vs. stable/regressed disease= 56.3/1,000 PY), significant excess risk was also found with earlier transitions, including from simple steatosis to incident fibrosis (difference vs. stable/regressed disease= 18.9/1,000 PY). In contrast, all-cause mortality rates did not appear to differ when NAFLD progression was compared to stable/regressed disease (difference= 4.7/1,000 PY; aHR 0.99, 95% CI 0.78-1.24). In a nationwide, real-world cohort of patients with paired NAFLD biopsies, histological disease progression contributed to significantly higher rates of developing incident ESLD, but did not appear to impact all-cause mortality. Currently, data are scarce regarding the long-term impact of histological progression or regression of non-alcoholic fatty liver disease (NAFLD) on subsequent risk of adverse clinical outcomes, including the development of end-stage liver disease and mortality. This is particularly important because randomized-controlled trials of NAFLD therapeutics currently focus on short-term histological endpoints as presumed surrogates for those major clinical outcomes. Thus, the results from this study can help inform the optimal design of future NAFLD therapeutic trials, while also providing the necessary evidence base for public health policies focused on preventing the development and progression of NAFLD.

#5214 RENAL TOLERABILITY OF SGLT-2 INHIBITORS COMBINING WITH RENIN-ANGIOTENSIN SYSTEM BLOCKERS AND MINERALOCORTICOID RECEPTOR ANTAGONISTS IN CKD

Abstract Background and aims Recently the sodium glucose cotransporter-2 (SGLT-2) inhibitors combining with angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor II blocker (ARBs) or angiotensin-receptor neprilysin inhibitor (ARNI)) and mineralocorticoid receptor antagonist (MRA) ((triple therapy (TT)), would help prevent further progression of renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease (ESKD). The degree to which data on TT initiation and discontinuation in cronic kidney disease (CKD) patients can be generalized to patients in real-world practice is unclear. Aims to evaluate renal tolerability to the TT at target doses as well as clinical incidents and dosage adjustments. To analyze the risk factors for TT discontinuation. Method A retrospective cohort study was carried out in patients ≥18 years old with chronic kidney disease (CKD) treated with TT in Rey Juan Carlos Hospital between January 2019 to December 2022. The collected clinical data included age, gender, associated morbidities, serum creatinine (Scr), estimated glomerular filtration rate (eGFR), potassium, sodium levels, dose adjustments before administration of TT and in the first year of follow up. Multivariate logistic models were performed to evaluate the risk factors to dosage adjusted and discontinuation of TT. Results Among 104 patients treated with TT were included. Medium age was 69 years old (range, 37-91). Most of them were men, 78% (81). The main cause to initiate TT was cardiorenal syndrome 59% (61). Before to initiate TT, in 35% patients the treatment was adjusted. The main modification was reduced or discontinuation of diuretics (loop or thiazide) therapy 23% (24/104). In the first year of follow up, in 69 patients (66%) it was necessary dosage adjustments, being the reduced of MRA (spironolactone and eplerenone) the main modification treatment 38% (26/69). The major cause of dose adjustment was developed of acute kidney injury (AKI) in 43 patients (41%). According to KDIGO criteria, 38 patients (88%) reached stage 1; 4 patients (9%) stage 2 and 1 case (2%) stage 3. The independent risk factor associated with dosage adjustment were AKI development (OR: 28.57; 95% CI 6.04-134.4; P = 0.0001) adjusted by sex and age. Despite the dosage adjustment and titers, in 29 patients (28%) TT was discontinued in a median time of 4 months (IQR 2–11) after its initiation. The risk factor associated with TT discontinuation were AKI developed (P = 0,003) and eGFR at the 12 months of follow up (P = 0,01). There were no significant excess risks of symptomatic hypotension, volume depletion, and hyperkalemia after a year of follow up. Conclusions The renal tolerability of use to triple therapy in chronic kidney disease appears to be low. The AKI development was the main risk factor of dosage adjustment and discontinuation of TT. Its necessary to clarify which is the best way to maximizing renal tolerability in this complex groups of patients. The use of early combination therapy requires careful assessment. Its important to find strategies to guide clinicians about the steps and challenges to improving overall use of triple therapy tolerability and dosage adjustment.

The risk of post-polio syndrome among immigrant groups in Sweden

To examine the risk of post-polio syndrome (PPS) in immigrant groups using native Swedish-born individuals as referents. This is a retrospective study. The study population included all individuals aged 18 years and older registered in Sweden. PPS was defined as having at least one registered diagnosis in the Swedish National Patient Register. The incidence of post-polio in different immigrant groups, using Swedish-born individuals as referents, was assessed by Cox regression, with hazard ratios (HRs) and 99% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, co-morbidities, and neighbourhood socioeconomic status. In total 5300 post-polio cases were registered, 2413 males and 2887 females. Fully adjusted HRs (99% CI) in immigrants versus Swedish-born were 1.77 in men (1.52–2.07) and 1.39 (1.19–1.62) in women. Statistically significant excess risks of post-polio were found in the following subgroups: men and women from Africa, HRs (with 99% CI) 7.40 (5.17–10.59) and 8.39 (5.44–12.95), respectively, and Asia, HRs 6.32 (5.11–7.81) and 4.36 (3.38–5.62) respectively, and in men from Latin America, HR 3.66 (2.17–6.18). It is of importance to be aware of risks of PPS in immigrants settled in Western countries, and that it is more common in immigrants from regions of the world where polio is still prevalent. Patients with PPS need treatment and proper follow-up until polio has been eradicated through global vaccination programs.

Heightened risks of cardiovascular disease in South Asian populations: causes and consequences

ABSTRACT Introduction South Asian individuals comprise almost a quarter of the world’s population and have an excess risk of atherosclerotic cardiovascular disease (ASCVD) compared to other ethnicities. In part, this can be explained by higher prevalence, earlier onset, and suboptimal control of traditional cardiovascular risk factors, such as insulin resistance, metabolic syndrome, and dyslipidaemia. However, there remains a significant residual excess risk associated with South Asian ethnicity after controlling for traditional risk factors. Areas covered In this review, we describe the epidemiology of ASCVD in both native and diaspora South Asian populations. We explore how traditional cardiovascular risk factors, novel cardiovascular risk factors, and social determinants of health may contribute to the excess ASCVD risk seen in South Asian populations. Expert opinion There should be increased awareness of the relative importance of South Asian ethnicity and related social determinants of health, as risk factors for ASCVD. Systematic screening processes should be tailored to this population, and modifiable risk factors should be treated aggressively. Further research is required to quantify determinants of the excess ASCVD risk seen in South Asian populations and to develop targeted interventions to address these factors.

52 Temporal association of new onset alcohol use disorder following SARS-CoV-2 infection from 2020-2022

OBJECTIVES/GOALS: During the pandemic, alcohol related deaths increased by 25%. To help understand how we might mitigate this negative outcome, we sought to examine the association of new diagnosis of alcohol use disorder (AUD) with SARS-CoV2 through two years of the pandemic. METHODS/STUDY POPULATION: Using a non-date-shifted TriNetX database, we conducted a retrospective cohort analysis of electronic health records of patients age ≥12 years who had been diagnosed either with COVID-19 (n=1,359,817) or other respiratory infections with no record of COVID-19 (n=2,013,031). Patients were then matched for propensity score risk for AUD, and results were analyzed by three-month intervals from January 2020 through January 2022, in blocks numbered 1-8. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CI) for diagnosis of AUD from two weeks to six months following COVID-19 diagnosis. RESULTS/ANTICIPATED RESULTS: There was significant excess risk compared to control cohorts of AUD following COVID-19 diagnoses made during the first three months of the pandemic (HR (CI)): block 1: 2.41(1.89,3.08); no excess risk was seen for the remainder of 2020 (blocks 2-4) (HR1.01-1.14, NS). The excess risk increased again in 2021 as the delta and omicron variants emerged (HR and 95% CI): block 5 were: 1.26(1.11, 1.43)); block 6: 1.88(1.62-2.18)); block 7: 1.24(1.10,1.41); block 8: 1.12(1.0-1.25). COVID-19 diagnosis was associated with clinically-evident AUD under some pandemic circumstances. DISCUSSION/SIGNIFICANCE: COVID-19 early in the pandemic (block 1) was associated with substantial excess risk for new diagnosis of AUD, with smaller excess risk after COVID-19 during 2021 (blocks 5-7), and no excess risk otherwise. Diagnosis of COVID-19 and pandemic contextual factors are associated with increased risk for AUD.

History of Low Hourly Wage and All-Cause Mortality Among Middle-aged Workers

Earning a low wage is an increasingly recognized public health concern, yet little research exists on the long-term health consequences of sustained low-wage earning. To examine the association of sustained low-wage earning and mortality in a sample of workers with hourly wage reported biennially during peak midlife earning years. This longitudinal study included 4002 US participants, aged 50 years or older, from 2 subcohorts of the Health and Retirement Study (1992-2018) who worked for pay and reported earning hourly wages at 3 or more time points during a 12-year period during their midlife (1992-2004 or 1998-2010). Outcome follow-up occurred from the end of the respective exposure periods until 2018. Low-wage-less than the hourly wage for full-time, full-year work at the federal poverty line-earning history was categorized as never earning a low wage, intermittently earning a low wage, and sustained earning a low wage. Cox proportional hazards and additive hazards regression models sequentially adjusted for sociodemographics, and economic and health covariates were used to estimate associations between low-wage history and all-cause mortality. We examined interaction with sex or employment stability on multiplicative and additive scales. Of the 4002 workers (aged 50-57 years at the beginning of exposure period and 61-69 years at the end), 1854 (46.3%) were female; 718 (17.9%) experienced employment instability; 366 (9.1%) had a history of sustained low-wage earning; 1288 (32.2%) had intermittent low-wage earning periods; and 2348 (58.7%) had never earned a low wage. In unadjusted analyses, those who had never earned low wages experienced 199 deaths per 10 000 person-years, those with intermittent low wages, 208 deaths per 10 000 person-years, and those with sustained low wages, 275 deaths per 10 000 person-years. In models adjusted for key sociodemographic variables, sustained low-wage earning was associated with mortality (hazard ratio [HR], 1.35; 95% CI, 1.07-1.71) and excess deaths (66; 95% CI, 6.6-125); these findings were attenuated with additional adjustments for economic and health covariates. Significant excess death and elevated mortality risk were observed for workers with sustained low-wage exposure and employment fluctuations (eg, for sustained low-wage × employment fluctuated, HR, 2.18; 95% CI, 1.35-3.53; for sustained low-wage × stable employment, HR, 1.17; 95% CI, 0.89,-1.54; P for interaction = .003). Sustained low-wage earning may be associated with elevated mortality risk and excess deaths, especially when experienced alongside unstable employment. If causal, our findings suggest that social and economic policies that improve the financial standing of low-wage workers (eg, minimum wage laws) could improve mortality outcomes.

Impact of vaccination against SARS-CoV-2 on the risk of hospital admission and death among infected patients with urologic cancers: A population-based study in northern Italy.

205 Background: Background: Hospital admission and death of infected cancer patients were investigated according to SARS-CoV-2 vaccination status. Methods: Population-based observational study on 1874 SARS-CoV-2 infected patients with prostate (n=1276), kidney (n=327), and bladder (n=271) cancers. Hazard ratios (HR) and their 95% confidence intervals (CI), adjusted for sex and age, were computed to assess the risk of hospital admission and death of unvaccinated patients as compared to vaccinated ones. Results: 24.5% of patients with prostate, 26.9% with kidney and 29.5% with bladder cancer were unvaccinated. As compared to vaccinated ones, a statistically significant excess risk of hospital admission emerged for unvaccinated ones with prostate (HR=3.33, 95% CI: 2.50-4.55), and kidney (HR=4.35, 95% CI: 2.33-8.33) cancer. The 312 unvaccinated prostate cancer patients were also at a nearly 3-fold higher risk of death than vaccinated ones (HR=2.98, 95% CI:1.89-4.70). Conclusions: Study findings stress the importance of SARS-CoV-2 vaccines in reducing hospital admission and death in patients with urologic cancers, particularly prostate cancer.

Prognostic importance of obstructive sleep apnea and CPAP treatment for cardiovascular and mortality outcomes in patients with resistant hypertension: a prospective cohort study.

The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events [CVEs] and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.

Perceived knowledge gained from school-based sexuality education - results from a national population-based survey among young people in Sweden.

School-based sexuality education is a core component of securing young people's right to attain health equity regarding sexual and reproductive health and rights. This paper aims to explore how perceived knowledge (sufficient or insufficient) of taking care of one's sexual health is associated with knowledge gained from school-based sexuality education and social determinants. The data material is drawn from a population-based survey conducted in Sweden in 2015. The survey had 7755 respondents and a response rate of 26%. To explore the aim descriptive statistics and logistic regression models were used. Our results show that perceived insufficient knowledge from school-based sexuality education was associated with higher odds of reporting not being able to take care of one's sexual health. The highest significant excess risk for insufficient knowledge was found among young people from sexual minorities. Young people in Sweden do not have equal abilities to receive knowledge needed to take care of their sexual health and thus attain sexual health literacy. There is an unequal distribution of perceived knowledge, and LGBTQI+ youth particularly face barriers in using school-based sexuality education as a resource for sexual health literacy.

Prospective multicentered study describing the health pathway of a short-stay geriatric population hospitalised through geriatric telephonic hotline

The ARS finance geriatric hotlines in order to improve the articulation between town medicine and the hospital. The objective of our study is to describe the health status and the care pathway of subjects aged over 75 years hospitalised in a geriatric short stay hospital via a geriatric hotline. This prospective multicentre study included 1,451 subjects over 24 months. The primary endpoint was the average length of stay. The secondary endpoints were medico-socio-demographic data. The population hospitalised via a hotline is comparable to that usually found in geriatric short stay services. The length of stay is correlated with the lifestyle and the mode of discharge (p < 0.001). There was a significant excess risk of non-return to the previous place of residence according to age, average length of stay, comorbidities and degree of dependence. The care pathway for elderly people over 75 years old hospitalised through the hotline is optimised, with an average length of stay of 14 days, demonstrating a good link between town medicine and hospital. This approach allows for the early management of elderly subjects in the geriatric care system.