Individual Risk Research Articles

Establishment and activity of the planning and acting network for low dose radiation research in Japan (PLANET): 2016-2023.

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection.

The cost of living crisis – how does it impact the health and life of individuals? A survey exploring perceptions in Italy, Germany, Sweden and the United Kingdom

BackgroundThe Cost of Living Crisis (CoLC), a real term reduction in basic income, risks individuals being unable to afford essentials such as heat, food and clothing. The impact of the CoLC is disproportionate – with different population sub-groups more likely to be negatively affected. The objective of this survey was to evaluate the perceived impact of the CoLC on the life and health of participants across four European countries.MethodsA survey housing two questions to investigate the relationship between the CoLC and its perceived impact on life and health was developed. Four European countries (U.K., Sweden, Italy and Germany) took part via the YouGov platform. Logistic regression models were created for each country and question to evaluate which population characteristics were associated with a negative reported impact of the CoLC.ResultsA total of 8,152 unique individuals responded between 17th March and 30th March 2023. Each country was equally represented. Those aged 36–64 were more likely to report a negative impact of the CoLC on their life and health than younger participants (p < 0.001, p = 0.02 respectively). Across all countries, females were significantly more likely to report a negative impact on their life and health, however, when analysed according to country, in Sweden females were less likely to report a negative impact (p < 0.001). Those in lower income families or who reported poor health in the preceding 12 months were significantly more likely to report a negative impact of the CoLC on their life and health. There was no difference within the participant group on the reported impact of the CoLC based on location (rural vs. urban).ConclusionsWe demonstrate the disproportionate negative impact of the CoLC on both life and health in different population subgroups. Germany and Sweden appeared to be more resilient to the effects of the CoLC, particularly for certain population subgroups. It is important to understand the differing effects of a CoLC, and to learn from successful health and economic strategies in order to create targeted policy and create a population resilient to economic shocks.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Gender-affirming hormone treatment. Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

The likelihood of detecting abnormal karyotypes in fetuses with a single major anomaly or "soft" marker on ultrasonographic scanning.

Fetuses with abnormal karyotypes often exhibit distinctive ultrasonographic markers, including major anomalies and "soft" markers, indicating potential chromosomal issues. A crucial consideration arises when a single fetal anomaly is detected, raising the question of whether karyotyping is warranted, given the associated procedural risks. Our objective was to establish correlations between single fetal anomalies identified through ultrasound and chromosomal abnormalities. A cross-sectional study analyzed the karyotype of 1493 fetuses and detected a single ultrasonographic anomaly over a 16-year period. Karyotyping was performed using the standard karyotype technique. Moreover, data regarding the type of anomaly detected ultrasonographically, karyotype results, and outcomes following interventions were collected. Among other methods, the use of positive likelihood ratios (LR+) was used to evaluate the diagnostic accuracy of ultrasound compared to karyotyping. In total, an aberrant karyotype was identified in 99 fetuses (6.6%). This was most commonly observed in cases involving a "soft" marker, occurring in 27 out of 218 fetuses (12.4%). The most frequently detected aberrant karyotype resulted from aneuploidies (80.6% of cases), notably trisomy 21 (50.5%). "Soft" markers predicted chromosomal issues (LR+ = 1.9; OR = 2.4), and isolated polyhydramnios (LR+ = 1.54; OR = 1.6) showed significance in predicting fetal chromosomal aberrations. When assessing the necessity for karyotyping in fetuses with single major anomalies or "soft" markers, it is crucial to consider individual risks for chromosomopathies, including the LR+ of the detected marker. In cases where fetuses exhibit isolated anomalies with a normal karyotype, additional diagnostic measures, such as molecular cytogenetic and molecular genetics techniques, may become necessary.

Eligibility for lipid-lowering therapy when applying systemic coronary risk estimation 2 (SCORE2) according to guidelines on apparently healthy middle-aged individuals.

To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

Bone mineral density and osteoporosis related risk factors in type 2 diabetes mellitus

Diabetes mellitus negatively affects bone tissue and unfavourably impacts bone mineral density (BMD), therfore increasing the probability of fractures through pathological mechanisms. This study aimed to explore the factors associated with BMD and osteoporosis risk in individuals with a diagnosis of type 2 diabetes mellitus (T2DM). An investigation was undertaken involving 49 patients diagnosed with T2DM who fulfilled the specified criteria. These individuals underwent BMD assessment as part of a cross-sectional study. The analysis encompassed both univariate and bivariate approaches, utilizing the Chi-square test (X2) and binary logistic regression methods. A total of 30 participants (61%) have decreased BMD. Among the participants aged 60 years and above, 83.4% exhibited a decreased BMD status (osteopenia and osteoporosis), in contrast to the under 60 years age group, in which 40% displayed decreased BMD status. Older age (&amp;gt;60 years) is a risk factor for decreasing bone density onset of diabetes mellitus (DM) diagnosis, duration of DM, glycemic control, body mass index (BMI), use of thiazolidinediones (TZD) drugs, kidney function, were not associated with lower BMD in T2DM patients.

A novel multi-cancer screening approach based on screening objectives, cancer occurrence mechanism, and cost modeling.

e22509 Background: The current cancer screening approach is relatively expensive and unable to cover all general population. Certain amount of information collected is possibly “overkill” at the expense of costs and technology complexity as statistically only 2-3 individuals in very one thousand individuals have cancer. We propose a novel multi-cancer screening for general population which is based on initial screening objectives, new cancer occurrence mechanism, and cost model. Since the step following cancer screening is cancer diagnosis in which significant tests will be carried out, we strongly believe that cancer screening should mainly focus on (1) separating high cancer risk individuals from low risk group, and (2) reduce screening costs and make screening available for everyone. Methods: We analyzed our own large size, multi-year, multi-cancer data as well as other reported studies. We have also studied new cancer occurrence mechanisms developed in recent years which included correlations between immune system and micro- environment change in human body (both of which could occur before the tumor is formed) and cancer occurrence. Finally, we have analyzed cost numbers for the new and traditional approaches. Results: In our extensive multi-year, multi-cancer general population screening of over 200,000 individuals and follow-up study, only 1.4% tested classified as high risk individuals, while this small group accounted for close to 92% of all cancer cases confirmed to date in the follow-up study when enrollment is normalize for all groups. This is very significant because this demonstrates that as long as screening is statistically meaningful and effective, a lot other information is not needed in screening as high risk people will undergo diagnosis anyway. The new screening approach does not require to obtain full information (for example, traceability (cancer location information), as over 98% of people do not likely have cancer) in order to reduce screening costs. The cost analysis results are shown in Table 1. Conclusions: We proposed a new cancer screening approach which is much more cost effective while it is still workable and meets screening objectives. [Table: see text]

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Patterns of screening and access to care in women diagnosed with breast cancer in a safety-net system.

1531 Background: Screening mammography reduces breast cancer specific mortality by allowing diagnosis at an earlier stage. Inconsistent guidelines and limitations in access to primary care are among factors that affect screening uptake. In this study, we reviewed patient characteristics, access to care, and uptake of screening mammogram (SMMG) prior to a breast cancer diagnosis at a safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Simmons Comprehensive Cancer Center. Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 and 2019 at PH were reviewed and data on demographics and clinical presentation were collected. Patients were categorized based on SMMG uptake prior to their cancer diagnosis: never-screened, ever-screened (SMMG &gt; 2 years prior to diagnosis) and recent-screened (SMMG within 2 years of diagnosis). Results: A total of 468 new breast cancer cases were identified (48.7% Hispanic; 32.9% Black). Of these, 12.2% were younger than 40 and 27.8% were 40-49. Payer mix included 64.7% uninsured and 34.8% Medicare/Medicaid. Half of the patients (50.6%) never had SMMG. Never-screened rate was higher among younger patients (98.2% in &lt; 40; 53.8% in 40-49; and 39.4% in &gt;50; p &lt; 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged &gt;40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients &gt;40 was 40.1% (165/411), of whom 22 (13.3% of screen-detects) were diagnosed with cancer on their first ever SMMG. Race/ethnicity, insurance status, and positive family history of cancer were not significantly different between never, ever, and recent-screened patients. Screening uptake correlated with nodal status, tumor size and stage at diagnosis. Patients who had a prior encounter at Parkland were more likely to have a SMMG. Patients established with Parkland primary care at diagnosis were more likely to have early-stage disease. In patients &lt; 40, 24.6% presented with stage IV disease at diagnosis and 57.9% did not have a primary care provider. A positive family history of breast/ovarian cancer or any cancer was noted in 38.6% and 57.9% of patients &lt; 40, respectively. Conclusions: In the cohort presented here, 27.8% of patients were between age 40-49, reflecting the impact of a gap in the guideline, which is now addressed in the most recent iteration of USPSTF guidelines. Connecting ED users to primary care, identifying higher risk individuals through family history, and increasing SMMG rate in the primary care setting are among strategies to reduce the rate of late-stage diagnosis of breast cancer, particularly among vulnerable patient populations.

Significant results from a major multi-year, multi-cancer follow-up study with an enrollment of over 19,000 individuals.

10539 Background: Multi-cancer screening has become a major approach for early stage cancer screening and prevention. However, there has been very few reported multi-year, multi-cancer follow-up studies to validate the effectiveness of multi-cancer screening. We report a number of significant, major findings from what we believe the first large scale, multi-year, multi-cancer follow-up study. Methods: In this study, cancer differentiation analysis (CDA) technology, a bio-physics based detection platform, has been used to screen over 200,000 individuals in a general population. Based on the CDA test values, individuals have been classified into high risk, medium risk and low risk (for cancer) groups. Up to January 31, 2024, a total of 19,141 individuals have been enrolled, with 1,122 in high risk, 15,784 in medium risk, and 2,235 in low risk group. In this follow-up study, enrolled individuals were initially contacted within 6 months (high risk individuals were contacted within 15 days after the test report became available) and subsequently on an annual basis, and their health conditions were recorded. Results: Up to January 31, 2024, 256 individuals have been confirmed with cancer, 1,607 confirmed with pre-cancer diseases and benign tumors, and finally, 1,378 confirmed with diseases. When enrollment is normalized (number of individuals enrolled into each group is equal), for confirmed cancer group, 91.4% is in high risk group, 7.5% in medium risk group and only 1.1% in low risk group. The above result is very significant, indicating that multi-cancer screening using CDA technology is very effective. As shown, there are 23 types of cancer (Table). There are close to 30 types of pre-cancer diseases and benign tumors confirmed. Above results showed that CDA technology is indeed very effective in screening out multiple cancer types (including some cancer types which do not yet have other effective IVD tests such as thyroid cancer and esophageal cancer). The results also show that this approach is very helpful for cancer prevention as it screened out large number of pre-cancer diseases and benign tumor types. Conclusions: A large scale, multi-year, multi-cancer follow-up study has been carried out. Results showed that CDA technology is effective for multi-cancer screening in a general population.[Table: see text]

Optimal Coefficient of Variance Threshold to Minimize Hypoglycemia Risk in Individuals with Well-Controlled Type 1 Diabetes Mellitus.

This study investigated the optimal coefficient of variance (%CV) for preventing hypoglycemia based on real-time continuous glucose monitoring (rt-CGM) data in people with type 1 diabetes mellitus (T1DM) already achieving their mean glucose (MG) target. Data from 172 subjects who underwent rt-CGM for at least 90 days and for whom 439 90-day glycemic profiles were available were analyzed. Receiver operator characteristic analysis was conducted to determine the cut-off value of %CV to achieve time below range (%TBR)<54 mg/dL <1 and =0. Overall mean glycosylated hemoglobin was 6.8% and median %TBR<54 mg/dL was 0.2%. MG was significantly higher and %CV significantly lower in profiles achieving %TBR<54 mg/dL <1 compared to %TBR<54 mg/dL ≥1 (all P<0.001). The cut-off value of %CV for achieving %TBR<54 mg/dL <1 was 37.5%, 37.3%, and 31.0%, in the whole population, MG >135 mg/dL, and ≤135 mg/dL, respectively. The cut-off value for %TBR<54 mg/dL=0% was 29.2% in MG ≤135 mg/dL. In profiles with MG ≤135 mg/dL, 94.2% of profiles with a %CV <31 achieved the target of %TBR<54 mg/dL <1, and 97.3% with a %CV <29.2 achieved the target of %TBR<54 mg/ dL=0%. When MG was >135 mg/dL, 99.4% of profiles with a %CV <37.3 achieved %TBR<54 mg/dL <1. In well-controlled T1DM with MG ≤135 mg/dL, we suggest a %CV <31% to achieve the %TBR<54 mg/dL <1 target. Furthermore, we suggest a %CV <29.2% to achieve the target of %TBR<54 mg/dL =0 for people at high risk of hypoglycemia.

Population-wide impact of a pragmatic program to identify and manage individuals at high-risk of cardiovascular disease: a cluster randomized trial in 120 villages from Northern China

ObjectivesTo explore the population-wide impacts of an evidence-based high-risk strategy for prevention of cardiovascular diseases in resource-poor populations.MethodsA cluster randomized controlled trial was conducted among 120 villages in rural China, with 60 on intervention and 60 on usual care as controls, for 2 years. The intervention emphasized training village doctors to identify high-risk individuals and administering standardized treatments focusing on hypertension management. A random sample of 20 men aged ≥50 years and 20 women aged ≥60 years was drawn from each village before randomization for the baseline survey, and another independent random sample with the same age and sex distribution was drawn at 2 years for the post-intervention survey. The primary outcome was the population mean systolic blood pressure (SBP). Secondary outcomes included the proportions of patients who received regular primary care, antihypertensive medications, aspirin, or lifestyle advice.ResultsA total of 5,654 high cardiovascular risk individuals were identified and managed by village doctors in intervention villages for 15 months on average, with mean SBP lowered by 19.8 mmHg and the proportion with blood pressure under control increased from 22.1% to 72.7%. The primary analysis of the two independent samples (5,050 and 4,887 participants each) showed that population-wide mean SBP in intervention villages did not differ from that in control villages at 2 years (mean difference = 1.0 mmHg, 95% CI: −2.19, 4.26; P = 0.528), though almost all secondary outcomes concerning primary care indicators significantly increased in intervention villages.ConclusionsIn our study, the pragmatic cardiovascular risk management program targeting on high-risk individuals significantly improved the quality of primary care. However, its impact on population blood pressure level and the burden of hypertension-related diseases appeared very limited. Clinical Trial RegistrationClinicalTrial.gov identifier, NCT01259700.

#783 Individualized net benefit of intensive blood pressure lowering among older adults in SPRINT

Abstract Background and Aims The optimal blood pressure (BP) target for older adults remains controversial. This study aimed to determine whether results from the Systolic Blood Pressure Intervention Trial (SPRINT) could be tailored to individual trial participants using risk estimates and simulated preferences about the relative importance of multiple outcomes related to BP lowering. Method This analysis included 4,850 SPRINT participants age ≥65 years. Parsimonious Cox models were internally validated to predict the absolute difference in risk between intensive versus standard BP lowering in each SPRINT participant for all-cause death, cardiovascular outcomes, cognitive outcomes, and serious adverse events. Treatment effects were combined using simulated preference weights into an individualized net benefit, which represents the weighted sum of risk differences across outcomes. Individualized net benefits among older SPRINT participants were compared across categories of age (65-74 years vs. ≥ 75 years), frailty (fit, less fit, and frail), and polypharmacy status. Results When simulating preferences for older adults who view death, cardiovascular events, and cognitive impairment as much more important than the harms of BP lowering, the median (IQR) individualized net benefit was 5% (3%, 7%), and 100% had a net benefit that favoured intensive BP lowering. When simulating benefits and harms to have similar importance, the median (IQR) individualized net benefit was 2% (1%, 3%), and 95.4% had a positive net benefit. In subgroup analyses, the predicted net benefit of intensive BP lowering was significantly greater among those with advanced age, frailty, and polypharmacy compared with lower risk individuals (P&amp;lt;0.001 for all comparisons). Conclusion Almost all older participants in SPRINT had a predicted net benefit that favoured intensive BP control, but the degree of net benefit varied considerably. Personalizing BP targets for older adults according to each person's estimated risks and preferences may provide more refined BP target recommendations.

The influence of assistive technologies on experiences of risk among older adults with age-related vision loss (ARVL).

Living with risk is a salient part of everyday living and although risk affects everyone, older adults are often regarded as a high-risk group, particularly older adults who are aging with a disability, such as vision loss. A prominent focus within low vision rehabilitation is the provision, and training, of older adults in the use of low vision assistive devices as a strategy to manage risks in both the home and community environment. This study aimed to unpack the influence of assistive technologies on experiences of risk among eleven older adults (aged 65+) with age-related vision loss. This critical ethnographic study used home tours, the go-along method, and a semi-structured in-depth interview. The study identified five prevailing themes including: 1) Moving away from the individualization of risk; 2) The cost of assistive technologies as a risk contributor; 3) Practicing 'responsible living'; Technology as an adaptive strategy to risk taking; 4) Resisting the label of 'at risk'; The influence of technology on self-identity; and 5) Technology as a substitution versus supplement for social connectedness. The study findings highlight the importance of moving beyond a technico-scientific perspective of risk, in which risk is framed as an objective phenomenon located in older adults' bodies, and instead framing risk within a broader sociocultural perspective which moves our attention to those contextual or environmental factors that shape experiences of risk for older adults with vision loss.

Apolipoprotein ɛ4 is associated with increased risk of fall- and fracture-related hospitalisation: the Perth Longitudinal Study of Ageing Women.

Apolipoprotein ɛ4 (APOE ɛ4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ɛ4 status and long-term fall- and fracture-related hospitalisation risk in older women. 1276 community-dwelling women from the Perth Longitudinal Study of Ageing Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ɛ4 with fall-, any fracture-, and hip fracture-related hospitalisations, obtained over 14.5 years from linked health records, were examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalisation, 360 (28.2%) women experienced a fracture-related hospitalisation, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to non-carriers, APOE ɛ4 carriers (n=297, 23.3%) had greater risk for a fall- (HR 1.48 95%CI 1.22-1.81), fracture- (HR 1.28, 95%CI 1.01-1.63) or hip fracture-related hospitalisation (HR 1.83 95%CI 1.29-2.61). The estimates remained similar when specific fall and fracture risk factors (fear of falling, plasma 25-hydroxyvitamin D, grip strength, timed-up-and-go, hip BMD, vitamin K status, prevalent diabetes, HbA1c, cholesterol, abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalisation in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher risk individuals to appropriate intervention strategies.

Unveiling Cardiovascular Connections between Familial Hypercholesterolemia (FH) and Left Ventricular Hypertrophy (LVH)

Left ventricular hypertrophy (LVH), a complex cardiac condition characterized by the enlargement and thickening of the left ventricle, is primarily associated with hypertension and valvular heart disease. Recent studies have identified familial hypercholesterolemia (FH) as a secondary cause of LVH. It is characterized by high low-density lipoprotein cholesterol (LDL-C) in blood. FH is an inherited disorder which involves genetic variations associated with abnormal metabolism of LDL-C. This review article aims to provide a comprehensive overview of the relationship between FH and LVH. It summarizes the current understanding of the pathophysiological mechanisms underlying this association and discusses its implications for clinical practice. Elevated LDL-C levels in FH patients lead to accelerated atherosclerosis and an increased risk of premature cardiovascular events. Animal models and clinical observations provide insights into the mechanistic links between elevated LDL-C levels, oxidative stress, inflammation, and LVH development. Early diagnosis of FH would certainly play a critical role in preventing or delaying the development of LVH and subsequent cardiovascular complications. Preemptive measures emphasize the identification of at risk individuals, in-depth clinical evaluations, and implementation of effective treatments including lifestyle modifications, statins, and adjunctive therapies, such as PCSK9 inhibitors or lipoprotein apheresis. By increasing the awareness of FH as a secondary cause of LVH, healthcare professionals can improve early detection and implement appropriate management strategies to mitigate the cardiovascular burden associated with this inherited disorder.

Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy

BackgroundDesmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. ObjectivesThis study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. MethodsWe collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. ResultsOf 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. ConclusionsDES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

Trends in simultaneous alcohol and marijuana use among US adult recent drinkers: Differences by sexual identity, 2015–2020

Simultaneous alcohol and marijuana (SAM) use has become increasingly prevalent among young adult populations. Moreover, lesbian, gay, and bisexual populations are at increased risk for substance use initiation. To date, little research has examined trends in SAM use by sexual identity. This study aimed to investigate trends in SAM use among recent drinkers using nationally representative data. Pooled data from the 2015–2019 and 2020 National Survey on Drug Use and Health (NSDUH) were examined among 120,061 individuals (5.75% LGB) 18 years or older who reported using alcohol in the past month. Given the methodological changes in the study design, we analyzed these waves separately. Covariates included age, race, biological sex, sexual identity, rurality, and past month use of tobacco. Weighted logistic regression models and trend analyses were conducted. An estimated 11,952 of the sample reported using marijuana during their last episode of drinking. A significant linear trend (b = 0.12) of increasing SAM use among recent drinkers from 2015 to 2019. When compared to heterosexual individuals, lesbian or gay (aPR: 1.44, 95% CI 1.26, 1.63) and bisexual (aPR: 1.92, 95% CI 1.77, 2.09) individuals were more likely to report SAM use. Among the entire sample, females had a lower risk of SAM use than males (aPR: 0.68, 95% CI 0.65, 0.72). For 2020, a total of 25,679 adults 18 years or older participated in the survey, with 2622 identifying as LGB and 54.1% reporting past month alcohol use. An estimated 1503 individuals reported SAM use. Consistent with our findings, of those reporting past month alcohol use, LGB populations were at higher risk for SAM use, with gay individuals (aPR: 1.59, 95% CI 1.11, 2.30) at increased risk and bisexual individuals having higher risk (aPR: 2.12, 95% CI 1.73, 2.60). SAM use among individuals presents several critical health concerns, especially for at-risk populations. Findings from the present study can inform tailored interventions to reduce minority stress and stigmatized identities are needed.

Protocolo de valoración de la fibrosis hepática. Pruebas no invasivas para el diagnóstico de la enfermedad hepática crónica compensada

Liver fibrosis should be assessed in all cases of chronic liver disease to adjust follow-up to each individual's risk of hepatic morbidity and mortality. Non-invasive tests can identify both patients with no risk of advanced fibrosis and those with a high probability of having compensated advanced chronic liver disease (cACLD). Simple serum-based tests are accessible and their use is recommended in non-specialized care, where the prevalence of cACLD is low. They should be used to rule out cACLD and only when there are risk factors for liver disease. Elastography techniques are more specific and are used to confirm cACLD in a second stage. Vibration-controlled transient elastography is the most validated and follows the rule of 5 (10-15-20-25kPa), indicating progressively higher risks of decompensation and death. Acoustic radiation force impulse techniques are becoming more widespread as they can be performed as abdominal the same time as ultrasound.

Risk individualisation and moral injury in the treatment of infection as impediments to the tackling of antimicrobial resistance

Antimicrobial resistance (AMR) is subject to extensive risk reduction approaches. A central strategy is reducing the unnecessary use of antimicrobials across agriculture and human and animal health care without jeopardising health outcomes for all species concerned. A prominent framework is antimicrobial stewardship which seeks to balance access to effective infection treatments with ensuring that effective antimicrobials are available for future generations. Balancing these goals has proven challenging and the consumption of antimicrobials and AMR both continue to grow. To shed light on this situation, we examined the risk reasoning that underpins AMR reduction in interviews with 51 practitioners, scientists and policy-makers working on AMR in Australia and the UK. Important themes in our analysis were that action to reduce infection risks clashed with AMR reduction rationalities. Participants were often not able to explain how treating an infection for an individual patient could harmonise with the longer-term goal of AMR reduction. Due to the potential for patient harm, making decisions to use antimicrobials was narrated as individualised and moralised. We argue that more effective AMR reduction depends on addressing this fundamental tension in AMR risk, and its individualising and moralising effects, as the starting point – not the outcome – of policy and practice for AMR reduction.