Large Population-based Prospective Study Research Articles

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research

Abstract Objective Traumatic Brain Injury (TBI) has been purported to increase risk for later developing neurodegenerative disorders (ND). Forensic neuropsychologists are frequently asked to opine on risk for ND after an alleged TBI. We provide an evidence-based foundation to aid forensic practice by summarizing the: role of the neuropsychologist in TBI-related litigation, complexities associated with identifying TBIs in forensic cases, science of TBI in relation to incident dementia, and current scientific evidence for chronic traumatic encephalopathy. Data Selection The most applicable studies to forensic settings are large prospective cohort and population-based cohort studies given their wider generalizability and long periods of follow-up/tracking for outcomes. Data Synthesis Developing ND after TBI is the exception rather than the rule. Only a small subset (< 5%) of individuals with moderate-to-severe TBI, and even fewer (< 1%) with mild TBI, appear to develop ND, and the characteristics that place some at risk remain unclear. Positive evidence for risk of ND after mild TBI is weak and mostly consists of observational studies characterized by methodological limitations. Conclusions Forensic methods used to establish the likely occurrence of TBI are typically more extensive than those used in clinical evaluations, while TBI definitions used in current research are even more rudimentary and inconsistent. Applying clinical research findings regarding TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote TBI/concussion in a causal manner to ND risk is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

1193P Ethical lung cancer screening selection? Comparison of the European 4 - In The Long Run (4ITLR) criteria with the 2021 USPSTF (US), and HUNT lung cancer risk model in a large Norwegian prospective population-based study

1193P Ethical lung cancer screening selection? Comparison of the European 4 - In The Long Run (4ITLR) criteria with the 2021 USPSTF (US), and HUNT lung cancer risk model in a large Norwegian prospective population-based study

Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study

BackgroundAlthough fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort.Methods390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk.ResultsFish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40–0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures.ConclusionsNo significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.

Lifestyle and genetic risk of chronic liver disease in metabolically healthy and unhealthy individuals from the general population

Background & AimsIt is unclear to what extent lifestyle and genetic factors affect incidence of chronic liver disease (CLD) in a general population and if lifestyle affects CLD independently of underlying cardiometabolic perturbations and genetic predisposition. MethodsWe examined 27,991 men and women aged 44-73 years from the Malmö Diet and Cancer Study recruited between 1991-1996 and followed until end of 2020 using registry-linkage (median follow-up time 25.1 years; 382 incident first-time CLD events). Associations between cardiometabolic factors, polygenic risk scores (PRSs), and lifestyle factors in relation to CLD were examined using multivariable Cox proportional hazards regression models. ResultsIncidence of CLD increased with number of cardiometabolic risk factors (the hazard ratio (HR) per each additional cardiometabolic risk factor was 1.33 (95% CI: 1.21-1.45; p= 5.1 x 10-10). Two novel polygenic risk scores (PRS) for metabolic dysfunction-associated steatotic liver disease (MASLD) and a PRS for liver cirrhosis associated with higher risk of CLD but provided marginal predictive utility on top of other risk factors and compared to the PNPLA3 rs738409 genetic variant. An unhealthy lifestyle (high alcohol intake, current smoking, physical inactivity and unhealthy diet) markedly increased risk of CLD (HR=3.97, 95% CI: 2.59-6.10). Observed associations between examined lifestyle factors and CLD were largely independent of cardiometabolic perturbations and polygenic risk. ConclusionsWe confirmed the importance of cardiometabolic dysfunction in relation to risk of CLD in a general population. Lifestyle risk factors were shown to independently associate with CLD and added predictive information on top of cardiometabolic risk factors. Information on the polygenic risk of liver disease does not currently add to prediction of CLD in a general population. Lay summaryIn this large longitudinal study of a general population, we found that cardiometabolic, genetic and lifestyle risk factors all contribute to the development of chronic liver disease (CLD). Our results suggest that an unhealthy lifestyle, including alcohol consumption, smoking, physical inactivity, and an unhealthy diet, substantially increase risk of CLD independently of underlying genetic risk or cardiometabolic health. This suggest that a large proportion of CLD cases are potentially preventable through adoption of healthy lifestyle changes. Impact and implicationsThis large population-based prospective study suggests largely independent roles of cardiometabolic, lifestyle, and genetic risk factors in the development of chronic liver disease. Findings strengthen the evidence base for a beneficial effect of modification of high-risk lifestyle behaviors in the primary prevention of chronic liver disease in the general population.

Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study

Background: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. Methods: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. Results: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. Conclusions: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.

Sleep disorders and mortality: A prospective study in the Canadian longitudinal study on aging

Background and objectivesSleep disorders are commonly linked to various health conditions, although it remains unclear to what degree they are linked with overall mortality. We compared mortality in different self-reported sleep disorders in a large population-based prospective study. MethodsIn this case-control study within the CLSA cohort, participants completed a questionnaire at baseline (2011–2015) measuring overall sleep satisfaction, daily sleep duration, sleep-onset and sleep-maintenance insomnia, daytime somnolence, REM sleep behavior disorder (RBD), restless leg syndrome (RLS), and obstructive sleep apnea (OSA). The vital status of participants was assessed in July 2019. Baseline sleep problems of participants who died (cases) were compared to those who survived (controls). For each case, five age/sex-matched controls were selected. Binary logistic regression was used to estimate the association between sleep symptoms and mortality, adjusting for age, sex, marital status, province, education, alcohol consumption, smoking, caffeine, and body mass index. In a complementary model, anxiety and depression were also added. ResultsAmong 30,097 participants at baseline, 974 deaths were reported in 2019 (60.7 % male, age = 72.3 ± 9.4 years). In the initial analysis, mortality cases reported more baseline sleep-maintenance insomnia (12.1 % vs. 8.0 %, Adjusted OR[95%CI] = 1.62[1.15,2.29]), daytime somnolence (2.4 % vs. 1.1 %, AOR = 2.70[1.34,5.44]), and higher possible RLS (16.4 % vs. 12.4 %, AOR = 1.50[1.09,2.05]). They were also more likely to screen positive for possible OSA (33.8 % vs. 24.2 %, AOR = 1.32[1.07,1.64]); however, this effect was not related to core apnea symptoms. Sleep durations exceeding 10 h/day were also associated with increased mortality (3.4 % vs. 1.9 %, AOR = 1.83[1.04,3.24]). Other sleep symptoms/disorders, such as sleep-onset insomnia (7.3 % vs. 4.3 %, AOR = 1.54 [1.00,2.37]), possible RBD (5.3 % vs. 5.1 %, AOR = 1.02[0.62,1.69]), and overall sleep dissatisfaction (26.5 % vs. 22.6 %, AOR = 1.14[0.93,1.41]) were not different among these groups. After adding anxiety and depression to the adjustment model, all differences attenuated to become statistically non-significant, except for daytime somnolence disorder. When stratified by sex, the association between sleep disorders and mortality was only observed in women, with men showing no association. DiscussionWe confirm a relationship between numerous sleep disorders and mortality. This effect is most evident in women, and appears to be strongly related to co-existing anxiety and depression.

Exposure to Multiple Air Pollutants and the Risk of Fractures: A Large Prospective Population-Based Study.

Atmospheric chemistry studies suggest air pollution impedes ultraviolet B photons and thus reduces cutaneous vitamin D3 synthesis. Biological evidence shows that inhaled pollutants disrupt circulating 25-hydroxyvitamin D (25[OH]D) metabolism and ultimately impact bone health. The hypothesis is that higher air pollution concentrations are associated with a higher risk of fractures, mediated by lower circulating 25(OH)D. The study included participants of the UK Biobank who were free of fracture history at enrollment (2006 to 2010) and analyzed their environmental exposure data (2007 to 2010). Air pollution measurements included the annual averages of air particulate matter (PM2.5 , PM2.5-10 , and PM10 ), nitrogen oxides (NO2 and NOx ), and a composite air pollution score. Multivariable Cox proportional hazard models were used to assess the associations of the individual pollutants and the score with fracture risks. Mediation analyses were conducted to assess the underlying role of serum 25(OH)D in such associations. Among 446,395 participants with a median of 8-year follow-up, 12,288 incident fractures were documented. Participants living in places with the highest quintile of air pollution score had a 15.3% increased risk of fractures (hazard ratio [95%CI]: 1.15[1.09,1.22]) compared to those in the lowest, and 5.49% of this association was mediated through serum 25(OH)D (pmediation < 0.05). Pollutant-specific hazard of top-to-bottom quintiles was 16% for PM2.5 , 4% for PM2.5-10 , 5% for PM10 , 20% for NO2 , and 17% for NOx , with a 4% to 6% mediation effect of serum 25(OH)D concentrations. The associations of the air pollution score with fracture risks were weaker among female participants, those who drank less alcohol, and consumed more fresh fruit than their counterparts (pinteraction < 0.05). © 2023 American Society for Bone and Mineral Research (ASBMR).

Adherence to the Diabetes Risk Reduction Diet and Bladder Cancer Risk in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cohort.

This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort. Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire. During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53-0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64-0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64-0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics. This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer. The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.

Association of oily fish and nonoily fish intakes with all-cause mortality and cause-specific mortality: a large population-based prospective study

BackgroundThere are inconsistent results of cohort studies analyzing the association between fish intake and mortality.ObjectiveThis study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality.MethodsA total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study.ResultsAmong the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05).ConclusionCompared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.

IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases, and all-causes in EPIC - Heidelberg.

The functional status of organs involved in IGF-1 signalling pathways such as the liver influence circulating levels of IGF-1 and hence its relationship with risk of chronic diseases and mortality, yet has received limited attention. To examine the relationship between IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases and all-causes, accounting for liver function. Case-cohort design nested within EPIC-Heidelberg. IGF-1 was measured in 7,461 stored serum samples collected from 1994 to 1998. Median follow-up for incident mortality events: 17.5 years. General community. The case-cohort included a subcohort of 1,810 men and 1,890 women, in addition to 1668 incident cases of cancer (623 breast, 577 prostate, 202 lung and 268 colorectal cancers), and 1428 cases of CVD (707 MIs and 723 strokes) and 2441 cases of death. Higher IGF-1 levels showed direct associations with risks of breast (1.25 95% CI: [1.06-1.47]) and prostate (1.31 [1.09-1.57]) cancers. Restricted cubic splines plots and models including IGF-1 as quintiles revealed a U-shaped relationship between the biomarker and mortality. Both participants with lowest and highest levels of IGF-1 experienced higher hazards of mortality from cancer, cardiovascular diseases and all-causes. The U-shaped form of the relationship persisted but was attenuated in analyses including only participants without any indications of liver dysfunction. This large population-based prospective study showed that both individuals with lowest and highest levels of circulating IGF-1 were at increased risk of deaths from cancer, cardiovascular and all-causes. For individuals with low IGF-1, the excess risks of death were more pronounced among individuals with liver cancer and cirrhosis but were also present among individuals without elevated liver enzymes.

Obstructive sleep apnoea and long-term risk of incident diabetes in the middle-aged and older general population.

Obstructive sleep apnoea (OSA) is associated with increased risk of type 2 diabetes. However, results from large population-based prospective cohort studies are rare. The main aim of the present study was to investigate the relative risk of 8-year incident type 2 diabetes in relation to OSA severity in a prospective cohort study of middle-aged and older adults. A total of 2918 participants (mean age 59 years) of the Korean Genome and Epidemiology Study (KoGES), who underwent home-based overnight polysomnography at baseline examination between 2011 and 2014, were followed up 4-yearly between 2015-2018 and 2019-2021. A total of 1697 participants were present in both follow-ups. After excluding participants who had diabetes at baseline (n=481), a total of 1216 participants were eligible for the analyses. OSA at baseline was categorised by apnoea-hypopnoea index levels as non-OSA (0-4.9 events·h-1), mild OSA (5.0-14.9 events·h-1) and moderate-severe OSA (≥15.0 events·h-1). Incident type 2 diabetes was identified at each follow-up. Compared with non-OSA, participants with moderate-severe OSA had 1.5 times higher risk of developing type 2 diabetes at the end of the 8-year follow-up after adjusting for potential covariates (relative risk 1.50, 95% CI 1.02-2.21). In the same analytical models for 4-year relative risk of incident type 2 diabetes, none of the OSA groups were at significantly higher risk compared with the non-OSA group. Moderate-severe OSA, a modifiable risk factor, poses a higher risk of incident type 2 diabetes compared with non-OSA over an 8-year period in general middle-aged and older adults.

A preoperative prediction model for anastomotic leakage after rectal cancer resection based on 13.175 patients

IntroductionThis study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. Materials and methodsA development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. ResultsA total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileostomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. ConclusionThe present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer.

Obesity- attributable costs of absenteeism among working adults in Portugal

BackgroundObesity leads to poor health outcomes and may adversely affect work productivity. This study, aimed to investigate the obesity- attributable costs of absenteeism among working adults in Portugal.MethodsThe study population included individuals actively working at baseline from the Epidemiology of Chronic Diseases Cohort (EpiDoC), a large Portuguese population-based prospective study. Body mass index was measured at baseline and in two follow-up interviews. Absenteeism in each wave of the EpiDoC was assessed by the question “Did you have a sick leave in the previous 12 months? yes/no”, followed by “How many days did you miss work due to sickness in the previous twelve months?”. Body mass index (BMI) was classified into underweight, normal weight, overweight, and obese, based on the standard World Health Organization definition.Association between obesity and absenteeism was estimated with the negative binomial regression model adjusted for BMI, chronic diseases, and lifestyle. Obesity- attributable costs were calculated using lost gross income during the time absent from work, through the human-capital approach.ResultsThe EpiDoC included 4338 working adults at baseline. Of these, 15.2% were obese at the beginning of the study and 22.7% of the population had been absent from work in the last 12 months. Participants with obesity missed 66% more days at work (IRR: 1.66; CI 95%:1.13–2.44; (p = 0.009.) than those with normal weight. The odds of having been absent from work were 1.4 times higher in obese compared to non-obese individuals (CI 95%: 1.18–1.67; p < 0.01) adjusted to sex and type of work. Obese individuals missed 3.8 more days per year than those with normal weight (95%CI: 3.1–4.5). Extrapolating to the entire Portuguese working population, absenteeism due to obesity incurred an additional cost of €238 million per year.ConclusionObesity imposes a financial burden due to absenteeism in Portugal. Employers and national health regulators should seek effective ways to reduce these costs.

A0362 - Long-term effects of 5α-reductase inhibitors on prostate cancer mortality: A large population-based prospective study

A0362 - Long-term effects of 5α-reductase inhibitors on prostate cancer mortality: A large population-based prospective study

Executive functions and eating behavior: Commentary on Steegers et al. (2021).

Alterations in executive functions have repeatedly been found in individuals suffering from eating and weight disorders. However, less is known about how these cognitive processes might contribute to the etiology of the disorders, as large prospective population-based studies have been missing. Here, we comment on the results of Steegers et al. (2021), a study that helped to fill this gap with a focus on set-shifting abilities predicting symptoms of anorexia nervosa (AN) in children. The main goal of this commentary is to encourage further interpretation of the population-based data beyond its relevance to AN. More specifically, we discuss the role of impaired inhibition as a risk factor for weight gain and obesity.

Association of Oily and Nonoily Fish Intake with All Cause and Cause Specific Mortality: A Large Population-Based Prospective Study

Association of Oily and Nonoily Fish Intake with All Cause and Cause Specific Mortality: A Large Population-Based Prospective Study

Mild anemia and 11- to 15-year mortality risk in young-old and old-old: Results from two population-based cohort studies.

Mild anemia is a frequent although often overlooked finding in old age. Nevertheless, in recent years anemia has been linked to several adverse outcomes in the elderly population. Objective of the study was to investigate the association of mild anemia (hemoglobin concentrations: 10.0-11.9/12.9 g/dL in women/men) with all-cause mortality over 11-15 years and the effect of change in anemia status on mortality in young-old (65-84 years) and old-old (80+ years). The Health and Anemia and Monzino 80-plus are two door-to-door, prospective population-based studies that included residents aged 65-plus years in Biella municipality and 80-plus years in Varese province, Italy. No exclusion criteria were used. Among 4,494 young-old and 1,842 old-old, mortality risk over 15/11 years was significantly higher in individuals with mild anemia compared with those without (young-old: fully-adjusted HR: 1.35, 95%CI, 1.15-1.58; old-old: fully-adjusted HR: 1.28, 95%CI, 1.14-1.44). Results were similar in the disease-free subpopulation (age, sex, education, smoking history, and alcohol consumption adjusted HR: 1.54, 95%CI, 1.02-2.34). Both age groups showed a dose-response relationship between anemia severity and mortality (P for trend <0.0001). Mortality risk was significantly associated with chronic disease and chronic kidney disease mild anemia in both age groups, and with vitamin B12/folate deficiency and unexplained mild anemia in young-old. In participants with two hemoglobin determinations, seven-year mortality risk was significantly higher in incident and persistent anemic cases compared to constant non-anemic individuals in both age groups. In participants without anemia at baseline also hemoglobin decline was significantly associated with an increased mortality risk over seven years in both young-old and old-old. Limited to the Monzino 80-plus study, the association remained significant also when the risk was further adjusted also for time-varying covariates and time-varying anemia status over time. Findings from these two large prospective population-based studies consistently suggest an independent, long-term impact of mild anemia on survival at older ages.

Screening for Monoclonal Gammopathy of Undetermined Significance: A Population-Based Randomized Clinical Trial. First Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Background:Cancer screening is performed worldwide for several malignancies. Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM) and related lymphoproliferative disorders (LP). However, less than 5% of all MM patients are diagnosed during their precursor state and individuals who develop MM while being monitored for MGUS have better overall survival and fewer complications, compared to MM patients diagnosed without knowledge of MGUS. Thus, population-based screening for MGUS could identify candidates for early treatment of MM/LPs. To evaluate whether systematic screening is beneficial, we performed the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, the first population-based screening study for MGUS that includes a randomized clinical trial (RCT) of follow-up and treatment strategies.Methods:All living residents of Iceland on September 9th, 2016 who were born before 1976 (N=148,708) were invited to participate. Of those, 80,759 (54.3%) provided informed consent for screening. Serum samples were collected from participants alongside clinical blood sampling in the Icelandic health service between September 2016 and the end of 2020. All samples were shipped to the Binding Site in Birmingham, UK, for screening. Samples were tested for M-proteins by capillary zone electrophoresis and immunofixation electrophoresis performed to confirm and characterize suspected M-proteins. Free light chains (FLCs) were measured using the FreeLite® assay. Individuals with a previous diagnosis of MM/LPs/MGUS (N=237) were excluded. Per protocol and informed consent, participants with MGUS were randomized to one of the three study arms: Arm 1 where participants are not contacted; Arm 2 where individuals are followed based on current guidelines; and Arm 3 where individuals are followed with a more intensive diagnostic and monitoring strategy. Participants who progress are offered early treatment. All participants repeatedly answered questionnaires on quality of life and mental health.Results:A total of 75,422 participants (93.4%) provided a serum sample for screening. Of those, 3,725 (4.9%) had MGUS. The prevalence of MGUS was dependent on age with 2.3%, 6.2%, and 12.9% diagnosed in age groups 40-59, 60-79, and 80-103 years, respectively. The prevalence of MGUS was higher in males, 5.9% vs 4.1% (p<0.0001). Most individuals with MGUS had either low-risk (38%) or low-intermediate (36%) risk MGUS, followed by high-intermediate (26%) risk MGUS. High-risk MGUS was only present in 0.2% of MGUS cases (n=9).The RCT includes 3,487 newly diagnosed MGUS individuals with 1164, 1159, and 1164 individuals in arms 1, 2 and 3, respectively (Table). The median age at diagnosis was 69 years in arms 1 and 2, and 70 years in arm 3. Females constituted 45.9% and the isotypes were IgG (50%), IgA (10%), IgM (18%) and biclonal (8%). The median M-protein concentration was 0.34 g/dL. A total of 428 light-chain MGUS cases were randomized. The demographic distribution was well balanced between the three arms.After a median follow-up of 3 years, 194 patients in the RCT have been diagnosed with any LP: 9 in arm 1, 92 in arm 2, and 133 in arm 3 (p<0.001). The participants in arm 1 were diagnosed with smoldering Waldenström's macroglobulinemia (SWM)(N=2), WM (N=2), chronic lymphocytic leukemia (CLL) (N=1), and MM (N=4). Participants in arm 2 were diagnosed with amyloidosis (N=1), SWM (N=18), WM (N=2), CLL (N=2), non-Hodgkin lymphoma (NHL) (N=1), smoldering MM (SMM) (N=56), and MM (N=12). Participants in arm 3 were diagnosed with amyloidosis (N=2), SWM (N=22), CLL (N=5), NHL (N=6), SMM (N=82), and MM (N=16). The difference between study arms was statistically significant for all LPs combined, and for SWM, SMM, and MM (Table).Conclusion:In this large prospective population-based screening study including >75,000 screened persons, we have identified 3,725 individuals with monoclonal gammopathy. In the RCT, after 3 years of follow-up, we show that active screening identifies significantly higher number of individuals with full-blown malignancy and smoldering disease, illustrating the fact that early detection and intervention is achievable. Although our findings are encouraging, until final results of the iStopMM study become available, including data on survival and quality of life, we advise against systematic MGUS screening in healthy individuals. [Display omitted] DisclosuresKristinsson: Amgen: Research Funding; Celgene: Research Funding. Kampanis: The Binding Site: Current Employment. Hultcrantz: Curio Science LLC: Consultancy; Daiichi Sankyo: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy. Durie: Amgen: Other: fees from non-CME/CE services ; Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy. Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Landgren: Janssen: Research Funding; Celgene: Research Funding; Janssen: Honoraria; Janssen: Other: IDMC; Amgen: Honoraria; Takeda: Other: IDMC; Amgen: Research Funding; GSK: Honoraria.

November 2021 Stroke Highlights

November 2021 <i>Stroke</i> Highlights

Chronic disease surveillance in Alberta's tomorrow project using administrative health data.

IntroductionAlberta’s Tomorrow Project (ATP) is the largest population-based prospective cohort study of cancer and chronic diseases in Alberta, Canada. The ATP cohort data were primarily self-reported by participants on lifestyle behaviors and disease risk factors at the enrollment, which lacks sufficient and accurate data on chronic disease diagnosis for longer-term follow-up.ObjectivesTo characterize the occurrence rate and trend of chronic diseases in the ATP cohort by linking with administrative healthcare data.MethodsA set of validated algorithms using ICD codes were applied to Alberta Health (AH) administrative data (October 2000-March 2018) linked to the ATP cohort to determine the prevalence and incidence of common chronic diseases.ResultsThere were 52,770 ATP participants (51.2±9.4 years old at enrollment and 63.7% females) linked to the AH data with average follow-up of 10.1±4.4 years. In the ATP cohort, hypertension (18.5%), depression (18.1%), chronic pain (12.8%), osteoarthritis (10.1%) and cardiovascular diseases (8.7%) were the most prevalent chronic conditions. The incidence rates varied across diseases, with the highest rates for hypertension (22.1 per 1000 person-year), osteoarthritis (16.2 per 1000 person-year) and ischemic heart diseases (13.0 per 1000 person-year). All chronic conditions had increased prevalence over time (p < for trend tests), while incidence rates were relatively stable. The proportion of participants with two or more of these conditions (multi-morbidity) increased from 3.9% in 2001 to 40.3% in 2017.ConclusionsThis study shows an increasing trend of chronic diseases in the ATP cohort, particularly related to cardiovascular diseases and multi-morbidity. Using administrative health data to monitor chronic diseases for large population-based prospective cohort studies is feasible in Alberta, and our approach could be further applied in a broader research area, including health services research, to enhance research capacity of these population-based studies in Canada.