Age Strata Research Articles

Spirometric and anthropometric improvements in response to elexacaftor/tezacaftor/ivacaftor depending on age and lung disease severity.

Introduction: Triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) was introduced in August 2020 in Germany for people with CF (pwCF) ≥12years (yrs.) of age and in June 2021 for pwCF ≥6yrs of age. In this single-center study, we analyzed longitudinal data on the percent-predicted forced expiratory volume (ppFEV1) and body-mass-index (BMI) for 12months (mo.) after initiation of ETI by linear mixed models and regression analyses to identify age- and severity-dependent determinants of response to ETI. Methods: We obtained data on 42 children ≥6-11yrs, 41 adolescents ≥12-17yrs, and 143 adults by spirometry and anthropometry prior to ETI, and 3 and 12mo. after ETI initiation. Data were stratified by the age group and further sub-divided into age-specific ppFEV1 impairment. To achieve this, the age strata were divided into three groups, each according to their baseline ppFEV1: lowest 25%, middle 50%, and top 25% of ppFEV1. Results: Adolescents and children with more severe lung disease prior to ETI (within the lowest 25% of age-specific ppFEV1) showed higher improvements in lung function than adults in this severity group (+18.5 vs. +7.5; p = 0.002 after 3mo. and +13.8 vs. +7.2; p = 0.012 after 12mo. of ETI therapy for ≥12-17years and +19.8 vs. +7.5; p = 0.007 after 3mo. for children ≥6-11yrs). In all age groups, participants with more severe lung disease showed higher BMI gains than those with medium or good lung function (within the middle 50% or top 25% of age-specific ppFEV1). Regression analyses identified age as a predictive factor for FEV1 increase at 3mo. after ETI initiation, and age and ppFEV1 at ETI initiation as predictive factors for FEV1 increase 12mo. after ETI initiation. Discussion: We report initial data, which suggest that clinical response toward ETI depends on age and lung disease severity prior to ETI initiation, which argue for early initiation of ETI.

Allostatic load and incident heart failure in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study

BackgroundAllostatic load (AL) is the physiologic “wear and tear” on the body from stress. Yet, despite stress being implicated in the development heart failure (HF), it is unknown whether AL is associated with incident HF events.MethodsWe examined 16,765 participants without HF at baseline from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The main exposure was AL score quartile. AL was determined according to 11 physiologic parameters, whereby each parameter was assigned points (0–3) based on quartiles within the sample, and points were summed to create a total AL score ranging from 0–33. The outcome was incident HF event. We examined the association between AL quartile (Q1-Q4) and incident HF events using Cox proportional hazards models, adjusted for demographics, socioeconomic factors, and lifestyle.ResultsThe mean age was 64 ± 9.6 years, 61.5% were women, and 38.7% were Black participants. Over a median follow up of 11.4 years, we observed 750 incident HF events (635 HF hospitalizations and 115 HF deaths). Compared to the lowest AL quartile (Q1), the fully adjusted hazards of an incident HF event increased in a graded fashion: Q2 HR 1.49 95% CI 1.12–1.98; Q3 HR 2.47 95% CI 1.89–3.23; Q4 HR 4.28 95% CI 3.28–5.59. The HRs for incident HF event in the fully adjusted model that also adjusted for CAD were attenuated, but remained significant and increased in a similar, graded fashion by AL quartile. There was a significant age interaction (p-for-interaction < 0.001), whereby the associations were observed across each age stratum, but the HRs were highest among those aged < 65 years.ConclusionAL was associated with incident HF events, suggesting that AL could be an important risk factor and potential target for future interventions to prevent HF.

Knee injury and osteoarthritis outcome score (KOOS) – National record-based reference values

BackgroundKnee Injury and Osteoarthritis Outcome Score (KOOS) and the short form KOOS-12 are commonly used in clinical practice and research but there are no national record-based reference values to aid interpretation. The aim of this study was to establish national record-based reference values for the KOOS and its short form KOOS-12. Patients and methodsA national record-based representative sample of 9996 adult citizens were derived from the Danish Civil Registration System. The selection of citizens was based on seven predefined age groups with an equal sex distribution across each age strata. The KOOS questionnaire was sent to all participants, together with two supplemental questions regarding previous knee problems and body mass index (BMI). ResultsA total of 2842 participants completed the KOOS, 1463 women (51.4%) and 1379 men (48.6%). The mean KOOS subscale scores were: pain 85.3 (95% confidence interval (CI): 84.6–85.9), symptoms 85.1 (95% CI: 84.5–85.8), activities of daily living (ADL) 86.7 (95% CI: 86.0–87.3), sport and recreation function 70.9 (95% CI: 69.8–72.0), quality of life (QOL) 74.9 (95% CI: 73.9–75.8).Age- and sex-specific reference values showed small differences in mean scores between the five KOOS subscales and all were below the threshold for clinically relevant improvement (10 points).Knee problems were associated with worse KOOS scores across all subscales. The difference in the mean subscale scores between the lowest (<24.9) and highest (>40) BMI groups ranged from 12.9 to 24.1. Comparable results were observed for KOOS-12. ConclusionKOOS and KOOS-12 reference values can, in most situations, be used without stratification for age and sex. Sport/recreation reference values stratified for age and BMI may be of importance.

The Incidence of Lyme Borreliosis Among Children.

First recognized in children in the United States, Lyme borreliosis (LB) is the most prevalent tickborne illness in North America and Europe. However, the incidence of LB in children, including geographic variation and difference from that in adults, is incompletely described. We compiled surveillance data from public health agency websites reporting age-stratified LB case data, which was combined with census data to derive incidence estimates. Additional incidence estimates were obtained through a systematic literature review. We identified 18 surveillance systems and 15 published studies for derivation of LB incidence in children. National incidence of >10 cases in children per 100,000 per year were estimated for the United States and parts of Eastern, Western and Northern Europe. However, there was substantial variation in incidence among countries in some European regions. National incidence estimates from the literature largely aligned with estimates from surveillance. Surveillance-reported pediatric incidence was lower than adult incidence in adults in 8 countries, similar to adult incidence in 3 countries, and higher than adult incidence in 1 country. Among all pediatric age strata, the 5-9 years of age stratum had the highest proportion of pediatric cases in most countries. As pediatric LB represents a substantial proportion of overall LB incidence across countries in Europe and North America, LB prevention and control efforts should target pediatric as well as adult populations. However, better data are needed to fully characterize the difference in incidence across geographic regions.

Evaluation of the Relationship Between Dental Caries and Anemia in Adult Patients

Abstract: This study investigated a possible association between dental caries and anaemia in adult patients. It screened 403 adults who had reported for routine blood investigation with regard to their haemoglobin (Hb) and dental caries status. The mean DMFT index was 5.2 for both genders in the anaemic group, while the mean DMFT score was 5.204.97 for anaemic group and 3.483.10 for non-anaemic group. The Mann-Whitney U test showed a statistically significant association between dental caries and anaemia (p0.001). The p-value was calculated for each age strata to eliminate the confounding effect of age on dental caries and anaemia. The study results confirmed a strong association between dental caries and anaemia in adults.

Regional assessments of supraspinatus muscle stiffness in normal adults using shear wave elastography

ObjectivesTo provide normal references for regional shear wave elastography assessments of supraspinatus muscle in a population. MethodsShear wave elastography images of supraspinatus muscles were evaluated on 100 shoulders of 50 normal adults in a fixed position with 30° shoulder abduction both at rest and contraction. Shear wave velocity values and activity values of intramuscular tendon, anterior superficial, anterior deep, posterior superficial, posterior deep, and central subregions were measured. The possible differences in hand dominance, sexes, stratified age groups, and internal muscular-component subregions were discussed. ResultsThe results showed that shear wave velocity values at rest and activity values differed significantly among supraspinatus muscular-component subregions. Shear wave velocity values at rest were normally highest in posterior deep and lowest in central subregions, whereas activity values were highest in central subregions. The results also showed evaluation of the intramuscular tendon using shear wave elastography to be practicable. The differences in shear wave velocity values at rest between the dominant and nondominant sides were not significant in each subregion, while the values at rest of the majority of subregions were significantly greater in males than in females. Stratified by age groups of 10 years, the shear wave velocity values at rest of some subregions tended to increase with age, with uncorrelations possibly related to insufficient sample sizes and different intensities of limb activities. ConclusionsThis study suggested that regional assessments of supraspinatus stiffness using shear wave elastography are feasible, with further research supporting that it can provide information on the surgery, training, and rehabilitation of rotator cuff tears.

Expiratory Diameter of the Inferior Vena Cava Diameter IVC Across Age Groups in CCF Subjects

Background: Dilatation of the Inferior Vena Cava (IVC) is used as the ultrasonic diagnostic feature in patients suspected of congestive heart failure. The IVC diameter has being reported to vary among the various age ranges. Knowledge of these variations is useful in precision diagnoses of CHF by imaging scientists. Aim: The study aimed to determining the ultrasonic mean expiratory diameter of the IVC across the various age ranges with CCF in Azare, Bauchi State-Nigeria. Methods: One hundred and ninety-nine subjects of both sexes diagnosed with Congestive Cardiac Failure were randomly grouped into six age groups. A structured questionnaire was used to rule out those that fell within the exclusion criteria. Their informed consent was sought for abdominal ultrasound scan. The probe was placed on the mid line of the body, half-way between the xiphoid process and the umbilicus with the marker on the probe directed towards the patient`s head to obtain a longitudinal view of the IVC. The maximum IVC diameter was measured from the subcostal view using the electronic caliper of the scan machine during expiration on a B mode. The mean value of each group was obtained and analyzed statistically. Results: It was observed that, the mean expiratory diameter of the IVC across the age group (18-27, 28-37, 38-47, 48-57, 58-67 and 68-77) years were (1.89, 1.96, 1.94, 2.06, 1.91, 1.97 and 1.94) cm, respectively P-value ≤ 0.05. Conclusion: In conclusion, the normal cutoff values for indicating a dilated IVC across the different age strata in the populace has been established.

Effect of a Nurse Navigation Intervention on Mental Symptoms in Patients With Psychological Vulnerability and Breast Cancer

The unmet needs regarding symptom management of psychological distress among patients with breast cancer must be addressed. However, little evidence exists on effective interventions, such as nurse navigation. To compare the long-term effects of the REBECCA (Rehabilitation After Breast Cancer) nurse navigation intervention vs usual care in patients with breast cancer who were psychologically vulnerable. This parallel randomized clinical trial recruited and evaluated for eligibility adult female patients with newly diagnosed breast cancer and symptoms of psychological distress (distress score of ≥7 points on Distress Thermometer) at Rigshospitalet in Copenhagen, Denmark, from August 2017 to October 2019. This study continued the work of a pilot study, extending the follow-up to 18 months. Patients who met the inclusion criteria were randomized to either standard care or the REBECCA intervention. Intention-to-treat analyses were performed from June 2021 to October 2022. Patients who were randomized to the REBECCA intervention received nurse navigation and symptom screening as well as standard care. Standard care included regular treatment, nurse support at chemotherapy and radiotherapy appointments, and municipality-based rehabilitation. The primary outcome was distress, as measured using the Distress Thermometer. The secondary outcomes included symptoms of anxiety, symptoms of depression, breast cancer-specific health-related quality of life, fear of recurrence, sleep, cognitive function, patient activation, pain, health behavior, body mass index, and need for support. Long-term effects at 6, 12, and 18 months were examined using mixed-effect models, adjusting for randomization strata of age and treatment modality. A total of 309 female patients were included in the analysis, with 153 patients randomized to the standard care group and 156 patients randomized to the REBECCA intervention group. Mean (SD) age was 56 (11) years with only small between-group differences. Patients receiving the REBECCA intervention compared with standard care had reduced (although not significant) symptoms of distress, especially at the 12-month follow-up (estimated effect = -0.51 [95% CI, -1.05 to 0.04]; effect size [ES] = -0.49). Significant effects were seen for symptoms of depression at 6 months (estimated effect = -1.39 [95% CI, -2.33 to -0.44]; ES = -0.27), and breast cancer-specific health-related quality of life at 12 months (estimated effect = 4.03 [95% CI, 1.28- 6.77]; ES = 0.31). Nonsignificant reductions were seen for symptoms of anxiety at 6 months (estimated effect = -1.00 [95% CI, -1.95 to -0.06]; ES = -0.21) and 12 months (estimated effect = -1.01 [95% CI, -1.97 to -0.04]; ES = -0.21), and a nonsignificant increase was seen for patient activation at 18 months (estimated effect = 3.52 [95% CI, -0.09 to 7.12]; ES = 0.25). Stronger intervention effects were observed for younger age, low patient activation, less education, and low social support. Results of this study indicate that patients with breast cancer who were psychologically vulnerable (ie, having moderate to high psychological distress) did not experience significant reduction in distress with nurse navigation. Further research is needed to develop the intervention's framework and investigate its potential use in clinical practice. ClinicalTrials.gov Identifier: NCT03254875.

Characterization of Pediatric Reports in the US Food and Drug Administration Adverse Event Reporting System from 2010-2020: A Cross-Sectional Study.

The Food and Drug Administration Adverse Event Reporting System (FAERS) is a database of adverse event (AE) and medication error reports for drugs and therapeutic biologics. Examining trends of reported individual case safety reports (ICSRs) provides context for evaluating safety concerns. Characterize pediatric FAERS ICSRs and compare trends (1) to adult reports; (2) within pediatric subgroups. This cross-sectional study examined FAERS ICSRs received between January 1, 2010, through December 31, 2020. Stratified age bands were neonates, infants, younger children, older children, adolescents, and adults. We characterized groups by patient demographic information, suspect products, AEs, and reporter type. From 2010 to 2020, there were 11,258,995 FAERS ICSRs; 3.1% described pediatric patients. Compared to adults, pediatric ICSRs had higher proportions of all serious outcomes except death. Within pediatric subgroups, neonates had the highest proportions of serious outcomes (96.2%) compared to infants, younger children, older children, and adolescents (79.8%, 67.9%, 59.5%, and 52.7%, respectively). Younger pediatric age groups were more likely to have weight information than older age groups but were less likely to include gender information. The most frequently reported AE was off label use for pediatrics and drug ineffective for adults. Products and AEs reported also differed among pediatric subgroups. Neonates, infants, and adolescents had entirely distinct sets of top five product-event combinations. Pediatric ICSRs represent a minority of FAERS reports but have distinctly different attributes relative to adult ICSRs. Reporting trends also vary within pediatric subgroups, which highlights the need for unique considerations for pediatric safety surveillance.

Discontinuation of Car Seat Tolerance Screening and Postdischarge Adverse Outcomes in Infants Born Preterm

To study the association between discontinuing predischarge car seat tolerance screening (CSTS) with 30-day postdischarge adverse outcomes in infants born preterm. Retrospective cohort study involving all infants born preterm from 2010 through 2021 who survived to discharge to home in a 14-hospital integrated health care system. The exposure was discontinuation of CSTS. The primary outcome was a composite rate of death, 911 call-triggered transports, or readmissions associated with diagnostic codes of respiratory disorders, apnea, apparent life-threatening event, or brief resolved unexplained events within 30days of discharge. Outcomes of infants born in the periods of CSTS and after discontinuation were compared. Twelve of 14 hospitals initially utilized CSTS and contributed patients to the CSTS period; 71.4% of neonatal intensive care unit (NICU) patients and 26.9% of non-NICU infants were screened. All hospitals participated in the discontinuation period; 0.1% was screened. Rates of the unadjusted primary outcome were 1.02% in infants in the CSTS period (n=21 122) and 1.06% after discontinuation (n=20 142) (P=.76). The aOR (95% CI) was 0.95 (0.75, 1.19). Statistically insignificant differences between periods were observed in components of the primary outcome, gestational age strata, NICU admission status groups, and other secondary analyses. Discontinuation of CSTS in a large integrated health care network was not associated with a change in 30-day postdischarge adverse outcomes. CSTS's value as a standard predischarge assessment deserves further evaluation.

O-144 Critical assessment of possible clinical benefits of culturing human embryos until day 7

Abstract Study question Is there any benefit of extending culture until day (D) 7 to increase euploid blastocysts yield and clinical outcomes in a PGT-Aneuploidy analysis (PGT-A) program? Summary answer Extended culture until D7 increases euploid blastocysts yield and cumulative live birth. Highest benefit was observed in patients aged ≤41 with ≤2 D5/D6 blastocysts biopsied. What is known already It is well-known that female age is the strongest predictive factor of embryo aneuploidy and has been associated with delayed blastocyst development in vitro. Culturing embryos until D7 might increase biopsied blastocyst yields and euploidy outcomes among women undergoing ART as already been published. However, extended culture until D7 increases IVF workload and implies extra cost. It is unclear whether the practice is justified when a certain number of blastocysts have already been biopsied on D5/D6. Therefore, the additive value of extended culture until D7 needs further evaluation. Studies published in the literature have small sample sizes and are controversial. Study design, size, duration This single center observational study included 30,941 blastocysts from 6,976 consecutive IVF/ICSI PGT-A fresh autologous cycles performed between 2017 and 2022. Patients who underwent PGT-A by Next Generation Sequencing (NGS) were considered for the analysis. Only blastocysts graded ≥BL3CC (Gardner) that underwent TE biopsy on D5, D6 or D7 were included. Data were stratified by age categories (&amp;lt;37, 37-41 and &amp;gt;41) and on number of biopsied blastocysts performed on D5 and/or D6 of embryo culture. Participants/materials, setting, methods The additive value of extended embryo culture was assessed in terms of absolute numbers (percentage of D7 euploid blastocysts obtained) and theoretical benefit to cumulative live birth rate (having at least 1 live birth by using all available euploid blastocysts) as calculated by binomial density function. Results was assessed between female age strata (&amp;lt;37, 37-41, &amp;gt;41) and number of embryos biopsied in D5/D6 (No biopsy, ≤2, 3-4, 5-6 or ≥ 6 biopsied). Main results and the role of chance A total of 18,478 blastocysts were biopsied on D5 (38.5%), D6 (55.2%) or D7(6.3%). Euploidy rate decreased significantly for blastocysts biopsied on D5, D6 and D7 (55.6%, 39.7% and 27.1%, P &amp;lt; 0.001, respectively). When stratifying patients by age, euploidy rates were consistently higher for D5 biopsied blastocysts compared to D6 and D7 (&amp;lt;37: 61.1%, 50.0% and 38.5%, P &amp;lt; 0.001; 37-41: 39.0%, 27.8% and 20.1%, P &amp;lt; 0.001; &amp;gt;41: 18.5%, 9.0% and 3.9%, P &amp;lt; 0.001, for D5, D6 and D7, respectively). The chances of obtaining at least one euploid D7 blastocyst was higher among patients &amp;lt;37 and 37–41 years compared to &amp;gt; 41 years (7.2% and 4.4% vs. 0.6%, P &amp;lt; 0.001). Among women &amp;lt;37, a &amp;gt; 25% increase in cumulative live birth rate (theoretical) was detected in 10.1% with no biopsy on D5/D6, 2.5% with 1-2 blastocysts biopsied on D5/D6 and only 0.3% with ≥3 blastocysts biopsied on D5/D6 (P &amp;lt; 0.001). In older women (37-41), a &amp;gt; 25% increase in cumulative live birth rate (theoretical) was found in 5.6% with no biopsy on D5/D6, 2.5% with 1-2 blastocysts biopsied on D5/D6, and only 0.4% with ≥3 blastocysts biopsied on D5/D6 (P &amp;lt; 0.001). Women &amp;gt;41 years rarely benefited from extended culture util D7 (&amp;lt;1%) regardless of the number of blastocysts biopsied on D5/D6. Limitations, reasons for caution The study was based on a retrospective analysis data and results were calculated on a theoretical cumulative live birth. While this study provides one of the largest number of blastocysts analyzed in PGT-A and “freeze all” strategy, results should not be extrapolated to other populations or different ART routine practices. Wider implications of the findings Usable blastocysts (6.3%) and euploidy rates (27.1%) are significantly lower with D7 blastocysts compared to D5/D6 blastocysts. Patients aged &amp;gt;41 do not benefit from extended embryo culture to D7 (&amp;lt;1%). Culturing blastocysts for 7 days should be mainly decided based on the number of blastocysts biopsied on D5 or D6. Trial registration number not applicable

Psychometric Properties of Controlled Oral Word Association (COWA) Test and Associations With Education and Bilingualism in American Indian Adults: The Strong Heart Study.

The Controlled Oral Word Association (COWA) test is used to assess phonemic fluency and executive function. Formal validation of test scores is important for accurate cognitive evaluation. However, there is a dearth of psychometric validation among American Indian adults. Given high burden of dementia risk and key contextual factors associated with cognitive assessments, this represents a critical oversight. In a large, longitudinal population-based cohort study of adult American Indians, we examined several validity inferences for COWA, including scoring, generalization, and extrapolation inferences, by investigation of factor structure, internal consistency, test-retest reliability, and differential test functioning. We found adequate unidimensional model fit, with high factor loadings. Internal consistency reliability and test-retest reliability were 0.88 and 0.77, respectively, for the full group. COWA scores were lowest among the oldest, lowest education, bilingual speakers; group effects for sex and bilingual status were small; age effect was medium; and education effect was largest. However, Wide Range Achievement Test (WRAT) score effect was stronger than education effect, suggesting better contextualization may be needed. These results support interpretation of total COWA score, including across sex, age, or language use strata.

Cosmetics and Detergents with Recycled CO2: A Cross-Country Study with a Modified by Risk Perception Values-Beliefs-Norms Model.

This paper presents the examination of a values-beliefs-norms (VBN) model, modified by climate change risk perception, in France, Germany, and Spain, to investigate consumers' intentions to purchase personal and house care products that are going to contain innovative ingredients made from recycled CO2. Electronic interviews were undertaken by a research agency on stratified (gender and age) samples in each country. Solely biospheric values indicated a statistically significant and positive causal relationship with risk perception. Risk perception provided the strongest of all impacts on awareness of consequences. Awareness of consequences affected the ascription of responsibility, and ascription of responsibility affected personal norms, which in turn generated consumption intentions. VBN was found powerful in explaining 58%, 60.2%, and 43.3% of the variance in intentions to buy CPGs with green chemical ingredients in French, German, and Spanish consumers, respectively. Moderation analysis indicated that the relationship between personal norms and consumption intentions is stronger in France and Germany than in Spain. Theoretical and practical implications are provided.

#5772 ESTIMATING CKD PREVALENCE AND INCIDENCE USING CROSS-SECTIONAL GERMAN CLAIMS DATA IN PERSONS AGED 70+

Abstract Background and Aims Little is known about trends over time and anticipated improvements in CKD diagnosis after the implementation of the Kidney Disease – Improving Global Outcomes (KDIGO) guidelines in 2012. We investigated CKD prevalence and incidence over time using claims data in persons aged 70+. Method We assessed CKD prevalence and incidence biennially in cross-sectional claims data of the German health insurance fund “AOK Nordost” for persons aged 70+ between 2012 and 2018. Data are available for n = 62,200 persons per year and were sampled equally distributed for five age strata (70-74, 75–79, 80–84, 85–89, ≥90) and for sex. CKD prevalence and incidence were estimated in 2012, 2014, 2016, and 2018 using in- and outpatient ICD-10 diagnoses (N18.3, N18.4, N18.5, N18.8, N18.9, N19). Incidence was defined as prevalent cases without a diagnosis in the four quarters preceding their first CKD diagnosis over all persons at risk (i.e., who were not prevalent in the respective previous year). Results are shown in total (standardized by age and sex using nationwide demographic distributions for a respective year) as well as stratified by age and sex. Cochran-Armitage test was applied to test time trends for incidence and prevalence from 2012–2018. Results Claims data-based CKD prevalence showed a significant constant increase from 0.18 in 2012 to 0.26 in 2018 (p &amp;lt;0.001). This time trend in CKD prevalence was consistent among all age and sex strata (Figure 1). Over the same time period, CKD incidence increased from 0.06 to 0.08 (p &amp;lt;0.001), while the percentage of persons at risk decreased from 0.81 to 0.72 between 2012 and 2018 due to increasing prevalence (Table 1). Both prevalence and incidence estimates were higher in males compared to females in all age strata (Figure 1). Conclusion The present cross-sectional analysis in claims data allows novel insights of CKD prevalence and incidence among older adults in Germany. CKD prevalence increased constantly over time after the introduction of the KDIGO guidelines in 2012. For CKD incidence, we detected only a small increase over the observation period. The extent of time trends for CKD incidence might be underestimated due to increasing prevalence.

Proton pump inhibitor use and risk of pneumonia: a self-controlled case series study.

Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account. This population-based and nationwide Swedish study conducted in 2005-2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia. Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71-1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02-1.14). PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia.

Decomposition of disparities in life expectancy with applications to administrative health claims and registry data

Research shows that geographic disparities in life expectancy between leading and lagging states are increasing over time while racial disparities between Black and White Americans have been going down. In the 65+ age strata morbidity is the most common cause of death, making differences in morbidity and associated adverse health-related outcomes between advantaged and disadvantaged groups an important aspect of disparities in life expectancy at age 65 (LE65). In this study, we used Pollard’s decomposition to evaluate the disease-related contributions to disparities in LE65 for two types of data with distinctly differing structures: population/registry and administrative claims. To do so, we analyzed Pollard’s integral, which is exact by construction, and developed exact analytic solutions for both types of data without the need for numerical integration. The solutions are broadly applicable and easily implemented. Applying these solutions, we found that the largest relative contributions to geographic disparities in LE65 were chronic lower respiratory diseases, circulatory diseases, and lung cancer; and, to racial disparities: arterial hypertension, diabetes mellitus, and cerebrovascular diseases. Overall, the increase in LE65 observed over 1998–2005 and 2010–2017 was primarily due to a reduction in the contributions of acute and chronic ischemic diseases; this was partially offset by increased contributions of diseases of the nervous system including dementia and Alzheimer’s disease.

The joint impacts of sex and race/ethnicity on incidence of grade 1 versus grades 2-3 meningioma across the lifespan.

Previous research has identified older age, African-American race, and female sex as meningioma risk factors, but there is limited information on their joint effects, or on how these demographic factors vary across strata of tumor grade. The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry combining data from the CDC's National Program of Cancer Registries and NCI's Surveillance, Epidemiology and End Results Program which covers ~100% of the U.S. population and aggregates incidence data on all primary malignant and nonmalignant brain tumors. These data were used to explore the joint impacts of sex and race/ethnicity on average annual age-adjusted incidence rates of meningioma. We calculated meningioma incidence rate ratios (IRRs) by sex and race/ethnicity, across strata of age and tumor grade. Compared to individuals who are non-Hispanic White, individuals who are non-Hispanic Black had significantly higher risk of grade 1 (IRR = 1.23; 95% CI: 1.21-1.24) and grade 2-3 meningioma (IRR = 1.42; 95% CI: 1.37-1.47). The female-to-male IRR peaked in the fifth decade of life across all racial/ethnic groups and tumor grades, but was 3.59 (95% CI: 3.51-3.67) for WHO grade 1 meningioma and 1.74 (95% CI: 1.63-1.87) for WHO grade 2-3 meningioma. This study reveals the joint effects of sex and race/ethnicity on meningioma incidence throughout the lifespan and across strata of tumor grade, highlighting incidence disparities among females and African-Americans that may inform future strategies for tumor interception.

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.

Prevalence of actionable oncogenic alterations (AGA) among patients with advanced (adv) non-squamous (NSQ) non-small cell lung cancer (NSCLC) by age, sex, and race in the United States (US).

e21206 Background: Identification of AGA in NSCLC has improved the understanding of lung cancer pathogenesis and introduced targeted therapies directed against specific genomic alterations. Given the limited data on the prevalence of AGA by demographics, we evaluated prevalence of AGA by age at diagnosis (dx), sex, and race. Methods: A descriptive study used the US nationwide de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database. Eligible patients were adults with a dx of adv NSQ NSCLC from Jan-2016 to Sep-2020 who initiated a first line therapy. The prevalence of AGA for each age, sex, or race stratum was calculated. Results: The cohort included 3938 patients; 67.9% White, 52.9% female, and median age at dx was 68 y. Table 1 presents the prevalence of AGA. The prevalence of EGFR and BRAF V600E mutations increased with age at dx. ALK rearrangement and ROS1 fusion were more prevalent among patients &lt; 50 y vs ≥50 y while MET exon 14 skipping mutation was more prevalent among patients ≥75 y vs &lt; 75 y. EGFR and KRAS G12C mutations were more prevalent in female vs male. Compared to White or Black, Asians had a higher prevalence of EGFR mutations and lower prevalence of KRAS G12C. Conclusions: The prevalence of certain AGA among patients with adv NSCLC vary by demographics, which may contribute to disproportionate disease burden in certain strata. These results highlight the need to enhance diversity of clinical trial populations and ensure the disease burden across demographics in the general population are represented in clinical trials. [Table: see text]

TOWARDS A RADIOCARBON-BASED CHRONOLOGY OF URBAN NORTHERN MESOPOTAMIA IN THE EARLY TO MID-SECOND MILLENNIUM BC: INITIAL RESULTS FROM KURD QABURSTAN

ABSTRACTRadiocarbon (14C) data for 2nd millennium BC urban sites in northern Mesopotamia have been lacking until recently. This article presents a preliminary dataset and Bayesian model addressing the Middle and early Late Bronze Age (Old Babylonian and pre/early Mittani) strata of Kurd Qaburstan—one of the largest archaeological sites on the Erbil plain of Iraqi Kurdistan. The results place the large, densely occupied and fortified Middle Bronze Age city in the first part of the 18th century BC, an outcome consistent with the site’s tentative identification as ancient Qabra. A long occupation gap (up to two centuries) probably ensued, before a smaller town confined to the high mound and part of the northeastern lower town resumed in the late 16th and early 15th centuries BC, possibly before this region became part of the Late Bronze Age kingdom of Mittani.