Age Strata Research Articles

A quantitative synthesis of disparities in the inclusion of racial/ethnic minorities and older women in breast cancer trials.

6557 Background: Trials that inadequately include underrepresented minority (URM) populations widen inequities in cancer care. We assessed reporting patterns, representation, and trends of URM representation in breast cancer (BC) trials. Methods: We analyzed all phase 2/3 trials for age disparity and trials recruiting from the US for racial/ethnic disparity amongst BC RCTs (1990-2021). Enrollment-incidence ratios (EIR), which compare trial proportions (TP) from age subgroups against global estimates of incidence in the corresponding age group (from Global Burden of Disease) and racial/ethnic subgroups against US-population-based incidence in the corresponding racial/ethnic group (from SEER 22), were calculated. Individual-trial EIRs were pooled using random-effects meta-analyses. EIRs of <0.80 indicated meaningful underrepresentation, while EIRs >1.20 indicated meaningful overrepresentation. Meta-regression was used to explore associations between key trial characteristics and EIR, and trends in EIR over the last three decades. Results: Of 842 global trials with 490,657 participants, 232 (27.6%) reported the number of participants in specific age strata and 144 (17.1%) reported outcomes by age. Only 60 trials recruited exclusively from the US. Of these, 41 (68.3%) reported race and 24 (40.0%) reported ethnicity, and 2 (3.3%) analyzed outcomes by race. Older adults aged ≥65 years (TP: 24.3%; EIR: 0.53 [95% CI: 0.47-0.60]) and Hispanic women (TP: 5.3%; 0.54; 0.40-0.75) were underrepresented across global trials and US-only trials respectively. Black women were significantly underrepresented in trials that led to FDA approval (0.38; 0.25-0.58) but not in US-only trials. Stratified analysis by BC subtype (with subtype-specific population incidence) showed underrepresentation of Black women in US-only trials for HER2+ BC (0.66; 0.47-0.93), Hispanic women in ER+ BC (0.42; 0.20-0.90), Asians in triple-negative BC (0.24; 0.11-0.53), and older women in HER2+ BC (0.35; 0.31-0.40) and triple-negative BC (0.36; 0.29-0.45). From 1990-2021, the representation of older women declined significantly (meta-regression coefficient for EIR: -0.4 per 10 years), while Black and Hispanic representation showed no significant change. Black (p = 0.02) and Hispanic representation (p = 0.05) worsened significantly in larger trials. Conclusions: Published reports of BC trials do not consistently report the inclusion of URM. Older and Hispanic women were consistently underrepresented, whereas Black women were underrepresented in large, practice-changing trials. [Table: see text]

Altered gut microbiota in older adults with mild cognitive impairment: a case-control study.

The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. This study provides insights into the role of gut microbiota in the neurodegenerative process.

Diabetes risk reduction diet and ovarian cancer risk: an Italian case-control study

PurposeTo investigate the relation between a diabetes risk reduction diet (DRRD) and ovarian cancer.MethodsWe used data from a multicentric case-control study conducted in Italy, including 1031 incident ovarian cancer cases and 2411 controls admitted to hospital centres for acute non-malignant disease. Subjects’ diet prior to hospital admission was collected using a validated food frequency questionnaire. Adherence to the DRRD was measured using a score based on 8 dietary components, giving higher scores for greater intakes of cereal fiber, coffee, fruit, nuts, higher polyunsaturated to saturated fatty acids ratio, lower glycemic index of diet, and lower intakes of red/processed meat, and sweetened beverages/and fruit juices. Higher scores indicated greater adherence to the DRRD. Multiple logistic regression models were fitted to calculate the odds ratios (OR) of ovarian cancer and the corresponding 95% confidence intervals (CI) for approximate quartiles of the DRRD score.ResultsThe DRRD score was inversely related to ovarian cancer, with an OR of 0.76 (95%CI: 0.60–0.95) for the highest versus the lowest quartile of the score (p for trend = 0.022). The exclusion of women with diabetes did not change the results (OR = 0.75, 95%CI: 0.59–0.95). Inverse associations were observed in strata of age, education, parity, menopausal status, and family history of ovarian/breast cancer.ConclusionHigher adherence to a diet aimed at reducing the risk of diabetes was inversely associated with ovarian cancer. Further evidence from prospective investigations will be useful to support our findings.

Risk Adjustment of ICD-10-CM Coded Potential Inpatient Complications Using Administrative Data.

To risk-adjust the Potential Inpatient Complication (PIC) measure set and propose a method to identify large deviations between observed and expected PIC counts. Acute inpatient stays from the Premier Healthcare Database from January 1, 2019 to December 31, 2021. In 2014, the PIC list was developed to identify a broader set of potential complications that can occur as a result of care decisions. Risk adjustment for 111 PIC measures is performed across 3 age-based strata. Using patient-level risk factors and PIC occurrences, PIC-specific probabilities of occurrence are estimated through multivariate logistic regression models. Poisson Binomial cumulative mass function estimates identify deviations between observed and expected PIC counts across levels of patient-visit aggregation. Area under the curve (AUC) estimates are used to demonstrate PIC predictive performance in an 80:20 derivation-validation split framework. We used N=3,363,149 administrative hospitalizations between 2019 and 2021 from the Premier Healthcare Database. PIC-specific model predictive performance was strong across PICs and age strata. Average area under the curve estimates across PICs were 0.95 (95% CI: 0.93-0.96), 0.91 (95% CI: 0.90-0.93), and 0.90 (95% CI: 0.89-0.91) for the neonate and infant, pediatric, and adult strata, respectively. The proposed method provides a consistent quality metric that adjusts for the population's case mix. Age-specific risk stratification further addresses currently ignored heterogeneity in PIC prevalence across age groups. Finally, the proposed aggregation method identifies large PIC-specific deviations between observed and expected counts, flagging areas with a potential need for quality improvements.

Tracing Water–Rock–Gas Reactions in Shallow Productive Mud Chambers of Active Mud Volcanoes in the Caspian Sea Region (Azerbaijan)

We present geochemical and mineralogical datasets for five new mud volcanoes in continental Azerbaijan (Hamamdagh and Bendovan) and the adjacent Caspian Sea (Khara-Zire, Garasu and Sangi-Mughan). The fluid ejects have a Na–Cl-type composition and are generated by the mixing of evaporated Caspian seawater and low- to high-salinity pore waters, as indicated by Br–B and Cl–B systematics and Na–K and SiO2 geo-thermometers. The fluids contain high concentrations of As, Ba, Cu, Si, Li, Sr and Zn (60 to 26,300 ppm), which are caused by surface evaporation, pyrite oxidation, ion exchange reactions and hydrocarbon maturation in Oligocene-Miocene ‘Maykop’ shales. The solid ejects comprise liquid, oily and brecciated mud, mud/claystones and sandstones. The mud heterogeneity of the volcanoes is related to the geological age and different sedimentological strata of the host rocks that the mud volcanoes pass through during their ascent. All ejects show evidence of chemical alterations via water–rock–gas reactions, such as feldspar weathering, smectite illitization and the precipitation of Fe-(hydr)oxides, calcite, calcian dolomite, kaolinite and smectite. The studied localities have petrographic similarities to northern extending mud volcano systems located on Bahar and Zenbil islands, which suggests that mud volcanoes in the Caspian Sea region are sourced from giant shallow mud chambers (~1–4 km depth) located in Productive Series strata. Our results document the complex architecture of the South Caspian Basin—the most prolific hydrocarbon region in the world.

Re: WHO Classification of Tumours, 5th Edition, Volume 8: Urinary and Male Genital Tumours

Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death.The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40–54 and 55–69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.Baseline PSA.We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5–0.9, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0–3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40–54 and 55–69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.We replicated prior studies that baseline PSA at age 40–69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15–20 yr.A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man’s risk of dying from prostate cancer in the next two decades.

The impact of China's zero markup drug policy on drug costs for managing Parkinson's disease and its complications: an interrupted time series analysis.

In April 2009, the Chinese government launched Zero Markup Drug Policy (ZMDP) to adjust medical institutions' revenue and expenditure structures. This study evaluated the impact of implementing ZMDP (as an intervention) on the drug costs for managing Parkinson's disease (PD) and its complications from the healthcare providers' perspective. The drug costs for managing PD and its complications per outpatient visit or inpatient stay were estimated using electronic health data from a tertiary hospital in China from January 2016 to August 2018. An interrupted time series analysis was conducted to evaluate the immediate change following the intervention (step change, β1) and the change in slope, comparing post-intervention with the pre-intervention period (trend change, β2). Subgroup analyses were conducted in outpatients within the strata of age, patients with or without health insurance, and whether drugs were listed in the national Essential Medicine List (EML). Overall, 18,158 outpatient visits and 366 inpatient stays were included. Outpatient (β1 = -201.7, 95%CI: -285.4, -117.9) and inpatient (β1 = -372.1, 95% CI: -643.6, -100.6) drug costs for managing PD significantly decreased when implementing ZMDP. However, for outpatients without health insurance, the trend change in drug costs for managing PD (β2 = 16.8, 95% CI: 8.0, 25.6) or PD complications (β2 = 12.6, 95% CI: 5.5, 19.7) significantly increased. Trend changes in outpatient drug costs for managing PD differed when stratifying drugs listed in EML (β2 = -1.4, 95% CI: -2.6, -0.2) or not (β2 = 6.3, 95%CI: 2.0, 10.7). Trend changes of outpatient drug costs for managing PD complications significantly increased in drugs listed in EML (β2 = 14.7, 95% CI 9.2, 20.3), patients without health insurance (β2 = 12.6, 95% CI 5.5, 19.7), and age under 65 (β2 = 24.3, 95% CI 17.3, 31.4). Drug costs for managing PD and its complications significantly decreased when implementing ZMDP. However, the trend in drug costs increased significantly in several subgroups, which may offset the decrease at the implementation.

Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death—Results from the Norwegian Prostate Cancer Consortium

Background and objectiveProstate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality. The objective of the study was to determine the association between midlife PSA levels <4.0 ng/ml, drawn aspart of routine medical care, and long-term risk of prostate cancer death. MethodsThe Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males (more than or equal to) 40 yr of age. We studied 176 099 men (predefined age strata: 40–54 and 55–69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1,1995 and December 31, 2005. We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5–0.9, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method. Key findings and limitationsThe median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0–3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40–54 and 55–69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation. Conclusions and clinical implicationsWe replicated prior studies that baseline PSA at age 40–69 yr can be used to stratify a man’s risk of dying from prostate cancer within the next 15–20 yr. Patient summaryA prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man’s risk of dying from prostate cancer in the next two decades.

Psychometric properties and measurement invariance of the 7-item General Anxiety Disorder scale (GAD-7) in an Italian coronary heart disease population

BackgroundGeneralized Anxiety Disorder is predominant in coronary heart disease (CHD) patients. 7-item Generalized Anxiety Disorder (GAD-7) scale psychometric properties have never been tested in CHD populations. This study aims to verify the GAD-7 psychometric properties and measurement invariance in an Italian CHD sample. MethodA baseline data secondary analysis from HEARTS-IN-DYADS study. Several healthcare facilities enrolled an adult inpatient sample. Anxiety and depression data were collected using GAD-7 and Patient Health Questionnaire 9 (PHQ-9). Factorial validity was assessed with confirmatory factor analysis; construct validity was tested by correlating GAD-7 scores with PHQ-9 scores and other sociodemographic characteristics; internal consistency reliability was assessed using Cronbach's alpha and the composite reliability index, while confirmatory multigroup factor analysis was employed to investigate measurement invariance across gender and age (65 vs. 65). ResultsWe enrolled 398 patients (mean age 64.7 years; 78.9 % male; 66.8 % married). Factor structure was confirmed as unidimensional. Construct validity was confirmed with significant associations between GAD-7 and PHQ-9 scores, female gender, having a caregiver, and being employed. Cronbach's alpha and composite reliability index were 0.89 and 0.90, respectively. Measurement invariance across gender and age was confirmed at the scalar level. LimitationsA convenience sample in one European country, a small female sample, validity testing against a single criterion. ConclusionStudy results demonstrate adequate validity and reliability of the GAD-7 in an Italian CHD sample. It showed satisfactory invariance properties; GAD-7 is suitable for measuring anxiety in CHD while making significant comparisons of scores among stratified gender and age groups.

Burden of disease in patients hospitalised with COVID-19 during the first and second pandemic wave in Switzerland: a nationwide cohort study

The first and second waves of the COVID-19 pandemic led to a tremendous burden of disease and influenced several policy directives, prevention and treatment strategies as well as lifestyle and social behaviours. We aimed to describe trends of hospitalisations with COVID-19 and hospital-associated outcomes in these patients during the first two pandemic waves in Switzerland. In this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalised with COVID-19 in Switzerland between January 1st and December 31st, 2020. First, stratified by wave (first wave: January to May, second wave: June to December), we estimated incidence rates (IR) and rate differences (RD) per 10,000 person-years of COVID-19-related hospitalisations across different age groups (0-9, 10-19, 20-49, 50-69, and ≥70 years). IR was calculated by counting the number of COVID-19 hospitalisations for each patient age stratum paired with the number of persons living in Switzerland during the specific wave period. Second, adjusted odds ratios (aOR) of outcomes among COVID-19 hospitalisations were calculated to assess the association between COVID-19 wave and outcomes, adjusted for potential confounders. Of 36,517 hospitalisations with COVID-19, 8,862 (24.3%) were identified during the first and 27,655 (75.7%) during the second wave. IR for hospitalisations with COVID-19 was highest during the second wave and among patients above 50 years (50-69 years: first wave: 31.49 per 10,000 person-years; second wave: 62.81 per 10,000 person-years; RD 31.32 [95% confidence interval [CI]: 29.56 to 33.08] per 10,000 person-years; IRR 1.99 [95% CI: 1.91 to 2.08]; ≥70 years: first wave: 88.59 per 10,000 person-years; second wave: 228.41 per 10,000 person-years; RD 139.83 [95% CI: 135.42 to 144.23] per 10,000 person-years; IRR 2.58 [95% CI: 2.49 to 2.67]). While there was no difference in hospital readmission, when compared with the first wave, patients hospitalised during the second wave had a lower probability of death (aOR 0.88 [95% CI: 0.81 to 0.95], ARDS (aOR 0.56 [95% CI: 0.51 to 0.61]), ICU admission (aOR 0.66 [95% CI: 0.61 to 0.70]), and need for ECMO (aOR 0.60 [95% CI: 0.38 to 0.92]). LOS was -16.1 % (95% CI: -17.8 to -14.2) shorter during the second wave. In this nationwide cohort study, rates of hospitalisations with COVID-19 were highest among adults older than 50 years and during the second wave. Except for hospital readmission, the likelihood of adverse outcomes was lower during the second pandemic wave, which may be explained by advances in the understanding of the disease and improved treatment options.

Characterization of the cell-mediated immune response to the NIH tetravalent dengue vaccine in an endemic population

Abstract Dengue is now endemic in more than 100 countries, with Southeast Asian and Pacific Island regions being the most seriously affected. The Department of Defense has long recognized the threat of dengue and has made great contributions to understanding it. The ideal dengue vaccine will provide long-lasting protection against all four serotypes of dengue virus (DENV1-4) and will be effective in both endemic and non-endemic populations. Several tetravalent dengue vaccines are either licensed or in advanced stages of clinical development, including the live attenuated vaccine candidate developed by the NIH. The purpose of this study is to characterize the cellular immune responses to the NIH vaccine, with particular attention to the activation and memory profiles of DENV-specific T and B cell populations. Our hypothesis is that the NIH vaccine induces a durable and tetravalent DENV-specific adaptive immune response, which varies in its magnitude and phenotype over time (3 years post-vaccination) and across age strata. To assess the magnitude, breadth, and evolution of DENV-specific T and B cells following vaccination, we use a suite of different assays, including IFNγ ELISpot, memory B cell fluorospot, and flow cytometry-based assays. This study evaluates the ability of the NIH vaccine to induce durable and balanced immune responses to all four DENV serotypes, and how that compares to naturally acquired immunity.

Abstract #1405106: The Associations of Total Testosterone with Nonalcoholic Fatty Liver Disease Inflammatory and Fibrotic Progression in Men with Type 2 Diabetes: A Cross-Sectional Study

Men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism. Testosterone has an impact on metabolic disorders and it may play different roles in the progression of nonalcoholic fatty liver disease (NAFLD). We aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM. It is a cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable). In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95%CI, 1.31-3.28, P for trend=0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72-0.92, P for trend<0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29-0.72, P for trend=0.001) with OR of 1 SD increment of ln(TT) 1.24 (95% CI 1.07-1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007,0.003 and 0.012 respectively); as for fibrotic progression, we found no interactoins (all P for interaction ≥0.05). In this population-based study including 1782 male patients with T2DM, we found that TT of male patients was negatively associated with probable NASH and NAFLD inflammatory progression but positively with fibrotic progression. Our results indicate that in male patients with T2DM, testosterone may play significant but opposite roles in inflammatory and fibrotic progression of NAFLD. Hence, understanding androgen hormone changes during T2DM and differentiating the stages of NAFLD may help clinicians personalize treatment strategy for male NAFLD patients with T2DM.

Epidemiología de la neumonía neumocócica en adultos mayores de 50 años: estudio de cohortes en Cataluña, 2017-2018

ObjectiveTo analyse population-based incidence and lethality of pneumococcal pneumonia (PP) requiring hospitalisation among Catalonian adults after universal vaccination implementation in infants. DesignPopulation-based cohort study. SettingPrimary care/hospital, Catalonia. Participants2,059,645 individuals ≥50 years old affiliated to the Institut Catala de la Salut retrospectively followed between 01/01/2017 and 31/12/2018. Main outcome measuresThe Catalonian information system for the development of research in primary care (SIDIAP, Sistema de Información para el Desarrollo de la Investigación en Atención Primaria) was used to establish baseline characteristics and risk-strata of cohort members at study start: low-risk (immunocompetent persons without risk conditions), intermediate-risk (immunocompetent persons with at-risk condition) and high-risk (immunocompromising conditions). PP requiring hospitalisation among cohort members across study period were collected from CMBD (Conjunto Mínimo Básico de Datos) discharge data of 64 reference Catalonian hospitals. ResultsAn amount of 3592 episodes of HPP were observed, with an incidence density of 90.7 cases per 100,000 person-years (95% CI: 85.2-96.5), being 11.9 bacteremic (95% CI: 10.8-13.1) and 78.8 non-bacteremic (95% CI: 74.0-83.8). Incidence rates substantially increased by age (37.3 in 50-64 years vs. 98.3 in 65-79 years vs. 259.8 in ≥80 years) and baseline-risk stratum (42.1, 120.7 and 238.6 in low-, intermediate- and high-risk stratum, respectively). Overall case-fatality rate was 7.6% (10.8% in invasive cases vs. 7.1% in non-invasive cases; pP=.004). In multivariable analyses, high-risk stratum and oldest age were the strongest predictors for invasive and non-invasive cases, respectively. ConclusionIncidence and lethality of PP remained moderate among adults >50 years in Catalonia during 2017–2018 (earlier period after universal vaccination introduction for infants).

NF2 mutation associated with accelerated time to recurrence for older patients with atypical meningiomas

Purpose Meningiomas occur more frequently in older adults, with the incidence rates increasing from 5.8/100,000 for adults 35-44 years old to 55.2/100,000 for those 85+. Due to the increased risk of surgical management in older adults, there is a need to characterize the risk factors for aggressive disease course to inform management decisions in this population. We therefore sought to determine age-stratified relationships between tumour genomics and recurrence after resection of atypical meningiomas. Methods We identified 137 primary and recurrent Grade 2 meningiomas from our existing meningioma genomic sequencing database. We examined the differential distribution of genomic alterations in those older than 65 compared to younger. We then performed an age stratified survival analysis to model recurrence for a mutation identified as differentially present. Results In our cohort of 137 patients with grade 2 meningiomas, alterations in NF2 were present at a higher rate in older adults compared to younger (37.8% in < 65 vs. 55.3% in > 65; recurrence adjusted p-value =0.04). There was no association between the presence of NF2 and recurrence in the whole cohort. In the age-stratified model for those less than 65 years old, there was again no relationship. For patients in the older age stratum, there is a relationship between NF2 and worsened recurrence outcomes (HR = 3.64 (1.125 − 11.811); p = 0.031). Conclusions We found that mutations in NF2 were more common in older adults. Further, the presence of mutant NF2 was associated with an increased risk of recurrence in older adults.

Epidemiology of Enteroaggregative, Enteropathogenic, and Shiga Toxin–ProducingEscherichia coliAmong Children Aged &amp;lt;5 Years in 3 Countries in Africa, 2015–2018: Vaccine Impact on Diarrhea in Africa (VIDA) Study

To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin-producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. Between May 2015 and July 2018, children aged 0-59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P < .01), aEPEC (27.3% vs 23.3%, P < .01), and STEC (9.3% vs 5.1%, P < .01). EAEC and tEPEC were more frequent in children aged <23 months, aEPEC was similar across age strata, and STEC increased with age. No association between nutritional status at follow-up and DEC pathotypes was found. DEC coinfection with Shigella/enteroinvasive E. coli was more common among cases (P < .01). No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease.

A Description of the Statistical Methods for the Vaccine Impact on Diarrhea in Africa (VIDA) Study

Diarrheal diseases remain a health threat to children in low- and middle-income countries. The Vaccine Impact on Diarrhea in Africa (VIDA) study was a 36-month, prospective, matched case-control study designed to estimate the etiology, incidence, and adverse clinical consequences of moderate-to-severe diarrhea (MSD) in children aged 0-59 months. VIDA was conducted following rotavirus vaccine introduction at 3 censused sites in sub-Saharan Africa that participated in the Global Enteric Multicenter Study (GEMS) ∼10 years earlier. We describe the study design and statistical methods of VIDA and where they differ from GEMS. We aimed to enroll 8-9 MSD cases every 2 weeks from sentinel health centers in 3 age strata (0-11, 12-23, 24-59 months) and 1 to 3 controls matched by age, sex, date of case enrollment, and village. Clinical, epidemiological, and anthropometric data were collected at enrollment and ∼60 days later. A stool specimen collected at enrollment was analyzed by both conventional methods and quantitative PCR for enteric pathogens. For the matched case-control study, we estimated the population-based, pathogen-specific attributable fraction (AF) and attributable incidence adjusted for age, site, and other pathogens, and identified episodes attributable to a specific pathogen for additional analyses. A prospective cohort study nested within the original matched case-control study allowed assessment of (1) the association between potential risk factors and outcomes other than MSD status and (2) the impact of MSD on linear growth. GEMS and VIDA together comprise the largest and most comprehensive assessment of MSD conducted to date in sub-Saharan Africa populations at highest risk for morbidity and mortality from diarrhea. The statistical methods used in VIDA have endeavored to maximize the use of available data to produce more robust estimates of the pathogen-specific disease burden that might be prevented by effective interventions.

The associations of socioeconomic status with incident dementia and Alzheimer’s disease are modified by leucocyte telomere length: a population-based cohort study

Socio-economic status (SES) and biological aging are risk factors for dementia, including Alzheimer’s disease, however, it is less clear if the associations with SES vary sufficiently across different biological age strata. We used data from 331,066 UK Biobank participants aged 38–73 with mean follow-up of 12 years to examine if associations between SES (assessed by educational attainment, employment status and household income) and dementia and Alzheimer’s disease are modified by biological age (assessed by leucocyte telomere length: LTL). Diagnosis of events was ascertained through hospital admissions data. Cox regressions were used to estimate hazard ratios [HRs]. A consistent dose–response relationship was found, with participants in low SES and shorter LTL strata (double-exposed group) reporting 3.28 (95% confidence interval [CI] 2.57–4.20) and 3.44 (95% CI 2.35–5.04) times higher risks of incident dementia and Alzheimer’s disease respectively, compared to those of high SES and longer LTL (least-exposed group). Of interest is a synergistic interaction between SES and LTL to increase risk of dementia (RERI 0.57, 95% CI 0.07–1.06) and Alzheimer’s disease (RERI 0.79, 95% CI 0.02–1.56). Our findings that SES and biological age (LTL) are synergistic risk factors of dementia and Alzheimer’s disease may suggest the need to target interventions among vulnerable sub-groups.

Neighborhood Physical and Social Environments and Social Inequalities in Health in Older Adolescents and Young Adults: A Scoping Review.

Poor health and well-being are prevalent among young people. Neighborhoods may play a role in promoting good health. Little is known on if and how neighborhood characteristics affect health, and social inequalities therein, among young people. In this scoping review, we asked: (1) what features of the neighborhood physical and social environments have been studied in association with the physical and mental health and well-being of young people 15 to 30 years old; and (2) to what extent have social differentials in these associations been studied, and how? We identified peer-reviewed articles (2000 to 2023) through database and snowball searches. We summarized study characteristics, exposure(s), outcome(s) and main findings, with an eye on social inequalities in health. Out of the 69 articles reviewed, most were quantitative, cross-sectional, conducted among 18-year-olds and younger, and focused on the residential neighborhood. Neighborhood social capital and mental health were the most common exposure and outcome studied, respectively. Almost half of the studies examined social inequalities in health, mostly across sex/gender, socioeconomic status, and ethnicity. Evidence gaps remain, which include exploring settings other than residential neighborhoods, studying the older age stratum of young adulthood, and assessing a broader range of social inequalities. Addressing these gaps can support research and action on designing healthy and equitable neighborhoods for young people.

Accuracy of identifying pediatric acute bacterial sinusitis diagnoses in outpatient claims data.

Acute bacterial sinusitis is among the most frequent outpatient infections in children and adolescents and is well suited to study in large healthcare utilization databases, but the validity of International Classification of Diseases, 10th Revision (ICD-10) codes together with antibiotic prescriptions to identify cases of acute bacterial sinusitis has not been established. We aimed to evaluate the validity of ICD-10 codes combined with antibiotic prescriptions to identify new diagnoses of acute bacterial sinusitis among pediatric patients evaluated in the outpatient setting. Children and adolescents aged 17 years and younger with an outpatient diagnosis of acute sinusitis along with an antibiotic prescription from an ambulatory facility affiliated with the Mass General Brigham health system were identified via a clinical data warehouse. Patients were stratified by age (0-5 years, 6-11 years, and 12-17 years), and 50 cases per age group were randomly sampled. Medical records were independently reviewed by two pediatric infectious diseases physicians to assess for the documentation of a clinician-defined diagnosis of acute bacterial sinusitis. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated. A total of 150 patients were included in the final cohort. Frontal, maxillary, and "unspecified" sinuses accounted for 88% of the diagnoses. The positive predictive value of the algorithm to identify clinician-defined diagnoses of acute bacterial sinusitis was 92% (95% CI 87%, 95%). The PPVs were consistent across age strata. ICD-10 codes for acute sinusitis, when paired with a same-day antibiotic prescription, have a high positive predictive value among a cohort of pediatric patients, suggesting that they can be used to study new acute bacterial sinusitis diagnoses with claims.

Accounting for age in prediction of discharge destination following elective lumbar fusion: a supervised machine learning approach

BACKGROUND CONTEXTThe number of elective spinal fusion procedures performed each year continues to grow, making risk factors for post-operative complications following this procedure increasingly clinically relevant. Nonhome discharge (NHD) is of particular interest due to its associations with increased costs of care and rates of complications. Notably, increased age has been found to influence rates of NHD. PURPOSETo identify aged-adjusted risk factors for nonhome discharge following elective lumbar fusion through the utilization of Machine Learning-generated predictions within stratified age groupings. STUDY DESIGNRetrospective Database Study. PATIENT SAMPLEThe American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database years 2008 to 2018. OUTCOME MEASURESPostoperative discharge destination. METHODSACS-NSQIP was queried to identify adult patients undergoing elective lumbar spinal fusion from 2008 to 2018. Patients were then stratified into the following age ranges: 30 to 44 years, 45 to 64 years, and ≥65 years. These groups were then analyzed by eight ML algorithms, each tasked with predicting post-operative discharge destination. RESULTSPrediction of NHD was performed with average AUCs of 0.591, 0.681, and 0.693 for those aged 30 to 44, 45 to 64, and ≥65 years respectively. In patients aged 30 to 44, operative time (p<.001), African American/Black race (p=.003), female sex (p=.002), ASA class three designation (p=.002), and preoperative hematocrit (p=.002) were predictive of NHD. In ages 45 to 64, predictive variables included operative time, age, preoperative hematocrit, ASA class two or class three designation, insulin-dependent diabetes, female sex, BMI, and African American/Black race all with p<.001. In patients ≥65 years, operative time, adult spinal deformity, BMI, insulin-dependent diabetes, female sex, ASA class four designation, inpatient status, age, African American/Black race, and preoperative hematocrit were predictive of NHD with p<.001. Several variables were distinguished as predictive for only one age group including ASA Class two designation in ages 45 to 64 and adult spinal deformity, ASA class four designation, and inpatient status for patients ≥65 years. CONCLUSIONSApplication of ML algorithms to the ACS-NSQIP dataset identified a number of highly predictive and age-adjusted variables for NHD. As age is a risk factor for NHD following spinal fusion, our findings may be useful in both guiding perioperative decision-making and recognizing unique predictors of NHD among specific age groups.