Age Strata Research Articles

Compounding Effects of Aging and Sex on Cerebrovascular Endothelial Mitochondria

Despite the increasing burden of age-related neurological diseases such as vascular cognitive impairment and dementia or Alzheimer’s disease, the underlying mechanisms of these pathologies are not clear. Nonetheless, structural and functional changes in the microvasculature represent probable pathological aspects of these age-associated diseases. The silent and cumulative changes in endothelial mitochondria with subsequently compromised cerebral vascular function are thought to play a central role in neurological disease development. We tested the hypothesis that mitochondrial morphological changes in endothelial cells facilitate the distinct aging- and sex-related differences in the cerebral microvascular proteome and energetics. Mito-dendra2 (mt-D2) labeled endothelial mitochondria were imaged in vivo via a cranial window using two-photon microscopy at 875 nm in young and old, male and female, mito-Dendra2 mice (YM, YF, OM, and OF, respectively). Mt-D2 associated signal was analyzed in 3D stacks using the Huygens Pro CE 23.04.0p3 object analyzer (160 images, originated from 4-5 mt-D2 mice/groups). We also measured mRNA copy numbers of mitochondrial fission and fusion genes in isolated, cortical microvessels (<70 μm) from YM, YF, OM, and OF C57Bl/6J mice (n=7-11/age/sex) using ddPCR. Kruskal-Wallis test with Dwass-Steel-Critchlow-Fligner post-hoc comparisons were used to compare mt-D2 signal among YM, YF, OM, and OF, whereas Mann-Whitney U test determined changes across age and sex strata. p<0.05 was considered statistically significant. mRNA copy numbers were normalized to housekeeping genes (GAPDH, β-actin, and HPRT-1) and compared with one-way ANOVA based on data distribution. Analysis of four object parameters revealed that object surface was smaller in old vs. young that was significant in YM vs. OM. We found significantly greater corrected lateral width in OM vs. YM, OF vs. YF, and in YF vs. YM. The lateral aspect ratio was significantly greater in YM vs. OM, in YF vs. OF, as well as in YM vs. YF. Accordingly, the axial sphericity of the principal box was significantly greater in OM vs. YM, in OF vs. YF, and in YF vs. YM. Normalized mRNA copy numbers of mitochondrial fission and fusion genes were not statistically different in our samples for DRP-1, Fis-1 or Mfn-1/2, Opa-1, respectively. These results suggest that aging driven morphological differences, such as the shortening of endothelial mt-D2 signal are, at least in part, facilitated by altered fission/fusion protein abundances and/or activity rather than transcriptional changes in our samples. Although we are still analyzing other morphological parameters, by assessing the effect sizes and their physiological relevance, we postulate that these morphological differences contribute to the vulnerability of the aged cerebral microvasculature to injury. AG083567, 3P30GM145498-01, U54GM104940, HL148836. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

COST-EFFECTIVENESS OF SINGLE-PILL AND SEPARATE-PILL ADMINISTRATION OF ANTIHYPERTENSIVE TRIPLE-COMBINATION THERAPY: A POPULATION-BASED MICROSIMULATION STUDY

Objective: To evaluate the lifetime cost-effectiveness profile of the perindopril/amlodipine/indapamide single-pill combination (SPC) compared with the combination of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic as a SPC of two drugs plus the third drug separately from the Italian payer perspective. Design and method: A cost-effectiveness analysis was conducted employing multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged >=40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug prescription until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. Results: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a reduction in total cost of –€12 (95% CI –9,719 to 8,131), making it the dominant strategy (ICER of –14, 95% CI –€15,871 to €7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17 to 7,813) and €2,027 (95% CI 19 to 8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574 to 10,640 vs. €3,710, 95% CI 263 to 11,955). This was the case for all strata of age, sex, and clinical status. Conclusions: The SPC was projected to increase survival and reduce costs compared with the two-pill combination. This is likely explained by an improvement in drug compliance. As three-drug SPC is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Safety, Tolerability, and Immunogenicity of aH5N1 Vaccine in Adults with and without Underlying Medical Conditions.

Influenza pandemics pose a serious risk to the global population, with the potential for high morbidity and mortality. An adjuvanted H5N1 vaccine (aH5N1) has been approved for prophylaxis against the avian influenza virus H5N1, which is a likely cause of future pandemics. In this phase-III, stratified, randomized, controlled, observer-blind, multicenter study, we evaluated the safety and immunogenicity of aH5N1 in four separate groups of adults: adults 18-60 years of age who were healthy or had high-risk medical conditions and older adults ≥61 years of age who were healthy or had high-risk medical conditions. Subjects were randomly assigned to aH5N1 or the comparator, adjuvanted trivalent seasonal influenza vaccine (aTIV). Antibody responses to aH5N1 were increased in all four subgroups and, within each age stratum, largely consistent between healthy subjects and those with medical conditions. Injection-site pain was reported by 66-73% of younger and 36-42% of older-aH5N1 recipients, and fatigue and myalgia were reported by 22-41% of subjects across age and health subgroups. No serious adverse events or deaths were considered related to the study vaccine. In conclusion, aH5N1 increased antibody responses regardless of age or health status and demonstrated a clinically acceptable safety and tolerability profile.

Feeding characteristics and growth among children with prenatal exposure to Zika virus with and without microcephaly in the microcephaly epidemic research group pediatric cohort

ObjectiveTo describe the feeding characteristics and growth of children with prenatal exposure to Zika virus (ZIKV) from birth to 48 months.DesignUsing data from the prospective Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC), children without microcephaly born to mothers with evidence of ZIKV infection during pregnancy (ZIKV-exposed children without microcephaly) and children with Zika-related microcephaly were compared using repeated cross-sectional analyses within the following age strata: birth; 1 to 12; 13 to 24; 25 to 36; and 37 to 48 months. The groups were compared in relation to prematurity, birth weight, breastfeeding, alternative feeding routes, dysphagia and anthropometric profiles based on the World Health Organization Anthro z-scores (weight-length/height, weight-age, length/height-age and BMI-age).ResultsThe first assessment included 248 children, 77 (31.05%) with microcephaly and 171 (68.95%) without microcephaly. The final assessment was performed on 86 children. Prematurity was 2.35 times higher and low birth weight was 3.49 times higher in children with microcephaly. The frequency of breastfeeding was high (> 80%) in both groups. On discharge from the maternity hospital, the frequency of children requiring alternative feeding route in both groups was less than 5%. After 12 months of age, children with microcephaly required alternative feeding route more often than children without microcephaly. In children with microcephaly, the z-score of all growth indicators was lower than in children without microcephaly.ConclusionsChildren with Zika-related microcephaly were more frequently premature and low birth weight and remained with nutritional parameters, i.e., weight-for-age, weight-for-length/height and length/height-for-age below those of the children without microcephaly.

Dog Consumption at Tell Zirāʿa: Is It a “Cultural Marker” for the “Sea Peoples”?

It has been argued that the increase in the consumption of dogs in the southern Levant during the Iron Age was due to the advent of the Philistines/“Sea Peoples” into the region. In this study, we test this proposal through the presentation of new information on dog consumption and its depositional context in Bronze and Iron Age strata from the archaeological site of Tell Zirāʿa (Jordan), and we compare the results to other sites in the region. Our study does not support that such behaviour is a signal of ethnic identity.

Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study.

Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata. Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent. In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60years, but we lacked evidence of association in other strata. Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk.

Геологическое строение четвертичных отложений в долине нижней Печоры

The geological structure of Neopleistocene deposits was specified along a 19-kilometer section of the right bank of the lower Pechora between the villages of Garevo and Sergeevo-Shchelya. The presence of three glacial and two interglacial horizons was revealed in coastal outcrops, and the material composition of the composing sediments was studied. The formation of the most ancient moraine horizon was associated with Fennoscandinavia and occurred in the early Quaternary Pomusov (Oka) time. The Pomusov moraine was overlain by Chirva (Likhvin) interglacial alluvial and lacustrine sediments. In the Middle Neopleistocene glacial complex, two morainic strata of different ages were distinguished: Pechora (Dnieper) and Vychegda (Moscovian), separated by a pack of predominantly coastal-marine littoral sediments, and alluvial and lacustrine sediments, the age of which was determined as Rodionov (Shklov) by the palynological method. Differences in the lithological composition of moraines confirmed a double glaciation of the European North-East of Russia in the Middle Neopleistocene.

Association Between Life's Essential 8 Cardiovascular Health Metrics With Cardiovascular Events in the Cardiovascular Disease Lifetime Risk Pooling Project.

The American Heart Association recently launched updated cardiovascular health metrics, termed Life's Essential 8 (LE8). Compared with Life's Simple 7 (LS7), the new approach added sleep health as an eighth metric and updated the remaining 7 health factors and behaviors. The association of the updated LE8 score with long-term cardiovascular disease (CVD) outcomes and death is unknown. We pooled individual-level data from 6 contemporary US-based cohorts from the Cardiovascular Lifetime Risk Pooling Project. Total LE8 score (0-100 points), LE8 score without sleep (0-100 points), and prior LS7 scores (0-14 points) were calculated separately. We used multivariable-adjusted Cox models to evaluate the association of LE8 with CVD, CVD subtypes, and all-cause mortality among younger, middle, and older adult participants. Net reclassification improvement analysis was used to measure the improvement in CVD risk classification with the addition of LS7 and LE8 recategorization based on score quartile rankings. Our sample consisted of 32 896 US adults (7836 [23.8%] Black; 14 941 [45.4%] men) followed for 642 000 person-years, of whom 9391 developed CVD events. Each 10-point higher overall LE8 score was associated with lower risk by 22% to 40% for CVD, 24% to 43% for congenital heart disease, 17% to 34% for stroke, 23% to 38% for heart failure, and 17% to 21% for all causes of mortality events across age strata. LE8 score provided more granular differentiation of the related CVD risk than LS7. Overall, 19.5% and 15.5% of the study participants were recategorized upward and downward based on LE8 versus LS7 categories, respectively, and the recategorization was significantly associated with CVD risk in addition to LS7 score. The addition of recategorization between LE8 and LS7 categories improved CVD risk reclassification across age groups (clinical net reclassification improvement, 0.06-0.12; P<0.01). These findings support the improved utility of the LE8 algorithm for assessing overall cardiovascular health and future CVD risk.

Use of a novel bluetooth-connected device to measure handgrip strength: A practical tool to help healthcare professionals identify adults at nutritional risk

Background and AimsLow muscle strength is strongly tied to poor nutrition status, and nutritional interventions are likewise linked to maintenance and restoration of muscle strength and functional status. Nutrition plays a vital role in muscle mass, strength, and function, and losses in muscle (strength, function, and mass) are associated with poor health outcomes and added costs for healthcare services. For this study of outpatients, the main objective was to identify those at risk for low muscle strength, as evidenced by low handgrip strength (HGS) measures with risk stratified by age and sex. MethodsThis was a two-part study on HGS measures in adults attending outpatient clinics in India. In part one, we conducted HGS tests on dominant and non-dominant hands of patients who qualified for the study. For HGS measures, we used a validated tool, the SQUEGG device, a smart handgrip trainer, along with its companion Bluetooth-connected app, the Muscle Strength Assessment Tool (MSAT) app. In part two, we collected Healthcare Practitioners’ (HCP) feedback via a short digital survey on the use of the SQUEGG device + the MSAT app to do HGS risk screening as an indicator of needed nutritional intervention. ResultsNearly a third of community-living adults in India exhibited low HGS among the 3036 sampled. At each age stratum, dominant-hand HGS in women was lower by 25% to 35% compared to men. Among 353 HCPs, 293 (83%) provided insights via survey, and 85% of surveyed HCPs (n=249) strongly agreed or agreed that the SQUEGG device + MSAT app helped them identify HGS issues among their patients, and 85% (n=248) agreed or strongly agreed they would like to continue using the SQUEGG device + MSAT app to inform their practice. Nearly all surveyed HCPs (98%, n=288) recommended an oral nutritional supplement (ONS) to their patients with identified low HGS. ConclusionsOur findings demonstrate that HCPs would like to continue use of the SQUEGG device + MSAT app as it helped them identify adult patients who had decreased HGS (about 30% of the study population), in turn identifying opportunities to use nutritional interventions such as ONS to address nutrition shortfalls and to restore functional status.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial

In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods. We aimed to evaluate the immunogenicity and safety of Euvichol-S (EuBiologics, Seoul, South Korea) compared with an active control vaccine, Shanchol (Sanofi Healthcare India, Telangana, India) in participants of various ages in Nepal. We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Nepal. Eligible participants were healthy individuals aged 1-40 years without a history of cholera vaccination. Individuals with a history of hypersensitivity reactions to other preventive vaccines, severe chronic disease, previous cholera vaccination, receipt of blood or blood-derived products in the past 3 months or other vaccine within 4 weeks before enrolment, and pregnant or lactating women were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block sizes of two, four, six, or eight) to one of four groups (groups A-D); groups C and D were stratified by age (1-5, 6-17, and 18-40 years). Participants in groups A-C were assigned to receive two 1·5 mL doses of Euvichol-S (three different lots) and participants in group D were assigned to receive the active control vaccine, Shanchol. All participants and site staff (with the exception of those who prepared and administered the study vaccines) were masked to group assignment. The primary immunogenicity endpoint was non-inferiority of immunogenicity of Euvichol-S (group C) versus Shanchol (group D) at 2 weeks after the second vaccine dose, measured by the seroconversion rate, defined as the proportion of participants who had achieved seroconversion (defined as ≥four-fold increase in V cholerae O1 Inaba and Ogawa titres compared with baseline). The primary immunogenicity endpoint was assessed in the per-protocol analysis set, which included all participants who received all their planned vaccine administrations, had no important protocol deviations, and who provided blood samples for all immunogenicity assessments. The primary safety endpoint was the number of solicited adverse events, unsolicited adverse events, and serious adverse events after each vaccine dose in all ages and each age stratum, assessed in all participants who received at least one dose of the Euvichol-S or Shanchol. Non-inferiority of Euvichol-S compared with Shanchol was shown if the lower limit of the 95% CI for the difference between the seroconversion rates in Euvichol-S group C versus Shanchol group D was above the predefined non-inferiority margin of -10%. The trial was registered at ClinicalTrials.gov, NCT04760236. Between Oct 6, 2021, and Jan 19, 2022, 2529 healthy participants (1261 [49·9%] males; 1268 [50·1%] females), were randomly assigned to group A (n=330; Euvichol-S lot number ES-2002), group B (n=331; Euvichol-S ES-2003), group C (n=934; Euvichol-S ES-2004]), or group D (n=934; Shanchol). Non-inferiority of Euvichol-S versus Shanchol in seroconversion rate for both serotypes at 2 weeks after the second dose was confirmed in all ages (difference in seroconversion rate for V cholerae O1 Inaba -0·00 [95% CI -1·86 to 1·86]; for V cholerae O1 Ogawa -1·62 [-4·80 to 1·56]). Treatment-emergent adverse events were reported in 244 (9·7%) of 2529 participants in the safety analysis set, with a total of 403 events; 247 events were reported among 151 (9·5%) of 1595 Euvichol-S recipients and 156 events among 93 (10·0%) of 934 Shanchol recipients. Pyrexia was the most common adverse event in both groups (57 events among 56 [3·5%] of 1595 Euvichol-S recipients and 37 events among 35 [3·7%] of 934 Shanchol recipients). No serious adverse events were deemed to be vaccine-related. A two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. The Bill & Melinda Gates Foundation. For the Nepali translation of the abstract see Supplementary Materials section.

Influence of age and sex on longitudinal metabolic profiles and body weight trajectories in the UK Biobank.

Accurate characterization of how age influences body weight and metabolism at different stages of life is important for understanding ageing processes. Here, we explore observational longitudinal associations between metabolic health and weight from the fifth to the seventh decade of life, using carefully adjusted statistical designs. Body measures and biochemical data from blood and urine (220 measures) across two visits were available from 10 104 UK Biobank participants. Participants were divided into stable (within ±4% per decade), weight loss and weight gain categories. Final subgroups were metabolically matched at baseline (48% women, follow-up 4.3 years, ages 41-70; n = 3368 per subgroup) and further stratified by the median age of 59.3 years and sex. Pulse pressure, haemoglobin A1c and cystatin-C tracked ageing consistently (P < 0.0001). In women under 59, age-associated increases in citrate, pyruvate, alkaline phosphatase and calcium were observed along with adverse changes across lipoprotein measures, fatty acid species and liver enzymes (P < 0.0001). Principal component analysis revealed a qualitative sex difference in the temporal relationship between body weight and metabolism: weight loss was not associated with systemic metabolic improvement in women, whereas both age strata converged consistently towards beneficial (weight loss) or adverse (weight gain) phenotypes in men. We report longitudinal ageing trends for 220 metabolic measures in absolute concentrations, many of which have not been described for older individuals before. Our results also revealed a fundamental dynamic sex divergence that we speculate is caused by menopause-driven metabolic deterioration in women.

Incidence of Influenza-related Medical Encounters and the Associated Healthcare Resource Use and Complications Across Adult Age Groups in the United States During the 2015-2020 Influenza Seasons.

Research on influenza burden in adults has focused on crude subgroups with cut-points at 65 years, limiting insight into how burden varies with increasing age. This study describes the incidence of influenza-related outpatient visits, emergency room visits, and hospitalizations, along with healthcare resource use and complications in the aging adult population. Individuals aged ≥18 years in the United States were evaluated retrospectively in 5 seasonal cohorts (2015-2020 seasons) in strata of age with 5-year increments. Person-level electronic medical records linked to pharmacy and medical claims were used to ascertain patient characteristics and outcomes. Influenza-related medical encounters were identified based on diagnostic codes (International Classification of Diseases, 10th Edition, codes J09*-J11*). Incidence of influenza-related outpatient visits was highest among people aged 18-34 years and declined with increasing age. For emergency room visits, incidence tended to be elevated for people aged 18-34 years, relatively stable from 35 through 60, and increased rapidly after age 60 years. Hospitalization incidence remained relatively stable until about 50 years of age and then increased with age. One in 3 patients was diagnosed with pneumonia after hospitalization, regardless of age. Across seasons, age groups, and clinical settings, on average, 40.8% of individuals were prescribed antivirals and 17.2% antibiotics. Incidence of influenza-related hospitalizations begins to increase around age 50 years rather than the more common cut-point of 65, whereas incidence of outpatient visits was highest among younger adults. Influenza infections frequently led to antiviral and antibiotic prescriptions, underscoring the role influenza vaccination can play in combating antimicrobial resistance.

Evaluation of Myo-Intimal Media Thickness and Atheromatous Plaques in People Living with HIV from the Archiprevaleat Cohort vs. HIV-Negative Subjects.

Antiretroviral therapy has allowed a clear improvement in prognosis for HIV patients, but metabolic problems, such as dyslipidemia, remain. This can lead to the development of atheromatous plaques. Our study aims to evaluate whether HIV-positive (HIV+) patients show higher myo-intimal media thickness (IMT) and atheromatous plaques compared to HIV-negative (HIV-) patients. To evaluate the association between HIV infection in experienced patients and vascular pathology, we performed a cross-sectional study, observing 1006 patients, 380 HIV+ enrolled in the Archiprevaleat cohort, and 626 HIV- as a control group. All patients underwent a Doppler scan of the supra-aortic vessels. We compared the prevalence of IMT > 1.0 mm and plaques in the two groups. Patients in the HIV+ group were younger than those in the HIV- group, with a lower prevalence of hypertension and diabetes and higher dyslipidemia. The prevalence of plaques in strata of age was higher in the HIV+ group than in the HIV- group and was associated with the length of ART exposure. Our cross-sectional, retrospective study shows that HIV+ experienced patients are at greater risk of IMT and atheromatous plaques compared to HIV-. The risk is associated with being HIV+ and with the length of ART exposure. This finding may be useful in preventing cardiovascular risk.

Switching to Dolutegravir/Lamivudine Two-Drug Regimen: Durability and Virologic Outcomes by Age, Sex, and Race in Routine US Clinical Care.

Two-drug regimens (2DR) may address drug-drug interactions and toxicity concerns. Dolutegravir/lamivudine (DTG/3TC) 2DR was approved in the US for both treatment-naïve and treatment-experienced individuals with a viral load <50 copies/mL. This study describes real-world DTG/3TC 2DR treatment outcomes among treatment-experienced individuals, stratified by age, sex, and race. From the OPERA® cohort, people with HIV with a viral load <50 copies/mL who switched from a commonly used three-drug regimen to DTG/3TC 2DR as per the label between April 8, 2019 and April 30, 2021 were included. Incidence rates (Poisson regression) for loss of virologic control (first viral load ≥50 copies/mL), confirmed virologic failure (2 viral loads ≥200 copies/mL or discontinuation after 1 viral load ≥200 copies/mL), and DTG/3TC 2DR discontinuation were estimated overall and stratified by age, sex, and race. The 787 individuals included were followed for a median of 13.6 months (IQR: 8.2, 22.3). Confirmed virologic failure occurred in ≤5 individuals. Loss of virologic control occurred at a rate of 14.0 per 100 person-years (95% CI: 11.7, 16.8). DTG/3TC 2DR discontinuation occurred at a rate of 17.5 per 100 person-years (95% CI: 15.0, 20.3); 4% discontinued for treatment-related reasons (viremia, adverse diagnosis, side effect, lab abnormality). For all outcomes, incidence rates were comparable across strata of age, sex, and race. This descriptive study demonstrates that DTG/3TC 2DR is an effective and well-tolerated treatment option for people with HIV with a viral load <50 copies/mL at switch, regardless of their age, sex, or race.

Efficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for pediatric elective colonoscopy: Phase 3 RCT.

Background and study aims Currently available polyethylene glycol (PEG)-based preparations continue to represent a challenge in children. The aim of this study was to compare the efficacy and safety of a new low-volume PEG preparation with a conventional PEG-electrolyte solution (PEG-ES) in children and adolescents. Patients and methods This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF104 (Clensia) and a conventional PEG-ES (Klean-Prep), and stratified by age stratum (2 to <6; 6 to < 12;12 to <18 years). The primary endpoint was to test the non-inferiority of PMF104 versus PEG-ES, in terms of colon cleansing. Safety, tolerability, acceptability, palatability, and compliance were also assessed. Efficacy endpoints were analyzed in the per protocol set (PPS) and full analysis set (FAS) and safety and tolerability endpoints in the safety set (SAF). Results Of the 356 patients enrolled, 258 were included in the PPS, 346 in the FAS, and 351 in the SAF. Non-inferiority of PMF104 was confirmed for children aged > 6 years and for all age groups in PPS and FAS, respectively. Optimal compliance was reported more frequently in the PMF104 than in the PEG-ES group, in both PPS (86.1% vs. 68.4%) and FAS (82.9% vs. 65.3%). Both preparations were equally safe and tolerable. Palatability and acceptability were considered better in the PMF104 group than in the PEG-ES group (27.1% vs. 15.3% and 15.3% vs. 3.5%, respectively). Conclusions In children aged 6 to 17 years, the new low-volume product PMF104 is non-inferior to the reference PEG-ES in terms of bowel cleansing, safety, and tolerability, with slightly better results in compliance, palatability, and acceptability.

Prevalence and Costs of Esophageal Strictures in the United States

Background and AimsEsophageal strictures are a leading cause of dysphagia, but data regarding the epidemiology of esophageal strictures are limited. This study aimed to investigate the prevalence, healthcare utilization, and financial burden of esophageal strictures in the United States. MethodsWe performed a retrospective cohort study utilizing two large national insurance claims databases (MarketScan and Medicare). Using ICD-9 and -10 diagnostic codes, annual prevalence was calculated for both cohorts overall, as well as stratified by age and sex strata. Most common diagnostic and procedural codes associated with esophageal strictures were extracted and analyzed to estimate healthcare utilization. Direct annual medical costs of esophageal strictures were calculated. ResultsThe annual prevalence of esophageal strictures in MarketScan in 2021 was 203.14 cases/100,000 people while the annual prevalence in Medicare cohort in 2017 was 1123.47 cases/100,000. While rates were relatively stable over time, esophageal stricture prevalence increased with advancing age. No prevalence differences were noticed between males and females. GERD/erosive esophagitis was the top diagnostic code associated with esophageal strictures, though an increase in the proportion of eosinophilic esophagitis codes was noted over time. Esophageal dilation codes were present in ∼50% of stricture cases. The total healthcare costs associated with esophageal strictures were estimated at $1.39 billion in 2017. ConclusionsEsophageal strictures are common, affecting between 1/100 to 1/1000 patients in the United States, with the highest rates seen in patients aged 75y and older. Accordingly, strictures have a significant financial burden on the healthcare system, with costs above $1 billion annually.

Vicarious calibration of GEDI biomass with Landsat age data for understanding secondary forest carbon dynamics

The recovery of biomass in secondary forests plays a vital role in global carbon sequestration processes and carbon emission mitigation. However, accurately quantifying the accumulation rate of aboveground biomass density in these forests is challenging owing to limited longitudinal field data. An alternative monitoring strategy is characterizing the mean biomass at a single point in time across stands with a range of known ages. This chronosequence approach can also be used with remotely sensed data by combining biomass measured with platforms such as NASA’s Global Ecosystem Dynamics Investigation (GEDI) mission with forest age strata provided by historic Landsat imagery. However, focusing on the low-biomass conditions common in newly regenerating forests will accentuate commonly observed over-prediction of low biomass values. We propose a vicarious calibration approach that develops a correction for GEDI’s biomass models in young forests, which may be mapped using Landsat time series, using an assumption that the aboveground biomass of newly cleared forests is zero. We tested this approach, which requires no additional local field data, in the U.S. Pacific Northwest, where extensive inventory data from the USDA Forest Service are available. Our results show that the calibration did not significantly improve the fit of predicted biomass as a function of age across 12 ecoregions (one-side t-test; p = 0.20), but it did significantly reduce bias for the youngest age groups with respect to reference data. Calibrated GEDI-based biomass estimates for < 20 year old forests were more accurate than 2006 IPCC defaults in most ecoregions (with respect to authoritative inventory estimates) and may represent a basis for refining carbon storage expectations for secondary forests globally.

Reports of COVID-19 Vaccine Adverse Events in Predominantly Republican vs Democratic States

Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored. To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs. This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican votes in the 2020 US presidential election. State-level percentage of Republican votes in the 2020 US presidential election. Rates of any AE among COVID-19 vaccine recipients, rates of any severe AE among vaccine recipients, and the proportion of AEs reported as severe. A total of 620 456 AE reports (mean [SD] age of vaccine recipients, 51.8 [17.6] years; 435 797 reports from women [70.2%]; a vaccine recipient could potentially file more than 1 report, so reports are not necessarily from unique individuals) for COVID-19 vaccination were identified from the VAERS database. Significant associations between state political inclination and state AE reporting were observed for all 3 outcomes: a 10% increase in Republican voting was associated with increased odds of AE reports (odds ratio [OR], 1.05; 95% CI, 1.05-1.05; P < .001), severe AE reports (OR, 1.25; 95% CI, 1.24-1.26; P < .001), and the proportion of AEs reported as severe (OR, 1.21; 95% CI, 1.20-1.22; P < .001). These associations were seen across all age strata in stratified analyses and were more pronounced among older subpopulations. This cross-sectional study found that the more states were inclined to vote Republican, the more likely their vaccine recipients or their clinicians reported COVID-19 vaccine AEs. These results suggest that either the perception of vaccine AEs or the motivation to report them was associated with political inclination.

Diabetes Risk Reduction Diet and Colorectal Cancer Risk.

Diabetes has been associated with colorectal cancer. We evaluated whether adherence to a diabetes risk reduction diet (DRRD) can favorably influence the risk of colorectal cancer. Data came from a multicentric Italian case-control study including 1,953 histologically confirmed colorectal cancer cases and 4,154 hospital controls admitted for acute nonneoplastic diseases. Diet was assessed through a validated and reproducible food frequency questionnaire. The DRRD score was computed assigning higher values for higher consumption of cereal fiber, fruit, coffee, nuts and a higher polyunsaturated/saturated fats ratio and for lower glycemic index and lower consumption of red/processed meat and sweetened beverages and fruit juices. The ORs and the corresponding 95% confidence intervals (CI) of colorectal cancer according to the DRRD score were obtained using logistic regression models adjusting for total energy intake and other major confounders. The DRRD was inversely related to colorectal cancer risk. The ORs of colorectal cancer were 0.77 (95% CI, 0.67-0.89) for the third versus first score tertile (Ptrend < 0.001) and 0.92 (95% CI, 0.87-0.96) for a 3-point increment in the score. Inverse associations were observed for colon and rectal cancers and were consistent in strata of sex, age, and other major covariates. A higher adherence to a DRRD was inversely associated with colorectal cancer risk. Given the high incidence and mortality rates of colorectal cancer, adherence to a DRRD can have relevant prevention and public health implications.

Mental and Physical Health Comorbidities in Traumatic Brain Injury: A Non-TBI Controls Comparison

ObjectiveTo examine whether aging with a TBI was associated with a greater burden of health-related comorbidities compared with a non-TBI control cohort and examine the associations between comorbidity burden, emotional outcomes, and health-related quality of life (HRQoL) after TBI across ages. DesignCross-sectional. SettingResearch center or telephone. ParticipantsThe study included 559 participants (NTBI=291, NControls=268). Participants with TBI were recruited during inpatient rehabilitation and had sustained a moderate-severe TBI 1-33 years previously. Non-TBI controls were a convenience sample recruited through advertisements in the community. InterventionsNot applicable. Main Outcome MeasuresThe number of cardiovascular, general physical health, and mental health comorbidities was compared between cohorts and age strata using Poisson regression. The relationships between comorbidities, age, emotional outcomes (Generalized Anxiety Disorder Scale-7, Patient Health Questionnaire-9), and HRQoL (PROMIS Global Health Measure) were examined with linear regression. Distinct subgroups of comorbidities were identified using latent class analysis. Associations between comorbidity classes with demographic and outcome variables were evaluated using multinomial logistic and linear regressions, respectively. ResultsTBI participants had a significantly higher comorbidity burden than controls, primarily driven by elevated rates of mental health disorders (RR=2.71, 95% confidence interval [1.37, 5.35]). Cardiovascular and physical health comorbidities were not elevated in the TBI group compared with controls. Both cohorts had 3 similar comorbidity subgroups, suggesting consistent patterns of co-occurring health conditions regardless of TBI exposure. Physical and mental health comorbidities were associated with elevated depression and anxiety symptoms and diminished HRQoL after TBI compared with controls. ConclusionTBI was associated with greater mental, but not physical, health comorbidities in the decades after injury. However, physical and mental health comorbidities significantly affected emotional and HRQoL status after TBI, underscoring a greater need for long-term support for individuals with TBI coping with both physical and mental health comorbidities.