Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

Abdominal computed tomography measurements of body composition and waitlist mortality in kidney transplant candidates.

Body mass index is often used to determine kidney transplant (KT) candidacy. However, this measure of body composition (BC) has several limitations, including the inability to accurately capture dry weight. Objective computed tomography (CT)-based measures may improve pre-KT risk stratification and capture physiological aging more accurately. We quantified the association between CT-based BC measurements and waitlist mortality in a retrospective study of 828 KT candidates (2010-2022) with clinically obtained CT scans using adjusted competing risk regression. In total, 42.5% of candidates had myopenia, 11.4% had myopenic obesity (MO), 68.8% had myosteatosis, 24.8% had sarcopenia (probable = 11.2%, confirmed = 10.5%, and severe = 3.1%), and 8.6% had sarcopenic obesity. Myopenia, MO, and sarcopenic obesity were not associated with mortality. Patients with myosteatosis (adjusted subhazard ratio [aSHR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; after confounder adjustment) or sarcopenia (probable: aSHR = 1.78, 95% CI: 1.10-2.88; confirmed: aSHR = 1.68, 95% CI: 1.01-2.82; and severe: aSHR = 2.51, 95% CI: 1.12-5.66; after full adjustment) were at increased risk of mortality. When stratified by age, MO (aSHR = 2.21, 95% CI: 1.28-3.83; P interaction = .005) and myosteatosis (aSHR = 1.95, 95% CI: 1.18-3.21; P interaction = .038) were associated with elevated risk only among candidates <65 years. MO was only associated with waitlist mortality among frail candidates (adjusted hazard ratio = 2.54, 95% CI: 1.28-5.05; P interaction = .021). Transplant centers should consider using BC metrics in addition to body mass index when a CT scan is available to improve pre-KT risk stratification at KT evaluation.

Advance Care Planning and Palliative Care Consultation in Kidney Transplantation.

RATIONALE & OBJECTIVE: Because of the high risk of waitlist mortality and posttransplant complications, kidney transplant (KT) patients may benefit from advance care planning (ACP) and palliative care consultation (PCC). We quantified the prevalence and racial disparities in ACP and PCC among KT candidates and recipients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,575 adult KT candidates and 1,233 adult recipients (2008-2020). EXPOSURE: Race and ethnicity. OUTCOMES: All reports of ACP and PCC were abstracted from chart review. ACP was defined as patient self-report of an advance directive, presence of an advance directive in the medical record, or a documented goals-of-care conversation with a provider. PCC was defined as an ordered referral or a documented palliative care note in the medical record. ANALYTICAL APPROACH: Racial/ethnic disparities in ACP/PCC were estimated using adjusted logistic regression. RESULTS: 21.4% of KT candidates and 34.9% of recipients engaged in ACP. There were racial/ethnic disparities in ACP among KT candidates (White, 24.4%; Black, 19.1%; Hispanic, 15%; other race and ethnicity, 21.1%; P=0.008) and recipients (White, 39.5%; Black, 31.2%; Hispanic, 26.3%; other race and ethnicity, 26.6%; P=0.007). After adjustment, Black KT recipients had a 29% lower likelihood of engaging in ACP (OR, 0.71; 95% CI, 0.55-0.91) than White KT recipients. Among older (aged≥65 years) recipients, those who were Black had a lower likelihood of engaging in ACP, but there was no racial disparity among younger recipients (P=0.020 for interaction). 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC; there were no racial disparities in PCC among KT candidates (White, 5.3%; Black, 3.6%; Hispanic, 2.5%; other race and ethnicity, 2.1%; P=0.13) or recipients (White, 5.5%; Black, 5.6%; Hispanic, 0.0%; other race and ethnicity, 1.3%; P = 0.21). LIMITATIONS: Generalizability may be limited to academic transplant centers. CONCLUSIONS: ACP is not common among KT patients, and minoritized transplant patients are least likely to engage in ACP; PCC is less common. Future efforts should aim to integrate ACP and PCC into the KT process. PLAIN-LANGUAGE SUMMARY: Kidney transplant (KT) candidates and recipients are at elevated risk of morbidity and mortality. They may benefit from completing a document or conversation with their palliative care provider that outlines their future health care wishes, known as advance care planning (ACP), which is a component of palliative care consultation (PCC). We wanted to determine how many KT candidates and recipients have engaged in ACP or PCC and identify potential racial disparities. We found that 21.4% of candidates and 34.9% of recipients engaged in ACP. After adjustment, Black recipients had a 29% lower likelihood of engaging in ACP. We found that 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC, with no racial disparities found in PCC.

Post-kidney transplant body mass index trajectories are associated with graft loss and mortality.

BACKGROUND: Early post-kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all-cause graft loss and mortality. METHODS: We estimated 5-year post-KT (n = 151 170; SRTR) BMI trajectories using an adjusted mixed effects model. We estimated long-term mortality and graft loss risks by 1-year BMI change quartile (decrease [1st quartile]: change < -.07 kg/m2 /month; stable [2nd quartile]: -.07 ≤ change ≤ .09 kg/m2 /month; increase [3rd, 4th quartile]: change > .09 kg/m2 /month) using adjusted Cox proportional hazards models. RESULTS: BMI increased in the 3 years post-KT (.64 kg/m2 /year, 95% CI: .63, .64) and decreased in years 3-5 (-.24 kg/m2 /year, 95% CI: -.26, -.22). 1-year post-KT BMI decrease was associated with elevated risks of all-cause mortality (aHR = 1.13, 95% CI: 1.10-1.16), all-cause graft loss (aHR = 1.13, 95% CI: 1.10-1.15), death-censored graft loss (aHR = 1.15, 95% CI: 1.11-1.19), and mortality with functioning graft (aHR = 1.11, 95% CI: 1.08-1.14). Among recipients with obesity (pre-KT BMI≥30 kg/m2 ), BMI increase was associated with higher all-cause mortality (aHR = 1.09, 95% CI: 1.05-1.14), all-cause graft loss (aHR = 1.05, 95% CI: 1.01-1.09), and mortality with functioning graft (aHR = 1.10, 95% CI: 1.05-1.15) risks, but not death-censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all-cause graft loss (aHR = .97, 95% CI: .95-.99) and death-censored graft loss (aHR = .93, 95% CI: .90-.96) risks, but not all-cause mortality or mortality with functioning graft risks. CONCLUSIONS: BMI increases in the 3 years post-KT, then decreases in years 3-5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post-KT.

Prenatal Antidepressant Exposures and Autism Spectrum Disorder or Traits: A Retrospective, Multi-Cohort Study.

Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.

Associations of maternal insulin sensitivity during pregnancy with childhood central adiposity in the Genetics of Glucose regulation in Gestation and Growth (Gen3G) cohort.

BACKGROUND: Childhood obesity has been associated with prenatal exposure to maternal hyperglycaemia, but we lack understanding about maternal insulin physiologic components that contribute to this association. OBJECTIVES: Evaluate the association between maternal insulin sensitivity during pregnancy and adiposity measures in childhood. METHODS: In 422 mother-child pairs, we tested associations between maternal insulin sensitivity measures at ~26 weeks of pregnancy and child adiposity measures, including dual-energy X-ray absorptiometry body composition and anthropometry (body mass index and waist circumference) at ~5 years. We used linear regression analyses to adjust for maternal age, ethnicity, gravidity, first-trimester body mass index, and child sex and age at mid-childhood. RESULTS: In early pregnancy, maternal mean age was 28.6 ± 4.3 years and median body mass index was 24.1 kg/m2 . Lower maternal insulin sensitivity indices were correlated with greater child adiposity based on anthropometry measures and on dual-energy X-ray absorptiometry total and trunk % fat in univariate associations (r = -0.122 to -0.159). Lower maternal insulin sensitivity was specifically associated with higher dual-energy X-ray absorptiometry trunk % fat (n = 359 for Matsuda; ß = -0.034 ± 0.013; p = 0.01) after adjustment for covariates, including maternal body mass index. CONCLUSIONS: Maternal insulin sensitivity during pregnancy may contribute to increased risk for higher offspring central adiposity in middle childhood.

Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination - PCORnet, United States, January 2021-January 2022.

Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.

Lifestyle interventions in pregnancy targeting GDM prevention: looking ahead to precision medicine.

Gestational diabetes mellitus (GDM) is the most prevalent pregnancy-related endocrinopathy, affecting up to 25% of pregnancies worldwide. Pregnant individuals who develop GDM have an increased risk of complications during pregnancy and birth, as well as future development of type 2 diabetes mellitus and CVD. This increased risk is subsequently passed along to the offspring, perpetuating a cycle of metabolic dysfunction across generations. GDM prevention strategies have had mixed results for many years, but more recent systematic reviews and meta-analyses have suggested potential new avenues of prevention. The objective of this review is to summarise the literature examining the efficacy of lifestyle interventions for the prevention of GDM and to uncover if specific individual-level characteristics influence this outcome. Based on the present literature, we determined that future trials should be designed to understand if initiation of lifestyle intervention in the preconception period is more effective to reduce GDM. Furthermore, trials initiated during pregnancy should be developed through the lens of precision prevention. That is, trials should tailor intervention approaches based on individual-level risk defined by the presence of modifiable and non-modifiable risk factors. Finally, future interventions might also benefit from just-in-time adaptive intervention designs, which allow for interventions to be modified in real-time based on objective assessments of an individual's response.

Early-pregnancy maternal body mass index is associated with common DNA methylation markers in cord blood and placenta: a paired-tissue epigenome-wide association study.

Women entering pregnancy with elevated body mass index (BMI) face greater risk of adverse outcomes during pregnancy, delivery, and for their offspring later in life, potentially via epigenetics. If epigenetic programming occurs early during in utero development, the differential marks should be detectable in multiple tissues despite the known unique epigenetic profile in each.We used early-pregnancy BMI as reflection of maternal metabolic milieu exposure in peri-conception and early-pregnancy period. We analysed DNA methylation in paired cord blood and placenta samples among 437 newborns from Gen3G, a pre-birth prospective cohort of primarily European descent. We measured DNA methylation in both tissues across the genome in >720,000 CpG sites using the Illumina MethylationEPIC array. At each site, we used linear mixed models (LMMs) with an unstructured variance-covariance matrix to test for an association between maternal early-pregnancy BMI and DNA methylation in both tissues (modelled as M-values). We adjusted for tissue-specific covariates, offspring sex, gestational age at delivery, and maternal smoking and age.Women had a mean (SD) BMI of 25.4 (5.7) kg/m2 measured at first trimester visit (mean=9.9 weeks). Early-pregnancy BMI was associated with differential DNA methylation levels in paired-tissue analyses at two sites: cg10593758 (ß=0.0126, SE=0.0025; P=4.07e-7), annotated to CRHBP, and cg0762168 (ß=-0.0094, SE=0.0018; P=2.78e-7), annotated to CCDC97.Application of LMMs in DNA methylation data from distinct fetal-origin tissues allowed us to identify CpG sites at which early-pregnancy BMI may have an epigenetic 'programming' effect on overall fetus development. One site (CRHBP) may play a role in hypothalamic-pituitary-adrenal axis regulation.

Social media effectiveness as a humanitarian response to mitigate influenza epidemic and COVID-19 pandemic.

Influenza and COVID-19 are infectious diseases with significant burdens. Information and awareness on preventative techniques can be spread through the use of social media, which has become an increasingly utilized tool in recent years. This study developed a dynamic transmission model to investigate the impact of social media, particularly tweets via the social networking platform, Twitter on the number of influenza and COVID-19 cases of infection and deaths. We modified the traditional Susceptible-Exposed-Infectious-Recovered (SEIR-V) model with an additional social media component, in order to increase the accuracy of transmission dynamics and gain insight on whether social media is a beneficial behavioral intervention for these infectious diseases. The analysis found that social media has a positive effect in mitigating the spread of contagious disease in terms of peak time, peak magnitude, total infected, and total death; and the results also showed that social media's effect has a non-linear relationship with the reproduction number R 0 and it will be amplified when a vaccine is available. The findings indicate that social media is an integral part in the humanitarian logistics of pandemic and emergency preparedness, and contributes to the literature by informing best practices in the response to similar disasters.

Cost-effectiveness of Hepatitis A vaccination in a developed and developing country.

PURPOSE: Hepatitis A is a prevalent disease that is largely preventable by vaccine usage. The vaccine for this illness is highly underused in most regions. In an attempt to find the strategies that are most beneficial in regard to quality-adjusted life years (QALYs) and cost in current environments, the purpose of this paper is to conduct cost-effectiveness analyses to investigate vaccination strategies in a more economically developed country (MEDC), generally known as a "developed" area: the USA, and a less economically developed country (LEDC), generally known as a "developing" area: the state of Rio de Janeiro, Brazil. DESIGN/METHODOLOGY/APPROACH: This study used a dynamic transmission model for comparative effectiveness analyses. The model ran two different scenarios. The two regions studied have different policies and strategies for Hepatitis A vaccination currently, and also used different strategies in 2009. In the USA, a universal vaccination policy was modeled, along with a scenario in which it was removed. In Rio de Janeiro, a no vaccination policy was modeled, along with a scenario in which a universal vaccination policy was effected. FINDINGS: The comparison of resulting incremental cost-effectiveness ratio values to accepted threshold values showed universal vaccination to be cost-effective in both the USA and Rio de Janeiro as compared to no vaccination. When episode and vaccination costs and vaccination efficacy were varied, this still remained true. Universal vaccination was found to result in lower incidence of Hepatitis A in both the USA and Rio de Janeiro. Over the twenty-year time horizon, universal vaccination is projected to prevent 506,945 cases of symptomatic Hepatitis A in the USA and 42,318 cases of Hepatitis A in Rio de Janeiro. Other benefits include a projected increase in cumulative QALYs through the use of universal vaccination. ORIGINALITY/VALUE: This analysis showed universal vaccination to be cost-effective as compared to no vaccination, and portions of the study's approach had not previously been applied in tandem to investigate Hepatitis A interventions. The results may help foster higher compliance rates for Hepatitis A vaccination and even greater per-person economic benefits of universal vaccination, particularly in the USA. The purpose of this study is also to encourage elevated levels of surveillance on age of infection in developing regions and consistent reevaluation utilizing dynamic transmission models in both the USA and Brazil, as well as other rapidly developing regions, in order to prevent future epidemics and costs associated with the disease.

Epidemiological shift of hepatitis A in EAGLE countries - a projection.

PURPOSE: Many world regions are developing quickly and experiencing increasing levels of sanitation, causing an epidemiological shift of hepatitis A in these areas. The shift occurs when children avoid being infected with the disease until a later age due to cleaner water sources, food, and hygiene practices in their environment; but if they are infected at later age, the disease is much more severe and lost productivity costs are higher. The purpose of this paper is to examine what could occur if an epidemiological shift of the disease continues in these regions, and what type of future burden hepatitis A may have in a hypothetical rapidly developing country. DESIGN/METHODOLOGY/APPROACH: Initially, annual hepatitis A mortality was regressed on the Human Development Index (HDI) for each country classified as an emerging and growth-leading economy (EAGLE) to provide an overview of how economic development and hepatitis A mortality related. Data from the various EAGLE countries were also fit to a model of hepatitis A mortality rates in relation to HDI, which were both weighted by each country's 1995-2010 population of available data, in order to create a model for a hypothetical emerging market country. A second regression model was fit for the weighted average annual hepatitis A mortality rate of all EAGLE countries from the years 1995 to 2010. Additionally, hepatitis A mortality rate was regressed on year. FINDINGS: Regression results show a constant decline of mortality as HDI increased. For each increase of one in HDI value in this hypothetical country, mortality rate declined by 2.3016 deaths per 100,000 people. The hypothetical country showed the HDI value increasing by 0.0073 each year. Also, results displayed a decrease in hepatitis A mortality rate of 0.0168 per 100,000 people per year. Finally, the mortality rate for hepatitis A in this hypothetical country is projected to be down to 0.11299 deaths per 100,000 people by 2030 and its economic status will fall just below the HDI criteria for a developed country by 2025. ORIGINALITY/VALUE: The hypothetical country as a prototype model was created from the results of regressed data from EAGLE countries. It is aimed to display an example of the health and economic changes occurring in these rapidly developing regions in order to help understand potential hepatitis A trends, while underscoring the importance of informed and regular policy updates in the coming years. The author believes this regression provides insight into the patterns of hepatitis A mortality and HDI as these EAGLE countries undergo rapid development.

Markov chain decision model for urinary incontinence procedures.

Purpose Urinary incontinence (UI) is a common chronic health condition, a problem specifically among elderly women that impacts quality of life negatively. However, UI is usually viewed as likely result of old age, and as such is generally not evaluated or even managed appropriately. Many treatments are available to manage incontinence, such as bladder training and numerous surgical procedures such as Burch colposuspension and Sling for UI which have high success rates. The purpose of this paper is to analyze which of these popular surgical procedures for UI is effective. Design/methodology/approach This research employs randomized, prospective studies to obtain robust cost and utility data used in the Markov chain decision model for examining which of these surgical interventions is more effective in treating women with stress UI based on two measures: number of quality adjusted life years (QALY) and cost per QALY. Treeage Pro Healthcare software was employed in Markov decision analysis. Findings Results showed the Sling procedure is a more effective surgical intervention than the Burch. However, if a utility greater than certain utility value, for which both procedures are equally effective, is assigned to persistent incontinence, the Burch procedure is more effective than the Sling procedure. Originality/value This paper demonstrates the efficacy of a Markov chain decision modeling approach to study the comparative effectiveness analysis of available treatments for patients with UI, an important public health issue, widely prevalent among elderly women in developed and developing countries. This research also improves upon other analyses using a Markov chain decision modeling process to analyze various strategies for treating UI.