Lower Decline Rate Research Articles

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2

ObjectivesThis study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. MethodsDanish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. ResultsA total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. ConclusionHybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

Fatigue and Metabolic Responses during Repeated Sets of Bench Press Exercise to Exhaustion at Different Ranges of Motion.

This study compared the acute effects of different ranges of motion (ROM) on fatigue and metabolic responses during repeated sets of bench press exercise. Ten resistance trained men performed three sets to momentary failure with two-min rest intervals at three different ROM: full ROM (FULL), and partial ROM in which the barbell was moved either at the bottom half (BOTTOM) or the top half (TOP) of the full barbell vertical displacement. In TOP, a higher load was lifted, and a higher total number of repetitions was performed compared to FULL and BOTTOM (130 ± 17.6 vs. 102.5 ± 15.9 vs. 98.8 ± 17.5 kg; 55.2 ± 9.8, 32.2 ± 6.5 vs. 49.1 ± 16.5 kg, respectively p < 0.01). Work per repetition was higher in FULL than TOP and BOTTOM (283 ± 43 vs. 205 ± 32 vs. 164 ± 31 J/repetition, p < 0.01). Mean barbell velocity at the start of set 1 was 21.7% and 12.8% higher in FULL compared to TOP and BOTTOM, respectively. The rate of decline in mean barbell velocity was doubled from set 1 to set 3 (p < 0.01) and was higher in FULL than both TOP and BOTTOM (p < 0.001). Also, the rate of mean barbell velocity decline was higher in BOTTOM compared to TOP (p = 0.045). Blood lactate concentration was similarly increased in all ROM (p < 0.001). Training at TOP ROM allowed not only to lift a higher load, but also to perform more repetitions with a lower rate of decline in mean barbell velocity. Despite the lower absolute load and work per repetition, fatigue was higher in BOTTOM than TOP and this may be attributed to differences in muscle length.

Cognitive Decline After Divorce and Widowhood: Is Marital Loss Always a Loss?

We used longitudinal data to determine whether the type of marital loss is associated with the rate of cognitive change before and after divorce or widowhood. Previous research found that relationship status was associated with older adults' cognitive performance: married persons performed better on memory assessments and had lower dementia risk than unmarried-cohabitating, never-married, divorced, and widowed persons. However, the end of a marriage may cause distress or reduce distress because a stressor disappears. Questions thus remain about the mechanisms by which marital change affects cognitive outcomes and, specifically, whether termination of marriage can improve cognitive performance for some. Using data from the 1998-2016 waves of the Health and Retirement Study (N = 23,393), we conducted two analyses. First, we used trajectory analysis to create clusters of participants with similar cognitive trajectories and tested the association between participants' cluster membership and marital loss type. Second, we used multilevel modeling to analyze the relationship between participants' cognitive scores while married and following divorce or widowhood and linked these to marital features. Participants who divorced showed no difference in trajectory distribution; widowed participants were more likely to be in the lower-performing and more quickly declining groups. Participants had lower rates of decline following divorce (β = .136, p < .001), while widowed participants had accelerated decline following spousal death (β = -0.183, p < .001) and an immediate decline following spousal death (β = -0.113, p = .028). We found that the type of marital loss was important, and predicted improvements in cognition for some and decrements for others, with individuals who were divorced performing best while those who were widowed or separated but not divorced performing worse.

Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety

BackgroundFibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients.MethodsWe...

Multivariate growth trajectories of parenting practices in adolescence predicting young adult relationships with parents.

Guided by the life course perspective, this study investigated the developmental antecedents of contact, closeness/warmth, and negativity in young adults' relationships with their parents. Taking the developmental systems approach, we considered interindividual differences in not only initial levels of parenting quality in early adolescence (Grade 6) but also developmental changes in parenting quality across adolescence (Grades 6-12) as predictors of young adult-parent relationship quality. Data were from a large sample of young adults (N = 1,631; Mage = 22.84; 57% female; 90% White; 25% received free/reduced-price school lunch in Grade 6) followed from the fall of Grades 6 to 12 at eight time points, plus a young adult assessment. Using multivariate latent growth curve modeling, we identified a nuanced pattern of predictors of the three relationship dimensions. Higher initial levels of and lower rates of decline in parental involvement across adolescence predicted more young adult contact with mothers and fathers. Higher initial levels of parental warmth and parental involvement, as well as lower rates of decline in parental warmth, predicted greater closeness/warmth with mothers and fathers in young adulthood. Higher initial levels of and lower rates of decline in effective discipline predicted less young adult negativity toward mothers and fathers. These results held even when accounting for important adolescent and young adult covariates (adolescent sex and race, adolescent family income and structure, adolescent aggressive behavior tendencies, young adult living arrangement). The study offers new insights into how parenting practices in adolescence contribute to parent-child relationship in young adulthood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A novel braided structure with enhanced feed flow state for hollow fiber air-gap membrane distillation performance improvement

The feed flow state affects temperature polarization (TP), concentration polarization (CP), and membrane fouling during the membrane distillation process. A novel braided structure for AGMD was proposed in this paper, in which hollow fiber membranes and heat exchange tubes are braided together. The braided structure can alter feed flow direction and reduces the membrane's contact area. Theoretical calculations show that the braided structure reduces the critical Reynolds number for the feed's unstable flow, and improves the feed flow state by forming Dean vortices. Comparative experiments of the braided module and parallel module were carried out. The results show that the braided module performs better than the parallel module. The braided module has a higher flux (J) and gained output ratio (GOR) when treating the tap water with significant TP; a lower decline rate in J and GOR besides a smaller concentration polarization coefficient (CPC) when treating 3.5 wt% NaCl aqueous solution; a slower formation of membrane fouling and a lower reduction in J and GOR when treating a humic acid/calcium carbonate mixed solution. It is proved that the braided structure can improve the performance of AGMD by enhancing the feed flow state to mitigate the TP, CP, and membrane fouling.

Impact of SARS-CoV-2 pandemic on the mental and physical health of children enrolled in a paediatric weight management clinic.

Obesity is a global public health concern. Given the widespread disruption caused by the SARS-CoV-2 pandemic, it is important to evaluate its impact on children with chronic health conditions. This study examines the health of paediatric patients with obesity enrolled in a tertiary hospital weight management program, before and 1 year into the COVID-19 pandemic. This is a retrospective chart review of patients aged 2 to 17 years enrolled in a paediatric weight management clinic. Mental health outcomes (i.e., new referrals to psychologist, social work, eating disorder program, incidence of dysregulated eating, suicidal ideation, and/or self-harm) and physical health (anthropometric measures) were compared before and 1 year into the pandemic. Among the 334 children seen in either period, there was an increase in referrals to psychologist (12.4% versus 26.5%; P=0.002) and the composite mental health outcome (17.2% versus 30.2%; P=0.005) during the pandemic compared with pre-pandemic. In a subset of children (n=30) with anthropometric measures in both periods, there was a lower rate of decline in BMIz score (-1.5 [2.00] versus -0.3 [0.73]/year; P=0.002) and an increase in adiposity (-0.8 [4.64] versus 2.7 [5.54]%/year; P=0.043) during the pandemic. The pandemic has impacted the mental and physical health of children with obesity engaged in a weight management clinic. While our study provides evidence of a negative impact on mental health outcomes and less improvement in anthropometric measures, future research when patients return to in-person care will enable further examination of our findings with additional objective measures.

Fatigue-Sensitivity Comparison of sEMG and A-Mode Ultrasound based Hand Gesture Recognition.

Though physiological signal based human-machine interfaces (HMIs) have recently developed rapidly, their practical use is restricted by many real-world environmental factors, one of which is muscle fatigue. This paper explores the sensitivities between surface electromyography (sEMG) and A-mode ultrasound (AUS) sensing modalities subject to muscle fatigue in the context of hand gesture recognition tasks. Two metrics, mean classification accuracy ( mCA) and decline rate ( DR), are proposed to evaluate the accuracy and muscle fatigue sensitivity between sEMG and AUS based HMIs. Muscle fatigue inducing experiment was designed and eight subjects were recruited to participate in the experiment. The gesture recognition accuracies of sEMG and AUS under non-fatigue state and fatigue state are compared through Mahalanobis distance based classifier linear discriminant analysis (LDA). In addition, Mahalanobis distance based metrics, repeatability index ( RI) and separability index ( SI), are introduced to evaluate the changes in the feature distribution during muscle fatigue and reveal the cause of the fatigue sensitivity difference between sEMG and AUS signals. The experimental results demonstrate that the fatigue robustness of AUS signal is better than that of sEMG signal. Specifically, with the employment of the LDA classifier trained under non-fatigue state, the testing accuracy of the sEMG signal on the non-fatigue state is 94.96%, while reduce to 68.26% on the fatigue state. The testing accuracy of the AUS signal on the corresponding states is 99.68% and 91.24% respectively. AUS signal attains higher mCA and lower DR, indicating that it has advantages over sEMG signal in terms of both accuracy and muscle fatigue sensitivity. In addition, the RI and RI/SI analysis reveal that before and after muscle fatigue, the consistency of AUS feature distribution is better than that of sEMG. These research outcomes validate that AUS is more tolerant to feature migration caused by muscle fatigue than sEMG.

Striatal dopamine transporter degeneration in right-handed REM sleep behavior disorder patients progresses faster in the left hemisphere

ObjectiveIn right-handed patients with idiopathic rapid eye movement sleep behavior disorder (IRBD) or Parkinson's disease (PD), dopamine transporter (DAT) single-photon emission computed tomography (SPECT) shows a predominant nigrostriatal deficit in the left striatum. To confirm this hypothesis, we longitudinally investigated whether the nigrostriatal function is asymmetric in Japanese patients with IRBD. MethodsIn 91 polysomnography-confirmed IRBD patients, which included 87 right-handed IRBD patients who underwent 33 repeat DAT-SPECT scans, we retrospectively examined the striatal dopaminergic terminals in each hemisphere using DAT-SPECT. We calculated the values of interhemispheric laterality index for the right and left sides. ResultsThe proportion of IRBD patients with lower SBR in the striatum was different between the left (n = 60, 69.0%) and right (n = 27, 31.0%) hemispheres. In the repeat DAT-SPECT scan (n = 33), the rate of decline in the striatum was greater on the left than on the right side, and the proportion of patients with lower decline rates in the left striatum (n = 25, 73.5%) was greater than the that in the right striatum (n = 3, 8.8%). The proportion of lower SBR side at baseline did not predict the development of PD or DLB. ConclusionRight-handed IRBD patients have asymmetric nigrostriatal dopaminergic function, as evidenced by the faster estimated rate of decline for the left striatum than the right striatum. The left-right hemispheric striatal predominance of the nigrostriatal deficit in the right-handed prodromal PD or DLB patients represents a difference in the early pathological process of the disease.

Kinetics of Anti-Sars-Cov-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

Background: Levels of neutralizing antibodies (NΑbs) against SARS-CoV-2 correlate with clinically relevant immune protection from COVID-19. However, a slight decline in antibody titers has become evident even at one month following the second BNT162b2 shot, whereas increased time since the second vaccine dose has been associated with decreased NAb activity against SARS-CoV-2 variants. The aim of this study was to investigate the kinetics of NAbs and anti-S-RBD IgGs after vaccination of health workers with the BNT162b2 mRNA vaccine over a period of up to three months after the second shot. The possible influence of comorbidities, characteristics of the subjects, co-medication, and adverse events was also investigated.Methods: All participants have been enrolled in a large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination. Main inclusion criteria for participation in this study were eligibility for vaccination according to the national program for COVID-19, age above 18 years, and ability to sign the informed consent form. Major exclusion criteria included the presence of active malignant disease, immunosuppressive therapy, and end-stage renal disease. According to National Immunization Program, access to the BNT162b2 mRNA vaccine was available to anyone 18 years of age or older.NΑbs and anti-S-RBD IgG titers were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111), using FDA approved methods, namely, cPass™ SARS-CoV2 NAbs Detection Kit (GenScript, Piscataway, NJ, USA) and Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH, Mannheim, Germany), respectively.Results: In total, 283 health workers (median age 48 years) were included in this study. On D1, immediately before vaccination, the median neutralizing inhibition was 14.2%, while 29 individuals (10.2%) had inhibition levels above the positive threshold of the method (30%). NAbs showed a rapid increase from D8 to D36 on a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50 a slight decrease in NAbs values was detected and it became more prominent between D50 and D111, when the rate of decline was determined at -0.11 per day. The median (SD) NAbs titers at D111 were 92.7% (11.8). Paired grouped comparisons using the Wilcoxon signed ranks test showed statistically significant differences in inhibition levels between pairs: D36 vs. D50, D36 vs. D111, and D50 vs. D111 (for all three comparisons p<0.001) (Figure A).A similar pattern was also observed for anti-S-RBD antibodies. It is worth mentioning that compared to NAbs, the maximum anti-S-RBD levels were reached two weeks later, i.e., at D36. Interestingly, anti-S-RBDs showed a steeper increase during D22-D36 and a lower decline rate during D36-D111. All consecutive pairs comparison, using Wilcoxon's test, led to p-values<0.001 (Figure B).There was an almost linear relationship between NAbs and anti-S-RBD at D22 (Spearman's rho correlation coefficient equal to 0.718). However, their relationship became non-linear from D36; this is due to the steep increase in anti-S-RBD levels that was observed during the D22-D36 period, while the corresponding increase rate for NAbs was much lower. Also, the decline of anti-S-RBD titers was lower compared to that of NAbs. The composite effect of these functions led to a non-linear pattern.Furthermore, prior COVID-19 and younger age were associated with superior antibody responses over time. Regarding those with previous positive PCR for SARS-CoV-2, significantly higher levels were observed at the initial phase (D1, D8) (Mann-Whitney p-values<0.001) and at D111 (p=0.046). From D50 there was a trend for a slower decline rate for those with previous positive PCR. Younger individuals had higher antibody titers at D36, D50, and D111, which is due to a slower decline in NAbs compared to the older group of participants (for all three comparisons, Wilcoxon's p-values were<0.05).Conclusions: We found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals. Our longitudinal study is ongoing to determine the time point of NAbs reduction below the positivity threshold; then a booster vaccine dose might be necessary to maintain humoral immunity against SARS-CoV-2. [Display omitted] DisclosuresTerpos: Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; BMS: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding. Gavriatopoulou: Janssen: Honoraria; Karyopharm: Honoraria; Genesis: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Dimopoulos: Takeda: Honoraria; Beigene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria.

Assessment of functional sit-to-stand muscle power: Cross-sectional trajectories across the lifespan.

The 30-s sit-to-stand (STS) muscle power test is a valid test to assess muscle power in older people; however, whether it may be used to assess trajectories of lower-limb muscle power through the adult lifespan is not known. This study evaluated the pattern and time course of variations in relative, allometric and specific STS muscle power throughout the lifespan. Subjects participating in the Copenhagen Sarcopenia Study (729 women and 576 men; aged 20 to 93 years) were included. Lower-limb muscle power was assessed with the 30-s version of the STS muscle power test. Allometric, relative and specific STS power were calculated as absolute STS power normalized to height squared, body mass and leg lean mass as assessed by DXA, respectively. Relative STS muscle power tended to increase in women (0.08 ± 0.05 W·kg-1·yr-1; p = 0.082) and increased in men (0.14 ± 0.07 W·kg-1·yr-1; p = 0.046) between 20 and 30 years, followed by a slow decline (-0.05 ± 0.05 W·kg-1·yr-1 and -0.06 ± 0.08 W·kg-1·yr-1, respectively; both p > 0.05) between 30 and 50 years. Then, relative STS power declined at an accelerated rate up to oldest age in men (-0.09 ± 0.02 W·kg-1·yr-1) and in women until the age of 75 (-0.09 ± 0.01 W·kg-1·yr-1) (both p < 0.001). A lower rate of decline was observed in women aged 75 and older (-0.04 ± 0.02 W·kg-1·yr-1; p = 0.039). Similar age-related patterns were noted for allometric and specific STS power. The STS muscle power test appears to provide a feasible and inexpensive tool to monitor cross-sectional trajectories of muscle power throughout the lifespan.

Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers.

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.

Тафамидис в лечении транстиретинового амилоидоза сердца

Transthyretin is primarily synthesized in the liver and transports thyroxine and vitamin A in the body. The transthyretin when dissociated into monomers can misfold and ultimately form amyloid fibrils. There are two types of ATTR amyloidosis: hereditary (caused by mutations in the TTR gene) and wild-type (also referred to as senile systemic amyloidosis). Amyloid cardiomyopathy can develop in patients with both types of ATTR amyloidosis, has a later onset and is characterized by progressive heart failure leading to death within a few years after diagnosis. Tafamidis is an oral-administered small molecule that binds to transthyretin and inhibits transthyretin tetramer dissociation, the rate-limiting step in the amyloidosis. Long-term efficacy and safety of tafamidis were shown in patients with transthyretin familial amyloid polyneuropathy. The objective of the phase 3 international, multicenter, double-blind, placebo-controlled, randomized ATTR-ACT study was to evaluate the efficacy, safety, and tolerability of tafamidis (20 or 80 mg orally QD) in comparison with placebo in 441 patients with hereditary and nonhereditary transthyretin cardiomyopathy (median age 75 years, 90% of males). At month 30, treatment with tafamidis was associated with a lower risk of all-cause mortality (by 30%) and a lower rate of cardiovascular related hospitalizations (by 32%) than placebo and resulted in a lower rate of decline in distance for the 6-minute walk test and a lower rate of decline in KCCQ-OS score. The data from extension study supports tafamidis 80 mg as the optimal dose (bioequivalent to tafamidis free acid 61 mg).

Blood Pressure in Young Adults and Cardiovascular Disease Later in Life.

Cardiovascular disease (CVD) mortality has declined markedly over the past several decades among middle-age and older adults in the United States. However, young adults (18-39 years of age) have had a lower rate of decline in CVD mortality. This trend may be related to the prevalence of high blood pressure (BP) having increased among young US adults. Additionally, awareness, treatment, and control of hypertension are low among US adults between 20 and 39 years of age. Many young adults and healthcare providers may not be aware of the impact of high BP during young adulthood on their later life, the associations of BP patterns with adverse outcomes later in life, and benefit-to-harm ratios of pharmacological treatment. This review provides a synthesis of the related resources available in the literature to better understand BP-related CVD risk among young adults and better identify BP patterns and levels during young adulthood that are associated with CVD events later in life, and lastly, to clarify future challenges in BP management for young adults.

Trust in government regarding COVID-19 and its associations with preventive health behaviour and prosocial behaviour during the pandemic: a cross-sectional and longitudinal study.

The effective implementation of government policies and measures for controlling the coronavirus disease 2019 (COVID-19) pandemic requires compliance from the public. This study aimed to examine cross-sectional and longitudinal associations of trust in government regarding COVID-19 control with the adoption of recommended health behaviours and prosocial behaviours, and potential determinants of trust in government during the pandemic. This study analysed data from the PsyCorona Survey, an international project on COVID-19 that included 23 733 participants from 23 countries (representative in age and gender distributions by country) at baseline survey and 7785 participants who also completed follow-up surveys. Specification curve analysis was used to examine concurrent associations between trust in government and self-reported behaviours. We further used structural equation model to explore potential determinants of trust in government. Multilevel linear regressions were used to examine associations between baseline trust and longitudinal behavioural changes. Higher trust in government regarding COVID-19 control was significantly associated with higher adoption of health behaviours (handwashing, avoiding crowded space, self-quarantine) and prosocial behaviours in specification curve analyses (median standardised β = 0.173 and 0.229, p < 0.001). Government perceived as well organised, disseminating clear messages and knowledge on COVID-19, and perceived fairness were positively associated with trust in government (standardised β = 0.358, 0.230, 0.056, and 0.249, p < 0.01). Higher trust at baseline survey was significantly associated with lower rate of decline in health behaviours over time (p for interaction = 0.001). These results highlighted the importance of trust in government in the control of COVID-19.

P0232REFERENCE INTERVALS FOR SERUM CREATININE, CYSTATIN C AND EGFR LEVELS IN THE HEALTHY ADULT POPULATION IN SOUTH CHINA

Abstract Background and Aims Serum creatinine (SCr), serum cystatin C (SCyc) and estimating GFR (eGFR) calculated by calculation formula are the most popular parameters to estimate renal function in clinical setting. Reference intervals (RIs) of these important indices are very essential for prompt and precise clinical diagnosis, treatment and management especially for early asymptomatic chronic kidney injury or acute kidney injury. There are few reports on RI for these renal function indices in Chinese healthy population. Hence, it is important to establish the RIs for Chinese. Our study was performed to determine the RIs of SCr, SCyc and eGFR in healthy adult population in South China in large sample size by age and sex group. Method Apparently healthy Chinese ethnic individuals without diagnosis of chronic diseases and medications according to the record of our hospital's outpatient service system, aged between 18 and 89 years old and performed health screening in Sun-Yat Sen Memorial Hospital in the last 5 years from Jan 01, 2014 to Dec 31, 2019 were recruited into this study. Individuals with abnormality of urinary system checked with ultrasound, abnormal dipstick urine test including proteinuria, hematuria, urinary infection and low urine osmolality, ALT or AST exceeds the upper limit of reference levels, fasting blood sugar&amp;gt;7.0 mmol/l, Hb&amp;lt;110 g/L or dyslipidemia, gout or hyperuricemia were excluded. Results A total of 3480 healthy individuals (female 1645 and male 1835) were enrolled in this study (Table 1). We analyzed the median, 2.5 and 97.5 percentile of SCr, SCysc and eGFR in each age group by sex. The RIs for SCr with respect to age (Table 2) (ranges of 18-29, 30-39, 40-49, 50-59 and 60+ years) were 52.00-87.47, 52.20-82.80, 53.00-86.00, 63.78-88.20 and 53.80-95.20μmol/L for females, and 72.38–112.00, 73.00–111.00, 71.00–112.00, 69.00-114.82 and 70.00-113.00μmol/L for males, respectively. Meanwhile, the RIs for SCysc with respect to age (Table 3) (ranges of 18–29, 30–39, 40–49, 50-59 and 60+ years) were 0.51-1.00, 0.47-1.03, 0.49-1.13, 0.51-1.19 and 0.63-1.25 mg/L for females, and 0.57-1.10, 0.57-1.23, 0.57-1.21, 0.60-1.28 and 0.67-1.39 mg/L for males, respectively. The levels of Scr in female were significantly lower than male (P&amp;lt;0.001) and remained relatively stable across different age group both in male and female (Figure 1). However, our results showed that the levels of SCyc were abruptly increased from 50 years old in healthy population especially in female, and the differences between male and female disappeared in more than 60 years old age group (Figure 2). The medians of reference GFRs(CKD-EPI2012Scr-SCy) (Table 4) are 108.68, 104.25, 97.80, 91.11 and 82.89 mL/min/1.73 m2 for males, and 113.35, 111.64, 104.74, 92.22 and 77.72 for females, in healthy adult aged 18-29, 30-39, 40-49, 50-59 and 60+ years, respectively. Our results showed that higher eGFR and lower decline rate per year of eGFR in female compared with male whose age were under 40 years old, as shown in Figure 3. However, thereafter, the decline rate of eGFR was faster in female than male, which shown as 0.77 in 40-49, 1.39 in 50-59 and 1.12 mL/min/1.73 m2 per year in over 60 years old in female and 0.65 mL/min/1.73 m2 in 40-49, 0.74in 50-59 and 0.82 mL/min/1.73 m2 per year in more than 60 years old in male. The levels of eGFR in female were decreased and lower than male after 60 years old. Similar trend was confirmed by CKD-EPI2009Scr. Conclusion In conclusion, this study provides sex and age specific normal reference values for SCr, SCyc and eGFR of healthy adult population in South China. Our results remind clinicians should consider the important effects of sex and age when evaluate the real renal function of patients and local RIs should be established in clinical setting.

Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial.

To investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine. The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment arms: oral placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex. Inosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [p < 0.001] and +98% [p < 0.001], respectively) than on placebo (in contrast to men: +10% [p = 0.6] and +14% [p = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson's Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = -0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = -0.44; p = 0.006). No significant associations were observed in men. Inosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the study's design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine. NCT00833690. This study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.

Apolipoprotein E Genotypes, Age, Race, and Cognitive Decline in a Population Sample.

To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample. Longitudinal study of 18 years' duration. Biracial urban US population sample. There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA). A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini-Mental State Examination. The frequencies of APOE ε2/ε3 (14% vs 12%), ε2/ε4 (4% vs 2%), ε3/ε4 (29% vs 22%), and ε4/ε4 (4% vs 2%) genotypes were higher among AAs than EAs. After adjusting for demographic factors, the rate of decline in global cognition was twice as high among participants with the APOE ε4/ε4 genotype compared to participants with the APOE ε3/ε3 genotype (0.097 vs 0.048 SD units [SDUs] per year; P < .0001). This doubling was not different between AAs (0.091 vs 0.045 SDUs per year) and EAs (0.118 vs 0.059 SDUs per year) (Pinteraction = .63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age (Pinteraction = .021), while the APOE ε2/ε4 genotype (Pinteraction = .016) and the APOE ε2/ε3 genotype (Pinteraction = .043) were associated with a lower rate of decline with higher age. The APOE ε2/ε2 genotype was associated with a lower rate of decline in episodic memory, while the APOE ε2/ε4 was associated with a higher rate of decline in episodic memory and perceptual speed. The association of the APOE genotypes with cognitive decline was not different between AAs and EAs. However, individuals with different APOE genotypes showed a lower or a higher rate of decline with age. J Am Geriatr Soc 67:734-740, 2019.

Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy

BackgroundTransthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis.MethodsIn a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein–Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), in which higher scores indicate better health status.ResultsIn the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year; 95% CI, 0.56 to 0.81). At month 30, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<0.001) and a lower rate of decline in KCCQ-OS score (P<0.001). The incidence and types of adverse events were similar in the two groups.ConclusionsIn patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo. (Funded by Pfizer; ATTR-ACT ClinicalTrials.gov number, NCT01994889.)

Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk

Many patients with chronic obstructive pulmonary disease (COPD) have an accelerated loss of lung function. It is unclear whether drug treatment can modify this in patients with moderately severe disease. In a prespecified analysis of the key secondary outcome in SUMMIT (Study to Understand Mortality and Morbidity), we investigated whether the inhaled corticosteroid fluticasone furoate (FF; 100 μg), the long-acting β-agonist vilanterol (VI; 25 μg), or their combination (FF/VI) modified the rate of decline in FEV1 compared with placebo. We also investigated how baseline covariates affected this decline. Spirometry was measured every 12 weeks in this event-driven, randomized, placebo-controlled trial of 16,485 patients with moderate COPD and heightened cardiovascular risk. An average of seven spirometric assessments per subject among the 15,457 patients with at least one on-treatment measurement were used in the analysis of rate of FEV1 decline. All statistical comparisons are considered nominal. The adjusted rates of FEV1 decline were -46 ml/yr (-3.0% of baseline) with placebo, -47 ml/yr (-3.1%) with VI, -38 ml/yr (-2.5%) with FF, and -38 ml/yr (-2.3%) with FF/VI. FF-containing regimens had lower rates of decline than placebo (P < 0.03), and FF/VI had a lower rate of decline than VI alone (P < 0.005). The FEV1 decline was faster in current smokers, those with a lower body mass index, males, and patients with established cardiovascular disease. In patients with moderate COPD and heightened cardiovascular risk, FF alone or in combination with VI appears to reduce the rate of FEV1 decline. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).