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Clinical trials are mostly designed to provide data that allow direct inference of the underlying hypotheses. This, however, is not the case for noninferiority trials where placebo controls are absent due to ethical considerations, resulting in the need for indirect inference about the underlying hypotheses of the treatment effect of a new drug against a putative placebo control. In particular, the European Committee for Medicinal Products for Human Use (CHMP) guideline for noninferiority trials requires indirect confidence bounds for the "putative" effect of the new drug. To meet this requirement, we develop a new approach by which the lower predictive bound of a given confidence level is used to determine the noninferiority margin. For this approach, we provide methods for calculating the sample size and for making indirect statistical inference (i.e., p-values, confidence intervals, and point estimates) on the putative effect of the new test drug. For an actual trial example, we assess designs by the lower predictive bound approach as well as other approaches for determining noninferiority margins.

Background: Frailty may increase the risk of adverse outcomes and the presence of comorbidities in hypertension. Understanding the prevalence of frailty in older adults with hypertension is of great importance, whereas estimates of the prevalence of frailty in this population vary greatly. Objectives: A systematic review and meta-analysis was conducted to estimate the pooled prevalence of frailty and prefrailty among community-dwelling older adults with hypertension, and to examine the risk factors associated with (pre)frailty in this population. Methods: PubMed, Web of Science, The Cochrane Library, EMBASE, and CINAHL were searched from the inception to May 10, 2023. Investigators assessed eligibility, extracted data, and evaluated methodological quality. The pooled prevalence of frailty and prefrailty was calculated using the random-effects model. Meta-regression analysis and subgroup analysis were conducted to explore sources of heterogeneity. Sensitivity analysis was undertaken by the leave-one-out method and by removing studies with moderate/high risk of bias. The Mantel-Haenszel or inverse variance method was used to estimate risk factors of frailty. Results: A total of 14 studies met the inclusion criteria, involving 185,249 participants. The pooled prevalence in older adults with hypertension was 23% (95% CI 0.09–0.36) for frailty and 46% (95% CI 0.38–0.54) for prefrailty. The pooled prevalence of frailty was greater in studies with a higher proportion of females (24%, 95% CI 0.05–0.50), using multidimensional tools to define frailty (30%, 95% CI 0.10–0.51) and conducted in Western Pacific (27%, 95% CI 0.17–0.39). Age, female sex, depression, and previous hospitalizations were risk factors of frailty among older adults with hypertension. Conclusion: Frailty and prefrailty are prevalent in community-dwelling older adults with hypertension, and limited risk factors are identified. This implicates the importance of frailty assessment integrated into the routine primary care for older adults with hypertension in community settings as well as the understanding of potential factors. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the safety and efficacy of chidamide to reverse HIV‐1 latency in vivo and to compare the effects of four clinically tested histone deacetylase (HDAC) inhibitors on non‐histone proteins in vitro. Methods: Participants received chidamide orally at 10 mg twice weekly for 4 weeks while maintaining baseline antiretroviral therapy. The primary outcome was plasma viral rebound during chidamide dosing and the secondary outcomes were safety, pharmacokinetic and pharmacodynamic profiles, changes in cell‐associated HIV‐1 RNA and HIV‐1 DNA, and immune parameters. Western blotting was used to compare the in vitro effects of the four HDAC inhibitors on HSP90, NF‐κB and AP‐1. Results: Seven aviraemic participants completed eight oral doses of chidamide, and only grade 1 adverse events were observed. Cyclic increases in histone acetylation were also detected. All participants showed robust and repeated plasma viral rebound (peak viraemia 147–3850 copies/mL), as well as increased cell‐associated HIV‐1 RNA, during chidamide treatment. Furthermore, we identified an enhanced HIV‐1‐specific cellular immune response and a modest 37.7% (95% CI: 12.7–62.8%, P = 0.028) reduction in cell‐associated HIV‐1 DNA. Compared with the other three HDAC inhibitors, chidamide had minimal cytotoxicity in vitro at clinically relevant concentrations and showed mechanistically superior effects on non‐histone proteins, including HSP90, NF‐κB and AP‐1. Conclusions: Chidamide safely and vigorously disrupts HIV‐1 latency in vivo, which makes it a promising latency‐reversing agent. [ABSTRACT FROM AUTHOR]

Summary: By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo. Introduction: No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups. Methods: We searched different databases to select relevant studies. We performed Bayesian random effects network meta-analysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture. Results: We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28–0.57), romosozumab (HR 0.49, 95% CI 0.29–0.75), risedronate (HR 0.62, 95% CI 0.50–0.79), zoledronate (HR 0.67, 95% CI 0.47–0.96), and alendronate (HR 0.69, 95% CI 0.47–0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33–0.92), romosozumab (HR 0.67, 95% CI 0.47–0.95), and denosumab (HR 0.68, 95% CI 0.50–0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4–2.6) and abaloparatide (RR 1.6, 95% CI 1.2–2.3). Conclusion: Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo. [ABSTRACT FROM AUTHOR]

Although infection rates may increase after relaxation of the zero COVID strategy, the extensive vaccination campaign in China could potentially curb the spread of COVID-19, which may be associated with a low level of risk perception and post-traumatic stress symptoms (PTSS). However, the relationship between vaccination, risk perception and PTSS has not been studied extensively. This study aims to examine the associations between the number of COVID-19 vaccine doses, consistency in the type of each dose and time since vaccination with PTSS, and the mediating role of risk perception on such relationships in China. Cross-sectional sampling with a self-report questionnaire was used to measure vaccination, PTSS and risk perception. The survey was conducted in Beijing, China, from 13 January to 9 February 2023. Linear regression analyses were conducted to test the relationship between vaccination, risk perception and PTSS. The analysis included 55,803 individuals. In total, 72.86 % of participants received two doses of the COVID-19 vaccine. Regression results indicated that people with two doses of the COVID-19 vaccine had a lower level of PTSS (β = −1.232, 95 % confidence interval [CI]: −1.930, −0.534) than those who had not received any doses of the COVID-19 vaccine. Only the negative relationship between two-dose vaccination and PTSS was mediated by risk perception, while the negative relationship between the time since vaccination and PTSS was suppressed by risk perception. This study showed that receiving the COVID-19 vaccine reduced PTSS by decreasing perceived risk. Vaccination time was negatively associated with PTSS, but this relationship was suppressed by risk perception. [ABSTRACT FROM AUTHOR]

The American Heart Association (AHA) has recently updated and enhanced the quantification of cardiovascular health by using the Life's Essential 8 (LE8) score. We intended to examine the correlation between cardiovascular health status, as measured by the new LE8 score, and cardiovascular disease (CVD) in US adults. National cross-sectional study. A total of 24,730 individuals without pregnancy and with complete data from 2007 to 2018 enrolled in the study. The overall LE8 score was divided into low, moderate, and high groups. Multivariate logistic regressions were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the LE8 score and the presence of CVD. Overall, the high LE8 group had a younger age (20–59 years, 82.95%) and more females (60.09%) compared to the low LE8 group. Moderate and high LE8 correlated negatively with the presence of CVD (moderate, OR: 0.46, 95% CI: 0.39–0.54; high, OR: 0.26, 95% CI: 0.21–0.33). One standard deviation increment in the LE8 score correlated significantly with lower odds of CVD (OR: 0.64; 95% CI: 0.60–0.69). Further stratification analysis also detected a significant relationship between the new LE8 score and CVD, and the result was enhanced among the young and women (P -interaction<0.001). Higher LE8 score correlated with lower odds of CVD, especially among the young and women. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we determined serum 25-hydroxyvitamin D [25(OH) D] levels in serum, and investigated their associations with risk of recurrent stroke and mortality in a 24-month follow up study in Chinese patients with first-ever ischemic stroke. Methods: In this preplanned post hoc analysis, serum levels of 25(OH) D and NIH stroke scale (NIHSS) were measured at the time of admission in a cohort of patients with ischemic stroke. We used logistic regression model to assess the relationship between 25(OH) D levels and risk recurrent stroke or mortality. Results: The follow-up rate was 98.2% in 220 stroke patients. Of 216 patients, 18.5% (95%CI: 13.3%-23.7%) patients had a stroke recurrence, and 30.1% (95% CI: 24.0%-36.2%) died. After adjustment for traditional risk factors, serum 25(OH) D levels were negatively associated with the risk of stroke recurrence (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.70-0.85; P< 0.001) and negatively associated with mortality during 24 months of follow-up (OR, 0.72; 95% CI, 0.64-0.80; P< 0.001). Compared with the first quartile of serum 25(OH) D levels, the ORs for stroke recurrence and mortality were as follows: second quartile, 0.80 (95% CI, 0.63-0.93) and 0.77 (95% CI, 0.65-0.89); third quartile, 0.42 (95% CI, 0.31-0.55) and 0.39 (95% CI, 0.30-0.52); fourth quartile, 0.12 (95% CI, 0.07-0.19) and 0.10 (95% CI, 0.06-0.15), respectively. Conclusions: Lower serum levels of 25(OH) D are independently associated with the stroke recurrence and mortality at 24 months in ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Background There is limited information involving population data about the role of maternal health, fetal growth and neonatal health on children's developmental status at ages 4-7 years. Our aim was to determine the contribution of maternal, fetal and neonatal health to developmental status at ages 4-7 years. Methods In this 7-year follow-up prospective cohort study, a sample of 26 803 mothers participated in the beginning. Among their children, 19 187 voluntarily completed the development screening test or the social life ability survey, which were designed for two different age groups (<6 or ≥6 years old, respectively). Logistic regression analysis was used to link the data with the prenatal outcome card and interview questionnaire applied to pregnant women in previous study, to the analysis of various related factors such as demographic, socio-economic, disease and menstrual history, marriage and pregnancy care. Result Univariate and multivariate logistic regression analysis were used separately in two age groups [4-6 ( n = 8439) and 6-7 ( n = 10 748) years old] to analyse relative factors. Maternal age of 25-30 years, maternal education of high school and greater, family income and not drinking during pregnancy were associated with higher scores in development. Conclusion Both preconception and pregnancy health education and health care are the important maternal factors closely associated with children's cognitive and social competence. Public health policies for preconception care and public welfare for high-quality childcare are essential for improving children's life. [ABSTRACT FROM AUTHOR]

Background:Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.Methods:We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.Results:Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37-0.98; P=0.040) for OS, 0.52 (95% CI, 0.24-1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27-0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (Ptrend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.Conclusion:A first-degree family history of NPC is associated with improved survival of patients. [ABSTRACT FROM AUTHOR]

This study provides the length-weight relationships ( LWRs) for four fish species [Leptobotia rubrilabris (Dabry de Thiersant, 1872); Opsariichthys bidens Günther, 1873; Xenocypris yunnanensis Nichols, 1925; and Sinogastromyzon sichangensis Chang, 1944] collected from the Niulan River, China. Samples were obtained between April 2008 and June 2011 using various types of fishing gear [drift gill nets (mesh: 5 × 5 cm), hook and electro fishing]. A total of 136 specimens belonging to four fish species were analyzed. For each species the sample size, length range, weight range, LWR, 95% confidence intervals of a and b, and coefficient of correlation were determined. Prior to this study, the LWRs for S. sichangensis and X. yunnanensis were unknown. New maximum sizes for S. sichangensis and X. yunnanensis are also provided. [ABSTRACT FROM AUTHOR]

Abstract: Published data on the association between ADIPOQ polymorphisms and type 2 diabetes are inconsistent. The present meta-analysis was performed to clarify the role of polymorphisms in proximal promoter region of ADIPOQ (rs17360539 and rs266729) in type 2 diabetes. The MEDLINE, EMBASE and Science Citation Index Expanded database were searched for eligible studies. Odd ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled ORs were performed for per-allele model (A/a) and others genetic models. A total of 10267 T2DM patients and 12837 controls was included in the meta-analysis. Overall the −11377G allele had an 8% elevated risk of T2DM compared to −11377C allele in all subjects (P =0.034, OR=1.08, 95% CI 1.01–1.15). The −11391A allele showed no significant effect on T2DM risk in all subjects (P =0.240, OR=1.10, 95% CI 0.94–1.29) compared to −11391G allele. In the subgroup analyses by ethnicity, −11391A allele increased T2DM risk in European population (P =0.046, OR=1.09, 95% CI 1.00–1.09). In conclusion, the accumulated evidence suggested that the ADIPOQ −11377G allele is a low-penetrant risk factor for developing type 2 diabetes, but −11391A is a risk factor only in European Caucasians. [Copyright &y& Elsevier]