Efficacy of Time-Restricted Eating and Behavioral Economic Intervention in Reducing Fasting Plasma Glucose, HbA1c, and Cardiometabolic Risk Factors in Patients with Impaired Fasting Glucose: A Randomized Controlled Trial.

This randomized controlled trial is aimed at assessing the efficacy of combining time-restricted eating (TRE) with behavioral economic (BE) interventions and comparing it to TRE alone and to the usual care for reducing fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and other cardiometabolic risk factors among patients with impaired fasting glucose (IFG). Seventy-two IFG patients aged 18-65 years were randomly allocated for TRE with BE interventions (26 patients), TRE alone (24 patients), or usual care (22 patients). Mean FPG, HbA1c, and other cardiometabolic risk factors among the three groups were compared using a mixed-effect linear regression analysis. Mean body weight, FPG, HbA1c, fasting insulin, and lipid profiles did not significantly differ among the three groups. When considering only patients who were able to comply with the TRE protocol, the TRE group showed significantly lower mean FPG, HbA1c, and fasting insulin levels compared to the usual care group. Our results did not show significant differences in body weight, blood sugar, fasting insulin, or lipid profiles between TRE plus BE interventions, TRE alone, and usual care groups. However, TRE might be an effective intervention in lowering blood sugar levels for IFG patients who were able to adhere to the TRE protocol.

Cost-effectiveness analysis of mesh fixation techniques for laparoscopic and open inguinal hernia surgeries.

PURPOSE: This study reports economic evaluation of mesh fixation in open and laparoscopic hernia repair from a prospective real-world cohort study, using cost-effectiveness analysis (CEA) and cost-utility analysis (CUA). METHODS: A prospective real-world cohort study was conducted in two university-based hospitals in Thailand from November 2018 to 2019. Patient data on hernia features, operative approaches, clinical outcomes, associated cost data, and quality of life were collected. Models were used to determine each group's treatment effect, potential outcome means, and average treatment effects. An incremental cost-effectiveness ratio was used to evaluate the incremental risk of hernia recurrences. RESULTS: The 261 patients in this study were divided into six groups: laparoscopic with tack (LT, n = 47), glue (LG, n = 26), and self-gripping mesh (LSG, n = 30), and open with suture (OS, n = 117), glue (OG, n = 18), and self-gripping mesh (OSG, n = 23). Hernia recurrence was most common in LSG. The mean utility score was highest in OG and OSG (both 0.99). Treatment costs were generally higher for laparoscopic than open procedures. The cost-effectiveness plane for utility and hernia recurrence identified LSG as least cost effective. Cost-effectiveness acceptability curves identified OG as having the highest probability of being cost effective at willingness to pay levels between $0 and $3,300, followed by OSG. CONCLUSION: Given the similarity of hernia recurrence among all major procedures, the cost of surgery may impact the decision. According to our findings, open hernia repair with adhesive or self-gripping mesh appears most cost-effective.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Deep-Learning-Based Pre-Diagnosis Assessment Module for Retinal Photographs: A Multicenter Study.

Purpose: Artificial intelligence (AI) deep learning (DL) has been shown to have significant potential for eye disease detection and screening on retinal photographs in different clinical settings, particular in primary care. However, an automated pre-diagnosis image assessment is essential to streamline the application of the developed AI-DL algorithms. In this study, we developed and validated a DL-based pre-diagnosis assessment module for retinal photographs, targeting image quality (gradable vs. ungradable), field of view (macula-centered vs. optic-disc-centered), and laterality of the eye (right vs. left). Methods: A total of 21,348 retinal photographs from 1914 subjects from various clinical settings in Hong Kong, Singapore, and the United Kingdom were used for training, internal validation, and external testing for the DL module, developed by two DL-based algorithms (EfficientNet-B0 and MobileNet-V2). Results: For image-quality assessment, the pre-diagnosis module achieved area under the receiver operating characteristic curve (AUROC) values of 0.975, 0.999, and 0.987 in the internal validation dataset and the two external testing datasets, respectively. For field-of-view assessment, the module had an AUROC value of 1.000 in all of the datasets. For laterality-of-the-eye assessment, the module had AUROC values of 1.000, 0.999, and 0.985 in the internal validation dataset and the two external testing datasets, respectively. Conclusions: Our study showed that this three-in-one DL module for assessing image quality, field of view, and laterality of the eye of retinal photographs achieved excellent performance and generalizability across different centers and ethnicities. Translational Relevance: The proposed DL-based pre-diagnosis module realized accurate and automated assessments of image quality, field of view, and laterality of the eye of retinal photographs, which could be further integrated into AI-based models to improve operational flow for enhancing disease screening and diagnosis.

Evaluation of the cost-utility of phosphate binders as a treatment option for hyperphosphatemia in chronic kidney disease patients: a systematic review and meta-analysis of the economic evaluations.

BACKGROUND: Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients. METHODS: Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income. RESULTS: A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively. CONCLUSIONS: Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Complement component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort.

PURPOSE: A non-synonymous single nucleotide polymorphism (SNP) in complement component 3 has been shown to increase the risk of age-related macular degeneration (AMD). We assess its effect on AMD risk in a Northern Irish sample, test for gene-gene and gene-environment interaction, and review a risk prediction model. METHODS: SNP rs2230199 was genotyped in 1,358 samples, which comprised 437 cases, 436 no-disease controls, and 485 participants randomly sampled from the Northern Ireland population. Allele frequencies were assessed in cases and controls. Logistic regression analysis was used to assess interaction and develop a risk prediction model. RESULTS: We report a minor allele frequency of 0.248 for rs2230199 in the population (n=485), 0.296 in cases (n=437), and 0.221 in controls (n=436; odds ratio [OR]=1.48; confidence interval [CI]: 1.19-1.85; p=0.0003). The significant association is retained following multivariate analysis with adjustment for age, smoking status, Complement Factor H (CFH), Age-Related Maculopathy Susceptibility 2 (ARMS2), Complement Component 2 (CC2), and Complement Factor B (CFB; OR=1.45; CI: 1.10-1.91; p=0.009). No evidence to support an interaction between any of the covariates within the regression model was found. The area under the receiver operator characteristic curve calculated for the fully adjusted model, including all variables, was 0.86 for late AMD. CONCLUSIONS: Our study confirmed the association between Complement Component 3 (C3) and late-stage AMD. There was no evidence for an interaction with environmental exposures, nor did we find data to support a gene-gene effect.

Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration.

PURPOSE: Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS: Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS: Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31-0.74; P<0.001), was in strong LD with CFB R32Q, rs641153 (r(2)=0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22-0.65; P<0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS: Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD.