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Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce.To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis.This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included.The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab.Nonrandomized allocation of duration of treatment and follow-up.Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

The effects of consuming specific types of nonnutritive sweeteners (NNSs) on adiposity changes in children have remained inconsistent. In this study, we aimed to investigate the effects of the intake of different kinds of NNSs on long-term adiposity changes during pubertal growth. Furthermore, we examined the above relationships among different sexes, pubertal stages, and levels of obesity. A total of 1893 6–15-year-old adults were recruited and followed-up every 3 months. The NNS-FFQ (Food Frequency Questionnaire) was conducted and urine samples were collected to investigate the effects of the selected sweeteners, which included acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides, and sorbitol. Multivariate linear mixed-effects models were used to examine the relationship between NNS intake and body composition. The consumption of aspartame, sucralose, glycyrrhizin, stevioside, and sorbitol was associated with decreased fat mass and increased fat-free mass. In the highest tertile group, the effects of NNS consumption on fat mass corresponded to values of −1.21 (95% CI: −2.04 to −0.38) for aspartame, −0.62 (95% CI: −1.42 to 0.19) for sucralose, −1.26 (95% CI: −2.05 to −0.47) for glycyrrhizin, −0.90 (95% CI: −2.28 to 0.48) for stevioside, and −0.87 (95% CI: −1.67 to −0.08) for sorbitol, while the effects on fat-free mass corresponded to values of 1.20 (95% CI: 0.36 to −0.38) for aspartame, 0.62 (95% CI: −0.19 to 1.43) for sucralose, 1.27 (95% CI: 0.48 to 2.06) for glycyrrhizin, 0.85 (95% CI: −0.53 to 2.23) for stevioside, and 0.87 (95% CI: 0.08 to 1.67) for sorbitol. Particularly, aspartame and sorbitol revealed a dose-responsiveness effect. The above finding was more prominent among girls than boys. Moreover, fat mass was significantly reduced in normal-weight children who consumed a moderate amount of aspartame and a large amount of glycyrrhizin and sorbitol compared with obese children. In conclusion, the NNS-specific and sex-specific effects of long-term NNS consumption revealed associations of decreasing fat mass and increasing fat-free mass for children undergoing pubertal growth.

Objective To investigate (1) whether the association of thyroid hormone with frailty risk is linear or nonlinear and (2) what level of thyroid hormones or thyroid stimulating hormone (TSH) is most suitable for preventing frailty in older adults.Design: Systematic review and dose–response meta-analysisMethods Medical electronic databases were searched for cross-sectional or longitudinal studies, published from database inception to February 2022. We focused on the relationship between TSH and frailty. Data on TSH reference range, TSH exposure categories, sample size of each exposure category, and adjusted odds ratios (ORs) for frailty with 95% confidence interval (CI) were extracted. In the dose–response meta-analysis, we set the OR for frailty as 1 at 0.3 mIU/L TSH.Results The systematic review included 10 studies, whereas the meta-analysis included 3 studies (n = 6388). TSH levels ranged from 0.3 to 4.8 mIU/L, and the dose–response meta-analysis revealed a significant J-shaped association (p = 0.0071). Frailty OR (95% CI) increased from 1.30 (1.06–1.59) for 2.7 mIU/L TSH to 2.06 (1.18–3.57) for 4.8 mIU/L TSH.Conclusions A significant nonlinear, J-shaped association was noted between TSH level and frailty. TSH levels within the upper half (2.7-4.8mIU/L) of reference range was noted to significantly increase frailty risk; by contrast, those in the lower half (0.6–1.5 mIU/L) had a lower frailty risk, though nonsignificantly so.

Objective:The purpose of the current study was to develop a validated FFQ to evaluate the intake of non-nutritive sweeteners (NNS) in child and adolescent Asian populations.Design:Intensive and overall market research was performed to create the applicable NNS-FFQ with thirteen food categories and 305 items. Six intense sweeteners, including acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides and sorbitol, were investigated. The validity and reproducibility of the NNS-FFQ were evaluated. The validity was further assessed by examining the consistency of reported NNS intake compared with urinary biomarkers using Cohen’s κ analysis.Settings:This work was considered to be relevant in Asian societies.Participants:One hundred and two children and adolescents recruited from several clinics were invited to participate in the current study.Results:High content validity indices and high content validity ratio levels were revealed for each sweetener and food category. Reproducibility among subjects was satisfactory. Significant moderate correlations between estimated steviol glycoside/sucralose consumption and sensitive urinary biomarker levels were demonstrated (κ values were 0·59 and 0·45 for steviol glycosides and sucralose, respectively), indicating that the NNS-FFQ can be used to assess an individual’s NNS intake. The dietary intense sweetener consumption pattern evaluated in this measurement was similar to those observed in other Asian countries but differed from those observed in Western populations with respect to types and amounts of NNS.Conclusions:This validated NNS-FFQ can be an applicable and useful tool to evaluate NNS intake in future epidemiological and clinical studies.

Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147-0.899) and β2MG (β = 1.502, 95% CI: 0.635-2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027-0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

ContextExtremely early age at menarche, also called precocious puberty, has been associated with various cardiometabolic traits, but their shared heritability remains unclear.ObjectivesThis work aimed to identify new shared genetic variants and their pathways for age at menarche and cardiometabolic traits and to investigate the influence of central precocious puberty on childhood cardiometabolic traits.MethodsUsing the conjunction false discovery rate method, this study analyzed genome-wide association study data from the menarche-cardiometabolic traits among 59 655 females of Taiwanese ancestry and systemically investigated pleiotropy between age at menarche and cardiometabolic traits. To support the novel hypertension link, we used the Taiwan Puberty Longitudinal Study (TPLS) to investigate the influence of precocious puberty on childhood cardiometabolic traits.ResultsWe discovered 27 novel loci, with an overlap between age at menarche and cardiometabolic traits, including body fat and blood pressure. Among the novel genes discovered, SEC16B, CSK, CYP1A1, FTO, and USB1 are within a protein interaction network with known cardiometabolic genes, including traits for obesity and hypertension. These loci were confirmed through demonstration of significant changes in the methylation or expression levels of neighboring genes. Moreover, the TPLS provided evidence regarding a 2-fold higher risk of early-onset hypertension that occurred in girls with central precocious puberty.ConclusionOur study highlights the usefulness of cross-trait analyses for identifying shared etiology between age at menarche and cardiometabolic traits, especially early-onset hypertension. The menarche-related loci may contribute to early-onset hypertension through endocrinological pathways.

BackgroundWe examined the effect of sugar-sweetened beverages (SSB) and common drink intake on pubertal development in both sexes.MethodsData were retrieved from Taiwan Children Health Study, which involved detailed pubertal stage assessments of 2,819 schoolchildren aged 11 years in 2011–2012. Drawings of secondary sexual characteristics and self-reported age at menarche or voice breaking were used to assess pubertal stages. Dietary intake was assessed using a detailed semi-quantitative food frequency questionnaire. Generalized estimating equation modeling was applied to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to represent the effects of each drink on early pubertal development outcomes.ResultsIn boys, an one cup/day increment of a SSB was associated with earlier voice breaking (β = −0.12; 95% CI = −0.20, −0.04), whereas consuming yogurt (≥2 cups/day) was a protective factor against early puberty (OR = 0.78; 95% CI = 0.73, 0.83). In girls, SSB consumption was associated with increased risk of early puberty in a dose–response manner, and a similar protective effect of yogurt consumption and fermented probiotic drink (≥2 cups/day) against early puberty was observed (OR = 0.96; 95% CI = 0.94, 0.99). Furthermore, the intake of both total sugar and added sugar within SSBs increased risk of early puberty in girls but not in boys.ConclusionsSugar-sweetened beverages were associated with early puberty, and probiotic drinks appeared to mitigate this link. These findings indicate that the gut–brain axis could play a crucial role in sexual maturation.

Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries.

Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved therapy in major depressive disorder. However, its treatment efficacy on depression after traumatic brain injury (TBI) remains inconclusive. We conducted a meta-analysis to assess the effectiveness of executing rTMS over dorsolateral prefrontal cortex (DLPFC) on depression, cognitive impairment and post-concussion syndrome in individuals with traumatic brain injury. This study contained seven randomized controlled trials that published before April 5, 2020 in PubMed, Embase, Scopus, Cochrane, and Web of Science databases. The rTMS had significant anti-depressant effect (SMD = 1.03, p = 0.02), but the effects dissipated at 1-month follow-up (SMD = 0.39, p = 0.62). In the subgroup analysis, only applying rTMS to left DLPFC area of post-TBI patients showed significant anti-depressant effect (SMD = 0.98, p = 0.04). Moreover, current data observed that rTMS on post-TBI patients possessed substantial improvement in visuospatial memory (SMD = 0.39, p p = 0.32) and selective attention (SMD = 0.21, p = 0.31). In addition, the effect of rTMS is not superior to sham on postconcussion syndrome. In conclusion, the short-term antidepressant effect of left DLPFC rTMS in patients with TBI was significant. However, the effectiveness of rTMS on cognition and postconcussion syndrome in patients with post-TBI depression was limited.

The brain−gut−microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota−bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague Dawley rats were fed a fish oil diet and administered D-galactose combined with chronic unpredictable mild stress (CUMS) to simulate geriatric depression. The cognitive function, psychological symptoms, microbiota compositions, and faecal bile acid profiles of the rats were assessed thereafter. A correlation analysis was conducted to determine whether the fish oil-induced alteration of the rats’ microbiota and bile acid profiles affected the rats’ behaviour. D-galactose and CUMS resulted in lower concentrations of Firmicutes, significantly altered bile acid profiles, and abnormal neurobehaviours. Fish oil intake alleviated the rats’ emotional symptoms and increased the abundance of Bacteroidetes, Prevotellaceae, Marinifilaceae, and Bacteroidesuniformis. It also elevated the concentrations of primary bile acids and taurine-conjugated bile acids in the rats’ faeces. The rats’ taurine-conjugated bile acid levels were significantly correlated with their behavioural outcomes. In short, fish oil intake may alleviate psychological symptoms by altering the microbial metabolites involved in the BGM axis, especially in the conjugation of bile acids.

Background Adiposity is a key risk factor for asthma and impaired pulmonary function. Objectives We aimed to identify the critical period of life course adiposity for asthma in childhood and young adulthood, and to determine whether associations of adiposity and asthma vary across ages. Methods Birth weight and body mass index (BMI) from birth to 17 years of age were assessed in 6130 children from the Taiwan Children Health Study. Logistic regression for asthma outcome and linear regression for pulmonary function outcome were used to investigate associations of adiposity with asthma. Seventeen BMI-related single-nucleotide polymorphisms were used to obtain genetic instrumental variables for adiposity to perform Mendelian randomisation (MR) analysis. Results Using both regression model and MR analyses, we confirmed that the critical period of adiposity in predicting childhood asthma would be before age 6 years. Further, we discovered that the sensitive period of adiposity gain related to young adulthood asthma was the prepubertal stage. Risks of asthma at age 17 per unit increase in z-score of the BMI increased from 0.94 (95% CI: 0.79, 1.11) at birth, and became greater than 1.00 between age 11-12, then increased to 1.08 (95% CI: 0.95, 1.22) at age 17. The associations of life course BMI with asthma and pulmonary function impairment at age 12 and with asthma at age 17 increased with age. The aforementioned association was most prominent among central obesity indicators. Conclusions To prevent asthma in childhood and young adulthood, we should aim at promoting healthy growth at the toddler period and prepubertal stage. This article is protected by copyright. All rights reserved.

The consumption of artificial sweeteners has been rapidly increasing, with potentially hazardous effects on human reproduction. This study aims to explore the effect of Acesulfame Potassium (Ace K) and its potential mechanism to induce uterine contraction through in vitro, ex vivo, in vivo, and clinical observation studies.Used ex vivo and in vitro studies to analyze its effect on uterine contraction and involved signaling pathway. Used the long-term, high-dose exposure to examine Ace K's affection for contractive-related protein expression. By involving a cohort of 613 participants, to assess the dose-responsiveness of Ace K consumption and calculate the odd ratio of Ace K consumption and the relationship with preterm risk. Animal studies show increasing uterine contraction, cytokine secretion, and altered contraction-related protein expression. Human data show that higher consumption of Ace K may be related to early delivery.Long-term high-dose exposure to Ace K can induce uterine hypercontraction, increase cytokine secretion, and alters contraction-related protein expression. These findings suggest that women who suffer from uterine hypercontraction causes painfulness should pay more attention to the zero- or low-calorie soft drinks or food products containing Ace K.

Aim To investigate the relationship between the implementation of real-time audiovisual cardiopulmonary resuscitation (CPR) feedback devices with cardiac arrest patient outcomes, such as return of spontaneous circulation (ROSC), short-term survival, and neurological outcome. Methods We systematically searched PubMed, Embase, and the Cochrane CENTRAL from inception date until April 30, 2020, for eligible randomized and nonrandomized studies. Pooled odds ratio (OR) for each binary outcome was calculated using R system. The primary patient outcome was ROSC. The secondary outcomes were short-term survival and favorable neurological outcomes (cerebral performance category scores: 1 or 2). Results We identified 11 studies (8 nonrandomized and 3 randomized studies) including 4851 patients. Seven studies documented patients with out-of-hospital cardiac arrest and four studies documented patients with in-hospital cardiac arrest. The pooled results did not confirm the effectiveness of CPR feedback device, possibly because of the high heterogeneity in ROSC (OR: 1.42, 95% CI: 1.03–1.94, I2: 80%, tau2: 0.1875, heterogeneity test p Conclusions Whether real-time CPR feedback devices can improve patient outcomes (ROSC and short-term survival) depend on the type of device used. Portable devices led to better outcomes than did AED-associated devices. Future studies comparing different types of devices are required to reach robust conclusion. Protocol registration Prospero registration ID CRD42020155388.

Background Family caregivers of patients on prolonged mechanical ventilation (PMV) may encounter challenges concerning medical decision-making besides witnessing patient suffering. Palliative care (PC) should be a good support for both patients and caregivers; however, for PMV families, PC is not always a choice through long companion time. This qualitative study clarifies family caregivers' burden of assisting patients on PMV and evaluates the need for PC information and support. Methods Interviews were caregivers of patients on ventilator support for more than 60 days in five hospitals of the Taipei City Hospital System. Based on phenomenology, this study was conducted by using a semistructured questionnaire comprising three questions: (I) what was the most crucial moment of deciding to intubate? (II) how would you describe the quality of life of your ventilator-dependent family member? (III) what type of assistance do you expect from the PC team for your ventilator-dependent family member? Results Twenty-one caregivers of patients on PMV in five hospitals of the Taipei City Hospital System agreed to participate in face-to-face interviews. The identified themes, including stressful decision-making, companion pain/discomfort, and unwillingness to accept PC, elucidated the difficulties experienced by caregivers when providing care. Conclusions Understanding family caregivers' experiences can enable physicians to improve communication with them, encourage the PC team to support them during surrogate decision-making for patients on PMV during critical moments, and enhance the overall PC service.

The prevalence of obesity has risen dramatically over recent years, and so has the prevalence of adverse obesity-associated pregnancy outcomes. To combat obesity, the calorie contents of many foods and beverages may be reduced by the use of artificial sweeteners, such as aspartame. However, animal studies suggest that aspartame and its metabolites may exhibit toxicity, and the effects of aspartame on pregnancy are largely unknown. In this study, we treated pregnant mice with aspartame by oral gavage and found that the treatment decreased fasting blood glucose level, whereas systolic blood pressure was elevated. Importantly, the aspartame-treated animals also had low placenta and fetus weights, as well as reduced thickness of the placenta decidua layer. Moreover, aspartame decreased the expression of epithelial-mesenchymal transition proteins and manganese superoxide dismutase (MnSOD) in mouse placentae. In order to clarify the mechanisms though which aspartame affects placenta, we performed experiments on 3A-sub-E trophoblasts. In the cells, aspartame treatments induced cell cycle arrest and reduced the proliferation rate, epithelial-mesenchymal transition, migration activity and invasion activity. We also found that aspartame increased reactive oxygen species (ROS) levels to hyper-activate Akt and downregulate MnSOD expression. Pretreatment with antioxidants or sweet taste receptor inhibitors reversed the effects of aspartame on trophoblast function. We also found that the aspartame metabolite phenylalanine similarly induced ROS production and affected proliferation of trophoblasts. Taken together, our data suggest that aspartame consumption during pregnancy may impact the structure, growth and function of the placenta via sweet taste receptor-mediated stimulation of oxidative stress.

BACKGROUND We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. METHODS In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. RESULTS In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per interquartile range (IQR) increase observed for sleep quality (odds ratio [OR] =1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00-1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). CONCLUSION Among the examined factors, the most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children's sleep quality and preventing obesity comorbidities such as SDB.

Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.

Introduction Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. Methods A systematic search was performed until November 30, 2021. We used a random-effects meta-analysis to calculate the pooled OR (95% CI). Results We included 61 studies (3,061,584 individuals). We found some medications protective against COVID-related death, including metformin, GLP-1RA and SGLT-2i. DPP-4i and insulin users were more likely to die during hospitalization. SU, TZD, and AGI were mortality neutral. Metformin use was associated with better outcome in a dose-response manner. Conclusions Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. SU, TZD and AGI were mortality neutral. Presentation: No date and time listed

Background: We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. Methods: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. Results: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per interquartile range (IQR) increase observed for sleep quality (odds ratio [OR] =1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). Conclusion: The most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children’s sleep quality and preventing obesity comorbidities such as SDB.

Studies in the field of neuroscience and psychology have hypothesized that a causal association exists between atopic diseases and attention-deficit/hyperactivity disorder (ADHD). Previous systematic reviews and meta-analyses have reported a higher risk of ADHD in children with atopic diseases; however, the relationship between ADHD symptoms and atopic diseases remains unclear. We systematically reviewed observational cross-sectional and longitudinal studies to investigate the relationship between atopic diseases and ADHD symptom severity (hyperactivity/impulsivity and inattention). The majority of studies showed a statistically significant association between atopic diseases and both ADHD symptoms, with substantial heterogeneity in the outcome of hyperactivity/impulsivity. Inconsistent results were observed in the subgroup analysis of different exclusion criteria for patients with ADHD. Our study indicated that atopic diseases not only increase the risk of ADHD but also are associated with ADHD symptom severity. This association was even observed in children with subthreshold ADHD, indicating that atopic diseases play a role in the spectrum of ADHD symptom severity. Trial registration: This study was registered on PROSPERO (registration ID: CRD42020213219).

Obesity is associated with the risk of cardiovascular disease, and non-nutritive sweetener, such as acesulfame potassium (AceK) has been used to combat obesity. However, the effects of AceK on cardiovascular disease are still unclear. In this study, high cholesterol diet (HCD)-fed ApoE−/− mice had dysregulated plasma lipid profile, and developed atherosclerosis, determined by atherosclerotic plaque in the aorta. Supplement of AceK in HCD worsened the dyslipidemia and increased atherosclerotic plaque, as compared with HCD-fed ApoE−/− mice. Since treatment of AceK in RAW264.7 macrophages showed no significant effects on inflammatory cytokine expressions, we then investigated the impacts of AceK on lipid metabolism. We found that AceK consumption enhanced hepatic lipogenesis and decreased β-oxidation in ApoE−/− mice. In addition, AceK directly increased lipogenesis and decreased β-oxidation in HepG2 cells. Taken together, a concurrent consumption of AceK exacerbated HCD-induced dyslipidemia and atherosclerotic lesion in ApoE−/− mice, and AceK might increase the risk of atherosclerosis under HCD.

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Studies in the field of neuroscience and psychology have hypothesized that a causal association exists between atopic diseases and attention-deficit/hyperactivity disorder (ADHD). Previous systematic reviews and meta-analyses have reported a higher risk of ADHD in children with atopic diseases; however, the relationship between ADHD symptoms and atopic diseases remains unclear. We systematically reviewed observational cross-sectional and longitudinal studies to investigate the relationship between atopic diseases and ADHD symptom severity (hyperactivity/impulsivity and inattention). The majority of studies showed a statistically significant association between atopic diseases and both ADHD symptoms, with substantial heterogeneity in the outcome of hyperactivity/impulsivity. Remarkably decreased heterogeneity and statistical significance were observed in the second meta-analysis of ADHD-related behavior symptoms in atopic patients without ADHD. Our study indicated that atopic diseases not only associated with ADHD but also ADHD symptoms severity. This association was even observed in children with subthreshold ADHD, indicating that atopic diseases may play a role in the spectrum of ADHD symptom severity. Trial registration: This study was registered on PROSPERO (registration ID: CRD42020213219).

Childhood body mass index (BMI) trajectory classes are rarely linked to early puberty risk, particularly among Chinese children. We estimated early puberty risk across BMI trajectory classes, investigated factors contributing to pubertal development, and examined differences in final adult height between children exhibiting early and nonearly pubertal maturation across the classes. The Taiwan Children Health Study recruited 10-year-old children in 2010 from 14 Taiwanese communities and resurveyed them at age 11, 12, and 18 years. The study comprised 3109 children (50.4% boys) with available data for BMI (age 6–11 years) and pubertal stages (age 11, 12, and 18 years). Classes 1–4 were persistently healthy weight, rapid BMI growth, chronically overweight/obese, and early transient overweight/obese. Children in class 3 exhibited the highest risk of early pubertal maturation. Puberty genetic score, low sleep quality, and high fat-free mass collectively explained 15% of the variance in Tanner stages among class 3 children. Early pubertal maturation was considered to cause short and tall stature in boys and girls, respectively. Modifying sleep quality and fat-free mass may reduce early puberty risk in children with chronic overweight/obesity. Vigorous physical activity may reduce adiposity and increase the final adult height in the children.

The effect of hospice care on place of death among centenarians remained unexplored. Using data obtained from National Health Insurance Research Database (2002-2010), we compared the differences in place and cause of death between centenarians and noncentenarians. These data were stratified into centenarian (n = 2495) and noncentenarian (n = 820 563) death. Data in place and cause of death and hospice care interventions were retrieved. Poisson regression models were used to evaluate factors associated with the centenarians’ place of death. Time series models were used to predict the number of centenarian deaths until 2025. Most (63.8%) of the centenarians died at their own homes, followed by 30.5% who died in hospital. Hospice home care was involved in only 0.3% of the centenarian deaths but in 1.8% of the noncentenarian deaths. The leading causes of death among centenarians were respiratory diseases (16.6%), circulatory diseases (15.2%), and pneumonia (14.8%). Among the centenarians, those who died of circulatory disease, old age, and respiratory diseases were more likely to die at their own homes. We forecasted the number of annual centenarian deaths to reach 800 in 2025. Therefore, an increase in the provision of advanced care planning and earlier home hospice care intervention may enable centenarians to die at their own residence.

Maternal nutrition intake during pregnancy may affect the mother-to-child transmission of bacteria, resulting in gut microflora changes in the offspring, with long-term health consequences in later life. Longitudinal human studies are lacking, as only a small amount of studies showing the effect of nutrition intake during pregnancy on the gut microbiome of infants have been performed, and these studies have been mainly conducted on animals. This pilot study explores the effects of high or low fruit and vegetable gestational intake on the infant microbiome. We enrolled pregnant women with a complete 3-day dietary record and received postpartum follow-up. The 16S rRNA gene sequence was used to characterize the infant gut microbiome at 2 months (n = 39). Principal coordinate analysis ordination revealed that the infant gut microbiome clustered differently for high and low maternal fruit and vegetable consumption (p &lt, 0.001). The linear discriminant analysis effect size and feature selection identified 6 and 17 taxa from both the high and low fruit and vegetable consumption groups. Among the 23 abundant taxa, we observed that six maternal intake nutrients were associated with nine taxa (e.g., Erysipelatoclostridium, Isobaculum, Lachnospiraceae, Betaproteobacteria, Burkholderiaceae, Sutterella, Clostridia, Clostridiales, and Lachnoclostridium). The amount of gestational fruit and vegetable consumption is associated with distinct changes in the infant gut microbiome at 2 months of age. Therefore, strategies involving increased fruit and vegetable consumption during pregnancy should be employed for modifying the gut microbiome early in life.

Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved therapy in major depressive disorder. However, its treatment efficacy on depression after traumatic brain injury (TBI) remains inconclusive. We conducted a meta-analysis to assess the effectiveness of executing rTMS over dorsolateral prefrontal cortex (DLPFC) on depression, cognitive impairment and post-concussion syndrome in individuals with traumatic brain injury. This study contained seven randomized controlled trials that published before April 5, 2020 in PubMed, Embase, Scopus, Cochrane, and Web of Science databases. The rTMS had significant anti-depressant effect (SMD = 1.03), but the effects dissipated at one-month follow-up (SMD = 0.39). In the subgroup analysis, only applying rTMS to left DLPFC area of post-TBI patients showed significant anti-depressant effect (SMD = 0.98). Moreover, current data observed that rTMS on post-TBI patients possessed substantial improvement in visuospatial memory (SMD = 0.39), but wasn’t in processing speed (SMD = -0.18) and selective attention (SMD = 0.21). In addition, the effect of rTMS on postconcussion syndrome was insignificant. In conclusion, the short-term antidepressant effect of left DLPFC rTMS in patients with TBI was significant. Furthermore, the effectiveness of rTMS on cognition and post-concussion syndrome in patients with post-TBI depression was limited.

Objective The optimal selection of prosthetic heart valve for dialysis-dependent patients remains controversial. We investigated the comparative effectiveness and safety of mechanical prosthesis (MP) and bioprosthesis (BP) for these patients. Methods After the systematic review, we included studies that involved patients on dialysis undergoing aortic valve replacement or mitral valve replacement (MVR) and reported comparative outcomes of MP and BP. Meta-analysis was performed using random-effects model. We conducted a subgroup analysis based on the valve position and postoperative international normalized ratio (INR), which was extracted from either tables or methods of each study. A meta-regression was used to examine the effects of study-level covariates. Results We included 24 retrospective studies without randomized-controlled trials, involving 10,164 participants (MP = 6934, BP = 3230). Patients undergoing aortic valve replacement with MP exhibited a better long-term survival effectiveness (hazard ratio, 0.64; 95% confidence interval [CI], 0.47-0.86). Conversely, studies including MVR demonstrated little difference in survival (hazard ratio, 0.90; 95% CI, 0.73-1.12). A meta-regression revealed that age had little effect on long-term survival difference between MP and BP (β = –0.0135, P = .433). MP had a significantly greater bleeding risk than did BP when INR was above 2.5 (incidence rate ratio, 10.58; 95% CI, 2.02-55.41). However, when INR was below 2.5, bleeding events were comparable (incidence rate ratio, 1.73; 95% CI, 0.78-3.82). The structural valve deterioration rate was significantly lower in MP (risk ratio, 0.24; 95% CI, 0.14-0.44). Conclusions MP is a reasonable choice for dialysis-dependent patients without additional thromboembolic risk requiring aortic valve replacement, for its better long-term survival, durability, and noninferior bleeding risk compared with BP. Conversely, BP might be an appropriate selection for patients with MVR, given its similar survival rate and lower bleeding risk. Although our meta-regression demonstrates little influence of age on long-term survival difference between MP and BP, further studies stratifying patients based on age cut-off are mandatory.

Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes.A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses.We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), IMetformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.

Background: The relationship between food insecurity and the experience of sleep disturbance has received little attention among researchers, although food insecurity is associated with poor physical and mental health globally. This study aimed to investigate the relationship between food security status and sleep disturbance among adults 20&ndash, 64 years old. Methods: The study&rsquo, s population-based sample included 20,212 Indonesian adults who participated in the fifth wave of the Indonesia Family Life Survey (IFLS5) in 2014. Dietary intake data, gathered using a food frequency questionnaire (FFQ), were used to assess the food security status. Sleep disturbance was assessed using the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. We used multiple linear and logistic regression models to test the study hypothesis. Results: A higher likelihood of experiencing sleep disturbance was recorded in people aged older than 56 years (OR = 1.78, 95% CI: 1.17&ndash, 2.72, p = 0.007), people with depressive symptoms (OR = 3.57, 95% CI: 2.77&ndash, 4.61, p &lt, 0.001), and food-insecure people (OR = 1.32, 95% CI: 1.02&ndash, 1.70, p = 0.036). A lower likelihood of experiencing sleep disturbance was recorded in people with low educational attainment (OR = 0.41, 95% CI: 0.30&ndash, 0.57, p &lt, 0.001). Sleep disturbance was dependent on the food consumption groups and food security status among men (p = 0.004). Conclusions: Sleep disturbance may be affected by the food-insecure status of adults, and later, may lead to serious health outcomes.

High birth weight indicates the future risk of obesity and increased fat mass in childhood. Maternal gestational diabetes mellitus (GDM) or overweight are powerful predictors of high birth weight. Studies on probiotic supplementation during pregnancy have reported its benefits in modulating gut microbiota composition and improving glucose and lipid metabolism in pregnant women. Therefore, probiotic intervention during pregnancy was proposed to interrupt the transmission of obesity from mothers to newborns. Thus, we performed a meta-analysis to investigate the effect of probiotic intervention in pregnant women with GDM or overweight on newborn birth weight. We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases up to 18 December 2019. Randomized controlled trials (RCTs) comparing pregnant women with GDM or overweight who received probiotic intervention during pregnancy with those receiving placebo were eligible for the analysis. Newborn birth weights were pooled to calculate the mean difference with a 95% confidence interval (CI). Two reviewers assessed the trial quality and extracted data independently. Seven RCTs involving 1093 participants were included in the analysis. Compared with the placebo, probiotics had little effect on newborn birth weight of pregnant women with GDM or overweight (mean difference = &minus, 10.27, 95% CI = &minus, 90.17 to 69.63, p = 0.801). The subgroup analysis revealed that probiotic intake by women with GDM decreased newborn birth weight, whereas probiotic intake by obese pregnant women increased newborn birth weight. Thus, no evidence indicates that probiotic intake by pregnant women with GDM or overweight can control newborn birth weight.

Purpose Studies have reported the influence of adolescent obesity on development of adult diabetes, but the effect of the growth pattern during this period has rarely been explored. Also, the tri-ponderal mass index (TMI) was thought to be a better estimation of adolescent body fat levels than the body mass index (BMI), so we sought to investigate whether growth trajectories derived by these two indices could predict incident diabetes. Methods We conducted a study by using the Taipei City Hospital Radiation Building Database, a longitudinal cohort established in 1996. Physical exam results including blood test results were collected annually and the BMI z-score/TMI growth trajectory groups during 13 to 18 years of age were identified using growth mixture modeling. A Cox proportional hazard model for incident diabetes was used to examine the risk of baseline obese status and different BMI/TMI growth trajectories. Results Five growth trajectory groups were identified for the BMI z-score and the TMI. During approximately 20 400 person-years follow-up, 33 of 1387 participants developed diabetes. Baseline obesity defined by the BMI z-score and the TMI were both related to adult diabetes. The persistent increase TMI growth trajectory exhibited a significantly increased risk of diabetes after adjusting for baseline obese status and other correlated covariates (hazard ratio: 2.85, 95% confidence interval: 1.01-8.09). There was no association between BMI growth trajectory groups and incident diabetes. Conclusions A specific TMI growth trajectory pattern during adolescence might be critical for diabetes prevention efforts.