Search

Tzu-Lin Yeh,1,2 Hsin-Hao Chen,1 Hsiao-Hui Chiu,3 Yu-Hua Chiu,4 Lee-Ching Hwang,5,6 Shang-Liang Wu7 1Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan; 2Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 3Department of Nursing, Taipei Veterans General Hospital, Taipei City, Taiwan; 4Occupational Safety and Health Office, Taipei Veterans General Hospital, Taipei City, Taiwan; 5Department of Family Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; 7School of Medicine, Griffith University, Gold Coast Campus, QLD, Australia Purpose: To investigate morbidity associated with overweight and obesity in health personnel and compare the differences among work roles.Materials and methods: This retrospective cohort study examined measurements obtained during employee medical checkups between 2007 and 2016 in a Taiwan medical center. BMI was used to define overweight (≥24 and

Wei-Te Lei,1 Hsin Hui Lin,2 Mu-Chieh Tsai,1 Hua-His Hung,1 Yu-Jyun Cheng,1 Shu-Jung Liu,3 Chien Yu Lin,1 Tzu-Lin Yeh4 1Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; 2Department of Family Medicine, Taipei Mackay Memorial Hospital, Taipei, Taiwan; 3Department of Medical Library, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, Taiwan; 4Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan Purpose: Childhood reactive airway diseases (RADs) are concerning problems in children’s airways and may be preceded by bronchiolitis and may progress to childhood asthma. The severity of the disease is indicated by deterioration in pulmonary functions, increased usage of rescue medications, and recurrent wheezing episodes. Macrolides have both antimicrobial and anti-inflammatory functions and have been used as adjunctive therapy in childhood RADs. Patients and methods: We conducted a meta-analysis to evaluate the effect of macrolides in children with RAD. Literature searches were systematically conducted using an electronic database from inception to August 2018. The Cochrane review risk of bias assessment tool was used to assess the quality of each randomized controlled trial. Results: Sixteen randomized controlled trials comprising 1,415 participants were investigated in this meta-analysis. Children treated with macrolide therapy showed significantly better pulmonary functions in both forced expiratory volume in one second (% predicted) (difference in means=-9.77, 95% CI=-14.18 to -5.35, P

Tzu-Lin Yeh,1 Pei-Ching Shih,1 Shu-Jung Liu,2 Chao-Hsu Lin,3 Jui-Ming Liu,4,5 Wei-Te Lei,3,* Chien-Yu Lin3,* 1Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, 2Department of Medical Library, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, 3Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, 4Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 5Department of Medicine, National Yang-Ming University, Taipei, Taiwan *These authors contributed equally to this work Background: Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination. Methods: We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review. Results: Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, P=0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, P=0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, P=0.03).Conclusion: Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted. Keywords: influenza, influenza vaccine, probiotics, prebiotics, synbiotics, antibody titer, immune response

No evidence-based consensus has been reached regarding effective interventions in the immediate and midterm post mass trauma phases. Through a community survey, the mental health of 14,013 evacuees was assessed to assist in the delivery of mental health programmes 2 months after a major earthquake. Three months later, 241 high-risk patients recruited in the second survey were actively served at mobile clinics, having been either identified through the first community survey or referred by mental health aides. The estimated psychiatric morbidity rate at the second month was 13.8 per cent. The sensitivity of the screening survey and the aide-referral method were 76.6 and 61.0 per cent, respectively. Post-traumatic stress disorder (PTSD), major depressive episode and dysthymia were the three most prevalent psychiatric diagnoses at the fifth month. Among those with diagnosis of PTSD, 57 per cent had psychiatric comorbidity, and approximately 50 per cent had other anxiety or depressive disorders before the earthquake. The psychiatrically morbid subjects rarely use health services. The rate of help seeking improved because of this programme. A high risk of mental disorder was found among middle-aged and nervous trait. According to our experience, in addition to development of a sensitive community screening tool, the implementation of programmes to mobilize local resources is critical. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although a correlation between the central dopaminergic system and intelligence may exist, the results from imaging studies remain inconclusive. The aim of this study was to explore the relationship between striatal dopamine D2/D3 receptor availability and verbal intelligence quotient (VIQ) using single photon emission computed tomography (SPECT). METHOD: Striatal D2/D3 receptor availability of 64 healthy subjects was determined with the [123I]iodobenzamide ([123I]IBZM) ligand. Intelligence quotients (IQs) of the subjects were measured by the Wechsler Adult Intelligence Scale--Revised (WAIS-R). RESULTS: In addition to age, left striatal D2/D3 receptor availability correlated positively with VIQ. In females, left striatal D2/D3 receptor availability was the only variable that correlated significantly with the similarities subtest of VIQ. CONCLUSIONS: There is a relationship between left striatal D2/D3 receptor availability and verbal intelligence, which varies, predominantly in males. [ABSTRACT FROM AUTHOR]

Objective. Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals.Method. Single photon emission computed tomography and [[1][2][3]I]IBZM (iodobenzamide) were used to assess the striatal dopamine D[2]/D[3] receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale-Revised test.Results. Dopamine D[2]/D[3] receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D[2]/D[3] measurements. These relationships remain significantly after controlling for age effects.Conclusions. Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments. [ABSTRACT FROM AUTHOR]

Context: The causal association and biological mechanism linking serum 25-hydroxyvitamin D to stroke risk lacks epidemiological evidence., Objective: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors., Design: The community-based prospective community-based cohort study, the Chin-Shan Community Cardiovascular Cohort, was conducted from 1990 to December 2011, with external validation using a two-sample Mendelian randomization (MR) study., Patients: A total of 1,778 participants with serum 25-hydroxyvitamin D data were enrolled., Methods: In the CCCC observational study, the outcome was ascertained as stroke, while in the two-sample MR study, it was defined as ischemic stroke. Causal effects were estimated using restricted cubic spline analysis, COX proportional hazard ratios, mediation analysis, and two-sample MR., Results: Over 12 years (21,598 person-years) of follow-up, 163 participants (9.17%) developed stroke. Higher 25(OH)D concentrations were associated with lower stroke risk (hazard ratio: 0.64; 95% confidence interval, 0.43-0.96) after full-model adjustments. Mediation analysis showed a significant association between 25(OH)D concentration and stroke risk mediated by hypertension in unadjusted models (mediation percentage 23.3%, p=0.008) that became non-significant in full models (mediation percentage, 15.5%; p=0.072). Two-sample MR confirmed a significant inverse association between genetically determined 25(OH)D and stroke risk (IVW OR: 0.92; 95% CI: 0.85-0.99; p=0.036). However, hypertension had an insignificant mediating role in the Mendelian randomization study., Conclusions: Higher 25(OH)D levels are linked to reduced stroke risk, potentially mediated by hypertension. Prioritizing blood pressure management may improve stroke prevention in 25(OH)D-deficient patients., (© Crown copyright 2024.)

Context: The association between colorectal cancer (CRC) and new-onset diabetes mellitus remains unclear., Objective: To examine the association between CRC and the risk of subsequent diabetes mellitus and to further investigate the impact of chemotherapy on diabetes mellitus risk in CRC., Design: A nationwide cohort study., Methods: Using the Taiwan Cancer Registry Database (2007-2018) linked with health databases, 86,268 patients with CRC and an equal propensity score-matched cohort from the general population were enrolled. Among them, 37,277 CRC patients from the Taiwan Cancer Registry (2007-2016) were analyzed for diabetes mellitus risk associated with chemotherapy. Chemotherapy exposure within 3 years of diagnosis was categorized as no chemotherapy, <90 days, 90-180 days, and >180 days. Differences in diabetes mellitus risk were assessed across these categories., Results: Each group involved 86,268 participants after propensity score matching. The patients with CRC had a 14% higher risk of developing diabetes mellitus than the matched general population (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.09-1.20). The highest risk was observed within the first year after diagnosis followed by a sustained elevated risk. Long-term chemotherapy (>180 days within 3 years) was associated with a 60-70% increased risk of subsequent diabetes mellitus (HR: 1.64, 95% CI: 1.07-2.49)., Conclusion: Patients with CRC are associated with an elevated risk of diabetes mellitus, and long-term chemotherapy, particularly involving capecitabine, increases diabetes mellitus risk. Thus, monitoring blood glucose levels is crucial for patients with CRC, especially during extended chemotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The cardio-related issues should be emphasized as the survival rates of breast cancer increased. We investigated the risk of coronary artery disease (CAD) and stroke due to breast cancer or radiotherapy., Methods: In this retrospective cohort study, breast cancer patients diagnosed between 2007 and 2016 were recruited from Taiwan Cancer Registry Database and were followed until the end of 2018 by linking with the Taiwan National Health Insurance Database. The general population was randomly selected from the whole population in 2007. Standardized incidence ratios (SIR) were calculated to compare the risk of CAD and stroke between patients and the general population. Within the cohort, we included the patients diagnosed between 2011 and 2016. Cox proportional hazards model and subdistribution hazard function were used to investigate the associations of radiotherapy with the risk of CAD and stroke., Results: Overall SIR of CAD was 0.82 (95% confidence interval [CI]: 0.78-0.86), while were 1.43 and 1.08 (95% CI: 1.30-1.55 and 1.00-1.16) 1 and 2 years after diagnosis, respectively. Overall SIR of stroke was 0.63 (95% CI: 0.60-0.67), the results were similar after considering the time since diagnosis. The adjusted hazard ratios (HR) for the associations of radiotherapy with CAD and stroke risk were 0.91 (95% [CI] = 0.76-1.09) and 0.84 (95% CI = 0.68-1.04), respectively. The results were similar by using subdistribution hazard function., Conclusions: The risk of CAD was higher within the first 2 years of breast cancer diagnosis. We found no association between radiotherapy and the risk of CAD and stroke., Competing Interests: Disclosure This work was supported by the Health Promotion Administration, Ministry of Health and Welfare (grant no. A1091115): Tobacco Health and Welfare Taxation. The content of this research may not represent the opinion of the Health Promotion Administration, Ministry of Health and Welfare. The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript. The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although diabetes is a poor prognostic factor for colorectal cancer (CRC), whether diabetes severity provides an additional predictive value for CRC prognosis remains unclear. The study aimed to investigate the prognostic differences after curative CRC resection among patients with different diabetic severities., Methods: This population-based retrospective cohort study analyzed data registered between 2007 and 2015 in the Cancer Registry Database, which is linked to the National Health Insurance Research Database and National Death Registry. Patients with CRC who underwent curative radical resection for stage I-III disease were evaluated, with their diabetic status subdivided into no diabetes, diabetes without complication, and diabetes with complications. Cox regressions were applied to determine the association between diabetes severity and CRC survival, including overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS)., Results: A total of 59,202 patients with CRC were included. Compared with the no diabetes group, the diabetes without complication group has insignificantly worse OS (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09), DFS (HR, 1.08; 95% CI, 1.04-1.12), and CSS (HR, 0.98; 95% CI, 0.93-1.03), whereas those with complicated diabetes had a significantly higher risk of poor survival (OS: HR, 1.85; 95% CI, 1.78-1.92; DFS: HR, 1.75; 95% CI, 1.69-1.82; CSS: HR, 1.41; 95% CI, 1.33-1.49). Patients with CRC and diabetes also had a higher risk of recurrence than did those without diabetes. Sex and TNM staging were important effect modifiers., Conclusions: Among patients with CRC who undergo curative resection, the severity of the diabetes is inversely correlated with long-term outcomes, especially in women and patients in the earlier stages of CRC., Plain Language Summary: The prognostic impact of diabetes severity in colorectal cancer (CRC) is yet to be clarified. In this cohort study of 59,202 patients with CRC, compared with patients with CRC and without diabetes, those with uncomplicated diabetes had an insignificantly worse CRC survival, whereas those with complicated diabetes had a significantly higher risk of poor survival. Multidisciplinary medical care to prevent progression into diabetes with complications is needed to improve survival among patients with CRC and diabetes., (© 2023 American Cancer Society.)

Background: This study aimed to determine whether primary parathyroid cancer patients were associated with increased metabolic and cardiovascular comorbidities in comparison to the general population., Methods: We used the National Taiwan Cancer Registry Database to construct a cohort of patients with parathyroid cancer from January 1, 2004, to December 31, 2019. We compared the incidence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary heart disease, and heart failure with the general population matched based on a propensity score in a one-to-five fashion., Results: A total of 72 parathyroid cancer patients and 360 matched general population (mean age: 55 years; 59% women) were included, with different exclusive numbers for each metabolic and cardiovascular comorbidity cohort. The number of cases based on a total of 2347.7 person-years of observation included 53 deaths, 29 hypertension, 9 diabetes, 13 hyperlipidemia, 10 atrial fibrillation, 18 coronary artery disease, and 13 heart failure. According to multivariate analysis, parathyroid cancer remained significantly associated with diabetes [hazard ratio (HR): 9.28; 95% confidence interval (CI): 1.72-50.07], hyperlipidemia (HR: 5.86; 95% CI: 1.61-21.31), and heart failure (HR: 4.46; 95% CI: 1.18-16.84). Sub-distribution of competing mortality events and subgroup analysis showed robust evidence of metabolic and cardiovascular comorbidities. This national cohort study demonstrated that adult parathyroid cancer patients had a significantly higher incidence of diabetes mellitus, hyperlipidemia, and heart failure than the general population., Conclusions: An increased risk of metabolic and cardiac comorbidities among parathyroid cancer patients required great caution., (© 2023. The Author(s).)

Background: Studies on disease burden in Taiwan are lacking. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high body mass index (BMI) in Taiwan., Methods: Using a comparative risk assessment approach from the Global Burden of Disease study, we estimated the population attributable fraction (PAF), attributable CVD burden, and disability-adjusted life years (DALYs) according to sex, age, and area of residence in Taiwan. The BMI distribution for the population was obtained from the National Health Interview Survey in 2013. CVD was defined as an ischemic heart disease or stroke., Results: The attributable PAF for CVD from high BMI was 18.0% (19.6% in men and 15.6% in women), and it was highest (42.7%) in those aged 25-30 years. Adults aged 60-65 years had the highest absolute DALYs (11,546). The average relative age-standardized attributable burden was 314 DALYs per 100,000 person-years, and it was highest in those aged 75-80 years (1,407 DALYs per 100,000 person-years). Those living in Taitung County had the highest PAF of 21.9% and the highest age-standardized attributable burden (412 DALYs)., Conclusions: In Taiwan, an 18% reduction in CVDs could be achieved if obesity/overweight was prevented. Prevention was most effective in early adulthood. The absolute CVD burden from obesity/overweight was highest in middle-aged men, and the relative burden was highest in older adults. Resource allocation in targeted populations and specific areas to eliminate CVD and health inequities is urgently required., Competing Interests: All the authors declare no conflict of interest.

Objective: Coronary artery disease (CAD) and cancer are the two leading causes of death worldwide. Evidence suggests the existence of shared mechanisms for these two diseases. We aimed to conduct a systematic review and meta-analysis to investigateassociation between CAD and incident cancer risk., Methods: We searched Cochrane, PubMed, and Embase from inception until October 20, 2021, without language restrictions. Observational cohort studies were used to investigate the association between CAD and incident cancer risk. Using random-effects models, the odds ratio (OR) and 95% confidence interval (CI) were calculated. We utilized subgroup and sensitivity analyses to determine the potential sources of heterogeneity and explore the association between CAD and specific cancers. This study was conducted under a pre-established, registered protocol on PROSPERO (CRD42022302507)., Results: We initially examined 8,533 articles, and included 14 cohort studies in our review, 11 of which were eligible for meta-analysis. Patients with CAD had significantly higher odds of cancer risk than those without CAD (OR = 1.15, 95% CI = [1.08-1.22], I 2 = 66%). Subgroup analysis revealed that the incident cancer risk was significantly higher in both sexes and patients with CAD with or without myocardial infarction. Sensitivity analysis revealed that the risk remained higher in patients with CAD even after >1 year of follow-up (OR = 1.23, 95% CI = [1.08-1.39], I 2 = 76%). Regarding the specific outcome, the incident risk for colorectal and lung cancers was significantly higher (OR = 1.06, 95% CI = [1.03-1.10], I 2 = 10%, and OR = 1.36, 95% CI = [1.15-1.60], I 2 = 90%, respectively) and that for breast cancer was lower (OR = 0.86, 95% CI = [0.77-0.97], I 2 = 57%) in patients with CAD than in those without CAD., Conclusion: CAD may be associated with incident cancer risk, particularly for lung and colorectal cancers, in men and women as well as patients with or without myocardial infarction. Early detection of new-onset cancer and detailed cancer surveillance programs should be implemented in patients with CAD to reduce cancer-related morbidity and mortality., Competing Interests: The authors declare that they have no competing interests., (© 2023 Chen et al.)

Aims: To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults., Methods: Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis., Results: A total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 = 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 = 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained., Conclusion: Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The associations with cancer and cardiovascular diseases (CVD) had inconsistent results. The study aimed to investigate the risk of cardiovascular diseases (CVD) between populations with and without cancer., Methods: Patients with common cancers in Taiwan were enrolled in the study between 2007 and 2018 using the Taiwan Cancer Registry. We focused on colorectal cancer, women's breast cancer, lung cancer, liver cancer, oral cancer, prostate cancer, and thyroid cancers. The study endpoint was fatal and non-fatal CVD, which was defined as ischemic heart disease and ischemic stroke according to the National Health Insurance Research Database. We compared the risk of CVD between patients with cancer and age- and sex-matched (1:1 ratio) participants who did not have cancer or CVD. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression analysis. To evaluate the chronological trend, we estimated the HRs and 95% CI yearly since the diagnosis., Results: Among the 552,485 cancer patients (mean age, 60.6 years; women, 47.7%) during the median follow-up period of 4.1 years, 32,634 cases of fatal and non-fatal CVD were identified. Compared with that noted in the non-cancer population, the overall fully adjusted HR with 95% CI was 1.28 (1.25, 1.30) in the cancer population. The CVD risk was the highest in the first year, the adjusted HR with 95% CI was 2.31 (2.23, 2.40), and this risk decreased yearly., Conclusions: Patients with cancer had a significantly higher risk of fatal or non-fatal CVD. The risk was the highest in the first year since diagnosis and decreased yearly., (© 2022. The Author(s).)

Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (< 65 and ≥ 65 years old). This observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with a follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. SIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (< 65, ≥ 65 years), and different follow-up years. After excluding 128 individuals (< 20 years or ≥ 85 years old) and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years among thyroid cancer patients, the observed number of new CHD events was 70; IS, 30; and AF, 20, respectively. The SIR was significantly higher for CHD (SIR, 1.57; 95% confidence interval [CI] 1.2-1.93) among thyroid cancer patients compared with the age- and sex-specific standardized population. However, the association between thyroid cancer and the risks of IS (SIR, 0.74; 95% CI 0.47-1), cardiovascular disease (SIR, 0.88; 95% CI 0.7-1.05), and atrial fibrillation (SIR, 0.74; 95% CI 0.42-1.06) were insignificant. Moreover, stratification by age < 65 or age ≥ 65 years old and by sex for CHD suggested that the diagnosis of thyroid cancer in the young may attenuate the CHD risk (SIR, 2.08; 95% CI 1.5-2.66), and the CVD risk was constant among both men (SIR, 1.63; 95% CI 1.03-2.24) and women (SIR, 1.53; 95% CI 1.06-1.99). The patients had persistent higher CHD risk for 5 years after cancer diagnosis. Thyroid cancer survivors have a substantial CHD risk, even at long-term follow-up, especially in those patients < 65 years old. Further research on the association between thyroid cancer and CHD risk is warranted., (© 2022. The Author(s).)

Background: The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels., Methods: We focused on the role of dopamine postsynaptic regulation using [ 123 I] iodobenzamide (IBZM) SPECT. We compared D 2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia., Result: The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores., Conclusions: Medication-naïve patients with recent-onset schizophrenia have similar D 2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Background: To investigate the standardized incidence ratios (SIR) of stroke in patients with head and neck cancer and their relationship to radiotherapy., Methods: Patients with head and neck cancer ages 20-85 years were enrolled from 2007 to 2016 using the Taiwan Cancer Registry. The study endpoint was fatal and non-fatal ischemic stroke, ascertained by the National Health Insurance Research Database. Age- and sex-adjusted SIRs, categorized by 10-year age standardization, were used to compare the patients with head and neck cancer with a randomly selected 2,000,000 general population. We compared the risk of stroke in patients with head and neck cancer who received radiotherapy or surgery alone. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox regression analysis with competing risk., Results: Among 41,266 patients (mean age, 54.1 years; men, 90.6%) in the median follow-up period of 3.9 years, 1,407 strokes occurred. Compared with the general population, the overall SIR of stroke was 1.37 (95% CI, 1.30-1.44) in patients with head and neck cancer. In patients with head and neck cancer, the fully adjusted HR of stroke in those who received radiotherapy was 0.96 (95% CI, 0.83-1.10), compared with those who received surgery alone., Conclusions: Patients with head and neck cancer had a higher risk of fatal or non-fatal ischemic stroke. The risk of stroke was not higher in patients initially treated with radiotherapy., Impact: Oncologists should emphasize stroke prevention in all patients with head and neck cancer, not only in those who received radiotherapy., (©2022 American Association for Cancer Research.)

Purpose: There have been few studies using mindfulness-based stress reduction (MBSR) to improve sexual function in Asian women with breast cancer. This study aimed to evaluate the impact of mindfulness intervention on female sexual function, mental health, and quality of life in patients with breast cancer., Methods: Fifty-one women with breast cancer were allocated into 6-week MBSR (n=26) sessions or usual care (n=25), without differences in group characteristics. The research tools included the Female Sexual Function Index (FSFI), the Depression Anxiety Stress Scales-21 (DASS-21), and the EuroQol instrument (EQ-5D). The Greene Climacteric Scale (GCS) was used to verify the foregoing scale. The effects of MBSR were evaluated by the differences between the post- and pre-intervention scores in each scale. Statistical analyses consisted of the descriptive dataset and Mann-Whitney ranked-pairs test., Results: Although MBSR did not significantly improve sexual desire and depression in patients with breast cancer, MBSR could improve parts of female sexual function [i.e., Δarousal: 5.73 vs. -5.96, Δlubrication: 3.35 vs. -3.48, and Δsatisfaction: 8.48 vs. 1.76; all p <.005], with a range from small to medium effect sizes. A significantly benefits were found on mental health [Δanxiety: -10.92 vs.11.36 and Δstress: -10.96 vs.11.40; both p <.001], with large effect sizes, ranging from 0.75 to 0.87., Conclusion: Our study revealed that MBSR can improve female sexual function and mental health except for sexual desire and depression in women with breast cancer. Medical staff can incorporate MBSR into clinical health education for patients with breast cancer to promote their overall quality of life., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Evidence regarding the relationship between colorectal cancer and the risk of cardiovascular disease (CVD) is limited. Thus, in this study, we aimed to determine the standardised incidence ratio (SIR) of CVDs in colorectal cancer patients in Taiwan., Methods: A population-based cohort study enrolling the incident colorectal cancer population based on the Cancer Registry Database from 2007 to 2016 was conducted (n = 94,233, mean age: 62.4 years, 43.0% women). New cases of CVD, including coronary heart disease and ischemic stroke, through 31 December 2018 were obtained from the National Health Insurance Research Database and National Death Registry. Compared with the general population (n = 1,977,659, mean age: 44.3 years, 49.6% women), age- and sex-specific SIRs for CVDs were calculated by the time since diagnosis., Results: A total of 6852 cardiovascular events occurred in colorectal cancer patients during a median follow-up of 4.4 years. The SIR of CVD was highest in the first year after diagnosis (SIR: 1.45, 95% confidence interval: 1.39-1.50); however, this decreased to the same value as that of the general population in later years. Similar patterns were observed for the SIR of coronary heart disease. However, the SIR of ischemic stroke among colorectal cancer patients was low from the second year following cancer diagnosis., Conclusions: Colorectal cancer patients are at an increased risk of developing CVD, especially coronary heart disease, during the first 3 years following colorectal cancer diagnosis., (© 2022. The Author(s).)

The protective effect of different healthy lifestyle scores for the risk of cardiovascular disease (CVD) was reported, although the comparisons of performance were lacking. We compared the performance measures of CVDs from different healthy lifestyle scores among Taiwanese adults. We conducted a nationwide prospective cohort study of 6042 participants (median age 43 years, 50.2% women) in Taiwan's Hypertensive, Hyperglycemia and Hyperlipidemia Survey, of whom 2002 were free of CVD at baseline. The simple and weighted the Mediterranean diet related healthy lifestyle (MHL) scores were defined as a combination of normal body mass index, Mediterranean diet, adequate physical activity, non-smokers, regular healthy drinking, and each dichotomous lifestyle factor. The World Cancer Research Fund and American Institute for Cancer Research cancer prevention recommended lifestyle and Life's Simple 7 following the guideline definition. The incidence of CVD among the four healthy lifestyle scores, each divided into four subgroups, was estimated. During a median 14.3 years follow-up period, 520 cases developed CVD. In the multivariate-adjusted Cox proportional hazard models, adherence to the highest category compared with the lowest one was associated with a lower incidence of CVD events, based on the simple (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.2-0.94) and weighted MHL scores (HR 0.44, 95% CI 0.28-0.68). Additionally, age played a role as a significant effect modifier for the protective effect of the healthy lifestyle scores for CVD risk. Specifically, the performance measures by integrated discriminative improvement showed a significant increase after adding the simple MHL score (integrated discriminative improvement: 0.51, 95% CI 0.16-0.86, P = 0.002) and weighted MHL score (integrated discriminative improvement: 0.38, 95% CI 0.01-0.74, P = 0.021). We demonstrated that the healthy lifestyle scores with an inverse association with CVD and reduced CVD risk were more likely for young adults than for old adults. Further studies to study the mechanism of the role of lifestyle on CVD prevention are warranted., (© 2021. The Author(s).)

Objective: Many cancers are caused by overweight; however, cancer risk varies among individuals with obesity. Few studies are addressing the relationship between metabolic obesity phenotypes and cancer. This study investigates the association between metabolically healthy overweight (MHOW) or metabolically healthy obesity (MHO) and cancer incidence., Methods: In a nationwide, representative community-based prospective cohort study, 5734 Taiwanese adults were classified into eight phenotypes according to body mass index (underweight <18.5; normal weight 18.5-23.9; overweight 24-26.9; and obese ≥27 kg/m 2 ) and metabolic status (healthy/unhealthy). Participants with healthy cardiometabolic blood profiles included in the metabolic syndrome criteria and an absence of hypertension, diabetes, and hyperlipidemia were considered metabolically healthy. We used the Cox proportional hazards models to estimate the adjusted hazard ratio (HR) and 95% confidence intervals (95% CI)., Results: During 73,389 person-years of follow-up, 428 incident cancers were identified. Compared to the participants with metabolically healthy normal weight, participants with MHOW (adjusted HR 1.39, 95% CI, 0.90-2.13) or MHO (adjusted HR 1.07, 95% CI, 0.51-2.22) had a tendency toward a higher risk of cancer. These associations were stronger in MHOW (adjusted HR 1.77, 95% CI, 1.09-2.86) or MHO (adjusted HR 1.39, 95% CI, 0.66-2.93) participants younger than 65 years., Conclusions: This study was the first to investigate the impact of metabolic obesity phenotype on the incidence of cancer in the Taiwanese population. Even in the absence of metabolic abnormalities, overweight, and obesity may cause a modest increase in the risk of developing cancer., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with breast cancer usually experience depression, anxiety, stress, fatigue, pain, poor sleep quality, and low quality of life after their cancer treatment. Some studies used mindfulness-based stress reduction (MBSR) interventions for reducing these symptoms; however, the results are conflicting., Objective: This study evaluated the clinical efficacy of MBSR interventions in the short term., Methods: Five databases were searched from their inception to April 2020. We included only randomized controlled trials (RCTs) comparing MBSR intervention and control groups for symptom reduction in women with breast cancer. Pooled mean difference (MD), standardized MD, and 95% confidence intervals (CIs) were calculated using random-effects models. We used the Cochrane risk-of-bias assessment tool to assess the included RCTs., Results: Nineteen RCTs with 36 to 336 participants were included, of which 11 studies with a total of 1687 participants (mean age, 53.3 years) were eligible for the meta-analysis. The pooled meta-analysis results indicated that, at the end of the MBSR interventions, participants' depression (standardized MD, -1.32; 95% CI, -2.18 to -0.46; I2 = 97%) and fatigue (MD, -0.47; 95% CI, -0.59 to -0.34; I2 = 0%) levels had significantly decreased; moreover, up to 3 months after baseline, their stress levels had significantly decreased (MD, -0.79; 95% CI, -1.34 to -0.24; I2 = 0%)., Conclusion: Mindfulness-based stress reduction interventions are highly beneficial for reducing depression, fatigue, and stress in the short term., Implications for Practice: Mindfulness-based stress reduction interventions are cost-effective and practical. Breast cancer survivors are recommended to practice MBSR as part of their daily care routine., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study assessed the associations of metabolic obesity phenotypes with the risk of atrial fibrillation (Afib)., Methods: This prospective cohort study categorized Taiwanese adults according to their body mass index (BMI) and metabolic health status at baseline. We assigned the participants to the underweight (BMI < 18.5 kg/m 2 ), normal weight (BMI = 18.5-23.9 kg/m 2 ), and overweight/obesity groups (BMI ≥ 24 kg/m 2 ). Metabolically healthy was defined as absence of hypertension, diabetes, and hyperlipidemia and the presence of healthy metabolic profiles., Results: In total, 5,742 adults were included. During a median follow-up of 13.7 years, 148 patients developed Afib. Compared to the metabolically healthy normal weight group, the risk of Afib was significantly higher than those in the metabolically unhealthy overweight/obesity (hazard ratio = 2.20, 95% confidence interval [1.12-4.33]) and metabolically unhealthy normal weight groups (HR = 2.64, 95% CI [1.34-5.17]). Additionally, the point estimate suggested a 1.97-fold greater risk among the metabolically healthy overweight/obesity group, although this difference was not significant given the wide confidence interval (HR = 1.97, 95% CI [0.80-4.86])., Conclusion: Our results demonstrated the relationships of metabolic health and weight regarding the risk of Afib in Taiwanese adults. The Afib risk among metabolic and obesity phenotypes is associated with a metabolically unhealthy status. A trend toward a higher Afib risk with obesity among metabolically healthy subjects was observed. However, the result was not robust and it still suggested further study., Competing Interests: The authors declare that they have no competing interests., (© 2021 Tsai et al.)

Background: Blood lipids are essential components for cellular growth. An inverse association between serum lipid levels and risk of cancer has led to a controversy among previous studies. The aim of this prospective cohort study was to investigate the association between blood lipids change and risk of cancer incidence., Methods: A cohort of 4130 Taiwanese adults from the Taiwanese Survey on the Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia database underwent repeated examinations in 2002 and 2007. Six groups were established based on the combined baseline (lower/higher) and interval change (decreasing/stable/increasing) in plasma lipid levels. Multivariable Cox proportional hazard model was used to investigate the relationship between lipids change and all-cause cancer incidence., Results: Two hundred and forty cancer events developed over a median follow-up of 13.4 years. Comparing these with individuals with decreasing lower-baseline lipid levels, cancer risk reduction was demonstrated in those with increasing lower-baseline total cholesterol (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.27 to 0.85), low-density lipoprotein cholesterol (LDL-C; aHR, 0.56; 95% CI, 0.35 to 0.92), and non-high-density lipoprotein cholesterol (non-HDL-C) (aHR, 0.54; 95% CI, 0.31 to 0.92) levels. A decreased risk for cancer incidence also presented in participants with stable lower-baseline, decreasing and increasing higher-baseline LDL-C levels, and with decreasing and stable higher-baseline non-HDL-C levels., Conclusions: The interval decline in lower-baseline total cholesterol, LDL-C, and non-HDL-C levels was linked to a higher risk for all-cause cancer incidence. More attention to a potential cancer risk may be warranted for an unexplained fall in serum lipids., (© 2021. The Author(s).)

Background: Health-care providers typically undergo shift work and are subjected to increased stress. Night shift work may induce disturbed sleep cycles and circadian rhythm. The objective of this study was to explore if night shift workers (NSWs) show an increased risk of abnormal thyroid-stimulating hormone (TSH)., Methods: We conducted a retrospective cohort study of 574 employees without thyroid disease and abnormal TSH at baseline who underwent annual check-ups between 2007 and 2016 in a medical center. NSWs were defined as those with working time schedules other than daytime hours. We calculated the incidence rate and estimated the adjusted hazard ratio (HR) for incident abnormal TSH and subclinical hypothyroidism compared with non-NSWs using a Cox regression model., Results: A total of 56 incident abnormal TSH cases and 39 subclinical hypothyroidism cases in NSWs were identified during 3000 person-years of follow-up. In models adjusted for age, sex, obesity, and working departments, we found no increased relative risk for incident abnormal TSH (HR: 0.72, 95% confidence interval: 0.33-1.60) or subclinical hypothyroidism (HR: 0.52, 95% confidence interval: 0.19-1.45) when comparing NSWs to non-NSWs; nor were incidence rates significantly different among exclusively medical employees after excluding administrative staff., Conclusion: In this hospital-based nine-year follow-up retrospective cohort study, NSWs were not associated with increased relative risk of incident abnormal TSH and subclinical hypothyroidism, in contrast to previous cross-sectional studies., Competing Interests: All authors have disclosed no conflicts of interest., (© 2021 The Authors.)

Although previous studies have investigated the relationship between fracture risk and type 2 diabetes (T2D), cohort studies that estimate composite osteoporosis risk are lacking. This retrospective cohort study sought to determine the risk of osteoporosis in Taiwanese patients with T2D. Patients diagnosed with T2D between 2002 and 2015 identified through the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia were included. A total of 1690 men and 1641 women aged ≥40 years linked to the National Health Insurance Research Database (NHIRD) were followed up to the end of 2015 to identify the incidences of osteoporosis through ICD9-CM codes for osteoporosis or osteoporotic fractures or usage of anti-osteoporotic agents according to Anatomical Therapeutic Chemical codes determined from NHIRD. The person year approach and Kaplan-Meier analysis were then used to estimate the incidences and cumulative event rates, whereas the Cox proportional hazard model was used to calculate adjusted hazard ratios (HR) for osteoporosis events. A total of 792 new osteoporosis events were documented over a median follow-up duration of 13.6 years. Participants with T2D had higher osteoporosis risk [adjusted HR: 1.37, 95% confidence interval (CI): 1.11-1.69] compared with those without T2D. Subgroup analyses revealed that age had a marginally significant effect, indicating that T2D had a more pronounced effect on osteoporosis risk in younger population (<65 years old). No difference was found between patients stratified according to sex. In conclusion, T2D was significantly associated with increased osteoporosis risk, especially in younger participants., Competing Interests: The authors have declared that no competing interests exist.

High baseline atherogenic lipid level has been an established risk factor for the risk of cardiovascular events. Evidence concerning the role of lipid changes in cardiovascular and death risks are inconclusive. A cohort study was conducted based on the Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (n = 4072, mean 44.8 years, 53.5% women) assessing lipid levels of the participants repeatedly measured in 2002 and 2007. Combined baseline and changes in lipid levels were classified into four groups-stable or decreasing lipid changes and increasing lipid changes with low- and high-risk baseline lipid levels. Developing cardiovascular events (n = 225) and all-cause deaths (n = 345) were ascertained during a median follow-up of 13.3 years. Participants with increasing and higher total cholesterol level were more likely to develop cardiovascular risks. Similar patterns for cardiovascular events were observed across other lipid profile changes. However, participants with increasing total cholesterol, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) levels were more likely to be at a lower risk for all-cause deaths. Baseline and changes in total cholesterol, triglycerides, and LDL-C levels were positively associated with the risk of cardiovascular diseases, whereas baseline and changes in total cholesterol and LDL-C and non-HDL-C levels were inversely associated with all-cause deaths.

Objectives: To investigate the relationship between metabolically healthy obesity and cardiovascular disease risk in Taiwanese individuals., Methods: Taiwanese individuals were recruited from a nationwide, representative community-based prospective cohort study and classified according to body mass index as follows: normal weight (18.5-23.9 kilogram (kg)/meter(m)2) and obesity/overweight (≥24 kg/m2). Participants without diabetes, hypertension, and hyperlipidemia and who did not meet the metabolic syndrome without waist circumference criteria were considered metabolically healthy. The study end points were cardiovascular disease morbidity and mortality. Multivariable adjusted hazard ratios and 95% confidence intervals were obtained from a Cox regression analysis., Results: Among 5 358 subjects (mean [standard deviation] age, 44.5 [15.3] years; women, 48.2%), 1 479 were metabolically healthy with normal weight and 491 were metabolically healthy with obesity. The prevalence of metabolically healthy obesity/overweight was 8.6% in the Taiwanese general population, which included individuals who were >20 years old, not pregnant, and did not have CVD (n = 5,719). In the median follow-up period of 13.7 years, 439 cardiovascular disease events occurred overall and 24 in the metabolically healthy obesity group. Compared with the reference group, the metabolically healthy obesity group had a significantly higher cardiovascular disease risk (adjusted hazard ratio: 1.74, 95% confidence interval: 1.02, 2.99)., Conclusions: Individuals with metabolically healthy obesity have a higher risk of cardiovascular disease and require aggressive body weight control for cardiovascular disease control., Competing Interests: The authors have declared that no competing interests exist.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.

The risk of cancer among adults with metabolically healthy obesity (MHO) has not yet been established. We systematically searched from inception to 15 March 2020. We included prospective cohort studies that compared participants with MHO and participants with metabolically healthy non-obesity (MHNO) for incidence of any type of cancer. Benign tumors, cancer mortality or cancer prognosis were not in the scope of our analysis. The Newcastle-Ottawa Scale was used for quality assessment. Ultimately, eight studies with a total of 12 542 390 participants were included. The pooled meta-analysis using random effect model showed participants with MHO demonstrated a significantly increased risk of developing cancer (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.05 to 1.23; and I 2 = 39%) than those with MHNO. The subgroup analysis revealed a higher pooled estimate (OR, 1.17; 95% CI, 1.01-1.35; and I 2 = 56%) in comparison with metabolically healthy normal weight. No evidence of effect modification by age, sex, ethnicity, smoking, sample size or length of follow-up was found. In conclusion, the present study reports a positive association between MHO and cancer incidence. All individuals with obesity, even in the absence of metabolic dysfunction, should be encouraged to lose weight., (© 2020 World Obesity Federation.)

Dietary sodium intake has received considerable attention as a potential risk factor of cardiovascular disease. However, evidence on the dose-response association between dietary sodium intake and cardiovascular disease risk is unclear. Embase and PubMed were searched from their inception to 17 August 2020 and studies that examined the association between sodium intake and cardiovascular disease in adolescents were not included in this review. We conducted a meta-analysis to estimate the effect of high sodium intake using a random effects model. The Newcastle-Ottawa Scale assessment was performed. A random-effects dose-response model was used to estimate the linear and nonlinear dose-response relationships. Subgroup analyses and meta-regression were conducted to explain the observed heterogeneity. We identified 36 reports, which included a total of 616,905 participants, and 20 of these reports were also used for a dose-response meta-analysis. Compared with individuals with low sodium intake, individuals with high sodium intake had a higher adjusted risk of cardiovascular disease (Rate ratio: 1.19, 95% confidence intervals = 1.08-1.30). Our findings suggest that there is a significant linear relationship between dietary sodium intake and cardiovascular disease risk. The risk of cardiovascular disease increased up to 6% for every 1 g increase in dietary sodium intake. A low-sodium diet should be encouraged and education regarding reduced sodium intake should be provided.

Background: Metabolically healthy obesity (MHO) is defined as obesity with less than two parameters of metabolic abnormalities. Some studies report that MHO individuals show similar risk of cardiovascular disease (CVD) compared with metabolically healthy non-obese (MHNO) individuals, but the results are conflicting. Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD. The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC., Method: We searched Cochrane, PubMed, and Embase up to April 19, 2019. Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models. Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity. We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006)., Results: A total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis. Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I 2 = 39%). In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR = 1.47, 95% CI [1.15,1.87], I 2 = 0%), and borderline significant in cross-sectional studies. The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR = 1.55, 95% CI [1.25,1.93], I 2 = 0%). The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk., Conclusion: Our meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis. People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present., Competing Interests: The authors declare there are no competing interests., (©2020 Hsueh et al.)

We investigated the association among metabolically healthy obesity (MHO), cardiovascular disease (CVD)risk, and all-cause mortality in the Asian population. We searched databases from inception to 16 November, 2019 and pooled data using a random-effects model. Subgroup analysis was conducted according to the following comparison groups: MHNW (without overweight or underweight participants) and MHNO (non-obese, including overweight and underweight participants). Nineteen studies were included. The mean Newcastle-Ottawa Scale score was 7.8. Participants with MHO had a significantly higher CVD risk (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.13-1.63) and significantly lower risk of all-cause mortality (OR = 0.88, 95% CI = 0.78-1.00) than the comparison group. Subgroup analyses revealed participants with MHO had a significantly higher CVD risk than MHNW participants (OR = 1.61; 95% CI = 1.24-2.08; I 2 = 73%), but there was no significant difference compared with MHNO participants (OR, 1.04; 95% CI, 0.80-1.36; I 2 = 68%). Participants with MHO had a significantly lower risk of all-cause mortality (OR = 0.83; 95% CI = 0.78-0.88; I 2 = 9%) than MHNO participants, but a borderline significantly higher risk of all-cause mortality than MHNW participants (OR = 1.30; 95% CI = 0.99-1.72; I 2 = 0%). The CVD risk and all-cause mortality of the MHO group changed depending on the control group. Thus, future studies should select control groups carefully.

The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Prenatal anxiety is extremely common and may result in adverse effects on both the mother and the baby. Music interventions have been used to reduce anxiety in various medical patients and in pregnant women during childbirth. This study aims to assess the clinical efficacy of music interventions in women during pregnancy rather than during labor. Seven databases were searched from inception to September 2019 without language restrictions. We included only randomized controlled trials that compared music intervention and control groups for anxiety reduction in pregnant women. We used the revised Cochrane risk-of-bias tool (RoB 2.0) for quality assessment. Finally, 11 studies with 1482 participants were included. The pooled meta-analysis results showed that music interventions significantly decreased anxiety levels (standardized mean difference (SMD), -0.42; 95% confidence interval (CI), -0.83 to -0.02; I 2 = 91%). Moreover, subgroup analysis showed that listening to music at home had significant anxiolytic benefits (SMD, -0.28; 95% CI, -0.47 to -0.08; I 2 = 0%). However, meta-regression revealed a nonsignificant trend for increase in the anxiety-reducing effects of music interventions with increasing maternal age. In conclusion, music interventions may be beneficial in reducing anxiety and may be applied in pregnant women.

Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are "epigenetic eraser" enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro . Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function.

Cardiovascular disease (CVD) risk in individuals with metabolically healthy obesity (MHO) is unclear. We searched databases from inception to May 2019. Data were pooled using a random effects model. Newcastle-Ottawa Scale assessment was performed. Primary and secondary outcomes were CVD risk and all-cause mortality. Forty-three studies involving 4,822,205 cases were included. The median percentage of females, age and duration of follow-up was 52%, 49.9 years and 10.6 years, respectively. The mean Newcastle-Ottawa Scale score of the articles was 7.9 ± 1.0. Compared to individuals with a metabolically healthy normal weight, individuals with MHO had higher adjusted risk of CVD and all-cause mortality. We identified a significant linear dose-response relationship between body mass index (BMI) and CVD risk among metabolically healthy individuals ( p < 0.001); every unit increase in BMI increased the CVD risk. Multivariate meta-regression analysis showed that an increased proportion of women and age resulted in the risk of CVD affected by MHO reduction ( p = 0.014, p = 0.030, respectively). Age and sex explained the observed heterogeneity and reported the adjusted R 2 . MHO resulted in a significantly increased risk for CVD; therefore, long-term weight loss should be encouraged.

Research into the association between heart rate variability (HRV) and cognitive function is scarce, particularly with regard to gender differences. HRV in 182 healthy volunteers was assessed by the root mean square of the successive difference (RMSSD) and spectrum analysis, while the Wechsler Memory Scale-Revised (WMS-R) was used to determine memory function. Robust and significant associations were found to exist between HRV (RMSSD and high-frequency HRV) and domains of the WMS-R in females. Caution should therefore be taken to control for gender when conducting studies on the relationships between HRV and cognitive variables.

Background: Anxiety is commonly experienced during the delivery process and has shown to have adverse effects on maternal and infant health outcomes. Music interventions tend to reduce the effects of anxiety in diverse populations, are low cost, are easily accessible, and have high acceptability. The aim of this review and meta-analysis was to assess the effectiveness of music interventions in reducing anxiety levels among women during labor., Methods: Seven databases from inception to the end of December, 2018, without any language or time restriction including Embase, PubMed, the Cochrane Library, the Cumulative Index to Nursing and Allied Health, PsycINFO, Airiti Library, and PerioPath: Index to Taiwan Periodical Literature were searched using key terms related to pregnancy, anxiety, and music. Randomized controlled trials that assessed the effect of music during labor and measured anxiety levels as an outcome were included. Meta-analyses were conducted to assess anxiety reduction following a music intervention compared to that after placebo treatment., Results: A total of 14 studies that investigated a total of 1,310 participants were included in this review. The meta-analyses indicated that those in the intervention group had a significant decrease in anxiety scores (standardized mean difference = -2.40, 95% confidence interval (CI) [-3.29 to -1.52], p < 0.001; I 2 = 97.66%), heart rate (HR) (difference in means = -3.04 beats/min, 95% CI [-4.79 to -1.29] beats/min, p = 0.001; I 2 = 0.00%), systolic blood pressure (SBP) (difference in means = -3.71 mmHg, 95% CI [-7.07 to -0.35] mmHg, p = 0.031; I 2 = 58.47%), and diastolic blood pressure (DBP) (difference in means = -3.54 mmHg, 95% CI [-5.27 to -1.81] mmHg, p < 0.001; I 2 = 0.00%) as compared to the women in the control group., Conclusions: Music interventions may decrease anxiety scores and physiological indexes related to anxiety (HR, SBP, and DBP). Music interventions may be a good non-pharmacological approach for decreasing anxiety levels during labor., Competing Interests: The authors declare that they have no competing interests.

Purpose: Investigate the relationship between pet ownership and cardiovascular (CV) outcomes., Methods: We searched the PubMed, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases up to August 2018. Eligible publications examining the association between pet ownership and all-cause and CV mortality (primary outcomes) and risks of cardiovascular disease (CVD), myocardial infarction (MI), and stroke (secondary outcomes) were included. We used the Newcastle-Ottawa Scale to assess the quality of the articles., Results: We included 12 studies, involving 488,986 participants (52.3% female, mean age 56.1 years), in our systematic review. The mean follow-up duration was 8.7 ± 6.3 years. Pet ownership had no association with adjusted all-cause mortality (odds ratio, OR = 1.01, 95% confidence interval, CI [0.94, 1.08], I2 = 76%), adjusted CV mortality (OR = 0.87, 95% CI [0.75, 1.00], I2 = 72%), or risk of cardiovascular disease (CVD) (OR = 0.87, 95% CI [0.72, 1.05], I2 = 73%), myocardial infarction (MI) (OR = 0.99, 95% CI [0.97, 1.01], I2 = 0%), or stroke (OR = 0.99, 95% CI [0.98, 1.01], I2 = 0%). However, subgroup analysis showed that pet ownership was associated with a lower adjusted CV mortality in the general population (OR = 0.93, 95% CI [0.86, 0.99], I2 = 27%) than in CVD patients. In patients with established CVD, pet ownership was associated with a lower adjusted CVD risk (OR = 0.71, 95% CI [0.60, 0.84], I2 = 0%)., Conclusion: Pet ownership is not associated with adjusted all-cause or CV mortality, or risk of CVD, MI, or stroke, but it is associated with a lower adjusted CV mortality in the general population and a lower CVD risk in patients with established CVD., Competing Interests: The authors have declared that no competing interests exist.

Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408) in the flexible C-terminal region of PHD2 to give a modified protein that retains catalytic activity.

Prolyl hydroxylation domain (PHD) enzymes catalyze the hydroxylation of the transcription factor hypoxia-inducible factor (HIF) and serve as cellular oxygen sensors. HIF and the PHD enzymes regulate numerous potentially tissue-protective target genes which can adapt cells to metabolic and ischemic stress. We describe a fluorescent PHD inhibitor (1-chloro-4-hydroxybenzo[g]isoquinoline-3-carbonyl)glycine which is suited to fluorescence-based detection assays and for monitoring PHD inhibitors in biological systems. In cell-based assays, application of the fluorescent PHD inhibitor allowed co-localization with a cellular PHD enzyme and led to live cell imaging of processes involved in cellular oxygen sensing., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial agents with anti-inflammatory effects. We conducted a comprehensive literature search and a systematic review of studies that investigated the influences of macrolide treatment on CWD. The primary outcomes were the impact of macrolides on hospitalization courses of patients with CWD. Data pertaining to the study population, macrolide treatment, hospital courses, and recurrences were analyzed. Twenty-three studies with a combined study population of 2210 patients were included in the systematic review. Any kind of benefit from macrolide treatment was observed in approximately two-thirds of the studies (15/23). Eight studies were included in the meta-analysis to investigate the influence of macrolides on the length of stay (LOS), duration of oxygen demand (DOD), symptoms and signs of respiratory distress, and re-admission rates. Although the benefits of macrolide treatment were reported in several of the studies, no significant differences in LOS, DOD, symptoms and signs of respiratory distress, or re-admission rates were observed in patients undergoing macrolide treatment. In conclusion, any kind of benefit of macrolide treatment was observed in approximately two-thirds of the studies; however, no obvious benefits of macrolide treatment were observed in the hospitalization courses of children with CWD. The routine use of macrolides to improve the hospitalization course of children with CWD is not suggested.

Background: The prevalence of cognitive impairment is increasing due to the aging population, and early detection is essential clinically. The Ascertain Dementia 8 (AD8) questionnaire is a brief informant-based measure recently developed to assess early cognitive impairment, however, its overall diagnostic performance is controversial. The objective of this meta-analysis was to assess the diagnostic accuracy of the AD8 for cognitive impairment., Methods: All relevant studies were collected from databases including MEDLINE, EMBASE and the Cochrane Library up to April 2017. We used QUADAS-2 to assess the methodological quality after the systematic search. The accuracy data and potential confounding variables were extracted from the eligible studies which included those in English and non-English. All analyses were performed using the Midas module in Stata 14.0 and Meta-DiSc 1.4 software., Results: Seven relevant studies including 3728 subjects were collected, and classified into two subgroups according to the severity of cognitive impairment. The overall sensitivity (0.72, 0.91) was superior to specificity (0.67, 0.78). The pooled negative likelihood ratio (0.17, 0.13) was better than the positive likelihood ratio (2.52, 3.94). The areas under the summary receiver operating characteristic curve were 0.83 and 0.92, respectively. Meta-regression analysis showed that location (community versus non-community) may be the source of heterogeneity. The average administration time was less than 3 minutes., Conclusion: Our findings suggest that the AD8 is a competitive tool for clinically screening cognitive impairment and has an optimal administration time in the busy primary care setting. Subjects with an AD8 score ≧2 should be highly suspected to have cognitive impairment and a further definite diagnosis is needed.

Affinity reagents are of central importance for selectively identifying proteins and investigating their interactions. We report on the development and use of cyclic peptides, identified by mRNA display-based RaPID methodology, that are selective for, and tight binders of, the human hypoxia inducible factor prolyl hydroxylases (PHDs) - enzymes crucial in hypoxia sensing. Biophysical analyses reveal the cyclic peptides to bind in a distinct site, away from the enzyme active site pocket, enabling conservation of substrate binding and catalysis. A biotinylated cyclic peptide captures not only the PHDs, but also their primary substrate hypoxia inducible factor HIF1-α. Our work highlights the potential for tight, non-active site binding cyclic peptides to act as promising affinity reagents for studying protein-protein interactions.

Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not clear. We performed a comprehensive literature search and systematic review of studies that investigated vitamin D and influenza vaccination. Data pertaining to study population, vaccine components, vitamin D levels, and immunogenic response were analyzed. Nine studies, with a combined study population of 2367 patients, were included in the systematic review. Four studies were included in the meta-analysis to investigate the influence of vitamin D deficiency (VDD) on the seroprotection (SP) rates and seroconversion (SC) rates following influenza vaccination. We found no significant association between vitamin D level and the immunogenic response to influenza vaccination. However, strain-specific differences may exist. We observed lower SP rates of influenza A virus subtype H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval (CI): 0.43-0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5-0.93, p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were not significantly different in VDD and control groups. In conclusion, no association was observed between VDD and immunogenic response to influenza vaccination., Competing Interests: The authors declare no conflict of interest.

Background: Nasogastric (NG) tube insertion is a common procedure in the clinical setting that causes much discomfort and pain for the patient. Pain control is often suboptimal, as many NG tube insertions are performed without any pain-relieving supplements. The aim of this study was to summarize and critically evaluate the evidence from randomized controlled trials (RCTs) on the effect and adverse effects of lidocaine agents in reducing pain and discomfort associated with NG tube insertion., Methods: Databases from the Cochrane Library, MEDLINE, EMBASE, Airiti Library, PerioPath Index to Taiwan Periodical Literature, and Cumulative Index of Nursing and Allied Health (CINAHL) were searched from inception to April 2017. RCTs focusing on lidocaine before NG tube insertion were appraised. The primary outcome was the visual analog scale (VAS) score. The modified Jadad scale was used for quality assessment. Mean difference (MD) with 95% confidence intervals (95% CIs) and odds ratio (OR) for binary outcomes were assessed by a random effects model. Heterogeneity was determined by using the Cochran Q test and I statistics. Publication bias was analyzed by using a funnel plot analysis., Results: Ten RCTs enrolling 734 patients were included in the meta-analysis. Eight of the 10 RCTs reporting VAS scores had sufficient quantitative data to be pooled through meta-analysis. Results revealed a significant reduction in VAS score, with a MD of -26.05 and a CI of -28.21 to -23.89 with moderate heterogeneity (P < .001, I = 56%). There were no significant changes in difficulty of NG tube insertions (MD = -0.30, 95% CI, -1.30 to 0.70, P = .55), number of NG tube insertion attempts (MD = -0.22, 95% CI, -0.98 to 0.53, P = .56), nasal bleeding (OR = 0.62, 95% CI, 0.11-3.41, P = .59), and vomiting (OR = 0.30, 95% CI, 0.07-1.27, P = .10)., Conclusion: This meta-analysis suggests that applying lidocaine before NG tube insertion can alleviate pain and discomfort by 26% without increasing nasal bleeding or vomiting.