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Aim: This study investigated the levels of depression and anxiety in nurses and nursing assistants working in long‐term care facilities during the COVID‐19 pandemic. We also explored the potential causes of depression and anxiety in nurses and nursing assistants working in long‐term care facilities during the pandemic. Background: The COVID‐19 pandemic has had a considerable impact on long‐term care facilities. The high infection and mortality rates for COVID‐19 have resulted in an increased workload for caregivers. Introduction: The COVID‐19 pandemic exposed caregivers working in long‐term care facilities to higher risks of anxiety and depression. Additionally, the high risk of infection in the work environment and concerns about spreading COVID‐19 to family members and long‐term care facility residents led to various forms of stress among caregivers. Methods: The present study was a cross‐sectional study. Questionnaires were used to investigate depression and anxiety among regarding nurses and nursing assistants working in long‐term care facilities during the pandemic. Results: The depression and anxiety levels of the nurses were higher than nursing assistants, but had no statistically significant difference (p = 0.551). The factors influencing levels of depression and anxiety in nurses contained facility affiliation and experience working. In terms of nursing assistants, age, marital status, and facility affiliation were correlated with the levels of depression and anxiety. Discussion: The pandemic has severely impacted caregivers. In the process of implementing pandemic prevention measures and providing care for COVID‐19 patients, safeguarding the psychological health of caregivers is also essential. Conclusion: The levels of depression and anxiety in nurses were higher than in nursing assistants working in long‐term care facilities during the pandemic. Implication for nursing and health policy: Long‐term care facilities managers are recommended to enhance the education and training process for caregivers. Managers are also recommended to ensure provision of sufficient amounts of pandemic prevention equipment and resources. [ABSTRACT FROM AUTHOR]

Most residents of long-term care facilities (LTCFs) are patients with chronic diseases requiring long-term care. Unplanned hospitalization of older and frailer residents from LTCFs reduces their mobility and increases the number of infections, complications, and falls that might lead to severe disability or death. This study aimed to identify the critical risk factors associated with unplanned hospitalization among LTCF residents in Taiwan, providing insights that could inform better care practices in similar settings globally. A retrospective study was conducted using inpatient data from a medical center in central Taiwan, covering the period from 2011 to 2019. A total of 1220 LTCF residents were matched with general patients using propensity score matching. Multiple logistic regression analyses were performed to identify factors associated with unplanned hospitalization, controlling for relevant variables. LTCF residents had a significantly higher risk of unplanned hospitalization compared to general patients (OR = 1.44, 95% CI = 1.21–1.73). Key risk factors included advanced age (≥85 years, OR = 1.25, 95% CI = 1.02–1.54), the presence of comorbidities such as diabetes (OR = 1.17, 95% CI = 1.03–1.33) and renal failure (OR = 1.63, 95% CI = 1.42–1.86), high fall risk (OR = 2.67, 95% CI = 2.30–3.10), and being bedridden (OR = 6.55, 95% CI = 5.48–7.85). The presence of a tracheostomy tube also significantly increased hospitalization risk (OR = 1.73, 95% CI = 1.15–2.59). LTCF residents are at a higher risk of unplanned hospitalization, particularly those with specific comorbidities, physical limitations, and indwelling medical devices. These findings underscore the need for targeted interventions to manage these risks, potentially improving care outcomes for LTCF residents globally. [ABSTRACT FROM AUTHOR]

With the proliferation of paid mobile learning applications (m-learning apps), understanding how to assess their success has become an important issue for academics and practitioners. Based on the information systems (IS) success models and the value-based adoption model, this study developed and validated a multidimensional model for assessing paid m-learning app success. The proposed model describes the interrelationships among seven paid m-learning app success variables: system quality, information quality, perceived enjoyment, perceived fee, user satisfaction, intention to reuse, and learning effectiveness. Data collected from 160 paid m-learning app users were tested against the research model using structural equation modeling (SEM). The empirical findings provide evidence that learning effectiveness is affected by user satisfaction and intention to reuse, which, in turn, are determined by system quality, information quality, perceived enjoyment, and perceived fee. The findings of this study provide several important theoretical and practical implications for the development, implementation, and promotion of paid m-learning apps.

Aims: Sodium‐glucose cotransporter 2 inhibitors (SGLT‐2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT‐2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan. Materials and Methods: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT‐2is during 2016–2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP‐4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use. Results: After controlling for relevant variables, the SGLT‐2i cohort (aHR = 0.90, 95% CI = 0.87–0.93) had a significantly lower risk of developing cancer than the DPP‐4i cohort, particularly when the SGLT‐2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87–0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86–0.94). Regarding cancer type, the SGLT‐2i cohort's risk of cancer was significantly lower than that of the DPP‐4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer. Conclusions: SGLT‐2i use was associated with a significantly lower risk of cancer than DPP‐4i use. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65–0.90], 0.77 [95% CI 0.64–0.92], and 0.69 [95% CI 0.54–0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26–0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16–1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk. [ABSTRACT FROM AUTHOR]

Objectives: Patients with terminal cancer often experience physical and mental distress. Signing a do-not-resuscitate order (DNR) is crucial to protect against invalid treatment. This study aims to explore the effect of hospice shared care intervention by medical staff on the completion of a DNR-S (DNR order signed by surrogates) for patients with terminal cancer. Method: The cross-sectional study in this research involved secondary analysis of data from the 2011–2015 clinical cancer case management database of a medical center in central Taiwan. Those with a DNR order signed by patients (DNR-P) or DNR-S before the hospice shared care consultation were excluded from this study; a total of 1,306 patients with terminal cancer were selected. Results: This study demonstrated that the percentage of DNR-S after consultation involving both nurse and physician was 75.4%. With other variables controlled, the number of DNR-Ss after consultation with a nurse was significantly lower [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.42–0.75] and that of DNR-Ss after consultation involving both nurse and physician was significantly higher (OR = 1.35, 95% CI = 1.01–1.79), than that of DNR-Ss after consultation with only the physician. Significance of results: Joint involvement of the nurse and physician in hospice care provides sufficient information to patients and family with terminal cancer about their condition and enhances doctor–patient communication. This effectively assists patients with terminal cancer and their family members in making the major decision of signing a DNR, alleviates the concerns of patients and family members about signing a DNR, and reduces terminal cancer patients' pain at the end of life to ensure that they die in peace and dignity. [ABSTRACT FROM AUTHOR]

The evidence of metformin's effect on dementia is conflicting. This study investigates the association between metformin use and the risk of dementia among patients with diabetes mellitus (DM). This study included patients with new-onset DM between 2002 and 2013. We divided the patients into patients who used metformin and patients who did not. Two models were used to assess metformin use: the cumulative defined daily dose (cDDD) of metformin use and the intensity of metformin use. This study with 3-year and 5-year follow-ups investigated the risk of dementia among patients with DM who used metformin. At the 3-year follow-up, patients who received cDDD < 300 had an odds ratio (OR) of developing dementia of 0.92 (95% confidence interval [CI] = 0.89–0.96); patients who used metformin at intensities <10 and 10–25 DDD/month had ORs of 0.92 (95% CI: 0.87–0.97) and 0.92 (95% CI: 0.85–1.00), respectively. Metformin use at cDDD 300–500 (OR = 0.80, 95% CI = 0.56–1.15) or >500 (OR = 1.48, 95% CI = 0.48–4.60) or at an intensity >25 DDD/month (OR = 0.84, 95% CI = 0.60–1.18) were not associated with an incident of dementia. There were similar results at the 5-year follow-up. Patients with a low intensity of metformin use had a lower risk of dementia. However, higher doses of metformin with higher intensity exhibited no protective role in dementia. Prospective clinical trials are warranted to evaluate the actual underlying mechanisms between metformin dosage and the risk of dementia. [ABSTRACT FROM AUTHOR]

In elderly patients with newly diagnosed breast cancer, clarity is lacking regarding the effects of influenza vaccines, particularly on clinical outcomes. This study conducted two nationwide, population-based, and propensity score-matched cohorts to estimate and compare the protective effects of influenza vaccine in elderly women and elderly patients with breast cancer. Data were derived from the National Health Insurance Research Database and Cancer Registry Database. Generalized estimating equations (GEEs) were used to compare outcomes between the vaccinated and unvaccinated cohorts. Adjusted odds ratios (aORs) were used to estimate the relative risks, and stratified analyses in the breast cancer cohort were performed to further evaluate elderly breast cancer patients undergoing a variety of adjuvant therapies. The GEE analysis showed that the aORs of death and hospitalization, including for influenza and pneumonia, respiratory diseases, respiratory failure, and heart disease, did not significantly decrease in vaccinated elderly patients with newly diagnosed breast cancer. Conversely, the aORs of all influenza-related clinical outcomes were significantly decreased in elderly women. No protective effects of influenza vaccination were found in the elderly patients with a newly diagnosed breast cancer. More studies focusing on identifying strategies to improve the real-world effectiveness of influenza vaccination to the immunocompromised are needed. Our clinical outcomes will be valuable for future public health policy establishment and shared decision making for influenza vaccine use in elderly patients with newly diagnosed breast cancer. According to our findings, regular influenza vaccine administration for elderly patients with newly diagnosed breast cancer may be reconsidered, with potential contraindications for vaccination. On the other hand, implementing the vaccination of close contacts of patients with breast cancer may be a more important strategy for enhancing protection of those fragile patients. [ABSTRACT FROM AUTHOR]

Background. Studies have demonstrated that patients with diabetes mellitus who receive metformin have a lower risk of developing Parkinson's disease (PD). However, studies have also suggested that metformin may increase the risk of PD. In this study, we investigated whether metformin use was associated with the risk of PD in type 2 diabetes mellitus (T2DM). Methods. In this population-based cross-sectional study, patients with T2DM diagnosed between 2001 and 2018 were enrolled. We categorized these patients as metformin users or nonusers. Participants below 50 years old were excluded. Two models were employed to evaluate the associations of metformin exposure and use intensity with PD after 3 and 5 years of follow-up. Results. Patients with T2DM who received <300 cumulative defined daily doses (cDDD) of metformin and those with metformin use intensity of <10 DDD/month had respective odds ratios (ORs) for PD of 0.88 (95% confidence interval [CI] = 0.83–0.94) and 0.87 (95% CI = 0.81–0.93) in a 3-year follow-up. In a 5-year follow-up, such patients had respective ORs for PD of 0.94 (95% CI = 0.90–0.98) and 0.93 (95% CI = 0.89–0.98). Patients with T2DM who received ≥300 cDDD of metformin or used metformin with intensity of ≥10 DDD/month experienced no neuroprotective effects after 3 or 5 years. Conclusions. Metformin was associated with PD odds in T2DM in a dose–response association manner. Patients who received low dosage and intensity of metformin use were associated with lower odds of PD, while higher dosage and intensity of metformin use had no neuroprotective effect. [ABSTRACT FROM AUTHOR]

Background: Association between nonalcoholic fatty liver disease (NAFLD) and future psoriasis has not yet been confirmed, although the two diseases partially share a common pathogenesis pathway. Studies have revealed an association between psoriasis and subsequent NAFLD; however, these studies were limited to small sample sizes and a cross-sectional study design. Hence, the main objective of this population-based longitudinal cohort study was to evaluate the bidirectional association between psoriasis and NAFLD. Methods: Data were retrieved from Taiwan's National Health Insurance Research Database. Patients with new-onset NAFLD and psoriasis were respectively enrolled in two cohorts. For each comparison cohort, propensity-score-matched controls with no record of NAFLD or psoriasis were selected. An adjusted hazard ratio (aHR) was applied to evaluate subsequent risks. Results: The risk of patients with new-onset NAFLD developing psoriasis was statistically significant, with an HR of 1.07 (95% CI, 1.01–1.14). For younger patients with NAFLD, the risk of developing psoriasis was 1.3-fold higher. The risk of patients with new-onset psoriasis developing NAFLD in the future was 1.28-fold higher than that of patients without psoriasis (95% CI, 1.21–1.35), and patients in younger psoriasis subgroups below the age of 40 years were at a higher risk than those in older subgroups, with an aHR of 1.55 (95% CI, 1.40–1.71). Conclusion: Evidence supports a bidirectional association between NAFLD and psoriasis, especially in patients below the age of 40 years. The correlation between the two diseases and the subsequent risk of disease development should be considered when caring for patients. [ABSTRACT FROM AUTHOR]

Ischemic stroke is the most prevalent stroke condition in the world resulted in either a transient ischemic attack or long‐lasting neurological problems due to the interrupted or reduced blood flow to the brain. Antrodia camphorata is a well‐known medicinal mushroom native to Taiwan and is familiar due to its medicinal effects. The current study investigated the protective effect of A. camphorata‐alcohol extracts (AC‐AE) against cobalt (II) chloride (CoCl2)‐induced oxidative stress in vitro and ischemia/reperfusion‐induced brain injury in vivo. The rats were pre‐treated with AC‐AE for 4 weeks. Our results showed that AC‐AE reduced cell damage and decreased reactive oxygen species (ROS) production in C6 and PC12 cells under CoCl2‐induced hypoxic condition. AC‐AE doses (385, 770, 1,540 mg/kg/day, 4 weeks) increased nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) mRNA expressions and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) mRNA expressions in Sprague Dawley rat. Besides, it decreased stroke infarct size and increased the level of antioxidants in both brain and serum. Furthermore, it reduced the formation of malondialdehyde (MDA) after ischemia/reperfusion (I/R). Our results suggested that AC‐AE exerted an effective reduction of ischemia stroke by regulating ROS production. [ABSTRACT FROM AUTHOR]

Background and Purpose: The mortality rate of cerebellar hemorrhage (CH) is generally higher than other types of intracranial hemorrhage. Recently, the increased survey rate of CH has come from improved clinical imaging and earlier surgical intervention. Hence, the predictors of intermittent- (1 to 6 months) and long-term (> 6months) mortality are clinically practical use for educational and therapeutic decisions. Unfortunately, the factors predictive mortality within six-month had not yet been systematically investigated. Methods: Seventy-two patients with acute spontaneous CH were retrospectively analyzed. The patients were divided into the six-month mortality group (n = 21, died within 6 months after CH onset) and survival group (n = 51, survived beyond 6 months). The independent predictors of six-month mortality were investigated by multivariate Cox proportional hazards regression. Results: The radiological brainstem compression (hazard ratios = 23.5; p < 0.001) was independent predictor of mortality within six-month after CH onset. The median onset time of six-month mortality was 5 days in patients with brainstem compression (p < 0.001) and the hazard ratios for the onset time was 13.1 compared with those without brainstem compression (95% CI, 4.7 to 36.3, p < 0.001). Conclusions: We report the first study that radiological brainstem compression predicted the mortality within six-month after onset of CH. Patients with radiological brainstem compression were about 23 times more likely to die within 6 months after CH than those without radiological brainstem compression. [ABSTRACT FROM AUTHOR]

Pigment epithelium-derived factor (PEDF) has been shown previously to prevent liver fibrosis and hepatic stellate cell (HSC) activation. By investigating the functional domains in PEDF, we identified a 34-mer peptide (residues Asp44-Asn77) that harbors the same function as the full-length PEDF protein. Not only did the 34-mer suppress the development of fibrosis in carbon tetrachloride (CCl4)-treated mouse liver but it also upregulated peroxisome proliferator-activated receptor-gamma (PPARγ) expression in HSCs in vivo. Platelet-derived growth factor (PDGF) plays a crucial role on the process of HSC activation in response to liver damage. The 34-mer suppressed PDGF-induced cell proliferation and expression of myofibroblastic marker proteins in primary rat HSC culture, increased the levels of PPARγ mRNA and protein in a dose-dependent manner and markedly reduced the level of active β-catenin protein, an HSC activating factor, in HSC-T6 cells. Similarly, IWR-1, an inhibitor of the Wnt response, displayed the same effect as the 34-mer in preventing HSC-T6 activation. The Wnt signaling-mediated PPARγ suppression was abolished by both the IWR-1 inhibitor and a small interfering RNA (siRNA) targeting β-catenin and the Wnt coreceptor, LRP6. Both PEDF and the 34-mer down-regulated PDGF receptor-α/β expression and blocked the PDGF-induced phosphorylation of Akt and ERK. Moreover, the inhibitory effect on PDGF receptor expression was abolished by PPARγ antagonists and PPARγ siRNA. Our observations indicate that the PEDF-derived 34-mer peptide can mimic PEDF in attenuating HSC activation. Investigation of this 34-mer peptide led to the identification of a signaling mechanism involving PPARγ induction, suppression of Wnt/β-catenin signaling and down-regulation of the PDGF receptor-α/β. [ABSTRACT FROM AUTHOR]

There are conflicting reports on cancer risk associated with angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). This retrospective cohort study was conducted to analyze the risk of cancer development in patients who received ACE inhibitors/ARBs as treatment for essential hypertension. Using the Taiwan National Health Insurance Research Database, 297,688 eligible study patients with essential hypertension were identified. According to their antihypertensive prescriptions, the study patients were stratified into an ACE inhibitor group, an ARB group, or a control group. After matching, participants were observed for the occurrence of cancer. In the ACE inhibitor group compared with the control group, the hazard ratio was 0.51 (95% confidence interval, 0.39-0.68). In the ARB group compared with the control group, the hazard ratio was 0.8 (95% confidence interval, 0.65-0.97). Regular use of ACE inhibitors/ARBs was not associated with an increased risk of cancer development and was actually found to decrease overall cancer risk in this study. [ABSTRACT FROM AUTHOR]

There are conflicting reports on cancer risk associated with angiotensin-converting enzyme ( ACE) inhibitors/angiotensin receptor blockers ( ARBs). This retrospective cohort study was conducted to analyze the risk of cancer development in patients who received ACE inhibitors/ ARBs as treatment for essential hypertension. Using the Taiwan National Health Insurance Research Database, 297,688 eligible study patients with essential hypertension were identified. According to their antihypertensive prescriptions, the study patients were stratified into an ACE inhibitor group, an ARB group, or a control group. After matching, participants were observed for the occurrence of cancer. In the ACE inhibitor group compared with the control group, the hazard ratio was 0.51 (95% confidence interval, 0.39-0.68). In the ARB group compared with the control group, the hazard ratio was 0.8 (95% confidence interval, 0.65-0.97). Regular use of ACE inhibitors/ ARBs was not associated with an increased risk of cancer development and was actually found to decrease overall cancer risk in this study. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Recently, children using antibiotics showed an increased incidence of neurodevelopmental disorders. The purpose of this study was to investigate the association between antibiotics use and the risk of ADHD in children. Population-based retrospective cohort study. The Taiwan National Health Insurance Research Database was used to collect data of children. Prevalence of antibiotics use was analyzed in the children (age, <2 years) included in this study. There were 1,601,689 children included in this study between 2004 and 2012. The risk of developing ADHD was estimated using the Cox proportional hazards model. 71.25 % of children used at least one antibiotic, and the mean follow-up period was 7.07 years. After controlling for other related influencing factors, children who used antibiotics had a 1.12 times higher risk of ADHD than those who did not. The risk of ADHD increased through the use of penicillin and cephalosporin regardless of the duration of antibiotics use. Antibiotics use in children—especially penicillin and cephalosporin—was associated with a higher risk of ADHD. • Providing real-world evidence of the association between antibiotics use and attention-deficit/hyperactivity disorder (ADHD) in children in Taiwan. • 71.25% of children in Taiwan used at least one antibiotic before 2 years old between 2004 and 2012. • Children using antibiotics had a higher risk of incident ADHD. • Penicillins and cephalosporins were associated with a higher risk of ADHD. [ABSTRACT FROM AUTHOR]

Background: How a person's Parkinson disease (PD) risk is affected by dipeptidyl peptidase-4 (DPP-4) inhibitors remains unclear. We evaluated the association of PD risk with use of these inhibitors in individuals diagnosed as having diabetes mellitus (DM)., Methods: Individuals diagnosed as having new-onset DM were enrolled into the case group and comparison group, comprising patients who received a DPP-4 inhibitor and a sulfonylurea, respectively. These groups were matched through propensity score matching on the basis of income level, gender, urbanization level, enrollment year, age, and diabetes complications severity index score. The case group was divided into subgroups on the basis of whether they had a cumulative defined daily dose (cDDD) of <75, 75-150, or >150. The DPP-4 inhibitor-PD risk association was evaluated through a Cox proportional hazards model. The Bonferroni adjustment test was employed to adjust P -values and reduce the false positive rate., Results: Compared with those in the comparison group (treatment with a sulfonylurea), patients with a DPP-4 inhibitor cDDD of >150 had a hazard ratio (HR) of 1.30 for PD development (95% confidence interval [CI]: 0.97-1.73; adjusted P = .263); the HRs for patients with a cDDD of <75 or 75-150 were 0.95 (95% CI: 0.71-1.27; adjusted P = .886) and 1.06 (95% CI: 0.75-1.50; adjusted P = .886), respectively. We noted nonsignificant differences regarding the associations between the use of the various DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) and PD risk after adjustment for any individual inhibitor (adjusted P > .05)., Conclusions: DPP-4 inhibitors were discovered in this study to not be associated with increased PD risk. This result was confirmed when the analysis was conducted individually for the 4 investigated DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and vildagliptin).

Pregnant women are at increased risk of influenza-related complications. However, the rate of influenza vaccination among pregnant women in Taiwan is low. By analyzing real-world data in this study, we investigated the factors associated with influenza vaccination during pregnancy in Taiwan. This study was a cross-sectional study. We collected real-world data from 2 databases in Taiwan: the Birth Certificate Database and the National Health Insurance Research Database. The study population was pregnant between October 2014 and December 2016 in Taiwan. The multivariate logistic regression was performed to identify factors associated with influenza vaccination, including maternal sociodemographics, trimester, comorbidities, and health-care utilization. The vaccination rate of among pregnant women was 8.2%. Factors significantly associated with a high likelihood of influenza vaccination were age between 30 and 34 years (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.10-1.19), second trimester (OR: 1.80; 95% CI: 1.75-1.85), income equal to or exceeding NT$ 38 201 (OR: 1.92; 95% CI: 1.86-1.99), hypertension (OR: 1.16; 95% CI: 1.05-1.29), cardiovascular disease (OR: 1.29; 95% CI: 1.17-1.42), autoimmune disease (OR: 1.47; 95% CI: 1.38-1.58), and chronic pulmonary disease (OR: 1.24; 95% CI: 1.18-1.31). A low level of urbanization, at least 1 hospitalization in the previous year, and the presence of pregnancy complications (eg, gestational diabetes, preeclampsia, and placenta previa) were associated with a lower likelihood rate of influenza vaccination. The influenza vaccination rate among pregnant women in Taiwan was low. Age, gestational age, income level, urbanization level, hypertension, cardiovascular disease, autoimmune disease, chronic pulmonary disease, and pregnancy complications may be associated with influenza vaccination among pregnant women., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Recent studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) who receive metformin have a decreased risk of developing age-related macular degeneration (AMD). However, other studies have also suggested that metformin may increase the risk of AMD development. Therefore, this study investigated the association between treatment with metformin and the risk of AMD in patients with T2DM by using Taiwan' National Health Insurance Research Database. Methods: Patients who received a diagnosis of new-onset T2DM between 2002 and 2013 were enrolled in this study. The patients were divided into patients treated and not treated with metformin to evaluate the risk of AMD after 5 years of follow-up. The logistic regression was used to estimate the risk of AMD associated with the intensity of treatment with metformin. Result: A total of 7 517 patients (103.16 patients per 10,000 people) developed AMD in 5 years after DM diagnosis. After adjusting for the relevant variables, patients with T2DM treated with <5 defined daily dose (DDD)/month of metformin had a lower risk of AMD (odds ratios [OR]: 0.93; 95% confidence interval [CI]: 0.88 0.99). Patients treated with >25 DDD/month of metformin had a higher risk of AMD (OR: 1.39; 95% CI: 1.08-1.78). Conclusion: Metformin use may be associated with a risk of AMD among patients with T2DM in a dose-dependent association manner, with the greater benefit at lower DDD/month. However, higher DDD/month exhibited an increased risk of AMD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Chang, Lee, Gau, Tsai, Chung and Lee.)

Background: In previous studies, it was reported that non-alcoholic fatty liver disease (NAFLD) incidence and prevalence increased in children with atopic dermatitis. Nevertheless, the actual association between the two diseases has not been fully proven in large-scale studies, and real-world evidence is missing. The objective of this nationwide, longitudinal cohort study was to evaluate the association between NAFLD and atopic dermatitis., Methods: The National Health Insurance Research Database in Taiwan was utilized in this study. Patients with records of NAFLD diagnosis were recruited as the experimental group, and patients having less than three outpatient visits or one inpatient visiting record due to NAFLD were excluded from the study design. Non-NAFLD controls were matched based on a 1:4 propensity score matching. Potential confounders including age, gender, comorbidity, and medical utilization status were considered as covariates. The risk of future atopic dermatitis would be evaluated based on multivariate Cox proportional hazard regression., Results: Compared with people without NAFLD, a decreased risk of atopic dermatitis in NALFD patients had been observed (aHR = 0.93, 95% CI 0.87-0.98). The trend was especially presented in young NAFLD patients. In patients younger than 40 years old, a 20% decreased risk of atopic dermatitis was reported (aHR = 0.80, 95% CI 0.70-0.92)., Conclusion: People with NAFLD were not associated with an increased risk of atopic dermatitis. Conversely, a 0.93-fold risk was noted in NAFLD patients, compared with NAFLD-free controls. Future studies are warranted to evaluate further the mechanism regarding the interplay between the inflammatory mechanisms of NAFLD and atopic dermatitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gau, Huang, Yang, Tsai, Huang and Lee.)

Background: Osteoporosis and fractures increase morbidity and mortality rates after solid organ transplantation (SOT), but few studies have analyzed the risk of osteoporosis and related fractures after SOT. In this retrospective cohort study, we investigated the risk of osteoporosis and fractures in different SOT recipients., Methods: This study was a retrospective cohort study using a nationally representative database in Taiwan. We collected the data of SOT recipients and used the propensity score matching method to obtain a comparison cohort. To reduce bias, we excluded patients who had been diagnosed with osteoporosis or fracture before inclusion. All participants were followed up until the date of diagnosis as having a pathological fracture, death, or the end of 2018, whichever occurred first. The Cox proportional hazards model was used to investigate the risk of osteoporosis and pathological fracture in SOT recipients., Results: After adjustment for the aforementioned variables, SOT recipients were observed to have a higher risk of osteoporosis (hazard ratio (HR) = 1.46, 95% confidence interval (CI): 1.29-1.65) and fracture (HR: 1.19, 95% CI: 1.01-1.39) than the general individuals. Among the different SOT recipients, the highest risk of fractures was noted in heart or lung transplant recipients, with a HR of 4.62 (95% CI: 2.05-10.44). Among the age groups, patients aged >61 years had the highest HRs for osteoporosis (HR: 11.51; 95% CI, 9.10-14.56) and fracture (HR: 11.75, 95% CI: 8.97-15.40)., Conclusion: SOT recipients had a higher risk of osteoporosis and related fractures than the general population, with the highest risks observed in patients receiving heart or lung transplants, older patients, and patients with CCI scores of >3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lai, Yang, Gau, Huang, Tsai, Huang and Lee.)

Background and Aims: Studies have demonstrated that the short-term use of metformin benefits liver function among patients with type 2 diabetes mellitus (T2DM). However, few studies have reported on the effects of long-term metformin treatment on liver function or liver histology. This study investigated the correlation between metformin use and the incidence of nonalcoholic fatty liver disease (NAFLD) among patients with T2DM., Methods: This population-based study investigated the risk of NAFLD among patients with T2DM who received metformin treatment between 2001-2018. Metformin users and metformin nonusers were enrolled and matched to compare the risk of NAFLD., Results: After 3 years, the patients who received <300 cDDD of metformin and those with metformin use intensity of <10 and 10-25 DDD/month had odds ratios (ORs) of 1.11 (95% confidence interval [CI] = 1.06-1.16), 1.08 (95% CI = 1.02-1.13), and 1.18 (95% CI = 1.11-1.26) for NAFLD, respectively. Moreover, metformin users who scored high on the Diabetes Complications and Severity Index (DCSI) were at high risk of NAFLD. Patients with comorbid hyperlipidemia, hyperuricemia, obesity, and hepatitis C were also at high risk of NAFLD., Conclusion: Patients with T2DM who received metformin of <300 cDDD or used metformin at an intensity of <10 and 10-25 DDD/month were at a high risk of developing NAFLD. The results of this study also indicated that patients with T2DM receiving metformin and with high scores on the DCSI were at a high risk of developing NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Lee, Cheng, Gau, Tsai, Chung and Lee.)

Background: Migraine is deemed a neurovascular disorder and there is growing evidence on the increased risk of cardiovascular disease, especially ischemic stroke, in patients with migraine. However the risk of peripheral artery disease (PAD) and stroke in migraineurs and the association between migraineurs with or without aura is still under debate. Our study aimed to identify the risk of PAD and stroke in migraineurs with or without aura. Methods: This was a population-based cohort study utilizing Taiwan Longitudinal Health Insurance Database (LHID2010). Patients with coding of migraine from 2002 to 2011 were enrolled and those with established cardiovascular disease defined as myocardial infarction, stroke, PAD, venous thromboembolism, atrial fibrillation and heart failure diagnosis before the index date were excluded. Participants were categorized into migraine group, migraine without aura group, and migraine with aura group respectively. The subjects in the three groups were propensity score-matched randomly to their counterparts without migraine. The study outcome was PAD and stroke. The Cox proportional hazard model was used to estimate the hazard ratios with 95% confidence interval (CI) for the association between migraine and the incident events of disease, after controlling for related variables. Results: The migraine, migraine without aura, and migraine with aura group included 5,173 patients, 942 patients and 479 patients respectively after propensity score-matching. The migraine group had an increased risk of PAD [adjusted hazard ratio (aHR): 1.93; 95% confidence interval (CI): 1.45-2.57; p < 0.001] and stroke (aHR: 1.55; 95% CI: 1.35-1.77; p < 0.001) compared to their non-migraine controls. Both the groups of migraine without aura and with aura had an increased risk of stroke (aHR: 1.49, 95% CI: 1.11-2.00; p = 0.008; aHR: 1.63, 95% CI: 1.10-2.43; p = 0.016). With regards to the outcome of PAD, the group of migraine with aura had a trend of an increased risk but did not reach statistical significance (aHR: 1.95, 95% CI: 0.86-4.40; p = 0.108). Conclusion: Migraineurs without established cardiovascular disease had a significantly increased risk of PAD and stroke, and the risk of stroke persists in migraineurs with or without aura, with an increased trend of PAD in migraineurs with aura. Our study result should remind clinical physicians of the risk of PAD in the future among migraineurs even without established cardiovascular disease currently, and screening for PAD and stroke may be needed in caring patients with migraine., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The patients with Parkinson's disease (PD) are associated with a higher risk of pneumonia. Antidepressants exert an anticholinergic effect in varying degrees and various classes of antidepressants also can produce a different effect on immune function. The relationship between the risk of pneumonia and the use of antidepressants among elderly patients with PD is unknown. The study investigated the risk of pneumonia associated with the use of antidepressants in elderly patients with PD. This case-control study was based on data from the longitudinal health insurance database in Taiwan. We analyzed the data of 551,975 elderly patients with PD between 2002 and 2018. To reduce the potential confounding caused by unbalanced covariates in non-experimental settings, we used propensity score matching to include older patients without pneumonia to serve as the comparison. The antidepressants in the study included tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin, and norepinephrine reuptake inhibitors (SNRIs). The conditional logistic regression was used to investigate the association between antidepressants and pneumonia. Control variables in the study included sex, age, income level, urbanization, Charlson comorbidity index score, and comorbidities related to pneumonia. In terms of TCAs users, compared with patients not receiving TCAs, current users had a lower risk of incident pneumonia (adjusted odds ratio [ aOR ] = 0.86, 95% CI = 0.82-0.90) and recent users (a OR = 0.83, 95% CI = 0.80-0.87). In terms of MAOIs users, current users had a lower risk of incident pneumonia (a OR = 0.88, 95% CI = 0.83-0.93), recent users (a OR = 0.89, 95% CI = 0.85-0.93). In terms of SSRIs users, current users had a higher risk of incident pneumonia (a OR = 1.13, 95% CI = 1.01-1.17), recent users (a OR = 1.01, 95% CI = 1.06-1.13), and past users (a OR = 1.19, 95% CI = 1.17-1.21). In terms of SNRIs users, past users had a higher risk of incident pneumonia (a OR = 1.07, 95% CI = 1.03-1.10). The incident pneumonia is associated with the use of individuals of different classes of antidepressants. The use of TCAs (such as, amitriptyline and imipramine) had a lower odds of incident pneumonia. The use of MAOIs (such as, selegiline and rasagiline) had a lower odds of pneumonia during recent use. The use of SSRIs (such as, fluoxetine, sertraline, escitalopram, paroxetine, and citalopram) and SNRIs (such as, milnacipran, and venlafaxine) had a higher odds of incident pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kuo, Huang, Kuan, Chang, Tsai and Lee.)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with an increased risk of developing non-Hodgkin lymphoma (NHL); however, adequate data corroborating these associations are lacking. Therefore, a study based on the national database was performed to investigate the correlation between HBV and HCV with NHL in Taiwan. This research was a retrospective cohort study using a nationally representative database established by the Health and Welfare Data Science Center of the Ministry of Health and Welfare, Taiwan. The participants were patients with HBV and HCV, analyzed using the propensity score matching method. The study results indicated that the incidence rate of NHL (0.13%) was significantly higher than that in patients from the general population. After controlling related variables, the hazard ratio (HR) of the incidence of NHL in patients with hepatitis was 2.37 (95% CI, 1.93-2.91). Furthermore, the incidence of NHL in patients with HBV was significantly higher than in patients from the general population (HR, 2.49; 95% CI, 1.94-3.19). The incidence of NHL in patients with HCV was significantly higher than in patients from the general population (HR, 2.36; 95% CI, 1.73-3.22). This study indicated that HBV and HCV significantly increase the risk of NHL.

Objective: To investigate the risk of pneumonia associated with the use of antipsychotic drugs in older-adult patients with Parkinson's disease (PD) in Taiwan. Methods: This case-control study was based on data from the longitudinal health insurance database in Taiwan. We analyzed the data of 51,158 older patients with PD for the period between 2001 and 2016. To reduce the potential confounding caused by unbalanced covariates in nonexperimental settings, we used propensity score matching to include older patients without pneumonia to serve as the control group. Results: Compared with patients who had never taken antipsychotics, current (adjusted odds ratios [aOR] =1.63, 95% confidence interval [CI] = 1.51-1.75), recent (aOR = 1.63, 95% CI = 1.52-1.74), and past (aOR = 1.89, 95% CI = 1.80-2.00) users of antipsychotics had a higher risk of incident pneumonia. Among typical and atypical antipsychotics, haloperidol and clozapine were associated with higher risks of incident pneumonia, respectively. By contrast, aripiprazole was not associated with a higher risk of pneumonia. Conclusion: Older patients with PD receiving typical antipsychotics or atypical antipsychotics had a higher risk of pneumonia. Among these antipsychotics, clozapine had the highest risk of pneumonia. Clinicians should pay attention to the risk of pneumonia in older patients with PD who receive typical antipsychotics and atypical antipsychotics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Two new sesquiterpenoids-13-hydroxycurzerenone ( 1 ) and 1-oxocurzerenone ( 2 )-have been isolated from the rhizomes of Curcuma zedoaria , together with 13 known compounds ( 3 - 15 ). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone ( 1 ), 1-oxocurzerenone ( 2 ), curzerenone ( 3 ), germacrone ( 4 ), curcolone ( 5 ), procurcumenol ( 6 ), ermanin ( 7 ), curcumin ( 8 ), and a mixture of stigmast-4-en-3,6-dione ( 12 ) and stigmasta-4,22-dien-3,6-dione ( 13 ) exhibited inhibition (with inhibition % in the range of 21.28%-67.58%) against collagen-induced platelet aggregation at 100 μM. Compounds 1 , 5 , 7 , 8 , and the mixture of 12 and 13 inhibited arachidonic acid (AA)-induced platelet aggregation at 100 μM with inhibition % in the range of 23.44%-95.36%.

There are no data on the incidence of new-onset diabetes mellitus (NODM ) in nondiabetic dyslipidaemia patients treated with fibrates. The aim of our study was to clarify these issues, to investigate the relationship between NODM and fibrate and whether the fibrates lead to increased risk for developing NODM. A retrospective cohort study was conducted by analyzing the Longitudinal Health Insurance Database (LHID 2005) of the National Health Insurance Research Database (NHIRD) from 2005 to 2010 to investigate all fibrate prescriptions for patients with dyslipidaemia. We estimated the hazard ratios (HRs) of NODM associated with fibrate use. We identified 145 NODM patients among 3,815 dyslipidaemic patients in the database for the study period. The risk estimates for NODM for users of fenofibrate (HR 1.30; 95% CI 0.82, 2.05) and gemfibrozil (HR 0.771; 95% CI 0.49, 1.22) were not associated with an increased risk of developing NODM (P > 0.05). Our results revealed that patients with dyslipidaemia who took fenofibrate and gemfibrozil had a neutral risk of NODM. The reasons may be associated with the fibrates have the properties that activate PPARα and in some cases also activated PPARγ, leading to showing a neutral risk of NODM.

Postoperative intracerebral hemorrhages occurring after evacuation of subdural fluid collections have been infrequently reported and remain a devastating complication. The pathophysiological mechanism is still unclear. Disturbed autoregulation and restoration of normal cerebral flow seems to play an important role in this type of event because of rapid decompression. Herein, we present a case of multiple intracerebral hemorrhages in the putamen and cerebellar hemisphere following evacuation of bilateral subdural effusions, and review the relevant literature.