Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson's disease among patients with diabetes mellitus: a retrospective cohort study.

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).

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis.

BACKGROUND: H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. OBJECTIVES: To explore dementia risk in patients with allergic rhinitis using AHs. METHODS: Taiwanese patients with new-onset allergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. RESULTS: FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). CONCLUSIONS: Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.

Depression and anxiety between nurses and nursing assistants working in long-term care facilities during the COVID-19 pandemic.

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.

Relationship between Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Disease in Chronic Respiratory Disease and Diabetes.

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.

Comparison between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real-world evidence study.

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.

Factors Associated With Influenza Vaccination During Pregnancy: A Real-World Evidence-Based Study.

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.

Risk of herpes simplex virus infection in solid organ transplant recipients: A population-based cross-sectional study.

BACKGROUND: Herpes simplex virus (HSV) is an opportunistic infection antigen in solid organ transplant (SOT) recipients. However, this phenomenon has received limited attention from epidemiologists. Our study aims to determine the HSV infection risk in SOT recipients. METHODS: This was a nationwide population-based cross-sectional study based on the National Health Insurance Research Database from 2002 to 2015. We used propensity score matching to avoid selection bias and analyzed the association between HSV infection and SOT recipients with multiple logistic regression analysis. RESULTS: At a 3-year follow-up, SOT recipients had a higher risk of developing HSV, with an adjusted odds ratio (aOR) of 3.28 (95% confidence interval (CI), 2.51-4.29). Moreover, at 6-month, 1-year, and 2-year follow-ups, SOT recipients also had an increased risk of HSV than general patients with aORs of 3.85 (95% CI, 2.29-6.49), 4.27 (95% CI, 2.86-6.36), and 3.73 (95% CI, 2.74-5.08), respectively. In the subgroup analysis, lung transplant recipients (aOR = 8.01; 95% CI, 2.39-26.88) exhibited a significantly higher chance of HSV among SOT recipients, followed by kidney transplant recipients (aOR = 3.33; 95% CI, 2.11-5.25) and liver transplant recipients (aOR = 3.15; 95% CI, 2.28-4.34). CONCLUSION: HSV can develop at any time after organ transplantation. SOT recipients had a higher risk of HSV infection than the general population at 6 months, 1 year, 2 years, and 3 years after transplantation, with the highest chance at 1 year after. In addition, the patients who underwent lung transplantion were at higher risk for HSV infection than liver or kidney transplant recipients.

The association between the workload of emergency physicians and the outcomes of acute myocardial infarction: a population-based study.

Acute myocardial infarction (AMI) is the second leading cause of mortality in Taiwan. The correlation between the workload of emergency physicians and the outcome of AMI remains unknown. To determine the effects of the workload of emergency physicians on the outcomes of AMI. We included 17 661 patients (age > 18 years) with STEMI undergoing PCI, who visited the emergency department between 2012 and 2018. We used the logistic regression model with generalized estimating equations (GEEs) to analyze the risk of death within 30 days after emergency department visit, the risk of emergency department revisits within 3 days, and the risk of readmission within 14 days in all subgroups. After covariate adjustment, the risk of mortality within 30 days after visiting the emergency department was significantly higher in the subgroup whose visiting emergency physicians had the highest workload (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.12 to 1.72). Furthermore, the risk of revisiting the emergency department within 3 days after discharge from the hospital was significantly higher in the subgroup whose visiting emergency physicians' workload was within the second and third quartiles (OR 1.85; 95% CI 1.18 to 2.89). The workload of emergency physicians appears to be positively correlated with the mortality risk of patients with STEMI undergoing PCI.

Dose-response association of metformin use and risk of age-related macular degeneration among patients with type 2 diabetes mellitus: a population-based study.

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.

Association between early-life antibiotics use and the risk of attention-deficit/hyperactivity disorder: A real-world evidence study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Recently, children using antibiotics showed an increased incidence of neurodevelopmental disorders. AIMS: The purpose of this study was to investigate the association between antibiotics use and the risk of ADHD in children. STUDY DESIGN: Population-based retrospective cohort study. SUBJECTS: 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. OUTCOME MEASURES: The risk of developing ADHD was estimated using the Cox proportional hazards model. RESULTS: 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. CONCLUSIONS: Antibiotics use in children-especially penicillin and cephalosporin-was associated with a higher risk of ADHD.

The association between non-alcoholic fatty liver disease and atopic dermatitis: a population-based cohort study.

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.

24-h PCI model does affect the outcome of STEMI patients: a population-based study.

Acute myocardial infarction has been the second leading cause of death in Taiwan. It's a novel issue to evaluate the relationship between the 24-h PCI service model and the outcome of STEMI patients. The objective of this study was to determine the effect of 24-h PCI service model in STEMI patients to improving survival rate. This population-based cohort study included those STEMI patients, older than 18 year-old, who had ever called emergency department from 2012 to 2018. We had two groups of our study participant, one group for STEMI patients with 24-h PCI model and the other group for STEMI patients with non-24-h PCI model. We used the Logistic regression model to analyze the risk of death within 30 days, emergency department (ED) revisits within 3 days, and readmission within 14 days. After the relevant variables were controlled, the risk of death after an ED visit among the patients with STEMI who were sent to hospitals with 24-h PCI services was significantly lower than that among the patients with STEMI who were sent to hospitals without 24-h PCI services (OR 0.85; 95% CI 0.75-0.98). However, the model could not reduce the risk of ER revisits and readmission.

High risk of osteoporosis and fracture following solid organ transplantation: a population-based study.

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.

The Correlation between Metformin Use and Incident Dementia in Patients with New-Onset Diabetes Mellitus: A Population-Based Study.

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.

The Incidence of Myocarditis Following an Influenza Vaccination: A Population-Based Observational Study.

BACKGROUND AND OBJECTIVE: Recently, studies have pointed to a link between coronavirus disease 2019 vaccinations and myocarditis. Myocarditis following an influenza vaccine has been sporadically reported. However, it is not known whether this adverse event occurs among elderly individuals who have received influenza vaccines. We used a population-based database and a self-controlled case-series design to estimate the incidence of myocarditis following an influenza vaccination. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. The study population consisted of elderly people aged ≥ 65 years who had de novo myocarditis, which required hospitalization, within 6 months after receiving an influenza vaccination between 2003 and 2017. The first 1-7, 1-14, and 1-42 days after vaccination were defined as risk intervals, and the other periods were defined as control intervals. Poisson regression was used to calculate the incidence rate ratio for myocarditis between the risk and control periods. RESULTS: Within 180 days following a vaccination, 191 people were hospitalized for myocarditis among 19,678,904 people. In comparison with control intervals, the incidence rate ratios of an admission for myocarditis for days 1-7, 1-14, and 1-42 were 0.80 (95% confidence interval 0.36-1.81), 0.72 (95% confidence interval 0.39-1.32), and 0.73 (95% confidence interval 0.50-1.05), respectively. Subgroup analyses by sex, age, Charlson Comorbidity Index scores, and comorbidities did not yield significant differences in the incidence rate ratio. CONCLUSIONS: Regardless of the post-vaccination time and underlying baseline characteristics, the incidence risk of myocarditis is not significantly increased in the elderly following an influenza vaccination.

The effect of joint involvement of nurse and physician in hospice care on terminal cancer patients on do-not-resuscitate orders signed by surrogates.

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.

Correlation between long-term use of metformin and incidence of NAFLD among patients with type 2 diabetes mellitus: A real-world cohort study.

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.

Risk of peripheral artery disease and stroke in migraineurs with or without aura: a nationwide population-based cohort study.

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.

The Protective Effects of Influenza Vaccination in Elderly Patients with Breast Cancer in Taiwan: A Real-World Evidence-Based Study.

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.

Dose-Response Association of Metformin with Parkinson's Disease Odds in Type 2 Diabetes Mellitus.

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.