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The purpose of this study was to identify the correlates of depressive symptoms and the prevalence of depression, distress, and demoralization among patients with cancer in Taiwan in relation to their sociodemographics. A cross-sectional study design with convenience sampling was used to recruit 191 consecutive patients with cancer from the Cancer Center of a teaching hospital in northern Taiwan. Multiple linear regression was applied to analyze the determinants of depressive symptoms. The prevalence rates of depression (including suspected cases), distress, and demoralization were 17.8%, 36.1%, and 32.5%, respectively. The regression model explained 42.2% of the total variance, with significant predictors including marital status, life dependence, comorbidity, demoralization, and distress. The results demonstrated that higher levels of distress and demoralization were associated with more depressive symptoms. Demoralization and distress played vital roles in moderating depressive symptoms among patients with cancer. Nursing interventions should integrate appropriate mental health services, such as alleviating distress and demoralization, to prevent the occurrence of depression in patients with cancer.

Objective: Statins have been demonstrated to improve outcomes in patients receiving immune checkpoint blockade (ICB). This study aimed to investigate whether the timing of statin administration influences the outcomes of patients receiving ICB., Methods: We conducted a retrospective cohort study utilizing electronic health records from two tertiary referral centers in Taiwan. We compared the overall survival (OS) and progression-free survival (PFS) of patients who received statins before and after ICB initiation., Results: We included 734 patients who received ICB. Among them, 606 were non-statin users, 76 started statins after ICB initiation, and 52 started statins before ICB initiation. Post-ICB statin users demonstrated significantly prolonged OS (median 37.6 versus 10.3 versus 11.3 months, p  = 0.009) and PFS (median 10.5 versus 6.3 versus 5.6 months, p  = 0.024) compared to pre-ICB statin and non-statin users. Statin use after ICB initiation had a reduced risk of all-cause mortality (HR, 0.65 [95% CI: 0.45-0.94], p  = 0.022) and progressive disease (HR, 0.71 [95% CI: 0.53-0.95], p  = 0.021) by approximately 30-35%, compared to non-statin users. However, statin use prior to ICB initiation did not affect the risk of all-cause mortality or progressive disease. Similar results were observed after controlling for potential cofounders such as age, sex, cancer stage, and cancer type., Conclusions: These findings suggest that initiating statin therapy after the initiation of ICB, regardless of indication, is associated with improved patient prognosis.

This study investigated the ability of a sarcopenia screening test to predict mortality among cancer inpatients. We conducted a prospective study of patients admitted to the oncology ward of a teaching hospital in southern Taiwan. Over a 5-month period, 82 patients were enrolled for evaluation and were followed for 3 years. All participants received a comprehensive assessment at the time of admission, including Eastern Cooperative Oncology Group (ECOG) performance status, cognitive ability, nutrition index, body mass index, and short physical performance battery (SPPB). Age, ECOG performance status, dementia, SPPB score, and albumin level were associated with sarcopenia. Of the enrolled participants, 53 (64.6%) were diagnosed with sarcopenia. Patients with sarcopenia were associated with worse overall survival (OS) than patients without sarcopenia (28.8% vs. 82%, p = 0.01). Metastasis (hazard ratio [HR]: 5.166; 95% confidence interval [CI]: 1.358-19.656) and albumin level (HR: 4.346; 95% CI: 1.493-12.654) were independent and significant predictors of OS for the whole study population. Age was a predictor of 2-year all-cause mortality among patients aged ≥65 years but not among those aged <65 years (OS: 25.6% vs. 100%, p = 0.04). To summarize, the sarcopenia screening results were found to predict OS and all-cause mortality and may be helpful for patient stratification during in-hospital care., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Recent guidelines for prognostic evaluation recommend clinicians' prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer., Methods: The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with "underestimation (less than 33% of actual survival)" and "overestimation (more than 33% of actual survival).", Results: A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01-1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51-0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06-1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05-1.72; P = 0.02) were identified as significant factors associated with overestimation., Conclusion: Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The long-term joint impacts of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) on mortality are inconclusive. To bridge this research gap, we included 283,568 adults from the Taiwan MJ cohort between 2005 and 2016 and linked with the mortality data until 31 May 2019. Participants' annual average exposures to PM 2.5 , NO 2 , and O 3 were estimated using satellite-based spatial-temporal models. We applied elastic net-regularised Cox models to construct a weighted environmental risk score (WERS) for the joint effects of three pollutants on non-accidental, cardiovascular, and cancer mortality and evaluated the contribution of each pollutant. The three pollutants jointly raised non-accidental mortality risk with a WERS hazard ratio (HR) of 1.186 (95% CI: 1.118-1.259) per standard deviation increase in each pollutant and weights of 72.8%, 15.2%, and 12.0% for PM 2.5 , NO 2 , and O 3 , respectively. The WERS increased cardiovascular death risk [HR: 1.248 (1.042-1.496)], with PM 2.5 as the first contributor and O 3 as the second. The WERS also elevated the cancer death risk [HR: 1.173 (1.083-1.270)], where PM 2.5 played the dominant role and NO 2 ranked second. Coordinated control of these three pollutants can optimise the health benefits of air quality improvements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks., Objective: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring., Methods: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers., Results: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth., Conclusions: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood., Methods: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period., Results: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001)., Conclusions: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops., (© 2024. The Author(s).)

Background: The literature on the association between diabetes severity and cancer risk is limited and inconclusive. The study aimed to evaluate the association between the adapted Diabetes Complications Severity Index (aDCSI) and the duration of type 2 diabetes and cancer risk., Methods: Patients ages 20 years or older with newly diagnosed type 2 diabetes between January 1, 2007, and December 31, 2011, were identified from Taiwan National Health Insurance claims data. Standardized incidence ratios (SIR) were calculated to compare cancer incidence in people with diabetes with that in the general population. Poisson regression was used to examine whether SIRs differed by age, sex, aDSCI, and duration of diabetes., Results: A total of 756,547 patients were included, with a median follow-up of 8.8 years. Excluding the first year after diagnosis, the SIR for overall cancer was 1.18 [95% confidence interval (CI) 1.17-1.19]. Higher aDCSI was associated with increased SIRs for overall [SIR ratio 1.03 (1.02-1.03) per point increase], head and neck (1.03; 1.01-1.04), liver (1.04; 1.03-1.05), pancreas (1.03; 1.00-1.05), kidney (1.13; 1.10-1.15), and leukemia (1.09; 1.06-1.13). There was no association between aDCSI and colorectal, extrahepatic biliary tract, uterus and thyroid cancer, and a negative association with breast cancer (0.97; 0.95-0.98). Type 2 diabetes duration was associated with increased SIRs for overall [1.01 (1.00-1.02) per year increase], head and neck (1.03; 1.01-1.05), and liver cancer (1.04; 1.02-1.05)., Conclusions: The heterogeneity in the association between diabetes severity and diabetes-related cancers suggests diverse underlying connections., Impact: Adopting distinct approaches in further research and prevention strategies for different kinds of diabetes-related cancers is important., (©2024 American Association for Cancer Research.)

Background: To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use., Methods: This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556., Inclusion Criteria: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs., Results: Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer., Conclusion: Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs., (© 2024. The Author(s).)

Background: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents., Methods: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality., Results: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups., Conclusions: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Air pollution is deemed a human carcinogen and can be linked to certain types of cancer other than lung cancer. The present study aimed to investigate the pollutant-cancer associations in a population-level cohort. We obtained the annual age-standardized incidence rates of 28 different cancer types between 2015 to 2019 from the Taiwan Cancer Registry. Outdoor concentrations of particulate matter with a diameter of 10 μm or less (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), ground-level ozone (O 3 ), and carbon monoxide (CO) between 2001 to 2010 were retrieved from the Taiwan Air Quality Monitoring Network. Weighted quantile sum (WQS) regression models were used to determine the combined effects of five air pollutants on the relationship to cancer incidence rates after controlling for sex ratio, age, average disposable income per household, overweight/obesity prevalence, current smoking rate, and drinking rate. Trend analyses showed that NO 2 and CO concentrations tended to decrease, while SO 2 concentrations increased in some counties. WQS regression analyses revealed significantly positive correlations between air pollutants and liver cancer, lung and tracheal cancer, colorectal cancer, thyroid cancer, kidney cancer, and small intestine cancer. Altogether, the results from this ecological study unravel that exposure to ambient air pollution is associated with the incidence of several non-lung cancer types., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk., Methods: From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports., Results: Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer., Conclusions: Persistent MetS was found to be associated with a high risk of incident cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was introduced globally in 2019 in response to the absence of a standardized reporting system for serous fluid cytology. This study presents experiences implementing this system across three distinct hospitals in Taiwan., Methods: A total of 6177 serous fluid specimens in three hospitals in Taiwan between 2018 and 2020 were retrospectively reviewed and reclassified according to the ISRSFC. Cytohistological correlation and chart review were further performed to investigate etiologies and risks of malignancy (ROMs)., Results: Reclassification showed that 34 (0.7%) of 4838 pleural effusions were nondiagnostic (ND), 4086 (84.5%) were negative for malignancy (NFM), 201 (4.2%) were atypia of undetermined significance (AUS), 92 (1.9%) were suspicious for malignancy (SFM), and 425 (8.8%) were malignant (MAL). The 1231 ascites cases contained 13 (1.1%) ND, 1004 (81.6%) NFM, 53 (4.3%) AUS, 31 (2.5%) SFM, and 130 (10.6%) MAL specimens. In pleural effusions, the ROM was 2.9% for ND, 14.0% for NFM, 52.2% for AUS, 85.9% for SFM, and 95.1% for MAL. In ascites, it was 15.4% for ND, 19.1% for NFM, 52.8% for AUS, 83.9% for SFM, and 92.3% for MAL. In pericardial effusions, it was 0.0% for ND, 11.6% for NFM, 30.8% for AUS, 100.0% for SFM, and 95.2% for MAL. Different effusions' most common benign and malignant etiologies were also disclosed., Conclusions: These multi-institutional data have determined the diagnostic usefulness of the ISRSFC, which provides pathologists and physicians with invaluable assistance in correctly classifying effusions for further management., (© 2023 American Cancer Society.)

Background: Research on the cardiovascular toxicity of angiogenesis inhibitors among patients with cancer in Taiwan is lacking. This observational study explored the risk of major adverse cardiovascular events (MACEs) associated with angiogenesis inhibitors in Taiwan., Methods and Results: We conducted a nested case-control study using the TCR (Taiwan Cancer Registry) linked with the Taiwan National Insurance Claim Database. We matched every case with 4 controls using risk-set sampling by index date, age, sex, cancer type, and cancer diagnosis date. Conditional logistic regression was used to evaluate the risks of MACEs and different cardiovascular events using propensity score adjustment or matching. Sensitivity analyses were used to evaluate the risks matched by cancer stages or exposure within 1 year. Among a cohort of 284 292 after the exclusion of prevalent cases, the incidences of MACEs among the overall cohort and those exposed to angiogenesis inhibitors were 22.5 and 32.5 events per 1000 person-years, respectively. We matched 17 817 cases with 70 740 controls, with a mean age of 74.9 years, and 56.8% of patients were men. After propensity score adjustment, angiogenesis inhibitors were associated with increased risks of MACEs (odds ratio, 4.56; 95% CI, 1.78-11.59). Significantly increased risks were noted for heart failure hospitalization, myocardial infarction, cerebrovascular accident, and venous thromboembolism, but not for new-onset atrial fibrillation. Similar results were observed after matching by cancer stage or restriction of 1-year exposure., Conclusions: Angiogenesis inhibitors were associated with increased risks of MACEs among patients with various malignancies in Taiwan but were not associated with new-onset atrial fibrillation.

Purpose: According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments., Methods: We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates., Results: We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20-0.22) and 0.22 (95 % CI: 0.21-0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001)., Conclusion: SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts of interest to declare. The data sets supporting the study conclusions are included within the manuscript., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD., Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan's National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization., Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions-especially cancer-and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1-2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1-2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years., Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Kao et al.)

Background: The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes., Methods: This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites., Results: The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk., Conclusions: The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature., Methods: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population., Results: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42)., Conclusion: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cancer treatment in female adolescent and young adult (AYA) cancer survivors (i.e., those diagnosed between 15 and 39 years of age) may adversely affect multiple bodily functions, including the reproductive system., Methods: We initially assembled a retrospective, nationwide population-based cohort study by linking data from two nationwide Taiwanese data sets. We subsequently identified first pregnancies and singleton births to AYA cancer survivors (2004-2018) and select AYA without a previous cancer diagnosis matched to AYA cancer survivors for maternal age and infant birth year., Results: The study cohort consisted of 5151 and 51,503 births to AYA cancer survivors and matched AYA without a previous cancer diagnosis, respectively. The odds for overall pregnancy complications (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18) and overall adverse obstetric outcomes (OR, 1.07; 95% CI, 1.01-1.13) were significantly increased in survivors compared with matched AYA without a previous cancer diagnosis. Specifically, cancer survivorship was associated with an increased risk of preterm labour, labour induction, and threatened abortion or threatened labour requiring hospitalisation., Conclusions: AYA cancer survivors are at increased risk for pregnancy complications and adverse obstetric outcomes. Efforts to integrate individualised care into clinical guidelines for preconception and prenatal care should be thoroughly explored., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The improvement of survival after hematopoietic stem cell transplantation has brought about a need to evaluate long-term complications, for instance, secondary malignancies. The risk of subsequent malignancies after hematopoietic stem cell transplantation must be clarified in a large population., Aims: To estimate the risk of secondary malignancies in hematopoietic stem cell transplantation survivors and compare it with the risk in patients without hematopoietic stem cell transplantation history., Study Design: We conducted a population-based retrospective cohort study of 3,059 hematopoietic stem cell transplantation recipients from the National Health Insurance Research Database of Taiwan, containing 1,378 autologous, 1,641 allogeneic, and 40 cord blood stem cell transplantation recipients between 2000 and 2013. A control group of 12,236 patients without an hematopoietic stem cell transplantation history was identified., Methods: The covariates included age, sex, comorbidities, stem cell source, facility level of care, and history of total body irradiation. Comorbidities were estimated by the revised Charlson comorbidity index, and a higher score suggested more severe comorbidity. Adjusted hazard ratios were determined by adjusting for age, sex, comorbidity, and facility level of care., Results: Overall, hematopoietic stem cell transplantation recipients had a higher risk of secondary malignancies with an adjusted hazard ratios of 1.348 ( p = 0.017). Being male and female (adjusted hazard ratios 1.395, p = 0.009 and adjusted hazard ratios 1.291, p = 0.042, respectively) and pre-hematopoietic stem cell transplantation total body irradiation (adjusted hazard ratios 1.591, p < 0.001) were correlated with a high risk of secondary malignancies. Among the subsequent neoplasms, bone cancer showed the highest risk (adjusted hazard ratios 27.899, p < 0.001), followed by laryngeal (adjusted hazard ratios 6.643, p < 0.001), kidney (adjusted hazard ratios 5.580, p < 0.001), esophageal, pancreatic, thyroid (adjusted hazard ratios 1.993, p < 0.001), and skin (adjusted hazard ratios 1.992, p < 0.001) cancers. The median follow-up duration was 2.16 years in the hematopoietic stem cell transplantation group and 2.57 years in the control group, and the overall median follow-up duration was 2.21 years., Conclusion: Medical practitioners should be aware of the high risk of secondary malignancies in hematopoietic stem cell transplantation recipients later in life. These recipients should be informed about the importance of regular follow-up and photoprotective measures. Lifelong surveillance is recommended.

Background: Childhood cancer may be related to maternal health in pregnancy. Maternal anemia is a common condition in pregnancy, especially in low-income countries, but the association between maternal anemia and childhood cancer has not been widely studied., Objective: To examine the potential relation between maternal anemia during pregnancy and childhood cancers in a population-based cohort study in Taiwan., Methods: We examined the relationship between maternal anemia and childhood cancer in Taiwan (N = 2160 cancer cases, 2,076,877 noncases). Cases were taken from the National Cancer Registry, and noncases were selected from birth records. Using national health registries, we obtained maternal anemia diagnoses. We estimated the risks for childhood cancers using Cox proportional hazard analysis., Results: There was an increased risk of cancers in children born to mothers with nutritional anemia (hazard ratio (HR): 1.32, 95% CI 0.99, 1.76). Iron deficiency anemia (HR: 1.30, 95% CI 0.97-1.75) carried an increased risk, while non-nutritional anemias were not associated with childhood cancer risk., Conclusion: Our results provide additional support for screening for anemia during pregnancy. Adequate nutrition and vitamin supplementation may help to prevent some childhood cancer., (© 2023 Wiley Periodicals LLC.)

Background: This cohort was established to evaluate whether 38-year radiation exposure (since the start of nuclear reactor operations) is related to cancer risk in residents near three nuclear power plants (NPPs)., Methods: This cohort study enrolled all residents who lived within 8 km of any of the three NPPs in Taiwan from 1978 to 2016 (n = 214,502; person-years = 4,660,189). The control population (n = 257,475; person-years = 6,282,390) from three towns comprised all residents having lived more than 15 km from all three NPPs. Radiation exposure will be assessed via computer programs GASPAR-II and LADTAP-II by following methodologies provided in the United States Nuclear Regulatory Commission regulatory guides. We calculated the cumulative individual tissue organ equivalent dose and cumulative effective dose for each resident. This study presents the number of new cancer cases and prevalence in the residence-nearest NPP group and control group in the 38-year research observation period., Conclusion: TNPECS provides a valuable platform for research and opens unique possibilities for testing whether radiation exposure since the start of operations of nuclear reactors will affect health across the life course. The release of radioactive nuclear species caused by the operation of NPPs caused residents to have an effective dose between 10 -7 and 10 -3 mSv/year. The mean cumulative medical radiation exposure dose between the residence-nearest NPP group and the control group was not different (7.69; standard deviation, 18.39 mSv and 7.61; standard deviation, 19.17 mSv; P = 0.114).

Palliative care has the ability to relieve both physical discomfort and psychological distress in terminally ill patients. However, unexpected death may still occur in palliative care settings. This study aimed to utilize Palliative Care Outcomes Collaboration (PCOC) data to better determine any associated factors which may surround unexpected death in palliative care settings. Data were extracted from the PCOC database by the palliative care team within Taichung Veterans General Hospital (TCVGH). Data of deceased patients were extracted during the period from January 2021 to December 2021 from multiple palliative care settings. The deaths of patients whose last recorded palliative phase was 1-3 were defined as unexpected. A total of 280 deceased patients were included, with mean age at death being 67.73, 61% being male, and 83.2% cancer patients. We discovered that shortness of breath, as assessed by the Symptom Assessment Scale (SAS), decreased risk of unexpected death (OR: 0.91, 95% CI: 0.84-0.98), while impending death discharge (OR: 3.93, 95% CI: 1.20-12.94) and a higher Australia-modified Karnofsky performance status (AKPS) score (OR: 1.15, 95% CI: 1.10-1.21) were associated with unexpected death. Thus, medical staff must inform the family of patients early on regarding any risk factors surrounding unexpected death to help everyone involved be prepared in advance.

Introduction: Sleep disorders, depression, and cancer have become increasingly prevalent worldwide. However, it is unknown whether coexistence of sleep disorders and depression influences the risk of cancer development. Therefore, we conducted a nationwide population-based study to examine this association among patients in Taiwan. Materials and Methods: A total of 105,071 individuals diagnosed with cancer and 420,284 age- and sex-matched patients without a diagnosis of cancer between 2000 and 2015 were identified from Taiwan’s National Health Insurance Research Database. The underlying chronic diseases of patients that may developed cancer were gathered and studied as the predictor. A multivariate Cox proportional odds model was used to estimate the crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to estimate the interaction effect between sleep disorders and depression on the risk of cancer. Results: After adjusting for age, sex, comorbidities, and other covariates, the cancer group was associated with increased exposure to sleep disorders than the non-cancer group (aOR = 1.440, 95% CI = 1.392−1.489, p < 0.001). In addition, patients with both sleep disorders and depression were at an even higher risk for cancer than the general population (aOR = 6.857, p < 0.001). Conclusions: This retrospective cohort study shows that patients with both sleep disorders and depression are at a higher risk of cancer. Clinically, a meticulous cancer risk evaluation is recommended for patients with both sleep disorders and depression.

Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age-matched unaffected siblings of patients with bipolar disorder and 101 422 age-matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio [OR] = 1.22, 95% confidence interval [CI]: [1.06, 1.40]) and unaffected siblings of such patients (OR = 1.17, 95% CI [1.02, 1.34]) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI [1.38, 2.61]) and unaffected siblings (OR = 1.65, 95% CI [1.19, 2.28]), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients., (© 2021 UICC.)

Smoking influences the risks of inflammatory bowel disease (IBD). A hospital-based cohort was conducted to evaluate the effect of smoking on the development and outcomes of IBD, with age, sex and comorbidities matched non-IBD controls from the National Health Interview Survey database of Taiwan. 700 IBD patients (360 ulcerative colitis (UC), 340 Crohn's disease (CD)) were analyzed for outcomes; and 575 patients (297 UC, 278 CD) were analyzed for prevalence. Smoking prevalence was significantly lower in UC patients than controls (20.9% vs. 30.4%, p < 0.01), but no difference between CD patients and controls (19.8% vs. 22.1%, p = 0.60). UC smokers had fewer admissions (1.6 vs. 2.5, p < 0.05) but higher rates of new cancer development (16% vs. 6.7%, p < 0.05) and mortality (16% vs. 4.9%, p < 0.01) than nonsmokers. CD smokers tended to have higher rates of stricturing and penetrating diseases (p < 0.05), and higher surgery risk (60.3% vs. 38.3%, p < 0.01) than nonsmokers. Smoking prevents UC occurrence and is associated with fewer hospitalization but increases risks of cancer and mortality. By contrast, smoking does not affect CD occurrence but is related to more aggressive behavior which results in a higher surgical rate., (© 2022. The Author(s).)

Background: Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study., Methods: Data on patients with opioid prescriptions, including morphine, fentanyl, pethidine, codeine, oxycodone, hydromorphone, and buprenorphine were collected using the Taiwan National Health Insurance Database (NHID)., Results: Our analysis of opioid prescriptions from 2008 to 2018 in Taiwan indicated that (1) A slow increase in prevalence of opioid prescription was found during the study period. Among the drugs studied, morphine accounted for the majority of the prescriptions written, with a gradual increase annually. Pethidine prescriptions showed a significant and rapid decline over the years; (2) medical centers prescribed the largest number of opioids, followed by regional hospitals, local hospitals, and clinics; (3) the number of prescriptions per year per capita in cancer group was much higher than that in noncancer group. In noncancer group, most of the prescriptions were used in acute pain service (98.7%); and (4) use of opioids increased with age in both cancer and noncancer patients., Conclusion: The total number of opioid prescriptions in Taiwan gradually increased annually, among which morphine was the most commonly used opioid. Cancer patients consumed more opioid prescriptions than noncancer patients and most of the prescriptions in noncancer patients were used in acute pain service. The number of prescriptions increased with the age of the patients in both cancer and noncancer patients. The low prescription rate of opioids in chronic pain in Taiwan is not similar as those in high opioid-consuming countries, such as United States., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Background: Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified., Methods: A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors., Results: After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer., Conclusions: We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different., (© 2022. The Author(s).)

The information on the outpatient expenditure of patients with oromaxillofacial cancer is minimal. This study aimed to compare the average annual expenditure on dental treatment for these patients 5 years before and 5 years after oromaxillofacial cancer diagnosis. In this study, 7731 patients who received oromaxillofacial cancer diagnosis in 2005 were selected from the Registry of Catastrophic Illness Database as the case-cohort. In the control cohort, 38,655 people without cancer were selected from the National Health Insurance Research Database, with the case-control ratio being 1:5. All participants were observed for 5 years before diagnosis and 5 years after diagnosis. The conditional logistic regression model was used to determine the odds ratios of annual expenditures incurred by participants in the case-cohort. The measurement results indicated that in the oromaxillofacial cancer cohort, the average annual dental expenditure levels at 1, 2, 3, 4, and 5 years after diagnosis were US $97.34, US $77.23, US $109.65, US $128.43, and US $128.03 and those at these years before diagnosis were US $37.52, US $32.10, US $31.86, US $29.14, and US $29.35, respectively. In conclusion, the average annual expenditure on the dental treatment of oromaxillofacial cancer patients after five years of diagnosis was increased compared to five years before diagnosis.

Background: Patients with childhood cancer are at increased risk for the development of second cancers., Methods: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed., Results: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer., Conclusion: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed., Competing Interests: Declaration of competing interest The authors confirm that there is no conflict of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

In this paper, the impact of both gender and age on the claim rates of dread disease and cancer insurance policies were examined using unique data taken from Taiwan's private health insurance policies issued by non-life insurers during the 2012 to 2015 policy years. Those aged 30-39 served as the reference group. For the total number of dread disease policies, male insureds had a higher non-cancer claim probability than female insureds, while an age under 20 was associated with much lower claim rates for dread disease policies than for ages over 50. The claim rate for dread disease policies increased rapidly beginning at age 40 for both cancerous and non-cancerous diseases amongst male insureds. Amongst female insureds, those under 20 had much lower claim rates for dread disease policies. Only those aged 50-59 had a higher claim rate for non-cancerous diseases. For the total number of cancer insurance policies, male insureds had lower claim rates than female insureds, with an upward trend being associated with age. For male (female) insureds aged over 40 (20), the claim rates of cancer increased with age.

Background/purpose: To quantify savings of loss-of-QALE (quality-adjusted life expectancy) and lifetime medical costs from prevention of different cancers., Methods: We collected nation-wide data on 808,700 new cancer cases of 14 different organ systems and followed them from 1998 to 2014 in Taiwan. We also collected 13,005 cancer patients from a medical center and 47,320 repeated measurements of quality of life (QoL) of EQ-5D to obtain utility values and multiplied them with the corresponding survival rates to calculate QALE. With Kaplan-Meier estimation to survival function to the end of follow-up, we extrapolated to lifetime through a rolling over algorithm on the logit transform of the survival ratio between the index cohort and age-, sex, and calendar year matched referents simulated from vital statistics. Lifetime costs for each cancer were estimated by multiplying survival with average monthly costs after adjustment with annual discount rate. The loss-of-QALE was estimated by the difference in QALE between the index cancer cohort and corresponding referents., Results: The dynamic changes and weighted averages of the QoL utility values of 14 different cancers ranged from 0.82 to 0.95. Successful prevention of liver, lung, esophagus, or nasopharynx cancer would save more than 10 quality-adjusted life years and more than 21,000 USD per case for both genders. Since the saving of loss-of-QALE was adjusted for different age, sex, and calendar-year distributions, it could be used in cost effectiveness evaluation., Conclusion: Savings of loss-of-QALE and lifetime costs could be used for comparison of prevention, diagnosis, treatment and rehabilitation from a lifetime horizon., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Cancer is increasing in rate globally and is leading cause of death among no communicable chronic diseases (NCDs) after cardiovascular disease (CVD). Most of the research focuses on the risk of occupational injury, job stress, mental illness, substance abuse and workplace safety in physicians and nurses. However, fewer studies have investigated the risk of cancer in pharmacists. We compared the matched general population to investigate the risk of cancer in pharmacists in Taiwan. Data were obtained from the Health and Welfare Data Science Center of the Ministry of Health and Welfare in Taiwan. We established a pharmacist group that included 11,568 pharmacists and selected a 4-fold comparison ( n = 46,272) for the non-clinics comparison group, frequency being matched by age, gender and Charlson Comorbidity Index (CCI) score. The pharmacists had a lower but non-significant risk of all cancer (Adjusted hazard ratio [aHR] = 0.96; 95% confidence interval [CI] = 0.85-1.07) compared with the general population. Female pharmacists had a higher risk of cancer than male pharmacists ([aHR] = 1.23; 95% CI = 1.06-1.43). Pharmacists had higher risks of breast cancer in females (aHR = 1.68; 95% CI = 1.35-2.08) and of prostate cancer in males (aHR = 2.18; 95% CI = 1.35-2.08) when compared with the general population. Occupational risk factors could play a role, but they were not evaluated. These epidemiological findings require additional studies to clarify cancer risk mechanisms in pharmacists.

The Taiwan Cancer Registry (TCR) is a nationwide population-based registry that collects the data of patients with newly diagnosed cancer from hospitals with ≥50 beds. TCR data are high quality in terms of completeness and timeliness. However, accuracy is also a crucial quality indicator. This study evaluated the accuracy rates of selected 55 major items in the long-form TCR data between 2014 and 2016 with 700 reported cases randomly selected from 25 long-form-reporting hospitals. We calculated the accuracy rates of the reported data by employing a reabstracted chart review. Among the 55 items, the accuracy rates of 38 (69%) were at least 95%, those of 10 (18%) were between 90% and 95%, those of 5 (9%) were between 85% and 90%, and the remaining 2 (4%) were between 80% and 85%. This demonstrates a high degree of accuracy in the TCR long-form data., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

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.)

This prospective study aimed to investigate the clinical and microbiological characteristics of different Aeromonas species. Clinical isolates of Aeromonas species between 2016 to 2018 were collected in a university hospital in southern Taiwan. The species was determined by rpoD or gyrB sequencing. A total of 222 Aeromonas isolates from 160 patients in 164 episodes were identified. The crude in-hospital mortality was 17.2%. The most frequently isolated species was Aeromonas veronii (30.6%), followed by A. caviae (24.8%), A. hydrophila (23%), and A. dhakensis (16.7%). The major clinical manifestations were primary bacteremia (31.1%), skin and soft tissue infection (22.6%), and biliary tract infection (18.3%). The most common underlying diseases were malignancy (45.1%), diabetes mellitus (27.4%), and liver cirrhosis or chronic hepatitis (26.2%). A. hydrophila and A. dhakensis predominated in the skin and soft tissue infection (p<0.0001), whereas A. vernoii and A. caviae prevailed in primary bacteremia and biliary tract infections (p=0.012). Pneumonia, malignancy, and ascF-ascG genotype were independent factors associated with mortality. Ertapenem susceptibility was decreased in A. sobria (42.9%), A. veronii (66.7%), A. dhakensis (73%), and A. hydrophila (84.3%). Cefotaxime resistance was found in 30.9% of A. caviae and 18.9% of A. dhakensis isolates, much more prevalent than the other species. The metallo-β-lactamase bla CphA was almost invariably present in A. dhakensis , A. hydrophila , and A. veronii (100%, 100% and 89.9%, respectively). Amp-C β-lactamases such as bla MOX and bla AQU-1 were identified in all A. caviae and 91.9% of A. dhakensis isolates. Cefepime, fluoroquinolones and tigecycline showed good in vitro activity against aeromonads., 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 © 2021 Chen, Su, Li, Tsai, Lo, Syue, Li, Lee, Lee, Ko and Chen.)

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).)

When a study population is relatively healthy, such as an occupational population, epidemiological studies are likely to underestimate risk. We used a case study on the cancer risk of workers with exposure to acid mists, a well-documented carcinogen, to demonstrate that using proportional mortality ratios (PMRs) is more appropriate than mortality ratios in assessing risk in terms of mortality. The study included 10,229 employees of a telecommunication company who worked in buildings with battery rooms. In these buildings, the battery rooms had the highest levels of sulfuric acid in the air (geometric mean = 10.7 μg/m 3 ). With the general population in Taiwan as a reference, a decreased standardized mortality ratio (0.42, p < 0.01) from all causes combined, between 1 January 1985 and 31 December 1996, was observed, indicating a healthy worker effect. When we reanalyzed the data using standardized PMR, elevated risks were observed for all cancers combined (1.46, p = 0.01) and cancers of the digestive organs and peritoneum (1.61, p = 0.02), especially stomach cancer (2.94, p = 0.01). The results showed that PMR can detect increases in mortality when a study population is generally healthier than the comparison population and call for further studies on the possible carcinogenic effects of low-level acid mist exposures on the stomach.

Early integration of palliative care for terminally ill cancer and non-cancer patients improves quality of life. However, there are sparse data on results of palliative care consultation services (PCCS) between cancer and non-cancer patients. In this 9-year observational study, data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill cancer and non-cancer patients who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in outcomes of PCCS, including duration of PCCS, the awareness of disease of patients and families before and after PCCS, status of PCCS termination, and DNR declaration before and after PCCS among cancer and non-cancer patients throughout study period. In total, 5223 cancer patients and 536 non-cancer patients received PCCS from 2011 to 2019. The number of people who received PCCS increased stably over the decade, both for cancer and non-cancer patients. The average duration of PCCS for cancer and non-cancer patients was 21.4 days and 18.4 days, respectively. Compared with non-cancer patients, cancer patients had longer duration of PCCS, less DNR declaration (82% vs. 98%, respectively), and more transfers to the palliative care unit (17% vs. 11%, respectively), or for palliative home care (12% vs.8%, respectively). Determinants of late referral to PCCS includes age (OR 0.992, 95% CI 0.987-0.996), DNR declaration after PCCS (OR 1.967, 95% CI 1.574-2.458), patients' awareness after PCCS (OR 0.754, 95% CI 0.635-0.895), and status of PCCS termination. This 9-year observational study showed that the trend of PCCS among cancer and non-cancer patients had changed over the duration of the study, and early integration of PCCS to all patients is essential for both cancer and non-cancer patients.

Purpose: This study assessed the benefits and efficacy of bariatric surgery (BS) in reducing the risk of cancer in Asians with morbid obesity., Methods: Records for patients aged between 18 and 55 years whose diagnoses corresponded with the ICD-9 codes for obesity and BS were extracted from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. The patients who underwent BS (BS group), those who did not undergo BS (NS group), and the general population (GP group) were propensity score matched. The outcome was newly diagnosed malignancy. Data were extracted from the Registry for Catastrophic Illness Patient Database (RCIPD) of the NHIRD., Results: The BS group developed significantly less malignancy (1.18%) than the GP group (1.46%, p = 0.0364). There was no statistically significant difference in malignancy risk between the BS and GP groups (aHR =1.00, p = 0.9997). The NS group developed significantly higher malignancy (2.48%) than the GP group (1.97%, p < 0.0001). There was a significantly higher malignancy risk in the NS group (aHR =1.22, p < 0.0001) than in the GP group. In the subgroup analysis, the malignancy risks of the NS group were significantly higher in the subgroup of men aged between 18 and 35 years (aHR =1.37, p = 0.003) and women aged between 18 and 35 years (aHR = 1.62, p < 0.0001), and 35-55 years (aHR = 1.27, p < 0.0001). All the subgroup analyses between the BS and GP groups demonstrated no significant differences., Conclusions: Our study demonstrated that BS reduced the risk of malignancy in patients with morbid obesity, particularly in women and young men., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We aimed to investigate the time-dependent association between cancer and the risk of tuberculosis (TB) before and after cancer diagnosis., Methods: This population-based cohort study incorporated the National Health Insurance Research Database and the National Health Interview Survey in Taiwan to estimate TB risk in cancer and noncancer populations. We estimated the period-specific incidence rate ratio (IRR) between cancer and risk of TB and used Cox proportional hazards models to estimate the average hazard ratio between cancer and TB during the peridiagnostic period., Results: From 2001 to 2015, 457 673 cancer and 3 738 122 noncancer individuals were enrolled. After stratifying the IRR of TB by year relative to the date of cancer diagnosis, the peak IRRs clustered in the year before and after the index date. In the peridiagnostic period of cancer, the adjusted hazard ratio was 2.29 (95% CI, 2.22-2.35) using the Cox model and 2.20 (95% CI, 2.09-2.32) after adjustment for missing confounders. Patients with cancers in the respiratory tract, upper digestive tract, and hematologic system were at the highest risk for TB., Conclusions: Cancer is an independent risk factor for TB, with the highest risk observed around the time of cancer diagnosis., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Due to advances in medical science and technology, the number of cancer survivors continues to increase. The workplace needs and employment difficulties cancer survivors face after treatment need to be addressed to protect these individuals' right to work and to maintain the overall labor force of the country. We conducted a retrospective cohort study with a follow-up period from 2004 to 2010. All data analyzed in the study were obtained from the Labor Insurance Database, the Taiwan Cancer Registry of the Ministry of Health and Welfare, and the National Health Insurance Research Database. The relationships between risk factors and the presence of returning to work were analyzed by a Cox proportional hazard model. The survival rates of patients with different cancer stages were evaluated using Kaplan-Meier survival analysis. Among the employees with an initial diagnosis of cancer, 70.4% remained employed through 1 year after the diagnosis, accounting for 83.4% of all cancer survivors; only 51.1% remained employed through 5 years after the diagnosis, accounting for 78.7% of all cancer survivors, a notable decrease. Age, gender, salary, treatment method, company size, and cancer stage were the factors that affected whether employees could return to work or not. The long-term survival of people diagnosed with cancer depends on their chances of returning to work. Strengthening existing return-to-work policies and assisting cancer survivors with returning to work after the treatment should be priorities for protecting these individuals' right to work and for maintaining the overall labor force.

Background/purpose: To verify the staging system of the American Joint Committee on Cancer (AJCC) 8th edition for uveal melanoma, and to propose the prognostic factors of uveal melanoma by a 45-year cohort study., Methods: We collected patients who underwent operation with pathological proof from 1973 to 2017. The demographic data including gender, age, laterality, metastatic pattern, and histopathology type were recorded. The predictability for survival and monotonicity of gradients of the AJCC 8th edition were evaluated. The prognostic factors for survival were analyzed by univariate and multivariate analysis., Results: A total of 72 patients were collected. The median age was 55 year-old (range 24-100). No specific gender predilection was revealed in our study. About 75.9% of metastases events happened in the first five-year of follow-up, and hepatic involvement was the most common. By the AJCC 8th edition, the distribution for stage I: II: III was 8 (11.1%), 37 (51.4%), and 27 (37.5%). The prognostic staging groups manifested fair predictability and monotonicity of gradients for survival outcome. The tumors with epithelioid cell type and ciliary body involvements had higher tumor-related mortality., Conclusion: The AJCC 8th edition prognostic staging groups for outcome prediction was validated. Periodic screening for metastases should be more frequent in the first five-year follow-up. The tumors with epithelioid cell pattern and ciliary body involvements were at risk of higher tumor-related mortality in Taiwanese patients., Competing Interests: Declaration of competing interest No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan's Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non-users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients' condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Using path modeling, this study aimed to explore whether mental adjustment was directly or indirectly related to comprehensive quality of life outcome (CoQoLO) among patients with terminal cancer. We conducted a cross-sectional designed study among patients with terminal cancer who underwent convenience sampling at our northern Taiwan clinic from August 2019 to August 2020. Patient characteristics data were collected via structured questionnaires, namely, the Mini-Mental Adjustment to Cancer Scale and the Comprehensive Quality of Life Outcome Inventory. Descriptive statistics and regression analyses were used to examine the relationship between mental adjustment and CoQoLO. Path analysis described the dependencies among variables. For the 117 enrolled patients analyzed, MAC (β = 1.2, 95% confidence interval (CI) = 0.8-1.6, p < 0.001) and living with others (β = 19.9, 95% CI = 4.1-35.7, p = 0.015) were significant predictors and correlated positively with a CoQoLO score. Path modeling showed that the patients' mental adjustment, economic status, perceived disease severity, palliative prognostic index, and symptom severity directly affected their CoQoLO. Our results indicate that the higher the mental adjustment, the better the CoQoLO among patients with terminal cancer. Thus, nurses need to assess mental adjustment levels when patients are hospitalized and accordingly develop interventions to improve the terminally ill patients' mental adjustment to the final stages of cancer, thereby helping them to achieve good CoQoLO.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43-14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To estimate the incidence of cancer among patients with ankylosing spondylitis (AS) and compare this risk with that of the general population. Method: We obtained data from Taiwan's National Health Insurance database on 19 289 patients with a first diagnosis of AS registered between 2000 and 2012 with no history of cancer before the diagnosis of AS. Standardized incidence ratios (SIRs) for all cancers and for site-specific cancers were used to assess whether AS was associated with an increased risk of cancer. Results: During the follow-up period, 485 patients developed cancer. The incidence rate was therefore 256.3 per 100 000 person-years. Compared with the general population, patients with AS had an increased risk of cancer [SIR 1.33, 95% confidence interval (CI) 1.20-1.47]. The SIR of cancer was higher in older patients; the risk increased from 8 years after initial diagnosis. Among solid tumours, the risk of melanoma was the highest (SIR 4.64, 95% CI 1.93-11.15), followed by prostate (SIR 2.53, 95% CI 2.01-3.19), thyroid (SIR 2.09, 95% CI 1.45-3.00), and bone cancer (SIR 2.00, 95% CI 1.01-3.99). Among haematological cancers, the risk of leukaemia was the highest (SIR 1.94, 95% CI 1.21-3.12). By contrast, the risks of oesophageal and oral cancers decreased in patients with AS. Conclusion: This nationwide population-based cohort study demonstrated that patients with AS in Taiwan are at an increased risk of cancer, particularly melanoma; prostate, thyroid, and bone cancers; and haematological malignancies.

Background: Existing epidemiological evidence regarding the association between the long-term use of drugs and cancer risk remains controversial., Objective: We aimed to have a comprehensive view of the cancer risk of the long-term use of drugs., Methods: A nationwide population-based, nested, case-control study was conducted within the National Health Insurance Research Database sample cohort of 1999 to 2013 in Taiwan. We identified cases in adults aged 20 years and older who were receiving treatment for at least two months before the index date. We randomly selected control patients from the patients without a cancer diagnosis during the 15 years (1999-2013) of the study period. Case and control patients were matched 1:4 based on age, sex, and visit date. Conditional logistic regression was used to estimate the association between drug exposure and cancer risk by adjusting potential confounders such as drugs and comorbidities., Results: There were 79,245 cancer cases and 316,980 matched controls included in this study. Of the 45,368 associations, there were 2419, 1302, 662, and 366 associations found statistically significant at a level of P<.05, P<.01, P<.001, and P<.0001, respectively. Benzodiazepine derivatives were associated with an increased risk of brain cancer (adjusted odds ratio [AOR] 1.379, 95% CI 1.138-1.670; P=.001). Statins were associated with a reduced risk of liver cancer (AOR 0.470, 95% CI 0.426-0.517; P<.0001) and gastric cancer (AOR 0.781, 95% CI 0.678-0.900; P<.001). Our web-based system, which collected comprehensive data of associations, contained 2 domains: (1) the drug and cancer association page and (2) the overview page., Conclusions: Our web-based system provides an overview of comprehensive quantified data of drug-cancer associations. With all the quantified data visualized, the system is expected to facilitate further research on cancer risk and prevention, potentially serving as a stepping-stone to consulting and exploring associations between the long-term use of drugs and cancer risk., (©Hsuan-Chia Yang, Md Mohaimenul Islam, Phung Anh Alex Nguyen, Ching-Huan Wang, Tahmina Nasrin Poly, Chih-Wei Huang, Yu-Chuan Jack Li. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 15.02.2021.)