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Background: OpenAI released versions ChatGPT-3.5 and GPT-4 between 2022 and 2023. GPT-3.5 has demonstrated proficiency in various examinations, particularly the United States Medical Licensing Examination. However, GPT-4 has more advanced capabilities., Objective: This study aims to examine the efficacy of GPT-3.5 and GPT-4 within the Taiwan National Pharmacist Licensing Examination and to ascertain their utility and potential application in clinical pharmacy and education., Methods: The pharmacist examination in Taiwan consists of 2 stages: basic subjects and clinical subjects. In this study, exam questions were manually fed into the GPT-3.5 and GPT-4 models, and their responses were recorded; graphic-based questions were excluded. This study encompassed three steps: (1) determining the answering accuracy of GPT-3.5 and GPT-4, (2) categorizing question types and observing differences in model performance across these categories, and (3) comparing model performance on calculation and situational questions. Microsoft Excel and R software were used for statistical analyses., Results: GPT-4 achieved an accuracy rate of 72.9%, overshadowing GPT-3.5, which achieved 59.1% (P<.001). In the basic subjects category, GPT-4 significantly outperformed GPT-3.5 (73.4% vs 53.2%; P<.001). However, in clinical subjects, only minor differences in accuracy were observed. Specifically, GPT-4 outperformed GPT-3.5 in the calculation and situational questions., Conclusions: This study demonstrates that GPT-4 outperforms GPT-3.5 in the Taiwan National Pharmacist Licensing Examination, particularly in basic subjects. While GPT-4 shows potential for use in clinical practice and pharmacy education, its limitations warrant caution. Future research should focus on refining prompts, improving model stability, integrating medical databases, and designing questions that better assess student competence and minimize guessing., (© Ying-Mei Wang, Hung-Wei Shen, Tzeng-Ji Chen, Shu-Chiung Chiang, Ting-Guan Lin. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

Introduction: Emotional variability has been identified as a risk factor for adolescent psychopathology. This study explored the cross-sectional and prospective associations between emotional variability and suicidal ideation and examined the moderating role of parent-adolescent connectedness., Methods: Participants included 108 Taiwanese late adolescents (Mage = 18.53, SDage = 0.39; 64% female) who completed ecological momentary assessment (EMA) over 14 days, and baseline and follow-up assessments over 6 months., Results: Results indicated that while negative emotional (NE) and positive emotional (PE) variability were not associated with suicidal ideation at baseline, both predicted increased suicidal ideation 6 months later. Furthermore, parent-adolescent connectedness moderated the relationship between NE variability and suicidal ideation, with high connectedness mitigating the adverse effects of NE variability., Conclusions: These findings suggest that emotional variability is a key predictor for the development of suicidal ideation and highlight the protective role of parent-adolescent connectedness. Interventions promoting family connectedness may be effective in reducing suicidal risk among emotionally variable youth., (© 2024 American Association of Suicidology.)

Background: Breast cancer patients receiving chemotherapy may develop a serious complication called febrile neutropenia (FN). We aimed to validate and compare three existing FN prediction models for breast cancer patients receiving chemotherapy in Taiwan., Patients and Methods: This was a retrospective observational real-world study. Data were acquired from the clinical research databases of three study hospitals. Breast cancer patients who have received at least one antineoplastic chemotherapy drug were chosen for the analysis. For evaluating the occurrence of FN, we used both broad (a body temperature above 38°C with an absolute neutrophil count (ANC) below 0.5 × 10 9 /L or a body temperature above 38°C with a diagnosis of neutropenia) and narrow definitions (having both fever and neutropenia diagnoses or having both neutropenia and infection diagnoses). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each selected FN model., Results: Among the 1903 patients identified, when the broad and narrow definitions of FN were applied, 70 (3.7%) and 60 (3.2%) patients developed FN in the first cycle, respectively. Using the broad FN definition, Aagaard's model was the highest in sensitivity (90.0%), followed by Chantharakhit's (40.0%) and Chen's (7.2%); in specificity, Chen's (93.6%) was the highest. In addition, the accuracy was highest with the Chen model (90.4%). All three models' PPVs were low, ranging from 0.5% to 4.2%, but all three models' NPVs were over 96.3%. When the narrow FN definition was used, Chantharakhit's model showed a relatively high improvement in sensitivity (53.3%) and PPV (3.9%) while negligible increases or even slight decreases were seen in the other two models and in the other performance indicators of Chantharakhit's model., Conclusion: The results of this study provide important information for clinicians when selecting models to identify patients at high-risk of FN. As the model performance observed was less than satisfactory, improving the prediction ability of the models is needed., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Building on the sensitization hypothesis, the present work aimed to examine how parent-adolescent conflict might be associated with heightened emotional reactivity to peer conflicts, which in turn shape the development of adolescent internalizing psychopathology. Participants were 108 Taiwanese adolescents between the ages of 18 and 19 ( M age = 18.53, SD age = 0.39; 64% female) who completed baseline assessments, 14-day daily surveys, and 6-month follow-up assessments. Emotional reactivity was measured by calculating the daily association between peer conflict and positive and negative emotions. Results indicated that greater baseline parent-adolescent conflict was associated with higher negative emotional reactivity to peer conflicts, which then predicted increased depressive symptoms and anxiety symptoms 6 months later. Moreover, greater positive emotional reactivity to peer conflicts (i.e., more declines in positive emotions in response to peer conflicts) predicted increased depressive symptoms. Thus, the findings of the current study support and extend the sensitization hypothesis and suggest that parent-adolescent conflict may contribute to family-of-origin sensitization in non-familial, interpersonal contexts. The results have key implications for understanding adolescent developmental psychopathology associated with family conflicts and emotional reactivity.

Objective: Simultaneous use of alcohol and cannabis is prevalent among young adults and associated with heightened risk for harms. Individuals who engage in simultaneous use report a variety of types of use occasions and risk factors driving use occasions are unique and dynamic in nature. Intervention content may thus need to adapt to address differences across occasions. As a first step toward developing momentary interventions, it is critical to identify whether and when psychosocial factors are associated with simultaneous use. The present study aimed to identify the most critical morning and afternoon risk factors for later-day simultaneous use., Method: Participants were 119 young adult college students (63% female; 73% non-Hispanic/Latinx White) who reported weekly simultaneous use at baseline. Participants completed an online baseline survey and an ecological momentary assessment protocol (eight prompts/day) across four consecutive weekends., Results: Multilevel models revealed that morning willingness to engage in simultaneous use and social motives were associated with higher odds of later-day simultaneous use. Afternoon willingness and cross-fading motives were significantly associated with higher odds of later-day use. Morning and afternoon conformity motives were associated with lower odds of use., Conclusions: Early-day willingness to use, morning social motives, and afternoon cross-fading motives were the most salient predictors of later-day simultaneous use and may serve as viable tailoring variables to incorporate in momentary interventions. As simultaneous use episodes commonly start after 9 p.m., there is a large time window in between early-day predictors and use behavior during which timely intervention content could be delivered. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emotional reactivity has been linked to adolescent psychopathology and mental health problems. However, limited research has investigated the distinct associations between emotional reactivity in multiple interpersonal contexts and the development of adolescent psychopathology. The current study examined emotional reactivity to interparental conflict, parent-adolescent conflict, and school problems as predictors of adolescent internalizing problems, depressive symptoms, and anxiety symptoms six months later. The sample included 139 adolescents (54% girls; M age = 13.30, SD age = 0.73) and their parents who completed 10-day daily reports and 6-month follow-up assessments in Taiwan. Results showed that negative emotional reactivity to interparental conflict was associated with increased internalizing problems, depressive symptoms, and anxiety symptoms, after controlling for emotional reactivity to parent-adolescent conflict and school problems, outcomes at baseline, mean negative emotions, and sex. Furthermore, the associations between both positive and negative emotional reactivity to interparental conflict and adolescent anxiety symptoms was stronger for girls than boys. Findings suggested that heightened emotional reactivity to interparental conflict is a risk factor for predicting adolescent psychopathology, especially for girls' anxiety symptoms. Results highlight the importance of emotional reactivity across multiple interpersonal contexts in adolescence., Competing Interests: Compliance with Ethical Standards. Funding: Data collection was supported by the Taiwan Ministry of Science and Technology (MOST 110-2410-H-004 -109 -). MOST had no role in the study design, collection, analysis, or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. Shou-Chun Chiang was supported by the Prevention and Methodology Training Program (T32 DA017629; MPIs: J. Maggs & S. Lanza) with funding from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethics Approval: The study was approved and followed by the Institutional Review Board of the National Chengchi University (NCCU-REC-202105-I038). The study is in accordance with the Declaration of Helsinki. Consent to Participate: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Emotion dysregulation is linked to adolescent psychological problems. However, little is known about how lability in daily closeness of parent-adolescent dyads affects the development of emotion dysregulation. This study examined how closeness lability with parents was associated with emotion dysregulation 12 months later. The sample included 144 adolescents (M = 14.62, SD = 0.83) who participated in a baseline assessment, 21-day daily diaries, and a 12-month follow-up assessment. Parents and adolescents both reported adolescent emotion dysregulation at baseline and follow-up assessments, while adolescents reported daily parent-adolescent closeness. Results indicate that lability in father-adolescent closeness was associated with increased emotion dysregulation at 12 months reported by adolescents. However, lability in mother-adolescent closeness was not associated with adolescent emotion dysregulation. Moreover, when baseline father-adolescent closeness was high, greater lability in father-adolescent closeness was associated with decreased emotion dysregulation. Findings indicate that daily fluctuations in father-adolescent closeness are a key family characteristic that links to long-term adolescent emotion dysregulation., (© 2024 The Authors. Family Process published by Wiley Periodicals LLC on behalf of Family Process Institute.)

Prior research suggests that feeling needed and useful plays a central role in adolescent psychosocial development and well-being. However, little is known about whether feeling needed and useful benefits adolescents' well-being in daily life, especially for those with suicidal ideation. The current study examined the daily association between feeling needed and useful and emotional and social well-being in a daily diary sample of adolescents (N = 122; M age  = 12.64) with and without suicidal ideation. Results from multilevel modeling showed that on days when youth experienced higher levels of feeling needed and useful, they reported lower negative emotions, higher positive emotions, and increased family connectedness. Furthermore, significant moderation effects indicated that daily feelings of being needed and useful were associated with higher positive emotions and peer connectedness only for youth with suicidal ideation. The findings support the importance of feeling needed and useful in adolescent development and highlight its beneficial effects among adolescents at risk for suicide., (© 2025 Society for Research on Adolescence.)

Emotion contagion between parents and adolescents is crucial for understanding adolescents' emotional experiences. However, little is known about how emotion contagion unfolds in daily life and the unique contributions of parent-adolescent relationships. This study examines the associations between parent and adolescent positive and negative emotions, and the moderating role of daily parent-adolescent connectedness. Participants were 191 Taiwanese adolescents (M age  = 12.93; SD age  = 0.75; 53% female) and their parents who completed 10-day diary reports of emotions and parent-adolescent connectedness. Results indicate that higher daily parent negative emotions were associated with more adolescent negative emotions, and higher average parent negative emotions were associated with greater average negative emotions and fewer positive emotions in adolescents. Similar bidirectional effects were also found in adolescent-to-parent emotion contagion. Moreover, on days when connectedness was high, parent negative emotions were not associated with adolescent negative emotions but were related to increased positive emotions. Parent positive emotions were related to more positive emotions and fewer negative emotions when connectedness was low. The findings provide important insights into daily parent-adolescent emotion contagion and highlight parent-adolescent connectedness as a modifying factor in shaping dyadic emotional processes., (© 2024 Society for Research on Adolescence.)

Background: The resettlement of Afghan refugees in Oklahoma City, OK, provides a critical context for examining the mental health challenges faced by this population due to post-migration stressors., Methods: This study utilized online surveys to recently resettled Afghan refugees in Oklahoma City, with support provided by bilingual research assistants to accommodate low literacy rates. Surveys, initially in English, were professionally translated into Dari and Pashto and validated through back-translation., Results: Participants ( N  = 348) were majority of Pashtun ethnicity. High rates of mental health issues were evident, with 62.1 % of participants screening positive for depression and 20.1 % for probable GAD. Logistic regression analysis revealed that lower pre-migration socioeconomic status (SES) and high post-migration stressors such as discrimination and loss of homeland were significantly associated with increased mental health problems. Stress related to the worry for and loss of their homeland was a substantial predictor of high distress (AOR = 2.71, p  < 0.001), anxiety (AOR = 1.99, p  = 0.001) and depression (AOR = 2.65, p <.001). Experiences of discrimination post-resettlement was also associated with anxiety (AOR 4.92, p  < 0.001)., Discussion: The findings highlight the profound impact of post-migration stressors on the mental health of Afghan refugees. This study underscores the need for targeted interventions to address the specific challenges faced by refugees, such as language barriers, employment, legal support, and anti-discrimination measures, to facilitate better integration and improve mental health outcomes., Conclusion: Enhanced community integration programs and comprehensive support services are essential to mitigate the mental health challenges faced by Afghan refugees, suggesting a broader application for such approaches in similar resettlement contexts globally., Competing Interests: 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., (© 2024 The Author(s).)

Cancer cells have a high demand for sugars and express diverse carbohydrate receptors, offering opportunities to improve delivery with multivalent glycopolymer materials. However, effectively delivering glycopolymers to tumors while inhibiting cancer cell activity, altering cellular metabolism, and reversing tumor-associated macrophage (TAM) polarization to overcome immunosuppression remains a challenging area of research due to the lack of reagents capable of simultaneously achieving these objectives. Here, the glycopolymer-like condensed nanoparticle (∼60 nm) was developed by a one-pot carbonization reaction with a single precursor, promoting multivalent interactions for the galactose-related receptors of the M2 macrophage (TAM) and thereby regulating the STAT3/NF-κB pathways. The subsequently induced M2-to-M1 transition was increased with the condensed level of glycopolymer-like nanoparticles. We found that the activation of the glycopolymer-like condensed galactose (CG) nanoparticles influenced monocarboxylate transporter 4 (MCT-4) function, which caused inhibited lactate efflux (similar to inhibitor effects) from cancer cells. Upon internalization via galactose-related endocytosis, CG NPs induced cellular reactive oxygen species (ROS), leading to dual functionalities of cancer cell death and M2-to-M1 macrophage polarization, thereby reducing the tumor's acidic microenvironment and immunosuppression. Blocking the nanoparticle-MCT-4 interaction with antibodies reduced their toxicity in glioblastoma (GBM) and affected macrophage polarization. In orthotopic GBM and pancreatic cancer models, the nanoparticles remodeled the tumor microenvironment from "cold" to "hot", enhancing the efficacy of anti-PD-L1/anti-PD-1 therapy by promoting macrophage polarization and activating cytotoxic T lymphocytes (CTLs) and dendritic cells (DCs). These findings suggest that glycopolymer-like nanoparticles hold promise as a galactose-elicited adjuvant for precise immunotherapy, particularly in targeting hard-to-treat cancers.

Objective: As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited., Methods: Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan-Meier survival analyses., Results: The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test)., Conclusions: This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes., (© 2024. The Author(s).)

Objectives: The cultural stress theory posits that immigrants experience a constellation of cultural stressors such as discrimination that could exacerbate alcohol- and other substance-related problems. Drawing on cultural stress theory, this study investigated the age-varying association between past-year discrimination and substance use disorders (SUDs) among Latin American immigrants aged 18-60 and whether childhood family support moderated the above association., Method: We used data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) among adults aged 18-60 who identified as a Latin American immigrant ( N = 3,049; 48% female)., Results: Time-varying effect models (TVEMs) revealed that experiencing past-year discrimination was associated with greater odds of having a SUD during young and middle adulthood for Latin American immigrants. Furthermore, for immigrants with lower childhood family support, discrimination was associated with SUD risk in young and middle adulthood., Conclusion: The present study documents that past-year discrimination was linked to greater SUD risk during young and middle adulthood. Childhood family support may serve as a protective factor in the association between discrimination and risk for SUD among Latin American immigrants. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: The shortage and distribution of nurses affect healthcare access in aging societies. Limited research has explored the nursing workforce in clinics, which is vital for healthcare delivery. This study aimed to investigate the shortage and distribution of nurses in clinics in Taiwan, considering geographical, institutional, and specialty variations., Methods: We conducted a cross-sectional analysis of the national nursing workforce in Western medicine clinics in Taiwan using open government data. The nursing practice rate (NPR) was calculated. The ratio of clinics employing nurses (RCN) was determined by calculating the percentage of clinics with nurses in each category. A logistic regression model was fitted to examine the factors associated with nurse employment, including urbanization level and different specialty clinics. Adjusted odds ratios (OR) and 95% CIs were calculated., Results: The study revealed an overall NPR as low as 59.1%, and a decreasing trend with age. Among the 11 706 clinics in the study, nearly a quarter did not employ nurses, with an overall RCN of 72.3%. Urbanization level and clinic specialty were associated with nurse employment ( p < 0.05). After adjusting for urbanization level, the fitted regression model identified the top three specialties as plastic surgery (OR = 11.37, RCN = 96.8%), internal medicine (OR = 1.94, RCN = 84.1%), and orthopedics (OR = 1.89, RCN = 83.6%), while the bottom three were otolaryngology (OR = 0.59, RCN = 61.5%), psychiatry (OR = 0.49, RCN = 57.1%), and rehabilitation medicine (OR = 0.30, RCN = 45.2%). Nurses were more likely to be employed in areas at urbanization level 1 (OR = 1.17), 3 (OR = 1.37), and 6 (OR = 1.48), which represent highly urbanized areas within the urban, suburban, and rural categories, respectively, than in urbanization level 4., Conclusion: Clinics in Taiwan showed nursing shortages and maldistribution, with 72.3% RCN and variations based on urbanization and specialty. These factors may be considered in nursing research conducted in other countries to inform future workforce planning., Competing Interests: Conflicts of interest: Dr. Tzeng-Ji Chen, and Dr. Yu-Chun Chen, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Despite the importance of emotions in our daily lives, less is known about the role of emotional reactivity in suicidal risk. This brief study investigated whether emotional reactivity is associated with adolescent suicidal ideation six months later. Participants were 139 adolescents (55% female; M age = 12.79, SD age = 0.73) who completed baseline assessments, a 10-day daily diary protocol, and six-month follow-up assessments. Results showed that higher emotional reactivity indicated by increased negative emotions and decreased positive emotions was associated with a greater risk for suicidal ideation. The findings suggest that adolescents with greater emotional reactivity to daily school problems had elevated risks for suicidal ideation. This study supports the importance of emotional reactivity in daily life for preventing adolescent suicidal ideation.

Objectives: To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration., Methods: A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results., Results: In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim., Conclusions: Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Child maltreatment is associated with substance use beginning in adolescence and throughout early adulthood. Substance use disorders (SUD) are most likely to develop during emerging adulthood (18-25 years old). Thus, to develop effective substance use prevention strategies, it is useful to know the ages at which associations between maltreatment exposure (prior to age 18) and SUD are most strongly tied. This study examined the age-varying association between child maltreatment and past-year SUD in emerging adulthood by sex and by maltreatment type using time-varying effect models (TVEM). Data were from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III). The analytic sample consisted of 5194 emerging adults. The association was strongest at younger ages, with individuals who experienced child maltreatment having three times greater odds of reporting SUD in the past-year. Differential associations were found by sex, racial-ethnic group, and maltreatment type across age. Prevention efforts may be more effective if their development is informed by these important differences and targeted at emerging adults rather than adolescents., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study investigated the associations between early parental warmth, harsh discipline, and adolescent depressive symptoms from early to late adolescence, with attention to gender differences in these associations. The sample was drawn from a longitudinal study, the Taiwan Youth Project, including 2,690 Taiwanese adolescents from wave 1 in 2000 (first year in junior high school) to wave 6 (third year in high school) in 2005. The results showed a nonlinear developmental trajectory of adolescent depressive symptoms during the middle- to high-school period. Harsh discipline was associated with the significantly higher initial presence and faster growth rate of depressive symptoms, while parental warmth and monitoring were associated with the significantly lower initial presence of depressive symptoms. In addition, female adolescents displayed a higher initial level of depressive symptoms than males when parents exercised higher levels of monitoring and harsh discipline. Finally, we provided suggestions for practice and research., Competing Interests: Conflicts of interest: none

What Is This Summary About?: The aim of this plain language review article is to help you to understand biosimilar medicines (called biosimilars) by giving a summary of biologic medicines and biosimilars. It is based on the experience of an international panel of physicians with expertise on biosimilars who discussed and agreed on the topics and information included in this review article. Biologic medicines are medicines that come from living organisms such as bacteria and animal or plant cells. Biosimilars are a group of approved biologic medicines that are similar to original biologic medicines that are already available. This review explains how biosimilars are developed and approved, and how they are used to treat people with cancer. It also answers some common important questions people with cancer might have when taking biosimilars. The purpose of this plain language review is to help you to understand the findings from recent research. This review reports information from peer-reviewed literature and other sources available in the public domain (e.g., regulatory documents or product information labels). The findings may differ from those of other review articles. Health professionals should make treatment decisions based on all available evidence.

The purpose of this article is to build upon prior work in social media research and ethics by highlighting an important and as yet underdeveloped research consideration: how should we consider vulnerability when conducting public health research in the social media environment? The use of social media in public health, both platforms and their data, has advanced the field dramatically over the past 2 decades. Applied public health research in the social media space has led to more robust surveillance tools and analytic strategies, more targeted recruitment activities, and more tailored health education. Ethical guidelines when using social media for public health research must also expand alongside these increasing capabilities and uses. Privacy, consent, and confidentiality have been hallmarks for ethical frameworks both in public health and social media research. To date, public health ethics scholarship has focused largely on practical guidelines and considerations for writing and reviewing social media research protocols. Such ethical guidelines have included collecting public data, reporting anonymized or aggregate results, and obtaining informed consent virtually. Our pursuit of the question related to vulnerability and public health research in the social media environment extends this foundational work in ethical guidelines and seeks to advance research in this field and to provide a solid ethical footing on which future research can thrive., (©Philip M Massey, Regan M Murray, Shawn C Chiang, Alex M Russell, Michael A Yudell. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 29.12.2023.)

With roots as a public health campaign in the United Kingdom, "Dry January" is a temporary alcohol abstinence initiative encouraging participants to abstain from alcohol use during the month of January. Dry January has become a cultural phenomenon, gaining increasing news media attention and social media engagement. Given the utility of capturing naturalistic discussions around health topics on social media, we examined Twitter chatter about Dry January and associated temporary abstinence experiences. Public tweets were collected containing the search terms "dry january" or "dryjanuary" posted between 15 December and 15 February across 3 years (2020-2). A random subsample stratified by year (n = 3145) was pulled for manual content analysis by trained coders. Final codebook accounted for user sentiment toward Dry January, user account type, and themes related to Dry January participation. Engagement metadata (e.g. likes) were also collected. Though user sentiment was mixed, most tweets expressed positive or neutral sentiment toward Dry January (74.7%). Common themes included encouragement and support for Dry January participation (14.1%), experimentation with and promotion of nonalcoholic drinks (14.0%), and benefits derived from Dry January participation (10.4%). While there is promise in the movement to promote positive alcohol-related behavior change, increased efforts to deliver the campaign within a public health context are needed. Health communication campaigns designed to inform participants about evidence-based treatment and recovery support services proven to help people quit or cut down on their drinking are likely to maximize benefits., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Parenting stress and child psychopathology are closely linked in parent-child dyads, but how the bidirectional association varies across childhood and adolescence, and shifts depending on maternal affection are not well understood. Guided by the transactional model of development, this longitudinal, prospective study examined the bidirectional relations between parenting stress and child internalizing and externalizing problems and investigated the moderating role of maternal affection from childhood to adolescence. Participants were from the Future of Families and Child Wellbeing Study, a diverse, nationally representative sample of 2,143 caregiving mothers who completed assessments at children ages 5, 9, and 15. Using cross-lagged panel modeling, we found bidirectional effects between parenting stress and child internalizing and externalizing problems. However, additional multigroup analyses showed that bidirectional associations depend on the levels of maternal affection. In the high maternal affection group, parenting stress at age 5 predicted higher internalizing and externalizing problems at age 9, and reverse child-to-parent paths were found from age 9 to age 15. In contrast, only one cross-lagged path was found in the low maternal affection group. Findings suggest that maternal affection can heighten the transactional associations between parenting stress and child psychopathology.

Introduction: In adolescence, life satisfaction is an early indicator of later psychological well-being. However, researchers know little about how daily family relationships shape adolescent life satisfaction. The current study examined the day-to-day associations between parent-adolescent relationships and life satisfaction, and whether adolescent emotion dysregulation moderated these associations., Methods: A total of 191 adolescents (M age  = 12.93, SD age  = 0.75, 53% female) recruited from junior high schools in Taiwan participated in a 10-day daily diary protocol. We conducted multilevel analyses to examine within-family and between-family processes., Results: At the within-family level, adolescents reported higher life satisfaction on days when parent-adolescent closeness was higher, but lower life satisfaction on days when parent-adolescent conflict was higher. At the between-family level, higher parent-adolescent closeness was associated with greater life satisfaction on average, while parent-adolescent conflict was not related to adolescent life satisfaction. Cross-level interactions indicated that within-family changes in parent-adolescent closeness and conflict were only associated with life satisfaction for adolescents with higher levels of emotion dysregulation, indicating emotion dysregulation may intensify the role of daily parent-adolescent relationships in shaping adolescent life satisfaction., Conclusions: This study expands current literature and provides novel evidence that changes in day-to-day parent-adolescent relationships have important implications for adolescent life satisfaction, especially for youth higher in emotion dysregulation. The findings underscore the importance of evaluating family and individual characteristics to better support adolescent well-being., (© 2023 The Authors. Journal of Adolescence published by Wiley Periodicals LLC on behalf of Foundation for Professionals in Services to Adolescents.)

Background and Objectives: Myelosuppressive chemotherapy is effective for breast cancer but carries a potential risk of febrile neutropenia (FN). Clinical practice guidelines have recommended prophylaxis with granulocyte colony-stimulating factor (G-CSF) to reduce the incidence of FN in patients receiving chemotherapy. We aimed to examine the use of G-CSFs for primary prophylaxis for FN and to see whether it follows the guidelines. In addition, we examined the changes in the use of long-acting and short-acting G-CSFs in patients with breast cancer over the past ten years., Methods: This was a retrospective observational real-world study. The data were obtained from the clinical research database of three hospitals affiliated with Taipei Medical University. Patients with breast cancer who initiated their first chemotherapy regimen between January 1, 2011, and December 31, 2020, were identified by the ICD codes and their use of filgrastim or pegfilgrastim was identified by the Anatomical Therapeutic Chemical codes. Whether and how G-CSF was prescribed during the study patients' first chemotherapy regimen was examined, and the annual change in the total number of short- and long-acting G-CSFs prescribed to the study patients from 2011 to 2020 was analyzed., Results: Among the 2,444 patients who were prescribed at least one of the examined 15 breast cancer chemotherapy drugs, 1,414 did not use any G-CSFs during their first chemotherapy regimen while 145 used G-CSFs for primary prophylaxis and 185 for treatment. Among the patients receiving high FN risk regimens, only 8.6% used G-CSF for primary prophylaxis. The average (± SD) number of days for short-acting G-CSF use was 2.3 (± 1.5) days with a median of 2 days. In addition, it was found that there was a significant reduction in long-acting G-CSF use (p = 0.03) whereas the changes in short-acting G-CSF use over time were not significant (p = 0.50)., Conclusions: Our study results show that G-CSFs are used for primary prophylaxis in a small percentage of patients with breast cancer and the duration of short-acting G-CSF use is relatively short. Considering the significant clinical and economic impact of FN, it is hoped that the prescription patterns of G-CSFs observed can provide an important reference for future clinical practice and reimbursement policy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Blackout drinking, or alcohol-induced memory loss during a drinking occasion, is associated with additional negative alcohol-related outcomes. Brief motivational interventions targeting higher-risk alcohol use behavior have largely ignored blackout drinking. Including personalized information on blackout drinking could maximize intervention impact. To move toward incorporating content on blackout drinking in prevention and intervention materials, it is imperative to understand individual-level differences in blackout drinking. The current study aimed to identify latent profiles of young adults based on blackout drinking experiences and to examine person-level predictors and outcomes associated with profile membership., Method: Participants were 542 young adults (ages 18-30) who reported 1+ past-year blackout episodes. Fifty-three percent of participants were female and 64% identified as non-Hispanic/Latinx white., Results: Four latent profiles were identified based on blackout drinking frequency, blackout intentions, blackout expectancies, and age of first blackout: Low-Risk Blackout (35% of the sample), Experimental Blackout (23%), At-Risk Blackout (16%), and High-Risk Blackout (26%). Profiles varied by demographic, personality, and cognition- and alcohol-related behaviors. Notably, At-Risk and High-Risk Blackout profiles had the highest alcohol use disorder risk, most memory lapses and cognitive concerns, and highest levels of impulsivity traits., Conclusions: Findings support the multifaceted nature of blackout drinking experiences and perceptions. Profiles were differentiated across person-level predictors and outcomes, which identify potential intervention targets and individuals at heightened alcohol-related risk. A more comprehensive understanding of the heterogeneity of blackout drinking characteristics may be useful for early detection and intervention of problematic alcohol use predictors and patterns among young adults., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Emotional variability has been posited as a risk factor for adolescent psychopathology. However, it is unclear whether parent emotional variability may also function as a risk factor that heightens adolescent mental health problems. To fill this gap, the present study examined whether parent and adolescent emotional variability in both positive emotion (PE) and negative emotion (NE) is associated with adolescent psychopathology and potential sex differences in these associations. Participants were 147 adolescents and their parents in Taiwan who completed a baseline assessment, a 10-day daily diary study, and a 3-month follow-up assessment. The results indicated that parent NE variability was associated with risk for adolescent internalizing problems and depressive symptoms, after accounting for baseline levels, adolescent NE variability, parent internalizing problems, and mean levels of parent and adolescent NE. Adolescent PE variability was also associated with the risk for adolescent externalizing problems. Furthermore, higher parent PE variability was associated with more internalizing problems only for female but not male adolescents. The findings highlight the importance of assessing emotion dynamics in both parents and adolescents to better understand the development of adolescent psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Our study measured parental confidence and intention/uptake of two adolescent vaccines (HPV and COVID-19), focusing on differences among community types including urban, suburban, and rural. Although social media provides a way for misinformation to spread, it remains a viable forum for countering misinformation and engaging parents with positive vaccine information across community types. Yet, little is understood about differences in social media use and vaccine attitudes and behaviors for parents living in rural, suburban and urban areas. We sought to determine how to better reach parents living in different community types with targeted social media channels and messaging. In August 2021, we used a cross-sectional survey programmed in Qualtrics to collect data from 452 parents of children ages 9 to 14 living in different community types across the United States. Participants came from a survey panel maintained by CloudResearch. Survey questions asked about demographics, political affiliation, community type, social media use, health and vaccine information sources, and attitudes and behaviors regarding the HPV and COVID-19 vaccines. Our sample of parents (n = 452) most frequently used Facebook (76%), followed by YouTube (55%), and Instagram (43%). When comparing social media use by community type, parents used the top platforms at similar rates. Social media use was associated with vaccine confidence and intention/uptake in unadjusted models but not in adjusted models. Further, there were no significant differences in HPV vaccine confidence or intention/uptake by community type (i.e., rural, suburban, urban). For the COVID-19 vaccine, parents in rural communities were less likely to have vaccine confidence and intention/uptake in the unadjusted model. For both HPV and COVID-19 vaccines, political affiliation was the only common factor associated with both vaccine confidence and intention/uptake. Parents who identified as Democrat compared to Republican had greater confidence in the vaccines and had higher odds of vaccine intention/uptake for their children. Although rurality has been associated with vaccine confidence in the past we did not find that in our study. Instead, political affiliation appeared to explain most of the variation in vaccine confidence and intention/uptake, suggesting that more research is needed to identify best practices for using social media to reach parents with different political beliefs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ellagic acid, the marker component of peels of Punica granatum L., is known traditionally to treat traumatic hemorrhage. In this study, the cellular mechanism underlying ellagic acid-induced anti-inflammation was investigated using lipopolysaccharides (LPSs) as a neuroinflammation inducer. Our in vitro data showed that LPS (1 μg/mL) consistently phosphorylated ERK and induced neuroinflammation, such as elevation in tumor necrosis factor-α (TNF-α) and nitric oxide production in treated BV-2 cells. Incubation of ellagic acid significantly inhibited LPS-induced ERK phosphorylation and subsequent neuroinflammation in treated BV-2 cells. Furthermore, our in vivo study of neuroinflammation employed an intranigral infusion of LPS that resulted in a time-dependent elevation in phosphorylated ERK levels in the infused substantia nigra (SN). Oral administration of ellagic acid (100 mg/kg) significantly attenuated LPS-induced ERK phosphorylation. A four-day treatment of ellagic acid did not alter LPS-induced ED-1 elevation but ameliorated LPS-induced reduction in CD206 and arginase-1 (two biomarkers of M2 microglia). A seven-day treatment of ellagic acid abolished LPS-induced increases in heme-oxygenase-1, cyclo-oxygenase 2, and α-synuclein trimer levels (a pathological hallmark) in the infused SN. At the same time, ellagic acid attenuated LPS-induced increases in active caspase 3 and receptor-interacting protein kinase-3 levels (respective biomarkers of apoptosis and necroptosis) as well as reduction in tyrosine hydroxylase-positive cells in the infused SN. In silico analysis showed that ellagic acid binds to the catalytic site of MEK1. Our data suggest that ellagic acid is capable of inhibiting MEK1-ERK signaling and then attenuated LPS-induced neuroinflammation, protein aggregation, and programmed cell deaths. Moreover, M2 microglial polarization is suggested as a novel antineuroinflammatory mechanism in the ellagic acid-induced neuroprotection.

Although the sensitization hypothesis posits that heightened reactivity to interparental conflict is linked to adolescent psychopathology, limited studies tested whether sensitization would emerge in parent-adolescent conflict and across ethnicity or culture. This study revisits the sensitization hypothesis by examining adolescent emotional reactivity to interparental and parent-adolescent conflicts on a daily timescale. The sample included 163 adolescents (55% girls; M age  = 12.79) and their parents (78% females; M age  = 45.46) who completed a 10-day reports in Taiwan. Multilevel modeling results showed that, instead of interparental conflict, adolescents with greater histories of parent-adolescent conflict exhibited higher emotional reactivity when parent-adolescent conflict was higher. The findings underscore the importance of parent-adolescent conflict in evaluating adolescent developmental risk., (© 2022 Society for Research on Adolescence.)

Purpose: Medication reconciliation (MedRec) is a process to ensure complete and accurate communication of patient medication information throughout care transitions to prevent medication errors. Hospitals in Taiwan have stride to implement a universal protocol for MedRec. To establish a feasible protocol indigenously, the World Health Organization (WHO) protocol was incorporated with the Taiwan National Health Insurance (NHI) PharmaCloud patient medication profile. The efficiency and error detection capability of this modified protocol was evaluated in two hospitals., Methods: A prospective, non-randomized, unblinded, multicenter cohort study was conducted. Subjects were recruited among patients admitted for colorectal or orthopedic surgery with at least 4 or more chronic drugs. To obtain the best possible medication history (BPMH), the control group was conducted according to the WHO protocol, and the experimental group used the modified WHO protocol with the medication data from the PharmaCloud system. The time spent on the two protocols was recorded. Admission and discharge orders were reconciled against the BPMH to identify any discrepancies. Discrepancies were evaluated by appropriateness, prescribing intentions, and types of inappropriateness. The levels of potential harm were classified for inappropriate discrepancies., Results: The mean time to obtain BPMH in the control group was 34.3±10.8 minutes and in the experimental group 27.5±11.5 minutes ( P = 0.01). The experimental group had more subjects with discrepancies (87.9%) than the control (58.3%) ( p < 0.001). The discrepancies in both admission and discharge orders for the experimental group (84.5 and 67.2%) were higher than those of the control (47.9 and 37.5%). Many inappropriate discrepancies were classified as the potential harm of level 2 (77.8%)., Conclusion: Through the establishment of BPMH with the medication data from the Taiwan NHI PharmaCloud, MedRec could be achieved with greater efficiency and error detection capability in both the admission and discharge order validation processes., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Huang et al.)

The role of negative affect in precipitating drug craving and relapse among young adults in recovery from substance use disorder (SUD) is well documented. However, most studies focus on negative affect as a trait-level congregate of multiple negative emotion states. The present study examined the associations between specific facets of negative affect, college stressors, and craving among young adult college students in SUD recovery. Data were drawn from a three-week daily diary study of 50 students participating in a collegiate recovery community at a U.S. university ( M age = 21.42, 76% males). At the within-person level, craving was higher on days when young adults experienced higher than usual anger, fear, and sadness, but not guilt. At the between-person level, individuals higher in agitation reported greater levels of craving on average. Moderation analyses further showed that college stressors heightened the within-person association between anger and craving. Findings demonstrate that negative affect is not monolithic and that its different aspects are uniquely associated with craving at both between- and within-person levels. Findings from this study could guide collegiate SUD recovery programs that wish to provide greater support to their members by helping them identify both individual- and time-specific relapse risks, such as generally high levels of agitation or days when anger, fear, or sadness are higher than usual for a particular individual. Our findings also suggest that future research should consider distinct features and implications of affective structures at between- and within-person levels, and how these may be uniquely associated with craving., Competing Interests: Disclosure statement. The authors report there are no competing interests to declare.

Diabetes Mellitus (DM) is a chronic disease characterized by abnormally uncontrolled high blood glucose level. The Risk Assessment and Management Program (RAMP) in Hong Kong has been providing long-term face-to-face follow-up to DM patients in the government out-patient clinics since 2009. However, under the current outbreak of COVID-19, these face-to-face consultations were ceased over and over again to lower the risk of disease transmission. With the advancement in technology, the recent emergence of telecare has provided an alternative to replace the conventional consultations in the clinics. Its clinical effectiveness on DM patients has also been supported by numerous studies. Yet, there is only a paucity of literatures discussing the practicality of such implementation design in the real-world settings. This study aims at studying both the effectiveness and implementation outcomes of telecare in Hong Kong DM patients. It adopts a type 2 hybrid effectiveness-implementation design. It will be conducted in seven government out-patient clinics in Hong Kong. The subjects will be randomly assigned to an intervention group or a control group when they 1) are aged 18 or above, 2) have a confirmed diagnosis of diabetes, and 3) are having regular follow-up appointment in the clinic. Subjects in the intervention group will receive a 84-week Risk Assessment and Management Program (RAMP) in an alternate telecare and face-to-face consultations mode, while the control group will receive the same program but in usual face-to-face consultation mode. RE-AIM is employed as the implementation and effectiveness outcome evaluation framework. The primary outcome measure will be HbA1c. Data will be collected pre-intervention (T1), 42-week (T2), and 84-week (T3). The study will provide effectiveness-implementation assessment of telecare mode for DM patients in Hong Kong, as an alternative or in addition to conventional face-to-face consultations. It also aimed to provide insights for the future adoption in a broader health care setting.

Background: Dry January, a temporary alcohol abstinence campaign, encourages individuals to reflect on their relationship with alcohol by temporarily abstaining from consumption during the month of January. Though Dry January has become a global phenomenon, there has been limited investigation into Dry January participants' experiences. One means through which to gain insights into individuals' Dry January-related experiences is by leveraging large-scale social media data (eg, Twitter chatter) to explore and characterize public discourse concerning Dry January., Objective: We sought to answer the following questions: (1) What themes are present within a corpus of tweets about Dry January, and is there consistency in the language used to discuss Dry January across multiple years of tweets (2020-2022)? (2) Do unique themes or patterns emerge in Dry January 2021 tweets after the onset of the COVID-19 pandemic? and (3) What is the association with tweet composition (ie, sentiment and human-authored vs bot-authored) and engagement with Dry January tweets?, Methods: We applied natural language processing techniques to a large sample of tweets (n=222,917) containing the term "dry january" or "dryjanuary" posted from December 15 to February 15 across three separate years of participation (2020-2022). Term frequency inverse document frequency, k-means clustering, and principal component analysis were used for data visualization to identify the optimal number of clusters per year. Once data were visualized, we ran interpretation models to afford within-year (or within-cluster) comparisons. Latent Dirichlet allocation topic modeling was used to examine content within each cluster per given year. Valence Aware Dictionary and Sentiment Reasoner sentiment analysis was used to examine affect per cluster per year. The Botometer automated account check was used to determine average bot score per cluster per year. Last, to assess user engagement with Dry January content, we took the average number of likes and retweets per cluster and ran correlations with other outcome variables of interest., Results: We observed several similar topics per year (eg, Dry January resources, Dry January health benefits, updates related to Dry January progress), suggesting relative consistency in Dry January content over time. Although there was overlap in themes across multiple years of tweets, unique themes related to individuals' experiences with alcohol during the midst of the COVID-19 global pandemic were detected in the corpus of tweets from 2021. Also, tweet composition was associated with engagement, including number of likes, retweets, and quote-tweets per post. Bot-dominant clusters had fewer likes, retweets, or quote tweets compared with human-authored clusters., Conclusions: The findings underscore the utility for using large-scale social media, such as discussions on Twitter, to study drinking reduction attempts and to monitor the ongoing dynamic needs of persons contemplating, preparing for, or actively pursuing attempts to quit or cut down on their drinking., (©Alex M Russell, Danny Valdez, Shawn C Chiang, Ben N Montemayor, Adam E Barry, Hsien-Chang Lin, Philip M Massey. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.11.2022.)

The continuing impact of daily stress during the COVID-19 pandemic has disrupted the lives of families worldwide, and increased the risk of psychological problems for parents and their children. The current study investigated the daily effect of COVID-19 cases on parents' positive and negative emotions among 163 Taiwanese families using daily diary methodology across 10 weekdays. Results of multilevel modeling indicated that parents reported fewer positive emotions on days when COVID-19 cases were higher than average. Further moderating analyses showed the adverse effect of COVID-19 cases was only evident when the same-day marital relationship quality was lower than usual. The findings highlight the psychological stress of COVID-19 cases on parents' daily emotions and identify the protective role of marital relationship quality. Policies and clinical interventions should consider the implications of daily COVID-19 stressors for parents' emotional well-being, and target the protective role of marital relationship quality in daily life., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest.Competing interestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Objective: Drawing on family systems framework, this study investigated the reciprocal prospective associations between marital relationship quality, parent-adolescent closeness and conflict, and adolescent depressive symptoms among families in Taiwan., Background: The family systems theory posits reciprocity between family subsystems. However, the direction of influences between marital relationship quality, parent-adolescent relationship quality and adolescent well-being may be more unidirectional in Chinese societies due to hierarchical family values., Method: Data were from a longitudinal survey of 2,292 parent-youth dyads in the Taiwan Youth Project. Cross-lagged path models were used to test the bidirectional associations between marital relationship quality, parent-adolescent closeness and conflict, and adolescent depressive symptoms from ages 12 to 18., Results: Our primary hypothesis that marital relationship quality predicts parent-adolescent relationship quality, which then predicts adolescent depressive symptoms in a unidirectional manner was partially substantiated. Moreover, marital relationship quality directly predicted fewer depressive symptoms from middle to late adolescence and indirectly from early to late adolescence via parent-adolescent relationship quality in middle adolescence. We also found that child depressive symptoms predicted less parent-adolescent closeness, and more conflicts which predicted poorer marital relationship quality, particularly in early adolescence., Conclusion: Extending the family systems theory, findings suggest that marital relationship quality plays a dominant role in the health and well-being of Taiwanese families, especially as adolescents mature. Results highlight the importance of testing theories in families from diverse cultures.

Background: Citrin deficiency is an autosomal recessive disorder caused by variants of the SLC25A13 gene. Although newborn screening (NBS) provides an opportunity for its early diagnosis and treatment, citrin deficiency detection rates remain lower than those estimated., Methods: Before 2018, NBS for citrin deficiency was based on citrulline levels alone. In June 2018, a second-tier molecular test was implemented to detect 11 common variants of the SLC25A13 gene and improve the NBS detection rates. This study compares the incidence rates and costs before and after the second-tier implementation., Results: Prior to 2018, five subjects were diagnosed via NBS, and 12 of 555,449 newborns screened were missed. In comparison, 11 subjects were diagnosed out of 198,071 newborns screened after 2018, and there were no false-negatives. The citrin deficiency detection rate increased from 1/32,673 to 1/18,006 after the second-tier test was implemented, with only a minimal increase in the total cost. The number of false-positive in our cohort was tolerable. Subjects with citrin deficiency may present with borderline elevated citrulline levels; these can remain slightly elevated or increase considerably on retest. Four patients (80%) detected prior to second-tier testing and six patients (55%) detected after it was implemented were identified based on the citrulline levels alone. However, at the time of second blood sampling, the normal citrulline level of five subjects did not exclude a citrin deficiency diagnosis., Conclusions: Our study shows that it is vital and cost-effective to employ second-tier molecular testing to improve the detection of citrin deficiency by NBS., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

With the spread of the new SARS-CoV-2 variants, many countries have begun COVID-19 vaccine booster programs with the mix-and-match strategy. However, research on the adverse events (AE) of booster doses is still scarce. The aim of our study was to analyze the reported incidence rate (IR), and factors associated with AE, including short-term serious adverse events (SAE) and short-term non-serious adverse events (NSAE), among different vaccine products through the hospital-based Vaccine Adverse Event Reporting System (VAERS). A total of 7432 records were collected during the three-month study period. While more than half of the responses (52.2%) reported the presence of AE after receiving a booster dose, only a few AE were considered SAE (2.4%). AE were significantly higher among women and people of younger age, and the brand of vaccines is the strongest factor associated with post-booster dose AE. The incidence of AE in mRNA1273 is higher than in BNT162b2 and MVC-COV1901 (IRR mRNA1273 vs. BNT162b2: 1.22, 95% CI: 1.11-1.34; BNT162b2 vs. MVC-COV1901: 2.77, 95% CI: 2.27-3.39). The IR of different groups were calculated to support the decision making of the booster vaccine. Although AE were not uncommon for booster vaccines, almost all AE were not serious and predictable using estimated IR. This result can be used to optimize booster vaccine decision making.

Background: Magnolol is a component of the bark of Magnolia officinalis, which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R)., Methods: Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R., Results: Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1β, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced., Conclusion: Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or material discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Cytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate tumor progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E 2 (PGE 2 ) production in cancer cells with pre-existing COX-2 activity. Screening a compound library of 1280 approved drugs, we find that all classes of chemotherapy drugs enhance COX-2 transcription whilst arresting cancer cell proliferation. Genetic manipulation of COX-2 expression or its gene promoter region uncover how augmented COX-2/PGE 2 activity post-treatment profoundly alters the inflammatory properties of chemotherapy-treated cancer cells in vivo. Pharmacological COX-2 inhibition boosts the efficacy of the combination of chemotherapy and PD-1 blockade. Crucially, in a poorly immunogenic breast cancer model, only the triple therapy unleashes tumor growth control and significantly reduces relapse and spontaneous metastatic spread in an adjuvant setting. Our findings suggest COX-2/PGE 2 upregulation by dying cancer cells acts as a major barrier to cytotoxic therapy-driven tumor immunity and uncover a strategy to improve the outcomes of immunotherapy and chemotherapy combinations., (© 2022. The Author(s).)

Background: For people who are overweight or obese, maintaining a metabolically healthy status can decrease the risks of developing cardiovascular diseases and Type 2 diabetes. Despite this, only a limited amount of research has discussed the metabolically healthy overweight and obesity (MHOO) population in Asia and the factors associated with them maintaining their metabolic health., Methods: This study enrolled 195 MHOO participants from communities in northern Taiwan during 2009-2010 (baseline). Of the 195 participants, 89 completed the follow-up assessment after a median follow-up time of nine years. Body type was determined by body mass index (BMI, kg/m 2 ). We defined overweight as a BMI ≥ 24 kg/m 2 and <27 kg/m 2 and defined obese as a BMI ≥ 27 kg/m 2 . Metabolic health was defined as the absence of cardiometabolic diseases and the presence of ≤1 of the cardiometabolic risk factors, namely hypertension, hyperglycemia, hypertriglyceridemia, and low serum high-density lipoprotein cholesterol. Metabolic health, BMI, and other covariates were evaluated at both baseline and follow-up. Generalized estimating equations (GEE) models were used to analyze the factors associated with maintenance of metabolic health during the follow-up period., Results: At baseline, the mean age of the study participants was 47.4 (SD 5.3) years and 46 (51.7%) of the participants were women. There were 51 (57.3%) individuals who maintained their metabolic health status at the time of the nine-year follow-up. The detrimental factors pertaining to metabolic health included older age, longer duration until follow-up, BMI ≥ 27 kg/m 2 , and increase in waist circumference. No significant relationships were observed between sociodemographic factors and lifestyle factors, such as sex, level of education, cigarette smoking, alcohol consumption, and physical activity, and sustained metabolic health among MHOO individuals., Conclusions: To maintain metabolic health and prevent negative changes in health status, control of bodyweight and waist circumference should remain a priority for MHOO individuals even when there are no metabolic disorders present., Competing Interests: The authors declare there are no competing interests., (©2022 Lin et al.)

Introduction: Identifying specific contextual factors that contribute to the development of internalizing symptoms in adolescents in poverty is critical for prevention. This study examined the longitudinal effects of neighborhood disadvantage, family cohesion, and teacher-student relationship on adolescent internalizing symptoms from economically disadvantaged families., Methods: Participants were 1404 Taiwanese adolescents (49% female) in the nationally representative Taiwan database of children and youth in poverty. Youth were enrolled in the seventh, eighth, or ninth grades (Time 1; M age  = 14.85, SD = 0.95) and completed biennial follow-up assessments 2 (Time 2; M age  = 16.47, SD = 0.74) and 4 years after baseline (Time 3; M age  = 18.21, SD = 0.70). Latent growth models examined longitudinal associations between contextual factors and internalizing symptoms over time., Results: Adolescents reported declines in neighborhood disadvantage and teacher-student relationship but increases in family cohesion over the 4 years. At baseline, greater neighborhood disadvantage was associated with higher levels of internalizing symptoms, whereas higher family cohesion was associated with lower levels of internalizing symptoms. Over time, an increase in family cohesion was associated with a decrease in internalizing symptoms., Conclusion: This study provides empirical support that family cohesion plays a critical role in shaping the development of adolescent internalizing symptoms despite poverty. There was an increase in family cohesion from early to late adolescence among Taiwanese adolescents in poverty and such change was correlated with decreases in youth internalizing symptoms. Family cohesion may be a key target of prevention programs aiming to reduce internalizing symptoms for youth in poverty., (© 2022 The Foundation for Professionals in Services for Adolescents.)

Despite the first approval of biosimilars' in 2010, biosimilar products usage has remained low in Taiwan. This cross-sectional survey study assessed healthcare professionals' (HCPs)-hospital pharmacists, oncologists, and rheumatologists-knowledge, and attitudes toward biosimilars. More precisely, their knowledge and attitude towards biosimilars' current usage and regulations in Taiwan were analyzed. The mean ± standard deviation knowledge score was 2.56 ± 0.86 out of 4 ( n = 395), and a difference in knowledge score was determined according to the hospital types ( p = 0.004). Rheumatologists possessed significantly higher confidence in their knowledge of biosimilars than other HCPs ( p = 0.001). Pharmacists showed the highest acceptance-and rheumatologists the least-for switching patients from reference drugs to biosimilars ( p = 0.02). Hospital type was associated with the respondent's confidence in their knowledge ( p = 0.04) and the preference for distinguishable naming of biosimilars ( p = 0.007). Their knowledge scores were associated with their confidence in the efficacy and safety of biosimilars ( p = 0.02). The study found that the current level of biosimilar knowledge of HCPs in Taiwan is low. The higher the knowledge score, the greater the confidence in biosimilars and the familiarity with relevant regulations.

The association between metabolically healthy obesity (MHO) and health-related quality of life (HRQOL) has not been thoroughly evaluated. This study enrolled 906 adult participants aged 35-55 years between 2009 and 2010 in Northern Taiwan; 427 participants were followed up after eight years. Normal weight, overweight, and obesity were evaluated via body mass index. Metabolic health was defined as the absence of cardiometabolic diseases and having ≤1 metabolic risk factor. HRQOL was evaluated using the 36-Item Short Form Health Survey (SF-36), Taiwan version. Generalized linear mixed-effects models were used to analyze the repeated, measured data with adjustment for important covariates. Compared with metabolically healthy normal weight individuals, participants with metabolically unhealthy normal weight and obesity had a significantly poorer physical component summary score (β (95% CI) = -2.17 (-3.38--0.97) and -2.29 (-3.70--0.87), respectively). There were no significant differences in physical and mental component summary scores among participants with metabolically healthy normal weight, overweight, and obesity. This study showed that metabolically healthy individuals with obesity and normal weight had similar HRQOL in physical and mental component summary scores. Maintaining metabolic health is an ongoing goal for people with obesity.

Abstract: To determine the economic burden of metastatic breast cancer (MBC) in Taiwan, we conducted a national retrospective claim database analysis to evaluate the incremental healthcare costs and utilization of MBC patients as compared to their breast cancer (BC) and breast cancer free (BCF) counterparts.Data were obtained from the National Health Insurance Claim Database and the Taiwan Cancer Registry database between 2012 and 2015. All healthcare utilization and costs were calculated on a per-patient-per-month (PPPM) basis and were compared among groups using the generalized linear model adjusting for age group, residential area, and Charlson comorbidity index group.A total of 1,606 MBC patients were matched to 6,424 BC patients and 6,424 BCF patients. The majority of overall MBC healthcare costs were attributed to outpatient costs (75.1%), followed by inpatient (23.2%) and emergency room costs (1.7%). The PPPM total healthcare costs of the MBC, BC, and BCF groups were TWD 7,422, 14,425, and 2,114, respectively. The adjusted PPPM total healthcare cost ratio of MBC to BCF was 4.1. Compared to BCF patients, the patients receiving both human epidermal growth factor receptor 2-targeted therapy and endocrine therapy incurred 28.1 times PPPM total costs. The adjusted PPPM total healthcare cost ratio of recurrent MBC to BCF was 2.3, while the ratio was 12.2 in the de novo MBC group.Patients with MBC are associated with substantial economic burden, particularly in outpatient costs. The study findings could be useful for MBC-related economic evaluations and health resource allocation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009-2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β - 4.20, 95% CI - 7.54 to - 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β - 4.42, 95% CI - 8.10 to - 0.73 and β - 3.47, 95% CI - 6.90 to - 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health., (© 2021. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) spread all over the world in 2020. In the face of the sudden pandemic, workforce mobilization has been of critical concern to medical institutions. During the pandemic, the public's behaviors of seeking medical assistance have also changed. Using the real-world data of a large medical center in Taiwan, this study aimed to analyze the fluctuations of outpatient visits among various departments and divisions in the early phase of the COVID-19 pandemic and to provide suggestions for staff allocation in similar future events., Methods: Data of outpatient visits at Taipei Veterans General Hospital were obtained for analysis. The weekly fluctuations of outpatient visits among 36 departments or divisions were computed for 8 weeks from February 3 to March 29, 2020, the early phase of the pandemic. The monthly data of outpatient visits by department and division in March 2020 were also extracted for comparison with those in March 2019. A simple regression equation was used to calculate the weekly trends., Results: Average outpatient visits decreased by 26% in 2 months following the outbreak. Among the 36 departments or divisions, ophthalmology, orthopedics, and cardiology underwent marked declines after the outbreak; the slopes of the simple regression equation were -110.8, -100.7, and -99.2, respectively. By contrast, transfusion medicine, toxicology, transplantation surgery, pediatric surgery, chest surgery, technical aid, and oncology were divisions less influenced. In the year-over-year comparison, infection was the only department or division with positive growth (20.5%), whereas all others exhibited negative growth., Conclusion: In the future, we can fulfil the additional personnel needs during a pandemic by redeploying physicians from departments experiencing a reduced workload. Hospitals should also establish preparatory employee training programs to ensure that the reassigned personnel are adequately equipped to serve in their new positions., Competing Interests: Conflicts of interest: Dr. Tzeng-Ji Chen and Dr. Shinn-Jang Hwang, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)