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Objective: Evaluate long-term safety, tolerability, and durability of the effect of olanzapine/samidorphan (OLZ/SAM) for up to 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I)., Methods: This phase 3, multicenter, open-label, long-term extension (conducted June 2017-September 2023) assessed OLZ/SAM in patients completing the ENLIGHTEN clinical program. Patients received ≥2-4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. The durability of the effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale., Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform disorder, and 48 (9%) had BD-I. Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients eligible for 4 years, 109 (32.5%) received it. The most common AEs were weight increased (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and weight decreased (5.7%). At 2 years, mean (SD) body weight change was 0.84 (6.84) kg; waist circumference change was -0.56 (6.24) cm. At 4 years, mean (SD) body weight change was 2.65 (8.12) kg; waist circumference change was 1.37 (8.65) cm. Changes in lipid/glycemic parameters were minimal. CGI-S scores remained stable., Conclusion: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies., Trials Registration: ClinicalTrials.gov identifier: NCT03201757., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Mental health is deteriorating quickly and significantly globally post-COVID. Though there were already over 1 billion people living with mental disorders pre-pandemic, in the first year of COVID-19 alone, the prevalence of anxiety and depression soared by 25% worldwide. In light of the chronic shortages of mental health provider and resources, along with disruptions of available health services caused by the pandemic and COVID-related restrictions, technology is widely believed to hold the key to addressing rising mental health crises. However, hurdles such as fragmented and often suboptimal patient protection measures substantially undermine technology's potential to address the global mental health crises effectively, reliably, and at scale. To shed light on these issues, this paper aims to discuss the post-pandemic challenges and opportunities the global community could leverage to improve society's mental health en masse.

Worldwide, women face a disproportionately heavy health burden than their male counterparts. Yet there is a chronic lack of research attention and investment in women's health, which may explain the absence of women-inclusive, let alone women-centred, understanding of the causes, consequences, and confounding factors that shape individuals' health and quality of life. In this manuscript, by analysing the U.S. National Health Expenditure data, we show how ingrained the issue of poor investment in women's health even in the 0-18 years age group in terms of per capita health expenditure. We hope this manuscript sheds light on how early-life poor health investment in women's health might be a potential cause for women's poor health in adulthood, and in turn, underscores the importance of investing resources into better understanding and improving women's health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: The impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end-stage renal disease (ESRD) risk in SLD., Methods: 234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI-proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB-4 score > 2.67) was determined using FIB-4 scores. eGFR < 60 mL/min/1.73 m 2 or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively., Results: 102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB-4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35-1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06-3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75-2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36-5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow-up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19-2.43)., Conclusions: In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Avoidable disasters are both saddening and baffling. In 2022, 159 people, mostly in their 20s, and 30s were crushed to death in Itaewon's narrow alleyway amid South Korea's first pandemic-restrictions-free Halloween celebration. What is particularly sobering about this tragedy is that although many people called police hotlines as crowds became cramped and static, their calls went unheeded for hours. Rather than order independent investigations into the catastrophe (as of January 2024), the President of South Korea at the time focused on superficial issues such as asking the public to refer to the disaster as an "accident" (which it was not, it was an avoidable disaster) and the casualties as "the dead" (who are casualties indeed, instead of victims of a preventable tragedy). In this paper, we examine how officials' complacency about public health and safety dangers, ineffective disaster prevention, and preparedness systems, as well as the government's chronic lack of prioritization of public health and safety may have contributed to the disaster. Furthermore, we discuss the importance of creating integrated public health and safety protection systems to prevent similar tragedies from happening.

Background: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort., Methods: A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk., Results: Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68-0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84-1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42-0.85] P = 0.004) compared to non-use., Discussion: Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials., Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted., Results: Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning., Conclusion: Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients' views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies., Competing Interests: AS, AKO, and JC-C were employed by of Alkermes, Inc. MKC and CS are employed by Quality Metric, LLC. DM is employed by Alkermes Pharma Ireland Limited and may own stock/options in the company. The authors declare that this study received funding from Alkermes, Inc. The funder was involved in the study design, data collection, data analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2024 Simmons, O’Sullivan, Carpenter-Conlin, Carty, Saucier and McDonnell.)

Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Older people often face varied and vicious abuse from care workers. Situations are typically more pronounced for older people who live with additional cognitive or physical difficulties, such as dementia and disabilities, the prevalence of which has been on the rise in China and elsewhere. Recent reported discoveries of elder abuse in China, which span alarming levels of verbal, physical, psychological, financial, and sexual abuse, have almost all been caused by nannies or 'bao mu'. Different from Western countries, the word nanny is often used to refer to people who offer caregiving help in residential settings at large, regardless of the age of the care recipients. What is also different is the lack of regulations or even rigorous training and evaluation processes for nannies in China: almost anyone can become a nanny—even though a background check is often required for nannies, this process is often highly variable and dependent on the specific labour agencies that nannies are registered with. Yet without structured studies and systematic data, little is known about the extent and severity of nanny-induced elder abuse in China. To this end, this article aims to discuss the unique elderly care environment—such as the '721 Rule'—in China, particularly in the post-COVID era, and highlight the critical need for timely and rigorous studies on the potential prevalence and severity of nannies' abuse and neglect of older people. [ABSTRACT FROM AUTHOR]

In recent years, air pollution has become the leading cause of illness and premature deaths worldwide, with adverse impacts on human health, the environment, and the economy. This empirical study aims to investigate the relationship between air quality and property values with a focus on six Spanish cities. The study utilizes property prices as a variable and particulate matter concentration as an air quality indicator. Key findings indicate a significant correlation between particulate matter and property prices in seaside cities, revealing a discernible relationship. However, in inland cities, the observed correlation is notably weak and nonsignificant, resulting in a negligible association between the two variables. These results highlight the presence of additional characteristics that influence property values beyond air quality, particularly in areas where air quality is already deemed satisfactory. This research contributes valuable insights into the intricate interplay between air quality and property values by providing nuanced perspectives on urban planning and policy formulation., 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 Authors.)

Background: When it comes to pandemic response, preparation can be the key. Between 2020 and 2024, the fast-paced development of COVID-19-often compounded by pubic policies' failures to reflect the latest reality and the public's divergent reactions to the pandemic and the policies-means that society should prepare for exit strategies that can reflect the reality of the pandemic and the interests of the people. Yet oftentimes societies only have one exit strategy with limited scope. This paper investigates the dangers of having only one pandemic exit strategy for pandemics like COVID-19., Methods: Analyses were based on a review of the literature on COVID-19 exit strategies and our own research. The PubMed literature search focused on two concepts-"COVID-19″ and "exit strategy"-and was limited to peer-reviewed papers published between 2020 and 2024 in English., Results: A total of 31 articles were included in the final review. Analyses showed that existing studies on COVID-19 exit strategies often focused on using the modelling method to gauge one exit strategy. Exit strategies were often discussed in the context of implementing, easing, or lifting specific pharmaceutical or non-pharmaceutical interventions. Staged and country-wide coordinated exit strategies were also discussed in the literature, both of which were often deemed as comparatively rigorous options compared to single or stand-alone exit strategies. Drawing on the overall development of COVID-19 and our own research, we presented and discussed the importance of having multiple exit strategies that are considerate of all possible pandemic trajectories, diverse interests of the public, and the communication challenges officials might face in introducing or implementing pandemic policies., Conclusion: This paper underscored the importance of having multiple exit strategies for societies to prepare for pandemics. The insights of this study can help inform health policies so that they can more comprehensively and compassionately protect the needs and wants of the "public" in public health, particularly in grave times like COVID-19., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: While childhood maltreatment is understood to be a significant risk factor for adolescent internalizing problems (depression and anxiety), underlying mechanisms linking each type of maltreatment to internalizing problems in adolescents remain unclear. Moreover, the current state of knowledge regarding the associations between maladaptive cognitive emotion regulation strategies and each type of maltreatment, as well as their impact on adolescent internalizing problems, is limited. Additionally, it remains unclear whether these maladaptive strategies mediate this relationship., Objective: This study sought to investigate the effects of childhood maltreatment types on adolescent internalizing problems and to explore whether the overall and specific types of maladaptive strategies mediate these associations., Methods: Using a cross-sectional design, adolescents (N = 7071, M age  = 14.05 years, SD age  = 1.54) completed online questionnaires assessing childhood maltreatment, maladaptive cognitive emotion regulation strategies (including rumination, catastrophizing, self-blame, and other-blame), anxiety, and depression. The hypothesized mediating effects were tested using the Lavaan package in R software (4.1.2)., Results: Different maltreatment types had varying effects on adolescent internalizing problems. Emotional neglect, emotional abuse, and sexual abuse significantly affected anxiety and depression, whereas physical neglect and physical abuse did not. Other than physical neglect and physical abuse, overall maladaptive strategies mediated the relationship between the other three types of maltreatment (emotional abuse, emotional neglect, and sexual abuse) and internalizing problems (anxiety and depression). For specific maladaptive strategies, rumination mediated the effects of physical abuse, emotional abuse, emotional neglect, and sexual abuse on internalizing problems (anxiety and depression). In contrast, catastrophizing mediated the relationship between physical neglect, emotional abuse, emotional neglect, sexual abuse and internalizing problems (anxiety and depression)., Conclusions: These results suggest that the effects of maltreatment types on internalizing problems are different and that maladaptive strategies, particularly rumination and catastrophizing, are important mechanisms through which childhood maltreatment affects internalizing problems. This is a reminder that mental health workers need to consider the different effects of maltreatment types when intervening and recognize the importance of prioritizing interventions for rumination and catastrophizing., Competing Interests: Declaration of competing interest It is no conflict of interest to declare in this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Exploratory behavior, as an essential component of decision-making, is indispensable for maximizing long-term benefits, making it a crucial factor in adolescents' psychological well-being and social adaptation. Despite the established understanding that this adaptive behavior is shaped by early adverse experiences, limited knowledge exists regarding the longitudinal relationship between childhood maltreatment and exploratory behavior., Objective: The present study examines whether childhood maltreatment would impede subsequent exploratory behavior, considering the mediating role of uncertainty stress and the moderating role of intolerance of uncertainty., Participants and Setting: Participants were 655 adolescents from a longitudinal design with two waves spanning six months (M age  = 15.99, SD age  = 0.92, 43.5 % female)., Methods: Correlation analysis and longitudinal moderated mediation effect testing were used to test our hypotheses., Results: Correlation analysis indicated that childhood maltreatment was negatively correlated with exploratory behavior only simultaneously but not longitudinally. After controlling age and gender, childhood maltreatment would accompany higher levels of uncertainty stress, which in turn may act as a driving force behind subsequent exploratory behavior. The heightened intolerance of uncertainty may potentially mitigate the direct link between childhood maltreatment and later exploratory behavior. Furthermore, this trait amplifies the experienced uncertainty stress in individuals who have undergone maltreatment, thereby increasing their inclination toward engaging in subsequent exploratory behavior., Conclusions: Given the critical role of uncertainty stress, promoting more exploration among these maltreated adolescents requires corresponding cognitive and behavioral interventions to adjust their perception and cognition of uncertainty., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Although previous studies have shown that childhood maltreatment is a risk factor for adolescent suicidal ideation, less is known about the mediating and moderating mechanisms underlying this association., Objective: The current study aimed to investigate the relationship between childhood maltreatment and suicidal ideation among adolescents, as well as the mediating role of maladaptive cognitive emotion regulation strategies (maladaptive CERSs) and the moderating role of perceived social support., Methods: In a cross-sectional design, 4005 adolescents (M age  = 14.24 years, SD = 1.53; 49.0 % males) completed self-report questionnaires regarding childhood maltreatment, maladaptive CERSs, perceived social support and suicidal ideation, along with their basic information., Results: After controlling for gender, family location, family structure, and depression, childhood maltreatment was positively related to adolescent suicidal ideation, and maladaptive CERSs were found to mediate this association. Moderated mediation analyses revealed that perceived social support buffered the associations between maladaptive CERSs and adolescent suicidal ideation., Conclusions: The findings assist in understanding the mechanisms of maladaptive CERSs and perceived social support in the relationship between childhood maltreatment and suicidal ideation and can provide new perspectives for researchers designing interventions for suicidal ideation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited., Aims: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients., Methods and Results: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed., Interpretation: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

Facing long-term separation from their parents, left-behind children are at risk of the co-occurrence of internalizing and externalizing problems. Although previous research has gained substantial information examining the relationship between anxiety, depression, and internet addiction at the aggregate level of variables, little is known about the heterogeneity and interactions between these components at the symptom level with a large-scale purposive sample. Adopting the network approach, two network pathways, depression and anxiety, and associations between these variables and internet addiction were constructed. Our sample included 5367 left-behind children (M age  = 13.57; SD age  = 1.37; 50.07% females). Relevant bridging, central symptoms, and network stability were identified. Two relatively stable networks were obtained. For the network of anxiety and depression, sleep problems and tachycardia were vital bridging symptoms. Central symptoms, including tachycardia, restlessness, fatigue, and emptiness, were symptoms of depression. For the network of symptoms of anxiety, depression, and internet addiction, the bridging symptoms remained the same, and the central symptoms included tachycardia, restlessness, loss of control, and emptiness. By identifying relevant bridging and central symptoms, those with higher levels of these symptoms could be regarded as intervention targets, providing a reference for the current issue of valuing diagnosis over prevention in left-behind children., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Alcohol use and abuse remain prevalent in China, though mounting evidence shows that even drinking in moderation is detrimental to health. While many countries' intake is on the decline, China's alcohol consumption is rising fast and is on the path to overtaking countries like the United States, even on a per capita level., Objectives: This paper aims to analyze the danger of lax enforcement of laws and regulations against alcohol use and abuse and underscores the imperative for effective health interventions to curb problematic alcohol consumption in China., Results: Different from their Western counterparts, Chinese drinkers often consume more spirit with a high percentage of alcohol in social settings that encourage the "ganbei culture"-making toasts with alcohol filled to the brim and downed in one go to show respect-which perpetuates excessive drinking at a fast pace. Though the country has various laws and regulations in place to curb problematic alcohol consumption, like workplace drinking, their impacts are dismal. Considering that China has 1.4 billion people, the country's uncurbed alcohol consumption trend could have a detrimental effect on national strategic objectives like "Healthy China 2030" and international ones like the Sustainable Development Goals. To further compound the situation, prevalent campaigns promoted by liquor companies-like alcohol-infused coffee, chocolate, and ice cream-may groom young people to develop alcohol consumption habits, if not addictions, for generations to come., Conclusions: We developed the Framework of 5Vs of China's "Ganbei Culture to shed light on the issue, with the hope that it, along with the overarching insights of this paper, can assist health professionals and policymakers in better guarding and improving public health against the harms of alcohol use and abuse in China and beyond.

Older people often face varied and vicious abuse from care workers. Situations are often more pronounced for older people who live with additional cognitive or physical difficulties, such as dementia and disabilities, the prevalence of which has been on the rise in China and elsewhere. Recent discoveries of elderly abuse in China, which span from alarming levels of verbal, physical, psychological, financial, to sexual abuse, are all caused by nannies or "bao mu". Different from Western countries, the word nanny is often used to refer to people who offer caregiving help in residential settings at large, regardless of the age of the care recipients. What is also different is the lack of regulations or even rigorous training and evaluation processes for nannies in China: almost anyone could become a nanny-even though a background check is often required for nannies, this process is often highly variable and dependent on the specific labour agencies that nannies are registered with. Yet without structured studies and systematic data, little is known about the extent and severity of nanny-induced elderly abuse in China. To this end, this paper aims to discuss the unique elderly care environment-such as the "721 Rule"-in China, particularly in the post-COVID era, and highlight the critical need for timely and rigorous studies on the potential prevalence and severity of nannies' abuse and neglect of older people., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case-control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13 C-mixed triglyceride breath test ( 13 C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57-71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70-0.96) for the 13 C-MTGBT, and 0.85 (95% CI: 0.75-0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted.

Coronavirus disease 2019 (COVID-19) both creates and complicates public health challenges. Yet, the pandemic also provides a unique lens for dissecting complex issues in global health that could benefit society in the long run. In this article, we discuss the underlying reasons that can help explain the divergent COVID-19 control outcomes between Beijing and Shanghai—two advanced metropolises that are similar in their municipal capacity, administrative capability and pandemic strategy. We hope insights from this investigation contribute to the development of disease prevention systems, such as context-specific and data-driven public health strategies that could yield optimal pandemic control outcomes with minimal unintended consequences, both amid and beyond COVID-19. [ABSTRACT FROM AUTHOR]

Background: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank., Methods: A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42-47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC., Results: PDAC occurred in 1157 participants during 11.6 (10.9-12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42-47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31-3.37, p = 0.002); and was 8.55 (4.58-15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis., Conclusions: Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing.

Competing Interests: Disclosures: This study was sponsored by Alkermes Inc. Medical writing and editorial support were provided by Omar H. Cabrera, PhD, and John H. Simmons, MD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Alkermes Inc. M.S.T., M.E.H.-W., M.J.D., and D.M. are employees of Alkermes Inc, and may own stock/options in the company. C.U.C. has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, Intra-Cellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedinCell, Merck, MindPax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris; has provided expert testimony for Janssen and Otsuka; has served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; has received grant support from Janssen and Takeda; has received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, MindPax, LB Pharma, and Quantic.

Objective: A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2., Methods: The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18-55 years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30 kg/m 2 , and stable body weight (self-reported change ≤5% for ≥3 months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24 weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted., Results: At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine., Conclusion: In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.

Background: Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population., Methods: PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5., Results: Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42-8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05-12.65) vs 5.51 (4.73-6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration., Conclusions: In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

War could be traumatic. War trauma could often lead to severe and sustained health consequences on people's physical and psychological health. War trauma is often prevalent in people who either participated in the war or lived near conflict zones, such as military professionals, refugees, and health workers. Advances in information and communication technologies, such as the speed, scale, and scope at which people worldwide could be exposed to the near-time happenings of the war, mean that an unprecedented number of people could face media-induced war trauma. Different from war experienced in person, which could be limited in scope and intensity, media-induced war trauma can be substantially more extensive and comprehensive-news reports on the war often cover all aspects and angles possible, possibly paired with disturbing, if not demoralizing, images, repeatedly 24/7. Although media-induced war trauma could have a profound influence on people's mental health, particularly factoring in the compounding challenges caused by the pandemic, there is a dearth of research in the literature. To shed light on this issue, in this article, we aim to examine the implications of media-induced war trauma on people's health and well-being. Furthermore, we discuss the duties and responsibilities of the media industry amid and beyond the current conflicts in Ukraine.

Background: Disasters like COVID-19 are oftentimes inevitable, which makes disaster preparedness indispensable to global health and social stability. However, there is a dearth of understanding of how well healthcare professionals, who often have to work at the epicenter of disasters as they evolve, are trained to be sufficiently prepared for these crises. To this end, this study aims to examine the characteristics and effectiveness of existing interventions that aim to improve healthcare professionals' disaster preparedness., Methods: We searched RCTs that aim to improve healthcare professionals' disaster preparedness in databases including PubMed, PsycINFO, CINAHL and Scopus. Results were screened against the eligibility criteria. The review was registered with PROSPERO (CRD42020192517) and conducted following the PRISMA guidelines., Results: A total of 7382 articles were screened for eligibility, among which, 27 RCTs, incorporating 35,145, met the inclusion criteria. Review results show that most of the eligible RCTs were conducted in high-income countries. Only two RCTs were developed in disaster contexts that share similarities with COVID-19. Most of the interventions did not address critical disaster coping abilities, such as how can healthcare professionals protect or improve their personal or the general public's mental health amid pandemics. Furthermore, almost half of the disaster preparedness RCTs failed to generate statistically significant outcomes., Conclusions: Albeit inevitable, disasters are preventable. Our study results underscore the imperative of designing and developing effective and comprehensive interventions that could boost healthcare professionals' disaster preparedness, so that these frontline workers can better protect personal and public health amid global crises like COVID-19., 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 Ltd. All rights reserved.)

A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine's unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder., (© 2021. The Author(s).)

A brain abscess is an enclosed focal infection within the brain that is either initiated by haematogenous seeding or spreads contiguously from oto-sinusitis, local trauma or neurosurgery. We describe the case of a 71-year-old man presenting with acute confusion and unilateral neurology in the absence of systemic signs of sepsis or associated laboratory biomarkers. While his initial clinical presentation mimicked an acute cerebrovascular event or brain tumour, he was subsequently diagnosed with a particularly large spherical temporal lobe brain abscess of 5 cm diameter on neuroimaging. This abscess was treated successfully with craniotomy, evacuation and a prolonged course of anti-microbials, enabling him to return to his pre-morbid level of functioning. His prolonged course of anti-microbials was complicated by candidaemia and colonisation of an indwelling central venous catheter that was treated successfully with anti-fungals., Learning Points: A high index of suspicion for brain abscess should be maintained when a ring-enhancing lesion is found on neuroimaging, even in the absence of signs of sepsis or associated laboratory biomarkers.Commensal yeasts may colonise indwelling lines in patients treated with long-term broad-spectrum antibiotics.Distracting concomitant diagnoses may delay recognition of the primary pathological process., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2023.)

Objective: Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness., Methods: Young adults (16-39 years) with DSM-5 schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m 2 , and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d). Primary endpoint was percent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, waist circumference change, and Clinical Global Impressions-Severity (CGI-S) change., Results: Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed. Percent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% vs 6.77%; least-squares mean [LSM] [SE] difference, -1.87% [0.75]; P  = .012). Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% vs 30.4%, respectively; OR = 0.64; 95% CI  =  0.39 to 1.05); hierarchical testing precluded further statistical evaluation of secondary endpoints. Proportions of patients with ≥ 7% weight gain (33.1% vs 44.8%; OR = 0.61, 95% CI = 0.39 to 0.94) and waist circumference change (2.99 vs 3.90 cm; LSM [SE] difference, -0.92 cm [0.58]; 95% CI = -2.06 to 0.22) favored OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was -0.82 (0.06). OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes., Conclusions: In patients with early-phase schizophrenia, schizophreniform disorder, or BD-I, OLZ/SAM treatment resulted in less weight gain versus olanzapine., Trial Registration: ClinicalTrials.gov identifier: NCT03187769., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Background and Hypotheses: Weight gain and adverse cardiometabolic effects often limit the clinical utility of olanzapine. In ENLIGHTEN-2, combining olanzapine with the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain. These analyses tested the hypothesis that OLZ/SAM would be associated with reduced adverse cardiometabolic effects compared with olanzapine., Study Design: This phase 3 double-blind study randomized adults with schizophrenia to OLZ/SAM or olanzapine for 24 weeks. Post hoc analyses assessed changes from baseline to week 24 in cardiometabolic risk parameters, including body mass index (BMI), risk of developing obesity (BMI ≥30 kg/m2) or metabolic syndrome, waist circumference, along with mean and potentially clinically significant changes in blood pressure, glucose, and lipids., Results: After 24 weeks' treatment, compared with olanzapine, OLZ/SAM was associated with smaller least-squares mean (LSM) changes from baseline in systolic blood pressure (LSM difference, -2.63 mm Hg; 95% CI: -4.78, -0.47), diastolic blood pressure (LSM difference, -0.75 mm Hg; 95% CI: -2.31, 0.80), and BMI (LSM difference, -0.65 kg/m2; 95% CI: -1.01, -0.28). OLZ/SAM treatment was also associated with reduced risk of shifting from normal blood pressure to stage 1/2 hypertension (odds ratio [OR], 0.48; 95% CI: 0.24, 0.96), becoming obese (OR, 0.52; 95% CI: 0.32, 0.82), and developing metabolic syndrome (OR, 0.55; 95% CI: 0.31, 0.99) compared with olanzapine. No treatment group differences were noted for risk of hyperglycemia or hyperlipidemia., Conclusions: OLZ/SAM treatment was associated with lower risk of worsening cardiometabolic risk factors related to obesity, hypertension, and metabolic syndrome relative to olanzapine. NCT02694328, https://clinicaltrials.gov/ct2/show/NCT02694328., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)