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Exploring Professional Experiences in Caring for Vulnerable Migrants in an Italian Rural Reception Centre: A Qualitative Study Using Multidimensional Textual Analysis-Professional Experiences in Rural Migrant Care.

AIM: This study aims to explore the experiences, strengths, challenges, and potential improvements for professionals in managing the complex needs of vulnerable migrants (VM) in an Italian rural reception centre. METHODS: A qualitative study using semi-structured interviews was conducted in April 2024. Data were analysed using the Automatic Analysis of Textual Data, based on Fraire's seven-step model for Exploratory Multidimensional Data Analysis. DATA SOURCES: Data were collected from 16 professionals working in a rural reception centre in southern Italy. Interviews were conducted and analysed using AATD in April 2024. FINDINGS: The analysis identified two main dimensions of professionals' roles: balancing systemic responsibilities with personal engagement and managing immediate needs versus long-term integration goals. Professionals face significant challenges, such as resource scarcity, bureaucratic inefficiencies, and emotional fatigue, which impact their well-being and the quality of care provided to migrants. Resilience, adaptability, and multidisciplinary collaboration were identified as key strengths. CONCLUSION: The study highlights the dual nature of professionals' work in reception centres, requiring them to balance operational tasks with emotional involvement in migrant care. Targeted interventions and systemic reforms are necessary to support professionals and enhance the quality of care for vulnerable migrants, particularly in resource-constrained rural settings. IMPLICATIONS FOR PRACTICE AND/OR PATIENT CARE: This study underscores the importance of providing targeted support to professionals working in reception centres, including training in intercultural competence, stress management, and coping strategies. Policies should address systemic challenges and provide resources to enhance healthcare delivery and social integration programs. REPORTING METHOD: This study adhered to the EQUATOR guidelines for reporting qualitative research (COREQ). The findings were reported in compliance with these guidelines, ensuring methodological rigour and transparency. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the critical need for targeted support and training for professionals working in reception centres, particularly in rural settings. To improve care for vulnerable migrants, professionals should receive training in intercultural competence, stress management, and coping strategies to better navigate the complex challenges they face. Furthermore, systemic changes are necessary to alleviate the pressures on reception centres, such as streamlining bureaucratic processes and enhancing healthcare infrastructure, particularly in rural areas where resources are limited. By addressing these needs, we can improve the well-being of both the professionals and the migrants they serve, fostering more effective support systems and better care outcomes. Additionally, fostering multidisciplinary collaboration and community engagement can contribute to more comprehensive and sustainable care models. PROTOCOL REGISTRATION: The Ethics Committee of the University of Rome Tor Vergata approved this study on 07/07/2021 (protocol registration number 160.21).

Humans

"Orphaned bereavement": Toward a public health model for bereavement.

Bereavement is increasingly recognized as a public health concern, yet support systems in many welfare states continue to allocate support according to the circumstances of death rather than the functional needs of bereaved families. Existing bereavement frameworks have substantially advanced understanding of social recognition and public legitimacy but provide more limited guidance for understanding how institutional responsibility for bereaved families is organized. using Israel as a bereavement-saturated case, this study introduces the concept of orphaned bereavement to describe bereavement in which no institution holds clearly defined and continuing responsibility for identifying needs, coordinating support, and ensuring continuity of care. Drawing on 25 semi-structured interviews with five bereaved family members and 20 professionals, analyzed using reflexive thematic analysis, the analysis generated three interrelated themes: institutionalized invisibility and unequal recognition; reorganizing life in the absence of institutional support; and pathways toward a needs-based model of bereavement support. The findings extend existing theories of disenfranchized grief and grievability by introducing institutional responsibility as a complementary lens for understanding bereavement inequality and support a needs-based public health approach in which support is organized according to families' evolving functional needs rather than the circumstances of death.

Journal Article

Final-year nursing students' clinical practice experiences: a reflection study.

OBJECTIVES: This study aimed to explore the most impactful clinical practice experiences of final-year nursing students and the future-oriented actions developed in response to these experiences. METHODS: A retrospective descriptive qualitative design was used. Following reflection training in the internship practice course, 134 final-year nursing students were asked to describe the experience that affected them most during clinical practice. A total of 123 written reflections were analyzed using content analysis. RESULTS: Three themes emerged: near-miss events, incivility behaviors, and positive preceptoring roles. Negative experiences were mainly related to patients, relatives, and nurses and often led students to feel fear and inadequacy. Students reported action plans focused on effective communication, safe patient care, and becoming positive role models. CONCLUSIONS: These findings highlight the importance of supportive clinical learning environments and positive professional socialization during the transition from student to nurse. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: Nursing students worldwide may encounter incivility and near-miss events during clinical practice, potentially adversely affecting their learning experiences and professional development.

Humans

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems

Leveraging environmental applications and risks of coal gangue: A critical review on authigenic inorganic heavy metals, organic contaminants, and the removal of exogenetic contaminants.

Coal gangue (CG) as bulk solid waste has seriously threatened the ecosystem. Therefore, identifying the key risk drivers and exploring feasible disposal methods for CG are essential for developing a sustainable strategy. However, there is currently a lack of comprehensive information that balances the contamination risks with the valuable constituents present in CG, which hinders its full potential for sustainable use without negative environmental impacts. Given the complex composition and associated risks, we propose that addressing the critical properties related to contamination is crucial for the efficient utilization of CG. On this premise, we summarized several practical resource pathways (ecological multifunctional materials, extraction of rare elements, and soil additives) that are more favorable for sustainable development relative to conventional disposals. Meanwhile, we also propose that coupling disposals could intensely reduce CG's environmental footprints and capital costs. Consequently, regardless of the number of challenges to be solved, we believe the CG has broad application prospects, and we hope this review will promote the conversion of CG into an asset with lower ecological and social impacts.

Metals, Heavy

Positive psychology interventions during pregnancy: A systematic review.

Positive psychology interventions (PPI) have been applied and demonstrated evidence in various population groups. The present systematic review focused on the types and influence of PPI on the physical and psychological health of pregnant women. Studies that matched the selection criteria were identified on EBSCOhost, PsychINFO, Web of Science, PubMed, Scopus and four positive psychology journals. From the 2528 records identified, finally eight studies were included in the review. PPI in this review were delivered utilising various positive psychology components such as hope, gratitude and optimism based on existing theories, for example, the strengths theory, broaden-and-build theory, and hope theory. Most interventions were conducted from 14 gestational weeks onwards and were delivered via virtual platforms or mobile applications. As a result of this systematic review, it was identified that PPIs for maternal well-being were aimed at improving (1) physical health, including labour pain, nausea and vomiting; (2) psychological health, including stress, emotions, anxiety and depression; and (3) subjective health, including life satisfaction, perceived social support and quality of life. Most of the selected studies provided significant evidence towards improvement of well-being outcomes from administering PPI. For future studies, in-depth PPI integrated coping and support approaches should be further evidenced among diverse pregnant populations.

Humans

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans

Identifying and Prioritizing Core Components of Relationship Education Programs: a Case Study of an Artificial Intelligence (AI) Assisted Systematic Review.

The field of prevention science seeks to identify and implement effective strategies to address social, emotional, and health challenges. A critical aspect of this endeavor is determining the core components of prevention programs that drive positive outcomes. This article presents a case study utilizing artificial intelligence (AI)-assisted systematic review methods to identify key components of healthy marriage and relationship education programs. Given the growing body of research in this domain, AI tools offer a promising means to enhance the efficiency and accuracy of literature reviews. This study employed AI to screen, code, and validate research articles, demonstrating its effectiveness in expediting systematic reviews while maintaining high accuracy in inclusion screening. This case study involved a systematic review of 22,028 resources (identified from PsycINFO, Academic Search Ultimate, and Google) and a final data set of 268 relevant studies. AI screening was integral in effectively conducting multiple rounds of screening. However, findings also highlight challenges in AI-assisted qualitative data abstraction, underscoring the continued need for human expertise in complex coding tasks. The study contributes to the ongoing discourse on integrating AI into prevention science methodologies and offers insights for optimizing AI applications in systematic reviews.

Artificial Intelligence

Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.

Central nervous system (CNS) injuries are the leading cause of permanent disability and premature death in adults worldwide, with their incidence continuing to rise amid social development. These injuries not only severely impair the quality of life but also impose a heavy burden on the global public health system. Current clinical interventions, such as decompression and thrombolysis, can alleviate primary injury but fail to effectively reverse the secondary neuroinflammatory damage. Traditional anti-inflammatory therapies, which cannot block the upstream source of the inflammatory cascade, have led to repeated failures in global clinical translation research over the past decades. Gasdermins were first characterized in studies of systemic inflammatory diseases. These proteins form transmembrane pores to drive the release of proinflammatory factors and inflammatory cell death, serving as key mediators of host innate immunity. Recent studies have revealed that gasdermins play critical roles in regulating the initiation and amplification of neuroinflammation following CNS injury. To clarify the therapeutic potential of gasdermins as targets for injury repair, this review systematically summarizes the structure and function of gasdermins, as well as their cell-specific activation and regulatory mechanisms. We further elaborate on their pathological roles in these injuries and the corresponding therapeutic strategies, aiming to provide a theoretical reference for basic research and clinical translation in this field.

Humans

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans

Technology-Facilitated Gender-Based Violence Against Politically Active Women: A Systematic Review of Psychological and Political Consequences and Women's Coping Behaviors.

Technology-facilitated gender-based violence presents critical challenges for politically active women, whose professional roles often expose them to elevated levels of online abuse with far-reaching impacts on their emotional well-being, professional engagement, and participation in public life. This systematic review synthesizes findings from 48 studies employing qualitative, quantitative, and mixed-methods research to examine the psychological and political consequences and coping mechanisms associated with online harassment. Eighty-one percent of the included studies (39/48) report psychological distress, anxiety, and fear among targeted women, with 31% of the studies (15/48) identifying online harassment as a trigger for (re-) traumatization. The political consequences are equally significant, with 62% of the studies (30/48) documenting modifications in political messaging, 39% (19/48) noting reduced engagement with online platforms, and 29% (14/48) showing that women abandon their online presence altogether. Additionally, 20% (10/48) of the studies report cases of women withdrawing from their political roles. In terms of coping strategies, 66% (32/48) report women blocking or muting harassers, while 37% (18/48) document women reporting abuse to authorities or platforms. This study highlights the pervasive impact of technology-facilitated violence on women's emotional well-being, and their political participation and underscores its broader implications for democratic discourse and social equity.

Humans

Teaching Engagement and Caregiving Help in the Intensive Care Unit (TEACH-ICU) Scale: Content Validity.

BACKGROUND: Having family members provide care to their loved ones in the intensive care unit (ICU) is a beneficial yet seldom implemented approach. For family members to perform caregiving, nurses must be willing to teach, and such willingness is a developing area of research. OBJECTIVES: To adapt an instrument validated in family members, the Family Willingness for Caregiving Scale, to address nurses' willingness to teach family members caregiving skills. METHODS: Purposive and snowball sampling were used to recruit 10 expert ICU nurses through the American Association of Critical-Care Nurses' research website and social media platforms. The researchers conducted cognitive interviews with the nurses to address the instrument's content validity. RESULTS: The scale was refined based on the participants' feedback. Items were deleted, added, and revised. Furthermore, scale instructions were adjusted to emphasize the willingness to teach families of patients receiving mechanical ventilation. Qualitative themes emerged related to barriers to family engagement, including time constraints, patient acuity, and nurse and family characteristics. CONCLUSIONS: Content validity of the scale was assessed, with future research aimed at pilot testing and evaluating construct validity before using the scale as a research instrument. Practical implications include using the scale as an evaluation tool to determine nurses' willingness to teach family members about caregiving. After evaluation, various strategies could be incorporated to enhance family engagement in adult ICUs.

Humans

Overcoming the hurdles: A systematic review of barriers to self-initiated exercise in trauma recovery.

There is substantial quantitative evidence in support of exercise as beneficial for trauma recovery, particularly in targeting the neurobiological mechanisms disrupted by trauma. It is therefore important to understand the circumstances under which individuals may avoid exercise, ultimately preventing them from accessing the wellbeing benefits. Some qualitative articles have identified the factors which may prevent an individual from choosing to engage in exercise outside of a structured intervention (self-initiated exercise), but there lacks a synthesis across these differing articles. This systematic review aimed to synthesise qualitative evidence on trauma survivors' experience of barriers to self-initiated exercise. A systematic search of six databases was conducted to identify peer-reviewed qualitative findings on the perceived barriers to self-initiated exercise engagement, with six articles meeting the inclusion criteria. Thematic synthesis revealed three key themes: Searching for Safety, Staying With The Trauma, and Costs of Exercise and Trauma. In their decision to exercise, trauma survivors negotiate many barriers: the physiological, social, and environmental threats to their safety, trauma-related dissociation, and the costs of both exercise and trauma weighed against competing recovery needs. The small number of included studies reflects the emerging nature of research in this area, but it may limit the transferability of the findings. Nonetheless, as the first of its kind, this systematic review collates the experience of barriers as a first meaningful, exploratory step towards addressing them in future research. Taken together, the findings underscore the importance of a trauma-informed approach to ensure exercise remains unimpeded for trauma survivors.

Humans

Disentangling oscillatory and aperiodic neural activity in autism: A spectral parameterization analysis of neurofeedback intervention.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by atypical neural oscillations and heterogeneous alterations in excitation/inhibition (E/I) balance, the directionality of which varies across individuals, neural circuits, and developmental stages. While Alpha-band neurofeedback (NFB) is a promising intervention, its underlying neurophysiological mechanisms remain unclear, partly due to the conflation of periodic and aperiodic signals in traditional EEG analysis. METHODS: This randomized controlled trial recruited 40 children with ASD, assigned to either an experimental group (Alpha-training NFB) or a no-feedback group. Resting-state EEG and behavioral assessments (SRS, ABC) were collected pre- and post-intervention. We employed spectral parameterization to decompose neural activity into aperiodic (1/f slope, offset) and periodic (periodic alpha power, center frequency) components. RESULTS: NFB training yielded significant behavioral improvements in social cognition and relating skills. Physiologically, the experimental group exhibited a significant steepening of the aperiodic slope (increased exponent), reflecting a reduction in neural noise and potential optimization of inhibitory modulation. Furthermore, we observed enhanced periodic alpha power and an acceleration of the alpha center frequency (ACF), indicative of improved neural efficiency and maturation. These physiological shifts in frontal and occipital regions were significantly correlated with improvements in behavioral scores. CONCLUSION: Alpha-training NFB was associated with improvements in caregiver-rated behavioral scores and modulated spectral features of resting-state EEG in children with ASD. These findings validate the utility of spectral parameterization markers in evaluating neuromodulatory interventions.

Humans

Silent crises in the COVID-19 pandemic shadow: a six-year medico-legal review of non-lethal intimate partner violence in Morocco.

Intimate partner violence (IPV) is a major global public health concern and one of the most prevalent forms of gender-based violence, with significant consequences. This study analyzes non-lethal IPV cases reported to a medico-legal unit of Casablanca between 2018 and 2023. Data from 4,784 female victims were reviewed, focusing on socio-demographics, violence types, perpetrator relationships, and judicial involvement across the pre-COVID, peak COVID-19, and post-COVID periods. Married women represented 59.2% of victims. Physical violence predominated (83.1%), while sexual violence was underreported (14.7%). The year 2020 marked a sharp increase in reported non-lethal IPV cases (n = 1,005), correlating with pandemic confinement. Among married women, judicial requisition (legal request for forensic examination) and medico-legal certification (medical documentation for judicial use) rates were high (81.5% and 81.0%, respectively). Post-pandemic years declined moderately but remained above pre-COVID levels. International comparison confirmed a global rise in IPV during COVID-19, with Morocco displaying comparatively higher rates of medico-legal documentation and judicial involvement. IPV in Morocco is entrenched and intensified by COVID-19. While the medico-legal system is robust in documentation, the system must evolve by integrating systematic psychological assessment into medico-legal evaluations, standardizing certification and referral protocols, and strengthening coordination between medico-legal, health, and social support services to improve victim protection.

Humans

Organizational bullying among nursing faculty: A systematic review of consequences, contributing factors, and interventions.

BACKGROUND: Organizational bullying among nursing faculty is a systemic and pervasive issue with profound psychological, professional, and institutional consequences. Despite increasing awareness, the literature remains fragmented, and a comprehensive synthesis is lacking. METHODS: This systematic review followed PRISMA guidelines and examined empirical studies on organizational bullying among nursing faculty, with no date restrictions applied. A structured search across five databases (PubMed, Scopus, Web of Science, CINAHL, and Embase) identified studies that met inclusion criteria related to the consequences, contributing factors, and interventions. The Mixed Methods Appraisal Tool (MMAT) was used to assess study quality. RESULTS: Fifteen studies meeting the quality threshold were included. Organizational bullying was consistently associated with psychological distress (e.g., anxiety, depression, burnout, suicidal ideation), professional disengagement, and intent to leave. Contributing factors were categorized into structural and organizational (e.g., hierarchical power imbalances, toxic workplace culture), managerial and HR-related (e.g., lack of leadership support, poor reporting mechanisms), and individual/social (e.g., gender or ethnic discrimination, early-career vulnerability). Intervention strategies identified included policy reforms, leadership training, supportive reporting systems, and psychological support services, though evidence on their effectiveness remains limited. CONCLUSIONS: Organizational bullying in nursing academia is a serious and multifaceted challenge with detrimental effects on individuals and institutions. Addressing it requires a comprehensive, evidence-based approach that includes structural reforms, leadership development, and psychosocial support systems. Academic institutions must prioritize the creation of safe, inclusive, and respectful environments to retain faculty and sustain the quality of nursing education.

Faculty, Nursing

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3 mg/day(SMD = -7.57;95%C.I. = -8.25;-5.85); tamoxifen 160 mg/day(SMD = -1.73;95%C.I. = -2.32;-1.13); rivastigmine 3 mg/day(SMD = -1.13;95%C.I. = -1.06;-0.58); haloperidol 30 mg/day(SMD = -0.96;95%C.I. = -1.25;-0.75); valproate 750 mg/day(SMD = -0.76;95%C.I. = -1.48;-0.58); tamoxifen 40 mg/day(SMD = -0.75;95%C.I. = -1.41;-0.59); celecoxib 400 mg/day(SMD = -0.74;95%C.I. = -1.20;-0.38); paliperidone extended-release 12 mg/day(SMD = -0.62; 95%C.I. = -0.91;-0.32); olanzapine 15 mg/day(SMD = -0.59;95%C.I. = -0.60;-0.38); olanzapine 20 mg/day(SMD = -0.52;95%C.I. = -0.66;-0.38); risperidone 4 mg/day(SMD = -0.53;95%C.I. = -0.76;-0.29); allopurinol 600 mg/day(SMD = -0.54;95%C.I. = -0.67;-0.22); cariprazine 12 mg/day(SMD = -0.49;95%C.I. = -0.66;-0.33); risperidone 4.2 mg/day(SMD = -0.46;95%C.I. = -0.75;-0.17); lithium 1500 mg/day(SMD = -0.42;95%C.I. = -0.57;-0.28); ziprasidone 160 mg/day(SMD = -0.49;95%C.I. = -0.68;-0.31); asenapine 20 mg/day(SMD = -0.38;95%C.I. = -0.53;-0.22); haloperidol 8 mg/day(SMD = -0.34;95%C.I. = -0.63;-0.05); aripiprazole 15 mg/day(SMD = -0.33;95%C.I. = -0.61;-0.06) outperformed placebo. Ziprasidone 160 mg/day, celecoxib 200 mg/day, asenapine 20 mg/day, and asenapine 10 mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans