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CONSORT 2025 statement: Updated guideline for reporting randomised trials
Get PDFBACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent
RNA helicases, DDX5 and DDX17, facilitate lytic reactivation of gammaherpesviruses
Get PDFHuman gammaherpesviruses comprise of Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), and are oncogenic viruses that cause life-long infections. The gammaherpesviruses utilize an extensive virus-host interaction network for facilitating viral replication, whereby virus-encoded proteins modulate host processes. Thus, identifying targets of viral proteins that aid in gammaherpesviral replication will help develop therapies to combat these viruses. We identified that host proteins DDX5 and DDX17 interact with gammaherpesviral protein kinases, KSHV-encoded vPK and EBV-encoded BGLF4. We found that DDX5 and DDX17 are required for gammaherpesviral lytic reactivation and loss of both DDX5 and DDX17 decreased KSHV and EBV lytic reactivation. Depletion of DDX5 and DDX17 lowered the transcription of KSHV RTA, the key viral gene that drives the lytic replication cascade, due to reduced occupancy of Brg1, a chromatin remodeler, at the RTA promoter. Consequently, inhibition of Brg1 decreased gammaherpesviral lytic reactivation. Here we demonstrate how gammaherpesviruses hijack the function of two host proteins to promote their lytic replication cycle
Violence Against Administrators: The Roles of Student, School, and Community Strengths and Cultural Pluralism
Get PDFScientific and public attention regarding educator-directed violence has increased over the past 15 years; however, research on violence against administrators is limited. Although school administrators are responsible for school performance and safety, they can be particularly vulnerable to violence from students, teachers, and parents. This study includes 497 pre-K–12th grade school administrators in the United States. A path analysis was conducted to examine the associations between administrator perceptions of student-, school-, and community-level strengths and administrator experiences of verbal/threatening and physical violence. Cultural pluralism, which incorporates student and staff support of cultural differences and honors different voices and cultures in curricula and discussion, was investigated as a moderator of these associations. Results indicate that (a) student strengths are associated with less student verbal/threatening violence against administrators; (b) school strengths are associated with less student and colleague verbal/threatening violence against administrators; and (c) community strengths are associated with less physical violence from students and less verbal/threatening violence from parents against administrators. Cultural pluralism practices significantly moderated the relationship between student strengths and physical violence from colleagues. Findings highlight school practices and policies across the school ecology that are associated with less administrator-directed violence
SPIRIT 2025 statement: Updated guideline for protocols of randomised trials
Get PDFImportance The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Objective To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. Design We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Findings Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Conclusions and relevance Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers
Testing a systematically braided alcohol reduction and HIV status neutral intervention among people receiving STI care in Malawi: study protocol for a pilot hybrid type 1 effectiveness-implementation randomized controlled trial
Get PDFBackground: Heavy alcohol use is common in Malawi among people receiving sexually transmitted infections (STI) care and is a critical barrier to the success of HIV prevention and treatment efforts. Methods: This protocol presents a pilot hybrid type 1 effectiveness implementation trial evaluating the short-term effectiveness and implementation of a scalable evidence-based intervention (EBI) to reduce alcohol use and provide HIV prevention and treatment counseling for people with heavy drinking receiving STI care in Malawi. We developed a 3-session intervention, Treat4All, that uses motivational interviewing, problem-solving skills, psychoeducation, alcohol refusal, HIV prevention and treatment skills building, and goal setting to reduce alcohol and facilitate engagement in HIV prevention and treatment. We have also integrated HIV prevention content to focus on persistent PrEP use and HIV treatment adherence to improve antiretroviral therapy (ART) adherence and viral suppression. We will conduct a two-arm pilot randomized controlled trial (RCT) in an STI care setting in urban Malawi to compare the preliminary effectiveness and implementation of Treat4All to usual care for decreasing the proportion of heavy drinking days, corroborated with phosphatidylethanol, an alcohol biomarker, and improving HIV outcomes (viral suppression among PWH; PrEP use among those at risk). We will randomly assign 160 people receiving STI care in Lilongwe who report heavy drinking (n = 80 people with HIV; PWH; n = 80 people at high risk of HIV acquisition) to Treat4All or usual care. Discussion: Our study will produce a systematically braided, scalable HIV status-neutral EBI for alcohol reduction and optimization of HIV prevention and treatment behaviors to evaluate in a larger effectiveness-implementation trial. Our study will directly expand alcohol reduction and HIV status-neutral programs for alcohol-impacted populations throughout sub-Saharan Africa and other regions where alcohol contributes to the ongoing HIV epidemic. Clinical trial registration: ClinicalTrials.gov, NCT06668363
Causal Inference with Machine Learning for Complex Data Contexts
Get PDFAs data volume, setting complexity, and computational capabilities expand, researchers in causal inference are tasked with developing methods that can meet the demands of this evolving landscape while maintaining robustness, efficiency, and (ultimately) effectiveness in addressing increasingly intricate counterfactual questions. This dissertation addresses challenges in causal inference within \textit{complex data contexts}, where the nuances of the observation patterns and the data's structure open both theoretical challenges and pathways for methodological innovation. Drawing on recent advancements in machine learning for causal inference and semiparametric theory, this dissertation develops new methodologies that aim to more fully leverage available information about treatment effects across several diverse settings. Chapters 2 and 3 focus on estimating causal effects in hybrid trials with external controls, systematically addressing the trade-off between causal assumptions and efficiency bounds through a semiparametric lens. Chapter 4 explores hierarchical data structures, where a specific treatment randomization scheme uncovers previously unobserved information about treatment effects. In this context, `proxy potential outcomes' are introduced as a novel tool for approximating the joint distribution of potential outcomes to improve estimation efficiency. In precision medicine (Chapter 5) contexts where acquiring certain features is costly, we extend the active feature acquisition (AFA) framework to prioritize gathering only the most relevant information, minimizing acquisition costs while optimizing treatment recommendations. Chapter 6 further develops AFA methodology in a more general context, where multiple feature sets can be acquired sequentially. Here, we introduce a nonparametric Acquisition Conditioned Oracle (ACO), which balances acquisition costs with prediction and decision-making objectives. Collectively, these contributions underscore the importance of critically examining the origins and structure of treatment effect information within complex data contexts to enhance the rigor and efficiency of causal inference.Doctor of Philosoph
High Gamma Stimulation (80 Hz) Optical Stimulation of the IL-NAcSh Pathway Alters Innate but not Learned Aversion in Female Rats
Get PDFThe infralimbic cortex (IL) to nucleus accumbens shell (NAcSh) circuit is implicated in hedonicprocessing. Our lab established that 20 Hz optical stimulation of this pathway reducedconditioned taste aversion (CTA) in male rats, but not females. Additionally, local field potential(LFP) activity in the IL and NAcSh, and its functional connectivity, was selectively restricted to thehigh gamma frequency range (70-90 Hz) during innate and learned aversion in females. Here, weexamined if 80 Hz optical stimulation could alter innate and/or learned aversion in female rats.Results showed that 80 Hz stimulation of the IL-NAcSh pathway had no effect on CTA butsignificantly decreased appetitive and aversive responses (primarily during the first 5 minutes ofthe session), and increased neutral responses, during quinine exposure. These findings indicatethat the IL-NAcSh pathway is not involved in learned aversion but may play a role in mediatinginnate aversion in females.Master of Art
IMPACTING CESAREAN SECTION RATES IN LOW-RISK NULLIPAROUS LABORING WOMEN
Get PDFCesarean births, when conducted for medical indications, can improve both maternal and fetal outcomes, however, when performed for non-medical reasons, increase mothers’ and their babies’ risk for negative outcomes. Women are considered low risk for cesarean birth if they are giving live birth for the first time, with a single full-term fetus in the vertex or head down position, known as nulliparous, term, singleton, vertex, or NTSV. Despite low risk among this population, first-time cesarean births represent the largest category of cesarean births. This doctoral quality improvement project aimed to reduce the rate of cesarean sections among low-risk nulliparous laboring women at WakeMed Cary Hospital using standardized, evidence-based guidelines and decision-making tools from the 2022 California Maternal Quality Care Collaborative (CMQCC) Toolkit to Support Vaginal Birth and Reduce Primary Cesareans. Nurses used the “Spontaneous Labor Algorithm” and the “Induction of Labor Algorithm” to guide care decision-making. At the same time, the “Pre-Cesarean Communication Tool for Labor Dystocia or Failed Induction” (CMQCC, 2022, p.142) served as a checklist to facilitate conversation with providers and track compliance with the evidence-based standards of care provided by each algorithm. From June 9th to July 20th, 2024, Wake Med Cary Women’s Pavilion delivered 394 babies. Of these 394 patients, n=153 (38.8%) met the NTSV criteria. Sixteen of 75 (21.33%) NTSV patients delivered in June, and 23 out of 78 (29.48%) NTSV patients delivered in July experienced a cesarean section. Although project outcomes (June, July, August) were not statistically different from baseline data (March, April, May) (t(2)=0.0853, p=0.9398), this project identified many important implications for practice. First, change strategies must target healthcare decision-makers, in this case, obstetric providers rather than labor nurses. Next, this project highlighted the importance of standardized practice guidelines and how practice discrepancies, even within a single organization, impact patient outcomes, such as the NTSV cesarean birth rate. Therefore, standardizing care practices and organizational policies is vital in reducing the risk of negative outcomes associated with unwarranted cesarean births for both mothers and their babies.Doctor of Nursing Practic
LINKING MACHINE LEARNING-PREDICTED BRAIN AGING WITH ALCOHOL-RELATED PHENOTYPES
Get PDFAlcohol use is proposed to be an accelerator of brain aging. Novel machine learning methods using structural brain images can estimate “brain age” as an individualized volume-based biomarker of aging; however, it currently remains unknown whether estimates of brain age are related to cognitive and physiological phenotypes typically associated with alcohol misuse. The goal of this dissertation is to first examine an estimation of brain aging with machine learning as it relates to alcohol misuse and a cognitive phenotype, behavioral inflexibility. In a sample of healthy adults, we found more hazardous alcohol use predicted more accelerated brain aging, which in turn was associated with more inflexible behavior in a task. Brain aging was then discovered to be a partial mediator of the relationship of hazardous alcohol use and behavioral inflexibility. We then evaluated inflammation as a physiological phenotype that may be a potential mechanism of alcohol-related brain aging. In a separate sample of males recruited as heavy or moderate alcohol drinkers (Sample 1), we tested the association of a composite measure of proinflammatory cytokines and accelerated brain aging, which did not reveal to be significant. We then tested this association an additional larger and older sample with female subjects (Sample 2), which revealed a female-specific relationship for more inflammation as a significant predictor more accelerated brain aging. In addition, we observed two non-linear relationships with a measure of alcohol use in relation to both brain aging and inflammation, indicating a higher frequency of alcohol drinking predicted more accelerated brain aging and a higher level of inflammation. Lastly, we explored the contribution of adolescent (under 21) binge drinking history on adulthood brain aging in addition to an interaction with current hazardous alcohol use. There was no specific effect of adolescent binge drinking nor a combined effect with current drinking on adulthood brain aging. Together, these results suggest a link between hazardous alcohol drinking and accelerated brain aging that contributes to impaired behavioral flexibility and is potentially mechanistically explained by systemic inflammation. These findings are consistent but require future work to dissect the neurobiological mechanisms underlying behavioral impairments and role of inflammation.Doctor of Philosoph
“Promoting [Birth Control] Among Workers and Peasants” – Reading Population from the Peiping Morning Post in the Early 1930s
Get PDFIn this thesis, I examine how the discourse of population and birth control changed through the newspaper Population Supplement (renkou fukan人口副刊) under the then Beiping newspaper, the Peiping Morning Post (Beiping chenbao 北平晨報) from 1932-1936. My work highlights the two registers in the Supplement: The highbrow discourses by dominantly Chinese sociologists on linking population/overpopulation to the issues of national strengthening and nation crisis, and the letters from the Beiping urban residents (selected by the editors of the Supplement) asking for advice on contraceptive and birth control advice. I argue that there existed a disjuncture between these two registers, as the PS form presented a curated vision of Chinese society, only to be undermined by the residents’ pragmatic demands of birth control and contraceptive advice and tools.Master of Art