Outcomes Framework Research Articles

Probing potential priming: Defining, quantifying, and testing the causal priming effect using the potential outcomes framework.

Having previously seen an item helps uncover the item another time, given a perceptual or cognitive cue. Oftentimes, however, it may be difficult to quantify or test the existence and size of a perceptual or cognitive effect, in general, and a priming effect, in particular. This is because to examine the existence of and quantify the effect, one needs to compare two outcomes: the outcome had one previously seen the item vs. the outcome had one not seen the item. But only one of the two outcomes is observable. Here, we argue that the potential outcomes framework is useful to define, quantify, and test the causal priming effect. To demonstrate its efficacy, we apply the framework to study the priming effect using data from a between-subjects study involving English word identification. In addition, we show that what has been used intuitively by experimentalists to assess the priming effect in the past has a sound mathematical foundation. Finally, we examine the links between the proposed method in studying priming and the multinomial processing tree (MPT) model, and how to extend the method to study experimental paradigms involving exclusion and inclusion instructional conditions.

Development of workplace‐based assessment tools to support postgraduate training of provisionally registered pharmacists in Australia

AbstractThe Australian Pharmacy Council (APC) is the national accreditation authority for pharmacy education and training in Australia. In 2020, APC published revised Accreditation Standards and a new Performance Outcomes Framework (POF). The POF details expected performance for pharmacy students at the point of graduation and for pharmacy graduates on completion of postgraduate training. The APC and the pharmacist regulator, the Pharmacy Board of Australia collaborated on a project to develop workplace‐based assessment (WBA) tools for use in assessing performance of pharmacy graduates in the postgraduate training period. The objectives of the project were to; identify and develop an initial suite of WBA tools; develop accompanying guidance and supporting documentation; seek feedback from stakeholders; and pilot the WBA tools in community and hospital settings. The WBA tools were developed through consultative process overseen by a group of education experts (a Technical Working Group) and a governance group. The latter comprising members from the Pharmacy Board and APC. The Technical Working Group agreed on the tools to develop based on an available Intern Year Assessment Blueprint and the tools were then drafted by a consultant. APC held consultative forums and a pilot study to gather feedback from intern pharmacists and preceptors. The project resulted in development of a suite of three types of WBA tools; Entrustable Professional Activities (EPAs), Case Based Discussions (CbD), and In Training Assessment (ITA) activities covering six areas of focus. All types of tools that were initially agreed upon were made available for use. The WBA tools address 15 performance outcomes in the POF. Future direction will involve further evaluation of the tools in diverse practice settings and expansion of the current suite of tools to cover additional performance outcomes.

ADLIFE health outcome framework

The International Journal of Integrated Care (IJIC) is an online, open-access, peer-reviewed scientific journal that publishes original articles in the field of integrated care on a continuous basis.IJIC has an Impact Factor of 2.913 (2021 JCR, received in June 2022)The IJIC 20th Anniversary Issue was published in 2021.

Fine Particulate Air Pollution and the "No-Multiple-Versions-of-Treatment" Assumption: Does Particle Composition Matter for Causal Inference?

Here we discuss possible violations of the "no-multiple-versions-of-treatment" assumption in studies of outdoor fine particulate air pollution (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5)) owing to differences in particle composition, which in turn influence health. This assumption is part of the potential outcomes framework for causal inference, and it is needed for well-defined potential outcomes, as multiple versions of the same treatment could lead to different health risks for the same level of treatment. Since 2 locations can have the same outdoor PM2.5 mass concentration (i.e., treatment) but different chemical compositions (i.e., versions of treatment), violations of the "no-multiple-versions-of-treatment" assumption seem likely. Importantly, violations of this assumption will not bias health risk estimates for PM2.5 mass concentrations if there are no unmeasured confounders of the "version of treatment"-outcome relationship. However, confounding can occur if these factors are not identified and controlled for in the analysis. We describe situations in which this may occur and provide simulations to estimate the magnitude and direction of this possible bias. In general, violations of the "no-multiple-versions-of-treatment" assumption could be an underappreciated source of bias in studies of outdoor PM2.5. Analysis of the health impacts of outdoor PM2.5 mass concentrations across spatial domains with similar composition could help to address this issue.

Effectiveness of the low-FODMAP diet in improving non-celiac gluten sensitivity: a systematic review.

Non-celiac gluten sensitivity is characterised by the presence of gastrointestinal and extraintestinal symptoms following gluten ingestion. Recent studies suggested an association between non-celiac gluten sensitivity and the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). This systematic review aimed to examine literature evidence on the relationship between non-celiac gluten sensitivity and FODMAP intake. A comprehensive search was carried out for randomised clinical trials addressing gastrointestinal symptoms as the primary outcome, published between 2010 and 2020 in Portuguese, English or Spanish, and indexed in Scopus, PubMed, SciELO, Cochrane Library, CINAHL, Embase or VHL (LILACS) databases. The systematic review was performed using the population, intervention, comparison and outcome (PICO) framework. A total of 1133 articles were retrieved for further assessment. Three articles were selected for systematic review, one of which included two interventions with different periods and assessments. Quality of evidence was assessed according to the GRADE protocol. The selected articles used different instruments to measure gastrointestinal symptoms and quality of life, hindering comparison of data. Clinical trials identified an association between decreased gastrointestinal symptoms and FODMAP restriction. There are few studies on the topic, and those available used different instruments to assess gastrointestinal symptoms and quality of life. Nevertheless, current evidence supports the gluten-free diet still represents first-line therapy. However, a FODMAP restriction can decrease gastrointestinal symptoms in individuals with non-celiac gluten sensitivity. Further research is needed to confirm this finding.

Effect of the COVID-19 pandemic on incidence of long-term conditions in Welsh residents: a population linkage study

BackgroundThe COVID-19 pandemic had direct and indirect effects on health. Indirect effects on long term medical conditions (LTCs) are unclear. We examined trends in recorded incidences of LTCs and quantified differences between expected rates and observed rates from 2020 onwards. MethodsThis is a population data linkage study using primary and secondary care data within the Secure Anonymised Information Linkage Databank. We included data of Welsh residents diagnosed with any of 17 identified LTCs for the first time between Jan 1, 2000, and Dec 31, 2021. LTC's include mental health conditions, respiratory diseases, and heart conditions among others, generally chosen in line with the Quality and Outcomes Framework. The primary outcome was incidence rates (monthly number of new cases per 100 000 population). For each LTC, we did interrupted time series analysis of incidence rates from 2015 to 2021. Expected rates from between Jan 1, 2020, to Dec 31, 2021, were predicted using overall trends and seasonal patterns from the preceding 5 years and compared with observed rates. FindingsWe included 5 476 012 diagnoses from 2 257 992 individuals diagnosed with at least one LTC between Jan 1, 2000, to Dec 31, 2021. Across multiple long-term conditions, there was an abrupt reduction in observed incidence of new diagnoses from March to April 2020, followed by a general increase in incidence towards prepandemic rates. The conditions with the largest percentage difference between the observed and expected incidence rates in 2020 and 2021 were chronic obstructive pulmonary disease (38·4% lower than expected), depression (28·3% lower), hypertension (25·5% lower), and anxiety disorders (24·9% lower). The condition with the largest absolute difference between observed and expected incidence rates was anxiety disorders, with 830 per 100 000 less in 2020 and 2021 compared with observed rates. InterpretationThe reduction in incidence rates of LTCs suggests an underreporting of LTCs, especially during 2020 and early 2021. The emergence of these yet undiagnosed cases could result in a surge of new patients in the near future. FundingThis work was supported by the Wales COVID-19 Evidence Centre, funded by Health and Care Research Wales.

A partnership approach to supporting the health and wellbeing of the Charedi (Orthodox Jewish) community in London

BackgroundThere is a need for a specific programme of engagement around COVID-19 vaccination with the Charedi Orthodox Jewish community in Stamford Hill, London, UK. We co-produced a live event for women on COVID-19 safety and vaccination and wider health topics to support vaccine uptake and improve awareness of health and wellbeing issues. MethodsFor this qualitative analysis, we organised an event that was designed and delivered by a local community organisation in partnership with regional and local health partners and community groups. The event was for Charedi women aged 16 years and older, and provided information on COVID-19, childhood immunisations, oral health and dental hygiene, childhood respiratory infections, and mental health. The event included health stalls, a panel session, co-designed culturally competent physical information, and the opportunity to speak with health professionals. We evaluated the event using attendees' feedback forms, collected in person at the end of the event, and a thematic analysis of semi-structured interviews with organisers from community and statutory organisations. The evaluation was informed by a co-produced logic model and outcomes framework. FindingsMore than 100 women attended the event on March 28, 2022. Feedback suggested the focus on wider health issues was valued, and a greater number of more targeted events (eg on health for women older than 40) would be beneficial. Dental health, COVID-19 vaccination, and childhood immunisations were identified as the most important topics by participants. 16 (55%) of 29 respondents stated they would attend a similar event again, 12 (41%) stated they were unsure, and one (3%) said they would not attend again. Informal feedback from the community highlighted that the event was useful and acted as a basis for further engagement and collaboration with the community. InterpretationOur findings emphasised the need to work in partnership with a lead community organisation to identify and address principal health challenges within communities, to share community-specific insights, and to promote community events through community communication channels. Statutory institutions should engage with local community organisations to support and facilitate public health interventions to increase relevant vaccine uptake and to improve awareness around wider health and wellbeing issues and services. FundingNone.

Causal Inference with Spatio-Temporal Data: Estimating the Effects of Airstrikes on Insurgent Violence in Iraq

Abstract Many causal processes have spatial and temporal dimensions. Yet the classic causal inference framework is not directly applicable when the treatment and outcome variables are generated by spatio-temporal point processes. We extend the potential outcomes framework to these settings by formulating the treatment point process as a stochastic intervention. Our causal estimands include the expected number of outcome events in a specified area under a particular stochastic treatment assignment strategy. Our methodology allows for arbitrary patterns of spatial spillover and temporal carryover effects. Using martingale theory, we show that the proposed estimator is consistent and asymptotically normal as the number of time periods increases. We propose a sensitivity analysis for the possible existence of unmeasured confounders, and extend it to the Hájek estimator. Simulation studies are conducted to examine the estimators' finite sample performance. Finally, we illustrate the proposed methods by estimating the effects of American airstrikes on insurgent violence in Iraq from February 2007 to July 2008. Our analysis suggests that increasing the average number of daily airstrikes for up to 1 month may result in more insurgent attacks. We also find some evidence that airstrikes can displace attacks from Baghdad to new locations up to 400 km away.

Instrumented difference-in-differences.

Unmeasured confounding is a key threat to reliable causal inference based on observational studies. Motivated from two powerful natural experiment devices, the instrumental variables and difference-in-differences, we propose a new method called instrumented difference-in-differences that explicitly leverages exogenous randomness in an exposure trend to estimate the average and conditional average treatment effect in the presence of unmeasured confounding. We develop the identification assumptions using the potential outcomes framework. We propose a Wald estimator and a class of multiply robust and efficient semiparametric estimators, with provable consistency and asymptotic normality. In addition, we extend the instrumented difference-in-differences to a two-sample design to facilitate investigations of delayed treatment effect and provide a measure of weak identification. We demonstrate our results in simulated and realdatasets.

Circular economy policies and their transformative outcomes: The transformative intent of Finland's strategic policy programme

This paper analyses how Finland's circular economy policy attends not only to the promotion and acceleration of innovation, but also the reconfiguration of resource intensive systems. Socio-technical transitions research has historically focused on niche innovation processes. Yet recently, increasing attention has been placed on policy processes that seek to destabilise and disrupt incumbent systems and practices. Furthermore, the social justice aspects of system phase out policies have been brought to the fore. Our qualitative analysis of Finland's circular economy policy programme draws upon the transformative innovation policy and sustainability transitions policy-mix literatures, extending the transformative outcome framework to include outcomes related to the repercussions of regime destabilisation, coordination and tilting the socio-technical landscape. Our analysis shows that Finland's circular economy policy programme aims predominantly at niche stimulation and acceleration, with little emphasis on the regime destabilisation or coordination. Overall, the policy proposals aim toward a strategy of progressive system change, an orientation shaped by the country's corporatist approach to policy making and pre-existing plans.

A risk-based mutual insurance premium framework for establishing indices of vulnerability to the intentional introduction of transboundary animal diseases.

Biological agents as weapons of agro-crime or agro-terrorism pose threats to peace and economic stability. Such agents pre-exist worldwide as hazards, adversely affecting animal health, as well as imposing substantial burdens on many nations. Few studies have quantified the global risks and vulnerabilities of countries and regions to potential terrorist or criminal operations targeting animal health. We present here a risk-based mutual insurance premium framework for animal health outcomes built upon the World Organisation for Animal Health (WOAH) quantitative risk assessment paradigm. Our objective was to generate dimensionless and relative domain indices related to release and exposure for several biological factors, as well as to assess the preparedness and response ability of each country. We also considered disease-specific measures relating to pathogens, targeted animal populations, the ongoing disease situation, within- and among-country peace or conflict, disease-specific control measures, and the availability of technical tools and personnel for successful disease management. National economic, political, and research and development competencies were used to assess each WOAH Member's potential for resilience. We formulated indices of vulnerability for 25 WOAH Members selected from five worldwide regions; initially, against four transboundary infectious animal diseases that target diverse animal species. We developed these indices using variables obtained from public databases arising from multiple intergovernmental organizations. Subsequently, we compared the relative vulnerability indices among countries for each given disease using three different index building methods: arithmetic mean, distance matrix, and principal component analysis (PCA). The PCA-based approach provided the greatest ability to discriminate among the components and among countries and regions. Due to its transparency and reliance on publicly available datasets, the risk premium framework proposed herein may readily be adjusted by policymakers and agencies and utilized to improve risk management strategies against agro-crime or agro-terror events, as well as for unintentional disease introductions.

Need for a competency-based approach for the Public Health Workforce training: the ISS proposal

Abstract Issue The COVID-19 pandemic acted as a catalyst for a reconsidering health care professional workforce (HCPW) competency needed to face future public health challenges, in line with the recent WHO “Global Competency and Outcomes Framework for UHC” document. In this context, in the Italian G20 Presidency framework, the Italian National Institute of Health (ISS), launched a program named “Laboratorium” - recognised in the G20 Declarations of Ministers of Health and Leaders - aimed to the development of training tools suitable for distance learning in whatever context they are placed. Description of the problem Common competencies and needs of the HCPW have to be fulfilled through cross-sectional and multilevel training, to overcome the current emergency and be able to face future challenges. The aim is to provide a modular educational approach that is finalized to actively involve the participant: health professionals step in their training pathway according to their knowledge gaps, identify their specific learning objectives and, through a problem-based learning approach, acquire the proper skills for their function and tasks. Results We propose a two-tiered approach to training: the development of competence based courses oriented to active learning. A pilot course on Epidemic Intelligence design according to this model is ready to be released. At the same time, a repository of everything available on the web systematically selected from authorised sources by a scientific committee was created to support the training objective. It is characterised by a detailed multilevel tagging that allows an effective modularisation to reach only the content useful for its user. Lessons Accessibility to health-related training materials is a required necessity at every level of HCPW. Profiles within healthcare are increasingly heterogeneous and there is a need to focus on disseminating tools that can provide knowledge to address different healthcare scenarios and common purposes. Key messages • Future public health challenges underline a need for a competencies-based learning approach in Healthcare Workforce training. • Italian National Institute of Health propose two methods within the ‘Laboratorium’ project to enable this type of learning: specifically designed courses and a structured document repository.

Causal inference for multiple treatments using fractional factorial designs

AbstractWe consider the design and analysis of multi‐factor experiments using fractional factorial and incomplete designs within the potential outcome framework. These designs are particularly useful when limited resources make running a full factorial design infeasible. We connect our design‐based methods to standard regression methods. We further motivate the usefulness of these designs in multi‐factor observational studies, where certain treatment combinations may be so rare that there are no measured outcomes in the observed data corresponding to them. Therefore, conceptualizing a hypothetical fractional factorial experiment instead of a full factorial experiment allows for appropriate analysis in those settings. We illustrate our approach using biomedical data from the 2003–2004 cycle of the National Health and Nutrition Examination Survey to examine the effects of four common pesticides on body mass index.

Applying implementation frameworks to the clinical trial context

BackgroundClinical trials advance science, benefit society, and provide optimal care to individuals with some conditions, such as cancer. However, clinical trials often fail to reach their endpoints, and low participant enrollment remains a critical problem with trial conduct. In these ways, clinical trials can be considered beneficial evidence-based practices suffering from poor implementation. Prior approaches to improving trials have had difficulties with reproducibility and limited impact, perhaps due to the lack of an underlying trial improvement framework. For these reasons, we propose adapting implementation science frameworks to the clinical trial context to improve the implementation of clinical trials.Main textWe adapted an outcomes framework (Proctor’s Implementation Outcomes Framework) and a determinants framework (the Consolidated Framework for Implementation Research) to the trial context. We linked these frameworks to ERIC-based improvement strategies and present an inferential process model for identifying and selecting trial improvement strategies based on the Implementation Research Logic Model. We describe example applications of the framework components to the trial context and present a worked example of our model applied to a trial with poor enrollment. We then consider the implications of this approach on improving existing trials, the design of future trials, and assessing trial improvement interventions. Additionally, we consider the use of implementation science in the clinical trial context, and how clinical trials can be “test cases” for implementation research.ConclusionsClinical trials can be considered beneficial evidence-based interventions suffering from poor implementation. Adapting implementation science approaches to the clinical trial context can provide frameworks for contextual assessment, outcome measurement, targeted interventions, and a shared vocabulary for clinical trial improvement. Additionally, exploring implementation frameworks in the trial context can advance the science of implementation through both “test cases” and providing fertile ground for implementation intervention design and testing.

Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis epidemiology in England from 2004 to 2020: An observational study using primary care electronic health record data.

SummaryBackgroundContemporary data on rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritits (SpA) epidemiology in England are lacking. This knowledge is crucial to planning healthcare services. We updated algorithms defining patients with diagnoses of RA, PsA, and axial SpA in primary care and applied them to describe their incidence and prevalence in the Clinical Practice Research Datalink Aurum, an electronic health record (EHR) database covering ∼20% of England.MethodsAlgorithms for ascertaining patients with RA, axial SpA, and PsA diagnoses validated in primary care EHR databases using Read codes were updated (to account for the English NHS change to SNOMED CT diagnosis coding) and applied. Updated diagnosis and synthetic disease-modifying anti-rheumatic drug code lists were devised by rheumatologists and general practitioners. Annual incidence/point-prevalence of RA, PsA, and axial SpA diagnoses were calculated from 2004 to 2020 and stratified by age/sex.FindingsPoint-prevalence of RA/PsA diagnoses increased annually, peaking in 2019 (RA 0·779% [95% confidence interval (CI) 0·773, 0·784]; PsA 0·287% [95% CI 0·284, 0·291]) then falling slightly. Point-prevalence of axial SpA diagnoses increased annually (except in 2018/2019), peaking in 2020 (0·113% [95% CI 0·111, 0·115]). RA diagnosis annual incidence was higher between 2013-2019 (after inclusion in the Quality and Outcomes Framework, range 49·1 [95% CI 47·7, 50·5] to 52·1 [95% CI 50·6, 53·6]/100,000 person-years) than 2004-2012 (range 34·5 [95% CI 33·2, 35·7] to 40·0 [95% CI 38·6, 41·4]/100,000 person-years). Increases in the annual incidence of PsA/axial SpA diagnosis occurred following new classification criteria publication. Annual incidence of RA, PsA and axial SpA diagnoses fell by 40·1%, 67·4%, and 38·1%, respectively between 2019 and 2020, likely reflecting the COVID-19 pandemic's impact on their diagnosis.InterpretationRecorded RA, PsA, and axial SpA diagnoses are increasingly prevalent in England, underlining the importance of organising healthcare services to provide timely, treat-to-target care to optimise the health of >1% of adults in England.FundingNational Institute for Health and Care Research (NIHR300826).

Effectiveness of adjunct therapy for the treatment of apical periodontitis: A systematic review and meta-analysis.

Adjunct therapy refers to any intracanal procedure going beyond chemomechanical preparation with instruments and traditionally delivered irrigants (excluding interim dressings). It is not clear whether and which of these adjunct therapies have a significant impact on the outcome of root canal treatment [healing of apical periodontitis (AP) and other patient-related outcomes]. This systematic review aimed to analyse available evidence on the effectiveness of adjunct therapy for the treatment of AP in permanent teeth, according to a population, intervention, comparison, outcome, time and study design framework formulated a priori by the European Society of Endodontology. Five electronic databases (PubMed, Embase, Scopus, Cochrane and Web of Science) were searched up to October 2021 to identify clinical studies comparing adjunct therapy to no adjunct therapy in adult patients with AP. Animal studies, reviews, studies with less than 10 patients per arm and studies with a follow-up time of less than 1year, or less than 7 days for postoperative pain, were excluded. The quality of the included studies was appraised by the appropriate tools [Risk of Bias 2 (RoB2) for randomized clinical trials (RCTs) and Newcastle-Ottawa Scale for observational studies]. Meta-analysis was performed using a random-effects model. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Fourteen studies (13 RCTs and one retrospective cohort) fulfilled the inclusion criteria for this review. They evaluated different types of adjunct therapy: antimicrobial photodynamic therapy (aPDT; three studies), diode laser canal irradiation (3), Nd:YAG laser canal irradiation (2), Er;Cr:YSGG laser canal irradiation (1), ozone therapy (2) and ultrasonically activated irrigation (UAI) (4). Radiographical healing was reported in seven studies, but meta-analysis was only possible for UAI (two studies), showing no statistically significant difference in healing after 12 months. Pain after 7 days was reported in seven studies. Meta-analysis on three studies that used aPDT and on two studies using diode laser irradiation showed no significant difference in the prevalence of pain after 7 days between the control and adjunct therapy. According to RoB2 tool, six studies had a high risk of bias, five studies had some concerns, and two studies low risk of bias. The GRADE assessment revealed a very low strength of evidence for diode laser, and low strength of evidence for PDT, ozone and UAI studies. The included studies displayed significant heterogeneity in terms of type of adjunct therapy, technical details per adjunct therapy, outcome reporting and several combinations of these, limiting the potential for meta-analysis. There is insufficient evidence to recommend any adjunctive therapy for the treatment of apical periodontitis. Prospero CRD42021261869.

Estimating social influence in a social network using potential outcomes.

Social influence occurs when an individual's outcome is affected by another individual's actions. Current approaches in psychology that seek to examine social influence have focused on settings where individuals are nested in predefined groups and do not interact across groups. Such study designs permit using standard estimation methods such as multilevel models for estimating treatment effects but restrict social influence to originate only from individuals within the same group. In more general settings, such as social networks where an individual is free to interact with any other individual, the absence of discernible clusters or scientifically meaningful groups precludes existing estimation methods. In this article, we introduce a new class of methods for assessing social influence in social networks in the context of randomized experiments in psychology. Our proposal builds on the potential outcomes framework from the causal inference literature. In particular, we exploit the concept of (treatment) interference, which occurs between individuals when one individual's outcome is affected by other individuals' treatments. Estimation proceeds using randomization-based approaches that are established in other disciplines and guarantee valid inference by construction. We compared the proposed methods with standard methods empirically using Monte Carlo simulation studies. We illustrated the method using publicly available data from an experiment assessing the effects of an anticonflict intervention among students' peer networks. The R scripts used to implement the proposed methods in the simulation studies and the applied example are freely available online. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

“We don’t routinely check vaccination background in adults”: a national qualitative study of barriers and facilitators to vaccine delivery and uptake in adult migrants through UK primary care

ObjectivesExplore primary care professionals’ views around barriers/facilitators to catch-up vaccination in adult migrants (foreign-born; over 18 years of age) with incomplete/uncertain vaccination status and for routine vaccines to inform development...

Key population-led community-based same-day antiretroviral therapy (CB-SDART) initiation hub in Bangkok, Thailand: a protocol for a hybrid type 3 implementation trial

BackgroundSame-day antiretroviral therapy (SDART) initiation, in which people living with HIV (PLHIV) who are antiretroviral therapy (ART)-naïve, willing, and clinically eligible start ART on the same day of HIV diagnosis, has been implemented in several healthcare facilities in Thailand since 2017. This evidence-based practice has demonstrated increased ART uptake, virologic suppression, and retention in care. However, linkage to care gaps exist in community-based organizations (CBOs) in Bangkok whereby as much as 20% of key populations (KP), mainly men who have sex with men and transgender women, living with HIV were lost to follow-up pre-ART initiation. To increase access to and uptake of ART among these populations, this study proposes that trained KP lay providers should lead community-based ART (CB-SDART) initiation service. This protocol describes the combined use of the Proctor’s implementation outcome framework and the Consolidated Framework for Implementation Research to guide and evaluate the CB-SDART implementation.MethodsThis study follows the hybrid design type 3: it is an implementation trial that secondarily assesses service and client outcomes by comparative interrupted time series analysis. Five strategies have been formulated to meet three implementation outcomes (i.e., feasibility, fidelity, and sustainability): (1) developing stakeholder relationships by engaging the CBO leaderships, (2) training and educating KP lay providers, (3) adapting and tailoring SDART to CBO-specific context, (4) using evaluative and iterative strategies to assess adherence to standard operating procedures, and (5) developing stakeholder relationships by engaging external stakeholders. Teleconsultation with physicians and ART home delivery will be integrated as another ART initiation option for clients and allow service provision during the COVID-19 pandemic. A mixed-method assessment will be conducted on key stakeholders and PLHIV diagnosed at two implementing CBOs, Rainbow Sky Association of Thailand and Service Workers in Group Foundation, in Bangkok, Thailand.DiscussionThis implementation research may be the first to provide robust data at the implementation, service, and client levels to inform how to successfully task-shift SDART initiation service to trained KP lay providers and facilitate the expansion of CB-SDART in the future.Trial registrationThis trial was registered with the Thai Clinical Trial Registry as TCTR20210709004 on July 9, 2021.

Pharmacological mechanism and therapeutic efficacy of Icariside II in the treatment of acute ischemic stroke: a systematic review and network pharmacological analysis

Background and objectiveEpimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS.MethodsFirst, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes.ResultsTwelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets.ConclusionsICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS.