How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms.

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but the mechanisms underlying this link are poorly understood. Associative learning encompasses key mechanisms through which individuals learn to link important environmental inputs to emotional and behavioral responses. ACEs may impact the normative maturation of associative learning processes, resulting in their enduring maladaptive expression manifesting in psychopathology. In this review, we lay out a systematic and methodological overview and integration of the available evidence of the proposed association between ACEs and threat and reward learning processes. We summarize results from a systematic literature search (following PRISMA guidelines) which yielded a total of 81 articles (threat: n=38, reward: n=43). Across the threat and reward learning fields, behaviorally, we observed a converging pattern of aberrant learning in individuals with a history of ACEs, independent of other sample characteristics, specific ACE types, and outcome measures. Specifically, blunted threat learning was reflected in reduced discrimination between threat and safety cues, primarily driven by diminished responding to conditioned threat cues. Furthermore, attenuated reward learning manifested in reduced accuracy and learning rate in tasks involving acquisition of reward contingencies. Importantly, this pattern emerged despite substantial heterogeneity in ACE assessment and operationalization across both fields. We conclude that blunted threat and reward learning may represent a mechanistic route by which ACEs may become physiologically and neurobiologically embedded and ultimately confer greater risk for psychopathology. In closing, we discuss potentially fruitful future directions for the research field, including methodological and ACE assessment considerations.

Systematic literature review comparing clinical utility of heparin-bonded expanded polytetrafluoroethylene graft to autologous saphenous vein graft for management of below-knee peripheral arterial disease.

INTRODUCTION: This systematic literature review compares the clinical outcomes of heparin-bonded expanded polytetrafluoroethylene with autologous saphenous vein in the management of patients undergoing below-the-knee bypass to treat peripheral arterial disease. METHODS: An electronic literature search was conducted in MEDLINE and EMBASE to identify comparative studies in patients undergoing below-the-knee surgical bypass. Studies were screened at abstract and full text review using pre-defined inclusion criteria by two independent reviewers and critically appraised for risk of bias. Meta-analyses were conducted using Review Manager 5 software (Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: Eight retrospective cohort studies were identified. Meta-analysis of primary patency demonstrated no significant difference between heparin-bonded expanded polytetrafluoroethylene and autologous saphenous vein grafts after one year (0.91 [0.52-1.59], P=0.74), two years (1.12 [0.60-2.10], P=0.77), three years (0.62 [0.26-1.48], P=0.28) and 4 years [0.36 -1.39], P=0.31). Similarly, for secondary patency, no significant difference was detected at one (0.62 [0.33-1.15], P=0.13), two (0.83 [0.32-2.13], P=0.69), three (0.60 [0.27-1.32], P=0.20) and 4 years (0.66 [0.32-1.36], P=0.26) respectively. There was no significant difference between autologous veins and heparin-bonded expanded polytetrafluoroethylene for limb salvage and mortality at all timepoints. A sensitivity analysis to compare outflow vessel was conducted in only tibial bypass identified no differences. All analyses were considered at high-risk bias due to heterogeneity in study populations and attrition in follow-up. CONCLUSION: This meta-analysis demonstrates similar outcomes between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene for patency, limb salvage, and mortality through 4 years. Primary and secondary patency are superior at four years with autologous veins, but limb salvage and overall survival remained similar. The use of heparin-bonded expanded polytetrafluoroethylene synthetic grafts is a satisfactory option to prevent amputation, particularly when autologous saphenous vein grafts are not available. Controlled clinical studies are needed to further inform future decision making and economic modeling related to the choice of conduit for below-the-knee graft construction.

Online Group Psychotherapy: A Systematic Review.

INTRODUCTION: There is a need within counselling and psychotherapy to ensure their ability to respond to endemic presences such as the COVID-19 pandemic, by utilising rapid technological advances without compromising effectiveness. To do so, existing research about online group therapy must be built upon to provide a comprehensive understanding of the efficacious delivery of this therapy modality. Thus, a systematic review was conducted to collate what is currently known in the published and grey literature on online group therapy, using the PRISMA framework. Thirty-three articles were identified as including information regarding facilitating group therapy online. After appraising each article using appropriate quality appraisal tools, a thematic analysis was conducted on the papers, arriving at seven main themes summarising the main findings regarding online versus in-person groups, group planning, counselling micro skills, group processes, ethics, technology, and unique online therapy issues. There is a growing but incomplete body of knowledge that informs the group therapist regarding the ethical delivery of groups online. A more comprehensive review can enable group therapists to feel confident they are across best practice guidelines. Limitations and research implications are considered.

Predicting Treatment Effects from Surrogate Endpoints in Historical Trials in First-Line Metastatic Castration-Resistant Prostate Cancer.

Surrogate endpoints are becoming increasingly important in health technology assessment, where decisions are based on complex cost-effectiveness models (CEMs) that require numerous input parameters. Daniels and Hughes Surrogate Model was used to predict missing effect estimates in randomized controlled trials (RCTs) evaluating first-line treatments in metastatic castration-resistant prostate cancer (mCRPC) patients. Network meta-analyses (NMAs) were conducted to assess the comparative efficacy of these treatments. Databases were searched (inception to October 2022) using Ovid®. Several grey literature searches were also conducted (PROSPERO: CRD42021283512). Available trial data for radiographic progression-free survival (rPFS) and overall survival (OS) were used to predict the unreported effect of rPFS or OS for relevant comparator treatments. Bayesian NMAs were conducted using observed and predicted treatment effects. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best (p-best) were obtained. Twenty-five RCTs met the eligibility criteria and of these, 8 reported jointly rPFS and OS; while rPFS was predicted for 12 RCTs and 10 comparators, and OS was predicted for 5 RCTs and 6 comparators. A nonstandard dose of docetaxel (docetaxel 50 mg/m2 every 2 weeks) had the highest probability of being the most effective for rPFS (p-best: 59%) and OS (p-best: 48%), followed by talazoparib plus enzalutamide (13% and 19%, respectively). Advanced surrogate modelling techniques allowed obtaining relevant parameter and indirect estimates of previously unavailable data and may be used to populate future CEMs requiring rPFS and OS in first-line mCRPC.

Urine output is an early and strong predictor of acute kidney injury and associated mortality: a systematic literature review of 50 clinical studies.

BACKGROUND: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype. METHODS: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle-Ottawa Quality Assessment Scale for observational studies. RESULTS: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4-46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality. CONCLUSIONS: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

Automation of systematic reviews of biomedical literature: a scoping review of studies indexed in PubMed.

BACKGROUND: The demand for high-quality systematic literature reviews (SRs) for evidence-based medical decision-making is growing. SRs are costly and require the scarce resource of highly skilled reviewers. Automation technology has been proposed to save workload and expedite the SR workflow. We aimed to provide a comprehensive overview of SR automation studies indexed in PubMed, focusing on the applicability of these technologies in real world practice. METHODS: In November 2022, we extracted, combined, and ran an integrated PubMed search for SRs on SR automation. Full-text English peer-reviewed articles were included if they reported studies on SR automation methods (SSAM), or automated SRs (ASR). Bibliographic analyses and knowledge-discovery studies were excluded. Record screening was performed by single reviewers, and the selection of full text papers was performed in duplicate. We summarized the publication details, automated review stages, automation goals, applied tools, data sources, methods, results, and Google Scholar citations of SR automation studies. RESULTS: From 5321 records screened by title and abstract, we included 123 full text articles, of which 108 were SSAM and 15 ASR. Automation was applied for search (19/123, 15.4%), record screening (89/123, 72.4%), full-text selection (6/123, 4.9%), data extraction (13/123, 10.6%), risk of bias assessment (9/123, 7.3%), evidence synthesis (2/123, 1.6%), assessment of evidence quality (2/123, 1.6%), and reporting (2/123, 1.6%). Multiple SR stages were automated by 11 (8.9%) studies. The performance of automated record screening varied largely across SR topics. In published ASR, we found examples of automated search, record screening, full-text selection, and data extraction. In some ASRs, automation fully complemented manual reviews to increase sensitivity rather than to save workload. Reporting of automation details was often incomplete in ASRs. CONCLUSIONS: Automation techniques are being developed for all SR stages, but with limited real-world adoption. Most SR automation tools target single SR stages, with modest time savings for the entire SR process and varying sensitivity and specificity across studies. Therefore, the real-world benefits of SR automation remain uncertain. Standardizing the terminology, reporting, and metrics of study reports could enhance the adoption of SR automation techniques in real-world practice.

Analysis of three primary prostatic sarcoma cases and literature review.

OBJECTIVE: The objective of this study is to evaluate the clinical presentations, diagnostic approaches, and treatment modalities for primary prostate sarcoma postradical prostatectomy, aiming to enhance its diagnosis and management. METHODS: We retrospectively reviewed the clinical records of three male patients diagnosed with primary prostate sarcoma at Beijing Chaoyang Hospital, affiliated with Capital Medical University, from February 2014 to February 2024. All patients underwent transrectal prostate biopsies, which informed the decision to proceed with laparoscopic radical prostatectomies. After surgery, one patient received a combination of epirubicin and ifosfamide as immunotherapy, along with external beam radiotherapy. After comprehensive discussions regarding potential benefits and risks, the remaining two patients decided against undergoing radiotherapy and chemotherapy. RESULTS: Based on the pathological examination results, two patients were diagnosed with stromal sarcoma and one with spindle cell sarcoma, all classified as high-grade sarcomas. Immunohistochemical analysis showed that all three cases were positive for VIMENTIN, but other results did not show significant specificity. During the follow-up period, one patient died within 12 months, and two patients were lost to follow-up after 6 months. However, there were no evident signs of recurrence observed during the follow-up period. CONCLUSIONS: Primary prostate sarcoma is extremely rare and typically has a poor prognosis once diagnosed. Early diagnosis should be based on pathological and immunohistochemical testing results, followed by prompt surgical treatment and adjuvant radiotherapy and chemotherapy. Despite these measures, recurrence is common, underscoring the need for a detailed and appropriate treatment plan and systematic therapy for affected patients.

Decision-making for community resilience: A review of decision support systems and their applications.

Decision Support Systems (DSS) have emerged as important tools for enhancing community resilience due to their ability to provide timely and efficient solutions to disaster-related problems while reflecting the perspectives of different stakeholders and utilizing multiple data sources. This paper provides a comprehensive summary of DSS applications to community resilience, emphasizing how the different modeling techniques are used in different disaster phases. We found that optimization techniques are the most frequently used methods for building DSS. Furthermore, we found that DSS tend to focus more on the preparedness and response phases of disaster management, rather than the recovery and mitigation phases. Moreover, the study highlights the main challenges in developing and implementing DSS for resilience, such as data availability, the uncertainty of the disaster context, and the need for cross-disciplinary collaboration. Based on the reviewed papers, we provide some guidelines to practitioners to select the most suitable decision-support tools for the needs of their community. The study aims to help decision-makers and researchers build effective decision support systems for enhancing community resilience, considering the current challenges.

The History of the Development and Use of Suction Devices in Neurosurgery.

This article reviews the major devices, individuals, and other historical landmarks in the development of suction in the field of neurosurgery, where the operating fields are characteristically deep and narrow. Our review spans the 159 years since the first use of aspiration in surgery to modern applications. This report exemplifies a comprehensive history of suction, the minute iteration of devices, and the massive impact this technological development has had on medicine and neurosurgery.

Smart Buildings: A Comprehensive Systematic Literature Review on Data-Driven Building Management Systems.

Buildings are complex structures composed of heterogeneous elements; these require building management systems (BMSs) to dynamically adapt them to occupants' needs and leverage building resources. The fast growth of information and communication technologies (ICTs) has transformed the BMS field into a multidisciplinary one. Consequently, this has caused several research papers on data-driven solutions to require examination and classification. This paper provides a broad overview of BMS by conducting a systematic literature review (SLR) summarizing current trends in this field. Unlike similar reviews, this SLR provides a rigorous methodology to review current research from a computer science perspective. Therefore, our goal is four-fold: (i) Identify the main topics in the field of building; (ii) Identify the recent data-driven methods; (iii) Understand the BMS's underlying computing architecture (iv) Understand the features of BMS that contribute to the smartization of buildings. The result synthesizes our findings and provides research directions for further research.

Comparative Efficacy of Neoadjuvant Nivolumab Plus Chemotherapy versus Conventional Comparator Treatments in Resectable Non-Small-Cell Lung Cancer: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: This study aimed to estimate the relative efficacy of neoadjuvant nivolumab in combination with chemotherapy (neoNIVO + CT) compared to relevant treatments amongst resectable non-metastatic non-small-cell lung cancer (rNSCLC) patients. METHODS: Treatment comparisons were based on a network meta-analysis (NMA) using randomized clinical trial data identified via systematic literature review (SLR). The outcomes of interest were event-free survival (EFS) and pathological complete response (pCR). NeoNIVO + CT was compared to neoadjuvant chemotherapy (neoCT), neoadjuvant chemoradiotherapy (neoCRT), adjuvant chemotherapy (adjCT), and surgery alone (S). Due to the potential for effect modification by stage, all-stage and stage-specific networks were considered. Fixed-effect (FE) and random-effects Bayesian NMA models were run (EFS = hazard ratios [HR]; pCR = odds ratios [OR]; 95% credible intervals [CrI]). RESULTS: Sixty-one RCTs were identified (base case = 9 RCTs [n = 1978 patients]). In the all-stages FE model, neoNIVO + CT had statistically significant EFS improvements relative to neoCT (HR = 0.68 [95% CrI: 0.49, 0.94]), S (0.59 [0.42, 0.82]), adjCT (0.66 [0.45, 0.96]), but not relative to neoCRT (HR = 0.77 [0.52, 1.16]). NeoNIVO + CT (5 RCTs) had statistically significant higher odds of pCR relative to neoCT (OR = 12.53 [5.60, 33.82]) and neoCRT (7.15 [2.31, 24.34]). Stage-specific model findings were consistent. CONCLUSIONS: This NMA signals improved EFS and/or pCR of neoNIVO + CT relative to comparators among patients with rNSCLC.

Beyond Belief and Practice: An Exploratory Literature Review and Discussion of the Differential Impact of Spirituality and Religiosity on Mental Health Disorders.

The relationship between spirituality and religiosity and their impact on mental health is intricate and underexplored. This exploratory review aims to elucidate the distinct effects of these constructs, highlighting their contributions to psychological well-being and clinical practices. By dissecting the impacts of spirituality and religiosity on mental health, the study focuses on their individual and combined roles in shaping therapeutic approaches and theoretical understandings in the field. A literature review was conducted using PubMed, focusing on articles discussing spirituality, religiosity, and their intersection with mental health and psychopathology. Out of 312 identified articles, 69 peer-reviewed articles were included after screening for relevance. The results indicate that spirituality and religiosity significantly influence mental health yet are often conflated, leading to research inconsistencies and clinical challenges. Spirituality, as a broad and individualistic pathway, enhances personal well-being and resilience, often transcending organized religious practices. In contrast, religiosity, with its structured community support, sometimes imposes constraints that exacerbate stress under specific doctrinal pressures. Neurobiological evidence suggests that both constructs interact with cognitive processes and brain function, influencing emotional regulation and stress response. The study concludes that distinguishing between spirituality and religiosity is essential for precise academic discourse and effective clinical practice. This differentiation allows for more personalized therapeutic approaches, accommodating an individual's spiritual and religious contexts. The authors propose a refined framework for future research and therapeutic applications to be sensitive to the nuanced experiences of individuals and to better tailor interventions in clinical settings.

Ambulance service recognition of health inequalities and activities for reduction: An evidence and gap map of the published literature.

Background: Emergency medical services (EMS) are often patients' first point of contact for urgent and emergency care needs. Patients are triaged over the phone and may receive an ambulance response, with potential conveyance to the hospital. A recent scoping review suggested disparities in EMS patient care in the United States. However, it is unknown how health inequalities impact EMS care in other developed countries and how inequalities are being addressed. Objectives: This rapid evidence map of published literature aims to map known health inequalities in EMS patients and describe interventions reducing health inequalities in EMS patient care. Methods: The search strategy consisted of EMS synonyms and health inequality synonyms. The MEDLINE/PubMed database was searched from 1 January 2010 to 26 July 2022. Studies were included if they described empirical research exploring health inequalities within ambulance service patient care. Studies were mapped on to the EMS care interventions framework and Core20PLUS5 framework. Studies evaluating interventions were synthesised using the United Kingdom Allied Health Professions Public Health Strategic Framework. Results: The search strategy yielded 771 articles, excluding duplicates, with two more studies added from hand searches. One hundred studies met the inclusion criteria after full-text review. Inequalities in EMS patient care were predominantly situated in assessment, treatment and conveyance, although triage and response performance were also represented. Studies mostly explored EMS health inequalities within ethnic minority populations, populations with protected characteristics and the core issue of social deprivation. Studies evaluating interventions reducing health inequalities (n = 5) were from outside the United Kingdom and focused on older patients, ethnic minorities and those with limited English proficiency. Interventions included community paramedics, awareness campaigns, dedicated language lines and changes to EMS protocols. Conclusions: Further UK-based research exploring health inequalities of EMS patients would support ambulance service policy and intervention development to reduce health inequality in urgent and emergency care delivery.

Niraparib Maintenance Therapy for Brain Metastasis in Ovarian Endometrioid Adenocarcinoma With Peritoneal Carcinomatosis: A Comprehensive Case Study and Literature Review.

Brain metastasis is a rare complication of ovarian cancer, always found at the advanced stage. Even though different multimodal approaches are available, including surgical intervention and radiotherapy, there are no official guidelines for handling this serious complication. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are a group of medications initially used for maintenance therapy in platinum-sensitive recurrent ovarian cancer. Niraparib has shown some efficacy in patients with brain metastasis due to its unique properties of penetrating the blood-brain barrier. Here, we present the case of a 51-year-old patient with advanced ovarian cancer with no germline breast cancer susceptibility gene (BRCA) mutations. Despite undergoing surgery and multiple rounds of chemotherapy, the patient's condition worsened, culminating in brain metastasis. Given her neurological issues, radiotherapy was not an option, prompting the initiation of a 300 mg dose of niraparib. To date, only sporadic case reports in the literature have described patients with ovarian cancer treated with niraparib and complicated by brain metastasis. Our case is unique because it is the first case of a patient with the endometrioid type of ovarian cancer.

Immune Checkpoint Inhibitor-Induced Guillain Barre Syndrome: A Single-Institution Case Report and Narrative Review.

Guillain-Barré syndrome (GBS) resulting from the use of immune checkpoint inhibitors (ICIs) is relatively uncommon but has been reported. Herein, we discuss a case of a 67-year-old patient who received neoadjuvant ICI for treatment of non-small cell lung cancer and then presented with lower extremity weakness and areflexia, progressing to respiratory muscle and upper extremity weakness. Given the increasing use of ICI in cancer management, awareness of neurological autoimmune side effects is essential. ICI-mediated GBS can be severe and fatal if not diagnosed promptly. We discuss a case of ICI-induced GBS and review literature on current management approaches.

M-Learning in education during COVID-19: A systematic review of sentiment, challenges, and opportunities.

The flexibility and relatively low cost of mobile devices make educational systems more accessible for learners and educators worldwide. When incorporated with the internet, it creates a better learning environment than the conventional classroom lecture. Many studies have been done to shed insight into the existing state of mobile learning (M-learning) studies. However, further research is needed into this topic at a specific time, i.e., during the COVID-19 pandemic. This study aims to retrieve, review, investigate, and critically assess the existing literature on M-learning that was conducted during the COVID-19 concerning our research theme. This study considered publications from four databases, narrowed our initial search results of 4056 articles down to 83 that are relevant to our research questions, and did an in-depth analysis based on the systematic review protocol. The findings explored the major focusing areas of M-learning applications, the regional sentiment of M-learning users, the determinants and perceptions of M-learning, as well as the benefits, challenges, and opportunities associated with M-learning. This systematic literature review (SLR) was performed to apportion a contribution toward an improved understanding of the basic principles that underpin the rethinking of M-learning applications for policymakers, online course designers, and blended learning facilitators.

Blockchain governance and trust: A multi-sector thematic systematic review and exploration of future research directions.

This paper aims to critically examine the scholarly work conducted in blockchain (BC) governance. Without venturing into the wide range of governance paradigms, this research considers governance structures based on trust as a foundation for BC governance. A thematic systematic literature review is conducted to understand the literature on this topic, employing the SALSA (Search, Appraisal, Synthesis and Analysis) technique. An examination of 155 papers shows that using BC technology (BCT) replaces the cognitive attribution of trust in the material and human-independent code. It is also found that further research anchored to the 'trust' concept is required in building BC governance structures. To provide the direction in which the literature is travelling, future research questions on trust and governance are documented. In general, the literature review suggests that BC has the potential to revolutionize the way in which businesses operate. By improving transparency, efficiency, and security, BC can help businesses to reduce costs, improve customer satisfaction, and make better decisions. This research can help policymakers, industrialists, and researchers to identify where BC governance is being used and which aspects of governance are to be focused on. This paper is a general review of literature and evidence on contemporary developmental issues.

Müllerian adenosarcoma with sarcomatous overgrowth and heterologous elements: A case report and literature review.

Uterine mullerian adenosarcoma (MA) is a rare biphasic tumour that accounts for less than 0.5% of uterine neoplasms. The age range of presentation is wide, with the median age in the 5th decade of life. It usually has a good prognosis; however, it worsens when it presents with sarcomatous overgrowth, heterologous elements or infiltrates the myometrium. We report the case of a 63-year-old woman presenting with abnormal vaginal bleeding and a sensation of solid material coming out of the cervical canal who was diagnosed with mullerian adenosarcoma with sarcomatous overgrowth (MASO) and presence of heterologous elements after performing a mass biopsy and subsequent hysterectomy. We reviewed the literature, focusing especially on the differential diagnoses to be evaluated, as well as the differences in prognosis and treatment according to whether or not they present histologic features of poor prognosis.

An Interesting Case of Coronavirus NL63 Encephalitis Diagnosed in a 14-Year-Old Immunocompetent Female: A Case Report and Literature Review.

Human coronavirus NL63 (HCoV-NL63) belongs to the human coronavirus family but is distinct from other common coronaviruses such as HCoV-043, HCoV-229E, and SARS-CoV-1 and SARS-CoV-2 viruses. It causes a mild upper respiratory tract infection, affecting children and adults. The usual symptoms associated with the HCoV-NL63 infection are vomiting, a runny nose, and a sore throat. In vivo, HCoV-NL63 showed neurotropism as it can be detected in the CSF, through which it disseminates into the brain and the spinal column. Herein, we describe the case of a 14-year-old female patient who initially presented with disorientation and a drop in consciousness level and was admitted as a case of encephalitis to the pediatric intensive care unit.

Analytical advances in horseracing medication and doping control from 2018 to 2023.

The analytical approaches taken by laboratories to implement robust and efficient regulation of horseracing medication and doping control are complex and constantly evolving. Each laboratory's approach will be dictated by differences in regulatory, economic and scientific drivers specific to their local environment. However, in general, laboratories will all be undertaking developments and improvements to their screening strategies in order to meet new and emerging threats as well as provide improved service to their customers. In this paper, the published analytical advances in horseracing medication and doping control since the 22nd International Conference of Racing Analysts and Veterinarians will be reviewed. Due to the unprecedented impact of COVID-19 on the worldwide economy, the normal 2-year period of this review was extended to over 5 years. As such, there was considerable ground to cover, resulting in an increase in the number of relevant publications included from 107 to 307. Major trends in publications will be summarised and possible future directions highlighted. This will cover developments in the detection of 'small' and 'large' molecule drugs, sample preparation procedures and the use of alternative matrices, instrumental advances/applications, drug metabolism and pharmacokinetics, the detection and prevalence of 'endogenous' compounds and biomarker and OMICs approaches. Particular emphasis will be given to research into the potential threat of gene doping, which is a significant area of new and continued research for many laboratories. Furthermore, developments in analytical instrumentation relevant to equine medication and doping control will be discussed.