Fine mapping with epigenetic information and 3D structure

Since 2005, thousands of genome-wide association studies (GWAS) have been published, identifying hundreds of thousands of genetic variants that increase risk of complex traits such as autoimmune diseases. This wealth of data has the potential to improve patient care, through personalized medicine and the identification of novel drug targets. However, the potential of GWAS for clinical translation has not been fully achieved yet, due to the fact that the functional interpretation of risk variants and the identification of causal variants and genes are challenging. The past decade has seen the development of great advances that are facilitating the overcoming of these limitations, by utilizing a plethora of genomics and epigenomics tools to map and characterize regulatory elements and chromatin interactions, which can be used to fine map GWAS loci, and advance our understanding of the biological mechanisms that cause disease.

Epigenome-wide epidemiologic studies of human immunodeficiency virus infection, treatment, and disease progression

Despite significant advances in the treatment and care of people with HIV (PWH), several challenges remain in our understanding of disease pathogenesis to improve patient care. HIV infection can modify the host epigenome and as such can impact disease progression, as well as the molecular processes driving non-AIDS comorbidities in PWH. Epigenetic epidemiologic studies including epigenome-wide association studies (EWAS) offer a unique set of tools to expand our understanding of HIV disease and to identify novel strategies applicable to treatment and diagnosis in this patient population. In this review, we summarize the current state of knowledge from epigenetic epidemiologic studies of PWH, identify the main challenges of this approach, and highlight future directions for the field. Emerging epigenetic epidemiologic studies of PWH can expand our understanding of HIV infection and health outcomes, improve scientific validity through collaboration and replication, and increase the coverage of diverse populations affected by the global HIV pandemic. Through this review, we hope to highlight the potential of EWAS as a tool for HIV research and to engage more investigators to explore its application to important research questions.

Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

Hydrocephalus is a neurological condition due to the aberrant circulation and/or obstruction of cerebrospinal fluid (CSF) flow with consequent enlargement of cerebral ventricular cavities. However, it is noticed that a lot of patients may still go through symptomatic progression despite standard shunting procedures, suggesting that hydrocephalus is far more complicated than a simple CSF circulative/obstructive disorder. Growing evidence indicates that genetic factors play a fundamental role in the pathogenesis of some hydrocephalus. Although the genetic research of hydrocephalus in humans is limited, many genetic loci of hydrocephalus have been defined in animal models. In general, the molecular abnormalities involved in the pathogenesis of hydrocephalus include brain development and ependymal cell dysfunction, apoptosis, inflammation, free radical generation, blood flow, and cerebral metabolism. Moreover, recent studies have indicated that the molecular abnormalities relevant to aberrant cerebral glymphatic drainage turn into an attractive subject in the CSF circulation disorder. Furthermore, the prevalent risk factors could facilitate the development of hydrocephalus. In this review, we elicited some possible fundamental molecular mechanisms and facilitating risk factors involved in the pathogenesis of hydrocephalus, and aimed to widen the diagnosis and therapeutic strategies for hydrocephalus management. Such knowledge could be used to improve patient care in different ways, such as early precise diagnosis and effective therapeutic regimens.

Addressing barriers to evidence-based medicine in pediatric surgery: an introduction to the Canadian Association of Paediatric Surgeons Evidence-Based Resource

BackgroundPediatric surgical practice lags behind medicine in presence and use of evidence, primarily due to time constraints of using existing tools that are not specific to pediatric surgery, lack of sufficient patient data and unstructured pediatric surgery training methods.MethodWe developed, disseminated and tested the effectiveness of an evidence-based resource for pediatric surgeons and researchers that provides brief, informative summaries of quality-assessed systematic reviews and meta-analyses on conflicting pediatric surgery topics.ResultsResponses of 91 actively practicing surgeons who used the resource were analysed. The majority of participants found the resource useful (75%), improved their patient care (66.6%), and more than half (54.2%) found it useful in identifying research gaps. Almost all participants reported that the resource could be used as a teaching tool (93%).ConclusionLack of awareness of the resource is the primary barrier to its routine use, leading to potential calls for more active dissemination worldwide. Users of the Canadian Association of Paediatric Surgeons Evidence-Based Resource find that the summaries are useful, identify research gaps, help mitigate multiple barriers to evidence-based medicine, and may improve patient care.

Effectiveness of Bi-lingual Multidisciplinary Simulation-based Training in Improving Communication and Breaking Bad-News Skills

Background: Healthcare worker (HCW)-patient communication is an essential element of every patient’s journey, and evidence links good communication with favourable patient experiences and outcomes. Simulation-based training (SBT) is a promising and effective tool to improve such communication. Aim: To develop a bilingual SBT programme in communication skills for all HCWs in an academic tertiary hospital, to improve patient care, experiences and outcomes. Methods: This was a quasi-experimental design, conducted in 2018 at King Abdulaziz University (KAU). We designed and delivered a bilingual, simulation-based, full-day course for HCWs (both clinical and administrative), and measured its impact by comparing pre- and post-course test scores, participant feedback, and instructor performance satisfaction indices. Results: We trained 318 HCWs over 15 days, using 10 instructors. Post-test scores showed individual and overall improvement. The average scores were 26.6% (14-40%) for the pre-test and 55.8% (37-70%) for the post-test, with an average improvement of 29% (P<0.005). Participant feedback was 77% positive and in favour of more training. The average instructor performance satisfaction score was 96.2% (92-99%). Conclusion: We demonstrated the positive impact of SBT on communication skills for both clinical and administrative HCWs. We also demonstrated the sustainability and scalability of this course.

Creating a small baby program: a single center’s experience

Creation of a small baby program requires special resources and multidisciplinary engagement. Such a program has the potential to improve patient care, parent and staff satisfaction, collaboration and communication. We have described benefits, challenges, and practical approaches to creating and maintaining a small baby program that could be a model for the development of special programs for other sub-populations within in the NICU.

Communication Vulnerability within Singapore’s Healthcare Environment

Communication difficulties can, and often do, create barriers between patients and healthcare workers (HCWs). We examined the perceptual differences between patients and caregivers; and HCWs with regards to their perceived communication vulnerabilities and identified communication needs in a tertiary hospital. A survey was conducted in selected outpatient settings among patients, their caregivers and HCWs, in a cross-sectional study. Respondents rated the reasons and frequency of encountering the communication difficulties during a hospital visit. Fifty-four percent of patients and caregivers cited poor hearing in the presence of noise, while HCWs cited patient’s poor vision (87%) as their primary communication barrier that requires improvement. Majority of HCWs (90%) had encountered patients who presented multiple communication barriers a quarter of the time. A third of HCWs felt that such encounters were especially challenging during communication, with very limited strategies available to deal with such communication vulnerable individuals. Patients, caregivers and HCWs universally experience communication challenges, even if their perceived barriers to communication happen to differ. Such perceptual difference between patients and HCWs may lead to inconsistent use of communication strategies by HCWs, potentially compromising patient’s healthcare needs. Nonetheless, the onus is on healthcare providers to bridge this communication gap to improve patient care.

Assessing Quality in Advance Care Planning Documentation: A Survey of Current Methods

Background High-quality advance care planning (ACP) documentation facilitates the communication of patients’ wishes as they progress in their disease course and travel between health care settings. No consensus exists regarding evaluation of documentation quality, and diverse strategies for assessing quality have been adopted in clinical ACP studies. Methodology We conducted a literature review in PubMed and via manual search to identify clinical studies that assessed ACP quality or completeness as an outcome measure over a 5-year period. Studies that treated ACP as a binary outcome variable (present or absent), studies that took place outside of the US, and studies in pediatric populations were excluded from review. Results We identified 11 studies for inclusion in our review. Across study methodologies, the following 8 quality domains were identified: discussion frequency, documentation accessibility, discussion timing, health care proxy, health goals or values, scope of treatment/code status, prognosis/illness understanding, and end of life (EOL) care planning. Each study assessed between 2 and 6 domains. Divergent methods for assessing quality domains were utilized, including manual qualitative analysis and natural language processing techniques. Conclusion Defining and measuring the quality of documentation is critical to developing ACP programs that improve patient care. Our review provides an adaptable framework centered around quality domains.