Citations

Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2 -related NDD.

As a new era of healthcare advocates a more valuable and intelligent approach to care management and delivery based on values and outcomes, shifts toward risk management to boost performance should be considered that encompass the capitalization of health assets or health strengths. To make full use of individuals’ or populations’ health assets, data capture and representation are needed. This paper uses a strengths-oriented case study mapped to an inter-disciplinary standardized terminology, the Omaha System, to illustrate and compare the conventional problem-based approach to care management with the strengths-oriented approach to care that demonstrates whole-person data capture of an individual’s health and health assets leveraged to promote health values and performance. The Omaha system provides a standardized framework to organize the concepts of all of health from a whole-person perspective for documentation to enable data analysis, interoperability, and health information exchange.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

Objective: The purpose of this report is to describe the elements of a Covid-19 Care Clinic (CCC), patient demographics, and outcomes. Methods: Descriptive statistics were used to describe demographics, clinical characteristics, and outcomes. This report is based on 4934 unique patients seen in the CCC who provided research authorization within a 10-month period of time (April 1, 2020-January 31, 2021). The CCC infection control processes consisted of a rooming process that mitigated SARS-COV-2 transmission, preparing examination rooms, using PPE by staff, in room lab drawing, and escorting services to minimize the time in clinic. Results: Of the 4934 unique patients seen (age range newborn-102 years), 76.8% were tested for COVID-19. Of those tested, 11.8% were positive for SARS-CoV-2. Ninety-two percent of the patients with the reason for the visit documented had COVID-19 type symptoms. Cough, shortness of breath, and chest pain were the most common presenting symptom in those with COVID-19. At the time of the visit in the CCC, 5.8% of the patients were actively contagious. Thirty days after being seen in the CCC, 9.1% of the patients were seen in the emergency department (ED) and 0.2% died. During the 10-month period there were no known occupationally related COVID-19 infections. Conclusion: The COVID-19 Care Clinic provided face-to-face access for all ages with COVID-19 type symptoms. A minority of patients had COVID-19 who were seen in the clinic. The clinic provided an additional venue of care outside of the ED. The infectious control measures employed were highly effective in protecting the staff. Lessons learned allow for decentralization of COVID-19 symptom care to the primary care practices employing the infection control measures.

Abstract Background:Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management interventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients' experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain. Objectives:This study aimed to gain insight into the experiences of people with chronic pain when engaging with EPIO, an application (app)-based cognitive-behavioral pain self-management intervention program.Methods: Participants (N=50) living with chronic pain received access to the EPIO intervention for 3 months. During this time, all participants received a follow-up phone call at 2-3 weeks, and a subsample (n=15) also participated in individual semi-structured interviews after 3 months. A qualitative design was used and thematic analysis was employed aiming to capture participants’ experiences when engaging with the EPIO intervention program. Results:Findings identifying program-related experiences and engagement were organized into three main topics, each with three sub-themes: (1) Engaging with EPIO; motivation to learn, fostering joy and enthusiasm, and helpful reminders and personalization, (2) Coping with pain in everyday life; awareness, practice and using EPIO, and (3) The value of engaging with the EPIO program; EPIO – a friend, making peace with the presence of pain, and fostering communication and social support. Conclusions: The current study explored participants’ experiences and engagement with EPIO, a digital self-management intervention program for people living with chronic pain. Findings highlighted identifying valued aspects related to motivation for engagement, incorporating content in support of daily coping, and encouraging a sense of acceptance and relatedness as vital components for facilitating program engagement.Trial Registration: ClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104

The poly(ADP-ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel-treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti-CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H-score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient-derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.