Exuberant fibroblast activity compromises lung function via ADAMTS4.

Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes-in particular the ECM protease ADAMTS4-and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus.

PURPOSE OF REVIEW: The aim of this study was to summarize current evidence regarding lenacapavir, a first in class HIV-1 capsid inhibitor, and its role as an emergent therapy for the treatment of HIV-1 infection. RECENT FINDINGS: HIV-1 capsid inhibitors (of which lenacapavir is the first in class) has been postulated to have activity against multidrug resistant HIV-1 viral isolates. Initial results from the phase 3 trial CAPELLA (combining oral and subcutaneous lenacapavir alongside failing drug therapies) suggest that there may be a role for these novel agents in a cohort of patients living with HIV-1 infection (PLWH) for whom multidrug resistance has previously been a barrier to effective therapy. Despite emergent lenacapavir resistance mutations detected in some study participants, virological suppression was still potentially attainable, offering some hope to PLWH with limited antiviral regimens available. Initial results from the CALIBRATE trial show promise for the role of lenacapavir-containing regimens in a treatment-naive cohort as well. SUMMARY: Lenacapavir may prove to be an adjunctive agent in the management of PLWH with significant HIV-1 drug resistance.

A National, County-Level Evaluation of the Association Between COVID-19 and Sexually Transmitted Infections Within the United States in 2020.

BACKGROUND: Shifts in public health infrastructure to respond to one emerging health threat may have unanticipated consequences for preexisting diseases. Previous research evaluating the impact of COVID-19 on sexually transmitted infections (STIs) has been conducted nationally, with little exploration of the impact on a granular geospatial level. This ecological study seeks to quantify the association between COVID-19 cases or deaths and chlamydia, gonorrhea, and syphilis cases for all US counties in 2020. METHODS: Separate, adjusted multivariable quasi-Poisson models with robust standard errors modeled the county-level association between 2020 COVID-19 cases and deaths per 100,000 and 2020 chlamydia, gonorrhea, or syphilis cases per 100,000. Models were adjusted for sociodemographic characteristics. RESULTS: Every 1000 additional COVID-19 cases per 100,000 was associated with a 1.80% increase in the average number of chlamydia cases ( P < 0.001) and a 5.00% increase in the average number of gonorrhea cases ( P < 0.001). Every 1000 additional COVID-19 deaths per 100,000 was associated with a 57.9% increase in the average number gonorrhea cases ( P < 0.001) and a 74.2% decrease in the average number of syphilis cases ( P = 0.004). CONCLUSIONS: Higher rates of COVID-19 cases and deaths were associated with increased rates of some STIs at the US county level. The underlying reasons for these associations could not be established by this study. The emergency response to an emerging threat may have unanticipated influence on preexisting diseases that varies by level of governance.

Gender differences in cancer spousal caregiving: A systematic review.

OBJECTIVES: Cancer does affect not only the lives of the patients but also that of their spouses. The aims of this systematic review are to (i) explore the gender differences in the impact of caregiving for cancer on spousal caregivers, (ii) facilitate the conceptual understanding of gender differences in caregiving, and (iii) identify directions for future research and clinical practice targeting spousal caregivers. METHODS: A comprehensive search was conducted of the electronic databases of MEDLINE, PsycINFO, EBSCO, and CINAHL Plus for papers published in English between 2000 and 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify, select, appraise, and synthesize the studies. RESULTS: A total of 20 studies from seven countries were reviewed. Findings of the studies were presented using the biopsychosocial model. Spousal caregivers of cancer patients suffered from physical, psychological, and socioeconomic morbidities, with female spousal caregivers reporting a higher level of distress. The gendered positioning of spousal caregivers in the societal context had further brought about over-responsibility and self-sacrifice among women. SIGNIFICANCE OF RESULTS: The gendered positions of cancer spousal caregivers further illustrated the gender differences in the caregiving experiences and consequences. Health-care professionals in routine clinical practice should be proactive in identifying physical, mental, and social morbidities among cancer spousal caregivers, particularly female ones, and providing timely interventions. Health-care professionals should recognize the pressing need for empirical research, political engagement, and action plans to address the health status and health-related behaviors of patients' spouses along the cancer trajectory.

Acute angle closure glaucoma misdiagnosed as sinusitis.

A 69-year-old woman developed severe right suprabulbar pain with blurred right-sided vision. There were no haloes around lights, photophobia, nausea or vomiting. Investigations in the emergency department excluded a posterior communicating/internal carotid artery aneurysm. However, she did not have an ophthalmological assessment and the initial diagnosis was of sinusitis-related headache. An urgent ear, nose and throat assessment found no abnormality, but a local ophthalmologist subsequently diagnosed and managed the patient's acute angle closure crisis. Periocular pain always deserves detailed assessment with an accurate history, visual acuity assessment and intraocular pressure measurement.

Factors contributing to long-term refractive error after cataract surgery.

PURPOSE: To evaluate factors that may influence the direction and extent of long-term refractive error after cataract surgery. METHODS: This was a retrospective observational study conducted across two private practices in Sydney, NSW, Australia. The study population consisted of patients who underwent cataract phacoemulsification surgery between January 1 and December 31, 2018. Patients who received cataract surgery combined with another procedure were excluded. Demographic and biometric data including anterior chamber depth (ACD), keratometry, central corneal thickness, axial length (AL) and lens thickness were obtained pre-operatively. Spherical equivalent (SEQ) refraction was measured at 2 months and 3 years after surgery and compared with target refraction. Factors associated with refractive error were analyzed. RESULTS: This study included 221 eyes of 122 patients. A refractive error within 1.00 D was achieved in 217 eyes (98.2%) at 3 years post-operatively. Mean prediction error decreased significantly between 2 months and 3 years after surgery irrespective of whether eyes were more myopic (p < 0.001) or more hypermetropic than predicted (p < .0001). Pre-operative ACD and ACD-to-AL ratio were significantly associated with SEQ prediction error. CONCLUSION: After cataract surgery, refractive outcomes may be influenced by ACD and ACD-to-AL ratio. The pre-operative assessment of these risk factors may better inform IOL selection in individual patients. Prospective studies in a larger cohort are required.

Changes in refraction after cataract phacoemulsification surgery.

PURPOSE: After cataract phacoemulsification surgery, spherical equivalent refraction (SER) may be affected by factors including corneal curvature, effective lens position and axial length. While refractive outcomes have been assessed in the immediate post-operative period, longer-term changes in refraction have not been reported. The purpose of this study was to investigate the timeline changes in refraction after cataract surgery over a period of 3 years. METHODS: This was a retrospective observational study that included 344 eyes of 204 patients who underwent cataract emulsification surgery between 1 January and 31 December 2018 at two private hospitals. Keratometry, anterior chamber depth (ACD), central corneal thickness (CCT) and axial length were measured at baseline and post-operatively at 1 month, 1 year, 2 years and 3 years. Changes in SER and ocular parameters were assessed at each post-operative timepoint. RESULTS: Between 1 month and 3 years post-operatively, an overall myopic shift (0.32 ± 0.21 D, p < 0.001) occurred in 33.6% of eyes and a hypermetropic shift in 45.2% of eyes (0.35 ± 0.22 D, p < 0.001). In 21.2% of eyes, there was no reported change in SER between 1 month and 3 years. Significant changes in ACD (p = 0.04) and CCT (p < 0.001) occurred during the first year after surgery. CONCLUSION: The 3-year timeline changes in SER after cataract surgery were evaluated. As hypermetropic shift was the most common refractive change observed, it may be beneficial to aim for a more myopic post-operative refraction target. Patients should be advised of the potential for refractive changes after surgery.

Quantification of fluoroscopic fundoplication anatomy: inter- and intraobserver reliability.

The etiology of postfundoplication dysphagia remains incompletely understood. Subtle changes of gastroesophageal junction (GEJ) anatomy may be contributory. Barium swallows have potential for standardization to evaluate postsurgical anatomical features. Using structured barium swallows, we aim to identify reproducible, objectively measured postfundoplication anatomical features that will permit future comparison between patients with/without dysphagia. At 6-12 months of postfundoplication, 31 patients underwent structured barium swallow with video-fluoroscopy recording: standing anteroposterior; standing oblique (×2); prone oblique (×2); and prone oblique with continuous free drinking. A primary observer recorded 11 variables of GEJ anatomy for each view, repeated 3 months later, forming two datasets to assess intraobserver consistency. Interobserver reliability was determined using a dataset each from the primary observer and two medical students (after training). Intraclass correlation coefficients (ICC) were based on two-way mixed-effects model (ICC agreement: 0.40-0.59 'fair'; 0.60-0.74 'good'; 0.75-1.00 'excellent'). Interobserver reliability was good-excellent for 47 of 66 measurements. Measures of maximal esophageal diameter cf. wrap opening diameter and posterior esophageal angle showed high interobserver reproducibility on all views (ICC range 0.84-0.91; 0.68-0.80, respectively). Interobserver agreement was good-excellent for 5/6 views when measuring anterior GEJ displacement and axis deviation (ICC range 0.56-0.79; 0.41-0.77, respectively). Measures of wrap length showed lower reproducibility. Prone oblique measurements showed highest reproducibility (good-excellent agreement in 19/22 measurements). Intraobserver consistency was excellent for 98% of measurements (ICC range 0.74-0.99). Objective measurements of postfundoplication GEJ anatomy using structured barium swallow are reproducible and may allow further interrogation of anatomical features contributing to postfundoplication dysphagia.

Identifying Medication-Related Intents From a Bidirectional Text Messaging Platform for Hypertension Management Using an Unsupervised Learning Approach: Retrospective Observational Pilot Study.

BACKGROUND: Free-text communication between patients and providers plays an increasing role in chronic disease management, through platforms varying from traditional health care portals to novel mobile messaging apps. These text data are rich resources for clinical purposes, but their sheer volume render them difficult to manage. Even automated approaches, such as natural language processing, require labor-intensive manual classification for developing training data sets. Automated approaches to organizing free-text data are necessary to facilitate use of free-text communication for clinical care. OBJECTIVE: The aim of this study was to apply unsupervised learning approaches to (1) understand the types of topics discussed and (2) learn medication-related intents from messages sent between patients and providers through a bidirectional text messaging system for managing participant blood pressure (BP). METHODS: This study was a secondary analysis of deidentified messages from a remote, mobile, text-based employee hypertension management program at an academic institution. We trained a latent Dirichlet allocation (LDA) model for each message type (ie, inbound patient messages and outbound provider messages) and identified the distribution of major topics and significant topics (probability >.20) across message types. Next, we annotated all medication-related messages with a single medication intent. Then, we trained a second medication-specific LDA (medLDA) model to assess how well the unsupervised method could identify more fine-grained medication intents. We encoded each medication message with n-grams (n=1-3 words) using spaCy, clinical named entities using Stanza, and medication categories using MedEx; we then applied chi-square feature selection to learn the most informative features associated with each medication intent. RESULTS: In total, 253 participants and 5 providers engaged in the program, generating 12,131 total messages: 46.90% (n=5689) patient messages and 53.10% (n=6442) provider messages. Most patient messages corresponded to BP reporting, BP encouragement, and appointment scheduling; most provider messages corresponded to BP reporting, medication adherence, and confirmatory statements. Most patient and provider messages contained 1 topic and few contained more than 3 topics identified using LDA. In total, 534 medication messages were annotated with a single medication intent. Of these, 282 (52.8%) were patient medication messages: most referred to the medication request intent (n=134, 47.5%). Most of the 252 (47.2%) provider medication messages referred to the medication question intent (n=173, 68.7%). Although the medLDA model could identify a majority intent within each topic, it could not distinguish medication intents with low prevalence within patient or provider messages. Richer feature engineering identified informative lexical-semantic patterns associated with each medication intent class. CONCLUSIONS: LDA can be an effective method for generating subgroups of messages with similar term usage and facilitating the review of topics to inform annotations. However, few training cases and shared vocabulary between intents precludes the use of LDA for fully automated, deep, medication intent classification. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1101/2021.12.23.21268061.

The mentorship experience of students and nurses in pre-registration nursing education: A thematic synthesis of qualitative studies.

Mentorship is considered to play a paramount role in empowering nursing students to recieve superlative benefit from clinical placement. Although the new standards for student supervision and assessment approved by the Nursing and Midwifery Council in 2018 seemed to lead to the disillusionment of mentorship, they support clinical education and devotion to nursing students' clinical learning globally. The aim of this synthesis was to review and explore the experiences of mentorship of preregistration nursing students and nurses. A systematic search of databases was performed for qualitative studies published in English from 2000 to 2018. Eleven qualitative studies were selected, from which three analytical themes emerged: mentors' capabilities and readiness for preregistration nursing student mentorship, humanistic approach as foundation to the effectiveness of preregistration nursing student mentorship, and the collaboration of stakeholders in health care and educational settings to enhance preregistration nursing student mentorship. A thematic framework of mentorship in preregistration nursing education was introduced. The thematic synthesis sheds light on how to improve a formal system of mentorship and clinical supervision for nursing education.

Development and Validation of a Test for Competence in Evidence-Based Medicine.

BACKGROUND: Medical educators need valid, reliable, and efficient tools to assess evidence-based medicine (EBM) knowledge and skills. Available EBM assessment tools either do not assess skills or are laborious to grade. OBJECTIVE: To validate a multiple-choice-based EBM test-the Resident EBM Skills Evaluation Tool (RESET). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 304 medicine residents from five training programs and 33 EBM experts comprised the validation cohort. MAIN MEASURES: Internal reliability, item difficulty, and item discrimination were assessed. Construct validity was assessed by comparing mean total scores of trainees to experts. Experts were also asked to rate importance of each test item to assess content validity. KEY RESULTS: Experts had higher total scores than trainees (35.6 vs. 29.4, P < 0.001) and also scored significantly higher than residents on 11/18 items. Cronbach's alpha was 0.6 (acceptable), and no items had a low item-total correlation. Item difficulty ranged from 7 to 86%. All items were deemed "important" by > 50% of experts. CONCLUSIONS: The proposed EBM assessment tool is a reliable and valid instrument to assess competence in EBM. It is easy to administer and grade and could be used to guide and assess interventions in EBM education.

Patient Interaction Phenotypes With an Automated Remote Hypertension Monitoring Program and Their Association With Blood Pressure Control: Observational Study.

BACKGROUND: Automated texting platforms have emerged as a tool to facilitate communication between patients and health care providers with variable effects on achieving target blood pressure (BP). Understanding differences in the way patients interact with these communication platforms can inform their use and design for hypertension management. OBJECTIVE: Our primary aim was to explore the unique phenotypes of patient interactions with an automated text messaging platform for BP monitoring. Our secondary aim was to estimate associations between interaction phenotypes and BP control. METHODS: This study was a secondary analysis of data from a randomized controlled trial for adults with poorly controlled hypertension. A total of 201 patients with established primary care were assigned to the automated texting platform; messages exchanged throughout the 4-month program were analyzed. We used the k-means clustering algorithm to characterize two different interaction phenotypes: program conformity and engagement style. First, we identified unique clusters signifying differences in program conformity based on the frequency over time of error alerts, which were generated to patients when they deviated from the requested text message format (eg, ###/## for BP). Second, we explored overall engagement styles, defined by error alerts and responsiveness to text prompts, unprompted messages, and word count averages. Finally, we applied the chi-square test to identify associations between each interaction phenotype and achieving the target BP. RESULTS: We observed 3 categories of program conformity based on their frequency of error alerts: those who immediately and consistently submitted texts without system errors (perfect users, 51/201), those who did so after an initial learning period (adaptive users, 66/201), and those who consistently submitted messages generating errors to the platform (nonadaptive users, 38/201). Next, we observed 3 categories of engagement style: the enthusiast, who tended to submit unprompted messages with high word counts (17/155); the student, who inconsistently engaged (35/155); and the minimalist, who engaged only when prompted (103/155). Of all 6 phenotypes, we observed a statistically significant association between patients demonstrating the minimalist communication style (high adherence, few unprompted messages, limited information sharing) and achieving target BP (P<.001). CONCLUSIONS: We identified unique interaction phenotypes among patients engaging with an automated text message platform for remote BP monitoring. Only the minimalist communication style was associated with achieving target BP. Identifying and understanding interaction phenotypes may be useful for tailoring future automated texting interactions and designing future interventions to achieve better BP control.

Haddenham Easywrap: an alternative to compression bandaging in chronic oedema and wound care.

Haddenham Easywrap has been available since 2016 and since then case studies have been presented to demonstrate the efficacy of the product in clinical practice. The aim of the article is to demonstrate how its use in chronic oedema, and wound care is beneficial and cost effective and how versatile one product can be in treating both of these conditions. Information gained from the evaluation of easywrap in wound care and management of chronic oedema, demonstrates that easywrap can be a suitable cost effective alternative to traditional compression therapy modalities, whilst improving concordance and quality of life.

Haddenham Star Cotton: improving treatment outcomes in maintaining chronic oedema.

The aim of compression therapy is to apply pressure on the skin and underlying structures to counteract the force of gravity, supporting venous and lymphatic function, to prevent or minimise oedema in the affected tissues. Compression therapy to manage lymphoedema is supported by a plethora of research, as it helps to increase the velocity of flow and lymphatic contraction of the lymphatic collecting vessels. This encourages drainage to the route of the limb, which increases fluid drainage from the tissues into the lymphatics. It is becoming more apparent that with an increase in clinical knowledge of how compression therapy works, clinicians are becoming less focused on the level of compression and more concerned with the stiffness of fabrics. This article looks at how adapting compression therapy regimes can improve patient outcomes of treatment and maintenance, while empowering patients to self-manage.

High-Cost Patients: Hot-Spotters Don't Explain the Half of It.

BACKGROUND: Understanding resource utilization patterns among high-cost patients may inform cost reduction strategies. OBJECTIVE: To identify patterns of high-cost healthcare utilization and associated clinical diagnoses and to quantify the significance of hot-spotters among high-cost users. DESIGN: Retrospective analysis of high-cost patients in 2012 using data from electronic medical records, internal cost accounting, and the Centers for Medicare and Medicaid Services. K-medoids cluster analysis was performed on utilization measures of the highest-cost decile of patients. Clusters were compared using clinical diagnoses. We defined "hot-spotters" as those in the highest-cost decile with ≥4 hospitalizations or ED visits during the study period. PARTICIPANTS AND EXPOSURE: A total of 14,855 Medicare Fee-for-service beneficiaries identified by the Medicare Quality Resource and Use Report as having received 100 % of inpatient care and ≥90 % of primary care services at Cleveland Clinic Health System (CCHS) in Northeast Ohio. The highest-cost decile was selected from this population. MAIN MEASURES: Healthcare utilization and diagnoses. KEY RESULTS: The highest-cost decile of patients (n = 1486) accounted for 60 % of total costs. We identified five patient clusters: "Ambulatory," with 0 admissions; "Surgical," with a median of 2 surgeries; "Critically Ill," with a median of 4 ICU days; "Frequent Care," with a median of 2 admissions, 3 ED visits, and 29 outpatient visits; and "Mixed Utilization," with 1 median admission and 1 ED visit. Cancer diagnoses were prevalent in the Ambulatory group, care complications in the Surgical group, cardiac diseases in the Critically Ill group, and psychiatric disorders in the Frequent Care group. Most hot-spotters (55 %) were in the "frequent care" cluster. Overall, hot-spotters represented 9 % of the high-cost population and accounted for 19 % of their overall costs. CONCLUSIONS: High-cost patients are heterogeneous; most are not so-called "hot-spotters" with frequent admissions. Effective interventions to reduce costs will require a more multi-faceted approach to the high-cost population.

Haddenham easywrap: the latest innovation in the management of lymphoedema.

The use of velcro compression wrapping devices in the management of lymphoedema and chronic oedema is not a new concept. Wraps have been available for many years and are being used widely in clinic and community settings where bandaging or traditional compression garments are not suitable. Furthermore, they are becoming more common when treating venous disease, patients with wounds and lipoedema. The aim of this article is to introduce the reader and clinician to the new Haddenham easywrap and to demonstrate why it is different to any other velcro wrapping device available. Case studies will be utilised from clinicians currently using easywrap in clinical practice, with both therapist and patient feedback given to demonstrate the efficacy of this new velcro compression wrapping device.

Haddenham easywrap as part of self-management in lymphoedema and lipoedema: The patient perspective.

Self-management and the use of adjustable velcro compression wraps are not new concepts and quite often both can form part of the maintenance phase of treatment in those with lymphoedema or lipoedema, as well as those diseases in which compression therapy is advised as long-term management. The aim of this article is to identify some aspects that contribute to effective self-management and how the use of easywrap adjustable velcro compression wraps have improved quality of life for those with lymphoedema, chronic oedema and lipoedema. Case studies are given from patients to demonstrate the individual experience of living with lymphoedema or lipoedema, how this has impacted on daily life, and how using easywrap has helped as part of self-management.