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Applying results of extended genotyping to management of positive cervicovaginal human papillomavirus test results: Enduring guidelines
Full text linkOBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.
METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group.
RESULTS: Colposcopy is recommended after positive tests for human papillomavirus (HPV) types 16 and 18. For those positive for HPV 45, 33/58, 31, 52, 35/39/68, or 51 but negative for 16 or 18, triage with cytology or dual stain testing is recommended. When screening with primary HPV testing, for patients who test positive for HPV types 56/59/66 and no other carcinogenic types, repeat HPV testing in 1 year is recommended. When screening with cotesting, for those who test positive for HPV types 56/59/66 and no other carcinogenic types, 1-year return is recommended for negative for intraepithelial lesion or malignancy, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, and colposcopy is recommended for atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma. When patients without prior high-grade cytology (atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma) or histology (cervical intraepithelial neoplasia [CIN]2, CIN3, or adenocarcinoma in situ) are being followed, use of extended genotyping results is acceptable. When high-grade cytology or histology results are present, or when patients are being followed after treatment of CIN2+, management using the 2019 guidelines is recommended.
CONCLUSIONS: Human papillomavirus extended genotyping can guide clinical management in the setting of a positive HPV test result
Machine learning reveals distinct neuroanatomical signatures of cardiovascular and metabolic diseases in cognitively unimpaired individuals
Full text linkComorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45-85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45-64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies
How much variance exists among published definitions of proximal junctional kyphosis? A retrospective cohort study of adult spinal deformity
Full text linkA standardized nomenclature for the rods and cones of the vertebrate retina
Full text linkVertebrate photoreceptors have been studied for well over a century, but a fixed nomenclature for referring to orthologous cell types across diverse species has been lacking. Instead, photoreceptors have been variably-and often confusingly-named according to morphology, presence/absence of \u27rhodopsin\u27, spectral sensitivity, chromophore usage, and/or the gene family of the opsin(s) they express. Here, we propose a unified nomenclature for vertebrate rods and cones that aligns with the naming systems of other retinal cell classes and that is based on the photoreceptor type\u27s putative evolutionary history. This classification is informed by the functional, anatomical, developmental, and molecular identities of the neuron as a whole, including the expression of deeply conserved transcription factors required for development. The proposed names will be applicable across all vertebrates and indicative of the widest possible range of properties, including their postsynaptic wiring, and hence will allude to their common and species-specific roles in vision. Furthermore, the naming system is open-ended to accommodate the future discovery of as-yet unknown photoreceptor types
Injured tubular epithelia-derived CCN1 promotes the mobilization of fibroblasts toward injury sites after kidney injury
Full text linkHumoral factors that prompt fibroblasts to migrate to an injury site at an appropriate time point are deemed indispensable for repair after kidney injury. We herein demonstrated the pivotal roles of injured tubule-derived cellular communication network factor 1 (CCN1) in the mobilization of fibroblasts to the injury site after kidney injury. Based on analyses of ligand-receptor interaction
Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease
Full text linkWhile most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains
Supportive supervision visits in a large community hypertension programme in Nigeria: Implementation methods and outcomes
Full text linkBACKGROUND: The Hypertension Treatment in Nigeria (HTN) Programme established a system for hypertension diagnosis and management in 60 public primary healthcare facilities in the Federal Capital Territory of Nigeria through the implementation of HEARTS, a multi-level strategy bundle including team-based care led by community health extension workers (CHEWs). To improve HEARTS implementation, supportive supervision was added as an implementation strategy in April 2020.
METHODS: A multidisciplinary supportive supervision team and data collection forms were developed and implemented at HTN-supported sites. Data from April 2020 to December 2023 from supportive supervision visits were used to measure supportive supervision implementation outcomes, including reach, fidelity, adoption and feasibility and effectiveness of quality of care, data reporting and facility readiness. Descriptive analyses were performed to summarise outcomes. Jonckheere-Terpstra or Cochran-Armitage trend test was used to measure change over time for medians or proportions, respectively.
RESULTS: The programme successfully designed and performed quarterly supportive supervision visits. There was high reach (100% sites with visits each year), fidelity (median 100% (IQR 89%-100%) of core components completed), adoption (100% teams provided quarterly visits) and increase in feasibility (planned visits completed) (90.8% to 97.8%, p=0.002). Effectiveness outcomes included an increase in patients with blood pressure (BP) checked in the last 3 days (78.4% to 84.4%, p=0.009), treatment cards without errors (71.5% to 85%. p\u3c 0.001), but a slight drop in CHEW fidelity to BP measurement technique (91.5% to 86.5%, p=0.02). Facility readiness increased in adequate staffing (56.7% to 98.3%, p\u3c 0.001), but decreased for equipment availability (98.3% to 90.0%, p=0.03). Overall, the proportion of facilities with all readiness components present increased from 0% to 63.3% (p\u3c 0.001).
CONCLUSIONS: We designed and implemented a supportive supervision strategy with strong implementation outcomes and most effectiveness outcomes including facility readiness to provide quality hypertension care in Nigeria. This approach can be modelled for supporting HEARTS implementation in other settings.
TRIAL REGISTRATION NUMBER: The trial was prospectively registered at www.
CLINICALTRIALS: gov under NCT04158154 on 8 November 2019; https://clinicaltrials.gov/ct2/show/NCT04158154
Poor sleep is common in treatment-resistant late-life depression and associated with poorer antidepressant response: Findings from the OPTIMUM clinical trial
Full text linkBACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep.
METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the beginning (week-0) and end (week-10) of treatment. The analyses examined whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep during depression treatment.
RESULTS: About half (51%, n = 323) of participants reported insufficient sleep at baseline. Both persistent insufficient sleep (25%, n = 158) and worsened sleep (10%, n = 62) during treatment were associated with antidepressant nonresponse. Participants who maintained sufficient sleep (26%, n = 164) or who improved their sleep (n = 25%, n = 158) were three times more likely to experience a depression response than those with persistent insufficient sleep or worsened sleep.
CONCLUSION: Insufficient sleep is common in TRLLD and it is associated with poorer treatment response to antidepressants
Cardiovascular considerations after cancer therapy: Gaps in evidence and JACC: CardioOncology expert panel recommendations
Full text linkCancer survivors, particularly those treated with anthracyclines and chest radiation, face an elevated risk of cancer therapy-related cardiovascular toxicity. These complications affect not only physical health, but also life expectancy. Risk factors for cancer therapy-related cardiovascular toxicity include age at which cancer treatment was received, the use of (potentially) cardiotoxic cancer therapies, and the presence of concomitant cardiovascular risk factors. Current guidelines provide recommendations for cardiovascular surveillance after cancer therapy, including type and frequency. All cancer survivors are advised to undergo annual clinical screenings and optimization of cardiovascular risk factors. Those at higher risk should undergo additional cardiovascular testing. This document aims to summarize the available evidence, present practical recommendations, and outline existent gaps in the current literature regarding cardiovascular care after cancer therapies
