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Infectious Diseases and Therapy Apr 2024Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC...
INTRODUCTION
Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA.
METHODS
TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described.
RESULTS
Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued.
CONCLUSION
Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.
PubMed: 38570443
DOI: 10.1007/s40121-024-00961-y -
Cureus Mar 2024Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss and cerebral abnormalities, including...
Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss and cerebral abnormalities, including ventriculomegaly and partial dysgenesis of the corpus callosum. CMS is caused by two inactivating mutations of the G protein signaling modulator 2 (GPSM2), which maintains inner hair cell polarity and spindle orientation. Since its initial description, CMS has been reported approximately 30 times in the medical literature with several individuals undergoing cochlear implantation to restore their hearing. Interestingly, within the past two years, we encountered two cases of CMS in our hospital, which primarily serves patients within a 30-mile radius. To our knowledge, the literature has yet to evaluate two unrelated cases of CMS occurring in such close succession. This case report describes two successful cases of bilateral cochlear implantation in two children with CMS. Notably, these individuals have no family history of consanguinity or prior hearing loss.
PubMed: 38567212
DOI: 10.7759/cureus.55440 -
Scientific Reports Apr 2024We have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions....
We have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities. iCAT allows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms. This project aims to promote best practices to bridge the gap in healthcare access, resources, education, and economic opportunities. The project aims to engage local and regional stakeholders in data collection and evaluation, including patients, providers, and organizations. Their active involvement helps refine the platform and guides targeted interventions for more effective outcomes. In this paper, we present two sample illustrations demonstrating how iCAT identifies healthcare disparities and analyzes the impact of social and environmental variables on outcomes. Over time, this platform can help communities make decisions to optimize resource allocation.
Topics: Humans; Artificial Intelligence; Geographic Information Systems; Machine Learning; Neoplasms
PubMed: 38565582
DOI: 10.1038/s41598-024-57604-y -
Biology Letters Apr 2024If a congenitally blind person learns to distinguish between a cube and a sphere by touch, would they immediately recognize these objects by sight once their vision is...
If a congenitally blind person learns to distinguish between a cube and a sphere by touch, would they immediately recognize these objects by sight once their vision is restored? This question, posed by Molyneux in 1688, has puzzled philosophers and scientists since then. To overcome ethical and practical difficulties in the investigation of cross-modal recognition, we studied inexperienced poultry chicks, which can be reared in darkness until the moment of a visual test with no detrimental consequences. After hatching chicks in darkness, we exposed them to either tactile smooth or tactile bumpy stimuli for 24 h. Immediately after the tactile exposure, chicks were tested in a visual recognition task, during their first experience with light. At first sight, chicks that had been exposed in the tactile modality to smooth stimuli approached the visual smooth stimulus significantly more than those exposed to the tactile bumpy stimuli. These results show that visually inexperienced chicks can solve Molyneux's problem, indicating cross-modal recognition does not require previous multimodal experience. At least in this precocial species, supra-modal brain areas appear functional already at birth. This discovery paves the way for the investigation of predisposed cross-modal cognition that does not depend on visual experience.
Topics: Cognition; Recognition, Psychology; Touch; Chickens; Animals
PubMed: 38565149
DOI: 10.1098/rsbl.2024.0025 -
Environmental Research Jul 2024Coal generates almost 40% of the world's electricity with 80 countries throughout the world using coal power. An inherent part of this generation is the rail transport...
Coal generates almost 40% of the world's electricity with 80 countries throughout the world using coal power. An inherent part of this generation is the rail transport of coal in uncovered cars, often up to a mile long. Existing studies document the subsequent increments of PM2.5 to the near-rail populations, which typically include a large number of economically disadvantaged residents and/or people of color. However, to date there is no assessment of the health implications of this stage in the use of coal. The present study quantifies such impacts on a region in the San Francisco Bay Area. The analysis shows important effects on mortality, hospitalization for cardiovascular and respiratory disease, asthma exacerbation, work loss, and days of restricted activity. Several of these outcomes exhibited a one to six percent increase over baseline. As such, it delineates the implications for the global effects of the transport of coal.
Topics: San Francisco; Particulate Matter; Humans; Coal; Air Pollutants; Health Impact Assessment; Environmental Exposure; Railroads; Male; Female; Middle Aged; Adult; Aged; Cardiovascular Diseases; Hospitalization; Respiratory Tract Diseases; Asthma
PubMed: 38555092
DOI: 10.1016/j.envres.2024.118787 -
Social Science & Medicine (1982) May 2024In the UK, the medical profession is socially exclusive and socially stratified as doctors from more advantaged backgrounds are more likely to train for specialities...
In the UK, the medical profession is socially exclusive and socially stratified as doctors from more advantaged backgrounds are more likely to train for specialities with more competitive entry. However, in research to date the causes and consequences of social stratification have been overlooked. We explore this subject here, drawing on a qualitative study comprising in-depth interviews with 30 medical students and doctors from less advantaged socio-economic backgrounds negotiating medical school and early careers. Using Bourdieu's 'theory of practice' we show how socialisation in the family and at school influences how aspirant medics from less advantaged backgrounds view the world, suggesting some inclination towards more community orientated careers, which may be less competitive. However, these tendencies are encouraged as they lack stocks of social, economic and cultural capital, which are convertible to power and position in the field. While allowing for both choice and constraint our core argument is that speciality outcomes are sometimes inequitable and potentially inefficient, as doctors from more advantaged backgrounds have privileged access to more competitive careers for reasons not solely related to ability or skill. Our main theoretical contribution is to literature in the sociology of medical education where ours is the first study to open-up the 'black box' of causal factors connecting medical students' resources on entering the field of education and training with speciality outcomes, though our findings also have important implications for practitioners, the profession and for patients. We discuss the implications for safe and effective healthcare and how this informs directions for future research.
Topics: Humans; United Kingdom; Career Choice; Male; Female; Qualitative Research; Social Class; Students, Medical; Physicians; Adult
PubMed: 38547804
DOI: 10.1016/j.socscimed.2024.116747 -
EClinicalMedicine Feb 2024SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by...
BACKGROUND
SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19.
METHODS
Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728).
FINDINGS
Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group.
INTERPRETATION
BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19.
FUNDING
Biophytis.
PubMed: 38545090
DOI: 10.1016/j.eclinm.2023.102383 -
Sensors (Basel, Switzerland) Mar 2024The last-mile logistics in cities have become an indispensable part of the urban logistics system. This study aims to explore the effective selection of last-mile...
The last-mile logistics in cities have become an indispensable part of the urban logistics system. This study aims to explore the effective selection of last-mile logistics nodes to enhance the efficiency of logistics distribution, strengthen the image of corporate distribution, further reduce corporate operating costs, and alleviate urban traffic congestion. This paper proposes a clustering-based approach to identify urban logistics nodes from the perspective of geographic information fusion. This method comprehensively considers several key indicators, including the coverage, balance, and urban traffic conditions of logistics distribution. Additionally, we employed a greedy algorithm to identify secondary nodes around primary nodes, thus constructing an effective nodal network. To verify the practicality of this model, we conducted an empirical simulation study using the logistics demand and traffic conditions in the Xianlin District of Nanjing. This research not only identifies the locations of primary and secondary logistics nodes but also provides a new perspective for constructing urban last-mile logistics systems, enriching the academic research related to the construction of logistics nodes. The results of this study are of significant theoretical and practical importance for optimizing urban logistics networks, enhancing logistics efficiency, and promoting the improvement of urban traffic conditions.
PubMed: 38544141
DOI: 10.3390/s24061878 -
International Journal of Environmental... Feb 2024In 2022, the Virginia Chickahominy Indian Tribe partnered with Virginia Commonwealth University Massey Comprehensive Cancer Center to investigate concerns about a...
The Chickahominy T.R.U.T.H. (Trust, Research, Understand, Teach, and Heal) Project-A Tribal Community-Academic Partnership for Understanding the Impact of Structural Factors on Perceived Cancer Risk in Rural Virginia.
In 2022, the Virginia Chickahominy Indian Tribe partnered with Virginia Commonwealth University Massey Comprehensive Cancer Center to investigate concerns about a potential cancer cluster near a local landfill. While investigating cancer clusters is complex due to long latency and multifactorial causes, the community's concerns about structural factors driving cancer risk warrant exploration. Thus, the Chickahominy T.R.U.T.H. (Trust, Research, Understand, Teach, and Heal) Project was created as a community-academic partnership to (1) identify structural factors and barriers associated with perceived cancer risk and care; (2) assess cancer knowledge, care access gaps, and perceived risks, including testing private and community water sources; (3) develop and deploy culturally tailored cancer education and resource navigation, including groundwater safety education, policies, and remediation. We will conduct 150 in-person interviews and water tests among residents within a four-mile radius of the landfill, and deploy 1000 structured questionnaires among Charles City County residents. In this paper, we provide an overview of the ongoing project design, development, and progress in support of the project's objectives. This collaborative investigation aims to address cancer health disparities, enhance research and health policy advocacy, and honor the sacred knowledge of an underserved community, laying the groundwork for a long-term partnership to guide future research questions.
Topics: Humans; Virginia; Trust; Health Education; Surveys and Questionnaires; Water; Community-Based Participatory Research; Neoplasms
PubMed: 38541264
DOI: 10.3390/ijerph21030262 -
Nature Communications Mar 2024The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of...
The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.
Topics: Animals; Mice; Oxygen; Longevity; Hypoxia; Mole Rats; Ischemia
PubMed: 38538579
DOI: 10.1038/s41467-024-46470-x