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1.
Nicotine Tob Res ; 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39394897

RESUMO

INTRODUCTION: Dual use of cigarettes and e-cigarettes is especially prevalent among lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) adults in the US. This is concerning as health risks of dual use may be as high or higher than exclusive smoking. We sought to learn about people who dual use and identify as LGBTQ+'s perspectives about dual use, quitting, and cessation ads. METHODS: Nineteen LGBTQ+ adults who dual use participated in virtual semi-structured interviews in North Carolina in 2022. We asked about perceptions of smoking and vaping in LGBTQ+ communities, their thoughts about quitting, and their opinions on four cessation ads. The ads advocated quitting one or both products. Transcripts were coded using ATLAS.ti and reviewed using a thematic content analysis approach. RESULTS: Participants described how within LGBTQ+ communities, smoking and vaping are common and accepted and are used to cope or to socialize. Most participants made past quit attempts. Many said they were not ready to quit both products, but some were open to quitting smoking. Some thought e-cigarettes may be as harmful as cigarettes, reducing their motivation to quit smoking cigarettes due to the lack of perceived health benefits. Participants sought cessation ads that explicitly address dual use and are representative and supportive. They disliked ads that felt stereotypical or patronizing. CONCLUSIONS: Dual use in LGBTQ+ communities appears driven by both internal and external pressures. Participants were generally open to quitting cigarettes, and LGBTQ+ smoking cessation may be best encouraged with authentic ads that explicitly address both products. IMPLICATIONS: These qualitative findings about smoking and vaping among LGBTQ+ individuals provide guidance for communication ad campaign design to help reduce the high dual use rates among LGBTQ+ young adults.

2.
Neuron ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39270654

RESUMO

Incentives tend to drive improvements in performance. But when incentives get too high, we can "choke under pressure" and underperform right when it matters most. What neural processes might lead to choking under pressure? We studied rhesus monkeys performing a challenging reaching task in which they underperformed when an unusually large "jackpot" reward was at stake, and we sought a neural mechanism that might result in that underperformance. We found that increases in reward drive neural activity during movement preparation into, and then past, a zone of optimal performance. We conclude that neural signals of reward and motor preparation interact in the motor cortex (MC) in a manner that can explain why we choke under pressure.

3.
Nat Comput Sci ; 4(9): 690-705, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39285002

RESUMO

Understanding brain function is facilitated by constructing computational models that accurately reproduce aspects of brain activity. Networks of spiking neurons capture the underlying biophysics of neuronal circuits, yet their activity's dependence on model parameters is notoriously complex. As a result, heuristic methods have been used to configure spiking network models, which can lead to an inability to discover activity regimes complex enough to match large-scale neuronal recordings. Here we propose an automatic procedure, Spiking Network Optimization using Population Statistics (SNOPS), to customize spiking network models that reproduce the population-wide covariability of large-scale neuronal recordings. We first confirmed that SNOPS accurately recovers simulated neural activity statistics. Then, we applied SNOPS to recordings in macaque visual and prefrontal cortices and discovered previously unknown limitations of spiking network models. Taken together, SNOPS can guide the development of network models, thereby enabling deeper insight into how networks of neurons give rise to brain function.


Assuntos
Potenciais de Ação , Modelos Neurológicos , Rede Nervosa , Neurônios , Animais , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/citologia , Simulação por Computador , Macaca , Córtex Visual/fisiologia , Córtex Visual/citologia , Algoritmos
4.
bioRxiv ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39185208

RESUMO

To generate movements, the brain must combine information about movement goal and body posture. Motor cortex (M1) is a key node for the convergence of these information streams. How are posture and goal information organized within M1's activity to permit the flexible generation of movement commands? To answer this question, we recorded M1 activity while monkeys performed a variety of tasks with the forearm in a range of postures. We found that posture- and goal-related components of neural population activity were separable and resided in nearly orthogonal subspaces. The posture subspace was stable across tasks. Within each task, neural trajectories for each goal had similar shapes across postures. Our results reveal a simpler organization of posture information in M1 than previously recognized. The compartmentalization of posture and goal information might allow the two to be flexibly combined in the service of our broad repertoire of actions.

6.
J Foot Ankle Res ; 17(2): e12012, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38627979

RESUMO

BACKGROUND: Diabetes-related foot disease (DFD) is a leading cause of the Australian and global disease burdens and requires proportionate volumes of research to address. Bibliometric analyses are rigorous methods for exploring total research publications in a field to help identify volume trends, gaps and emerging areas of need. This bibliometric review aimed to explore the volume, authors, institutions, journals, collaborating countries, research types and funding sources of Australian publications investigating DFD over 50 years. METHODS: A systematic search of the Scopus® database was conducted by two independent authors to identify all Australian DFD literature published between 1970 and 2023. Bibliometric meta-data were extracted from Scopus®, analyzed in Biblioshiny, an R Statistical Software interface, and publication volumes, authors, institutions, journals and collaborative countries were described. Publications were also categorised for research type and funding source. RESULTS: Overall, 332 eligible publications were included. Publication volume increased steadily over time, with largest volumes (78%) and a 7-fold increase over the last decade. Mean co-authors per publication was 5.6, mean journal impact factor was 2.9 and median citation was 9 (IQR2-24). Most frequent authors were Peter Lazzarini (14%), Vivienne Chuter (8%) and Jonathon Golledge (7%). Most frequent institutions affiliated were Queensland University Technology (33%), University Sydney (30%) and James Cook University (25%). Most frequent journals published in were Journal Foot and Ankle Research (17%), Diabetic Medicine (7%), Journal Diabetes and its Complications (4%) and International Wound Journal (4%). Most frequent collaborating countries were the United Kingdom (9%), the Netherlands (6%) and the United States (5%). Leading research types were etiology (38%), treatment evaluation (25%) and health services research (13%). Leading funding sources were no funding (60%), internal institution (16%) and industry/philanthropic/international (10%). CONCLUSIONS: Australian DFD research increased steadily until more dramatic increases were seen over the past decade. Most research received no funding and mainly investigated etiology, existing treatments or health services. Australian DFD researchers appear to be very productive, particularly in recent times, despite minimal funding indicating their resilience. However, if the field is to continue to rapidly grow and address the very large national DFD burden, much more research funding is needed in Australia, especially targeting prevention and clinical trials of new treatments in DFD.


Assuntos
Diabetes Mellitus , Doenças do Pé , Humanos , Austrália , Bibliometria , Fator de Impacto de Revistas
7.
Curr Biol ; 34(7): 1519-1531.e4, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38531360

RESUMO

How are we able to learn new behaviors without disrupting previously learned ones? To understand how the brain achieves this, we used a brain-computer interface (BCI) learning paradigm, which enables us to detect the presence of a memory of one behavior while performing another. We found that learning to use a new BCI map altered the neural activity that monkeys produced when they returned to using a familiar BCI map in a way that was specific to the learning experience. That is, learning left a "memory trace" in the primary motor cortex. This memory trace coexisted with proficient performance under the familiar map, primarily by altering neural activity in dimensions that did not impact behavior. Forming memory traces might be how the brain is able to provide for the joint learning of multiple behaviors without interference.


Assuntos
Interfaces Cérebro-Computador , Córtex Motor , Aprendizagem , Encéfalo , Mapeamento Encefálico , Eletroencefalografia
8.
Tob Control ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307719

RESUMO

BACKGROUND: Little is known about how nicotine pouch products are perceived by people who smoke, including if they are perceived as a cessation aid or a substitute for when they cannot smoke. We qualitatively investigated the reactions and perceptions about On!, a leading brand of nicotine pouches. METHODS: We conducted online semistructured interviews with 30 adults who smoke cigarettes. Participants viewed an On! brochure and an image of an opened nicotine pouch and were asked about their initial impression, who the intended user is, and how they thought of the product's safety compared with other tobacco and cessation products. Transcripts were independently coded and the data were analysed using thematic content analysis. RESULTS: Among the participants, half identified as female and slightly more than half were white (n=16). The mean age was 43 years old. The following are the central themes that emerged: (1) participants perceived the concealability, flavours and packaging of On! as appealing to youth and young adults; (2) participants perceived nicotine pouches as a product that would supplement rather than replace tobacco use; and (3) the product raised health concerns, which decreased interest in trying nicotine pouches. CONCLUSIONS: Participants believed that the On! nicotine pouch promotional material may promote youth and young adult nicotine product initiation and dual product use for people who smoke. Most viewed On! as a product to use with cigarettes, rather than a way to quit cigarettes. Increased surveillance of nicotine pouches is warranted to monitor the trajectory of this emerging tobacco product and prevent youth initiation.

9.
bioRxiv ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38260549

RESUMO

The manner in which neural activity unfolds over time is thought to be central to sensory, motor, and cognitive functions in the brain. Network models have long posited that the brain's computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate. We leveraged a brain-computer interface (BCI) to challenge monkeys to violate the naturally-occurring time courses of neural population activity that we observed in motor cortex. This included challenging animals to traverse the natural time course of neural activity in a time-reversed manner. Animals were unable to violate the natural time courses of neural activity when directly challenged to do so. These results provide empirical support for the view that activity time courses observed in the brain indeed reflect the underlying network-level computational mechanisms that they are believed to implement.

10.
Nat Hum Behav ; 8(4): 729-742, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287177

RESUMO

The most prominent characteristic of motor cortex is its activation during movement execution, but it is also active when we simply imagine movements in the absence of actual motor output. Despite decades of behavioural and imaging studies, it is unknown how the specific activity patterns and temporal dynamics in motor cortex during covert motor imagery relate to those during motor execution. Here we recorded intracortical activity from the motor cortex of two people who retain some residual wrist function following incomplete spinal cord injury as they performed both actual and imagined isometric wrist extensions. We found that we could decompose the population activity into three orthogonal subspaces, where one was similarly active during both action and imagery, and the others were active only during a single task type-action or imagery. Although they inhabited orthogonal neural dimensions, the action-unique and imagery-unique subspaces contained a strikingly similar set of dynamic features. Our results suggest that during motor imagery, motor cortex maintains the same overall population dynamics as during execution by reorienting the components related to motor output and/or feedback into a unique, output-null imagery subspace.


Assuntos
Imaginação , Córtex Motor , Humanos , Córtex Motor/fisiologia , Córtex Motor/diagnóstico por imagem , Imaginação/fisiologia , Masculino , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Movimento/fisiologia , Feminino , Punho/fisiologia , Atividade Motora/fisiologia , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia
11.
Sensors (Basel) ; 23(13)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37447670

RESUMO

Regular physical activity is an important component of diabetes management. However, there are limited data on the habitual physical activity of people with or at risk of diabetes-related foot complications. The aim of this study was to describe the habitual physical activity of people with or at risk of diabetes-related foot complications in regional Australia. Twenty-three participants with diabetes from regional Australia were recruited with twenty-two participants included in subsequent analyses: no history of ulcer (N = 11) and history of ulcer (N = 11). Each participant wore a triaxial accelerometer (GT3X+; ActiGraph LLC, Pensacola, FL, USA) on their non-dominant wrist for 14 days. There were no significant differences between groups according to both participant characteristics and physical activity outcomes. Median minutes per day of moderate-to-vigorous physical activity (MVPA) were 9.7 (IQR: 1.6-15.7) while participants recorded an average of 280 ± 78 min of low-intensity physical activity and 689 ± 114 min of sedentary behaviour. The sample accumulated on average 30 min of slow walking and 2 min of fast walking per day, respectively. Overall, participants spent very little time performing MVPA and were largely sedentary. It is important that strategies are put in place for people with or at risk of diabetes-related foot complications in order that they increase their physical activity significantly in accordance with established guidelines.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Humanos , Acelerometria , Exercício Físico , Caminhada , Comportamento Sedentário
12.
Nat Comput Sci ; 3(1): 71-85, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37476302

RESUMO

Calcium imaging has been widely adopted for its ability to record from large neuronal populations. To summarize the time course of neural activity, dimensionality reduction methods, which have been applied extensively to population spiking activity, may be particularly useful. However, it is unclear if the dimensionality reduction methods applied to spiking activity are appropriate for calcium imaging. We thus carried out a systematic study of design choices based on standard dimensionality reduction methods. We also developed a method to perform deconvolution and dimensionality reduction simultaneously (Calcium Imaging Linear Dynamical System, CILDS). CILDS most accurately recovered the single-trial, low-dimensional time courses from simulated calcium imaging data. CILDS also outperformed the other methods on calcium imaging recordings from larval zebrafish and mice. More broadly, this study represents a foundation for summarizing calcium imaging recordings of large neuronal populations using dimensionality reduction in diverse experimental settings.

13.
J Manag Care Spec Pharm ; 29(7): 758-768, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37404070

RESUMO

BACKGROUND: Niraparib is a highly selective poly (adenosine diphosphateribose) polymerase-1 and poly (adenosine diphosphate-ribose) polymerase-2 inhibitor indicated for select patients with ovarian, fallopian tube, and primary peritoneal cancer. The phase 2 GALAHAD trial (NCT02854436) demonstrated that niraparib monotherapy is tolerable and efficacious in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, particularly those with breast cancer gene (BRCA) alterations who had progressed on prior androgen signaling inhibitor therapy and taxane-based chemotherapy. OBJECTIVE: To report the prespecified patient-reported outcomes analysis from GALAHAD. METHODS: Eligible patients with alterations to BRCA1 and/or BRCA2 (BRCA cohort) and with pathogenic alterations in other HRR genes (other HRR cohort) were enrolled and received niraparib 300 mg once daily. Patient-reported outcome instruments included the Functional Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form. Changes from baseline were compared using a mixed-effect model for repeated measures. RESULTS: On average, health-related quality of life (HRQoL) improved in the BRCA cohort by cycle 3 (mean change = 6.03; 95% CI = 2.76-9.29) and was maintained above baseline until cycle 10 (mean change = 2.84; 95% CI = -1.95 to 7.63), whereas the other HRR cohort showed no early change in HRQoL from baseline (mean change = -0.07; 95% CI = -4.69 to 4.55) and declined by cycle 10 (mean change = -5.10; 95% CI = -15.3 to 5.06). Median time to deterioration in pain intensity and pain interference could not be estimated in either cohort. CONCLUSIONS: Patients with advanced mCRPC and BRCA alterations treated with niraparib experienced more meaningful improvement in overall HRQoL, pain intensity, and pain interference compared with those with other HRR alterations. In this population of castrate, heavily pretreated patients with mCRPC and HRR alterations, stabilization, and improvement in HRQoL may be relevant to consider when making treatment decisions. DISCLOSURES: This work was supported by Janssen Research & Development, LLC (no grant number). Dr Smith has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly; and has received personal fees from Astellas Pharma, Novartis, and Pfizer. Dr Sandhu has received grants from Amgen, Endocyte, and Genentech; has received grants and personal fees from AstraZeneca and Merck; and has received personal fees from Bristol Myers Squibb and Merck Serono. Dr George has received personal fees from the American Association for Cancer Research, Axess Oncology, Capio Biosciences, Constellation Pharma, EMD Serono, Flatiron, Ipsen, Merck Sharp & Dohme, Michael J. Hennessey Association, Millennium Medical Publishing, Modra Pharma, Myovant Sciences, Inc., NCI Genitourinary, Nektar Therapeutics, Physician Education Resource, Propella TX, RevHealth, LLC, and UroGPO; has received grants and personal fees from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, and Pfizer; has received personal fees and nonfinancial support from Bayer and UroToday; has received grants from Calithera and Novartis; and has received grants, personal fees, and nonfinancial support from Exelixis, Inc., Sanofi, and Janssen Pharma. Dr Chi has received grants from Janssen during the conduct of the study; has received grants and personal fees from AstraZeneca, Bayer, Astellas Pharma, Novartis, Pfizer, POINT Biopharma, Roche, and Sanofi; and has received personal fees from Daiichi Sankyo, Merck, and Bristol Myers Squibb. Dr Saad has received grants, personal fees, and nonfinancial support from Janssen during the conduct of the study; and has received grants, personal fees, and nonfinancial support from AstraZeneca, Astellas Pharma, Pfizer, Bayer, Myovant, Sanofi, and Novartis. Dr Thiery-Vuillemin has received grants, personal fees, and nonfinancial support from Pfizer; has received personal fees and nonfinancial support from AstraZeneca, Janssen, Ipsen, Roche/Genentech, Merck Sharp & Dohme, and Astellas Pharma; and has received personal fees from Sanofi, Novartis, and Bristol Myers Squibb. Dr Olmos has received grants, personal fees, and nonfinancial support from AstraZeneca, Bayer, Janssen, and Pfizer; has received personal fees from Clovis, Daiichi Sankyo, and Merck Sharp & Dohme; and has received nonfinancial support from Astellas Pharma, F. Hoffman-LaRoche, Genentech, and Ipsen. Dr Danila has received research support from the US Department of Defense, the American Society of Clinical Oncology, the Prostate Cancer Foundation, Stand Up to Cancer, Janssen Research & Development, Astellas Pharma, Medivation, Agensys, Genentech, and CreaTV. Dr Gafanov has received grants from Janssen during the conduct of the study. Dr Castro has received grants from Janssen during the conduct of the study; has received grants and personal fees from Janssen, Bayer, AstraZeneca, and Pfizer; and has received personal fees from Astellas Pharma, Merck Sharp & Dohme, Roche, and Clovis. Dr Moon has received research funding from SeaGen, HuyaBio, Janssen, BMS, Aveo, Xencor, and has received personal fees from Axess Oncology, MJH, EMD Serono, and Pfizer. Dr Joshua has received nonfinancial support from Janssen; consulted or served in an advisory role for Neoleukin, Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Noxopharm, IQvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, and Eisai; and received research funding from Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, MacroGenics, Lilly, Pfizer, AstraZeneca, and Corvus Pharmaceuticals. Drs Mason, Liu, Bevans, Lopez-Gitlitz, and Francis and Mr Espina are employees of Janssen Research & Development. Dr Mason owns stocks with Janssen. Dr Fizazi has participated in advisory boards and talks for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Pfizer, and Sanofi, with honoraria to his institution (Institut Gustave Roussy); has participated in advisory boards for, with personal honoraria from, Arvinas, CureVac, MacroGenics, and Orion. Study registration number: NCT02854436.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Qualidade de Vida , Masculino , Feminino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Indazóis/uso terapêutico , DNA
14.
Viruses ; 15(6)2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37376610

RESUMO

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Chlorocebus aethiops , Recém-Nascido , Animais , Feminino , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Placenta , Células Vero , Trofoblastos , Complicações Infecciosas na Gravidez/diagnóstico , Transmissão Vertical de Doenças Infecciosas
15.
J Foot Ankle Res ; 16(1): 27, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170147

RESUMO

BACKGROUND: Removable cast walkers (RCWs), with or without modifications, are used to offload diabetes-related foot ulcers (DRFUs), however there is limited data relating to their offloading effects. This study aimed to quantify plantar pressure reductions with an RCW with and without modification for DRFUs. METHODS: This within-participant, repeated measures study included 16 participants with plantar neuropathic DRFUs. Walking peak plantar pressures at DRFU sites were measured for four conditions: post-operative boot (control condition), RCW alone, RCW with 20 mm of felt adhered to an orthosis, and RCW with 20 mm of felt adhered to the foot. RESULTS: Compared to the control condition, the greatest amount of peak plantar pressure reduction occurred with the RCW with felt adhered to the foot (83.1% reduction, p < .001). The RCW with felt adhered to the foot also offered greater peak plantar pressure reduction than the RCW alone (51.3%, p = .021) and the RCW with felt adhered to an orthosis (31.4%, p = .009). CONCLUSION: The largest offloading effect recorded was with the RCW with felt adhered to the foot. High-quality randomised trials are now needed to evaluate the effectiveness of this device for healing DRFUs.


Assuntos
Diabetes Mellitus , Pé Diabético , Úlcera do Pé , Humanos , Andadores , Pé Diabético/terapia , , Caminhada
16.
bioRxiv ; 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37090659

RESUMO

Incentives tend to drive improvements in performance. But when incentives get too high, we can "choke under pressure" and underperform when it matters most. What neural processes might lead to choking under pressure? We studied Rhesus monkeys performing a challenging reaching task in which they underperform when an unusually large "jackpot" reward is at stake. We observed a collapse in neural information about upcoming movements for jackpot rewards: in the motor cortex, neural planning signals became less distinguishable for different reach directions when a jackpot reward was made available. We conclude that neural signals of reward and motor planning interact in the motor cortex in a manner that can explain why we choke under pressure. One-Sentence Summary: In response to exceptionally large reward cues, animals can "choke under pressure", and this corresponds to a collapse in the neural information about upcoming movements.

17.
Microbiol Spectr ; 11(3): e0026823, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37039648

RESUMO

Advances in diagnostic microbiology allow for the rapid identification of a broad range of enteropathogens; such knowledge can inform care and reduce testing. We conducted a randomized, unblinded trial in a tertiary-care pediatric emergency department. Participants had stool (and rectal swabs if stool was not immediately available) tested using routine microbiologic approaches or by use of a device (BioFire FilmArray gastrointestinal panel), which identifies 22 pathogens with a 1-h instrument turnaround time. Participants were 6 months to <18.0 years and had acute bloody diarrhea. Primary outcome was performance of blood tests within 72 h. From 15 June 2018 through 7 May 2022, 60 children were randomized. Patients in the BioFire FilmArray arm had a reduced time to test result (median 3.0 h with interquartile range [IQR] of 3.0 to 4.0 h, versus 42.0 h (IQR 23.5 to 47.3 h); difference of -38.0 h, 95% confidence interval [CI] of -41.0 to -22.0 h). Sixty-five percent (20/31) of participants in the BioFire FilmArray group had a pathogen detected-most frequently enteropathogenic Escherichia coli (19%), Campylobacter (16%), and Salmonella (13%). Blood tests were performed in 52% of children in the BioFire FilmArray group and 62% in the standard-of-care group (difference of -10.5%, 95% CI of -35.4% to 14.5%). There were no between-group differences in the proportions of children administered intravenous fluids, antibiotics, hospitalized, or who had diagnostic imaging performed. Testing with the BioFire FilmArray reduced the time to result availability by 38 h. Although statistical significance was limited by study power, BioFire FilmArray use was not associated with clinically meaningful reductions in health care utilization or improved outcomes. IMPORTANCE Advances in diagnostic microbiology now allow for the faster and more accurate detection of an increasing number of pathogens. We determined, however, that in children with acute bloody diarrhea, these advances did not necessarily translate into improved clinical outcomes. While a greater number of pathogens was identified using a rapid turnaround multiplex stool diagnostic panel, with a reduction in the time to stool test result of over 1.5 days, this did not alter the practice of pediatric emergency medicine physicians, who continued to perform blood tests on a large proportion of children. While our conclusions may be limited by the relatively small sample size, targeted approaches that educate clinicians on the implementation of such technology into clinical care will be needed to optimize usage and maximize benefits.


Assuntos
Gastroenterite , Humanos , Criança , Gastroenterite/microbiologia , Diarreia/diagnóstico , Diarreia/microbiologia , Serviço Hospitalar de Emergência , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia
18.
Antimicrob Resist Infect Control ; 12(1): 21, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949510

RESUMO

BACKGROUND: Risk factors for nosocomial COVID-19 outbreaks continue to evolve. The aim of this study was to investigate a multi-ward nosocomial outbreak of COVID-19 between 1st September and 15th November 2020, occurring in a setting without vaccination for any healthcare workers or patients. METHODS: Outbreak report and retrospective, matched case-control study using incidence density sampling in three cardiac wards in an 1100-bed tertiary teaching hospital in Calgary, Alberta, Canada. Patients were confirmed/probable COVID-19 cases and contemporaneous control patients without COVID-19. COVID-19 outbreak definitions were based on Public Health guidelines. Clinical and environmental specimens were tested by RT-PCR and as applicable quantitative viral cultures and whole genome sequencing were conducted. Controls were inpatients on the cardiac wards during the study period confirmed to be without COVID-19, matched to outbreak cases by time of symptom onset dates, age within ± 15 years and were admitted in hospital for at least 2 days. Demographics, Braden Score, baseline medications, laboratory measures, co-morbidities, and hospitalization characteristics were collected on cases and controls. Univariate and multivariate conditional logistical regression was used to identify independent risk factors for nosocomial COVID-19. RESULTS: The outbreak involved 42 healthcare workers and 39 patients. The strongest independent risk factor for nosocomial COVID-19 (IRR 3.21, 95% CI 1.47-7.02) was exposure in a multi-bedded room. Of 45 strains successfully sequenced, 44 (97.8%) were B.1.128 and differed from the most common circulating community lineages. SARS-CoV-2 positive cultures were detected in 56.7% (34/60) of clinical and environmental specimens. The multidisciplinary outbreak team observed eleven contributing events to transmission during the outbreak. CONCLUSIONS: Transmission routes of SARS-CoV-2 in hospital outbreaks are complex; however multi-bedded rooms play a significant role in the transmission of SARS-CoV-2.


Assuntos
COVID-19 , Infecção Hospitalar , Humanos , COVID-19/epidemiologia , SARS-CoV-2/genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Estudos de Casos e Controles , Estudos Retrospectivos , Surtos de Doenças , Fatores de Risco , Centros de Atenção Terciária , Alberta
19.
Adv Sci (Weinh) ; 10(15): e2206615, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36995043

RESUMO

The widespread accessibility of commercial/clinically-viable electrochemical diagnostic systems for rapid quantification of viral proteins demands translational/preclinical investigations. Here, Covid-Sense (CoVSense) antigen testing platform; an all-in-one electrochemical nano-immunosensor for sample-to-result, self-validated, and accurate quantification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N)-proteins in clinical examinations is developed. The platform's sensing strips benefit from a highly-sensitive, nanostructured surface, created through the incorporation of carboxyl-functionalized graphene nanosheets, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conductive polymers, enhancing the overall conductivity of the system. The nanoengineered surface chemistry allows for compatible direct assembly of bioreceptor molecules. CoVSense offers an inexpensive (<$2 kit) and fast/digital response (<10 min), measured using a customized hand-held reader (<$25), enabling data-driven outbreak management. The sensor shows 95% clinical sensitivity and 100% specificity (Ct<25), and overall sensitivity of 91% for combined symptomatic/asymptomatic cohort with wildtype SARS-CoV-2 or B.1.1.7 variant (N = 105, nasal/throat samples). The sensor correlates the N-protein levels to viral load, detecting high Ct values of ≈35, with no sample preparation steps, while outperforming the commercial rapid antigen tests. The current translational technology fills the gap in the workflow of rapid, point-of-care, and accurate diagnosis of COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Sensibilidade e Especificidade , Nucleocapsídeo , Antígenos
20.
Neuron ; 111(6): 764-766, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36924762
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