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1.
Stat Methods Med Res ; : 9622802241242313, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38623615

RESUMEN

The focus of precision medicine is on decision support, often in the form of dynamic treatment regimes, which are sequences of decision rules. At each decision point, the decision rules determine the next treatment according to the patient's baseline characteristics, the information on treatments and responses accrued by that point, and the patient's current health status, including symptom severity and other measures. However, dynamic treatment regime estimation with ordinal outcomes is rarely studied, and rarer still in the context of interference - where one patient's treatment may affect another's outcome. In this paper, we introduce the weighted proportional odds model: a regression based, approximate doubly-robust approach to single-stage dynamic treatment regime estimation for ordinal outcomes. This method also accounts for the possibility of interference between individuals sharing a household through the use of covariate balancing weights derived from joint propensity scores. Examining different types of balancing weights, we verify the approximate double robustness of weighted proportional odds model with our adjusted weights via simulation studies. We further extend weighted proportional odds model to multi-stage dynamic treatment regime estimation with household interference, namely dynamic weighted proportional odds model. Lastly, we demonstrate our proposed methodology in the analysis of longitudinal survey data from the Population Assessment of Tobacco and Health study, which motivates this work. Furthermore, considering interference, we provide optimal treatment strategies for households to achieve smoking cessation of the pair in the household.

2.
Popul Health Metr ; 22(1): 6, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594706

RESUMEN

BACKGROUND: Targeted marketing of menthol cigarettes in the US influences disparities in the prevalence of menthol smoking. There has been no analysis of sub-national data documenting differences in use across demographic subgroups. This study estimated trends in the prevalence of menthol use among adults who smoke in the nine US census divisions by sex, age, and race/ethnicity from 2002 to 2020. METHODS: Data from 12 waves of the US ITC Survey were used to estimate the prevalence of menthol cigarette use across census divisions and demographic subgroups using multilevel regression and post-stratification (n = 12,020). Multilevel logistic regression was used to predict the prevalence of menthol cigarette use in 72 cross-classified groups of adults who smoke defined by sex, age, race/ethnicity, and socioeconomic status; division-level effects were fit with a random intercept. Predicted prevalence was weighted by the total number of adults who smoke in each cross-classified group and aggregated to divisions within demographic subgroup. Estimates were validated against the Tobacco Use Supplement to the Current Population Survey (TUS-CPS). RESULTS: Overall modeled prevalence of menthol cigarette use was similar to TUS-CPS estimates. Prevalence among adults who smoke increased in each division from 2002 to 2020. By 2020, prevalence was highest in the Middle (46.3%) and South Atlantic (42.7%) and lowest in the Pacific (25.9%) and Mountain (24.2%) divisions. Prevalence was higher among adults aged 18-29 (vs. 50+) and females (vs. males). Prevalence among non-Hispanic Black people exceeded 80% in the Middle Atlantic, East North Central, West North Central, and South Atlantic in all years and varied most among Hispanic people in 2020 (Pacific: 26.5%, New England: 55.1%). CONCLUSIONS: Significant geographic variation in the prevalence of menthol cigarette use among adults who smoke suggests the proposed US Food and Drug Administration (FDA) menthol cigarette ban will exert differential public health benefits and challenges across geographic and demographic subgroups.


Asunto(s)
Mentol , Productos de Tabaco , Adulto , Femenino , Humanos , Masculino , Censos , Prevalencia , Fumar/epidemiología , Control del Tabaco , Estados Unidos/epidemiología , Adolescente , Adulto Joven
3.
Addiction ; 119(5): 885-897, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38186201

RESUMEN

BACKGROUND AND AIMS: Nicotine vaping products (NVPs) can potentially help adult tobacco users quit smoking. This study evaluated how adult consumers compare the costs between NVPs and cigarettes. METHOD: We used data from the US arm of the 2016-2020 International Tobacco Control Four Country Smoking and Vaping (ITC 4CV) surveys to perform a multinomial logit model with two-way fixed effects to measure how perceived cost comparisons are associated with NVP and cigarette taxes, use patterns, NVP device types and individual sociodemographic factors. RESULTS: Higher cigarette taxes are associated with a greater likelihood of perceiving NVPs and cigarettes as costing the same for the overall population and among people who exclusively smoke, and a lower likelihood of perceiving NVPs as more expensive among people who exclusively vape, compared with lower cigarette taxes. Pre-filled cartridge and tank users are more likely to perceive NVPs as less expensive than cigarettes, compared with people who use other types of NVPs. The associations between taxes and perceived cost comparison were more pronounced among males, younger and low-income populations. CONCLUSIONS: Higher cigarette taxes are associated with perceived financial incentives for nicotine vaping products (NVPs) over cigarettes, whereas NVP taxes are not associated with perceived cost comparison between NVPs and cigarettes.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Adulto , Masculino , Humanos , Estados Unidos , Vapeo/epidemiología , Nicotina , Control del Tabaco , Costos y Análisis de Costo
4.
Vet Q ; 44(1): 1-9, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38288972

RESUMEN

Feline infectious peritonitis (FIP) is a potentially fatal coronavirus-driven disease of cats. Treatment with nucleoside analogue GS-441524 and or prodrug remdesivir (RDV) have produced remission in both experimentally induced and naturally occurring FIP, yet information regarding metabolism of RDV into GS-441524 in cats is scarce. This study assessed possible phase I metabolism of RDV in cats, utilising an in vitro feline microsome model with in vitro t1/2 and in vitro Clint calculated using the substrate depletion method. A previously validated high-performance liquid chromatography (HPLC) fluorescence method was utilised for detection and analysis of RDV and GS-441524. Qualitative yield of RDV and intermediate metabolite GS-441524 were determined following microsome incubation, then compared to whole blood and plasma incubations. In vitro microsome incubation resulted in rapid depletion of RDV, though it did not appear to resemble a conventional phase I-dependent reaction in cats, as it is in humans and dogs. Depletion of RDV into GS-441524 was demonstrated in whole blood in vitro, suggesting cats convert RDV to GS-441524, likely via blood esterases, as observed in mice and rats. RDV metabolism is unlikely to be impacted by impaired liver function in cats. Furthermore, as RDV depletes within minutes, whereas GS-441524 is very stable, whole blood or plasma GS-441524 concentrations, rather than plasma RDV concentrations, are more appropriate for therapeutic drug monitoring (TDM) in cats receiving RDV.


Asunto(s)
Adenosina Monofosfato , Adenosina , Alanina , Enfermedades de los Gatos , Infecciones por Coronavirus , Peritonitis Infecciosa Felina , Animales , Gatos , Adenosina/análogos & derivados , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Enfermedades de los Gatos/tratamiento farmacológico , Infecciones por Coronavirus/veterinaria , Peritonitis Infecciosa Felina/tratamiento farmacológico , Plasma
5.
J Sch Nurs ; : 10598405241226805, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291656

RESUMEN

School nurses encountered many workplace struggles while providing care during the COVID-19 pandemic. Several struggles involved organizational support, including having sufficient time, resources, compensation, and school leadership support. The purpose of this mixed methods study was to explore the experiences of school nurses working during the COVID-19 pandemic as they related to sufficient time to complete COVID-related activities, sufficient COVID-19 resources, compensation, and perceived organizational (school leadership) support. We obtained data from 1,564 National Association of School Nurses members regarding respondent characteristics, school characteristics, measures of organizational support, and qualitative perceived organizational support using a 17-question survey. Perceptions of having sufficient time to complete COVID-related tasks and infringement of these tasks on routine activities were worse for those with greater years of experience and education. Compensation for additional COVID-related work was more favorable for LPNs. School leaders should be aware of their role in bolstering organizational support and its impact.

6.
J Am Vet Med Assoc ; 262(4): 1-12, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38096664

RESUMEN

OBJECTIVE: To describe the imaging findings in Australian cats and dogs with CNS cryptococcosis. ANIMALS: 23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review. METHODS: Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certified radiologist. Imaging findings were described and the differences between cats and dogs explored. RESULTS: Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-field brain MRI scans. Meningeal abnormalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions affecting the brain, sinonasal cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was more common in dogs than cats, particularly affecting the cribriform plate. All 13 dogs and many (6/10) cats had at least 1 lesion affecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10 cats; 11/13 dogs). CLINICAL RELEVANCE: Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare, should prompt consideration of cryptococcosis.


Asunto(s)
Enfermedades de los Gatos , Criptococosis , Enfermedades de los Perros , Gatos , Perros , Animales , Estudios Retrospectivos , Australia/epidemiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/veterinaria , Criptococosis/diagnóstico por imagen , Criptococosis/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/patología , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/patología
7.
BMJ Open ; 13(11): e073027, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37914306

RESUMEN

INTRODUCTION: In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data. METHODS AND ANALYSIS: Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated. ETHICS AND DISSEMINATION: Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.


Asunto(s)
Demencia , Trastornos Neurocognitivos , Humanos , Estudios Longitudinales , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/epidemiología , Envejecimiento , Demencia/diagnóstico , Demencia/epidemiología , Algoritmos , Nueva Escocia , Estudios Observacionales como Asunto
8.
Vet Q ; 43(1): 1-9, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37556736

RESUMEN

The adenosine analogue GS-441524 has demonstrated efficacy in treatment of feline infectious peritonitis (FIP). With no commercially registered formulations of GS-441524 available, global focus shifted to its pro-drug remdesivir, as it became more accessible throughout the COVID-19 pandemic. This study developed and validated a simple liquid chromatography equipped with a fluorescence detector to quantify plasma concentrations of GS-441524 applicable for routine therapeutic monitoring of remdesivir or GS-441524 therapy for FIP infected cats. A Waters X-Bridge C18, 5 µm, 150 × 4.6 mm, column was used and mixtures of 20 mM ammonium acetate (pH 4.5) with acetonitrile of 5% and 70% were prepared for gradient mobile phase. With a simple protein precipitation using methanol to clean plasma sample, GS-441524 was monitored at excitation and emission wavelengths of 250 nm and 475 nm, respectively. Using an external standard, the lowest and highest limits of quantification were 19.5 ng/mL to 10,000 ng/mL, respectively. The intra- and inter day trueness of the quality controls (QCs) were within 10% of their nominal concentrations and intra- and inter day precision of the QCs (expressed as the coefficient of variation) ranged from 1.7 to 5.7%, This assay was able to quantify plasma trough levels of GS-441524 (23.7-190.1 ng/mL) after the administration of remdesivir (9.9-15.0 mg/kg BW, IV or SC) in FIP cats (n = 12). Accordingly, this study generated an alternative and cost-effective way to quantify GS-441524 in feline biological fluids at least up to 24 hr after administrations of remdesivir.


Asunto(s)
COVID-19 , Enfermedades de los Gatos , Peritonitis Infecciosa Felina , Gatos , Animales , Cromatografía Líquida de Alta Presión/veterinaria , Cromatografía Líquida de Alta Presión/métodos , COVID-19/veterinaria , Pandemias , Peritonitis Infecciosa Felina/tratamiento farmacológico
9.
J Vet Intern Med ; 37(5): 1772-1783, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37439383

RESUMEN

BACKGROUND: Nucleoside analog GS-441524 is effective in treating cats with feline infectious peritonitis (FIP). Investigation into the use of parent nucleotide analog remdesivir (GS-5734) is needed. OBJECTIVES: To assess efficacy and tolerability of remdesivir with or without transition to GS-441524 in cats with FIP and document clinical and clinicopathologic progression over 6 months. ANIMALS: Twenty-eight client-owned cats with FIP. METHODS: Cats were prospectively recruited between May 2021 and May 2022. An induction dosage of remdesivir 10 to 15 mg/kg intravenously or subcutaneously q24h was utilized for 4 doses, with a maintenance dosage of remdesivir (6-15 mg/kg SC) or GS-441524 (10-15 mg/kg per os) every 24 hours continued for at least 84 days. Laboratory testing, veterinary, and owner assessments were recorded. RESULTS: Twenty-four cats survived to 6 months (86%). Three cats died within 48 hours. Excluding these, survival from 48 hours to 6 months was 96% (24/25). Remission was achieved by day 84 in 56% (14/25). Three cats required secondary treatment for re-emergent FIP. Remission was achieved in all 3 after higher dosing (15-20 mg/kg). Adverse reactions were occasional site discomfort and skin irritation with remdesivir injection. Markers of treatment success included resolution of pyrexia, effusions, and presenting signs of FIP in the first half of treatment and normalization of globulin concentration, and continued body weight gains in the latter half of the treatment period. CONCLUSIONS AND CLINICAL IMPORTANCE: Parenteral administration of remdesivir and oral administration of GS-441524 are effective and well-tolerated treatments for FIP. Early emphasis on clinical, and later emphasis on clinicopathologic response, appears prudent when monitoring treatment efficacy.


Asunto(s)
Enfermedades de los Gatos , Coronavirus Felino , Peritonitis Infecciosa Felina , Humanos , Gatos , Animales , Peritonitis Infecciosa Felina/tratamiento farmacológico , Exudados y Transudados , Enfermedades de los Gatos/tratamiento farmacológico
10.
Gynecol Oncol Rep ; 47: 101210, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37273764

RESUMEN

Objective: The primary objective of this study was to estimate the prevalence of cannabis use in patients with gynecologic malignancies and to describe patterns of cannabis use. Secondary objectives included identifying sources of cannabis information used by patients. Methods: This is a single institution cross sectional survey conducted in Calgary, Alberta. Patients with a current or prior gynecologic cancer diagnosis were considered for inclusion. Planned analysis included descriptive statistics of patient demographics, and the patterns of cannabis use were described using frequencies and proportions. Results: Forty-six patients participated in the survey. The most common disease sites were ovarian cancer and uterine cancer, with the majority of patients receiving chemotherapy as part of their treatment (n = 35). Seventeen participants were current cannabis users (37%). The most common symptoms participants used cannabis for were pain (9/17), anxiety (9/17), and insomnia (9/17).Most patients using cannabis did not have a prescription and obtained their cannabis from a recreational dispensary (11/17). Many participants using cannabis had not talked to their doctor about cannabis (9/17). Instead, the most common sources of information about cannabis were cannabis retailers (20/46), and friends/family (20/46). Over 50% of patients would be interested in discussing cannabis if their physician broached the subject (26/46). Conclusions: The results from this survey indicate that patients would like to talk to their oncologist about cannabis. Further research is needed to inform physician training and direct patient education to ensure that patients have access to unbiased, evidence-based information to make decisions about cannabis use.

11.
J Cell Biol ; 222(6)2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37145332

RESUMEN

While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila nervous system. 97.5% of the genes studied showed discordance between the distribution of mRNA and the proteins they encode in at least one region of the nervous system. These data suggest that post-transcriptional regulation is very common, helping to explain the complexity of the nervous system. We also discovered that 68.5% of these genes have transcripts present at the periphery of neurons, with 9.5% at the glial periphery. Peripheral transcripts include many potential new regulators of neurons, glia, and their interactions. Our approach is applicable to most genes and tissues and includes powerful novel data annotation and visualization tools for post-transcriptional regulation.


Asunto(s)
Proteínas de Drosophila , ARN Mensajero , Animales , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Factores de Transcripción/metabolismo , ARN Mensajero/genética , Procesamiento Postranscripcional del ARN
12.
BMC Public Health ; 23(1): 872, 2023 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-37170234

RESUMEN

BACKGROUND: Older adults have been disproportionately impacted by COVID-19 and related preventative measures undertaken during the pandemic. Given clear evidence of the relationship between loneliness and health outcomes, it is imperative to better understand if, and how, loneliness has changed for older adults during the COVID-19 pandemic, and whom it has impacted most. METHOD: We used "pre-pandemic" data collected between 2015-2018 (n = 44,817) and "during pandemic" data collected between Sept 29-Dec 29, 2020 (n = 24,114) from community-living older adults participating in the Canadian Longitudinal Study on Aging. Loneliness was measured using the 3-item UCLA Loneliness Scale. Weighted generalized estimating equations estimated the prevalence of loneliness pre-pandemic and during the pandemic. Lagged logistic regression models examined individual-level factors associated with loneliness during the pandemic. RESULTS: We found the adjusted prevalence of loneliness increased to 50.5% (95% CI: 48.0%-53.1%) during the pandemic compared to 30.75% (95% CI: 28.72%-32.85%) pre-pandemic. Loneliness increased more for women (22.3% vs. 17.0%), those in urban areas (20.8% vs. 14.6%), and less for those 75 years and older (16.1% vs. 19.8% or more in all other age groups). Loneliness during the pandemic was strongly associated with pre-pandemic loneliness (aOR 4.87; 95% CI 4.49-5.28) and individual level sociodemographic factors [age < 55 vs. 75 + (aOR 1.41; CI 1.23-1.63), women (aOR 1.34; CI 1.25-1.43), and no post-secondary education vs. post-secondary education (aOR 0.73; CI 0.61-0.86)], living conditions [living alone (aOR 1.39; CI 1.27-1.52) and urban living (aOR 1.18; CI 1.07-1.30)], health status [depression (aOR 2.08; CI 1.88-2.30) and having two, or ≥ three chronic conditions (aOR 1.16; CI 1.03-1.31 and aOR 1.34; CI 1.20-1.50)], health behaviours [regular drinker vs. non-drinker (aOR 1.15; CI 1.04-1.28)], and pandemic-related factors [essential worker (aOR 0.77; CI 0.69-0.87), and spending less time alone than usual on weekdays (aOR 1.32; CI 1.19-1.46) and weekends (aOR 1.27; CI 1.14-1.41) compared to spending the same amount of time alone]. CONCLUSIONS: As has been noted for various other outcomes, the pandemic did not impact all subgroups of the population in the same way with respect to loneliness. Our results suggest that public health measures aimed at reducing loneliness during a pandemic should incorporate multifactor interventions fostering positive health behaviours and consider targeting those at high risk for loneliness.


Asunto(s)
COVID-19 , Humanos , Femenino , Anciano , COVID-19/epidemiología , Soledad , Pandemias , Estudios Longitudinales , Prevalencia , Canadá/epidemiología , Envejecimiento , Factores de Riesgo
13.
Gac Sanit ; 37: 102307, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37247520

RESUMEN

OBJECTIVE: The ITC EUREST-PLUS Spain Survey is a longitudinal study of a representative sample of Spanish adult (≥18 years old) smokers. This protocol describes the methods of the 2021 follow-up survey. METHOD: The ITC EUREST-PLUS Survey, a prospective cohort study of a representative sample of smokers in six European countries, was conducted in 2016 (baseline) and 2018 (waves 1 and 2). The 2021 ITC EUREST-PLUS Spain Survey is a continuation of the Spanish cohort with a new interview in 2021 (wave 3). Lost participants were replaced with new smokers recruited using the same multi-stage sampling design. This latest follow-up aims to examine current patterns and transitions of tobacco use and to evaluate the impact of new tobacco-related policies. COMMENTS: The ITC EUREST-PLUS Spain Survey will provide recent information about the impact of tobacco control policies on smoking behaviour.


Asunto(s)
Fumadores , Fumar , Adulto , Humanos , Adolescente , Estudios Prospectivos , Estudios Longitudinales , España , Fumar/epidemiología
14.
RNA ; 29(7): 1020-1032, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37041032

RESUMEN

The level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefore unclear whether the determinants of RNA decay found in cultured cells are preserved in an intact tissue, and whether they differ between neighboring cell types and are regulated during development. To address these questions, we measured RNA synthesis and decay rates genome wide via metabolic labeling of whole cultured Drosophila larval brains using 4-thiouridine. Our analysis revealed that decay rates span a range of more than 100-fold, and that RNA stability is linked to gene function, with mRNAs encoding transcription factors being much less stable than mRNAs involved in core metabolic functions. Surprisingly, among transcription factor mRNAs there was a clear demarcation between more widely used transcription factors and those that are expressed only transiently during development. mRNAs encoding transient transcription factors are among the least stable in the brain. These mRNAs are characterized by epigenetic silencing in most cell types, as shown by their enrichment with the histone modification H3K27me3. Our data suggest the presence of an mRNA destabilizing mechanism targeted to these transiently expressed transcription factors to allow their levels to be regulated rapidly with high precision. Our study also demonstrates a general method for measuring mRNA transcription and decay rates in intact organs or tissues, offering insights into the role of mRNA stability in the regulation of complex developmental programs.


Asunto(s)
Drosophila , Factores de Transcripción , Animales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Drosophila/genética , Larva/genética , Larva/metabolismo , Encéfalo/metabolismo , Estabilidad del ARN
15.
Paediatr Child Health ; 28(1): 8-16, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36865761

RESUMEN

Introduction: Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods: MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results: Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = -0.27 (95% CI = -0.60 to 0.07)], global intelligence quotient [-0.16 (-0.42 to 0.10)], reading [-0.05 (-0.29 to 0.20)], written comprehension [-0.09 (-0.40 to 0.22)], spelling [-0.04 (-0.26 to 0.17)], and mathematics [-0.01 (-0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions: The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes.

16.
Commun Med (Lond) ; 3(1): 36, 2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36906677

RESUMEN

BACKGROUND: Symptom persistence in non-hospitalized COVID-19 patients, also known as Long COVID or Post-acute Sequelae of COVID-19, is not well characterized or understood, and few studies have included non-COVID-19 control groups. METHODS: We used data from a cross-sectional COVID-19 questionnaire (September-December 2020) linked to baseline (2011-2015) and follow-up (2015-2018) data from a population-based cohort including 23,757 adults 50+ years to examine how age, sex, and pre-pandemic physical, psychological, social, and functional health were related to the severity and persistence of 23 COVID-19-related symptoms experienced between March 2020 and questionnaire completion. RESULTS: The most common symptoms are fatigue, dry cough, muscle/joint pain, sore throat, headache, and runny nose; reported by over 25% of participant who had (n = 121) or did not have (n = 23,636) COVID-19 during the study period. The cumulative incidence of moderate/severe symptoms in people with COVID-19 is more than double that reported by people without COVID-19, with the absolute difference ranging from 16.8% (runny nose) to 37.8% (fatigue). Approximately 60% of male and 73% of female participants with COVID-19 report at least one symptom persisting >1 month. Persistence >1 month is higher in females (aIRR = 1.68; 95% CI: 1.03, 2.73) and those with multimorbidity (aIRR = 1.90; 95% CI: 1.02, 3.49); persistence >3 months decreases by 15% with each unit increase in subjective social status after adjusting for age, sex and multimorbidity. CONCLUSIONS: Many people living in the community who were not hospitalized for COVID-19 still experience symptoms 1- and 3-months post infection. These data suggest that additional supports, for example access to rehabilitative care, are needed to help some individuals fully recover.


Some people who develop COVID-19 experience persistence of symptoms. Here, we aimed to understand the factors associated with the severity and persistence of these symptoms in adults 50 years and older living in the community who had COVID-19. Using information provided by 23,757 participants from across Canada we compared the symptoms between those who had COVID-19 and those who did not. The number and severity of symptoms in participants who had COVID-19 was beyond what would be expected due to other causes. Over two-thirds of participants who had COVID-19 reported symptoms persisting for more than one month, and over half of the participants more than three months. Symptom persistence was higher in females, those with multiple chronic conditions, and lower perceived social status. This suggests that a substantial proportion of people who were not hospitalized for COVID-19 may require further healthcare assistance.

17.
Arch Phys Med Rehabil ; 104(4): 523-532, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36539174

RESUMEN

OBJECTIVE: To develop and validate a patient-specific multivariable prediction model that uses variables readily available in the electronic medical record to predict 12-month mobility at the time of initial post-amputation prosthetic prescription. The prediction model is designed for patients who have undergone their initial transtibial (TT) or transfemoral (TF) amputation because of complications of diabetes and/or peripheral artery disease. DESIGN: Multi-methodology cohort study that identified patients retrospectively through a large Veteran's Affairs (VA) dataset then prospectively collected their patient-reported mobility. SETTING: The VA Corporate Data Warehouse, the National Prosthetics Patient Database, participant mailings, and phone calls. PARTICIPANTS: Three-hundred fifty-seven veterans who underwent an incident dysvascular TT or TF amputation and received a qualifying lower limb prosthesis between March 1, 2018, and November 30, 2020 (N=357). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Amputee Single Item Mobility Measure (AMPSIMM) was divided into a 4-category outcome to predict wheelchair mobility (0-2), and household (3), basic community (4), or advanced community ambulation (5-6). RESULTS: Multinomial logistic lasso regression, a machine learning methodology designed to select variables that most contribute to prediction while controlling for overfitting, led to a final model including 23 predictors of the 4-category AMPSIMM outcome that effectively discriminates household ambulation from basic community ambulation and from advanced community ambulation-levels of key clinical importance when estimating future prosthetic demands. The overall model performance was modest as it did not discriminate wheelchair from household mobility as effectively. CONCLUSIONS: The AMPREDICT PROsthetics model can assist providers in estimating individual patients' future mobility at the time of prosthetic prescription, thereby aiding in the formulation of appropriate mobility goals, as well as facilitating the prescription of a prosthetic device that is most appropriate for anticipated functional goals.


Asunto(s)
Amputados , Miembros Artificiales , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Amputación Quirúrgica , Amputados/rehabilitación , Prescripciones , Extremidad Inferior
18.
J Sch Nurs ; 39(2): 105-113, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36540020

RESUMEN

This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions. The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students' education.


Asunto(s)
COVID-19 , Síndrome de Fatiga Crónica , Humanos , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/epidemiología , Absentismo , Estudios de Factibilidad , Rol de la Enfermera , Síndrome Post Agudo de COVID-19 , Espera Vigilante
19.
J Womens Health (Larchmt) ; 32(2): 239-247, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36450120

RESUMEN

Background: Although lumbopelvic muscle stiffness is commonly clinically assessed in women with chronic pelvic pain (CPP), it has not been objectively quantified in this population, and its association with other pain-related impairments has not yet been established. Objective: To compare superficial lumbopelvic muscle stiffness in women with and without CPP. In addition, pressure pain threshold (PPT) was compared between groups and the associations between muscle stiffness and PPT were assessed in women with CPP. Study Design: Case-control. Methods: Muscle stiffness and PPT of 11 lumbopelvic muscles were assessed in 149 women with CPP and 48 asymptomatic women. Subjective outcome measures, including pelvic floor function, health history, and psychosocial outcomes, were collected before muscle stiffness and PPT measurements. Analysis of covariance was used to compare muscle stiffness differences between groups, and independent t-tests were used to compare PPT between groups. Associations between measurements of PPT and muscle stiffness were calculated using correlation analysis. Results: Five of the 11 muscles measured were significantly stiffer in women with CPP than those without CPP (p < 0.05). PPT was significantly decreased in all muscles measured in women with CPP; however, there was not a significant association between muscle stiffness and PPT in women with CPP. Conclusion: The study identified the abdominal lumbopelvic muscles that have increased stiffness in women with CPP compared to asymptomatic women. In addition, muscle stiffness and PPT are two distinct impairments within this population. The results suggest that women with CPP have peripheral muscle impairments, which may be addressed without intravaginal or intrarectal intervention. Clinical Trial Registration: NCT04851730.


Asunto(s)
Dolor Crónico , Dolor Pélvico , Femenino , Humanos , Estudios Transversales , Dimensión del Dolor/métodos , Diafragma Pélvico
20.
Am J Hosp Palliat Care ; 40(9): 1004-1012, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36469746

RESUMEN

Background: With disease progression, a terminally ill person may experience loss of physical and cognitive skills required to perform everyday activities. Such functional loss can erode autonomy and cause existential suffering. Supported engagement in everyday activities may help terminally ill people stay involved in living and cope with dying. Occupational therapy enables people to engage in valued activities at the end of life, yet remains under-utilized. Objectives: To address the perceived under-utilization of end-of-life care occupational therapy, the authors investigated how utilization of occupational therapy in end-of-life care is determined from the perspective of decision-makers and occupational therapists and then developed a model of the process. Methods: Using a grounded theory method, authors conducted two semi-structured interviews with 20 decision-makers and 21 occupational therapists. Theoretical sampling followed by paradigm analysis, yielded a data-grounded model. Results: The authors developed The Model of Occupational Therapy Utilization in End-of-Life Care. Service utilization was primarily contingent upon the decision-makers' awareness of occupational therapy's role in end-of-life care and further influenced by place of care cost constraints and participants' ability to adjust focus of the occupational therapy to accommodate the patient's dying process. Conclusion: Limited awareness of occupational therapy's role in end-of-life care warrants research on whether modification of model constructs may increase awareness and utilization. Education is indicated to teach providers about suffering due to functional loss and how to adjust focus of occupational therapy to sustain occupational participation through decline, across different care settings, and along a range between rehabilitation-focused to participation-focused outcomes.


Asunto(s)
Cuidados Paliativos al Final de la Vida , Terapia Ocupacional , Cuidado Terminal , Humanos , Cuidado Terminal/psicología , Cuidados Paliativos/psicología , Enfermo Terminal/psicología
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