RESUMO
BACKGROUND: In 2020, the Veterans Affairs (VA) health care system deployed a heart failure (HF) dashboard for use nationally. The initial version was notably imprecise and unreliable for the identification of HF subtypes. We describe the development and subsequent optimization of the VA national HF dashboard. MATERIALS AND METHODS: This study describes the stepwise process for improving the accuracy of the VA national HF dashboard, including defining the initial dashboard, improving case definitions, using natural language processing for patient identification, and incorporating an imaging-quality hierarchy model. Optimization further included evaluating whether to require concurrent ICD-codes for inclusion in the dashboard and assessing various imaging modalities for patient characterization. RESULTS: Through multiple rounds of optimization, the dashboard accuracy (defined as the proportion of true results to the total population) was improved from 54.1% to 89.2% for the identification of HF with reduced ejection fraction (HFrEF) and from 53.9% to 88.0% for the identification of HF with preserved ejection fraction (HFpEF). To align with current guidelines, HF with mildly reduced ejection fraction (HFmrEF) was added to the dashboard output with 88.0% accuracy. CONCLUSIONS: The inclusion of an imaging-quality hierarchy model and natural-language processing algorithm improved the accuracy of the VA national HF dashboard. The revised dashboard informatics algorithm has higher use rates and improved reliability for the health management of the population.
Assuntos
Insuficiência Cardíaca , Gestão da Saúde da População , Disfunção Ventricular Esquerda , Veteranos , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Volume Sistólico , Prognóstico , Reprodutibilidade dos Testes , Função Ventricular EsquerdaRESUMO
Utilization of fluorescent proteins is widespread for the study of microbial pathogenesis and host-pathogen interactions. Here, we discovered that linkage of the 36 N-terminal amino acids of FTL_0580 (a hypothetical protein of Francisella tularensis) to fluorescent proteins increases the fluorescence emission of bacteria that express these recombinant fusions. This N-terminal peptide will be referred to as 580N. Western blotting revealed that the linkage of 580N to Emerald Green Fluorescent Protein (EmGFP) in F. tularensis markedly improved detection of this protein. We therefore hypothesized that transcripts containing 580N may be translated more efficiently than those lacking the coding sequence for this leader peptide. In support, expression of emGFPFt that had been codon-optimized for F. tularensis, yielded significantly enhanced fluorescence than its non-optimized counterpart. Furthermore, fusing emGFP with coding sequence for a small N-terminal peptide (Serine-Lysine-Isoleucine-Lysine), which had previously been shown to inhibit ribosomal stalling, produced robust fluorescence when expressed in F. tularensis. These findings support the interpretation that 580N enhances the translation efficiency of fluorescent proteins in F. tularensis. Interestingly, expression of non-optimized 580N-emGFP produced greater fluorescence intensity than any other construct. Structural predictions suggested that RNA secondary structure also may be influencing translation efficiency. When expressed in Escherichia coli and Klebsiella pneumoniae bacteria, 580N-emGFP produced increased green fluorescence compared to untagged emGFP (neither allele was codon optimized for these bacteria). In conclusion, fusing the coding sequence for the 580N leader peptide to recombinant genes might serve as an economical alternative to codon optimization for enhancing protein expression in bacteria.
Assuntos
Francisella tularensis , Francisella tularensis/genética , Francisella tularensis/química , Francisella tularensis/metabolismo , Lisina/metabolismo , Peptídeos/genética , Códon/genética , Sinais Direcionadores de Proteínas/genéticaRESUMO
INTRODUCTION: Providing access to a vape shop-based smoking cessation intervention may simultaneously increase e-cigarette use and increase the effectiveness of e-cigarettes for smoking cessation. The aim of this study was to identify the most important elements of vape shop-based smoking intervention to stakeholders who would be involved in delivering or accessing such an intervention. METHODS: We conducted a three-round Delphi study of vape shop staff (n=40), stop smoking professionals and tobacco control leads (n=30), and smokers, vapers and dual users (n=30) in the United Kingdom in May-August 2021. In each round participants were asked whether they agreed or disagreed statements related to vape shop-based interventions. RESULTS: Forty-six of 95 statements reached consensus in round one, 29 out of 49 in round two and eight out of 20 in round three. There was support for a vape shop-based intervention across stakeholder groups (96%). There was consensus that the service should comprise both product (98%) and behavioural support (97%), and that quitting vaping should not be a goal of the service (79%). Although there was consensus that there should be some free product provision, there was less consensus as to what this should involve. Views were mostly consistent across stakeholder groups. CONCLUSIONS: There was broad consensus on how to deliver a vape shop-based smoking cessation intervention, providing a strong basis for future intervention development and implementation. Challenges around misuse of the service and misperceptions about vaping would need to be addressed for such an intervention to be feasible and effective. IMPLICATIONS: Many smokers who make a quit attempt using e-cigarettes purchase their vaping products in vape shops. Delivering vape-shop based smoking cessation interventions could help to maximise the effectiveness of e-cigarettes for quitting smoking. This study used a Delphi approach to identify the most important elements of a vape shop-based intervention among stakeholders. The findings could be used to help develop future interventions.
RESUMO
BACKGROUND: Peripherally inserted central catheters (PICCs) facilitate diagnostic and therapeutic interventions in health care. PICCs can fail due to infective and non-infective complications, which PICC materials and design may contribute to, leading to negative sequelae for patients and healthcare systems. OBJECTIVES: To assess the effectiveness of PICC material and design in reducing catheter failure and complications. SEARCH METHODS: The University of Queensland and Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the WHO ICTRP and ClinicalTrials.gov trials registers to 16 May 2023. We aimed to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, as well as relevant systematic reviews, meta-analyses, and health technology assessment reports. We contacted experts in the field to ascertain additional relevant information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating PICC design and materials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were venous thromboembolism (VTE), PICC-associated bloodstream infection (BSI), occlusion, and all-cause mortality. Secondary outcomes were catheter failure, PICC-related BSI, catheter breakage, PICC dwell time, and safety endpoints. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 RCTs involving approximately 2913 participants (one multi-arm study). All studies except one had a high risk of bias in one or more risk of bias domain. Integrated valve technology compared to no valve technology for peripherally inserted central catheter design Integrated valve technology may make little or no difference to VTE risk when compared with PICCs with no valve (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.19 to 2.63; I² = 0%; 3 studies; 437 participants; low certainty evidence). We are uncertain whether integrated valve technology reduces PICC-associated BSI risk, as the certainty of the evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Integrated valve technology may make little or no difference to occlusion risk when compared with PICCs with no valve (RR 0.86, 95% CI 0.53 to 1.38; I² = 0%; 5 studies; 900 participants; low certainty evidence). We are uncertain whether use of integrated valve technology reduces all-cause mortality risk, as the certainty of evidence is very low (RR 0.85, 95% CI 0.44 to 1.64; I² = 0%; 2 studies; 473 participants). Integrated valve technology may make little or no difference to catheter failure risk when compared with PICCs with no valve (RR 0.80, 95% CI 0.62 to 1.03; I² = 0%; 4 studies; 720 participants; low certainty evidence). We are uncertain whether integrated-valve technology reduces PICC-related BSI risk (RR 0.51, 95% CI 0.19 to 1.32; I² = not applicable; 2 studies (no events in 1 study); 542 participants) or catheter breakage, as the certainty of evidence is very low (RR 1.05, 95% CI 0.22 to 5.06; I² = 20%; 4 studies; 799 participants). Anti-thrombogenic surface modification compared to no anti-thrombogenic surface modification for peripherally inserted central catheter design We are uncertain whether use of anti-thrombogenic surface modified catheters reduces risk of VTE (RR 0.67, 95% CI 0.13 to 3.54; I² = 15%; 2 studies; 257 participants) or PICC-associated BSI, as the certainty of evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces occlusion (RR 0.69, 95% CI 0.04 to 11.22; I² = 70%; 2 studies; 257 participants) or all-cause mortality risk, as the certainty of evidence is very low (RR 0.49, 95% CI 0.05 to 5.26; I² = not applicable; 1 study; 111 participants). Use of anti-thrombogenic surface modified catheters may make little or no difference to risk of catheter failure (RR 0.76, 95% CI 0.37 to 1.54; I² = 46%; 2 studies; 257 participants; low certainty evidence). No PICC-related BSIs were reported in one study (111 participants). As such, we are uncertain whether use of anti-thrombogenic surface modified catheters reduces PICC-related BSI risk (RR not estimable; I² = not applicable; very low certainty evidence). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces the risk of catheter breakage, as the certainty of evidence is very low (RR 0.15, 95% CI 0.01 to 2.79; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Antimicrobial impregnation compared to non-antimicrobial impregnation for peripherally inserted central catheter design We are uncertain whether use of antimicrobial-impregnated catheters reduces VTE risk (RR 0.54, 95% CI 0.05 to 5.88; I² = not applicable; 1 study; 167 participants) or PICC-associated BSI risk, as the certainty of evidence is very low (RR 2.17, 95% CI 0.20 to 23.53; I² = not applicable; 1 study; 167 participants). Antimicrobial-impregnated catheters probably make little or no difference to occlusion risk (RR 1.00, 95% CI 0.57 to 1.74; I² = 0%; 2 studies; 1025 participants; moderate certainty evidence) or all-cause mortality (RR 1.12, 95% CI 0.71 to 1.75; I² = 0%; 2 studies; 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter failure (RR 1.04, 95% CI 0.82 to 1.30; I² = not applicable; 1 study; 221 participants; low certainty evidence). Antimicrobial-impregnated catheters probably make little or no difference to PICC-related BSI risk (RR 1.05, 95% CI 0.71 to 1.55; I² = not applicable; 2 studies (no events in 1 study); 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter breakage (RR 0.86, 95% CI 0.19 to 3.83; I² = not applicable; 1 study; 804 participants; low certainty evidence). AUTHORS' CONCLUSIONS: There is limited high-quality RCT evidence available to inform clinician decision-making for PICC materials and design. Limitations of the current evidence include small sample sizes, infrequent events, and risk of bias. There may be little to no difference in the risk of VTE, PICC-associated BSI, occlusion, or mortality across PICC materials and designs. Further rigorous RCTs are needed to reduce uncertainty.
Assuntos
Infecções Relacionadas a Cateter , Cateterismo Periférico , Desenho de Equipamento , Falha de Equipamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa , Humanos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Infecções Relacionadas a Cateter/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Obstrução do Cateter , Cateteres Venosos Centrais/efeitos adversos , Causas de Morte , Viés , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Bacteriemia/prevenção & controle , Bacteriemia/etiologiaRESUMO
Objective: School Health Profiles (Profiles) is a national surveillance system operated by the US Centers for Disease Control and Prevention. A school-based system of surveys, Profiles monitors school health policies and practices in US states and other jurisdictions through questionnaires completed by school principals and lead health education teachers. This study used the Profiles principal survey to identify trends in US schools' implementation of diversity-related learning opportunities (i.e., opportunities to learn about people who are different from them) in secondary classroom and extracurricular settings. Methods: Logistic regression models using data from three cycles of School Health Profiles from 35 US states examined trends in the percentages of secondary schools offering students diversity-related learning opportunities in the following settings, each measured by using dichotomous yes/no response options: a) clubs; b) lessons in class; and c) special events (e.g., multicultural week, family night) sponsored by the school or community organisations. Results: During 2014-2018, no states experienced decreases in opportunities for students to learn about people who are different from them; most states demonstrated no significant change. Conclusion: Findings suggest efforts are needed to strengthen capacity for and prioritisation of policies, programmes, and practices promoting diversity and culturally relevant education in schools, and in turn, promote positive health and educational outcomes for youth.
RESUMO
INTRODUCTION: Encouraging smokers to quit smoking tobacco using e-cigarettes could substantially reduce smoking-related diseases. Vape shops therefore have the potential to play an important role in supporting smoking cessation. The aim of this study was to explore how to deliver a vape shop-based smoking cessation intervention in the United Kingdom. METHOD: Semi-structured telephone interviews were undertaken with four stakeholder groups: 20 stop smoking service (SSS) providers, seven tobacco control leads (TCL), seven smokers/vapers and five vape shop staff). Interviews were analysed thematically. RESULTS: Stakeholder groups were positive about the idea of delivering a vape shop-based intervention. Themes that were identified were the characteristics of the intervention (duration and timing; delivery; style and content; and product provisions); barriers to the intervention (challenges for new vapers; false information; tobacco company involvement; and conflicts of interest); facilitators to the intervention (positive views on vaping; cost-effectiveness; popularity; and accessibility); and considerations for the intervention (data protection and privacy; aesthetics; and regulation and management). The results suggest that the intervention should be delivered by vape shop workers with mandatory training with the support of SSS. Most stakeholders agreed quitting vaping was not a priority, but that information on how to reduce nicotine use should be given. Concerns around privacy, GDPR, misinformation about vaping and tobacco company involvement would need to be addressed. CONCLUSIONS: Stakeholders agree that vape shops should offer stop smoking interventions and hold similar opinions on how this should be delivered. IMPLICATIONS: This study suggests that smokers, vapers and other key stakeholders are positive about the idea of a stop smoking vape-shop based intervention and that they hold similar opinions on how this should be delivered. Most participants felt that this should be primarily delivered by trained vape shop staff and run with support from SSS. Participants agreed that a stop smoking vape shop-based intervention should be flexible in terms of the type, duration and frequency of support provided, and that the intervention should comprise both technical guidance on using a vape and behavioural support to prevent a return to smoking.
RESUMO
Information about state and local education policies regarding sexually transmitted infections, including human immunodeficiency virus, and unintended pregnancy prevention is available, yet less is known about school-level implementation of such policies. We examine trends in the percentage of US secondary schools teaching sexual and reproductive health (SRH) topics in a required course in Grades 6-8 and 9-12, including healthy relationships, sexual abstinence, condoms and condoms with other contraceptive methods. We analyze representative data from 38 states across six cycles of School Health Profiles (2008-18) assessed through self-administered questionnaires completed by lead health teachers. Logistic regression models examined linear trends in the percentages of schools teaching topics for Grades 6-8 and 9-12, separately. Trends were calculated for states having representative data for at least three cycles, including 2018. During 2008-18, it was more common to have increases in teaching how to obtain condoms, correct condom use and use condoms with other contraceptive methods in Grades 6-12 than decreases. More states showed decreases in teaching abstinence in Grades 6-12 than increases. Most states had no change in teaching SRH topics across grades. Findings suggest some improvement in school-based SRH education, yet efforts are needed to improve comprehensive, developmentally appropriate content.
Assuntos
Saúde Reprodutiva , Infecções Sexualmente Transmissíveis , Gravidez , Feminino , Humanos , Infecções Sexualmente Transmissíveis/prevenção & controle , Educação Sexual , Instituições Acadêmicas , Preservativos , Comportamento SexualRESUMO
BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. METHODS: A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie's Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. DISCUSSION: Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. TRIAL REGISTRATION: Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).
Assuntos
Hospitais , Tecnologia , Adulto , Humanos , Criança , Austrália , Queensland , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: To investigate the reimbursement trends for interventional radiology (IR) procedures from 2012 to 2020. MATERIALS AND METHODS: Reimbursement data from the Physician Fee Schedule look-up tool from the Centers for Medicare and Medicaid Services was compiled for 20 common IR procedures. The authors then investigated compensation trends after adjusting for inflation and from the unadjusted data between 2012 and 2020. RESULTS: From 2012 to 2020, the mean unadjusted reimbursement for procedures decreased by -6.9% (95% confidence interval [CI], -13.5% to -0.34%). This trend was even more profound after inflation was taken into account, with a mean decline in adjusted reimbursement of -18.7% (95% CI, -24.4% to -12.9%) during the study period, with a mean yearly decline of -2.8%. The difference between the mean unadjusted and adjusted payment amounts was significant (P = .012). Similarly, linear regression analysis of the adjusted average reimbursement across all procedures revealed an overall decline from 2012 to 2020 (R2 = 0.97), indicating a steady decline in reimbursement over time. CONCLUSIONS: In just under a decade, IR has experienced significant reimbursement cuts by Medicare, as demonstrated by both the unadjusted and inflation-adjusted payment trends. Knowledge of these trends is critically important for practicing interventional radiologists, leaders within the field, and legislators, who may play a role in formulating future reimbursement schedules for IR. These data may be used to help support more amenable reimbursement plans to sustain and facilitate the growth of the specialty.
Assuntos
Centers for Medicare and Medicaid Services, U.S./tendências , Planos de Pagamento por Serviço Prestado/tendências , Custos de Cuidados de Saúde/tendências , Reembolso de Seguro de Saúde/tendências , Medicare/tendências , Radiografia Intervencionista/tendências , Centers for Medicare and Medicaid Services, U.S./economia , Planos de Pagamento por Serviço Prestado/economia , Humanos , Reembolso de Seguro de Saúde/economia , Medicare/economia , Radiografia Intervencionista/economia , Fatores de Tempo , Estados UnidosRESUMO
BACKGROUND: There is limited evidence describing long-term implant survivorship and modes of failure in simultaneous concurrent bilateral total knee arthroplasty (TKA). METHODS: We performed a retrospective review of 266 consecutive patients (532 knees) who underwent simultaneous concurrent bilateral TKA. We reviewed medical records for preoperative characteristics, perioperative complications, and revision surgeries. The primary outcome was TKA survivorship. Secondary outcomes included indication and type of revision surgery. We used the Kaplan-Meier method to estimate survivorship and characterize risk of revision up to 20 years post-TKA. RESULTS: Our cohort had median follow-up of 9.8 years (interquartile range, 3.9-15.9). Forty-four patients (17%) underwent revision. Revision was more common among younger and male patients. The cumulative incidence of first-time revision per knee (n = 532) was 1.27 per 100 component-years. Implant survival was 99% (confidence interval, 97%-99%) at 5 years, 92% (89%-95%) at 10 years, 83% (77%-87%) at 15 years, and 62% (50%-73%) at 20 years. Five and 10-year survivorship compared favorably to estimates of TKA survivorship in the literature. The cumulative incidence of revision surgery per patient was 1.91 per 100 component-years. Implant survival at 5-, 10-, 15-, and 20-year time points was 96% (CI, 92%-98%), 84% (77%-89%), 71% (62%-79%), and 59% (46%-70%), respectively. Aseptic loosening (40%), polyethylene wear (34%), and infection (11%) were the most common indications for revision. CONCLUSION: Simultaneous concurrent bilateral TKA is associated with a higher risk of reoperation for the patient when both knees are evaluated but similar implant survivorship to the literature when each knee was evaluated in isolation.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Masculino , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos Retrospectivos , Sobrevivência , Resultado do TratamentoRESUMO
BACKGROUND: The underlying pathophysiology of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unknown. However, an increasing number of observational studies report intralabyrinthine signal alterations in patients with ISSNHL using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI). These findings warrant a meta-analysis. OBJECTIVE OF REVIEW: To conduct a meta-analysis assessing the value of 3D-FLAIR MRI in identifying possible underlying labyrinthine pathophysiologic mechanisms and prognostication in patients with ISSNHL. SEARCH STRATEGY: Two reviewers independently searched the Pubmed, Embase and Cochrane Library from inception until October 10, 2018 and evaluated eligibility based on titles and abstracts of all retrieved studies. All studies reporting on 3D-FLAIR imaging in ISSNHL were included. Subsequently, the full text of eligible studies were evaluated. EVALUATION METHOD: Adhering to the MOOSE guideline, two independent reviewers extracted data, assessed risk of bias and evaluated the relevance and quality of evidence. Data on the number of patients and events were extracted and hearing levels were converted to standardised mean differences (SMD) for conducting meta-analyses. Random effects models for meta-analyses were applied. RESULTS: Eight observational studies met our inclusion criteria (n = 638 patients). In 29%, high signal intensity was found on 3D-FLAIR imaging, suggesting labyrinthine pathology (labyrinthitis [79%], intralabyrinthine haemorrhage [21%]). High signal intensity on 3D-FLAIR was associated with poorer hearing (SMD: 14 dB, 95% CI 5.67-22.94) and vertigo (RR: 1.92, 95% CI 1.16-3.17) at baseline. Multivariate analyses demonstrated that patients with high 3D-FLAIR signal intensity had 21 dB lower final hearing pure-tone averages (SMD: 21 dB, 95% CI 9.08-33.24). CONCLUSIONS: Three-dimensional fluid-attenuated inversion recovery MR imaging can identify an underlying labyrinthine condition in up to 29% of patients with sudden hearing loss in whom previously no cause could be identified. Their final pure-tone averages are more than 20 dB worse than 3D-FLAIR-negative patients, suggesting more severe labyrinthine damage. Findings such as these may contribute to our understanding of pathophysiologic mechanisms of ISSNHL.
Assuntos
Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/fisiopatologia , Orelha Interna , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , PrognósticoRESUMO
The evolution of behavior relies on changes at the level of the genome; yet the ability to attribute a behavioral change to a specific, naturally occurring genetic change is rare in vertebrates. In the white-throated sparrow (Zonotrichia albicollis), a chromosomal polymorphism (ZAL2/2(m)) is known to segregate with a behavioral phenotype. Individuals with the ZAL2(m) haplotype engage in more territorial aggression and less parental behavior than individuals without it. These behaviors are thought to be mediated by sensitivity to sex steroids, and the chromosomal rearrangement underlying the polymorphism has captured a prime candidate gene: estrogen receptor 1 (ESR1), which encodes estrogen receptor α (ERα). We therefore hypothesized that the behavioral effects of the ZAL2(m) rearrangement are mediated by polymorphism in ESR1. We report here that (i) the ESR1 promoter region contains fixed polymorphisms distinguishing the ZAL2(m) and ZAL2 alleles; (ii); those polymorphisms regulate transcription efficiency in vitro and therefore potentially do the same in vivo (iii); the local expression of ERα in the brain depends strongly on genotype in a free-living population; and (iv) ERα expression in the medial amygdala and medial preoptic area may fully mediate the effects of genotype on territorial aggression and parenting, respectively. Thus, our study provides a rare glimpse of how a chromosomal polymorphism has affected the brain and social behavior in a vertebrate. Our results suggest that in this species, differentiation of ESR1 has played a causal role in the evolution of phenotypes with alternative life-history strategies.
Assuntos
Comportamento Animal/fisiologia , Receptor alfa de Estrogênio/genética , Polimorfismo Genético , Isoformas de Proteínas/genética , Aves Canoras/fisiologia , Comunicação Animal , Animais , Evolução Biológica , Feminino , Regulação da Expressão Gênica , Haplótipos , Masculino , Fenótipo , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: To establish the reliable change parameters for the Automated Neuropsychological Assessment Metrics (ANAM) using a healthy normative sample of active duty service members (SMs) and apply the parameters to sample of recently deployed SMs. METHODS: Postdeployment neurocognitive performance was compared in 1893 US Marines with high rates of combat exposure during deployment. Of the sample, 289 SMs had data for 2 predeployment assessments and were used as a normative subsample and 502 SMs had data for predeployment and postdeployment assessments and were used as a deployed subsample. On the basis of self-report, the deployed subsample were further classified as concussed (n = 238) or as nonconcussed controls (n = 264). Reliable change parameters were estimated from the normative sample and applied data for both deployed groups. Postdeployment performance was quantified using a general linear model (2 group × 2 time) multivariate analysis of variance with repeated measures. RESULTS: Both deployed groups demonstrated a pattern of meaningful decreases in performance over time. CONCLUSIONS: Information from this effort, specifically the reliable change parameters and the base rates of reliable decline, can be used to assist with the identification of postdeployment cognitive issues.
Assuntos
Concussão Encefálica/diagnóstico , Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos , Adulto , Estudos de Casos e Controles , Cognição , Humanos , Masculino , Militares , Autorrelato , Adulto JovemRESUMO
These studies examined the roles of dopamine D1- and D2-like receptors within the nucleus accumbens (Acb) in the acquisition and expression of ethanol-induced (2g/kg) conditioned place preference (CPP) in adult male DBA/2J mice. Bilateral intra-Acb infusions of the D1-like dopamine receptor antagonist SCH23390 (0.05, 0.5µg/side) or the D2-like dopamine receptor antagonist raclopride (0.5-5.0µg/side) were administered 30min before each ethanol conditioning trial (acquisition studies) or before preference tests (expression studies). CPP was conditioned to tactile cues using an unbiased apparatus and procedure. Intra-Acb infusion of SCH23390 prevented CPP acquisition, whereas intra-Acb infusion of raclopride did not. Intra-Acb infusion of both antagonists, however, dose-dependently reduced ethanol-stimulated locomotor activity during conditioning. In contrast, intra-Acb antagonist infusion had no effect on ethanol CPP expression, suggesting that dopamine's role in the Acb is limited to neurobiological processes engaged during the learning of the relationship between contextual cues and ethanol reward. Control experiments showed that intra-Acb injection of SCH23390 alone produced no place conditioning and did not interfere with the acquisition of conditioned place aversion induced by lithium chloride, suggesting that the antagonist's effect on ethanol CPP was not due to a more general detrimental effect on associative learning. Overall, these data suggest that D1-like (but not D2-like) dopamine Acb receptors play an important role in the learning of context-ethanol associations, either by modulating the magnitude of ethanol reward or the rate of learning about ethanol reward.
Assuntos
Comportamento de Procura de Droga/fisiologia , Aprendizagem/fisiologia , Núcleo Accumbens/metabolismo , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Comportamento de Procura de Droga/efeitos dos fármacos , Etanol , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Racloprida/farmacologia , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
Introduction: Medication errors can lead to significant adverse events. Nearly 50% of medication errors occur during the prescription-writing stage of the medication use process, and effective interprofessional collaboration and communication are key to reducing error in this process. Methods: We developed a three-part, 60-minute, interprofessional education activity providing medical, physician assistant, and pharmacy students the opportunity to practice collegial interprofessional communication surrounding prescribing practices. Learners met virtually initially as a large group and divided into small groups facilitated by a health professional. Part 1 involved reviewing two prescriptions prepared by learners; part 2 was a discussion about the education, roles, and responsibilities of each profession; and part 3 focused on identifying prescription errors in examples provided by faculty. Students completed a post-pre survey measuring their perception of learning the Interprofessional Collaborative Competency Attainment Survey (ICCAS) areas. Results: Of 317 participants (151 doctor of osteopathy, 68 master of physician assistant studies, and 98 doctor of pharmacy students), 286 completed the post-pre survey, for a 90% response rate. Students reported statistically significant (p < .001) increases in all 20 questions spanning the six ICCAS areas. Discussion: The virtual format allowed multiple institutions to participate from various locations. It broadened the learners' experience by fostering interaction among those with varied perspectives and allowed collaboration between locations and programs that otherwise could not have participated. The activity introduced students to virtual collaboration and key telehealth skills, enhancing their confidence and familiarity with virtual interactions in a professional setting.
Assuntos
Comportamento Cooperativo , Relações Interprofissionais , Assistentes Médicos , Humanos , Assistentes Médicos/educação , Inquéritos e Questionários , Educação Interprofissional/métodos , Erros de Medicação/prevenção & controle , Estudantes de Farmácia/estatística & dados numéricos , Competência Clínica , Educação em Farmácia/métodos , Medicina Osteopática/educação , Prescrições de MedicamentosRESUMO
Background: During intraoperative care, ventilatory parameters including peak inflating pressure (PIP) and exhaled tidal volumes are continuously monitored to assess changes in respiratory resistance and compliance. Changes in these parameters, such as an increase in PIP or a decrease in the exhaled tidal volume, may indicate various pathologic processes that may require immediate attention to prevent inadequate ventilation resulting in hypoxemia or hypercarbia. A kinked endotracheal tube (ETT) may mimic other pathologic processes including bronchospasm, mainstem intubation, or ventilator malfunction. As newer ETTs are developed, a key factor in their design should be resistance to kinking or occlusion due to patient positioning. Methods: The current project developed and describes the process for using a repeatable in vitro mechanical test to determine resistance to kinking by an ETT. Results: The mechanical testing procedure can be used to determine the compression force and distance required to kink an ETT under different conditions including temperature. The force required to induce devastating kink failure was lower during heated testing conditions. The addition of airflow through the ETTs during compression testing confirms the occurrence of airway obstruction at approximately the same time a mechanical kink is observed on the force-versus-distance curves. Conclusions: These procedures may be used to characterize and evaluate ETT designs under in vitro conditions mimicking those in the clinical practice.
RESUMO
Neisseria gonorrhoeae has developed resistance to every antibiotic currently approved for the treatment of gonorrhea, prompting the development of new therapies. The phenoxazine dye resazurin exhibits robust antimicrobial activity against N. gonorrhoeae in vitro but fails to limit vaginal colonization by N. gonorrhoeae in a mouse model. The lack of in vivo efficacy may be due to oxygen limitation as in vitro susceptibility assays with resazurin are conducted under atmospheric oxygen while a microaerophilic environment is present in the vagina. Here, we utilized broth microdilution assays to determine the susceptibility of N. gonorrhoeae to resazurin under low and atmospheric oxygen conditions. The minimal inhibitory concentration of resazurin for multiple N. gonorrhoeae clinical isolates was significantly higher under low oxygen. This effect was specific to resazurin as N. gonorrhoeae was equally susceptible to other antibiotics under low and atmospheric oxygen conditions. The reduced susceptibility of N. gonorrhoeae to resazurin under low oxygen was largely attributed to reduced oxidative stress, as the addition of antioxidants under atmospheric oxygen mimicked the reduced susceptibility to resazurin observed under low oxygen. Together, these data suggest oxygen concentration is an important factor to consider when evaluating the efficacy of new antibiotics against N. gonorrhoeae in vitro.
RESUMO
PURPOSE: To examine trends and racial and ethnic disparities in early adolescent suicidal thoughts and behaviors in the years immediately prior to the COVID-19 pandemic. METHODS: This study used pooled data from Centers for Disease Control and Prevention's middle school Youth Risk Behavior Survey (n = 127,912) between 2015 and 2019. Three dichotomized measures of suicide-related behaviors were assessed: suicidal thoughts, planning, and attempts. Weighted prevalence estimates with 95% confidence intervals were calculated for each survey year. Linear trends examined disparities in the prevalence of suicidal thoughts and behaviors, overall and by student demographic characteristics. Main effects odds ratios compared estimates among racial and ethnic minority adolescents with non-Hispanic White students, controlling for sex and grade. RESULTS: Significant linear increases were observed for the percentage of middle school students who reported seriously thinking about suicide (18.2%-22.3%), ever making a suicide plan (11.8%-14.7%), and ever attempting suicide (6.9%-9.3%). Racial and ethnic minority students, other than non-Hispanic Asian, showed higher odds of suicidal thoughts and behaviors compared with non-Hispanic White students. DISCUSSION: Findings indicate a need for comprehensive suicide prevention to address health equity and disparities in suicide-related behaviors among middle school-aged adolescents.
Assuntos
Comportamento do Adolescente , Ideação Suicida , Humanos , Adolescente , Criança , Tentativa de Suicídio , Etnicidade , Pandemias , Grupos Minoritários , Assunção de Riscos , EstudantesRESUMO
IMPORTANCE: Mesenchymal stem cells (MSCs) have the capability of providing ongoing paracrine support to degenerating tissues. Since MSCs can be extracted from a broad range of tissues, their specific surface marker profiles and growth factor secretions can be different. We hypothesized that MSCs derived from different sources might also have different neuroprotective potential. OBJECTIVE: In this study, we extracted MSCs from rodent olfactory mucosa and compared their neuroprotective effects on auditory hair cell survival with MSCs extracted from rodent adipose tissue. METHODS: Organ of Corti explants were dissected from 41 cochlea and incubated with olfactory mesenchymal stem cells (OMSCs) and adipose mesenchymal stem cells (AMSCs). After 72 hours, Corti explants were fixed, stained, and hair cells counted. Growth factor concentrations were determined in the supernatant and cell lysate using Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Co-culturing of organ of Corti explants with OMSCs resulted in a significant increase in inner and outer hair cell stereocilia survival, compared to control. Comparisons between both stem cell lines, showed that co-culturing with OMSCs resulted in superior inner and outer hair cell stereocilia survival rates over co-culturing with AMSCs. Assessment of growth factor secretions revealed that the OMSCs secrete significant amounts of insulin-like growth factor 1 (IGF-1). Co-culturing OMSCs with organ of Corti explants resulted in a 10-fold increase in IGF-1 level compared to control, and their secretion was 2 to 3 times higher compared to the AMSCs. CONCLUSIONS: This study has shown that OMSCs may mitigate auditory hair cell stereocilia degeneration. Their neuroprotective effects may, at least partially, be ascribed to their enhanced IGF-1 secretory abilities compared to AMSCs.
Assuntos
Células Ciliadas Auditivas , Fator de Crescimento Insulin-Like I , Células-Tronco Mesenquimais , Animais , Fator de Crescimento Insulin-Like I/metabolismo , Células-Tronco Mesenquimais/metabolismo , Ratos , Células Ciliadas Auditivas/metabolismo , Mucosa Olfatória/citologia , Ensaio de Imunoadsorção Enzimática , Técnicas de Cocultura , Sobrevivência Celular , Células Cultivadas , Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
OBJECTIVES: Arterial catheters (ACs) are critical for haemodynamic monitoring and blood sampling but are prone to complications. We investigated the incidence and risk factors of AC failure. METHODS: Secondary analysis of a multi-centre randomised controlled trial (ACTRN 12610000505000). Analysis included a subset of adult intensive care unit patients with an AC. The primary outcome was all-cause device failure. Secondary outcomes were catheter associated bloodstream infection (CABSI), suspected CABSI, occlusion, thrombosis, accidental removal, pain, and line fracture. Risk factors associated with AC failure were investigated using Cox proportional hazards and competing-risk models. RESULTS: Of 664 patients, 173 (26%) experienced AC failure (incidence rate [IR] 37/1000 catheter days). Suspected CABSI was the most common failure type (11%; IR 15.3/1000 catheter days), followed by occlusion (8%; IR 11.9/1,000 catheter days), and accidental removal (4%; IR 5.5/1000 catheter days). CABSI occurred in 16 (2%) patients. All-cause failure and occlusion were reduced with ultrasound-assisted insertion (failure: adjusted hazard ratio [HR] 0.43, 95% CI 0.25, 0.76; occlusion: sub-HR 0.11, 95% CI 0.03, 0.43). Increased age was associated with less AC failure (60-74 years HR 0.63, 95% CI 0.44 to 0.89; 75 + years HR 0.36, 95% CI 0.20, 0.64; referent 15-59 years). Females experienced more occlusion (adjusted sub-HR 2.53, 95% CI 1.49, 4.29), while patients with diabetes had less (SHR 0.15, 95% CI 0.04, 0.63). Suspected CABSI was associated with an abnormal insertion site appearance (SHR 2.71, 95% CI 1.48, 4.99). CONCLUSIONS: AC failure is common with ultrasound-guided insertion associated with lower failure rates. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN 12610000505000); date registered: 18 June 2010.