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1.
Acad Pediatr ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719092

RESUMO

OBJECTIVE: The purpose of this study was to compare three models of pediatric physiatry care (in-person, hybrid, and all-virtual) in terms of parent experience and physician- and therapist-reported quality of care. We hypothesized that the all-virtual model would have lower parent experience scores and lower quality scores compared with the other two models of care. METHODS: We designed a convergent parallel mixed methods study incorporating a cluster-randomized crossover design. Quantitative data included surveys of parents, physicians, and therapists after visits to 13 medical therapy units in Northern California between January 2020 and January 2022. Qualitative data were collected in six focus groups with parents, physicians, and therapists. RESULTS: A total of 2455 visits were completed for 1281 unique children during the study period, including 507 in-person visits, 246 hybrid visits, and 1702 all-virtual visits. There were no differences in parent experience scores between the three models of care. Physicians and therapists rated all-virtual visits significantly lower in terms of quality of care, parent education, and physical exam, compared with the other two models of care, but qualitative results highlighted specific instances where all-virtual visits could be useful. CONCLUSIONS: Our findings suggest that parents, therapists, and physicians find a hybrid virtual model is an acceptable model of care that maintains the quality of care and facilitates parent education. All-virtual models may be appropriate for specific circumstances but are perceived as lower quality. Research exploring implementation of these models would be valuable for providing practical guidance in the future.

2.
Cell Rep Med ; 5(5): 101547, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38703764

RESUMO

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Proteogenômica , Humanos , Proteogenômica/métodos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Transcriptoma/genética , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica
3.
J Telemed Telecare ; : 1357633X241238780, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515372

RESUMO

BACKGROUND: Telehealth has the potential to increase access to care for medically underserved patients. This qualitative study aimed to identify telecare practices used during the COVID-19 pandemic to meet the needs of patients experiencing homelessness, patients with disabilities, and patients with language preference other than English (LOE). METHODS: We conducted a secondary qualitative data analysis of 47 clinician interviews at Federally Qualified Health Centers (FQHCs) around the country. Using thematic analysis, transcripts were coded by line-by-line by five qualitative researchers. A multidisciplinary team of telehealth experts, researchers and primary care clinicians reviewed memos and excerpts to generate major themes. RESULTS: We identified six main areas demonstrating how community providers developed strategies or practices to improve access to care for vulnerable patients: reaching patients experiencing homelessness, serving deaf and hard of hearing patients, improving access for patients with disabilities, serving patients with LOE, improving access for mental and behavioral health services, and educating patients about telehealth. During the pandemic, FQHCs developed innovative solutions to provide access to care for the unhoused, including using telehealth in shelters, vans, and distributing devices like mobile phones and tablets. Telehealth reduced transportation burdens for patients with disabilities and reduced no-show rates for mental health services by adapting group therapy via telehealth features (like break-out rooms) and increasing provider capacity. CONCLUSION: Our study identified strategies adopted by FQHCs to serve underserved populations during the COVID-19 pandemic. Our findings highlight the need for enduring strategies to improve health equity through telehealth..

5.
Telemed J E Health ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512471

RESUMO

Background: Prior research suggests that pediatric patients and their parents/guardians are generally satisfied with care provided through telehealth. The objective of this study was to compare Press Ganey provider-oriented experience survey scores between telehealth and in-person patient encounters among a variety of pediatric clinical specialties at a large academic medical center. Methods: We analyzed Press Ganey survey data from pediatric patient encounters from UC Davis Health, collected between August 2020 and February 2022. Survey results analyzed respondents' satisfaction with care providers, including satisfaction with explanations given, discussions led, concern showed, and inclusion by providers; and the likelihood the survey respondent would recommend the provider to others. We used logistic regression models, which included case mix variables and clinical specialty to compare the odds of scoring the highest possible survey response ("top box" score). Results: Of the 6,093 survey responses that met inclusion criteria, 1,157 (19%) were associated with telehealth encounters and 4,936 (81%) were associated with in-person encounters. We found no significant difference in the odds of respondents giving a top box score to rate their satisfaction with their care provider between telehealth and in-person encounters. When respondents were asked whether they would recommend the care provider to others, the odds of giving a top box score following a telehealth encounter relative to an in-person encounter was 1.22 (95% confidence interval [0.97-1.52]; p-value = 0.09). Discussion: We found that survey respondents' experiences with their care provider are high and comparable for telehealth and in-person encounters in a pediatric population.

6.
Digit Health ; 9: 20552076231219123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107976

RESUMO

Objective: To develop a nurse-to-family telehealth intervention for pediatric inter-facility transfers using the human-centered design approach. Methods: We conducted the inspiration and ideation phases of a human-centered design process from July 2022 to December 2022. For the inspiration phase, we conducted a qualitative cross-sectional case study design over 3 months. We used thematic analysis with the framework approach of parent and provider interviews. Five team members individually coded transcripts and then met to discuss memos, update a construct summary sheet, and identify emerging themes. The team adapted themes into "How Might We" statements. For the ideation phase, multidisciplinary stakeholders brainstormed solutions to the "How Might We" statements in a design workshop. Workshop findings informed the design of a nurse-to-family telehealth intervention, which was iteratively revised over 2 months based on stakeholder feedback sessions. Results: We conducted interviews with nine parents, 11 nurses, and 13 physicians. Four themes emerged supporting the promise of a nurse-to-family telehealth intervention, the need to effectively communicate the intervention purpose, the value of a user-friendly workflow, and the essentiality of ensuring that diverse populations equitably benefit from the intervention. "How Might We" statements were discussed among 22 total workshop participants. Iterative adaptations were made to the intervention until feedback from workshop participants and 67 other stakeholders supported no further improvements were needed. Conclusion: Human-centered design phases facilitated stakeholder engagement in developing a nurse-to-family telehealth intervention. This intervention will be tested in an implementation phase as a feasibility and pilot trial.

7.
Elife ; 122023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910016

RESUMO

Conventional kinesin-1 is the primary anterograde motor in cells for transporting cellular cargo. While there is a consensus that the C-terminal tail of kinesin-1 inhibits motility, the molecular architecture of a full-length autoinhibited kinesin-1 remains unknown. Here, we combine crosslinking mass spectrometry (XL-MS), electron microscopy (EM), and AlphaFold structure prediction to determine the architecture of the full-length autoinhibited kinesin-1 homodimer (kinesin-1 heavy chain [KHC]) and kinesin-1 heterotetramer (KHC bound to kinesin light chain 1 [KLC1]). Our integrative analysis shows that kinesin-1 forms a compact, bent conformation through a break in coiled-coil 3. Moreover, our XL-MS analysis demonstrates that kinesin light chains stabilize the folded inhibited state rather than inducing a new structural state. Using our structural model, we show that disruption of multiple interactions between the motor, stalk, and tail domains is required to activate the full-length kinesin-1. Our work offers a conceptual framework for understanding how cargo adaptors and microtubule-associated proteins relieve autoinhibition to promote activation.


Assuntos
Cinesinas , Proteínas Associadas aos Microtúbulos , Transporte Biológico , Consenso , Espectrometria de Massas
8.
J Org Chem ; 88(20): 14413-14422, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37768172

RESUMO

Photolysis of 1-(2-adamantylidene)-1a,9b-dihydro-1H-cyclopropa[l]phenanthrene in benzene (or benzene-d6) at ambient temperature produces adamantylidenecarbene. The carbene undergoes dimerization to a cumulene and may also be trapped in a stereospecific fashion by cis- and trans-4-methyl-2-pentene. No products attributable to 4-homoadamantyne, resulting from ring expansion of the carbene, could be detected. Coupled cluster/density functional theory calculations place the singlet carbene ∼49 kcal/mol below the triplet and show that the former must overcome a barrier of ∼13.5 kcal/mol to rearrange into 4-homoadamantyne.

9.
BMC Pregnancy Childbirth ; 23(1): 186, 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36932353

RESUMO

BACKGROUND: Gestational Diabetes Mellitus (GDM) incidence and adverse outcomes have increased globally. The validity of the oral glucose tolerance test (OGTT) for GDM diagnosis has long been questioned, with no suitable substitute reported yet. Continuous Glucose Monitoring (CGM) is potentially a more acceptable and comprehensive test. The aim of this study was to assess the Freestyle Libre Pro 2 acceptability as a diagnostic test for GDM, then triangulating its results with OGTT results as well as risk factors and sonographic features of GDM. METHODS: Women wore the CGM device for 7 days at 24-28 weeks, undergoing the OGTT before CGM removal. CGM/OGTT acceptability as well as GDM risk factors evaluation occurred via three online surveys. CGM distribution/variability/time in range parameters, combined in a CGM Score of Variability (CGMSV), were triangulated with OGTT results and a risk-factor-based Total Risk Score (TRS). In a subgroup, GDM ultrasound features (as modified Ultrasound Gestational Diabetes Score - m-UGDS) were also incorporated. RESULTS: Of 107 women recruited, 87 (81%) were included: 74 (85%) with negative OGTT (NGT) and 13 (15%) positive (GDM). No significant difference was found between NGT and GDM in terms of demographics (apart from family history of diabetes mellitus), CGM parameters and perinatal outcomes. Women considered CGM significantly more acceptable than OGTT (81% versus 27% rating 5/5, p < 0.001). Of the 55 NGT with triangulation data, 28 were considered 'true negative' (TRS concordant with OGTT and CGMSV): of these 4/5 evaluated at ultrasound had m-UGDS below the cut-off. Five women were considered 'false negative' (negative OGTT with both TRS and CGMSV above the respective cut-offs). Triangulation identified also six 'false positive' women (positive OGTT but TRS and CGM both below the cut-offs). Only one woman for each of the last two categories had m-UGDS evaluated, with discordant results. CONCLUSIONS: CGM represents a more acceptable alternative for GDM diagnosis to the OGTT. CGM triangulation analysis suggests OGTT screening may result in both false positives and negatives. Further research including larger cohorts of patients, and additional triangulation elements (such as GDM biomarkers/outcomes and expanded m-UGDS) is needed to explore CGM potential for GDM diagnosis.


Assuntos
Diabetes Gestacional , Gravidez , Humanos , Feminino , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Glicemia , Projetos Piloto , Automonitorização da Glicemia , Teste de Tolerância a Glucose
10.
bioRxiv ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36747757

RESUMO

Conventional kinesin-1 is the primary anterograde motor in cells for transporting cellular cargo. While there is a consensus that the C-terminal tail of kinesin-1 inhibits motility, the molecular architecture of a full-length autoinhibited kinesin-1 remains unknown. Here, we combine cross-linking mass spectrometry (XL-MS), electron microscopy (EM), and AlphaFold structure prediction to determine the architecture of the full-length autoinhibited kinesin-1 homodimer [kinesin-1 heavy chain (KHC)] and kinesin-1 heterotetramer [KHC bound to kinesin light chain 1 (KLC1)]. Our integrative analysis shows that kinesin-1 forms a compact, bent conformation through a break in coiled coil 3. Moreover, our XL-MS analysis demonstrates that kinesin light chains stabilize the folded inhibited state rather than inducing a new structural state. Using our structural model, we show that disruption of multiple interactions between the motor, stalk, and tail domains is required to activate the full-length kinesin-1. Our work offers a conceptual framework for understanding how cargo adaptors and microtubule-associated proteins relieve autoinhibition to promote activation.

11.
JAMA Netw Open ; 6(2): e2255770, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36780158

RESUMO

Importance: Pediatric referral centers are increasingly using telemedicine to provide consultations to help care for acutely ill children presenting to rural and community emergency departments (EDs). These pediatric telemedicine consultations may help improve physician decision-making and may reduce the frequency of overtriage and interfacility transfers. Objective: To examine the use of pediatric critical care telemedicine vs telephone consultations associated with risk-adjusted transfer rates of acutely ill children from community and rural EDs. Design, Setting, and Participants: A cluster-randomized crossover trial was conducted between November 18, 2015, and March 26, 2018. Analyses were conducted from January 19, 2018, to July 23, 2022, 2022. Participants included acutely ill children aged 14 years and younger presenting to a participating ED in 15 rural and community EDs in northern California. Interventions: Participating EDs were randomized to use telemedicine or telephone for consultations with pediatric critical care physicians according to 1 of 4 unbalanced (3 telemedicine:1 telephone) crossover treatment assignment sequences. Main Outcomes and Measures: Intention-to-treat, treatment-received, and per-protocol analyses were performed to determine the risk of transfer using mixed effects Poisson regression analyses with random intercepts for presenting EDs to account for hospital-level clustering. Results: A total of 696 children (392 boys [56.3%]; mean [SD] age, 4.2 [4.6] years) were enrolled. Of the 537 children (77.2%) assigned to telemedicine, 251 (46.7%) received the intervention. In the intention-to-treat analysis, patients assigned to the telemedicine arm were less likely to be transferred compared with patients assigned to the telephone arm after adjusting for patient age, severity of illness, and hospital study period (risk rate [RR], 0.93; 95% CI, 0.88-0.99). The adjusted risk of transfer was significantly lower in the telemedicine arm compared with the telephone arm in both the treatment-received analysis (RR, 0.81; 95% CI, 0.71-0.94) and the per-protocol analysis (RR, 0.79; 95% CI, 0.68-0.92). Conclusions and Relevance: In this randomized trial, the use of telemedicine to conduct consultations for acutely ill children in rural and community EDs resulted in less frequent overall interfacility transfers than consultations done by telephone. Trial Registration: ClinicalTrials.gov Identifier: NCT02877810.


Assuntos
Serviços de Saúde Rural , Telemedicina , Masculino , Criança , Humanos , Pré-Escolar , Estudos Cross-Over , Estudos Retrospectivos , Telemedicina/métodos , Encaminhamento e Consulta
12.
Telemed J E Health ; 29(8): 1114-1126, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36595515

RESUMO

Background: Previous research has demonstrated high patient satisfaction with telehealth encounters. The objective of this study was to compare patient satisfaction scores regarding their physician using the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) surveys between in-person and telehealth outpatient encounters during the pandemic at a large academic health center. Methods: We analyzed CAHPS patient satisfaction survey data within the UC Davis Health system between August 2020 and February 2022. The questions analyzed pertained to patients' satisfaction with their care provider; whether they felt included in discussions, would recommend their physician, received clear explanations, and that their concerns were heard. Using logistic regression models adjusting for confounders, we compared CAHPS care provider top box scores-a score of 4 or 5 on the 5-point scale-for 5 survey items. Results: Survey results from 76,687 (84.2%) in-person encounters and 14,404 (15.8%) telehealth encounters were evaluated. The odds of a telehealth patient giving a top box score for whether they would recommend their care provider to others were 0.97 those of an in-person patient (95% confidence interval [0.87-1.06]; p = 0.494). Similarly, there was no significant difference in odds of giving a top box score between telehealth and in-person patients for the other four questions analyzed. Discussion: Our findings indicate that patient experience and care provider rankings for in-person care and telehealth care are comparable across a variety of specialties and conditions at a large academic health center. Future studies should investigate patient satisfaction with in-person and telehealth encounters by diagnosis and specialty.


Assuntos
COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , Satisfação do Paciente , Pandemias , Pessoal de Saúde , Centros Médicos Acadêmicos
13.
J Telemed Telecare ; 29(2): 126-132, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33226895

RESUMO

BACKGROUND: Children in rural communities often lack access to subspecialty medical care. Telemedicine has the potential to improve access to these services but its effectiveness has not been rigorously evaluated for paediatric patients with endocrine conditions besides diabetes. INTRODUCTION: The purpose of this study was to assess the association between telemedicine and visit attendance among patients who received care from paediatric endocrinologists at an academic medical centre in northern California between 2009-2017. METHODS: We abstracted demographic data, encounter information and medical diagnoses from the electronic health record for patients ≤18 years of age who attended at least one in-person or telemedicine encounter with a paediatric endocrinologist during the study period. We used a mixed effects logistic regression model - adjusted for age, diagnosis and distance from subspecialty care - to explore the association between telemedicine and visit attendance. RESULTS: A total of 40,941 encounters from 5083 unique patients were included in the analysis. Patients who scheduled telemedicine visits were predominantly publicly insured (97%) and lived a mean distance of 161 miles from the children's hospital. Telemedicine was associated with a significantly higher odds of visit attendance (odds ratio 2.55, 95% confidence interval 2.15-3.02, p < 0.001) compared to in-person care. CONCLUSIONS: This study demonstrates that telemedicine is associated with higher odds of visit attendance for paediatric endocrinology patients and supports the conclusion that use of telemedicine may improve access to subspecialty care for rural and publicly insured paediatric populations.


Assuntos
Diabetes Mellitus , Telemedicina , Criança , Humanos , Centros Médicos Acadêmicos , Modelos Logísticos
14.
J Proteome Res ; 22(2): 520-525, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36475762

RESUMO

Here, we describe the implementation of the fast proteomics search engine MSFragger as a processing node in the widely used Proteome Discoverer (PD) software platform. PeptideProphet (via the Philosopher tool kit) is also implemented as an additional PD node to allow validation of MSFragger open (mass-tolerant) search results. These two nodes, along with the existing Percolator validation module, allow users to employ different search strategies and conveniently inspect search results through PD. Our results have demonstrated the improved numbers of PSMs, peptides, and proteins identified by MSFragger coupled with Percolator and significantly faster search speed compared to the conventional SEQUEST/Percolator PD workflows. The MSFragger-PD node is available at https://github.com/nesvilab/PD-Nodes/releases/.


Assuntos
Proteoma , Ferramenta de Busca , Ferramenta de Busca/métodos , Proteoma/metabolismo , Algoritmos , Espectrometria de Massas em Tandem/métodos , Software , Bases de Dados de Proteínas
15.
Telemed Rep ; 3(1): 137-148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185467

RESUMO

Background: This article describes factors related to adoption, implementation, and effectiveness of the Virtual Pediatric Trauma Center intervention, which uses telehealth for trauma specialist consultations for seriously injured children. We aimed at (1) measuring RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) implementation outcomes and (2) identifying PRISM (Practical, Robust, Implementation, and Sustainability Model) contextual factors that influenced the implementation outcomes. Methods: This interim implementation evaluation of our telehealth trial used a convergent mixed-methods design. The quantitative component was a cross-sectional analysis of pediatric trauma encounters using electronic health records. The qualitative component was a thematic analysis of written and verbal feedback from providers and family advisory board meetings. We compared the quantitative and qualitative data by synthesizing them in a joint display table, organized by RE-AIM dimensions. We categorized these key findings into the PRISM domains. Results: During the first 10 months of this trial, 246 subjects were randomized, with 177 assigned to standard care and 69 assigned to telehealth. Four referring sites transitioned from standard care into their intervention period. PRISM contextual factors that influenced RE-AIM implementation outcomes included the following findings: Providers struggle to remember, interpret, and navigate intervention workflows; providers have preconceived ideas about the intervention purpose; the intervention mitigates parents' anxieties about the transfer process. Discussion: This study revealed implementation challenges that influence the overall success of this telehealth trial. Early identification of these challenges allows our team the opportunity to address them now to optimize the intervention reach, adoption, and implementation. This early action will ultimately enhance the success of our trial and the ability of our intervention to achieve broad impact.

16.
Br J Anaesth ; 129(5): 716-725, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36167682

RESUMO

Postpartum haemorrhage continues to be a leading cause of morbidity and mortality in the obstetric population worldwide, especially in patients at extremes of body weight. Quantification of blood loss has been considered extensively in the literature. However, these volumes must be contextualised to appreciate the consequences of blood loss for individual parturients. Knowledge of a patient's peripartum circulating blood volume is essential to allow accurate interpretation of the significance of haemorrhage and appropriate resuscitation. Greater body weight in obesity can lead to overestimation of blood volume, resulting in inappropriately high thresholds for blood product transfusion and delays in treatment. The most recent Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK) surveillance report demonstrated the risk to this population, with more than half of all maternal mortality recorded in parturients who were either overweight or obese. Current linear calculations used to estimate circulating blood volumes based on patients' weights could be contributing to this phenomenon, as blood volume increases at a disproportional rate to body composition. In this review, we summarise the relevant physiology and explore the existing literature on the estimation of circulating blood volume, both during pregnancy and in obesity. Building on key works and principal findings, we present a practical, nonlinear approach to the adjustment of estimated blood volume with increasing body mass. This clinical tool aims to reduce the clinical bias influencing the management of obstetric haemorrhage in a population already at increased risk of morbidity and mortality. Discussion of the limitations of this approach and the call for further research within this field completes this review.


Assuntos
Hemorragia Pós-Parto , Gravidez , Feminino , Humanos , Hemorragia Pós-Parto/terapia , Peso Corporal , Obesidade/complicações , Obesidade/terapia , Transfusão de Sangue , Volume Sanguíneo
17.
Adv Pediatr ; 69(1): 1-11, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35985702

RESUMO

The accelerated uptake of telemedicine during the coronavirus disease 2019 pandemic has resulted in valuable experience and evidence on the delivery of telemedicine for pediatric patients. The pandemic has also highlighted inequities and opportunities for improvement. This review discusses lessons learned during the pandemic, focusing on provider-to-patient virtual encounters. Recent evidence on education and training, developing and adapting clinical workflows, patient assessment and treatment, and family-centered care is reviewed. Opportunities for future research in pediatric telemedicine are discussed, specifically with regard to engaging pediatric patients, improving and measuring access to care, addressing health equity, and expanding the evidence base.


Assuntos
COVID-19 , Telemedicina , Criança , Humanos , Pandemias , Telemedicina/métodos
18.
Curr Biol ; 32(18): 3898-3910.e14, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-35963242

RESUMO

Tubulin post-translational modifications (PTMs) alter microtubule properties by affecting the binding of microtubule-associated proteins (MAPs). Microtubule detyrosination, which occurs by proteolytic removal of the C-terminal tyrosine from ɑ-tubulin, generates the oldest known tubulin PTM, but we lack comprehensive knowledge of MAPs that are regulated by this PTM. We developed a screening pipeline to identify proteins that discriminate between Y- and ΔY-microtubules and found that echinoderm microtubule-associated protein-like 2 (EML2) preferentially interacts with Y-microtubules. This activity depends on a Y-microtubule interaction motif built from WD40 repeats. We show that EML2 tracks the tips of shortening microtubules, a behavior not previously seen among human MAPs in vivo, and influences dynamics to increase microtubule stability. Our screening pipeline is readily adapted to identify proteins that specifically recognize a wide range of microtubule PTMs.


Assuntos
Microtúbulos , Tubulina (Proteína) , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Processamento de Proteína Pós-Traducional , Tubulina (Proteína)/metabolismo , Tirosina/metabolismo
19.
Semin Speech Lang ; 43(3): 244-254, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35858609

RESUMO

Cost-effectiveness analysis, the most common type of economic evaluation, estimates a new option's additional outcome in relation to its extra costs. This is crucial to study within the clinical setting because funding for new treatments and interventions is often linked to whether there is evidence showing they are a good use of resources. This article describes how to analyze a cost-effectiveness dataset using the framework of a net benefit regression. The process of creating estimates and characterizing uncertainty is demonstrated using a hypothetical dataset. The results are explained and illustrated using graphs commonly employed in cost-effectiveness analyses. We conclude with a call to action for researchers to do more person-level cost-effectiveness analysis to produce evidence of the value of new treatments and interventions. Researchers can utilize cost-effectiveness analysis to compare new and existing treatment mechanisms.


Assuntos
Fala , Análise Custo-Benefício , Humanos
20.
BMJ Open Qual ; 11(1)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241438

RESUMO

BACKGROUND: Children with neurodisability are at an increased risk of respiratory problems and complications, which often result in prolonged, frequent hospital admissions and are the biggest cause of mortality in this client group. The Children's Community Respiratory Physiotherapy Service (CCRPS) was established in 2010 to support children with severe neurodisabilities at home during acute chest infections and to prevent emergency department attendances and hospital admissions. This service evaluation looked at patient/parent satisfaction and prevented admissions to ensure clinical and cost-effectiveness, despite the rising demand for the service. METHODS: Over a 3-month period, patients and parents/carers on the CCRPS caseload were given a Picker feedback survey following 100 emergency visits from the team. The number of prevented hospital admissions for respiratory tract infection over 12 months (April 2019-March 2020) was identified from existing CCRPS data and hospital admissions costs saved were estimated. RESULTS: The Picker survey responses were extremely positive with all respondents reporting that they felt well looked after and that the main reason for the emergency visit was dealt with well. Based on key indicators, the CCRPS prevented 182 hospital admissions for respiratory tract infection in 2019/2020, equating to 1638 bed days and estimated cost savings ranging between £751 728 and £1 009 986. CONCLUSIONS: The Picker survey response demonstrates the positive impact that the CCRPS has on both quality of life and experience for patients and families. The CCRPS rapid response service prevents hospital admissions for respiratory tract infections in children and young people with severe neurodisability and the cost savings from admissions prevented allows the service to more than pay for itself.


Assuntos
Qualidade de Vida , Infecções Respiratórias , Adolescente , Criança , Análise Custo-Benefício , Hospitalização , Humanos , Modalidades de Fisioterapia , Infecções Respiratórias/terapia
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