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1.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009389

RESUMO

Psoriasis and psoriatic arthritis are associated with an increased risk of mental health conditions such as depression and anxiety. People with psoriatic disease (PsD) are also more likely to die by suicide than those without. Mood disorders affect people with PsD in a multitude of ways, such as in effectiveness of care, response to treatment, remission rates, and quality of life. Although the links between PsD and mental health conditions have not been fully elucidated, this review will highlight recent studies investigating shared biologic mechanisms between depression and PsD. Since mental health disorders can be assessed and treated effectively, dermatologists and rheumatologists should be aware of the mental health burden in individuals with PsD to accomplish the following: (1) educate their patients with PsD about this association, (2) screen for mental health conditions on an ongoing basis in their clinical practice, (3) refer their patients with PsD to a mental health professional when needed, and (4) ensure selection of a safe PsD treatment in the setting of comorbid mental health disease. Finally, important treatment considerations for individuals with PsD and depression are reviewed. This topic was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting.

2.
J Rheumatol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089826

RESUMO

Two presentations at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting focused on unintended consequences of immunomodulatory therapy for psoriasis (PsO). Dr. Elizabeth Wallace presented on unintended consequences of tumor necrosis factor inhibitors for treating PsO and other inflammatory disorders. These consequences include paradoxical PsO, which is defined as unexpected new PsO cases or worsening PsO symptoms seemingly induced by treatment. Dr. Bruce Kirkham focused on unintended consequences of dupilumab treatment, which can include a musculoskeletal syndrome similar to psoriatic arthritis.

3.
J Am Acad Dermatol ; 91(2): 251.e1-251.e11, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38499181

RESUMO

BACKGROUND: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication. OBJECTIVE: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery. METHODS: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery. RESULTS: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. CONCLUSION: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib.


Assuntos
Artrite Psoriásica , Metotrexato , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Psoríase/tratamento farmacológico , Psoríase/imunologia , Metotrexato/uso terapêutico , Assistência Perioperatória/métodos , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Talidomida/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Piperidinas/uso terapêutico , Ciclosporina/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Inibidores da Fosfodiesterase 4/efeitos adversos , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Agentes de Imunomodulação/uso terapêutico , Abatacepte/uso terapêutico , Abatacepte/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos
4.
J Am Acad Dermatol ; 90(6): 1170-1181, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331098

RESUMO

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.


Assuntos
Artrite Psoriásica , Produtos Biológicos , Consenso , Técnica Delphi , Psoríase , Humanos , Psoríase/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/administração & dosagem , Administração Oral , Vacinação/normas , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2 , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico
5.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38928454

RESUMO

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Matriz Extracelular , Proteômica , Microambiente Tumoral , Humanos , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Proteômica/métodos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Proteoma/metabolismo , Proteoma/análise , Invasividade Neoplásica , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Pessoa de Meia-Idade
6.
J Am Acad Dermatol ; 89(5): 974-983, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37495173

RESUMO

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

7.
Neuropsychol Rev ; 32(1): 149-160, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33860906

RESUMO

Mild cognitive changes, including executive dysfunction, are seen in Parkinson's Disease (PD). Approximately 30% of individuals with PD develop Parkinson's disease dementia (PDD). Mild cognitive impairment (MCI) has been identified as a transitional state between normal cognition and dementia. Although PD-MCI and its cognitive correlates have been increasingly studied as a risk indicator for development of PDD, investigations into the PD-MCI construct have yielded heterogeneous findings. Thus, a typical PD-MCI cognitive profile remains undefined. The present meta-analysis examined published cross-sectional studies of PD-MCI and cognitively normal PD (PD-CN) groups to provide aggregated effect sizes of group test performance by cognitive domain. Subsequently, longitudinal studies examining PD-MCI to PDD progression were meta-analyzed. Ninety-two cross-sectional articles of PD-MCI vs. PD-CN were included; 5 longitudinal studies of PD-MCI conversion to PDD were included. Random effects meta-analytic models were constructed resulting in effect sizes (Hedges' g) for cognitive domains. Overall performance across all measures produced a large effect size (g = 0.83, 95% CI [0.79, 0.86], t2 = 0.18) in cross-sectional analyses, with cognitive screeners producing the largest effect (g = 1.09, 95% CI [1.00, 1.17], t2 = 0.19). Longitudinally, overall measures produced a moderate effect (g = 0.47, 95% CI [0.40, 0.53], t2 = 0.01), with measures of executive functioning exhibiting the largest effect (g = 0.70, 95% CI [0.51, 0.89], t2 = 0.01). Longitudinal effects were made more robust by low heterogeneity. This report provides the first comprehensive meta-analysis of PD-MCI cognitive outcomes and predictors in PD-MCI conversion to PDD. Limitations include heterogeneity of cross-sectional effect sizes and the potential impact of small-study effects. Areas for continued research include visuospatial skills and visual memory in PD-MCI and longitudinal examination of executive dysfunction in PD-MCI.


Assuntos
Disfunção Cognitiva , Demência , Doença de Parkinson , Cognição , Disfunção Cognitiva/etiologia , Estudos Transversais , Demência/etiologia , Progressão da Doença , Humanos , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia
8.
Pediatr Res ; 90(2): 464-471, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33184499

RESUMO

BACKGROUND: In this study, trauma-specific risk factors of prolonged length of stay (LOS) in pediatric trauma were examined. Statistical and machine learning models were used to proffer ways to improve the quality of care of patients at risk of prolonged length of stay and reduce cost. METHODS: Data from 27 hospitals were retrieved on 81,929 hospitalizations of pediatric patients with a primary diagnosis of trauma, and for which the LOS was >24 h. Nested mixed effects model was used for simplified statistical inference, while a stochastic gradient boosting model, considering high-order statistical interactions, was built for prediction. RESULTS: Over 18.7% of the encounters had LOS >1 week. Burns and corrosion and suspected and confirmed child abuse are the strongest drivers of prolonged LOS. Several other trauma-specific and general pediatric clinical variables were also predictors of prolonged LOS. The stochastic gradient model obtained an area under the receiver operator characteristic curve of 0.912 (0.907, 0.917). CONCLUSIONS: The high performance of the machine learning model coupled with statistical inference from the mixed effects model provide an opportunity for targeted interventions to improve quality of care of trauma patients likely to require long length of stay. IMPACT: Targeted interventions on high-risk patients would improve the quality of care of pediatric trauma patients and reduce the length of stay. This comprehensive study includes data from multiple hospitals analyzed with advanced statistical and machine learning models. The statistical and machine learning models provide opportunities for targeted interventions and reduction in prolonged length of stay reducing the burden of hospitalization on families.


Assuntos
Tempo de Internação , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Ferimentos e Lesões/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Redução de Custos , Análise Custo-Benefício , Feminino , Custos Hospitalares , Humanos , Tempo de Internação/economia , Aprendizado de Máquina , Masculino , Modelos Estatísticos , Melhoria de Qualidade/economia , Indicadores de Qualidade em Assistência à Saúde/economia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/economia , Ferimentos e Lesões/epidemiologia
9.
J Surg Res ; 257: 370-378, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32892133

RESUMO

BACKGROUND: Return visits within 72 h are an important metric in evaluating the performance of emergency rooms. This has not been well studied in the pediatric trauma population. We sought to determine novel risk factors for return visits to the emergency department (ED) after trauma that may assist in identifying patients most at risk of revisit. METHODS: We used the Cerner Health Facts Database to retrieve data from 34 EDs across the United States that care for pediatric trauma patients aged <15 y. The data consist of 610,845 patients and 816,571 ED encounters. We retrieved variables encompassing demographics, payor, current and past health care resource utilization, trauma diagnoses, other diagnoses/comorbidities, medications, and surgical procedures. We built a nested mixed effects logistic regression model to provide statistical inference on the return visits. RESULTS: Traumas resulting from burns and corrosion, injuries to the shoulder and arms, injuries to the hip and legs, and trauma to the head and neck are all associated with increased odds of returning to the ED. Patients suffering from poisoning relating to drugs and other biological substances and patients with trauma to multiple body regions have reduced odds of returning to the ED. Longer ED length of stay and prior health care utilization (ED or inpatient) are associated with increased odds of a return visit. The sex of the patient and payor had a statistically significant effect on the risk of a return visit to the ED within 72 h of discharge. CONCLUSIONS: Certain traumas expose patients to an increased risk for return visits to the ED and, as a result, provide opportunity for improved quality of care. Targeted interventions that include education, observation holds, or a decision to hospitalize instead of discharge home may help improve patient outcomes and decrease the rate of ED returns. LEVEL OF EVIDENCE: III (Prognostic and Epidemiology).


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Modelos Estatísticos , Readmissão do Paciente/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estados Unidos/epidemiologia
10.
J Fish Biol ; 98(3): 855-864, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33258479

RESUMO

The management of bonefishes Albula spp. has been hindered by unresolved species distributions and a general lack of life-history information. This study provides the first genetic species identifications of Albula spp. from the northern Indian Ocean. The roundjaw bonefish Albula glossodonta was documented in the Red Sea, and the smallscale bonefish A. oligolepis was identified in the Gulf of Aden with no evidence supporting sympatry. Estimates of genetic differentiation indicate three closely related lineages of A. glossodonta in the Red Sea, Indian Ocean and Pacific Ocean (Red Sea-Pacific Ocean, Fst = 0.295; Red Sea-Seychelles, Fst = 0.193; Pacific Ocean-Seychelles, Fst = 0.141). In addition, the authors provide the first life-history information of Albula spp. in the Indian Ocean. Age-based growth models of A. glossodonta from the Red Sea demonstrated statistically significant differences compared to previously published data from the Pacific Ocean. Spawning activity during winter months was derived from gonado-somatic index values of A. glossodonta from the Red Sea and corresponded with spawning seasonality previously documented for the species in the Pacific Ocean. The results of this study aid in refining biogeographical uncertainties of Albula spp. and illustrate the importance of collecting regional growth information for subsequent management of A. glossodonta.


Assuntos
Peixes/genética , Variação Genética , Características de História de Vida , Animais , Peixes/classificação , Deriva Genética , Oceano Índico , Oceano Pacífico , Filogenia , Estações do Ano , Seicheles
11.
J Surg Res ; 253: 254-261, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388388

RESUMO

BACKGROUND: Pediatric patients admitted for trauma may have unique risk factors of unplanned readmission and require condition-specific models to maximize accuracy of prediction. We used a multicenter data set on trauma admissions to study risk factors and predict unplanned 7-day readmissions with comparison to the 30-day metric. METHODS: Data from 28 hospitals in the United States consisting of 82,532 patients (95,158 encounters) were retrieved, and 75% of the data were used for building a random intercept, mixed-effects regression model, whereas the remaining were used for evaluating model performance. The variables included were demographics, payer, current and past health care utilization, trauma-related and other diagnoses, medications, and surgical procedures. RESULTS: Certain conditions such as poisoning and medical/surgical complications during treatment of traumatic injuries are associated with increased odds of unplanned readmission. Conversely, trauma-related conditions, such as trauma to the thorax, knee, lower leg, hip/thigh, elbow/forearm, and shoulder/upper arm, are associated with reduced odds of readmission. Additional predictors include the current and past health care utilization and the number of medications. The corresponding 7-day model achieved an area under the receiver operator characteristic curve of 0.737 (0.716, 0.757) on an independent test set and shared similar risk factors with the 30-day version. CONCLUSIONS: Patients with trauma-related conditions have risk of readmission modified by the type of trauma. As a result, additional quality of care measures may be required for patients with trauma-related conditions that elevate their risk of readmission.


Assuntos
Readmissão do Paciente/estatística & dados numéricos , Ferimentos e Lesões/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Fatores de Tempo , Estados Unidos
13.
Dermatol Online J ; 22(11)2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28329567

RESUMO

Nutritional deficiency is rare in developed countries, but can be acquired from decreased nutrient intake, reduced absorption, and increased gastrointestinal excretion. We report a patient with acquired acrodermatitis enteropathica (AE) who exhibited low plasma zinc levels and concurrent nutritional deficiencies (pyridoxine, selenium and fatty acids). Our patient had undergone Roux-en-Y gastric bypass 13 years prior to presentation. The rash, consistent with AE clinically and histologically, nearly resolved one week after starting IV zinc supplementation, total parenteral nutrition, and micronutrient supplements. This case highlights the importance of long-term post-operative follow-up for gastric bypass patients who are at high risk for micronutrient and macronutrient deficiencies and illustrates the potential for rapid improvement with IV supplementation.


Assuntos
Acrodermatite/diagnóstico , Derivação Gástrica , Desnutrição/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Zinco/deficiência , Acrodermatite/tratamento farmacológico , Acrodermatite/patologia , Administração Intravenosa , Adulto , Feminino , Humanos , Desnutrição/terapia , Nutrição Parenteral Total , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/patologia , Oligoelementos/uso terapêutico , Zinco/uso terapêutico
14.
BMC Psychiatry ; 14: 234, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25196125

RESUMO

BACKGROUND: People with serious mental illness (SMI) exhibit a high prevalence of cardiovascular diseases. Mental health services have a responsibility to address poor physical health in their consumers. One way of doing this is to conduct metabolic monitoring (MM) of risk factors for cardiovascular diseases. This study compares two models of MM among consumers with SMI and describes referral pathways for those at high risk of cardiovascular diseases. METHODS: A retrospective cross-sectional comparison design was used. The two models were: (1) MM integrated with case managers, and (2) MM integrated with case managers and specialist roles. Retrospective data were collected for all new episodes at two community mental health services (CMHS) over a 12-month period (September 2012 - August 2013). RESULTS: A total of 432 consumers with SMI across the two community mental health services were included in the analysis. At the service with the specialist roles, MM was undertaken for 78% of all new episode consumers, compared with 3% at the mental health service with case managers undertaking the role. Incomplete MM was systemic to both CMHS, although all consumers identified with high risk of cardiovascular diseases were referred to a general practitioner or other community based health services. The specialist roles enabled more varied referral options. CONCLUSIONS: The results of this study support incorporating specialist roles over case manager only roles for more effective MM among new episode consumers with SMI.


Assuntos
Doenças Cardiovasculares/diagnóstico , Transtornos Mentais/complicações , Adulto , Idoso , Doenças Cardiovasculares/psicologia , Administração de Caso/organização & administração , Serviços Comunitários de Saúde Mental/organização & administração , Estudos Transversais , Diagnóstico Precoce , Exercício Físico/fisiologia , Feminino , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Saúde Mental , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/organização & administração , Papel Profissional , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
15.
AEM Educ Train ; 8(4): e11018, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39220774

RESUMO

Background: Use of ultrasound (US) for procedural needle guidance can improve success rates, safety, and accuracy. Often, training is performed on task trainers, which can be prohibitively expensive. Determining undesired needle placement is difficult when the needle is poorly visualized with US. Currently available simulation phantoms cannot provide real-time feedback on the location of needle placement. Objectives: The primary objective was to develop and determine feasibility of a low-cost simulation phantom with an internal circuit and LED light system to determine when a needle contacts internal structures. We also aimed to determine whether its use was associated with increased comfort level. Methods: Emergency medicine (EM) residents (PGY-1 to PGY-3) performed in-plane and out-of-plane US needle guidance using homemade phantoms. Comfort levels were assessed by pre- and post intervention survey. Outcomes were measured on Likert scale (minimum = 1, maximum = 5). The primary outcome was change in confidence markers before and after the simulation task. Secondary outcomes were survey results of comparisons of these models to prior training experiences on simulators and humans. Results: All EM residents (30) in our program were invited to participate. Twenty participants enrolled and completed the study. In the primary outcome, median comfort with out-of-plane and in-plane guidance increased after using the model but was more pronounced for out-of-plane guidance. On a posttest survey, residents rated the models overall very similar to prior experience on simulators (median 5/5 [IQR 4.0-5.0]) and moderately similar to humans (median 3/5 [IQR 3.0-4.0]). Conclusions: We created a low-cost ballistic gelatin phantom with an internal electric needle guidance system. Use of the phantom for training was associated with increased learner comfort with the procedure. Learners rated the characteristics of the phantom as similar to higher-cost commercial equipment and humans.

16.
Nat Commun ; 15(1): 816, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280878

RESUMO

Despite increased Atlantic hurricane risk, projected trends in hurricane frequency in the warming climate are still highly uncertain, mainly due to short instrumental record that limits our understanding of hurricane activity and its relationship to climate. Here we extend the record to the last millennium using two independent estimates: a reconstruction from sedimentary paleohurricane records and a statistical model of hurricane activity using sea surface temperatures (SSTs). We find statistically significant agreement between the two estimates and the late 20th century hurricane frequency is within the range seen over the past millennium. Numerical simulations using a hurricane-permitting climate model suggest that hurricane activity was likely driven by endogenous climate variability and linked to anomalous SSTs of warm Atlantic and cold Pacific. Volcanic eruptions can induce peaks in hurricane activity, but such peaks would likely be too weak to be detected in the proxy record due to large endogenous variability.

17.
Sci Rep ; 14(1): 489, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177192

RESUMO

N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell-cell signaling, and immune detection. As different tissue types display different N-glycan profiles, changes in N-glycan compositions occur in tissue-specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N-glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study a broad range of human tissue N-glycomes, N-glycan targeted MALDI imaging mass spectrometry was applied to custom formalin-fixed paraffin-embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in-depth comparisons of the N-glycome differences between tumor and normal and across tissue types. Using established MALDI-IMS workflows and existing N-glycan databases, the N-glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N-acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N-glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI-IMS.


Assuntos
Processamento de Proteína Pós-Traducional , Sarcoma , Masculino , Feminino , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Glicosilação , Polissacarídeos/metabolismo
18.
Pediatr Neurol ; 153: 103-112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367484

RESUMO

BACKGROUND: Although millions of children sustain concussions each year, a rapid and objective test for concussion has remained elusive. The aim of this study was to investigate quantitative pupillometry in pediatric patients in the acute, postinjury setting. METHODS: This was a prospective case-control study of concussed patients presenting to the emergency department within 72 hours of injury. Pupillary measurements were gathered using NeurOptics' PLR 3000; evaluation included a symptom checklist and neurocognitive assessment. Data were analyzed using descriptive statistics and regression models. RESULTS: A total of 126 participants were enrolled. One significant difference in pupillometry between concussed and control participants was found: left minimum pupil diameter in 12- to 18 year-olds (P = 0.02). Models demonstrating odds of a concussion revealed significant associations for time to 75% recovery (T75) of the left pupil in five- to 11-year-olds and average dilation velocity of the left pupil in 12- to 18-year-olds (P = 0.03 and 0.02 respectively). Models predicting symptom improvement showed one significant association: percent change of the right pupil in five-to-11-year-olds (P = 0.02). Models predicting neurocognitive improvement in 12- to 18-year-olds demonstrated significant association in T75 in the left pupil for visual memory, visual motor processing speed, and reaction time (P = 0.002, P = 0.04, P = 0.04). CONCLUSIONS: The limited statistically significant associations found in this study suggest that pupillometry may not be useful in pediatrics in the acute postinjury setting for either the diagnosis of concussion or to stratify risk for prolonged recovery.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Humanos , Criança , Estudos de Casos e Controles , Testes Neuropsicológicos , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Traumatismos em Atletas/diagnóstico , Percepção Visual
19.
medRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38946973

RESUMO

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.

20.
Healthc (Amst) ; 11(2): 100690, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36996736

RESUMO

This article describes the implementation of an equity-focused strategy to increase the uptake of COVID-19 vaccination among communities of color and in traditionally underserved geographic areas using mobile health clinics (MHCs). The MHC Vaccination Program was implemented through a large integrated healthcare system in North Carolina using a grassroots development and engagement strategy along with a robust model for data-informed decision support to prioritize vulnerable communities. Several valuable lessons from this work can replicated for future outreach initiatives and community-based programming: •Health systems can no longer operate under the assumption that community members will come to them, particularly those experiencing compounding social and economic challenges. The MHC model had to be a proactive outreach to community members, rather than a responsive delivery mechanism. •Barriers to access included financial, legal, and logistical challenges, in addition to mistrust among historically underserved and marginalized communities. •A MHC model can be adaptable and responsive to data-informed decision-making approaches for targeted service delivery. •A MHC model is not a one-dimensional solution to access, but part of a broader strategy to create diverse points of entry into the healthcare system that fall within the rhythm of life of community members.


Assuntos
COVID-19 , Telemedicina , Humanos , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Atenção à Saúde , Telemedicina/métodos , Vacinação
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