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Background The coronavirus disease 2019 (COVID-19) pandemic reaffirmed health disparities in the United States (US) and highlighted the need for public health strategies to combat vaccine hesitancy, especially amongst vulnerable populations. The Green Family Foundation Neighborhood Health Education Learning Program (NeighborhoodHELP) at Florida International University (FIU) serves a predominantly uninsured population, making it a critical area of opportunity for addressing vaccine hesitancy. Motivational interviewing (MI), a technique that supports individuals in making autonomous health decisions, has shown promise in encouraging vaccine acceptance. Medical students at FIU's Herbert Wertheim College of Medicine (HWCOM) are involved in the longitudinal care of the individuals in NeighborhoodHELP and receive training in MI within their clinical skills curriculum, making them optimally positioned to conduct outreach to encourage COVID-19 vaccination. Project goals There were two primary goals of this project: first, to systematically track and improve COVID-19 vaccination rates among individuals in NeighborhoodHELP, and second, to equip future physicians with hands-on experience in MI. Methods The COVID-19 Vaccination Promotion Initiative recruited medical students previously trained in MI to conduct outreach to unvaccinated individuals within NeighborhoodHELP. Students engaged in discussions about the COVID-19 vaccine with NeighborhoodHELP members, assisted in scheduling vaccination appointments, and updated medical records. The student team regularly met with faculty advisors to discuss changes in vaccine and public health data and to discuss challenges and successes with outreach efforts. To incentivize participation and enhance vaccine uptake, $25 gift cards were offered to individuals who agreed to receive the vaccine following the outreach conversations. Results From June 2021 to January 2023, the team made an estimated 720-1516 phone calls to NeighborhoodHELP individuals. The team encountered a challenge of low answering rates, with 35% of individuals being unreachable despite multiple attempts. Among those reached, 20% expressed no interest in receiving the vaccine, while 50% were interested in receiving the vaccine or had already been vaccinated. Vaccination rates among NeighborhoodHELP adults rose from 15.2% to 44.3% during this time. Student experiences with MI were generally positive, with many noting success in engaging hesitant individuals. However, the team also encountered challenges, such as growing vaccine apathy within the community and difficulties in reaching patients via cold calls, which limited the overall impact of their outreach efforts. Conclusions By using MI techniques, medical students engaged with community members in meaningful conversations about the importance and safety of COVID-19 vaccination. However, the initiative fell short of the 50% vaccination target, facing challenges such as reliance on unsolicited phone calls and the complexities of incentivizing vaccinations through this outreach method. Future initiatives could benefit from exploring alternative outreach methods, such as in-person engagement at community events or through partnerships with local organizations, to overcome the limitations of phone-based outreach. Additionally, investigating the relative efficacy of in-person versus telephone-based communication in promoting vaccination could provide valuable insights.
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X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of growth/differentiation factor 5 (Gdf5) is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.
X-linked hypophosphatemia (XLH) is a rare bone disorder that leads to short stature and poorly mineralized bones. As adults, patients with XLH often develop a mineralization of the bone-tendon attachment site, called enthesopathy, which results in significant pain. We previously showed that Achilles bone-tendon attachment sites (entheses) in mice with XLH (Hyp) have an enthesopathy characterized by increased bone morphogenetic protein (BMP) signaling. In the current studies, we show that treating Hyp mice with the BMP signaling inhibitor palovarotene prevents enthesopathy, demonstrating that the increased BMP signaling in Hyp entheses leads to enthesopathy development. We also reported that gene expression of Gdf5, which activates BMP signaling, is enhanced in Hyp entheses. Therefore, to determine if the enhanced Gdf5 expression leads to the increased BMP signaling seen Hyp entheses, Gdf5 was deleted from Hyp mice and also deleted specifically in the entheses of Hyp mice. In both mouse models, enthesopathy development was attenuated, demonstrating that the increased Gdf5 expression in Hyp entheses plays a role in enthesopathy development. These data indicate that blocking GDF5 and BMP signaling may prevent enthesopathy in patients with XLH.
Assuntos
Entesopatia , Raquitismo Hipofosfatêmico Familiar , Fator 5 de Diferenciação de Crescimento , Animais , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Modelos Animais de Doenças , Entesopatia/genética , Entesopatia/metabolismo , Entesopatia/patologia , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/metabolismo , Raquitismo Hipofosfatêmico Familiar/patologia , Fator 5 de Diferenciação de Crescimento/metabolismo , Fator 5 de Diferenciação de Crescimento/genética , Transdução de SinaisRESUMO
BACKGROUND: Patients with cardiovascular disease (CVD) and risk factors have increased rates of adverse events and mortality after hospitalization for coronavirus disease 2019 (COVID-19). In this study, we attempted to identify and assess the effects of CVD on COVID-19 hospitalizations in the USA using a large national database. METHODS: The current study was a retrospective analysis of data from the US National (Nationwide) Inpatient Sample from 2020. All adult patients 18 years of age and older who were admitted with the primary diagnosis of COVID-19 were included. The primary outcome was in-hospital mortality, while secondary outcomes included prolonged hospital length of stay, mechanical ventilation, and disposition other than home. Prolonged hospital length of stay was defined as a length of stay greater than the 75th percentile for the full sample. The diagnoses were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes. RESULTS: A total of 1â 050â 040 patients were included in the study, of which 454â 650 (43.3%) had prior CVD. Patients with CVD had higher mortality during COVID-19 hospitalization (19.3 vs. 5.0%, Pâ <â 0.001). Similarly, these patients had a higher rate of prolonged hospital length of stay (34.5 vs. 21.0%, Pâ <â 0.001), required mechanical ventilation (15.4 vs. 5.6%, Pâ <â 0.001), and were more likely to be discharged to a disposition other than home (62.5 vs. 32.3%, Pâ <â 0.001). Mean hospitalization cost was also higher in patients with CVD during hospitalization ($24â 023 vs. $15â 320, Pâ <â 0.001). Conditional logistic regression analysis showed that the odds of in-hospital mortality [odds ratio (OR), 3.23; 95% confidence interval (CI), 2.91-3.45] were significantly higher for COVID-19 hospitalizations with CVD, compared with those without CVD. Similarly, prolonged hospital length (OR, 1.82; 95% CI, 1.43-2.23), mechanical ventilation (OR, 3.31; 95% CI, 3.06-3.67), and disposition other than home (OR, 2.01; 95% CI, 1.87-2.21) were also significantly higher for COVID-19 hospitalizations with coronary artery disease. CONCLUSION: Our study showed that the presence of CVD has a significant negative impact on the prognosis of patients hospitalized for COVID-19. There was an associated increase in mortality, length of stay, ventilator use, and adverse discharge dispositions among COVID-19 patients with CVD. Adjustment in treatment for CVD should be considered when providing care to patients hospitalized for COVID-19 to mitigate some of the adverse hospital outcomes.
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In this study, using a large database, we examined the association between atrial fibrillation (AF) in hospitalized patients with pulmonary hypertension (PH) and in-hospital mortality and other adverse hospital outcomes. This study was a retrospective analysis of the United States National (Nationwide) Inpatient Sample from 2005 to 2014. All hospitalizations for patients diagnosed with primary PH and over the age of 65 years were included and then grouped based on the presence AF. The outcomes were in-hospital mortality rate, hospital length of stay, and hospitalization costs. Weighted regression analyses were performed to find the association between AF and outcomes. Of the 5,428,332 hospitalizations with PH, 2,531,075 (46.6%) had concomitant AF. The Cox proportional regression analysis showed that in patients with PE, all-cause mortality (hazard ratio 1.35, confidence interval [CI] 1.15 to 1.55) was significantly higher in patients with AF than those without AF. In addition, PH hospitalizations with AF had a longer hospital length of stay (ß coefficient 1.74, 95% CI 1.58 to 1.83) and higher hospitalization cost (ß coefficient 1.33, 95% CI 1.12 to 1.42). In patients aged over 65 years admitted for PH, the presence of AF was very frequent and worsened the prognosis. In conclusion, to improve patient outcomes and decrease hospital burden, it is important to consider AF during risk stratification for patients with PH to provide timely and prompt interventions. An interdisciplinary approach to treatment should be used to account for the burden of co-morbidities in this population.
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Fibrilação Atrial , Hipertensão Pulmonar , Humanos , Estados Unidos/epidemiologia , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Estudos Retrospectivos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/complicações , Hospitalização , Mortalidade Hospitalar , HospitaisRESUMO
X-linked hypophosphatemia (XLH) is characterized by high serum fibroblast growth factor 23 (FGF23) levels, resulting in impaired 1,25-dihydroxyvitamin D3 (1,25D) production. Adults with XLH develop a painful mineralization of the tendon-bone attachment site (enthesis), called enthesopathy. Treatment of mice with XLH (Hyp) with 1,25D or an anti-FGF23 Ab, both of which increase 1,25D signaling, prevents enthesopathy. Therefore, we undertook studies to determine a role for impaired 1,25D action in enthesopathy development. Entheses from mice lacking vitamin D 1α-hydroxylase (Cyp27b1) (C-/-) had a similar enthesopathy to Hyp mice, whereas deletion of Fgf23 in Hyp mice prevented enthesopathy, and deletion of both Cyp27b1 and Fgf23 in mice resulted in enthesopathy, demonstrating that the impaired 1,25D action due to high FGF23 levels underlies XLH enthesopathy development. Like Hyp mice, enthesopathy in C-/- mice was observed by P14 and was prevented, but not reversed, with 1,25D therapy. Deletion of the vitamin D receptor in scleraxis-expressing cells resulted in enthesopathy, indicating that 1,25D acted directly on enthesis cells to regulate enthesopathy development. These results show that 1,25D signaling was necessary for normal postnatal enthesis maturation and played a role in XLH enthesopathy development. Optimizing 1,25D replacement in pediatric patients with XLH is necessary to prevent enthesopathy.
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Entesopatia , Raquitismo Hipofosfatêmico Familiar , Camundongos , Animais , Raquitismo Hipofosfatêmico Familiar/genética , Calcitriol , 25-Hidroxivitamina D3 1-alfa-Hidroxilase , Fatores de Crescimento de Fibroblastos , Vitamina DRESUMO
Peripheral nerve injuries account for roughly 3% of all trauma patients with over 900,000 repair procedures annually in the US. Of all extremity peripheral nerve injuries, 51% require nerve repair with a transected gap. The current gold-standard treatment for peripheral nerve injuries, autograft repair, has several shortcomings. Engineered constructs are currently only suitable for short gaps or small diameter nerves. Here, we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine (4-AP) for peripheral nerve regeneration in a critical-size (15 mm) rat sciatic nerve transection model. The results of functional walking track analysis, morphometric evaluations of myelin development, and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls. Repaired nerves showed formation of thick myelin, presence of S100 and neurofilament markers, and promising functional recovery. The conduit's aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation, while the sustained release of 4-AP may increase nerve conduction, and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors. Overall, our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.
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Peripheral nerve injuries can be extremely debilitating, resulting in sensory and motor loss-of-function. Endogenous repair is limited to non-severe injuries in which transection of nerves necessitates surgical intervention. Traditional treatment approaches include the use of biological grafts and alternative engineering approaches have made progress. The current article serves as a comprehensive, in-depth perspective on peripheral nerve regeneration, particularly nerve guidance conduits and drug delivery strategies. A detailed background of peripheral nerve injury and repair pathology, and an in-depth look into augmented nerve regeneration, nerve guidance conduits, and drug delivery strategies provide a state-of-the-art perspective on the field.