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1.
Artigo em Inglês | MEDLINE | ID: mdl-38934569

RESUMO

Renal cancer, although still rare among individuals under 45 years of age, is on the rise in the general population. The risk and timing of subsequent renal cancer in survivors of childhood cancer is not well established. Using the SEER registry, we reported the incidence of subsequent malignant renal neoplasms after treatment for primary malignancy diagnosed under 20 years of age. We evaluated clinical characteristics, standardized incidence ratio (SIR), and Kaplan-Meier survival estimates. Fifty-three survivors developed subsequent renal cancer (54 total cases). Of these, 54.7% were female, 88.7% were white, and 13.2% were Hispanic. Mean ages at primary malignancy and subsequent renal cancer were 10.1 and 31.1 years, respectively. Forty-seven cases were second cancers, 6 were third, and 1 was fourth. For survivors of childhood cancer, the overall SIR for renal cancer was 4.52 (95% CI: 3.39-5.89). The 5-year overall survival rate after development of subsequent renal cancer was 73% (95% CI: 58%-83%). Renal cancer occurs 4.5 times more frequently in childhood cancer survivors than in the general population, necessitating long-term care considerations.

2.
J Antibiot (Tokyo) ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890386

RESUMO

Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6'-position to produce trospectomycin and to the 3'-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3',6'-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins. Computational experiments predicted that these disubstituted analogs would be capable of binding within the SPC ribosomal binding site. The new analogs were synthesized from trospectomycin, adapting the previously established routes for the spectinamide and aminomethyl spectinomycin series. In a cell-free translation assay, the disubstituted analogs showed ribosomal inhibition similar to spectinomycin or trospectomycin. These disubstituted analogs demonstrated inhibitory MIC activity against various bacterial species with the 3'-modification dictating spectrum of activity, leading to improved activity against mycobacterium species. Notably, N-ethylene linked aminomethyl trospectomycins exhibited increased potency against Mycobacterium abscessus and trospectinamide displayed robust activity against M. tuberculosis, aligning with the selective efficacy of spectinamides. The study also found that trospectomycin is susceptible to efflux in M. tuberculosis and M. abscessus. These findings contribute to the understanding of the structure-activity relationship of spectinomycin analogs and can guide the design and synthesis of more effective spectinomycin compounds.

3.
Can J Anaesth ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877135

RESUMO

PURPOSE: The benefits of intraoperative dialysis during orthotopic liver transplantation remain controversial. In patients with anuric renal failure and portopulmonary hypertension, maintaining venous return during caval clamping and unclamping along with minimizing fluid overload is critical to avoiding right ventricular strain and failure. CLINICAL FEATURES: We present the case of a 54-yr-old female who underwent orthotopic liver transplantation for alcohol-related liver disease with acute decompensation including severe hepatorenal syndrome (anuric requiring dialysis), probable hepatopulmonary syndrome, moderate pulmonary hypertension (right ventricular systolic pressure, 44 mm Hg), hepatic encephalopathy (grade 2), and esophageal varices. Prior to incision, pulmonary arterial pressures were 48/28 (mean, 35) mm Hg with a central venous pressure of 30 mm Hg, cardiac output of 7.4 L·min-1, and pulmonary vascular resistance of 98 dynes·sec·cm-5. In the context of right ventricular strain and volume overload observed on transthoracic echocardiography, we inserted an additional dialysis catheter into the right femoral vein. We initiated dialysis using the two catheters as a circuit (femoral line to the dialysis machine; blood was reinjected via the subclavian line) acting as a limited venovenous bypass, allowing right ventricular offloading and hemodialysis throughout the case. We removed 4.5 L via hemodialysis during the surgery, while avoiding acidosis, hyperkalemia, and sodium shifts. The patient tolerated reperfusion adequately despite pre-existing right ventricular dilation and dysfunction. CONCLUSION: We report on the use two hemodialysis catheters in a patient undergoing orthotopic liver transplantation as a circuit for simultaneous anuric hepatorenal syndrome and moderate pulmonary hypertension with right ventricular dilation and dysfunction. We believe this technique was instrumental in the patient's successful transplant.


RéSUMé: OBJECTIF: Les avantages de la dialyse peropératoire pendant une transplantation hépatique orthotopique demeurent controversés. Chez la patientèle atteinte d'insuffisance rénale anurique et d'hypertension portopulmonaire, il est essentiel de maintenir le retour veineux pendant le clampage et le déclampage de la veine cave ainsi que de minimiser la surcharge hydrique, afin d'éviter la déformation et l'insuffisance ventriculaires droites. CARACTéRISTIQUES CLINIQUES : Nous présentons le cas d'une femme de 54 ans qui a bénéficié d'une transplantation hépatique orthotopique pour une maladie hépatique liée à l'alcool avec une décompensation aiguë comprenant un syndrome hépatorénal sévère (anurie nécessitant une dialyse), un syndrome hépatopulmonaire probable, une hypertension pulmonaire modérée (pression systolique ventriculaire droite, 44 mm Hg), une encéphalopathie hépatique (grade 2) et des varices œsophagiennes. Avant l'incision, les pressions artérielles pulmonaires étaient de 48/28 (moyenne, 35) mm Hg avec une pression veineuse centrale de 30 mm Hg, un débit cardiaque de 7,4 L·min−1 et une résistance vasculaire pulmonaire de 98 dynes·sec·cm−5. Dans le contexte de la déformation ventriculaire et de la surcharge volémique droites observées à l'échocardiographie transthoracique, nous avons inséré un cathéter de dialyse supplémentaire dans la veine fémorale droite. Nous avons amorcé la dialyse en créant un circuit avec les deux cathéters (ligne fémorale en direction de l'appareil de dialyse; sang réinjecté via la ligne sous-clavière) agissant comme un pontage veino-veineux limité, permettant la décharge du ventricule droit et l'hémodialyse tout au long du cas. Nous avons retiré 4,5 L par hémodialyse pendant la chirurgie, tout en évitant l'acidose, l'hyperkaliémie et les changements en sodium plasmatique. La patiente a toléré la reperfusion de manière adéquate malgré la dilatation et le dysfonctionnement préexistants du ventricule droit. CONCLUSION: Nous rapportons l'utilisation de deux cathéters d'hémodialyse pour créer un circuit chez une patiente bénéficiant d'une transplantation hépatique orthotopique pour le traitement d'un syndrome hépatorénal anurique simultané à une hypertension pulmonaire modérée avec dilatation et dysfonctionnement du ventricule droit. Nous pensons que cette technique a joué un rôle déterminant dans la réussite de la greffe chez la patiente.

4.
Proc Natl Acad Sci U S A ; 121(2): e2314101120, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38165935

RESUMO

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.


Assuntos
Anti-Infecciosos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Animais , Camundongos , Espectinomicina/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Micobactérias não Tuberculosas , Anti-Infecciosos/farmacologia , Etilenos/farmacologia , Testes de Sensibilidade Microbiana
6.
Can J Anaesth ; 70(8): 1397-1400, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37280458

RESUMO

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide are a class of medications prescribed to treat type 2 diabetes mellitus, and more recently, as an adjunct for weight loss because of its effects of delaying gastric emptying and suppressing appetite. Semaglutide is a long-acting agent with a half-life of approximately one week, and there are currently no guidelines that address the perioperative management of such agents. CLINICAL FEATURES: We describe an unexpected case of regurgitation of a large volume of gastric contents upon induction of general anesthesia in a nondiabetic, nonobese patient despite a long preoperative fasting period (20 hr for solids and eight hours for clear fluids). This patient had no traditional risk factors for regurgitation or aspiration but was taking the GLP-1 RA semaglutide for weight loss and had last taken the medication two days before their scheduled procedure. CONCLUSIONS: Patients taking long-acting GLP-1 RAs such as semaglutide may be at risk of pulmonary aspiration under anesthesia. We propose strategies to mitigate this risk including holding the medication four weeks prior to a scheduled procedure when feasible and considering full stomach precautions.


RéSUMé: OBJECTIF: Les agonistes des récepteurs du glucagon-like peptide-1 (AR GLP-1) tels que le sémaglutide sont une classe de médicaments prescrits pour traiter le diabète sucré de type 2 et, plus récemment, comme complément à la perte de poids en raison de ses effets de retardement de la vidange gastrique et de suppression de l'appétit. Le sémaglutide est un agent à action prolongée dont la demi-vie est d'environ une semaine, et il n'existe actuellement aucune ligne directrice traitant de la prise en charge périopératoire de ces agents. CARACTéRISTIQUES CLINIQUES: Nous décrivons un cas inattendu de régurgitation d'un important volume de contenu gastrique lors de l'induction de l'anesthésie générale chez une personne non diabétique et non obèse malgré une longue période de jeûne préopératoire (20 heures pour les solides et huit heures pour les liquides clairs). Cette personne ne présentait aucun facteur de risque traditionnel de régurgitation ou d'aspiration, mais prenait du sémaglutide (AR GLP-1) à des fins de perte de poids et avait pris le médicament pour la dernière fois deux jours avant l'intervention prévue. CONCLUSION: Les patient·es prenant des AR GLP-1 à action prolongée tels que le sémaglutide peuvent être à risque d'aspiration pulmonaire sous anesthésie. Nous proposons des stratégies pour atténuer ce risque, y compris d'interrompre la prise du médicament quatre semaines avant une intervention prévue lorsque cela est possible et d'envisager de prendre les précautions requises pour un estomac plein.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Redução de Peso , Jejum , Anestesia Geral
7.
Workplace Health Saf ; 71(9): 400-410, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37077169

RESUMO

PURPOSE: Although medicinal cannabis is prescribed for conditions such as pain, epilepsy, nausea and vomiting during cancer treatment, evidence about associated adverse side effects is still evolving. Because adverse events (AEs) might impact the performance of workers, it is important to consider their implications on workplace health and safety (WHS). This study aimed to map the types and prevalence of the AEs associated with medical cannabis and articulate how those events could impact WHS. METHODS: A scoping review of systematic reviews and/or meta-analyses published between 2015 and March 2021 was performed to identify the AEs of medicinal cannabis in adults. Publications in English and full text available online were collected from Embase, MEDLINE, PsychINFO, PubMed, Scopus, and Web of Science. RESULTS: Of 1,326 papers identified from the initial search, 31 met the inclusion criteria and were analyzed. The studies reported various AEs with the most predominant being sedation, nausea/vomiting, dizziness, and euphoria. Acute and chronic pain was the most prevalent disorder under review. CONCLUSIONS: Adverse events associated with the use of medicinal cannabis could increase workplace risks, including decreased alertness and reaction times, increased absenteeism, reduced ability to safely drive or operate machinery and an increased probability of falling. Focused research into the risk to workers and workplaces from the use of medical cannabis and related human performance impairment is urgently warranted.


Assuntos
Maconha Medicinal , Adulto , Humanos , Maconha Medicinal/efeitos adversos , Revisões Sistemáticas como Assunto , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Condições de Trabalho
8.
J Cancer Surviv ; 17(2): 360-369, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35726114

RESUMO

PURPOSE: The current study examined the relationships between religious resources (i.e., certainty of belief in God and attendance at religious services), religious struggle (e.g., belief that cancer is evidence of God's punishment or abandonment), and physical and mental health-related quality of life (HRQoL), including fear of cancer recurrence (FCR), in a large, geographically and clinically diverse sample of long-term survivors of cancer. METHODS: Participants were 2021 9-year survivors of cancer from the American Cancer Society's Study of Cancer Survivors - I. Religious resources included belief in God and attendance at religious services. Items from the Brief RCOPE and the PROMIS Psychosocial Impact of Illness were combined to assess religious struggle. Survivors also completed the Fear of Cancer Recurrence Inventory, SF-12, and Meaning and Peace subscales of the FACIT-Sp. Regression models were used to predict HRQoL and FCR from religious resources and struggle. RESULTS: In multivariable models, certain belief in God predicted greater mental HRQoL (B = 1.99, p < .01), and attendance at religious services was associated with greater FCR (B = .80, p < .05) as well as better mental (B = .34, p < .01) and physical (B = .29, p < .05) HRQoL. In addition, religious struggle predicted greater FCR (B = 1.32, p < .001) and poorer mental (B = - .59, p < .001) and physical (B = - .29, p < .001) HRQoL. Many of these relationships were mediated through Meaning. CONCLUSIONS: With the exception of FCR, religious resources predicted better HRQoL outcomes in these long-term survivors of cancer. Conversely, religious struggle consistently predicted poorer HRQoL, including greater FCR. IMPLICATIONS FOR CANCER SURVIVORS: Given the documented importance of its role in coping with the cancer experience, religion/spirituality should be a consideration in every survivorship care plan. Multidisciplinary assessment and support of religious resources and identification of and referral for religious struggle are needed to ensure the well-being of most long-term survivors of cancer.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Sobreviventes de Câncer/psicologia , Qualidade de Vida/psicologia , American Cancer Society , Neoplasias/psicologia , Adaptação Psicológica , Espiritualidade
9.
Health Promot Int ; 38(4)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738107

RESUMO

Higher Education Institutions (HEIs) have the potential to impact positively on the health and wellbeing of their staff and students. Using and expanding on the 'health promoting university' (HPU) platform within HEIs, this article provides a description of 'Healthy Trinity', which is an initiative underway in Trinity College Dublin, the University of Dublin. First, Healthy Trinity is contextualized in background literature including international and national policy and practice. Second, an overview of Healthy Trinity is provided including its vision and goals. Third, the article describes the steps taken relating to the identification of stakeholders and use of a network and a co-lead model. Within this approach, the article describes a partnership approach whereby responsibilities regarding health and wellbeing are shared by individuals and the institution. Fourth, the design and implementation of Healthy Trinity is discussed by taking a 'settings approach', in which the emphasis for change is placed on individual behaviours, environment, policy and organizational culture. Consideration is given to the interplay between intervention, implementation strategy and context for successful systemic implementation. The fifth element presented is the early-stage challenges encountered during implementation, such as the need to secure recurrent funding and the importance of having a direct input to the governance of the University to enable systemic change. The sixth and final component of the article is an outline of Healthy Trinity's intention to utilize a process evaluation of the early implementation phases of this complex intervention within a settings approach. Potential deliverables and impacts of this HPU initiative are presented and discussed.


Universities, such as Trinity College Dublin, the University of Dublin, can be looked at as a community of staff and students. The university community has needs in terms of health and wellbeing. 'Healthy Trinity' attempted to build strategies and practices to meet these needs for its community. The approach taken was from multiple angles and involved students and staff, focusing on both individual and organizational responsibility to promote and encourage healthy behaviours. Healthy Trinity achieved some successes as well as encountering some challenges. This article explores how the university might build upon the successes of Healthy Trinity in order to embed a culture which prioritizes health and wellbeing for the entire university community. The article also looks at the broader impact of achieving this goal, namely the University's contribution to a healthier community beyond the university setting.


Assuntos
Políticas , Instituições Acadêmicas , Humanos , Universidades , Estudantes , Promoção da Saúde
10.
MMWR Morb Mortal Wkly Rep ; 71(36): 1141-1147, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36074735

RESUMO

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.


Assuntos
Infecções por HIV , Mpox , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Animais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Mpox/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle
11.
Healthc Q ; 24(4): 48-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35216649

RESUMO

While the importance of physician involvement in organizational quality and safety (Q&S) activities has been well established, a paucity of information exists on tangible supports needed to effectively execute this role. Interviews with 13 MD Q&S leads uncovered common enablers, including valuing Q&S work academically, hiring skilled collaborators, ensuring appropriate power and authority to advance Q&S initiatives, facilitating connections, emphasizing culture change and strong action by leadership. To operationalize these enablers and drive quality innovation, organizations should prioritize the identification and appointment of MD Q&S leads for each department/division and facilitate their assembly as a formal physician Q&S committee.


Assuntos
Liderança , Médicos , Hospitais , Humanos , Cultura Organizacional , Inovação Organizacional
12.
Dysphagia ; 37(6): 1349-1374, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34981255

RESUMO

COVID-19 has had an impact globally with millions infected, high mortality, significant economic ramifications, travel restrictions, national lockdowns, overloaded healthcare systems, effects on healthcare workers' health and well-being, and large amounts of funding diverted into rapid vaccine development and implementation. Patients with COVID-19, especially those who become severely ill, have frequently developed dysphagia and dysphonia. Health professionals working in the field have needed to learn about this new disease while managing these patients with enhanced personal protective equipment. Emerging research suggests differences in the clinical symptoms and journey to recovery for patients with COVID-19 in comparison to other intensive care populations. New insights from outpatient clinics also suggest distinct presentations of dysphagia and dysphonia in people after COVID-19 who were not hospitalized or severely ill. This international expert panel provides commentary on the impact of the pandemic on speech pathologists and our current understanding of dysphagia and dysphonia in patients with COVID-19, from acute illness to long-term recovery. This narrative review provides a unique, comprehensive critical appraisal of published peer-reviewed primary data as well as emerging previously unpublished, original primary data from across the globe, including clinical symptoms, trajectory, and prognosis. We conclude with our international expert opinion on what we have learnt and where we need to go next as this pandemic continues across the globe.


Assuntos
COVID-19 , Transtornos de Deglutição , Disfonia , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Pandemias/prevenção & controle , Disfonia/epidemiologia , Disfonia/etiologia , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Controle de Doenças Transmissíveis
13.
Laryngoscope ; 132(6): 1251-1259, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34622966

RESUMO

OBJECTIVE: To investigate the presence, degree, predictors, and trajectory of dysphagia, dysphonia, and dysarthria among adults hospitalized with COVID-19 across the Republic of Ireland (ROI) during the first wave of the pandemic. STUDY DESIGN: Prospective observational cohort study. METHODS: Adults with confirmed COVID-19 who were admitted into 14 participating acute hospitals across ROI and referred to speech and language therapy between March 1st and June 30th, 2020 were recruited. Outcomes obtained at initial SLT evaluation and at discharge were oral intake status (Functional Oral Intake Scale), perceptual voice quality (GRBAS), and global dysarthria rating (Dysarthria Severity Scale). RESULTS: Data from 315 adults were analyzed. At initial SLT assessment, 84% required modified oral diets, and 31% required tube feeding. There were high rates of dysphonia (42%) and dysarthria (23%). History of intubation (OR 19.959, 95% CI 6.272, 63.513; P = .000), COVID-19 neurological manifestations (OR 3.592, 95% CI 1.733, 7.445; P = .001), and age (OR 1.034; 95% CI 1.002, 1.066; P = .036) were predictive of oral intake status. History of intubation was predictive of voice quality (OR 4.250, 95% CI 1.838, 9.827; P = .001) and COVID-19 neurological manifestations were predictive of dysarthria (OR 2.275; 95% CI 1.162, 4.456; P = .017). At discharge, there were significant improvements in oral intake (Z = -7.971; P = .000), voice quality (Z = -5.971; P = .000), and dysarthria severity (Z = -2.619; P = .009), although need for modified oral intake (59%), dysphonia (23%), and dysarthria (14%) persisted. CONCLUSION: Dysphagia, dysphonia, and dysarthria were widespread among adults hospitalized with COVID-19 and they persisted for many at discharge. Prompt SLT evaluation is required to minimize complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1251-1259, 2022.


Assuntos
COVID-19 , Transtornos de Deglutição , Disfonia , Adulto , COVID-19/complicações , COVID-19/epidemiologia , Transtornos de Deglutição/complicações , Transtornos de Deglutição/etiologia , Disartria/epidemiologia , Disartria/etiologia , Disartria/terapia , Disfonia/epidemiologia , Disfonia/etiologia , Rouquidão , Humanos , Irlanda/epidemiologia , Estudos Prospectivos
14.
Drug Discov Today ; 27(3): 690-696, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34896625

RESUMO

Sleep is rarely considered in drug development studies. Pre-existing sleep problems or changes in sleep parameters in response to therapeutics have the potential to diminish the true utility of the agent under development. Sleep is integral to human health and affects virtually every disease. We present evidence that indicates how sleep quality and quantity can be predictive of disease risk, progression, remission, and recurrence. Supporting the premise that we should conceptualize sleep as a 'vital sign' and measure sleep as an integral component in drug development. We highlight the emergence of digital health technologies that have enabled the capture of this 'vital sign' and ask the question: why is sleep still largely ignored in drug development studies?


Assuntos
Sono , Sinais Vitais , Desenvolvimento de Medicamentos , Humanos
15.
J Neurosci ; 42(5): 762-776, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-34916258

RESUMO

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Danio Rerio (zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify robo2 as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate that robo2 function in regenerating axons is required and sufficient to drive target-selective regeneration, and that robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined, our results reveal a glia-derived mechanism that acts locally via axonal robo2 to promote target-selective regeneration.SIGNIFICANCE STATEMENT Despite its relevance for functional recovery, the molecular mechanisms that direct regenerating peripheral nerve axons toward their original targets are not well defined. Zebrafish spinal motor nerves are composed of a dorsal and a ventral branch that diverge at a stereotyped nerve branch-point, providing a unique opportunity to decipher the molecular mechanisms critical for target-selective regeneration. Using a combination of live cell imaging and molecular-genetic manipulations, we demonstrate that the robo2 guidance receptor is necessary and sufficient to promote target-selective regeneration. Moreover, we demonstrate that robo2 is part of a genetic pathway that generates transient, spatially restricted, and tightly coordinated signaling events that direct axons of the dorsal nerve branch toward their original, pre-injury targets.


Assuntos
Axônios/fisiologia , Regeneração Nervosa/fisiologia , Neuroglia/fisiologia , Nervos Periféricos/fisiologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Axônios/química , Neurônios Motores/química , Neurônios Motores/fisiologia , Neuroglia/química , Nervos Periféricos/química , Receptores Imunológicos/análise , Peixe-Zebra , Proteínas de Peixe-Zebra/análise
16.
J Midwifery Womens Health ; 66(4): 435-436, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34383356
17.
Br J Community Nurs ; 26(7): 328-333, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34232712

RESUMO

The COVID-19 pandemic has necessitated innovations in practice in almost all areas of healthcare, not least community nursing services. This article details how one organisation planned and executed a home vaccination programme for housebound members of the population in its remit. It discusses the challenges faced by the team, as well as the key learnings achieved from this programme, which will guide future home immunisation programmes. Implementation of this programme required excellent coordination between clinicians and administrative staff. Importantly, support from the procurement and IT teams and the medicines management committee went a long way in the ironing out of early hiccups and in ensuring smooth running of the programme.


Assuntos
Vacinas contra COVID-19 , Serviços de Assistência Domiciliar/organização & administração , Pacientes Domiciliares , Vacinação em Massa/organização & administração , Medicina Estatal , Humanos , Reino Unido
18.
Clin Otolaryngol ; 46(6): 1290-1299, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34197688

RESUMO

OBJECTIVES: This study aims to (i) investigate post-extubation dysphagia and dysphonia amongst adults intubated with SARS-COV-2 (COVID-19) and referred to speech and language therapy (SLT) in acute hospitals across the Republic of Ireland (ROI) between March and June 2020; (ii) identify variables predictive of post-extubation oral intake status and dysphonia and (iii) establish SLT rehabilitation needs and services provided to this cohort. DESIGN: A multi-site prospective observational cohort study. PARTICIPANTS: One hundred adults with confirmed COVID-19 who were intubated across eleven acute hospital sites in ROI and who were referred to SLT services between March and June 2020 inclusive. MAIN OUTCOME MEASURES: Oral intake status, level of diet modification and perceptual voice quality. RESULTS: Based on initial SLT assessment, 90% required altered oral intake and 59% required tube feeding with 36% not allowed oral intake. Age (OR 1.064; 95% CI 1.018-1.112), proning (OR 3.671; 95% CI 1.128-11.943) and pre-existing respiratory disease (OR 5.863; 95% CI 1.521-11.599) were predictors of oral intake status post-extubation. Two-thirds (66%) presented with dysphonia post-extubation. Intubation injury (OR 10.471; 95% CI 1.060-103.466) and pre-existing respiratory disease (OR 24.196; 95% CI 1.609-363.78) were predictors of post-extubation voice quality. Thirty-seven per cent required dysphagia intervention post-extubation, whereas 20% needed intervention for voice. Dysphagia and dysphonia persisted in 27% and 37% cases, respectively, at hospital discharge. DISCUSSION: Post-extubation dysphagia and dysphonia were prevalent amongst adults with COVID-19 across the ROI. Predictors included iatrogenic factors and underlying respiratory disease. Prompt evaluation and intervention is needed to minimise complications and inform rehabilitation planning.


Assuntos
Extubação/efeitos adversos , COVID-19/terapia , Transtornos de Deglutição/etiologia , Disfonia/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/reabilitação , Disfonia/reabilitação , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2
19.
BMC Med Ethics ; 22(1): 29, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761938

RESUMO

BACKGROUND: Immense volumes of personal health information (PHI) are required to realize the anticipated benefits of artificial intelligence in clinical medicine. To maintain public trust in medical research, consent policies must evolve to reflect contemporary patient preferences. METHODS: Patients were invited to complete a 27-item survey focusing on: (a) broad versus specific consent; (b) opt-in versus opt-out approaches; (c) comfort level sharing with different recipients; (d) attitudes towards commercialization; and (e) options to track PHI use and study results. RESULTS: 222 participants were included in the analysis; 83% were comfortable sharing PHI with researchers at their own hospital, although younger patients (≤ 49 years) were more uncomfortable than older patients (50 + years; 13% versus 2% uncomfortable, p < 0.05). While 56% of patients preferred broad consent, 38% preferred specific consent; 6% preferred not sharing at all. The majority of patients (63%) preferred to be asked for permission before entry into a contact pool. Again, this trend was more pronounced for younger patients (≤ 49 years: 76%). Approximately half of patients were uncomfortable sharing PHI with commercial enterprises (51% uncomfortable, 27% comfortable, 22% neutral). Most patients preferred to track PHI usage (61%), with the highest proportion once again reported by the youngest patients (≤ 49 years: 71%). A majority of patients also wished to be notified regarding study results (70%). CONCLUSIONS: While most patients were willing to share their PHI with researchers within their own institution, many preferred a transparent and reciprocal consent process. These data also suggest a generational shift, wherein younger patients preferred more specific consent options. Modernizing consent policies to reflect increased autonomy is crucial in fostering sustained public engagement with medical research.


Assuntos
Inteligência Artificial , Registros de Saúde Pessoal , Humanos , Consentimento Livre e Esclarecido , Preferência do Paciente , Confiança
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