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The 2021-2026 Strategic Plan of the National Institute of Neurological Disorders and Stroke began with a vision, a mission, and strategic objectives elaborated from within the institute. This plan is a collaborative product of the institute and its many stakeholders, emphasizing cross-cutting operational principles including scientific rigor, communication, workforce culture, and equity.
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National Institute of Neurological Disorders and Stroke (U.S.) , Planificación Estratégica , Estados UnidosRESUMEN
BACKGROUND: Pneumococcal diseases (PD) cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from pneumococcal serotypes responsible for the majority of residual PD. This phase 3 study evaluated safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-experienced adults ≥50 years. METHODS: A total of 717 adults were enrolled to receive a single dose of pneumococcal vaccine as follows: Cohort 1 (n=350) previously received PPSV23 and were randomized 2:1 to receive V116 or PCV15, respectively; Cohort 2 (n=261) previously received PCV13 and were randomized 2:1 to receive V116 or PPSV23, respectively; Cohort 3 (n=106) previously received PPSV23+PCV13, PCV13+PPSV23, PCV15+PPSV23, or PCV15 and all received open-label V116. Immunogenicity was evaluated 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) for all V116 serotypes. Safety was evaluated as the proportion of participants with adverse events (AEs). RESULTS: V116 was immunogenic across all 3 cohorts as assessed by serotype-specific OPA GMTs and IgG GMCs postvaccination for all 21 serotypes. V116 elicited comparable immune responses to serotypes shared with PCV15 (Cohort 1) or PPSV23 (Cohort 2), and higher immune responses to serotypes unique to V116. The proportions of participants with solicited AEs were generally comparable across cohorts. CONCLUSIONS: V116 is well tolerated with a safety profile comparable to currently licensed pneumococcal vaccines and generates IgG and functional immune responses to all V116 serotypes, regardless of prior pneumococcal vaccine received.
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BACKGROUND: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults. METHODS: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1â×â1010 or 1â×â1011 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056. FINDINGS: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1â×â1010 pu (n=20) or 1â×â1011 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1â×â1010 pu group and 545 [276-1078] in the 1â×â1011 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1â×1010 pu group and 27 [95-156] in the 1â×1011 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination. INTERPRETATION: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions. FUNDING: National Institutes of Health.
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Adenovirus de los Simios , Marburgvirus , Animales , Adulto , Humanos , Pan troglodytes , Anticuerpos Antivirales , Vacunas Sintéticas/efectos adversos , Adenoviridae , Glicoproteínas , Método Doble CiegoRESUMEN
OBJECTIVE: To develop and psychometrically evaluate an adapted version of the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale in men with a history of cancer. METHODS: This psychometric instrument development and validation study used a two-phase approach to first adapt the FSACS Scale items to reflect the experience of men with a history of cancer and then evaluate the psychometric properties of the adapted scale compared to the original FSACS Scale. The study was conducted from December 2018 through April 2022 through cancer clinics, patient registries, and national advocacy organizations. We evaluated scale reliability and validity using reliability coefficients, exploratory and confirmatory factor analyses, and item analyses to determine a final set of scale items. RESULTS: Item responses from N = 171 men with a history of cancer were evaluated to determine scale validity. After removing poor-performing items based on item-level analyses, factor analyses confirmed that a 3-factor structure of both the adapted and original FSACS Scale best fit the scale. The 10 new items did not outperform the original 20-item scale and were therefore excluded from the final scale. The final 20-item scale explained 87.94% of item variance and subscale's Cronbach α varied from 0.65 to 0.86. CONCLUSION: The SACS Scale can be used in research and clinical contexts to assess the propensity of men and women to get their needs, values, and priorities met in the face of a challenge.
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Supervivientes de Cáncer , Neoplasias , Humanos , Masculino , Femenino , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , PsicometríaRESUMEN
ABSTRACT: Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.
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Inmunosupresores , Miocarditis , Miocarditis/inmunología , Miocarditis/terapia , Miocarditis/tratamiento farmacológico , Humanos , Enfermedad Aguda , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Animales , Agentes Inmunomoduladores/uso terapéutico , InmunomodulaciónRESUMEN
BACKGROUND: In an ageing population, low impact fragility fractures are becoming increasingly common. However, fracture risk can be reduced where low bone density can be identified at an early stage. In this study we aim to demonstrate that IBEX Bone Health (IBEX BH) can provide a clinically useful prediction from wrist radiographs of aBMD and T-score at the ultra-distal (UD) and distal-third (DT) regions of the radius. METHODS: A 261-participant single-centre, non-randomised, prospective, study was carried out to compare a) IBEX BH, a quantitative digital radiography software device, to b) Dual-energy X-ray Absorptiometry (DXA). A total of 257 participants with wrist digital radiograph (DR), forearm DXA pairs were included in the analysis after exclusions. RESULTS: The adjusted R2 value for IBEX BH outputs to the radial areal bone mineral density (aBMD) produced by a GE Lunar DXA system for the UD region is 0.87 (99% Confidence Interval (CI) [0.84, 0.89]). The adjusted R2 value for IBEX BH outputs to aBMD for the DT region is 0.88 (99% CI [0.85, 0.90]). The Area Under the Receiver Operating Characteristic curve (AUC) for the forearm T-score ≤ - 2.5 risk prediction model at the UD region is 0.95 (99% CI [0.93, 0.98]). The AUC for the forearm T-score ≤ - 2.5 risk prediction model at the DT region is 0.98 (99% CI [0.97, 0.99]). CONCLUSION: From a DR of the wrist, IBEX BH provides a clinically useful i) estimate of aBMD at the two regions of interest on the radius and ii) risk prediction model of forearm T-score ≤ - 2.5 at the UD and DT regions.
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Absorciometría de Fotón , Densidad Ósea , Radio (Anatomía) , Humanos , Absorciometría de Fotón/métodos , Femenino , Densidad Ósea/fisiología , Masculino , Radio (Anatomía)/diagnóstico por imagen , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Fracturas del Radio/diagnóstico por imagen , Osteoporosis/diagnóstico por imagenRESUMEN
Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV-like Sarbecovirus vaccine development.
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Vacunas contra la COVID-19/administración & dosificación , COVID-19/virología , Macaca mulatta/inmunología , Nanopartículas/química , Receptores Virales/metabolismo , SARS-CoV-2/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Ferritinas/química , SARS-CoV-2/metabolismo , Linfocitos T/inmunologíaRESUMEN
Documenting surgical supply items in the operating room can be a burdensome task for circulating nurses because of manual input within the electronic medical record. This can lead to documentation fatigue and contribute to nursing burnout. The aim of this quality improvement project was to design and implement a supply item scanning process and evaluate the effect on intraoperative documentation completion time, room turnover time, picklist documentation accuracy, nurse satisfaction, and burnout. The sample included nine acute care hospitals throughout the United States, with 189 total circulating nurses and 31 718 procedures occurring during the study timeframe of 8 months. Results indicated that nurses were able to complete documentation on average 37.33 minutes sooner, and the operating room turnover time decreased by 1.88 minutes. Although nurses reported that their perceived picklist documentation accuracy did not improve, and the presence of new scanning technology did not influence their hospital employment decision, subjective feedback was mostly positive, with most responses citing the helpfulness of scanning for documentation. This study shows that an interdisciplinary team can effectively work to optimize documentation efficiency and performance improvement using a scanning intervention. Lessons learned through this process can translate into optimizations elsewhere in the electronic medical record.
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Registros Electrónicos de Salud , Quirófanos , Humanos , Hospitales , Documentación , Agotamiento PsicológicoRESUMEN
BACKGROUND: Nurse practitioners (NPs) can enhance NP care and improve access to care by autonomously managing their patient panels. Yet, its impact on workforce outcomes such as burnout, job satisfaction, and turnover intention remains unexplored. PURPOSE: To estimate the impact of NP panel management on workforce outcomes. METHODS: Structural equation modeling was conducted using survey data from 1,244 primary care NPs. NP panel management was categorized into co-managing patients with other providers, both co-managing and autonomously managing, and fully autonomous management. DISCUSSION: Fully autonomous management led to more burnout than co-managing (B = 0.089, bias-corrected 95% bootstrap confidence interval [0.028, 0.151]). Work hours partially (27%) mediated this relationship. This findings indicate that greater autonomy in panel management among NPs may lead to increased burnout, partially due to longer work hours. CONCLUSION: Interventions to reduce work hours could help NPs deliver quality care without burnout.
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Agotamiento Profesional , Satisfacción en el Trabajo , Enfermeras Practicantes , Reorganización del Personal , Atención Primaria de Salud , Humanos , Enfermeras Practicantes/psicología , Enfermeras Practicantes/estadística & datos numéricos , Agotamiento Profesional/psicología , Reorganización del Personal/estadística & datos numéricos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Due to the ageing population, patients often present to the hospital with a high burden of comorbidities and polypharmacy. For patients admitted with decompensated heart failure (HF), the evidence on the effects of contraindicated drugs on long-term mortality is scarce. Therefore, we aimed to investigate the effect of contraindicated medications on outcomes of patients admitted with decompensated HF. We analyzed all consecutive patients from the National Heart Failure Audit admitted to two tertiary centers with acutely decompensated HF between April 2020 and October 2021. We included medication classes listed as contraindicated (class III) in the most recent European and American guidelines on the management of HF. The primary outcome measure was in-hospital mortality. The secondary outcome measure was overall mortality. Overall, 716 patients admitted with acute HF were included. One-fifth (n = 156, 21.8%) were on at least one contraindicated medication at admission. The prevalence of comorbidities was comparable between medication groups. During hospitalization, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased in-hospital mortality (29% versus 9%, P = 0.013). On multivariable analyses, NSAID use was independently associated with worse in-hospital mortality (hazard ratio, 6.86; 95% confidence interval, 1.61-25.5; P = 0.005). However, other contraindicated medications were not associated with adverse outcomes. Postdischarge, the use of erythropoietin during admission was associated with increased mortality (54% versus 31%, P = 0.031). NSAID use is associated with increased in-hospital mortality for patients admitted with acute HF. However, inpatient use of other contraindicated medications was not associated with adverse in-hospital outcomes. Further studies are needed to confirm these results in larger and prospective cohorts. SIGNIFICANCE STATEMENT: Use of nonsteroidal anti-inflammatory drugs is associated with a worse in-hospital mortality in patients with decompensated heart failure. The prognostic role of other contraindicated medications remains still uncertain.
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Cuidados Posteriores , Insuficiencia Cardíaca , Humanos , Estados Unidos , Pronóstico , Estudios Prospectivos , Alta del Paciente , Insuficiencia Cardíaca/tratamiento farmacológico , AntiinflamatoriosRESUMEN
Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S. Army post. Our analysis revealed unique aspects of basic training that require customized approaches to outbreak prevention, which draws attention to the possibility that customized approaches may be necessary in other settings, too. In particular, we showed that introductions by trainers and support staff may be a major vulnerability, given that those individuals remain at risk of community exposure throughout the training period. We also found that increased testing of trainees upon arrival could actually increase the risk of outbreaks, given the potential for false-positive test results to lead to susceptible individuals becoming infected in group isolation and seeding outbreaks in training units upon release. Until an effective transmission-blocking vaccine is adopted at high coverage by individuals involved with basic training, need will persist for non-pharmaceutical interventions to prevent outbreaks in military basic training. Ongoing uncertainties about virus variants and breakthrough infections necessitate continued vigilance in this setting, even as vaccination coverage increases.
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COVID-19 , Personal Militar , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Brotes de Enfermedades/prevención & control , Estudios de CohortesRESUMEN
PURPOSE: To evaluate the feasibility and safety of early and proactive involvement of interventional radiology (IR) in the management of placenta accreta spectrum (PAS) by performing the cesarean operation and prophylactic uterine artery embolization in the IR angiography suite as a combined procedure. MATERIALS AND METHODS: This study evaluated the effectiveness and safety of prophylactic uterine artery embolization prior to placental separation in cases of antenatally proven or suspected abnormal placentation. Over a 5-year period, 16 consecutive patients with PAS underwent combined IR and obstetric intervention. In all cases, cesarean delivery was performed in the IR angiography suite. Vascular access was obtained prior to surgery with balloon placement into both internal iliac arteries. These balloons were inflated after delivery, followed by uterine artery embolization (14 of 16) if there was evidence of active postpartum bleeding or inability to deliver the placenta. RESULTS: There was no fetal or maternal mortality and no significant IR or surgical adverse events. Mean blood loss was 1900 mL. Seven patients (44%) underwent hysterectomy. CONCLUSIONS: In patients with PAS, cesarean section in the angiography suite preceded by prophylactic balloon placement and followed by uterine artery embolization was feasible, safe, and effective in preventing massive blood loss, with a 56% uterine sparing rate.
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Oclusión con Balón , Placenta Accreta , Hemorragia Posparto , Embolización de la Arteria Uterina , Embarazo , Humanos , Femenino , Placenta Accreta/terapia , Placenta Accreta/cirugía , Embolización de la Arteria Uterina/efectos adversos , Cesárea/efectos adversos , Placenta , Oclusión con Balón/efectos adversos , Oclusión con Balón/métodos , Histerectomía , Arteria Ilíaca , Hemorragia Posparto/etiología , Hemorragia Posparto/prevención & control , Morbilidad , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica/prevención & controlRESUMEN
AIMS: There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. METHODS AND RESULTS: Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). CONCLUSION: Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.
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Desfibriladores Implantables , Humanos , Estudios Retrospectivos , Desfibriladores Implantables/efectos adversos , Pronóstico , Factores de Riesgo , Síncope/diagnóstico , Síncope/epidemiología , Síncope/etiologíaRESUMEN
BACKGROUND: In 2020, preventive measures were implemented to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among 600-700 recruits arriving weekly at a basic combat training (BCT) facility in the southern United States. Trainees were sorted into companies and platoons (cocoons) at arrival, tested, quarantined for 14 days with daily temperature and respiratory-symptom monitoring and retested before release into larger groups for training where symptomatic testing was conducted. Nonpharmaceutical measures, such as masking, and social distancing, were maintained throughout quarantine and BCT. We assessed for SARS-CoV-2 transmission in the quarantine milieu. METHODS: Nasopharyngeal (NP) swabs were collected at arrival and at the end of quarantine and blood specimens at both timepoints and at the end of BCT. Epidemiological characteristics were analyzed for transmission clusters identified from whole-genome sequencing of NP samples. RESULTS: Among 1403 trainees enrolled from 25 August to 7 October 2020, epidemiological analysis identified three transmission clusters (n = 20 SARS-CoV-2 genomes) during quarantine, which spanned five different cocoons. However, SARS-CoV-2 incidence decreased from 2.7% during quarantine to 1.5% at the end of BCT; prevalence at arrival was 3.3%. CONCLUSIONS: These findings suggest layered SARS-CoV-2 mitigation measures implemented during quarantine minimized the risk of further transmission in BCT.
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COVID-19 , Personal Militar , Humanos , Estados Unidos/epidemiología , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Cuarentena , Prueba de COVID-19RESUMEN
STUDY OBJECTIVES: To determine the sensitivity of the Multivariable Apnea Prediction (MAP) index for obstructive sleep apnea (OSA) in pre- and post-menopausal women with the goal of developing a tailored scoring classification approach. METHODS: Data from two studies (N = 386); the diabetes sleep treatment trial (N = 236) and EMPOWER (N = 150) were used to assess the sensitivity and specificity of the MAP index by comparing men (n = 129) to women (n = 257), and premenopausal (n = 100) to post-menopausal women (n = 136). We evaluated participants at two cut points, apnea-hypopnea index (AHI) values of ≥ 5 and ≥ 10, using 0.5 as a predicted probability cut point to establish baseline sensitivity and specificity. Contingency tables and receiver operating characteristic (ROC) analysis were conducted to evaluate the accuracy of the MAP index in predicting OSA in men versus women, and in pre-versus post-menopausal women. To select optimal predicted probabilities for classification by sex and menopausal status, Youden's J statistic was generated from ROC coordinates. RESULTS: The MAP index was more sensitive to women in the AHI ≥ 5 group (76%) compared to AHI ≥ 10 group (30%). Among post-menopausal women with AHI ≥ 5, sensitivity was similar to men (98%), but less than men when AHI ≥ 10 (32%). Suggested probability cut points for women with an AHI ≥ 10 are 0.24 overall; 0.15 for premenopausal, and 0.38 for postmenopausal women. CONCLUSIONS: Because women's risk for OSA (AHI ≥ 10) was underestimated by the MAP index, we suggest the use of tailored cut points based on sex and menopausal status or assessing for OSA risk with an AHI of ≥ 5.
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Apnea Obstructiva del Sueño , Femenino , Humanos , Masculino , Menopausia , Polisomnografía , Medición de Riesgo , Sensibilidad y Especificidad , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Ensayos Clínicos como AsuntoRESUMEN
The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages.
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Betacoronavirus/genética , Genoma Viral , Vacunas Virales/genética , Betacoronavirus/inmunología , COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/prevención & control , Variación Genética , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Mutación Puntual , SARS-CoV-2 , Selección GenéticaRESUMEN
BACKGROUND: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. METHODS: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. RESULTS: Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. CONCLUSIONS: Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Sensibilidad y Especificidad , ARN , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.
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Miocarditis , Función Ventricular Izquierda , Adulto , Medios de Contraste , Femenino , Gadolinio , Humanos , Imagen por Resonancia Cinemagnética , Espectroscopía de Resonancia Magnética , Masculino , Miocarditis/diagnóstico por imagen , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Volumen SistólicoRESUMEN
BACKGROUND: Over the past 10 years, incidence of sexually transmitted infections (STIs) has increased to record numbers in the United States, with the most significant increases observed among adolescents and young adults. The US military, where the majority of active duty personnel are 18-30 years old, has seen similar increases. However, the US military does not yet have a standardized, service-wide program for STI education and prevention. METHODS: The KISS intervention (Knocking out Infections through Safer-sex and Screening) was adapted from an evidence-based intervention endorsed by the US Centers for Disease Control and Prevention and consisted of a one-time, small group session. Content included STI/HIV knowledge and prevention, condom use skills, and interpersonal communication techniques. The intervention was pilot tested for feasibility and acceptability among a population of service members and medical beneficiaries at Joint Base Lewis-McChord in Washington state. RESULTS: A total of 79 participants aged 18-30 years were consented to participate in the pilot study and met entry criteria, 66/79 (82.5%) attended the intervention session, and 46/66 (69.7%) returned at 3 months for the final follow-up assessment. The intervention sessions included 31 male (47.0%) and 35 female (53.0%) participants. Almost all participants felt comfortable discussing sexual issues in the group sessions, reported that they intended to practice safer sex after the intervention, and would also recommend the intervention to friends. Knowledge about STI/HIV prevention significantly increased after the intervention, and intervention effects were maintained at 3 months. About one-fifth of participants tested positive for N. gonorrhea or C. trachomatis infection at enrollment, while none had recurrent STIs at the final visit. Use of both male and female condoms increased after the intervention. CONCLUSIONS: The KISS intervention was feasible to implement in the military setting and was acceptable to the active duty service members and other medical beneficiaries who participated in the pilot project. Further studies are needed to determine if the KISS intervention, or others, effectively decrease STI incidence in active duty personnel and would be appropriate for more widespread implementation. TRIAL REGISTRATION: Retrospectively registered as the pilot phase of clinicaltrials.gov NCT04547413 , "Prospective Cohort Trial to Assess Acceptability and Efficacy of an Adapted STI/HIV Intervention Behavioral Intervention Program in a Population of US Army Personnel and Their Medical Beneficiaries-Execution Phase."
Asunto(s)
Infecciones por VIH , Personal Militar , Enfermedades de Transmisión Sexual , Adolescente , Adulto , Familia , Estudios de Factibilidad , Femenino , Infecciones por VIH/prevención & control , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Enfermedades de Transmisión Sexual/prevención & control , Estados Unidos/epidemiología , Adulto JovenRESUMEN
PURPOSE OF THE REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. RECENT FINDINGS: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.