RESUMEN
Measuring and optimizing a health system is challenging when patient care is split between many independent organizations. For example, patients receive care from their primary care provider, outpatient specialist clinics, hospitals, private providers and, in some instances, family members. These silos are maintained through different funding sources (or lack of funding) which incentivize siloed service delivery. A shift towards prioritizing patient outcomes and keeping the patient at the centre of care is emerging. However, competing philosophies on patient needs, how health is defined and how health is produced and funded is creating and engraining silos in the delivery of health services. Healthcare and health outcomes are produced through a series of activities conducted by diverse teams of health professionals working in concert. Health professionals are continually learning from each patient interaction; however, silos are barriers to information exchange, collaborative evidence generation and health system improvement. This paper presents a systems view of healthcare and provides a systems lens to approach current challenges in health systems. The first part of the paper provides a background on the current state and challenges to healthcare in Canada. The second part presents potential reasons for continued health system underperformance. The paper concludes with a system perspective for addressing these challenges.
Asunto(s)
Atención a la Salud , Humanos , Canadá , Calidad de la Atención de Salud , Personal de Salud , Atención Primaria de Salud/organización & administraciónRESUMEN
Background: Cardiovascular disease (CVD) risk factors such as sedentary behaviour, decreased physical activity (PA), and low cardiorespiratory fitness lead to an increased and accelerated risk of cardiovascular disease and mortality. Medical students tend to adopt sedentary lifestyles due to a demanding curriculum. This may have a negative effect on CVD risk factors and cardiorespiratory fitness levels of medical students. Objectives: To compare physical activity and cardiorespiratory fitness levels in a cohort of third- and fifth-year undergraduate medical students in a South African university. Methods: Data from 123 third-year and 139 fifth-year medical students in the Graduate Entry Medical Programme (GEMP) at the Faculty of Health Sciences, University of the Witwatersrand, were collected. Measurements included CVD risk factors, height, weight, blood pressure, waist circumference, cardiorespiratory fitness, physical activity vital signs and pre-participation health screening questionnaires. Descriptive statistics were presented as mean ± standard deviation or median [interquartile range] depending whether the data were normally distributed or not. Results: Both groups had low cardiorespiratory fitness when compared to norm values (GEMPI VO2 peak was 29.1 ± 5.9 ml.kg-1.min-1 and GEMPIII VO2 peak was 30.0[11.0] ml.kg-1.min-1). Most participants did not meet WHO physical activity requirements (GEMP I: 72%; GEMP III: 78%). There were significant differences in BMI (p=0.046), diastolic blood pressure (p=0.034) and VO2 peak (p=0.00001) between students meeting and not meeting WHO physical activity requirements (p<0.05). Conclusion: Third- and fifth-year medical students at a South African university fail to meet recommended WHO physical activity levels and are below cardiorespiratory fitness norms. Therefore, medical institutions should promote and implement targeted physical activity interventions to reduce the prevalence of low fitness levels and the associated health hazards among their students.
RESUMEN
BACKGROUND: Traumatic vascular injuries of the lower extremity in the pediatric population are uncommon but can result in significant morbidity. The objective of this study is to demonstrate our experience with these injuries by describing patterns of traumatic vascular injury, the initial management, and data regarding early outcomes. METHODS: In total, 506 patients presented with lower extremity vascular injury between January 1, 2009 and January 1, 2021 to Grady Memorial Hospital, an urban, adult Level I trauma center in Atlanta, Georgia. Thirty-two of the 506 patients were aged less than 18 years and were evaluated for a total of 47 lower extremity vascular injuries. To fully elucidate the injury patterns and clinical course in this population, we examined patient demographics, mechanism of injury, type of vessel injured, surgical repair performed, and early outcomes and complications. RESULTS: The median (interquartile range) age was 16 (2) years (range, 3-17 years), and the majority were male (n = 29, 90.6%). Of the vascular injuries identified, 28 were arterial and 19 were venous. Of these injuries, 14 patients had combined arterial-venous injuries. The majority of injuries were the result of a penetrating injury (n = 28, 87.5%), and of these, all but 2 were attributed to gunshot wounds. Twenty-seven vascular interventions were performed by nonpediatric surgeons: 11 by trauma surgeons, 13 by vascular surgeons, 2 by orthopedic surgeons, and 1 by an interventional radiologist. Two patients required amputation: 1 during the index admission and 1 delayed at 3 months. Overall survival was 96.9%. CONCLUSIONS: Vascular injuries as the result of trauma at any age often require early intervention, and we believe that these injuries in the pediatric population can be safely managed in adult trauma centers with a multidisciplinary team composed of trauma, vascular, and orthopedic surgeons with the potential to decrease associated morbidity and mortality from these injuries.
Asunto(s)
Lesiones del Sistema Vascular , Heridas por Arma de Fuego , Adulto , Humanos , Niño , Masculino , Femenino , Preescolar , Adolescente , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/cirugía , Centros Traumatológicos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Heridas por Arma de Fuego/terapia , Heridas por Arma de Fuego/complicaciones , Resultado del Tratamiento , Extremidad Inferior/irrigación sanguínea , Estudios RetrospectivosRESUMEN
We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.
Asunto(s)
Aterosclerosis , Isquemia Encefálica , COVID-19 , Accidente Cerebrovascular Embólico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/genética , Isquemia Encefálica/complicaciones , Isquemia Encefálica/genética , COVID-19/complicaciones , COVID-19/genética , Accidente Cerebrovascular Isquémico/genética , ArteriasRESUMEN
Human sewage contamination of waterways is a major issue in the United States and throughout the world. Models were developed for estimation of two human-associated fecal-indicator and three general fecal-indicator bacteria (HIB and FIB) using in situ optical field-sensor data for estimating concentrations and loads of HIB and FIB and the extent of sewage contamination in the Menomonee River in Milwaukee, Wisconsin. Three commercially available optical sensor platforms were installed into an unfiltered custom-designed flow-through system along with a refrigerated automatic sampler at the Menomonee River sampling location. Ten-minute optical sensor measurements were made from November 2017 to December 2018 along with the collection of 153 flow-weighted discrete water samples (samples) for HIB, FIB, dissolved organic carbon (DOC), and optical properties of water. Of those 153 samples, 119 samples were from event-runoff periods, and 34 were collected during low-flow periods. Of the 119 event-runoff samples, 43 samples were from event-runoff combined sewer overflow (CSO) influenced periods (event-CSO periods). Models included optical sensor measurements as explanatory variables with a seasonal variable as an interaction term. In some cases, separate models for event-CSO periods and non CSO-periods generally improved model performance, as compared to using all the data combined for estimates of FIB and HIB. Therefore, the CSO and non-CSO models were used in final estimations for CSO and non-CSO time periods, respectively. Estimated continuous concentrations for all bacteria markers varied over six orders of magnitude during the study period. The greatest concentrations, loads, and proportion of sewage contamination occurred during event-runoff and event-CSO periods. Comparison to water quality standards and microbial risk assessment benchmarks indicated that estimated bacteria levels exceeded recreational water quality criteria between 34 and 96% of the entire monitoring period, highlighting the benefits of high-frequency monitoring compared to traditional grab sample collection. The application of optical sensors for estimation of HIB and FIB markers provided a thorough assessment of bacterial presence and human health risk in the Menomonee River.
Asunto(s)
Ríos , Aguas del Alcantarillado , Humanos , Ríos/microbiología , Aguas del Alcantarillado/microbiología , Wisconsin , Monitoreo del Ambiente , Bacterias , Heces/microbiología , Microbiología del AguaRESUMEN
Circulating biomarkers reflecting cardiac inflammation are needed to improve the diagnostics and guide the treatment of heart failure patients. The cardiac production and shedding of the transmembrane proteoglycan syndecan-4 is upregulated by innate immunity signaling pathways. Here, we investigated the potential of syndecan-4 as a blood biomarker of cardiac inflammation. Serum syndecan-4 was measured in patients with (i) non-ischemic, non-valvular dilated cardiomyopathy (DCM), with (n = 71) or without (n = 318) chronic inflammation; (ii) acute myocarditis (n = 15), acute pericarditis (n = 3) or acute perimyocarditis (23) and (iii) acute myocardial infarction (MI) at day 0, 3 and 30 (n = 119). Syndecan-4 was investigated in cultured cardiac myocytes and fibroblasts (n = 6-12) treated with the pro-inflammatory cytokines interleukin (IL)-1ß and its inhibitor IL-1 receptor antagonist (IL-1Ra), or tumor necrosis factor (TNF)α and its specific inhibitor infliximab, an antibody used in treatment of autoimmune diseases. The levels of serum syndecan-4 were comparable in all subgroups of patients with chronic or acute cardiomyopathy, independent of inflammation. Post-MI, syndecan-4 levels were increased at day 3 and 30 vs. day 0. IL-1Ra attenuated IL-1ß-induced syndecan-4 production and shedding in vitro, while infliximab had no effect. In conclusion, syndecan-4 shedding from cardiac myocytes and fibroblasts was attenuated by immunomodulatory therapy. Although its circulating levels were increased post-MI, syndecan-4 did not reflect cardiac inflammatory status in patients with heart disease.
RESUMEN
BACKGROUND: Traumatic abdominal wall hernias (TAWH) are relatively uncommon; however, the shearing force that results in fascial disruption could indicate an increased risk of visceral injury. The aim of our study was to evaluate whether the presence of a TAWH was associated with intra-abdominal injury requiring emergent laparotomy. METHODS: The trauma registry was queried over an 8-year period (7/2012-7/2020) for adult patients with blunt thoracoabdominal trauma diagnosed with a TAWH. Those patients who were identified with a TAWH and greater than 15 years of age were included in the study. Demographics, mechanism of injury, ISS, BMI, length of stay, TAWH size, type of TAWH repair, and outcomes were analyzed. RESULTS: Overall, 38,749 trauma patients were admitted over the study period, of which 64 (.17%) had a TAWH. Patients were commonly male (n = 42, 65.6%); the median age was 39 years (range 16-79 years) and a mean ISS of 21. Twenty-eight percent had a clinical seatbelt sign. Twenty-seven (42.2%) went emergently to the operating room, the majority for perforated viscus requiring bowel resection (n = 16, 25.0%), and 6 patients (9.4%) who were initially managed nonoperatively underwent delayed laparotomy. Average ventilator days was 14 days, with a mean ICU LOS of 14 days and mean hospital LOS of 18 days. About half of the hernias were repaired at the index operation, 6 of which were repaired primarily and 10 with mesh. CONCLUSION: The presence of a TAWH alone was an indication for immediate laparotomy to evaluate for intra-abdominal injury. In the absence of other indications for exploration, nonoperative management may be safe.
Asunto(s)
Traumatismos Abdominales , Pared Abdominal , Hernia Ventral , Perforación Intestinal , Heridas no Penetrantes , Adulto , Humanos , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Laparotomía/métodos , Hernia Ventral/etiología , Hernia Ventral/cirugía , Hernia Ventral/diagnóstico , Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/cirugía , Heridas no Penetrantes/diagnóstico , Perforación Intestinal/cirugía , Pared Abdominal/cirugíaRESUMEN
Interventional radiology has had an expanding role in women's health over the past few decades, with recent accelerated growth and development. Interventional radiology is fundamental in the treatment of multiple conditions that affect women, including pelvic venous disease, uterine fibroids, and adenomyosis, and in postpartum management. Patient workup, classification, and treatment techniques have continued to evolve as interventional radiology has become more prevalent in the treatment of patients affected by these conditions. The authors provide a review of the pathophysiology of, patient workup for, and treatment of pelvic venous disease and uterine artery embolization for various disease processes. The authors also highlight updates from the past 5-10 years in diagnosis, classification, and treatment strategies. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.
Asunto(s)
Ginecología , Obstetricia , Neoplasias Uterinas , Enfermedades Vasculares , Embarazo , Femenino , Humanos , Radiología Intervencionista , Salud de la MujerRESUMEN
BACKGROUND: Cardiomyocyte hypertrophy is a hallmark of cardiac dysfunction in patients with aortic stenosis (AS), and can be triggered by left ventricular (LV) pressure overload in mice by aortic banding (AB). Syndecan-4 is a transmembrane heparan sulphate proteoglycan which is found increased in the myocardium of AS patients and AB mice. The role of syndecan-4 in cardiomyocyte hypertrophy is not well understood. PURPOSE OF THE STUDY: We developed mice with cardiomyocyte-specific overexpression of syndecan-4 (Sdc4-Tg) and subjected these to AB to examine the role of syndecan-4 in hypertrophy and activation of the pro-hypertrophic calcineurin-NFAT signalling pathway. METHODS AND RESULTS: Sdc4-Tg mice showed exacerbated cardiac remodelling upon AB compared to wild type (WT). At 2-6 weeks post-AB, Sdc4-Tg and WT mice showed similar hypertrophic growth, while at 20 weeks post-AB, exacerbated hypertrophy and dysfunction were evident in Sdc4-Tg mice. After cross-breeding of Sdc4-Tg mice with NFAT-luciferase reporter mice, we found increased NFAT activation in Sdc4-Tg hearts after AB. Immunoprecipitation showed that calcineurin bound to syndecan-4 in Sdc4-Tg hearts. Isolated cardiomyocytes from Sdc4-Tg mice showed alterations in Ca2+ fluxes, suggesting that syndecan-4 regulated Ca2+ levels, and thereby, activating the syndecan-4-calcineurin complex resulting in NFAT activation and hypertrophic growth. Similarly, primary cardiomyocyte cultures from neonatal rats showed increased calcineurin-NFAT-dependent hypertrophic growth upon viral Sdc4 overexpression. CONCLUSION: Our study of mice with cardiomyocyte-specific overexpression of Sdc4 have revealed that syndecan-4 is important for activation of the Ca2+-dependent calcineurin-NFAT signalling pathway, hypertrophic remodelling and dysfunction in cardiomyocytes in response to pressure overload.
Asunto(s)
Calcineurina , Miocitos Cardíacos , Sindecano-4 , Animales , Ratones , Ratas , Calcineurina/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Células Cultivadas , Miocitos Cardíacos/metabolismo , Factores de Transcripción NFATC/metabolismo , Transducción de Señal/fisiología , Sindecano-4/genética , Sindecano-4/metabolismoRESUMEN
OBJECTIVES: To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform. DESIGN: Biobank-based recontacting pilot study. SETTING: Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021. PARTICIPANTS: All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s). OUTCOME MEASURES: The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies. RESULTS: The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18-69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92. CONCLUSION: In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.
Asunto(s)
Bancos de Muestras Biológicas , Deber de Recontacto , Adolescente , Cognición , Humanos , Estilo de Vida , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different study designs and multiple disease phenotype definitions to identify several genomic regions associated with COVID-19. Along with a multitude of follow-up studies, these findings have increased our understanding of disease aetiology and provided routes for management of COVID-19. Important emergent opportunities include the clinical translatability of genetic risk prediction, the repurposing of existing drugs, exploration of variable host effects of different viral strains, study of inter-individual variability in vaccination response and understanding the long-term consequences of SARS-CoV-2 infection. Beyond the current pandemic, these transferrable opportunities are likely to affect the study of many infectious diseases.
Asunto(s)
COVID-19 , COVID-19/epidemiología , COVID-19/genética , Humanos , Epidemiología Molecular , Pandemias , SARS-CoV-2/genéticaRESUMEN
Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants1. Although genes under the strongest selective constraint are highly enriched for associations with Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known2. Here we show that genetic variants that damage these genes are associated with markedly reduced reproductive success, primarily owing to increased childlessness, with a stronger effect in males than in females. We present evidence that increased childlessness is probably mediated by genetically associated cognitive and behavioural traits, which may mean that male carriers are less likely to find reproductive partners. This reduction in reproductive success may account for 20% of purifying selection against heterozygous variants that ablate protein-coding genes. Although this genetic association may only account for a very minor fraction of the overall likelihood of being childless (less than 1%), especially when compared to more influential sociodemographic factors, it may influence how genes evolve over time.
Asunto(s)
Reproducción , Selección Genética , Mapeo Cromosómico , Femenino , Heterocigoto , Humanos , Masculino , Fenotipo , Reproducción/genéticaRESUMEN
In this study, we evaluated the suitability of body feathers, preen oil and plasma for estimation of organohalogen compound (OHC) exposure in northern goshawk Accipiter gentilis nestlings (n = 37; 14 nests). In addition, body feathers received further examination concerning their potential to provide an integrated assessment of (1) OHC exposure, (2) its dietary sources (carbon sources and trophic position) and (3) adrenal gland response (corticosterone). While tetrabromobisphenol A was not detected in any sample, the presence of polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers and hexabromocyclododecane in body feathers (median: 23, 19, 1.6 and 3.5 ng g-1 respectively), plasma (median: 7.5, 6.2, 0.50 and 1.0 ng g-1 ww, respectively) and preen oil (median: 750, 600, 18 and 9.57 ng g-1 ww, respectively) suggests analytical suitability for biomonitoring of major OHCs in the three matrices. Furthermore, strong and significant associations (0.20 ≤ R2 ≤ 0.98; all P < 0.05) among the OHC concentrations in all three tissues showed that body feathers and preen oil reliably reflect circulating plasma OHC levels. Of the dietary proxies, δ13C (carbon source) was the most suitable predictor for variation in feather OHCs concentrations, while no significant relationships between body feather OHCs and δ15N (trophic position) were found. Finally, body feather corticosterone concentrations were not related to variation in OHC concentrations. This is the first study to evaluate feathers of a terrestrial bird of prey as an integrated non-destructive tool to jointly assess nestling ecophysiology and ecotoxicology.
Asunto(s)
Águilas , Contaminantes Ambientales , Halcones , Animales , Carbono , Corticosterona , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Plumas/químicaRESUMEN
Fibrosis accompanies most heart diseases and is associated with adverse patient outcomes. Transforming growth factor (TGF)ß drives extracellular matrix remodelling and fibrosis in the failing heart. Some members of the ADAMTSL (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs-like) family of secreted glycoproteins bind to matrix microfibrils, and although their function in the heart remains largely unknown, they are suggested to regulate TGFß activity. The aims of this study were to determine ADAMTSL2 levels in failing hearts, and to elucidate the role of ADAMTSL2 in fibrosis using cultured human cardiac fibroblasts (CFBs). Cardiac ADAMTSL2 mRNA was robustly increased in human and experimental heart failure, and mainly expressed by fibroblasts. Over-expression and treatment with extracellular ADAMTSL2 in human CFBs led to reduced TGFß production and signalling. Increased ADAMTSL2 attenuated myofibroblast differentiation, with reduced expression of the signature molecules α-smooth muscle actin and osteopontin. Finally, ADAMTSL2 mitigated the pro-fibrotic CFB phenotypes, proliferation, migration and contractility. In conclusion, the extracellular matrix-localized glycoprotein ADAMTSL2 was upregulated in fibrotic and failing hearts of patients and mice. We identified ADAMTSL2 as a negative regulator of TGFß in human cardiac fibroblasts, inhibiting myofibroblast differentiation and pro-fibrotic properties.
Asunto(s)
Proteínas ADAMTS/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Transducción de Señal , Proteínas ADAMTS/genética , Animales , Biomarcadores , Diferenciación Celular/genética , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Proteínas de la Matriz Extracelular/genética , Regulación de la Expresión Génica , Insuficiencia Cardíaca/patología , Humanos , Ratones , Ratas , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Pelvic venous disease (PeVD) in women encompasses a wide variety of entities all resulting in pelvic pain and varices. Successful treatment with percutaneous interventions is dependent on identifying underlying factors contributing to the disease and addressing them with either embolization of incompetent veins or stenting for venous stenoses. There are a multitude of embolization methods with marked practice heterogeneity. Moreover, with the ongoing development of dedicated venous stents in the treatment of chronic venous disease, there are more opportunities to consider this modality for the treatment of PeVD, as many patients present with combined vein reflux and central venous stenosis. The necessity to address both and the order of interventions in these patients is still to be elucidated. Here, we describe when to choose stenting or embolization for PeVD, their limitations, and our practice and identify further areas of research in this field.
RESUMEN
An 86-year old asymptomatic male was incidentally found to have a variant of levoatrial cardinal vein (LACV) forming a complete venous ring. This is the first report of this variant. Although rare, the ability to identify LACV in the adult population is clinically significant because it may result in bi-directional shunt and the development of symptoms is an indication for intervention.
Asunto(s)
Malformaciones Vasculares , Venas , Adulto , Anciano de 80 o más Años , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. METHODS: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. RESULTS: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. INTERPRETATION: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04329611.
Asunto(s)
Atención Ambulatoria , Tratamiento Farmacológico de COVID-19 , COVID-19 , Hospitalización/estadística & datos numéricos , Hidroxicloroquina , Respiración Artificial/estadística & datos numéricos , Atención Ambulatoria/métodos , Atención Ambulatoria/estadística & datos numéricos , Antivirales/administración & dosificación , Antivirales/efectos adversos , COVID-19/diagnóstico , COVID-19/mortalidad , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Vida Independiente/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Evaluación de Resultado en la Atención de Salud , Servicios Preventivos de Salud/métodos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la EnfermedadRESUMEN
Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders.
Asunto(s)
Discapacidades del Desarrollo/genética , Genes Ligados a X , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Variación Genética , Cromosomas Humanos X/genética , Femenino , Genes Recesivos , Humanos , Patrón de Herencia/genética , Masculino , Herencia Multifactorial/genética , Mutación/genética , Fenotipo , Caracteres SexualesRESUMEN
PURPOSE: This study aimed to assess the efficacy of a virtual information session hosted by a diagnostic radiology residency program at addressing applicant concerns about the 2020-2021 interview cycle and highlighting key aspects of the residency program. METHODS: Participants were recruited to attend the virtual information session over a 2-week period via social media and communication with medical school radiology interest groups. Attendees were able to submit questions or topics of interest prior to the session. The virtual information session was hosted by trainees and faculty from a radiology residency. Data regarding the demographics of the attendees and the efficacy of the session were obtained through interactive live polling during the virtual session and a voluntary anonymous postsession survey. RESULTS: A total of 171 attendees participated in the virtual information session. Of the attendees, 42% learned about the session from Twitter and 72% were fourth-year medical students applying for residency. Among topics addressed during the session, attendees indicated that they were most interested in learning about "Application strategies during COVID-19" during an in-session poll. On the post-session survey, 96% of attendees reported being more knowledgeable about the residency program culture and the breadth of research and educational opportunities. CONCLUSION: Given the virtual nature of the 2020-2021 residency application cycle, utilization of web-based platforms for recruitment will be essential. Virtual information sessions can be effective at providing insight into aspects of a residency program that are typically gained during the in-person interview experience.
Asunto(s)
COVID-19/prevención & control , Difusión de la Información/métodos , Internado y Residencia , Radiología/educación , Estudiantes de Medicina , Femenino , Humanos , Masculino , SARS-CoV-2 , Adulto JovenRESUMEN
Background Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling mechanisms are not well understood. Herein, we examine the effect of thrombin-cleaved osteopontin on fibrosis in the heart and explore the role of syndecan-4 in regulating cleavage of osteopontin. Methods and Results Osteopontin was upregulated and cleaved by thrombin in the pressure-overloaded heart of mice subjected to aortic banding. Cleaved osteopontin was higher in plasma from patients with aortic stenosis receiving crystalloid compared with blood cardioplegia, likely because of less heparin-induced inhibition of thrombin. Cleaved osteopontin and the specific osteopontin peptide sequence RGDSLAYGLR that is exposed after thrombin cleavage both induced collagen production in cardiac fibroblasts. Like osteopontin, the heparan sulfate proteoglycan syndecan-4 was upregulated after aortic banding. Consistent with a heparan sulfate binding domain in the osteopontin cleavage site, syndecan-4 was found to bind to osteopontin in left ventricles and cardiac fibroblasts and protected osteopontin from cleavage by thrombin. Shedding of the extracellular part of syndecan-4 was more prominent at later remodeling phases, at which time levels of cleaved osteopontin were increased. Conclusions Thrombin-cleaved osteopontin induces collagen production by cardiac fibroblasts. Syndecan-4 protects osteopontin from cleavage by thrombin, but this protection is lost when syndecan-4 is shed in later phases of remodeling, contributing to progression of cardiac fibrosis.