RESUMEN
An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.
Asunto(s)
COVID-19/epidemiología , COVID-19/inmunología , COVID-19/transmisión , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/virología , Niño , Preescolar , Trazado de Contacto/métodos , Brotes de Enfermedades , Femenino , Genoma Viral , Humanos , Lactante , Recién Nacido , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , SARS-CoV-2/clasificación , Vacunación , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
The 2022 multicountry mpox outbreak concurrent with the ongoing Coronavirus Disease 2019 (COVID-19) pandemic further highlighted the need for genomic surveillance and rapid pathogen whole-genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early mpox infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there was an urgent need for a more sensitive and broadly applicable sequencing approach. Highly multiplexed amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented in public health laboratories during the COVID-19 pandemic. We sequenced clinical specimens that tested presumptively positive for human monkeypox virus with amplicon-based and metagenomic sequencing approaches. We found notably higher genome coverage across the virus genome, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach, particularly in higher PCR cycle threshold (Ct) (lower DNA titer) samples. Further testing demonstrated that Ct value correlated with the number of sequencing reads and influenced the percent genome coverage. To maximize genome coverage when resources are limited, we recommend selecting samples with a PCR Ct below 31 Ct and generating 1 million sequencing reads per sample. To support national and international public health genomic surveillance efforts, we sent out primer pool aliquots to 10 laboratories across the United States, United Kingdom, Brazil, and Portugal. These public health laboratories successfully implemented the human monkeypox virus primer scheme in various amplicon sequencing workflows and with different sample types across a range of Ct values. Thus, we show that amplicon-based sequencing can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole-genome sequencing in response to newly emerging pathogens. Importantly, through the implementation of our primer scheme into existing SARS-CoV-2 workflows and across a range of sample types and sequencing platforms, we further demonstrate the potential of this approach for rapid outbreak response.
Asunto(s)
COVID-19 , Mpox , Infección por el Virus Zika , Virus Zika , Humanos , COVID-19/epidemiología , Pandemias , SARS-CoV-2/genética , GenómicaRESUMEN
Quantifying how contaminants change across life cycles of species that undergo metamorphosis is critical to assessing organismal risk, particularly for consumers. Pond-breeding amphibians can dominate aquatic animal biomass as larvae and are terrestrial prey as juveniles and adults. Thus, amphibians can be vectors of mercury exposure in both aquatic and terrestrial food webs. However, it is still unclear how mercury concentrations are affected by exogenous (e.g., habitat or diet) vs endogenous factors (e.g., catabolism during hibernation) as amphibians undergo large diet shifts and periods of fasting during ontogeny. We measured total mercury (THg), methylmercury (MeHg), and isotopic compositions (δ 13C, δ15N) in boreal chorus frogs (Pseudacris maculata) across five life stages in two Colorado (USA) metapopulations. We found large differences in concentrations and percent MeHg (of THg) among life stages. Frog MeHg concentrations peaked during metamorphosis and hibernation coinciding with the most energetically demanding life cycle stages. Indeed, life history transitions involving periods of fasting coupled with high metabolic demands led to large increases in mercury concentrations. The endogenous processes of metamorphosis and hibernation resulted in MeHg bioamplification, thus decoupling it from the light isotopic proxies of diet and trophic position. These step changes are not often considered in conventional expectations of how MeHg concentrations within organisms are assessed.
Asunto(s)
Mercurio , Compuestos de Metilmercurio , Contaminantes Químicos del Agua , Animales , Estanques , Mercurio/análisis , Compuestos de Metilmercurio/metabolismo , Ecosistema , Cadena Alimentaria , Anfibios/metabolismo , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Peces/metabolismoRESUMEN
BACKGROUND: Although pediatric cancer survivors in the United States are at an increased risk of developing chronic conditions, to the authors' knowledge there is limited information regarding the types and combinations of conditions they experience in the years immediately after the completion of cancer therapy. METHODS: An observational cohort study of early pediatric cancer survivors (children who were ≥2 years from the end of therapy and aged ≤18 years) was conducted using the Truven Health MarketScan (r) Commercial Claims and Encounters database (2009-2014). Latent class analysis was used to identify comorbidity groups among the subset with ≥2 conditions. Group-level health care use was compared with survivors without chronic conditions using multivariate regression. RESULTS: A total of 3687 early survivors were identified, of whom approximately 41.2% had no chronic conditions, 22.5% had 1 chronic condition, and 36.3% had ≥2 chronic conditions. Among those with ≥2 chronic conditions, 5 groups emerged: 1) general pediatric morbidity (35.4%); 2) central nervous system (CNS) (22.4%); 3) mental health conditions (22.2%); 4) endocrine (26.2%); and 5) CNS with endocrine (3.8%). The CNS group experienced the highest expenditures, at $17,964 more per year (95% CI, $1446-$34,482) compared with survivors without chronic conditions. The CNS group also had the highest odds of an emergency department visit (adjusted odds ratio, 1.71; 95% CI, 1.15-2.56). The endocrine group had the highest odds of hospitalization (odds ratio, 2.29; 95% CI, 1.24-4.22). CONCLUSIONS: Multimorbidity is common among pediatric cancer survivors. The current study identified 5 distinct comorbidity subgroups, all of which experienced high, yet differential, rates of health care use. The results of the current study highlight the complex health care needs of early survivors and provide evidence for the design of targeted survivorship services and interventions.
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Supervivientes de Cáncer , Multimorbilidad , Neoplasias/mortalidad , Pediatría , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Atención a la Salud , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Masculino , Neoplasias/patología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: Lack of clarity on the definition of "patient engagement" has been highlighted as a barrier to fully implementing patient engagement in research. This study identified themes within existing definitions related to patient engagement and proposes a consensus definition of "patient engagement in research." METHODS: A systematic review was conducted to identify definitions of patient engagement and related terms in published literature (2006-2018). Definitions were extracted and qualitatively analyzed to identify themes and characteristics. A multistakeholder approach, including academia, industry, and patient representation, was taken at all stages. A proposed definition is offered based on a synthesis of the findings. RESULTS: Of 1821 abstracts identified and screened for eligibility, 317 were selected for full-text review. Of these, 169 articles met inclusion criteria, from which 244 distinct definitions were extracted for analysis. The most frequently defined terms were: "patient-centered" (30.5%), "patient engagement" (15.5%), and "patient participation" (13.4%). The majority of definitions were specific to the healthcare delivery setting (70.5%); 11.9% were specific to research. Among the definitions of "patient engagement," the most common themes were "active process," "patient involvement," and "patient as participant." In the research setting, the top themes were "patient as partner," "patient involvement," and "active process"; these did not appear in the top 3 themes of nonresearch definitions. CONCLUSION: Distinct themes are associated with the term "patient engagement" and with engagement in the "research" setting. Based on an analysis of existing literature and review by patient, industry, and academic stakeholders, we propose a scalable consensus definition of "patient engagement in research."
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Investigación Biomédica/organización & administración , Participación del Paciente , Proyectos de Investigación , Atención a la Salud/organización & administración , Humanos , Evaluación de Resultado en la Atención de Salud/organización & administración , Atención Dirigida al PacienteRESUMEN
Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009-2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4-2.1) and of a hospitalization almost four-fold (OR, 3.8; 95% CI], 2.5-5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.
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Supervivientes de Cáncer/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Multimorbilidad , Neoplasias/terapia , Aceptación de la Atención de Salud/estadística & datos numéricos , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Using aggregated data available on the interactive website from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Network (HCUPnet), we examined the annual volume of invasive aspergillosis (IA)-related hospitalizations in the US. METHODS: This was a population study. Age-adjusted volumes were derived through population incidence calculated using year-specific censal and intercensal US population estimates available from the US Census Bureau. We additionally examined IA as the principal diagnosis and its associated outcomes in patients with ICD-9-CM codes 117.3, 117.9 and 484.6. RESULTS: The age-adjusted number of annual hospitalizations with IA grew from 35,968 cases in 2004 to 51,870 in 2013, a 44.2% overall increase, 4.4% per annum. Regionally, the South contributed the plurality of the cases (40%), and the Northeast the fewest (17%). While IA as principal diagnosis dropped, from 14.4 to 9.3%, mortality rose from 10 to 12%. Despite mean hospital length of stay decreasing from 13.3 (standard error [SE] 0.07) to 11.5 (SE 0.6) days, the corresponding mean hospital charges rose from $71,164 (SE $5248) to $123,005 (SE $9738). The aggregate US inflation-adjusted hospital charges for IA principal diagnosis rose from $436,074,445 in 2004 to $592,358,369 in 2013. CONCLUSIONS: Given the substantial volume and rate of growth in IA-related hospitalizations in the US between 2004 and 2013, an increase in mortality and high costs, IA may represent an attractive target for intensive preventive efforts.
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Aspergilosis/epidemiología , Costo de Enfermedad , Hospitalización/estadística & datos numéricos , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Background: Though invasive aspergillosis (IA) complicates care of up to 13% of patients with immunocompromise, little is known about its morbidity and mortality burden in the United States. Methods: We analyzed the Health Care Utilization Project's data from the Agency for Healthcare Research and Quality for 2009-2013. Among subjects with high-risk conditions for IA, IA was identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). Using propensity score matching, we calculated the IA-associated excess mortality and 30-day readmission rates, length of stay, and costs. Results: Of the 66634683 discharged patients meeting study inclusion criteria, 154888 (0.2%) had a diagnosis of IA. The most common high-risk conditions were major surgery (50.1%) in the non-IA and critical illness (41.0%) in the IA group. After propensity score matching, both mortality (odds ratio, 1.43; 95% confidence interval, 1.36-1.51) and 30-day readmission (1.39; 1.34-1.45) rates were higher in the IA group. IA was associated with 6.0 (95% confidence interval, 5.7-6.4) excess days in the hospital and $15542 ($13869-$17215) in excess costs per hospitalization. Conclusions: Although rare even among high-risk groups, IA is associated with increased hospital mortality and 30-day readmission rates, excess duration of hospitalization, and costs. Given nearly 40000 annual admissions for IA in the United States, the aggregate IA-attributable excess costs may reach $600 million annually.
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Aspergilosis/mortalidad , Mortalidad Hospitalaria , Hospitalización/economía , Infecciones Fúngicas Invasoras/economía , Infecciones Fúngicas Invasoras/mortalidad , Anciano , Anciano de 80 o más Años , Aspergilosis/economía , Costo de Enfermedad , Femenino , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Alta del Paciente , Evaluación del Resultado de la Atención al Paciente , Readmisión del Paciente/estadística & datos numéricos , Puntaje de Propensión , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Studies examining the association between use of oseltamivir and neuropsychiatric events (including suicide) among children have had mixed findings and have been limited by small sample size, reliance on older data, and potential confounding. We undertook an analysis that addresses these limitations. METHODS: Using a national administrative claims database and a case-crossover design that minimized confounding, we analyzed data from 5 contemporary influenza seasons (2009-2013) for individuals aged 1 to 18 years and ascertained oseltamivir exposure from pharmacy dispensing. RESULTS: We identified 21,407 suicide-related events during this study period, 251 of which were in oseltamivir-exposed children. In case-crossover analysis, we did not find any significant association with suicide either for oseltamivir exposure (odds ratio = 0.64; 95% CI, 0.39-1.00; P = .05) or for influenza diagnosis alone (odds ratio = 0.63; 95% CI, 0.34-1.08; P = .10). CONCLUSION: Our findings suggest that oseltamivir does not increase risk of suicide in the pediatric population.
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Antivirales/uso terapéutico , Gripe Humana/tratamiento farmacológico , Oseltamivir/uso terapéutico , Suicidio/estadística & datos numéricos , Adolescente , Antivirales/efectos adversos , Niño , Preescolar , Estudios Cruzados , Bases de Datos Factuales , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Oportunidad Relativa , Oseltamivir/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. CONCLUSIONS: Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.
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Antivirales/uso terapéutico , Costo de Enfermedad , Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Antivirales/economía , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/economía , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Pruebas Serológicas , Receptores de Trasplantes/estadística & datos numéricos , Trasplante Autólogo/efectos adversos , Trasplante Homólogo/efectos adversosRESUMEN
This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive Candida culture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics, Candida species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow test P value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.
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Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candidemia/tratamiento farmacológico , Candidemia/mortalidad , Fluconazol/uso terapéutico , Farmacorresistencia Fúngica , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Modelos Teóricos , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the use of at least one drug that resulted in a severe DDI. The findings of this study demonstrate that a majority of hospitalized patients receiving MAT are at risk for severe drug-drug interactions and highlight the need for antifungal stewardship.
Asunto(s)
Antifúngicos/farmacología , Interacciones Farmacológicas , Triazoles/farmacología , Hospitalización , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Voriconazol/farmacologíaRESUMEN
BACKGROUND: Mucormycosis is a rare but devastating fungal infection primarily affecting immunocompromised patients such as those with hematological malignancy, bone marrow and solid organ transplantation, and patients with diabetes, and, even more rarely, immunocompetent patients. The objective of this study was to assess the prevalence and burden, both clinical and economic, of mucormycosis among hospitalized patients in the U.S. METHODS: This is a retrospective study using the Premier PerspectiveTM Comparative Database, with more than 560 participating hospitals covering 104 million patients (January 2005-June 2014). All hospitalizations in the database were evaluated for the presence of mucormycosis using either an ICD-9 code of 117.7 or a positive laboratory result for Mucorales. Hospitalizations were further required to have prescriptions of amphotericin B or posaconazole to be considered as mucormycosis-related hospitalizations. The prevalence of mucormycosis-related hospitalizations among all hospital discharges was estimated. Mortality rate at discharge, length of hospital stay, and readmission rates at 1 and 3 months were evaluated among mucormycosis-related hospitalizations. Cost per hospital stay and average per diem cost (inflated to 2014 USD) were reported. RESULTS: The prevalence of mucormycosis-related hospitalizations was estimated as 0.12 per 10,000 discharges during January 2005-June 2014. It increased to 0.16 per 10,000 discharges if the definition of mucormycosis was relaxed to not require the use of amphotericin B or posaconazole. The median length of stay was 17 days, with 23% dead at discharge; readmission rates were high, with 30 and 37% of patients readmitted within one and three months of discharge, respectively. The average cost per hospital stay was $112,419, and the average per diem cost was $4,096. CONCLUSIONS: The study provides a recent estimate of the prevalence and burden of mucormycosis among hospitalized patients. The high clinical and economic burden associated with mucormycosis highlights the importance of establishing active surveillance and optimizing prophylactic and active treatment in susceptible patients.
Asunto(s)
Costo de Enfermedad , Hospitalización/estadística & datos numéricos , Mucormicosis/epidemiología , Adolescente , Adulto , Anciano , Antifúngicos/economía , Antifúngicos/uso terapéutico , Niño , Bases de Datos Factuales , Femenino , Costos de Hospital/estadística & datos numéricos , Hospitalización/economía , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Mucormicosis/economía , Mucormicosis/terapia , Prevalencia , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
The 2022 multi-country monkeypox (mpox) outbreak concurrent with the ongoing COVID-19 pandemic has further highlighted the need for genomic surveillance and rapid pathogen whole genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early mpox infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there was an urgent need for a more sensitive and broadly applicable sequencing approach. Highly multiplexed amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for SARS-CoV-2. Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented in public health laboratories during the COVID-19 pandemic. We sequenced clinical samples that tested presumptive positive for human monkeypox virus with amplicon-based and metagenomic sequencing approaches. We found notably higher genome coverage across the virus genome, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach, particularly in higher PCR cycle threshold (lower DNA titer) samples. Further testing demonstrated that Ct value correlated with the number of sequencing reads and influenced the percent genome coverage. To maximize genome coverage when resources are limited, we recommend selecting samples with a PCR cycle threshold below 31 Ct and generating 1 million sequencing reads per sample. To support national and international public health genomic surveillance efforts, we sent out primer pool aliquots to 10 laboratories across the United States, United Kingdom, Brazil, and Portugal. These public health laboratories successfully implemented the human monkeypox virus primer scheme in various amplicon sequencing workflows and with different sample types across a range of Ct values. Thus, we show that amplicon based sequencing can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole genome sequencing in response to newly emerging pathogens. Importantly, through the implementation of our primer scheme into existing SARS-CoV-2 workflows and across a range of sample types and sequencing platforms, we further demonstrate the potential of this approach for rapid outbreak response.
RESUMEN
Contaminants alter the quantity and quality of insect prey available to terrestrial insectivores. In agricultural regions, the quantity of aquatic insects emerging from freshwaters can be impacted by insecticides originating from surrounding croplands. We hypothesized that, in such regions, adult aquatic insects could also act as vectors of pesticide transfer to terrestrial food webs. To estimate insect-mediated pesticide flux from wetlands embedded in an important agricultural landscape, semipermanetly and temporarily ponded wetlands were surveyed in cropland and grassland landscapes across a natural salinity gradient in the Prairie Pothole Region of North Dakota (USA) during the bird breeding season in 2015 and 2016 (n = 14 and 15 wetlands, respectively). Current-use pesticides, including the herbicide atrazine and the insecticides bifenthrin and imidacloprid, were detected in newly emerged insects. Pesticide detections were similar in insects emerging from agricultural and grassland wetlands. Biomass of emerging aquatic insects decreased 43%, and insect-mediated pesticide flux increased 50% along the observed gradient in concentrations of insecticides in emerging aquatic insects (from 3 to 577 ng total insecticide g-1 insect). Overall, adult aquatic insects were estimated to transfer between 2 and 180 µg total pesticide wetland-1 d-1 to the terrestrial ecosystem. In one of the 2 study years, biomass of emerging adult aquatic insects was also 73% lower from agricultural than grassland wetlands and was dependent on salinity. Our results suggest that accumulated insecticides reduce the availability of adult aquatic insect prey for insectivores and potentially increase insectivore exposure to insect-borne pesticides. Adult aquatic insects retain pesticides across metamorphosis and may expose insectivores living near both agricultural and grassland wetlands to dietary sources of toxic chemicals. Environ Toxicol Chem 2021;40:2282-2296. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
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Insecticidas , Plaguicidas , Animales , Ecosistema , Pradera , Insectos , Insecticidas/toxicidad , HumedalesRESUMEN
Frameworks exclusively considering functional diversity are gaining popularity, as they complement and extend the information provided by taxonomic diversity metrics, particularly in response to disturbance. Taxonomic diversity should be included in functional diversity frameworks to uncover the functional mechanisms causing species loss following disturbance events. We present and test a predictive framework that considers temporal functional and taxonomic diversity responses along disturbance gradients. Our proposed framework allows us to test different multidimensional metrics of taxonomic diversity that can be directly compared to calculated multidimensional functional diversity metrics. It builds on existing functional diversity-disturbance frameworks both by using a gradient approach and by jointly considering taxonomic and functional diversity. We used previously unpublished stream insect community data collected prior to, and for the two years following, an extreme flood event that occurred in 2013. Using 14 northern Colorado mountain streams, we tested our framework and determined that taxonomic diversity metrics calculated using multidimensional methods resulted in concordance between taxonomic and functional diversity responses. By considering functional and taxonomic diversity together and using a gradient approach, we were able to identify some of the mechanisms driving species losses following this extreme disturbance event.
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Inundaciones , Ríos , Animales , Biodiversidad , Colorado , InsectosRESUMEN
Streamflow duration information underpins many management decisions. However, hydrologic data are rarely available where needed. Rapid streamflow duration assessment methods (SDAMs) classify reaches based on indicators that are measured in a single brief visit. We evaluated a proposed framework for developing SDAMs to develop an SDAM for the Arid West United States that can classify reaches as perennial, intermittent, or ephemeral. We identified 41 candidate biological, geomorphological, and hydrological indicators of streamflow duration in a literature review, evaluated them for a number of desirable criteria (e.g., defensibility and consistency), and measured 21 of them at 89 reaches with known flow durations. We selected metrics for the SDAM based on their ability to discriminate among flow duration classes in analyses of variance, as well as their importance in a random forest model to predict streamflow duration. This approach resulted in a "beta" SDAM that uses five biological indicators. It could discriminate between ephemeral and non-ephemeral reaches with 81% accuracy, but only 56% accuracy when distinguishing 3 classes. A final method will be developed following expanded data collection. This Arid West study demonstrates the effectiveness of our approach and paves the way for more efficient development of scientifically informed SDAMs.
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Multiple summer events, including large indoor gatherings, in Provincetown, Massachusetts (MA), in July 2021 contributed to an outbreak of over one thousand COVID-19 cases among residents and visitors. Most cases were fully vaccinated, many of whom were also symptomatic, prompting a comprehensive public health response, motivating changes to national masking recommendations, and raising questions about infection and transmission among vaccinated individuals. To characterize the outbreak and the viral population underlying it, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of sequenced outbreak-associated cases. Phylogenetic analysis suggests over 40 sources of Delta in the dataset, with one responsible for a single cluster containing 83% of outbreak-associated genomes. This cluster was likely not the result of extensive spread at a single site, but rather transmission from a common source across multiple settings over a short time. Genomic and epidemiological data combined provide strong support for 25 transmission events from, including many between, fully vaccinated individuals; genomic data alone provides evidence for an additional 64. Together, genomic epidemiology provides a high-resolution picture of the Provincetown outbreak, revealing multiple cases of transmission of Delta from fully vaccinated individuals. However, despite its magnitude, the outbreak was restricted in its onward impact in MA and the US, likely due to high vaccination rates and a robust public health response.
RESUMEN
OBJECTIVE: A qualitative study using a phenomenological approach, to explore stroke survivors' needs and their perceptions of whether a community stroke scheme met these needs. METHODS: Semi-structured in-depth interviews of 12 stroke survivors, purposively selected from participants attending a new community stroke scheme. Interpretative phenomenological analysis of interviews by two researchers independently. RESULTS: Participants attending the community stroke scheme sought to reconstruct their lives in the aftermath of their stroke. To enable this they needed internal resources of confidence and sense of purpose to 'create their social self', and external resources of 'responsive services' and an 'informal support network', to provide direction and encouragement. Participants felt the community stroke scheme met some of these needs through exercise, goal setting and peer group interaction, which included social support and knowledge acquisition. CONCLUSION: Stroke survivors need a variety of internal and external resources so that they can rebuild their lives positively post stroke. A stroke-specific community scheme, based on exercise, life-centred goal setting, peer support and knowledge acquisition, is an external resource that can help with meeting some of the stroke survivor's needs.
Asunto(s)
Actividades Cotidianas/psicología , Educación del Paciente como Asunto/métodos , Apoyo Social , Accidente Cerebrovascular/psicología , Anciano , Redes Comunitarias , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Satisfacción del Paciente , Modalidades de Fisioterapia , Calidad de Vida , Perfil de Impacto de Enfermedad , Rehabilitación de Accidente CerebrovascularRESUMEN
OBJECTIVE: The evaluation of a community-based exercise and education scheme for stroke survivors. DESIGN: A single blind parallel group randomized controlled trial. SETTING: Leisure and community centres in the south-west of England. SUBJECTS: Stroke survivors (median (IQR) time post stroke 10.3 (5.4-17.1) months). 243 participants were randomized to standard care (124) or the intervention (119). INTERVENTION: Exercise and education schemes held twice weekly for eight weeks, facilitated by volunteers and qualified exercise instructors (supported by a physiotherapist), each with nine participants plus carers or family members. METHOD: Participants were assessed by a blinded independent assessor at two weeks before the start of the scheme, nine weeks and six months. One-year follow-up was by postal assessment. PRIMARY OUTCOMES: Subjective Index of Physical and Social Outcome (SIPSO); Frenchay Activities Index; Rivermead Mobility Index. NHS, social care and personal costs. Secondary outcomes included WHOQoL-Bref. ANALYSIS: Intention-to-treat basis, using non-parametric analysis to investigate change from baseline. Economic costs were compared in a cost-consequences analysis. RESULTS: There were significant between-group changes in SIPSO physical at nine weeks (median (95% confidence interval (CI)), 1 (0, 2): P = 0.022) and at one year (0 (-1, 2): P = 0.024). (WHOQol-Bref psychological (6.2 (-0.1, 9.1): P = 0.011) at six months. Mean cost per patient was higher in the intervention group. The difference, excluding inpatient care, was pound296 (95% CI: - pound321 to pound913). CONCLUSION: The community scheme for stroke survivors was a low-cost intervention successful in improving physical integration, maintained at one year, when compared with standard care.