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In the current landscape, regulatory agencies face the challenge of reconciling timely authorizations for novel medicines addressing life-threatening conditions with thorough evaluations of their benefits and risks. This challenge is pronounced with advanced therapy medicinal products (ATMPs), where expedited approval mechanisms and orphan drug designations are often applied, making post-authorization measures a crucial mechanism to address uncertainties. We compared post-authorization measures imposed by the U.S. Food and Drug Administration and the European Medicines Agency on ATMPs approvals, from 2009 to 2023. A systematic extraction of FDA postmarketing requirements (PMRs) and EMA-imposed post-authorization measures (PAMs) from publicly available regulatory documents was conducted. Descriptive analysis focused on post-authorization measure categories, objectives, study designs, and their status and registration rates. A total of 15 ATMPs were approved in both jurisdictions over the study period. For these products, the EMA imposed 53 PAMs (34 Annex II conditions and 19 Specific Obligations), whereas the FDA imposed 27 PMRs. As of December 2023, 15 EMA-imposed PAMs were fulfilled, with no explicit fulfilments indicated for FDA PMRs. Both agencies promoted real-world data use in around half of the imposed PAMs (23 by EMA vs. 15 by FDA), marking regulators' growing recognition of Real-World Evidence for decision-making. This study highlights disparities between imposed PAMs: EMA imposed more PAMs, covering efficacy, safety, and quality aspects, while the FDA required fewer measures focusing on specific safety concerns. These discrepancies primarily reflect distinct regulatory structures and approaches to further post-authorization data collection between the EMA and FDA, rather than disparities in initial benefit/risk assessments.
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Lyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations. IMPORTANCE: Lyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.
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Ixodes scapularis ticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirochete Borrelia burgdorferi . The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without excessive activation of the proinflammatory branch of the vertebrate immune system. While the ability for nymphal ticks to feed on a variety of hosts has been well-documented, the host-parasite interactions between larval I. scapularis and different vertebrate hosts is relatively unexplored. Here we report on the changes in the vertebrate transcriptome present at the larval tick bite site using the natural I. scapularis host Peromyscus leucopus deermouse, a non-natural rodent host Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite site. We also note that bite sites on BALB/c mice and humans, but not deermice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval I. scapularis and P. leucopus as well as expand our overall understanding of I. scapularis feeding. Significance: Ixodes scapularis tick bites expose humans to numerous diseases in North America. While larval tick feeding enables pathogens to enter the tick population and eventually spread to humans, how larval ticks interact with mammals has been understudied compared to other tick stages. Here we examined the transcriptomic response of a natural I. scapularis rodent host ( Peromyscus leucopus ), a non-native I. scapularis rodent host ( Mus musculus ), and an incidental host (humans). We find that there are differences in how all three species respond to larval I. scapularis , with the natural host producing the smallest transcriptomic signature of a canonical proinflammatory immune response and the incidental human host producing the most robust signature of inflammation in response to the larval tick. These data expand our understanding of the pressures on ticks in the wild and inform our ability to model these interactions in laboratory settings.
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Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice. Here, we compiled 45 colorectal cancer studies utilizing numerical thresholds for high-TMB. In this group of studies, TMB cut-offs ranged from 6.88 to 41 mut/Mb and were most often set at 10, 17, or 20 mut/Mb. Additionally, we observed divergent TMB definitions and inconsistent disclosure of specific methodological details, which collectively emphasize the substantial lack of harmonization within the field. Ongoing efforts to harmonize TMB assessment will be critical to validate TMB as a predictive marker of immunotherapy response.
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Biomarcadores Tumorais , Neoplasias Colorretais , Mutação , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Biomarcadores Tumorais/genética , Imunoterapia/métodos , Instabilidade de Microssatélites , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.
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BACKGROUND: Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. METHODS: The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. RESULTS: Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. CONCLUSIONS: In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. IMPACT: The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.
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Doença de Lyme , Qualidade de Vida , Adolescente , Humanos , Criança , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Antibacterianos/uso terapêutico , Dor/tratamento farmacológico , Fadiga/tratamento farmacológicoRESUMO
Tickborne diseases are a significant public health problem in the United States and worldwide. Ticks are obligate blood-feeding arthropods; an ixodid tick must remain attached to the skin of the host and complete its multi-day feeding process to acquire its blood meal. Exposing animals to ticks is a common practice for studying host responses to tick bites and tickborne diseases. We developed the procedure, conducted the first human research study, and published the findings on exposing human volunteers to uninfected larval Ixodes scapularis ticks. This article describes the methodology used to construct the containment dressing, how to apply and secure the ticks to the host, how to maintain the dressing, and how to remove the ticks from the host. Exposing volunteers to tick bites is an experimental procedure and must be performed under a clinical research protocol approved by the appropriate regulatory authorities. This method allows for translational research to better understand the human response to tick bites and foster the development of diagnostics, prevention, and therapies for tickborne diseases.
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Artrópodes , Ixodes , Ixodidae , Picadas de Carrapatos , Animais , Humanos , Bandagens , LarvaRESUMO
Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock is a subset of sepsis defined by persistent hypotension, and hospital mortality rates are higher than 40%. Although early sepsis mortality has greatly improved in the past few years, sepsis patients who survive the hyperinflammation and subsequent organ damage often die from long-term complications, such as secondary infection, and despite decades of clinical trials targeting this stage of the disease, currently, no sepsis-specific therapies exist. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy has emerged as a promising path forward. Highly investigated treatment strategies include cytokines and growth factors, immune checkpoint inhibitors, and even cellular therapies. There is much to be learned from related illnesses, and immunotherapy trials in oncology, as well as the recent COVID-19 pandemic, have greatly informed sepsis research. Although the journey ahead is a long one, the stratification of patients according to their immune status and the employment of combination therapies represent a hopeful way forward.
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From a country with one of the highest SARS-CoV-2 morbidity and mortality rates, Brazil has implemented one of the most successful vaccination programs. Brazil's first model city vaccination program was performed by the CoronaVac vaccine (Sinovac Biotech) in the town of Serrana, São Paulo State. To evaluate the vaccination effect on the SARS-CoV-2 molecular dynamics and clinical outcomes, we performed SARS-CoV-2 molecular surveillance on 4375 complete genomes obtained between June 2020 and April 2022 in this location. This study included the period between the initial SARS-CoV-2 introduction and during the vaccination process. We observed that the SARS-CoV-2 substitution dynamics in Serrana followed the viral molecular epidemiology in Brazil, including the initial identification of the ancestral lineages (B.1.1.28 and B.1.1.33) and epidemic waves of variants of concern (VOC) including the Gamma, Delta, and, more recently, Omicron. Most probably, as a result of the immunization campaign, the mortality during the Gamma and Delta VOC was significantly reduced compared to the rest of Brazil, which was also related to lower morbidity. Our phylogenetic analysis revealed the evolutionary history of the SARS-CoV-2 in this location and showed that multiple introduction events have occurred over time. The evaluation of the COVID-19 clinical outcome revealed that most cases were mild (88.9%, 98.1%, 99.1% to Gamma, Delta, and Omicron, respectively) regardless of the infecting VOC. In conclusion, we observed that vaccination was responsible for reducing the death toll rate and related COVID-19 morbidity, especially during the gamma and Delta VOC; however, it does not prevent the rapid substitution rate and morbidity of the Omicron VOC.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Brasil/epidemiologia , Filogenia , COVID-19/epidemiologia , COVID-19/prevenção & controle , VacinaçãoRESUMO
Most patients with Lyme disease will fully recover with recommended antibiotic therapy. However, some patients report persisting nonspecific symptoms after treatment, referred to as posttreatment Lyme disease symptoms (PTLDs) or syndrome (PTLDS), depending on the degree to which the individual's symptoms impact their quality of life. PTLDs occur in a portion of patients diagnosed with chronic Lyme disease (CLD), a controversial term describing different patient populations, diagnosed based on unvalidated tests and criteria. Practitioners should review the evidence for the Lyme disease diagnosis and not overlook unrelated conditions. Current evidence shows that prolonged antibiotic therapy provides little benefit and carries significant risk. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and to understand CLD is needed.
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Doença de Lyme , Qualidade de Vida , Antibacterianos/uso terapêutico , Atenção à Saúde , Humanos , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , SíndromeRESUMO
Anaplasma phagocytophilum and Babesia microti are emerging tick-borne pathogens in the United States. Although active infection is typically diagnosed by direct diagnostic tests, such as blood smear or polymerase chain reaction assay, serologic assays can be helpful to identify past infections, and the use of acute plus convalescent testing can potentially identify recent infections. We employed a peptide array to select sets of linear peptides for serologic diagnosis of infections with A. phagocytophilum and B. microti. Three optimal peptides were selected for each agent based on their performance with clinical specimens. All three A. phagocytophilum peptides were located within the conserved fragments of the MSP2 antigen. Two B. microti peptides were located in the N terminus of the SA-1 antigen; the third was in the BMN 1-17 antigen. We found that these peptides can be a useful tool for detection of antibody reactivity to both of these pathogens.
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Anaplasma phagocytophilum , Babesia microti , Babesiose , Borrelia burgdorferi , Anticorpos , Babesiose/diagnóstico , Humanos , PeptídeosRESUMO
BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.
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COVID-19 , Doença Aguda , Adulto , COVID-19/complicações , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Qualidade de Vida , SARS-CoV-2RESUMO
A close association with its vertebrate and tick hosts allows Borrelia burgdorferi, the bacterium responsible for Lyme disease, to eliminate many metabolic pathways and instead scavenge key nutrients from the host. A lipid-defined culture medium was developed to demonstrate that exogenous lipids are an essential nutrient of B. burgdorferi, which can accumulate intact phospholipids from its environment to support growth. Antibody responses to host phospholipids were studied in mice and humans using an antiphospholipid ELISA. Several of these environmentally acquired phospholipids including phosphatidylserine and phosphatidic acid, as well as borrelial phosphatidylcholine, are the targets of antibodies that arose early in infection in the mouse model. Patients with acute infections demonstrated antibody responses to the same lipids. The elevation of antiphospholipid antibodies predicted early infection with better sensitivity than did the standardized 2-tier tests currently used in diagnosis. Sera obtained from patients with Lyme disease before and after antibiotic therapy showed declining antiphospholipid titers after treatment. Further study will be required to determine whether these antibodies have utility in early diagnosis of Lyme disease, tracking of the response to therapy, and diagnosis of reinfection, areas in which current standardized tests are inadequate.
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Borrelia burgdorferi , Doença de Lyme , Animais , Anticorpos Antifosfolipídeos/metabolismo , Anticorpos Antibacterianos , Ensaio de Imunoadsorção Enzimática , Humanos , Camundongos , Fosfolipídeos/metabolismoRESUMO
OBJECTIVES: Facial palsy is the most common manifestation of Lyme neuroborreliosis (LNB) in the United States. This study aimed to describe features of patients with early LNB presenting with facial palsy and to determine if corticosteroids in addition to antibiotic therapy was associated with unfavorable outcome. METHODS: Retrospective analysis of participants enrolled in clinical studies investigating Lyme disease (N = 486) identified 44 patients who had facial palsy from LNB. The House-Brackmann scale was used to quantify the facial nerve dysfunction. RESULTS: Most patients presented in the summer months. Erythema migrans, frequently associated with systemic symptoms, occurred in 29 patients. Thirteen patients presented with bilateral facial palsy, usually with sequential involvement. Fourteen patients had painful radiculopathy. Of the 38 patients treated with antibiotics before the resolution of the palsy who had complete follow-up, 24 received both antibiotics and corticosteroids. Of these 38 patients, 34 recovered completely, 3 had nearly complete recovery, and 1 had moderate dysfunction. There were no differences between the treatment groups in achieving complete resolution of the palsy at 12 months or in time to complete recovery. INTERPRETATION: A history of rash compatible with erythema migrans or febrile illness in the weeks preceding the palsy are helpful clues pointing toward LNB and should be actively sought when evaluating patients with acute-onset peripheral facial palsy, particularly bilateral facial palsy. Treatment with antibiotic therapy is highly effective and most patients will fully recover facial nerve function. Adjunctive corticosteroid therapy appears to not affect the speed of recovery or overall outcome in this retrospective observational study.
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Corticosteroides/farmacologia , Antibacterianos/farmacologia , Doenças do Nervo Facial , Paralisia Facial , Neuroborreliose de Lyme , Adolescente , Adulto , Doenças do Nervo Facial/tratamento farmacológico , Doenças do Nervo Facial/epidemiologia , Doenças do Nervo Facial/etiologia , Doenças do Nervo Facial/fisiopatologia , Paralisia Facial/tratamento farmacológico , Paralisia Facial/epidemiologia , Paralisia Facial/etiologia , Paralisia Facial/fisiopatologia , Feminino , Humanos , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The role that microorganisms might have in the development of Alzheimer disease is a topic of considerable interest. In this article, we discuss whether there is credible evidence that Lyme disease is a cause of Alzheimer disease and critically review a recent publication that claimed that Borrelia burgdorferi sensu stricto infection, the primary cause of Lyme disease in the United States, may cause Lewy body dementia. We conclude that no convincing evidence exists that Lyme disease is a cause of either Alzheimer disease or Lewy body dementia.
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Doença de Alzheimer , Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Doença por Corpos de Lewy , Doença de Lyme , Doença de Alzheimer/etiologia , Humanos , Doença de Lyme/complicações , Estados UnidosRESUMO
Lyme disease, or Lyme borreliosis, is the most common tickborne disease in the United States and Europe. In both locations, Ixodes species ticks transmit the Borrelia burgdorferi sensu lato bacteria species responsible for causing the infection. The diversity of Borrelia species that cause human infection is greater in Europe; the 2 B. burgdorferi s.l. species collectively responsible for most infections in Europe, B. afzelii and B. garinii, are not found in the United States, where most infections are caused by B. burgdorferi sensu stricto. Strain differences seem to explain some of the variation in the clinical manifestations of Lyme disease, which are both minor and substantive, between the United States and Europe. Future studies should attempt to delineate the specific virulence factors of the different species of B. burgdorferi s.l. responsible for these variations in clinical features.
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Grupo Borrelia Burgdorferi , Borrelia , Ixodes , Doença de Lyme , Animais , Europa (Continente)/epidemiologia , Humanos , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Inadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.
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Babesia microti/genética , Babesiose/microbiologia , Borrelia burgdorferi/genética , Técnicas de Genotipagem/métodos , Doença de Lyme/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Análise de Sequência de DNA/métodos , Animais , Babesia microti/patogenicidade , Babesiose/diagnóstico , Borrelia burgdorferi/patogenicidade , Genoma Bacteriano , Técnicas de Genotipagem/normas , Humanos , Doença de Lyme/diagnóstico , Camundongos , Técnicas de Diagnóstico Molecular/normas , Sensibilidade e Especificidade , Análise de Sequência de DNA/normas , Carrapatos/microbiologiaRESUMO
As equipas de emergência intra-hospitalar, inicialmente conhecidas como equipas de reanimação, surgiram com o objetivo primário de reverter paragens cardiorrespiratórias, que ocorriam dentro dos hospitais. Mais tarde, percebeu-se que o melhor caminho para diminuir a mortalidade e morbilidade hospitalar é a prevenção desses eventos críticos, que em muitas situações podem ser potencialmente detetados e antecipados. Daí que, atualmente, a ativação destas equipas passa pela identificação de alterações de sinais vitais importantes e interpretados como deterioração clínica aguda. Em Portugal, também se assistiu a essa evolução. Em 2010, por via da Circular Normativa nº 15/DQS/DQCO da Direção Geral de Saúde, as equipas de reanimação evoluíram para Equipas de Emergência Médica Intra-hospitalar (EEMI), tendo como critérios de ativação todas as situações de paragem cardiorrespiratória acontecidas ou eminentes, assim como, disfunções agudas entendidas como potencialmente emergentes. Neste contexto, emerge a importância e a necessidade de solidificar um sistema integrado de resposta à emergência intra-hospitalar, que permita uma intervenção coordenada, eficaz e eficiente por parte de todos os profissionais de saúde, que se venha a traduzir em ganhos em saúde. Como objetivo principal deste trabalho, pretende-se promover a criação e implementação da Equipa de Emergência Médica Intra-hospitalar, numa Unidade Hospitalar da região Norte do país, para uma intervenção precoce e diferenciada à pessoa em situação crítica, em contexto intra-hospitalar. Para a sua realização, optou-se pela Metodologia de Projeto, uma vez que permite estudar um problema atual, centrada na investigação, análise e na implementação de estratégias para a sua resolução. Assim, iniciou-se com o diagnóstico de situação, através da aplicação de um questionário dirigido à equipa médica e de enfermagem e uma entrevista semiestruturada a elementos pertencentes aos órgãos de gestão hospitalar. Os resultados do estudo diagnóstico salientam e reforçam a importância da implementação de equipas dedicadas para a abordagem em situações de emergência intra-hospitalar, uma vez que trará ganhos diretos para o doente, nomeadamente no que concerne a uma atuação mais rápida e diferenciada, refletindo-se na melhoria da qualidade dos cuidados, aumento da sobrevivência e diminuição de complicações imediatas e tardias; e que existem dificuldades na abordagem ao doente crítico, nomeadamente no que respeita à inexistência de uma metodologia de atuação, uniformização de protocolos e necessidade de um plano de formação continua. Depois de validar o objetivo do projeto pelo diagnóstico de necessidades, o plano de ação desenvolveu-se em sete atividades que permitiram desde a divulgação do projeto e dos resultados obtidos, à identificação dos recursos necessários à implementação da EEMI, bem como, a elaboração de um plano de formação para os profissionais que integram a EEMI e a apresentação de uma proposta de protocolo de atuação imediata e ativação da mesma. Acreditamos que os resultados deste trabalho possam constituir a base de trabalho para a implementação da EEMI na referida Unidade Hospitalar, com o propósito da mudança de práticas e aperfeiçoamento dos cuidados, com vista à qualidade dos mesmos e à segurança do doente.
In-hospital emergency teams, initially known as resuscitation teams, appeared with the primary goal of reversing cardiorespiratory arrest, which occurred within hospitals. Later, they realized that the best way to decrease hospital mortality and morbidity is the prevention of these critical events, which in many situations can potentially be detected and anticipated. Hence, currently, the activation of these teams goes through the identification of changes of important vital signs, considered as acute clinical deterioration. In Portugal, this evolution has also been noted. In 2010, through Normative Circular nº 15/DQS/DQCO of the General Directorate of Health, resuscitation teams have evolved into In-Hospital Medical Emergency Teams, with activation criteria of all of cardiopulmonary arrest situations that occurred or are eminent, as well as acute dysfunctions understood as potentially emerging. In this context, the importance and the need to solidify an integrated response system to the intra-hospital emergency emerges, which allows a coordinated, effective and efficient intervention by all health professionals, which will translate into health gains. As the main goal for this research, it is intended to promote the creation and implementation of an In-Hospital Medical Emergency Team, in a Hospital unit in the northern side the country, for an early and differentiated intervention to a person in a critical situation and in an in-hospital context. For its realization, we opted for the Project Methodology, since it allows us to study a current problem, centered on investigation, analysis and implementation of strategies for its resolution. Thus, it started with the diagnosis of the situation, through the application of a questionnaire addressed to the medical and nursing team and a semi-structured interview with elements belonging to the hospital management bodies. The results of the diagnostic study highlight and reinforce the importance of implementing dedicated teams to face in-hospital emergency situations, since it will bring direct benefits for the patient, particularly with a faster and differentiated performance, reflecting it on the improvement in the quality of care, in the increasing of survival and in the decreasing immediate and late complications; and that there are difficulties in approaching critically ill patients, namely when it comes to the lack of a working methodology, the standardization of protocols and the need for a continuous training plan. After validating the project's goal through the needs diagnosis, the action plan was developed in seven activities that allowed, ever since the dissemination of the project and the results obtained, to the identification of the necessary resources for the implementation of In-Hospital Medical Emergency Team, as well as the elaboration of a training plan for the professionals who are part of In-Hospital Medical Emergency Team and the presentation of a proposal for a protocol for immediate action and activation. We believe that the results of this work can form the foundation of work for the implementation of In-Hospital Medical Emergency Team in the referred Hospital, with the purpose of changing practices and improving care, envisioning their quality and patient safety.