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Neutrophils are an important cell type often considered the body's first responders to inflammatory insult or damage. They are recruited to the tissue of the lungs in patients with inflammatory airspace diseases and have unique and complex functions that range from helpful to harmful. The uniqueness of these functions is due to the heterogeneity of the inflammatory cascade and retention in the vasculature. Neutrophils are known to marginate, or remain stagnant, in the lungs even in nondisease conditions. This review discusses the ways in which the recruitment, presence, and function of neutrophils in the airspace of the lungs are unique from those of other tissues, and the complex effects of neutrophils on pathogenesis. Inflammatory mediators produced by neutrophils, such as neutrophil elastase, proresolving mediators, and neutrophil extracellular traps, dramatically affect the outcomes of patients with disease of the lungs.
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Armadilhas Extracelulares , Neutrófilos , Humanos , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Pulmão , Armadilhas Extracelulares/metabolismoRESUMO
Antiviral passive antibody therapy includes convalescent plasma, hyperimmune globulin, and monoclonal antibodies. Passive antibodies have proven effective in reducing morbidity and mortality for SARS-CoV-2 and other infectious diseases when given early in the disease course with sufficiently high specific total and neutralizing antibody levels. Convalescent plasma can be delivered to patients before vaccination implementation or novel drug production. Carefully designed and executed randomized controlled trials near the pandemic outset are important for regulatory bodies, healthcare workers, guideline committees, the public, and the government. Unfortunately, many otherwise well-designed antibody-based clinical trials in COVID-19 were futile, either because they intervened too late in the disease or provided plasma with insufficient antibodies. The need for early treatment mandates outpatient clinical trials in parallel with inpatient trials. Early outpatient COVID-19 convalescent plasma transfusion with high antibody content within 9 days of symptom onset has proven effective in blunting disease progression and reducing hospitalization, thus reducing hospital overcrowding in a pandemic. Convalescent plasma offers the opportunity for hope by enabling community participation in outpatient curative therapy while monoclonal therapies, vaccines, and drugs are being developed. Maintaining the appropriate infrastructure for antibody infusion in both outpatient and inpatient facilities is critical for future pandemic readiness.
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Influenzavirus is among the most relevant candidates for a next pandemic. We review here the phylogeny of former influenza pandemics, and discuss candidate lineages. After briefly reviewing the other existing antiviral options, we discuss in detail the evidences supporting the efficacy of passive immunotherapies against influenzavirus, with a focus on convalescent plasma.
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Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias , ImunoterapiaRESUMO
Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and ß-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, ß-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.
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Apolipoproteína C-III , Apolipoproteínas E , Colesterol , Lipoproteínas , Esquizofrenia , Triglicerídeos , Humanos , Esquizofrenia/sangue , Esquizofrenia/metabolismo , Masculino , Feminino , Triglicerídeos/sangue , Adulto , Colesterol/sangue , Lipoproteínas/sangue , Apolipoproteína C-III/sangue , Apolipoproteínas E/sangue , Pessoa de Meia-Idade , Proteína 4 Semelhante a Angiopoietina/sangue , Proteínas Semelhantes a Angiopoietina/sangue , Apolipoproteína C-II/sangue , Proteína 8 Semelhante a Angiopoietina , Proteína 3 Semelhante a Angiopoietina/sangue , Estudos de Casos e Controles , Hormônios Peptídicos/sangueRESUMO
PURPOSE: Intra-Discal Vacuum phenomenon (IDVP) is well-recognised, yet poorly visualised and poorly understood radiological finding in disc degeneration, particularly with regard to its role in spinal alignment. CT analysis of the lumbar spine in an aging population aims to identify patterns associated with IDVP including lumbopelvic morphology and associated spinal diagnoses. METHODS: An analysis was performed of an over-60s population sample of 2020 unrelated abdominal CT scans, without acute spinal presentations. Spinal analysis included sagittal lumbopelvic reconstructions to assess for IDVP and pelvic incidence (PI). Subjects with degenerative pathologies, including previous vertebral fractures, auto-fusion, transitional vertebrae, and listhesis, were also selected out and analysed separately. RESULTS: The prevalence of lumbar spine IDVP was 50.3% (955/1898) and increased with age (125 exclusions). This increased in severity towards the lumbosacral junction (L1L2 8.3%, L2L3 10.9%, L3L4 11.5%, L4L5 23.9%, and L5S1 46.3%). A lower PI yielded a higher incidence of IDVP, particularly at L5S1 (p < 0.01). A total of 292 patients had IDVP with additional degenerative pathologies, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to a lumbosacral transitional vertebra (p < 0.05). CONCLUSIONS: This study identified the prevalence and severity of IDVP in an aging population. Sagittal patterns that influence the pattern of IVDP, such as pelvic incidence and degenerative pathologies, provide novel insights into the function of aging spines.
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Degeneração do Disco Intervertebral , Vértebras Lombares , Humanos , Vértebras Lombares/diagnóstico por imagem , Idoso , Masculino , Feminino , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/fisiologia , Vácuo , Tomografia Computadorizada por Raios X , PrevalênciaRESUMO
This COVID-19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO-CRD42022369181). Risk of bias was extracted from COVID-19-NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID-19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24-0.40]) had highest hospital reduction efficacy, followed by COVID-19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53-0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48-1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72-0.93]). Earlier in disease onset interventions performed better than later. This meta-analysis allows approximate head-to-head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID-19 in the immunocompromised.
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COVID-19 , Humanos , COVID-19/terapia , Pacientes Ambulatoriais , Soroterapia para COVID-19 , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Hospitalização , Antivirais/uso terapêuticoAssuntos
Células T Invariantes Associadas à Mucosa , Animais , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Camundongos , Humanos , Especificidade de Órgãos/imunologia , Inflamação/imunologia , Hipersensibilidade Respiratória/imunologiaRESUMO
Although recruitment and perceptions of fit are inherently social-as they reflect the interactions between applicants and recruiting firms-applicants' social networks during recruitment can exert both positive and potentially negative consequences for subsequent applicant perceptions and behaviors. In this study, we examine the role of applicants' friends' perceptions of fit with the same recruiting organizations. Integrating ideas from social information processing theory and the person-organization (P-O) fit literature, we argue that friends' P-O fit perceptions drive social learning and social influence processes for applicants, thus predicting applicant perceptions and behaviors toward recruiting firms. In addition, we posit that the direct and indirect relationships between friends' P-O fit perceptions and applicants' own fit perceptions and job choices with recruiting firms are further strengthened by how centrally connected applicants are within their friend networks. Using a sample of 576 applicant-firm observations from 178 job applicants, we found that friends' P-O fit perceptions are positively related to applicant P-O fit perceptions and job choice decisions. Furthermore, applicants' position in their network-assessed via applicants' outdegree centrality within their friend group-strengthened the relationship between friends' P-O fit and applicant P-O fit as well as with their job choice decisions. Our research provides important theoretical and empirical findings on the influence of applicants' friends during recruitment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Infectious diseases are emerging and re-emerging far more frequently than many appreciate. In the past two decades alone, there have been numerous outbreaks (e.g., Ebola, chikungunya, Zika, and Mpox) and pandemics (i.e., swine flu and coronavirus disease 2019) with profound effects to public health, the economy, and society at large. Rather than view these in isolation, there are important lessons pertaining to how best to contend with future outbreaks of emerging infectious diseases. Those lessons span definition (i.e., what constitutes a pandemic), through deficiencies in surveillance, data collection and reporting, the execution of research in a rapidly changing environment, the nuances of study design and hierarchy of clinical evidence, triage according to clinical need as supply chains become overwhelmed, and the challenges surrounding forecasting of outbreaks. Understanding those lessons and drawing on both the successes and failures of the past are imperative if we are to overcome the challenges of outbreak/pandemic responsiveness.
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COVID-19 , Doenças Transmissíveis Emergentes , Surtos de Doenças , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Pandemias , Saúde Pública , PrevisõesRESUMO
Hemozoin is a crystal synthesized by Plasmodium parasites during hemoglobin digestion in the erythrocytic stage. The hemozoin released when the parasites egress from the red blood cell, which is complexed with parasite DNA, is cleared from the circulation by circulating and tissue-resident monocytes and macrophages, respectively. Recently, we reported that intravenous administration of purified hemozoin complexed with Plasmodium berghei DNA (HzPbDNA) resulted in an innate immune response that blocked liver stage development of sporozoites that was dose-dependent and time-limited. Here, we further characterize the organismal, cellular, and molecular events associated with this protective innate response in the liver and report that a large proportion of the IV administered HzPbDNA localized to F4/80+ cells in the liver and that the rapid and strong protection against liver-stage development waned quickly such that by 1 week post-HzPbDNA treatment animals were fully susceptible to infection. RNAseq of the liver after IV administration of HzPbDNA demonstrated that the rapid and robust induction of genes associated with the acute phase response, innate immune activation, cellular recruitment, and IFN-γ signaling observed at day 1 was largely absent at day 7. RNAseq analysis implicated NK cells as the major cellular source of IFN-γ. In vivo cell depletion and IFN-γ neutralization experiments supported the hypothesis that tissue-resident macrophages and NK cells are major contributors to the protective response and the NK cell-derived IFN-γ is key to induction of the mechanisms that block sporozoite development in the liver. These findings advance our understanding of the innate immune responses that prevent liver stage malaria infection.
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Hemeproteínas , Imunidade Inata , Interferon gama , Fígado , Malária , Plasmodium berghei , Esporozoítos , Animais , Plasmodium berghei/imunologia , Esporozoítos/imunologia , Malária/imunologia , Malária/prevenção & controle , Malária/parasitologia , Hemeproteínas/imunologia , Camundongos , Fígado/parasitologia , Fígado/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/imunologia , Macrófagos/parasitologia , DNA de Protozoário/genética , FemininoRESUMO
BACKGROUND: Return to play (RTP) protocols are an important part of recovery management following a sport-related concussion (SRC) and can prevent athletes from returning to competition too early and thereby avoid prolonged recovery times. To assist sporting organizations in the development of RTP guidelines, the Concussion in Sports Group (CISG) provides scientific-based recommendations for the management of SRC in its consensus statement on concussion in sport. OBJECTIVES: This study investigates commonalities and differences among current RTP protocols of international sporting organizations and examines the implementation of the most recent CISG recommendations. METHODS: Concussion guidelines and medical rules of 12 international sporting organizations from contact, collision and combat sports were accessed via the organizations websites and compared regarding the management of SRC and the RTP decision. RESULTS: Only six of the included organizations developed and published their own concussion guidelines, which included an RTP protocol on their website. The number of steps until RTP was similar across the different protocols. Each protocol required at least one medical examination before clearing an athlete to RTP. A high variation among organizations was found for initial resting period after injury, the implementation of sport-specific training drills and the time needed to complete the protocol before returning to competition. At the date of this study (9 September 2023), none of the accessible RTP protocols were updated to include the latest version of the CISG consensus statement. CONCLUSION: To improve the safety of athletes after a head injury, sporting organizations should develop sport-specific guidelines according to the latest CISG consensus statement, and this should be updated regularly. Implementation is especially important in combat sports, where there is a high incidence of head injury. Thus, there is a requirement for the most up-to-date concussion management protocols in these sports.
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Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56-0.97; p = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34-1.51; p = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids.
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Background: Surgical site infections (SSIs) are common healthcare-associated infections, and national guidelines recommend that antimicrobial prophylaxis (AP) be administered 60 min prior to incision. However, there are limited data regarding the "most optimal" time for administration within the 60-min window. Patients and Methods: This was a multicenter, retrospective study of adult (≥18-year-old) patients that underwent an abdominal hysterectomy, colorectal surgery, or craniotomy and received AP within 60 min of incision. Incidence of SSI was compared between patients who received AP 0-30 versus 31-60 min of incision. In addition, a predefined subgroup analysis evaluated incidence of SSI for 15-min intervals within the 60-min timeframe. Results: Of the 277 patients included in the primary analysis, 233 (84.1%) and 44 (15.9%) received AP 0-30 min and 31-60 min prior to incision, respectively. SSIs were documented in 6.0% (14/233) versus 4.5% (2/44) of patients in the primary analysis (p = 0.703). In the secondary analysis, 137 (49.5%), 95 (34.3%), 34 (12.3%), and 11 (4.0%) patients received AP 0-15, 16-30, 31-45, and 46-60 min prior to incision, respectively. There was no difference in incidence of SSIs among the 15-min intervals (4.4% vs. 8.4% vs. 2.9% vs. 9.1%, p = 0.487). Of the 16 patients in this study that incurred a SSI, 5 patients had positive cultures, of which 3 contained bacteria that proved to be resistant to the antibiotic used for AP. Conclusions: The results of our analysis support current national guidelines. Future investigation of different intervals (e.g., AP 15-45 min prior to incision) may be beneficial on the basis of pharmacokinetics of routinely prescribed AP.
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Antibioticoprofilaxia , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Antibioticoprofilaxia/métodos , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Incidência , Fatores de Tempo , Idoso , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Histerectomia/métodos , Craniotomia/efeitos adversosRESUMO
Background: In primary total knee arthroplasty (TKA), there is ongoing controversy about optimal fixation (cemented vs cementless). Cemented TKA remains the gold standard, with the largest body of long-term evidence available to support it. However, cementless TKA implants are gaining popularity due to potential biomechanical advantages and a growing body of literature supporting survivorship. Due to paucity of literature investigating fixation methods in robotic-assisted TKA (Ra-TKA), we aim to compare clinical outcomes of cementless Ra-TKA with those of cemented Ra-TKA. Methods: This is a retrospective cohort study of patients who underwent Ra-TKA by 19 surgeons comparing results of cases using cementless vs cemented fixation. We observed short-term complications, emergency room visits, and readmissions. We collected patient-reported outcomes measurement information system and knee injury and osteoarthritis outcome scores preoperatively and 12 weeks after surgery. Results: A total of 582 TKA cases were included: 335 cementless and 247 cemented. The patients in the cementless group were younger and had a higher body mass index. The cemented group had a higher rate of return to the operating room, with manipulation under anesthesia for stiffness being the most common indication in both groups. There were no statistically significant differences in 30-day readmissions, 90-day emergency room visits, or patient-reported outcomes. Conclusions: Our retrospective study demonstrated higher return to operating room in the cemented group vs the cementless group. We reported no differences in any other short-term outcomes between the cementless and cemented Ra-TKA. Our data support efficacy and safety of cementless Ra-TKA at 3-month follow-up.
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INTRODUCTION: Powered robotic exoskeleton (PRE) physiotherapy programmes are a relatively novel frontier which allow patients with reduced mobility to engage in supported walking. Research is ongoing regarding their utility, risks, and benefits. This article describes the case of two fractures occurring in one patient using a PRE. CASE: We report the case of a 54 year old man who sustained bilateral tibial fractures while using a PRE, on a background of T10 AIS A SCI. The initial session was discontinued due to acute severe bilateral knee swelling after approximately 15 min. The patient attended their local hospital the following day, where radiographs demonstrated bilateral proximal tibial fractures. The patient was treated with manipulation under anaesthetic and long-leg casting for five weeks, at which point he was stepped down to hinged knee braces which were weaned gradually while he remained non-weight bearing for 12 weeks. The patient was investigated with DEXA scan and was diagnosed with osteoporosis. He was liaised with rheumatology services and bone protection was initiated. Fracture healing was achieved and weight-bearing precautions were discontinued, however this period of immobilisation led to significant spasticity. The patient was discharged from orthopaedic services, with ongoing rehabilitation and physiotherapy follow-up. CONCLUSION: PRE assisted physiotherapy programmes are a promising concept in terms of rehabilitation and independence, however they are not without risk and it is important that both providers and patients are aware of this. Furthermore, SCI patients are at increased risk for osteoporosis and should be monitored and considered for bone protection.
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Exoesqueleto Energizado , Osteoporose , Traumatismos da Medula Espinal , Fraturas da Tíbia , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/reabilitação , Fraturas da Tíbia/complicações , CaminhadaRESUMO
Contact tracing, the practice of isolating individuals who have been in contact with infected individuals, is an effective and practical way of containing disease spread. Here we show that this strategy is particularly effective in the presence of social groups: Once the disease enters a group, contact tracing not only cuts direct infection paths but can also pre-emptively quarantine group members such that it will cut indirect spreading routes. We show these results by using a deliberately stylized model that allows us to isolate the effect of contact tracing within the clique structure of the network where the contagion is spreading. This will enable us to derive mean-field approximations and epidemic thresholds to demonstrate the efficiency of contact tracing in social networks with small groups. This analysis shows that contact tracing in networks with groups is more efficient the larger the groups are. We show how these results can be understood by approximating the combination of disease spreading and contact tracing with a complex contagion process where every failed infection attempt will lead to a lower infection probability in the following attempts. Our results illustrate how contact tracing in real-world settings can be more efficient than predicted by models that treat the system as fully mixed or the network structure as locally treelike.
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Busca de Comunicante , Epidemias , Humanos , Busca de Comunicante/métodos , Quarentena , Epidemias/prevenção & controle , Rede SocialRESUMO
INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality. This study aims to implement a primary-tertiary shared care model to improve detection rates for FH. The primary objective is to evaluate the implementation of a shared care model and support package for genetic testing of FH. This protocol describes the design and methods used to evaluate the implementation of the shared care model and support package to improve the detection of FH. METHODS AND ANALYSIS: This mixed methods pre-post implementation study design will be used to evaluate increased detection rates for FH in the tertiary and primary care setting. The primary-tertiary shared care model will be implemented at NSW Health Pathology and Sydney Local Health District in NSW, Australia, over a 12-month period. Implementation of the shared care model will be evaluated using a modification of the implementation outcome taxonomy and will focus on the acceptability, evidence of delivery, appropriateness, feasibility, fidelity, implementation cost and timely initiation of the intervention. Quantitative pre-post and qualitative semistructured interview data will be collected. It is anticipated that data relating to at least 62 index patients will be collected over this period and a similar number obtained for the historical group for the quantitative data. We anticipate conducting approximately 20 interviews for the qualitative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by the ethics review committee (Royal Prince Alfred Hospital Zone) of the Sydney Local Health District (Protocol ID: X23-0239). Findings will be disseminated through peer-reviewed publications, conference presentations and an end-of-study research report to stakeholders.
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Hiperlipoproteinemia Tipo II , Atenção Primária à Saúde , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Hiperlipoproteinemia Tipo II/genética , Atenção Primária à Saúde/métodos , Testes Genéticos/métodos , Projetos de Pesquisa , New South Wales , Diagnóstico PrecoceRESUMO
BACKGROUND: Plasma collected from recovered patients with COVID-19 (COVID-19 convalescent plasma [CCP]) was the first antibody-based therapy employed to fight the COVID-19 pandemic. While the therapeutic effect of early administration of CCP in COVID-19 outpatients has been recognized, conflicting data exist regarding the efficacy of CCP administration in hospitalized patients. OBJECTIVES: To examine the effect of CCP compared to placebo or standard treatment, and to evaluate whether time from onset of symptoms to treatment initiation influenced the effect. DATA SOURCES: Electronic databases were searched for studies published from January 2020 to January 2024. STUDY ELIGIBILITY CRITERIA: Randomized clinical trials (RCTs) investigating the effect of CCP on COVID-19 mortality in hospitalized patients with COVID-19. PARTICIPANTS: Hospitalized patients with COVID-19. INTERVENTIONS: CCP versus no CCP. ASSESSMENT OF RISK OF BIAS: Cochrane risk of bias tool for RCTs. METHODS OF DATA SYNTHESIS: The random-effects model was used to calculate the pooled risk ratio (RR) with 95% CI for the pooled effect estimates of CCP treatment. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the certainty of evidence. RESULTS: Twenty-seven RCTs were included, representing 18,877 hospitalized patients with COVID-19. When transfused within 7 days from symptom onset, CCP significantly reduced the risk of death compared to standard therapy or placebo (RR, 0.76; 95% CI, 0.61-0.95), while later CCP administration was not associated with a mortality benefit (RR, 0.98; 95% CI, 0.90-1.06). The certainty of the evidence was graded as moderate. Meta-regression analysis demonstrated increasing mortality effects for longer interval to transfusion or worse initial clinical severity. CONCLUSIONS: In-hospital transfusion of CCP within 7 days from symptom onset conferred a mortality benefit.