RESUMO
Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
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Autopsia/métodos , COVID-19/mortalidade , COVID-19/virologia , Bulbo Olfatório/virologia , Mucosa Olfatória/virologia , Mucosa Respiratória/virologia , Idoso , Anosmia , COVID-19/fisiopatologia , Endoscopia/métodos , Feminino , Glucuronosiltransferase/biossíntese , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Transtornos do Olfato , Neurônios Receptores Olfatórios/metabolismo , Sistema Respiratório , SARS-CoV-2 , OlfatoRESUMO
Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260 BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3 months, increasing to 17.4% within 6 months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6 months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.
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Anticorpos Monoclonais , Infecções Irruptivas , COVID-19 , Profilaxia Pré-Exposição , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos Retrospectivos , Transplantados , PulmãoRESUMO
PURPOSE: Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. The most frequent genetic defects are found in IL12 or a subunit of its receptor. IL23R deficiency in MSMD has only been reported once, in two pediatric patients from the same kindred with isolated disseminated Bacille Calmette-Guérin disease. We evaluated the impact of a homozygous stop mutation in IL23R (R381X), identified by whole exome sequencing, in an adult patient with disseminated non-tuberculous mycobacterial disease. METHODS: We performed functional validation of the R381X mutation by evaluating IL23R expression and IL-23 signaling (STAT3 phosphorylation, IFN-γ production) in primary cells (PBMCs, EBV-B cells) and cell lines (HeLa) with or without back-complementation of wild-type IL23R. RESULTS: We report on a 48-year-old male with disseminated non-tuberculous mycobacterial disease. We identified and characterized a homozygous loss-of-function stop mutation underlying IL23R deficiency, resulting in near absent expression of membrane bound IL23R. IL23R deficiency was characterized by impaired IL-23-mediated IFN-γ secretion in CD4+, CD8+ T, and mucosal-associated invariant T (MAIT) cells, and low frequencies of circulating Th17 (CD3+CD45RA-CCR4+CXCR3-RORγT+), Th1* (CD45RA-CCR4-CXCR3+RORγT+), and MAIT (CD3+CD8+Vα7.2+CD161+) cells. Although the patient did not have a history of recurrent fungal infections, impaired Th17 differentiation and blunted IL-23-mediated IL-17 secretion in PBMCs were observed. CONCLUSION: We demonstrate that impaired IL-23 immunity caused by a homozygous R381X mutation in IL23R underlies MSMD, corroborating earlier findings with a homozygous p.C115Y IL23R mutation. Our report further supports a model of redundant contribution of IL-23- to IL-17-mediated anti-fungal immunity.1.
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Infecções por Mycobacterium não Tuberculosas , Infecções por Mycobacterium , Masculino , Adulto , Humanos , Criança , Pessoa de Meia-Idade , Interleucina-17/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Infecções por Mycobacterium/etiologia , Infecções por Mycobacterium não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/complicações , Mutação/genética , Interleucina-23 , Predisposição Genética para Doença , Receptores de Interleucina/genéticaRESUMO
BACKGROUND: Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. METHODS: A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. RESULTS: Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7-12.9) in EM patients and 20.9% (95% CI 6.8-64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98-12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. CONCLUSIONS: In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.
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Eritema Migrans Crônico , Doença de Lyme , Síndrome Pós-Lyme , Bélgica , Eritema Migrans Crônico/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologia , Humanos , Doença de Lyme/complicações , Doença de Lyme/tratamento farmacológico , Doença de Lyme/epidemiologia , Síndrome Pós-Lyme/complicações , Estudos ProspectivosRESUMO
BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.
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Infecções por HIV , Saúde Pública , Atenção à Saúde , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Instalações de Saúde , Humanos , Assistência Centrada no PacienteRESUMO
BACKGROUND: Clinical decision support systems are implemented in many hospitals to prevent medication errors and associated harm. They are however associated with a high burden of false positive alerts and alert fatigue. The aim of this study was to evaluate a drug-drug interaction (DDI) clinical decision support system in terms of its performance, uptake and user satisfaction and to identify barriers and opportunities for improvement. METHODS: A quantitative evaluation and end-user survey were performed in a large teaching hospital. First, very severe DDI alerts generated between 2019 and 2021 were evaluated retrospectively. Data collection comprised alert burden, override rates, the number of alert overrides reviewed by pharmacists and the resulting pharmacist recommendations as well as their acceptance rate. Second, an e-survey was carried out among prescribers to assess satisfaction, usefulness and relevance of DDI alerts as well as reasons for overriding. RESULTS: A total of 38,409 very severe DDI alerts were generated, of which 88.2% were overridden by the prescriber. In 3.2% of reviewed overrides, a recommendation by the pharmacist was provided, of which 79.2% was accepted. False positive alerts were caused by a too broad screening interval and lack of incorporation of patient-specific characteristics, such as QTc values. Co-prescribing of a non-vitamin K oral anticoagulant and a low molecular weight heparin accounted for 49.8% of alerts, of which 92.2% were overridden. In 88 (1.1%) of these overridden alerts, concurrent therapy was still present. Despite the high override rate, the e-survey revealed that the DDI clinical decision support system was found useful by prescribers. CONCLUSIONS: Identified barriers were the lack of DDI-specific screening intervals and inclusion of patient-specific characteristics, both leading to a high number of false positive alerts and risk for alert fatigue. Despite these barriers, the added value of the DDI clinical decision support system was recognized by prescribers. Hence, integration of DDI-specific screening intervals and patient-specific characteristics is warranted to improve the performance of the DDI software.
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Sistemas de Apoio a Decisões Clínicas , Sistemas de Registro de Ordens Médicas , Interações Medicamentosas , Humanos , Erros de Medicação/prevenção & controle , Estudos RetrospectivosRESUMO
BACKGROUND: The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. METHODS: This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). RESULTS: All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. CONCLUSIONS: Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.
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Infecções por HIV , Transplante de Órgãos , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , Anticorpos Antivirais , HIV , Infecções por HIV/complicações , Humanos , Imunogenicidade da Vacina , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: Periprosthetic shoulder infection (PSI) remains a devastating complication after reverse shoulder arthroplasty (RSA). Currently, scientific data related to the management of PSI are limited, and the optimal strategy and related clinical outcomes remain unclear. Guidelines from the Infectious Diseases Society of America for the management of periprosthetic joint infection are mainly based on data from patients after hip and knee arthroplasty. The aim of this study was to evaluate whether these guidelines are also valid for patients with PSI after RSA. In addition, the functional outcome according to the surgical intervention was assessed. METHODS: An RSA database was retrospectively reviewed to identify infections after primary and revision RSAs, diagnosed between 2004 and 2018. Data collected included age, sex, indication for RSA, causative pathogen, surgical and antimicrobial treatment, functional outcome, and recurrence. RESULTS: Thirty-six patients with a PSI were identified. Surgical treatment was subdivided into débridement and implant retention (DAIR) (n = 6, 17%); 1-stage revision (n = 1, 3%); 2-stage revision (n = 16, 44%); multiple-stage revision (>2 stages) (n = 7, 19%); definitive spacer implantation (n = 2, 6%); and resection arthroplasty (n = 4, 11%). The most common causative pathogens were Staphylococcus epidermidis (n = 11, 31%) and Cutibacterium acnes (n = 9, 25%). Recurrence was diagnosed in 4 patients (11%), all of whom were initially treated with a DAIR approach. The median follow-up period was 36 months (range, 24-132 months). CONCLUSION: PSI is typically caused by low-virulence pathogens, which often are diagnosed with a delay, resulting in chronic infection at the time of surgery. Our results indicate that treatment of patients with chronic PSI with DAIR has a high recurrence rate. In addition, implant exchange (ie, 1- and 2-stage exchange) does not compromise the functional result as compared with implant retention. Thus, patients with chronic PSI should be treated with implant exchange. Future research should further clarify which surgical strategy (ie, 1-stage vs. 2-stage exchange) has a better outcome overall.
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Artroplastia do Ombro , Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Artroplastia do Ombro/efeitos adversos , Desbridamento , Humanos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Evidence supports the implementation of outpatient parenteral antimicrobial therapy (OPAT) as standard of care. Until 2015 the overall experience with OPAT in Belgium remained limited. The aim of this study was to evaluate the efficacy and safety of a Belgian 'OPAT at home' program, which was implemented in University Hospitals Leuven starting from January 2017. METHODS: A mono-centric, prospective, observational study was carried out. All OPAT cases discharged between 10 January 2017 and 10 January 2019 were included in the study. Relevant demographic and clinical patient data were collected. The outcomes were clinical cure rate, OPAT related readmission rate, adverse event rate and patients' satisfaction. RESULTS: Over the two-year study period, 152 OPAT episodes were started in 130 patients, resulting in 3153 avoided hospitalization days which corresponds to 5.4 freed hospital beds. Urinary tract infections accounted for 40.8% of OPAT courses and temocillin was the most frequently used antibiotic (24.3%). Cure was achieved in 97.9% of the OPAT episodes. During 22 (14.5%) OPAT episodes, patients experienced adverse events, including line related adverse events (7.9%) and adverse drug events (6.6%). An OPAT related readmission rate of 9.2% was observed, mostly related to line-associated adverse events. All patients who completed the satisfaction survey (n = 23) were very satisfied with their OPAT course. CONCLUSION: The University Hospitals Leuven OPAT program is associated with a high level of clinical cure and low all-cause readmission and adverse event rates. Improvement actions are described to further reduce the readmission rate to less than 5.0%.
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Assistência Ambulatorial/estatística & dados numéricos , Anti-Infecciosos/uso terapêutico , Infusões Parenterais/estatística & dados numéricos , Atenção Terciária à Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Coxiella burnetii is the etiological agent of Q fever, a zoonosis. Vascular infections are associated with significant morbidity and mortality. Osteoarticular Q fever infections are rare. We describe a case of vertebral osteomyelitis with associated infection of an abdominal aortic endograft, caused by C. burnetii. Most probably, an initial pyogenic vertebral osteomyelitis extended locally to the endograft. Treatment consisted of antibiotic therapy and surgical resection of the infected aortic endograft and in situ reconstruction with autogenous superficial femoral vein grafts.
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Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Coxiella burnetii/isolamento & purificação , Procedimentos Endovasculares/efeitos adversos , Osteomielite/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Febre Q/microbiologia , Idoso , Antibacterianos/uso terapêutico , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Implante de Prótese Vascular/instrumentação , Coxiella burnetii/efeitos dos fármacos , Remoção de Dispositivo , Procedimentos Endovasculares/instrumentação , Feminino , Veia Femoral/transplante , Humanos , Osteomielite/complicações , Osteomielite/diagnóstico , Osteomielite/terapia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/terapia , Febre Q/diagnóstico , Febre Q/terapia , Resultado do TratamentoRESUMO
SUMMARY: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. AVAILABILITY AND IMPLEMENTATION: Source code, binaries and documentation are available on http://rega.kuleuven.be/cev/regadb. RegaDB is written in the Java programming language, using a web-service-oriented architecture.
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Bases de Dados Factuais , Software , Viroses , Sistemas de Gerenciamento de Base de Dados , Humanos , Viroses/diagnóstico , Viroses/terapia , Viroses/virologiaRESUMO
BACKGROUND: The presence of anti-interferon (IFN)-α2 autoantibodies is a strong indicator of severe disease course during viral infections and is observed in autoimmune diseases (e.g., myasthenia gravis). Detection of these autoantibodies during severe bacterial infections is understudied. Multiple anti-IFN-α2 autoantibody screening assays are available. However, the results do not always correlate with the neutralizing capacity of the autoantibodies. METHODS: Anti-IFN-α2 antibodies were measured by a Luminex-based assay in serum samples from individuals admitted to the intensive care unit infected with influenza (n = 38), invasive bacteria (n = 152), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 52). Anti-IFN-α2 antibodies were also studied in individuals with myasthenia gravis (n = 22) and in healthy individuals (n = 37). Individuals testing positive by Luminex were subsequently tested by enzyme-linked immunosorbent assay (ELISA) and tested for nonspecific reactivity and neutralization. RESULTS: Three of 16 Luminex-positive samples had nonspecific reactivity, 11/16 were positive by ELISA, and 10/16 had neutralizing activity. Anti-IFN-α2 antibodies were found in individuals infected with SARS-CoV-2 (7/52), influenza (3/38), invasive bacteria [2/152, of which 1 was Legionella pneumophilia and was 1 Escherichia coli (E. coli) (out of 39 E. coli infections)], and in individuals with myasthenia gravis (2/22). CONCLUSIONS: Anti-IFN-α2 autoantibodies were detected in viral infections, myasthenia gravis, and rarely in bacterial infections. ELISA and Luminex screening assays do not give similar results. Nonspecific reactivity and functional assays are necessary to validate the screening test result.
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OBJECTIVE: Describe the prevalence and characteristics of people living with HIV (PLWH) in Belgium with limited/exhausted treatment options. METHODS: A cross-sectional, multicenter study involving adult treatment-experienced individuals with limited/exhausted treatment options defined as having a multi-drug resistant HIV-1 or a history of multiple treatment changes. The primary outcome was to determine the prevalence of these individuals and classify them based on their two most recent consecutive HIV-1 viral loads (VLs): suppressed (2 VLs < 50 copies/mL), intermediate (≥1 VL between 50-200 copies/mL), or unsuppressed (2 VLs > 200 copies/mL). Secondary outcome was to characterize the participants included in this analysis. RESULTS: There were 119 individuals included (prevalence of 0.97%; 119 of 12 282 in care). The majority were aged > 50 years (88.2%), women represented 35.3%, and individuals were primarily White (54.7%). Median (IQR) CD4+ T-cell count was 635 (400-875) cells/µL and most (42%) were on a 3-drug ART regimen. Overall, 87.4% were classified as suppressed, 9.2% as intermediate, and 3.4% as unsuppressed. On multivariable analysis, CD4+ T-cell count < 200 cells/µL was associated with being classified as intermediate or unsuppressed (p = 0.004). CONCLUSION: In this analysis of PLWH in Belgium, individuals with limited/exhausted treatment options represented a small fraction. Most were on a 3-drug ART regimen, were virologically suppressed, and had a CD4+ T-cell count within normal range. A small proportion were not virologically suppressed while others, despite being suppressed, were on ≥ 4-drug ART regimens. As such, new therapeutic options are needed to achieve and maintain virologic suppression in such individuals while decreasing their pill burden.
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Infecções por HIV , Carga Viral , Humanos , Bélgica/epidemiologia , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Fármacos Anti-HIV/uso terapêutico , HIV-1 , Prevalência , Contagem de Linfócito CD4RESUMO
BACKGROUND: The rising incidence of immune-mediated inflammatory diseases (IMID) requires innovative management strategies, including effective vaccination. We aimed to assess the impact of an electronic medical record (EMR)-integrated vaccination tool on vaccination coverage among patients with inflammatory bowel diseases (IBD), rheumatological and dermatological conditions. METHODS: A prospective observational study compared vaccination coverage before (2018) and after (2021) implementing the module. Vaccination data for influenza, pneumococcus, hepatitis B and tetanus, and potential predictors were collected from 1430 IMID patients (44.9% male, median age (interquartile range [IQR]) 54 (40-66) years, 789 with IBD, 604 with rheumatological and 37 with dermatological conditions). Data were analysed using McNemar, chi-square tests and multinominal logistic regression. RESULTS: Significant increases in pneumococcus (56.6% to 73.1%, p < .001) and hepatitis B vaccination (62.2% to 75.9%, p < .001) were observed. Influenza vaccination rates increased among IBD (76.2% to 80.5%, p = .006) but remained stable overall (73.1% to 73.2%, p = 1.000). Tetanus vaccination rates decreased (71.5% to 55.0%, p < .001). The proportion of fully vaccinated patients (against influenza in the past year for patients >50 years old and/or under immunosuppressive therapy, against pneumococcus in the past 5 years for patients >65 years old and/or under immunosuppressive therapy and additionally against hepatitis B for IBD patients) rose from 41.3% to 54.8% (p < .001 all using McNemar). Factors associated with vaccinations included age, immunosuppressive therapy and education level. CONCLUSIONS: Increased vaccination coverage was measured after implementing the vaccination tool. The COVID19 pandemic and the 2018 measurement might have increased vaccination awareness. Education of patients and healthcare professionals remains crucial.
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OBJECTIVES: Currently existing pneumococcal vaccines have contributed to a major reduction in pneumococcal disease. However, there remains an unmet need for vaccine coverage of serotypes not included in PCV13 to further reduce the burden of disease. The objective of this review is to assess the potential impact of implementation of the investigational 20-valent pneumococcal conjugate vaccine (PCV20) in the childhood and adult immunization programme in Belgium and Europe. METHODS: A literature search was conducted to identify publications and surveillance reports concerning the effectiveness and safety of pneumococcal vaccines, epidemiological data on pneumococcal disease or serotype distribution dynamics after introduction of systematic vaccination. RESULTS: Serotypes included in PCV20 currently account for the majority of pneumococcal disease in Belgium and Europe. In Belgium, PCV20-serotypes accounted for 71.4% of invasive pneumococcal disease (IPD) cases across all age groups in 2019, of which 39.2% were caused by PCV20-non-PCV13-serotypes. In Europe, these seven serotypes accounted for 37,6% of IPD cases in 2018. PCV20 has proven to be well tolerated in vaccine-naïve adults and elicits a substantial immune response against all serotypes included. CONCLUSION: Due to serotype replacement following the introduction of PCV7 and PCV13, a considerable proportion of pneumococcal disease is currently caused by PCV20-serotypes. PCV20 has the potential of preventing more pneumococcal disease in children and the adult population at risk than the existing conjugate vaccines. The available evidence on safety and immunogenicity of PCV20 is promising, but further research is needed to provide data about vaccine effectiveness, immune response duration and replacement phenomenon after introduction of PCV20.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Adulto , Humanos , Lactente , Vacina Pneumocócica Conjugada Heptavalente , Vacinas Conjugadas , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas PneumocócicasRESUMO
Background: Surgical management of septic arthritis (SA) of the hip aims at treating the infection by either preserving, resecting or replacing the joint. In some cases, joint preservation should be attempted, whereas other cases would benefit from immediate joint resection or replacement. Prognostic factors have been proposed to guide decision-making. We hypothesized that most of these factors can be simplified to three subgroups based on the route of infection: contiguous spreading, direct inoculation or hematogenous seeding. Methods: A total of 41 patients have been treated surgically for SA of the native hip at our tertiary hospital during the last 16 years. Medical records were studied, and various patient and disease characteristics were collated. Results: Significant differences between (1) level of fitness, (2) condition of the hip joint, (3) micro-organisms and (4) chance of femoral head preservation were found for patients with SA of the native hip resulting from the three aforementioned subgroups. Femoral head resection was necessary at one point in 85â¯% of patients. Patients with hematogenous infections of undamaged hips had a reasonable chance (53â¯%) of avoiding joint resection or replacement. Hip arthroplasty was performed on 46.3â¯% of patients, with an infection rate of 10.5â¯%. Conclusion: Patients with SA of the native hip resulting from contiguous spreading, hematogenous seeding or direct inoculation differ significantly and should be considered distinct clinical entities. Route of infection is directly related to the chance of femoral head preservation and should, therefore, guide decision-making. Only patients with hematogenous infection to a previously healthy hip had the possibility of femoral head preservation.
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Advancements in lab-on-a-chip technologies have revolutionized the single-cell analysis field. However, an accessible platform for in-depth screening and specific retrieval of single cells, which moreover enables studying diverse cell types and performing various downstream analyses, is still lacking. As a solution, FLUIDOT is introduced, a versatile microfluidic platform incorporating customizable microwells, optical tweezers and an interchangeable cell-retrieval system. Thanks to its smart microfluidic design, FLUIDOT is straightforward to fabricate and operate, rendering the technology widely accessible. The performance of FLUIDOT is validated and its versatility is subsequently demonstrated in two applications. First, drug tolerance in yeast cells is studied, resulting in the discovery of two treatment-tolerant populations. Second, B cells from convalescent COVID-19 patients are screened, leading to the discovery of highly affine, in vitro neutralizing monoclonal antibodies against SARS-CoV-2. Owing to its performance, flexibility, and accessibility, it is foreseen that FLUIDOT will enable phenotypic and genotypic analysis of diverse cell samples and thus elucidate unexplored biological questions.
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COVID-19 , Microfluídica , Humanos , Microfluídica/métodos , SARS-CoV-2 , Anticorpos , Saccharomyces cerevisiae/genéticaRESUMO
OBJECTIVES: Several sets of criteria have been proposed to classify adult-onset Still's disease (AOSD), those of Yamaguchi being the most commonly used. The Yamaguchi criteria demand the exclusion of other conditions. A clinical scale, recently proposed by Crispin et al., but not yet validated, would allow a positive diagnosis of AOSD in a majority of patients, without the need of thorough diagnostic procedures. METHODS: From a database of 447 patients with classical fever of unknown origin (FUO), collected over a 10-year period (2000-2009) at a general internal medicine department of a university hospital, 22 patients with AOSD according to the Yamaguchi criteria were extracted and compared with 44 controls, matched to index year. Clinical and laboratory parameters were recorded. Sensitivity, specificity and accuracy of the Yamaguchi criteria and of the clinical score were assessed. RESULTS: Lower age, joint symptoms, rash, throat ache, neutrophilic leukocytosis, and elevated erythrocyte sedimentation rate were the principal characteristics supporting a diagnosis of AOSD in patients with FUO. Sensitivity, specificity, and accuracy of the Yamaguchi criteria were 95% or more. The clinical scale, while being specific (98%), lacked sensitivity (55%) and had lower accuracy (83%). CONCLUSIONS: In patients with FUO, the Yamaguchi criteria are a time honored and reliable guide to a diagnosis of AOSD. The clinical scale may serve to rule in, rather than to rule out, AOSD. In many patients, Still's disease is still a diagnosis of exclusion.