RESUMO
Influenza infection is associated with cardiovascular complications that range significantly in presentation and severity. The cumulative incidence of cardiovascular complications due to laboratory-confirmed influenza, however, is not reported in the literature. We conducted a systematic review and random-effects meta-analysis to evaluate the cumulative incidence and mortality rate of influenza virus-related cardiovascular complications in hospitalized patients. We searched the PubMed and EMBASE databases for studies reporting acute myocardial infarction (AMI), heart failure (HF), arrhythmia of any kind, stroke or transient ischemic attack (TIA), and myocarditis in hospitalized patients with laboratory-confirmed influenza virus infection. Prospective studies, retrospective cohort studies, and randomized controlled trials (RCTs) were included in the analysis. We followed the PRISMA checklist and used 95% confidence intervals (CIs) to report meta-analysis outcomes. This study was registered on PROSPERO (CRD42023427849). After retrieving 2803 studies, we identified 19 studies (18 observational and 1 RCT) with relevant data, and we included 6936 patients in our analysis, of whom 690 (9.9%) developed a cardiovascular outcome of interest. The cumulative incidence of HF was 17.47% (95% CI: 5.06%-34.54%), arrhythmia of any kind 6.12% (95% CI: 0.00%-21.92%), myocarditis 2.56% (95% CI: 0.66%-5.38%), AMI 2.19% (95% CI: 1.03%-3.72%), and stroke or TIA 1.14% (95% CI: 0.00%-4.05%). The in-hospital mortality rate from cardiovascular events was 1.38% (95% CI: 0.00%-4.80%). Cardiovascular complications occur in patients with influenza virus infection, with the cumulative incidence of specific cardiac manifestations varying considerably (1.51%-17.47%). Preventive strategies and close clinical monitoring after infection remain a priority.
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Doenças Transmissíveis , Insuficiência Cardíaca , Influenza Humana , Ataque Isquêmico Transitório , Infarto do Miocárdio , Miocardite , Orthomyxoviridae , Acidente Vascular Cerebral , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Incidência , Infarto do Miocárdio/complicações , Arritmias Cardíacas , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown. AIMS: To investigate the prevalence of SLD and liver fibrosis among patients with RA. METHODS: We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02-47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89-23.07%) and 10.35% (95% CI: 5.55-18.48%), respectively. BMI ≥ 30 kg/m2, (aOR 6.23; 95% CI: 1.95-19.88), diabetes (aOR 5.90; 95% CI: 1.94-17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12-7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69-79.70) was also independently associated with high-risk NASH. CONCLUSIONS: The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD.
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Artrite Reumatoide , Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Inquéritos Nutricionais , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Cirrose Hepática/epidemiologiaRESUMO
BACKGROUND: Thymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. METHODS: Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. RESULTS: A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25]) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to Tα1. CONCLUSIONS: Tα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. CLINICAL TRIALS REGISTRATION: NCT04487444.
Assuntos
COVID-19 , Linfopenia , Timosina , Humanos , Timalfasina/uso terapêutico , Timosina/uso terapêutico , COVID-19/complicações , Projetos Piloto , Estudos Prospectivos , Hipóxia/terapia , Hipóxia/tratamento farmacológico , OxigênioRESUMO
BACKGROUND AND AIMS: Liver disease remains a leading cause of morbidity and mortality among people living with HIV (PLWH). Emerging data suggest that PLWH are at high risk for developing nonalcoholic fatty liver disease (NAFLD). The aim of this review is to examine the current literature and provide an accurate estimate of the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, and identify potential risk factors for NAFLD in PLWH. METHODS: We searched PubMed and Embase databases to identify studies reporting the prevalence of NAFLD and/or fibrosis in PLWH monoinfection. We performed a random effects meta-analysis of proportions to estimate the pooled prevalence of NAFLD, NASH, and fibrosis among PLWH monoinfection. We also examined potential risk factors for NAFLD by comparing characteristics of PLWH monoinfection with and without NAFLD. RESULTS: A total of 43 studies, reporting data for 8230 patients, met our eligibility criteria and were included in the meta-analysis. Based on imaging studies the overall pooled prevalence of NAFLD and moderate liver fibrosis (METAVIR ≥ F2) among PLWH monoinfection was 33.9% (95% confidence interval [CI], 29.67%-38.39%), and 12.00% (95% CI, 10.02%-14.12%), respectively. Based on biopsy studies, prevalence of NASH and significant liver fibrosis (stage ≥F2 on histology) was 48.77% (95% CI, 34.30%-63.34%) and 23.34% (95% CI, 14.98%-32.75%), respectively. Traditional metabolic syndrome and HIV-related factors were associated with NAFLD in PLWH. CONCLUSIONS: Our study confirms that the burden of NAFLD, NASH, and fibrosis is high among PLWH monoinfection. Prospective longitudinal studies are needed to delineate NAFLD, NASH, and fibrosis risk factors, and identify early interventions and new therapies for NAFLD in this population.
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Infecções por HIV , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Estudos Prospectivos , Fígado/patologia , Cirrose Hepática/patologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/patologiaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.
Assuntos
Vírus da Hepatite A , Hepatite A , Vírus da Hepatite E , Hepatite E , Hepatopatia Gordurosa não Alcoólica , Humanos , Vírus da Hepatite B , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Anticorpos Anti-Hepatite A , Fatores de Risco , Hepatite A/complicações , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Hepatite E/epidemiologia , Cirrose Hepática , Anticorpos Anti-Hepatite BRESUMO
BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.
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Tratamento Farmacológico da COVID-19 , Adulto , Proteínas de Repetição de Anquirina Projetadas , Método Duplo-Cego , Humanos , Proteínas Recombinantes de Fusão , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy of convalescent plasma (CP) for the treatment of coronavirus disease 2019 (COVID-19) remains unclear. METHODS: In a matched cohort analysis of hospitalized patients with severe COVID-19, the impact of CP treatment on in-hospital mortality was evaluated using univariate and multivariate Cox proportional-hazards models, and the impact of CP treatment on time to hospital discharge was assessed using a stratified log-rank analysis. RESULTS: In total, 64 patients who received CP a median of 7 days after symptom onset were compared to a matched control group of 177 patients. The incidence of in-hospital mortality was 12.5% and 15.8% in the CP and control groups, respectively (Pâ =â .52). There was no significant difference in the risk of in-hospital mortality between the 2 groups (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] .39-2.20). The overall rate of hospital discharge was not significantly different between the 2 groups (rate ratio [RR] 1.28, 95% CI .91-1.81), although there was a significantly increased rate of hospital discharge among patients 65-years-old or greater who received CP (RR 1.86, 95% CI 1.03-3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% reaction rate observed per unit transfused). CONCLUSIONS: We did not demonstrate a significant difference in risk of mortality or rate of hospital discharge between the CP and control groups. There was a signal for improved outcomes among the elderly, and further adequately powered randomized studies should target this subgroup when assessing the efficacy of CP treatment.
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COVID-19 , Idoso , COVID-19/terapia , Estudos de Coortes , Humanos , Imunização Passiva , SARS-CoV-2 , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
BACKGROUND: Hospital readmissions are associated with poor patient outcomes and increased health resource utilisation. The need to study readmission patterns is even bigger during a pandemic because the burden is further stretching the healthcare system. METHODS: We reviewed the initial hospitalisation and subsequent readmission for 19 patients with confirmed COVID-19 in the largest statewide hospital network in Rhode Island, US, from March 1st through April 19th, 2020. We also compared the characteristics and clinical outcomes between readmitted and non-readmitted patients. RESULTS: Of the 339 hospitalised patients with COVID-19, 279 discharged alive. Among them, 19/279 were readmitted (6.8%) after a median of 5 days. There was a significantly higher rate of hypertension, diabetes, chronic pulmonary disease, liver disease, cancer and substance abuse among the readmitted compared with non-readmitted patients. The most common reasons of readmissions happening within 12 days from discharge included respiratory distress and thrombotic episodes, while those happening at a later time included psychiatric illness exacerbations and falls. The length of stay during readmission was longer than during index admission and more demanding on healthcare resources. CONCLUSION: Among hospitalised patients with COVID-19, those readmitted had a higher burden of comorbidities than the non-readmitted. Within the first 12 days from discharge, readmission reasons were more likely to be associated with COVID-19, while those happening later were related to other reasons. Readmissions characterisation may help in defining optimal timing for patient discharge and ensuring safe care transition.
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COVID-19 , Readmissão do Paciente , Humanos , Tempo de Internação , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Objectives. To identify spatiotemporal patterns of epidemic spread at the community level.Methods. We extracted influenza cases reported between 2016 and 2019 and COVID-19 cases reported in March and April 2020 from a hospital network in Rhode Island. We performed a spatiotemporal hotspot analysis to simulate a real-time surveillance scenario.Results. We analyzed 6527 laboratory-confirmed influenza cases and identified microepidemics in more than 1100 neighborhoods, and more than half of the neighborhoods that had hotspots in a season became hotspots in the next season. We used data from 731 COVID-19 cases, and we found that a neighborhood was 1.90 times more likely to become a COVID-19 hotspot if it had been an influenza hotspot in 2018 to 2019.Conclusions. The use of readily available hospital data allows the real-time identification of spatiotemporal trends and hotspots of microepidemics.Public Health Implications. As local governments move to reopen the economy and ease physical distancing, the use of historic influenza hotspots could guide early prevention interventions, while the real-time identification of hotspots would enable the implementation of interventions that focus on small-area containment and mitigation.
Assuntos
COVID-19/epidemiologia , Influenza Humana/epidemiologia , Humanos , Vírus da Influenza A , Pandemias , Vigilância em Saúde Pública , Rhode Island/epidemiologia , SARS-CoV-2 , Análise Espaço-TemporalRESUMO
BACKGROUND: T2Bacteria assay uses T2 magnetic resonance (T2MR) technology for the rapid diagnosis of bacterial bloodstream infections (BSIs). This FDA cleared technology can detect 5 of the most prevalent pathogens causing bacteremia (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium). Because the significance of discordant results between the T2Bacteria assay and blood culture (BC) remains a challenge, in this case series we reviewed the medical records of patients who had a positive T2Bacteria test and a concurrent negative BC. METHODS: Among 233 participants, we identified 20 patients with 21 (9%) discordant T2Bacteria-positive/BC-negative (T2+/BC-) results. We classified these results based on clinical cultures and clinical evidence. RESULTS: When we analyzed these 21 discordant results in-depth, 11 (52.5%) fulfilled criteria for probable BSI, 4 (19%) for possible BSI, and 6 (28.5%) were presumptive false positives. Among the probable/possible BSIs, discordant results were often associated with patients diagnosed with closed space and localized infections [pyelonephritis (n = 7), abscess (n = 4), pneumonia (n = 1), infected hematoma (n = 1), and osteomyelitis (n = 1)]. Also, within the preceding 2 days of the T2+/BC- blood sample, 80% (16/20) of the patients had received at least one dose of an antimicrobial agent which was active against the T2Bacteria-detected pathogen. CONCLUSIONS: In the majority of discrepant results, the T2Bacteria assay detected a plausible pathogen that was supported by clinical and/or microbiologic data. Discrepancies appear to be associated with closed space and localized infections and the recent use of effective antibacterial agents. The clinical significance and potential implications of such discordant results should be further investigated.
Assuntos
Bacteriemia/microbiologia , Técnicas Bacteriológicas/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Hemocultura , Infecções por Escherichia coli/microbiologia , Reações Falso-Positivas , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Adulto JovemRESUMO
Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, -$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, -$23,587/quality-adjusted life year), PCR with an ASP (ICER, -$19,833/quality-adjusted life year), and PCR without an ASP (ICER, -$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.
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Gestão de Antimicrobianos , Bacteriemia/diagnóstico , Análise Custo-Benefício , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/normas , Simulação por Computador , Humanos , Modelos Teóricos , Fatores de TempoRESUMO
Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.
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Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.
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Produtos Biológicos , Hidradenite Supurativa , Infecções Oportunistas , Humanos , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/epidemiologia , Hidradenite Supurativa/induzido quimicamente , Produtos Biológicos/efeitos adversos , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Infecções Oportunistas/epidemiologia , Fatores Imunológicos/efeitos adversosRESUMO
Patients with rheumatoid arthritis (RA) who receive immunosuppressive medications have a heightened risk of infection. The goal of our study was to calculate the pooled cumulative incidence and risk of infection in patients with RA treated with Janus kinase inhibitors (JAKi). The PubMed and EMBASE databases were queried for randomized controlled trials comparing patients with RA treated with JAKi (upadacitinib, baricitinib, tofacitinib, peficitinib, or filgotinib), defined as the treatment group, compared with control subjects, defined as participants receiving placebo or treatment regimen that was similar to that of participants in the treatment group, with the exception of JAKi. The primary study endpoint was the relative risk (RR) of any-grade and severe infection. The secondary endpoints were RR and cumulative incidence of opportunistic infections, herpes zoster, and pneumonia. The Stata v17 software was used for all data analysis. Results showed that treatment with baricitinib was associated with an increased risk of any-grade (RR 1.34; 95% CI: 1.19-1.52) and opportunistic (RR 2.69; 95% CI: 1.22-5.94) infection, whereas treatment with filgotinib (RR 1.21; 95% CI: 1.05-1.39), peficitinib (RR 1.40; 95% CI: 1.05-1.86) and upadacitinib (RR 1.30; 95% CI: 1.09-1.56) was associated with increased risk of any-grade infection only. Analysis based on type of infection showed a pooled cumulative incidence of 32.44% for any-grade infections, 2.02% for severe infections, 1.74% for opportunistic infections, 1.56% for herpes zoster, and 0.49% for pneumonia in patients treated with any JAKi during the follow-up period. Treatment with specific JAKi in patients with RA is associated with an increased risk of any-grade and opportunistic infections but not severe infection. Close clinical monitoring of patients with RA treated with JAKi is required to establish the long-term infection risk profile of these agents.
Assuntos
Artrite Reumatoide , Azetidinas , Inibidores de Janus Quinases , Piperidinas , Purinas , Pirazóis , Pirimidinas , Sulfonamidas , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Humanos , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Incidência , Purinas/efeitos adversos , Purinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Herpes Zoster/epidemiologia , Herpes Zoster/induzido quimicamente , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/induzido quimicamente , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Niacinamida/análogos & derivados , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Infecções/epidemiologia , Infecções/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Adamantano/análogos & derivados , PiridinasRESUMO
BACKGROUND: Antimicrobial resistance is a major public health threat, and new agents are needed. Computational approaches have been proposed to reduce the cost and time needed for compound screening. AIMS: A machine learning (ML) model was developed for the in silico screening of low molecular weight molecules. METHODS: We used the results of a high-throughput Caenorhabditis elegans methicillin-resistant Staphylococcus aureus (MRSA) liquid infection assay to develop ML models for compound prioritization and quality control. RESULTS: The compound prioritization model achieved an AUC of 0.795 with a sensitivity of 81% and a specificity of 70%. When applied to a validation set of 22,768 compounds, the model identified 81% of the active compounds identified by high-throughput screening (HTS) among only 30.6% of the total 22,768 compounds, resulting in a 2.67-fold increase in hit rate. When we retrained the model on all the compounds of the HTS dataset, it further identified 45 discordant molecules classified as non-hits by the HTS, with 42/45 (93%) having known antimicrobial activity. CONCLUSION: Our ML approach can be used to increase HTS efficiency by reducing the number of compounds that need to be physically screened and identifying potential missed hits, making HTS more accessible and reducing barriers to entry.
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BACKGROUND: Early in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear. METHODS: PubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021-2022. Meta-regression was performed to assess associations between trial characteristics and group representation. RESULTS: We retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%-67.3%]; 2021-2022: 73.8% [95% CI, 71.5%-76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%-47.4%)]; 2021-2022: 51.1% [95% CI, 49.3%-52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03-0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08-0.25]) and lower Asian (coefficient, -0.03 [95% CI, -0.06- -0.003]) and female representation (coefficient, -0.03 [95% CI, -0.07- -0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13-0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13-0.18]), and lower Black representation (coefficient, -0.10 [95% CI, -0.10- -0.08]). CONCLUSIONS: Despite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity.
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COVID-19 , Ensaios Clínicos como Assunto , Humanos , COVID-19/etnologia , COVID-19/epidemiologia , Feminino , Ensaios Clínicos como Assunto/estatística & dados numéricos , Fatores Sexuais , SARS-CoV-2 , Masculino , Etnicidade/estatística & dados numéricos , Seleção de Pacientes , Grupos Raciais , Estados UnidosRESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.
Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.
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Background: Remdesivir is widely used for the management of COVID-19 and several studies have reported bradycardia as a potential side effect associated with this agent. The aim of the present study was to evaluate the incidence rate, severity, and potential risk factors of remdesivir-associated bradycardia. Methods: We performed a retrospective cohort study among hospitalized adult patients with COVID-19 who were treated with remdesivir from March 2020 to October 2021. Our primary outcome of interest was the incidence rate and severity of bradycardia after remdesivir administration. We defined mild bradycardia as a heart rate of 51-59 beats per minute, moderate bradycardia as a heart rate of 41-50 beats per minute, and severe bradycardia as a heart rate of ≤40 beats per minute. We also performed univariable and multivariable regression analyses to determine potential bradycardia risk factors. Baseline characteristics were reported as means with standard deviations or medians with interquartile ranges (IQRs). All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In total, 1,635 patients were included in this study. The median age with IQR was 68 (57-79) years and 51.7% of the patients were male. In total, 606 (37.1%) patients developed bradycardia. Among them, 437 patients (26.7%) developed mild bradycardia, 158 patients (9.7%) moderate bradycardia, while 11 patients (0.7%) experienced severe bradycardia. In our adjusted multivariate logistic regression, the odds of bradycardia development after remdesivir administration were higher among patients with age ≥65 years (OR 1.76, 95% CI: 1.04-2.99, p = 0.04), those with hypertension (OR 1.37, 95% CI: 1.07-1.75, p = 0.01), and obesity (OR 1.32, 95% CI: 1.02-1.68, p = 0.03). Conclusion: More than 1 out of 3 patients (37%) who received remdesivir for COVID-19 developed bradycardia with the majority of these patients developing mild or moderate bradycardia that is usually a benign manifestation not needing treatment in most cases. Age ≥65 years, hypertension, and obesity were potential risk factors for remdesivir-associated bradycardia among hospitalized COVID-19 patients. Clinicians should be aware of this adverse event and consider close clinical monitoring for patients at high risk for this adverse event.
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Introduction: Rituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period. Methods: We searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269). Results: From 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95-27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43-11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02-1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00-0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19-19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19-13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56-43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20-26.00%) for rituximab. Discussion: The cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings. Systematic review registration: Identifier: PROSPERO (CRD42022366269).
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Background: Invasive infection with Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature. Methods: We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia. Results: We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25). Conclusions: Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.