Invasive Aspergillosis in Liver Transplant Recipients in The Current Era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Management of infectious disease syndromes in thoracic organ transplants and mechanical circulatory device recipients: a Delphi panel.

PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. RESULTS: Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. CONCLUSIONS: Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study.

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus vs Influenza in Adults Hospitalized With Acute Respiratory Illness From a Prospective Multicenter Study.

BACKGROUND: Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016-2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P < .0001; COPD: 47.6% vs 35.8%, P < .0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06-1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09-1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI, .82-1.28 and OR, 1.17; 95% CI, .91-1.49, respectively). CONCLUSIONS: The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI.

The crown lengthening double guide and the digital Perio analysis.

OBJECTIVE: This article describes a surgical crown lengthening double guide, which was digitally obtained to improve diagnosis, treatment outcome, and follow-up. CLINICAL CONSIDERATIONS: The rehabilitation of anterior dental esthetics should involve interdisciplinary and facially driven planning for achieving pleasant long-term outcomes. Surgical crown lengthening is one of the most common periodontal surgery, which can be assisted by digital tools to improve surgical planning and follow-up. CONCLUSION: The double guide for surgical crown lengthening allows the proper management of hard and soft tissues for achieving a predefined goal based on biological requirements and facially driven planning. In addition, the digital quality control allows the follow-up compared with the pre-operative condition and planned treatment plan. CLINICAL SIGNIFICANCE: The use of digital tools allow the clinician to develop a facially driven planning with proper communication with the team and patient, leading to a shorter, more predictable, and less invasive surgical technique, reducing postoperative inflammation and increasing patient comfort.

Diretriz brasileira para detecção precoce do câncer de mama: desafios para implantação / Brazilian breast cancer early detection guideline: challenges for implementation

Objetivo: Avaliar o acesso e a adesão da população feminina, atendida pelo Sistema Único de Saúde (SUS), à Diretriz Brasileira de Detecção Precoce do Câncer de Mama, em duas cidades de médio porte de uma região metropolitana do estado de São Paulo, Brasil. Métodos: Estudo transversal. Os dados foram coletados no Sistema de Informação do Câncer (Siscan) e nas Secretarias Municipais de Saúde no período de 01/01 a 31/12 de 2017. Resultados: Em Santa Bárbara d'Oeste, foram realizadas 3.106 mamografias: 2.931 (94,4%) BI-RADS® 1-2; 21 (0,7%) BI-RADS® 3; 12 (0,4%) BI-RADS® 4-5; 142 (4,5%) BI-RADS® 0. A maioria dos exames (1.855 ­ 59,7%) foi realizada em mulheres de 50 a 69 anos. A cobertura mamográfica na população de risco foi de 11,2%. O envelhecimento foi relacionado ao BI-RADS® 4-5 (p = 0,005). A idade jovem esteve relacionada ao maior número de BI-RADS® 0 (p = 0,03). Em Vinhedo, foram realizadas 1.996 mamografias: 1.835 (91,9%) BI-RADS® 1-2; 9 (0,45%) BI-RADS® 3; 7 (0,35%) BI-RADS® 4-5; 145 (7,3%) BI-RADS® 0. A maioria dos exames (975 ­ 48,8%) foi realizada em mulheres de 50-69 anos. A população coberta pela mamografia foi de 17%. Reunindo ambas as análises populacionais, evidenciou-se que o envelhecimento esteve relacionado ao maior número de casos suspeitos (p = 0,007). Conclusão: A maioria das mamografias foi realizada em mulheres de 50-69 anos. A cobertura mamográfica ficou aquém da encontrada no Brasil e recomendada pela Organização Mundial da Saúde.

Objective: To evaluate the access and adherence of the female population, assisted by Health Unic System (SUS), to Brazilian Breast Cancer Early Detection Guideline in two medium-sized cities of a metropolitan region in the State of São Paulo, Brazil. Methods: Cross-sectional study. Data were collected from the Cancer Information System (Siscan) and from the Municipal Health Secretariats between 01/01 to 12/31, 2017. Results: In Santa Bárbara d'Oeste 3,106 mammograms were performed: 2,931 (94.4%) BI-RADS® 1-2; 21 (0.7%) BI-RADS® 3; 12 (0.4%) BI-RADS® 4-5; 142 (4.5%) BI-RADS® 0. Most of the exams (1,855 ­ 59.7%) among women aged 50-69 years. The mammographic coverage at risk population was 11.2%. Aging was related to BI-RADS® 4-5 (p = 0.005). The young age was related to the highest number of BI-RADS® 0 (p = 0.03). In Vinhedo 1,996 mammograms were performed: 1,835 (91.9%) BI-RADS® 1-2; 9 (0.45%) BI-RADS® 3; 7 (0.35%) BI-RADS® 4-5; 145 (7.3%) BI-RADS® 0. Most of the exams (975 ­ 48.8%) among women aged 50-69 years. The population covered by mammography was 17%. Gathering both population analysis, it was shown that aging was related to the highest number of suspected cases (p = 0.007). Conclusion: Most mammograms were performed between 50-69 years. Mammographic coverage fell short of that found in Brazil and recommended by the World Health Organization.

Population-based hospitalization burden estimates for respiratory viruses, 2015-2019.

BACKGROUND: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the United States. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of those respiratory viruses (RVs) over 4 years, from July 1, 2015 to June 30, 2019, among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. METHODS: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. RESULTS: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2552; 30.1%), influenza A (2,299; 27.1%), RSV (1082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and White (71%) patients with 60% of patients ≥65 years, 24% 50-64 years, and 16% 18-49 years. The annual burden ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; and 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. CONCLUSIONS: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Práticas alimentares dos trabalhadores da enfermagem e fatores associados: revisão sistemática da literatura / Práticas alimentares dos trabalhadores da enfermagem e fatores associados: revisão sistemática da literatura Feeding practices of Prácticas de alimentación de trabajadores de enfermería y factores asociados: revisión sistemática de la literatura / Feeding practices of nursing workers and associated factors : systematic literature review

Objetivo: descrever práticas alimentares dos trabalhadores da enfermagem relatadas na literatura e os fatores associados. Método: revisão sistemática de artigos publicados entre 2014 e 2021, a partir das bases eletrônicas Publisher Medline, Portal Regional da Biblioteca Virtual de Saúde e Web of Science. Resultados: identificaram-se 982 publicações, sendo 124 duplicadas, permanecendo 858. Após leitura dos títulos e resumos, 34 artigos foram lidos na íntegra. As práticas alimentares adequadas variaram de 23,6% a 55,4%, as práticas alimentares parcialmente adequadas de 25,8% a 52,0% e as práticas alimentares inadequadas de 11,6% a 26,6%. As práticas alimentares saudáveis mostraram-se associadas ao sexo feminino, pessoas com idade mais avançada, maior renda, com filhos, praticantes de atividade física, com melhor qualidade do sono, trabalho diurno e com maior engajamento no trabalho. Conclusões: as práticas alimentares sofrem a influência de múltiplos fatores, entre eles demográficos, socioeconômicos, comportamentais, condições de saúde e laborais.(AU)

Objective: to describe feeding practices of nursing workers reported in the literature and the associated factors. Method: systematic review of articles published betwe en 2014 and 2021, from the electronic databases Publisher Medline, Regional Portal of the Virtual Health Library and Web of Science. Results: 982 publications were identified, of which 124 were duplicates, remaining 858. After reading the titles and abstra cts, 34 articles were read in full. Adequate food practices ranged from 23.6% to 55.4%, partially adequate food practices from 25.8% to 52.0% and inadequate food practices from 11.6% to 26.6%. Healthy eating practices were associated with females, older pe ople, higher incomes, with children, practitioners of physical activity, with better sleep quality, daytime work, and greater engagement at work. Conclusions: dietary practices are influenced by multiple factors, including demographic, socioeconomic, behav ioral, health and work conditions.(AU)

Objetivo: describir prácticas de alimentación de trabajadores de enfermería relatadas en la literatura y factores asociados. Método: revisión sistemática de artículos publicados entre 2014 y 2021, utilizando las bases de datos electrónicas Publisher Medline, Portal Regional de la Biblioteca Virtual en Salud y Web of Science. Resultados: se identificaron 982 publicaciones, siendo 124 duplicadas, quedando 858. De la lectura de títulos y resúmenes, se leyeron 34 artículos. Las prácticas alimentarias adecuadas oscilaron entre el 23,6 % y el 55,4 %, las parcialmente adecuadas entre el 25,8 % y el 52,0 % y , inadecuadas entre el 11,6 % y el 26,6 %. Las prácticas de alimentación saludable se asociaron con mujeres, ancianos, mayores ingresos, con niños, practicantes de activi dad física, con mejor calidad de sueño, trabajo diurno y mayor compromiso en el trabajo. Conclusión: las prácticas s están influenciadas por condiciones demográficas, socioeconómicas, de comportamiento, de salud y trabajo. (AU)

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Prevalência de diabéticos, hipertensos e atividade física em Porto Alegre, Rio Grande do Sul / Prevalencia de diabéticos, hipertensos y actividad física en Porto Alegre, Rio Grande do Sul / Prevalence of diabetic, hypertensive, and physical activity in Porto Alegre, Rio Grande do Sul

Objetivo: identificar a prevalência de diabéticos e hipertensos, a partir dos 18 anos, de acordo com perfil sociodemográfico e de prática de atividade física, no município de Porto Alegre, capital do Estado do Rio Grande do Sul. Método: estudo com dados da Vigilância de Fatores de Risco e proteção para Doenças Crônicas por Inquérito Telefônico do ano de 2019, do tipo transversal, com análise bivariada. Resultados: dos 2.058 indivíduos, predominou o sexo feminino (65,5%), com mais de 60 anos (55,1%), escolaridade até o primeiro grau (31,2%) e que praticavam atividade física (93,4%). A prevalência de diabéticos foi de 279 (13,6%) e de hipertensos, 866 (42,1%). Idade, escolaridade, frequência e duração da atividade física foi associada à Hipertensão. E idade, e escolaridade, com Diabetes. Conclusão: houve alta prevalência de hipertensos e baixa frequência, na prática de atividade física.(AU)

Objective: to identify the prevalence of diabetic and hypertensive patients aged 18 years and over, according to the sociodemographic profile and physical activity practice, in the city of Porto Alegre, capital of the State of Rio Grande of Sul. Method: study with surveillance data of Risk and Protection Factors for Chronic Diseases by Telephone Survey of the year 2019, cross-sectional, with bivariate analysis. Results: of the 2,058 individuals, there was a predominance of females (65.5%), aged over 60 (55.1%), educated up to elementary school (31.2%) and practiced physical activity (93.4 %). The prevalence of diabetics was 279 (13.6%) and of hypertensive patients, 866 (42.1%). Age, education, frequency, and duration of physical activity were associated with Hypertension. And age, and education, with Diabetes. Conclusion: there was high prevalence of hypertensive and low frequency in the practice of physical activity.(AU)

Objetivo: identificar la prevalencia de pacientes diabéticos e hipertensos de 18 años y más, según perfil sociodemográfico y práctica de actividad física, en la ciudad de Porto Alegre, capital del estado de Rio Grande do Sul. Método: estudio con datos de vigilancia de Factores de Riesgo y Protección de Enfermedades Crónicas por Encuesta Telefónica del año 2019, transversal, con análisis bivariado. Resultados: de los 2.058 individuos, hubo predominio del sexo femenino (65,5%), mayores de 60 años (55,1%), con estudios hasta primaria (31,2%) y actividad física practicada (93,4%). La prevalencia de diabéticos fue 279 (13,6%) y de hipertensos, 866 (42,1%). La edad, la educación, la frecuencia y la duración de la actividad física se asociaron con la hipertensión. Y edad y educación, con la diabetes. Conclusión: hubo una alta prevalencia de hipertensos y baja frecuencia en la práctica de actividad física.(AU)

Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial.

BACKGROUND: Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. METHODS: In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. RESULTS: 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. CONCLUSIONS: Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).

Unexpected Cytomegalovirus (CMV) Replication Kinetics in CMV Donor-Seropositive, Recipient-Seronegative Liver Transplant Recipients Receiving Preemptive Antiviral Therapy.

BACKGROUND: Detailed cytomegalovirus (CMV) kinetics in donor CMV-seropositive, recipient CMV-seronegative (D+/R-) transplant recipients receiving preemptive therapy (PET) have not been fully defined. METHODS: The study population consisted of the PET arm of a randomized CMV prevention trial in D+/R- liver transplant recipients. CMV DNA polymerase chain reaction (PCR) assays were performed weekly for 100 days using a sensitive assay. Viral load and clinical parameters were compared for patients with or without high-level increase (defined as higher than the group median log10 increase in viral load from baseline after PET initiation). RESULTS: Among 79 patients, 93.6% (74/79) developed an increase from baseline viral loads of median 120 IU/mL to 3350 IU/mL; 25.7% (19/74) of the patients had peak levels >10 000 IU/mL. None of the patients with rise in viral load underwent testing for CMV resistance, and viremia resolved with PET with valganciclovir. Patients with high-level increase in viral load had a significantly lower rate of recurrent viremia than those without such increase (16/40 [40%] vs 28/39 [71.8%], respectively; P = .004). CONCLUSIONS: A majority of D+/R- recipients had a marked increase in viral load after initiation of PET before resolution of viremia. This phenomenon is associated with lower rates of subsequent recurrent viremia and does not necessarily imply antiviral resistance.

Vaccine Effectiveness Against Acute Respiratory Illness Hospitalizations for Influenza-Associated Pneumonia During the 2015-2016 to 2017-2018 Seasons: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

BACKGROUND: Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). METHODS: Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of "definite/probable pneumonia." We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing reverse transcriptase-polymerase chain reaction-confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. RESULTS: Of 4843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had "definite/probable pneumonia" and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI], 17-53%); by type/subtype, it was 74% (95% CI, 52-87%) influenza A (H1N1)pdm09, 25% (95% CI, -15% to 50%) A (H3N2), and 23% (95% CI, -32% to 54%) influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19-77%). CONCLUSIONS: Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B.

Using capture-recapture methods to estimate influenza hospitalization incidence rates.

BACKGROUND: Accurate population estimates of disease incidence and burden are needed to set appropriate public health policy. The capture-recapture (C-R) method combines data from multiple sources to provide better estimates than is possible using single sources. METHODS: Data were derived from clinical virology test results and from an influenza vaccine effectiveness study from seasons 2016-2017 to 2018-2019. The Petersen C-R method was used to estimate the population size of influenza cases; these estimates were then used to calculate adult influenza hospitalization burden using a Centers for Disease Control and Prevention (CDC) multiplier method. RESULTS: Over all seasons, 343 influenza cases were reported in the clinical database, and 313 in the research database. Fifty-nine cases (17%) reported in the clinical database were not captured in the research database, and 29 (9%) cases in the research database were not captured in the clinical database. Influenza hospitalizations were higher among vaccinated (58%) than the unvaccinated (35%) in the current season and were similar among unvaccinated (51%) and vaccinated (49%) in the previous year. Completeness of the influenza hospitalization capture was estimated to be 76%. The incidence rates for influenza hospitalizations varied by age and season and averaged 307-309 cases/100,000 adult population annually. CONCLUSION: Using C-R methods with more than one database, along with a multiplier method with adjustments improves the population estimates of influenza disease burden compared with relying on a single-data source.

Clinical Influenza Testing Practices in Hospitalized Children at United States Medical Centers, 2015-2018.

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

Coronavirus disease 2019 (COVID-19) Versus Influenza in Hospitalized Adult Patients in the United States: Differences in Demographic and Severity Indicators.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. METHODS: Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016-2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. RESULTS: Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). CONCLUSIONS: While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths.