Acute musculoskeletal infection in children: assessment and management.

Musculoskeletal infection in children is challenging to treat, and includes septic arthritis, deep tissue infection, osteomyelitis, discitis and pyomyositis. Delays to diagnosis and management, and under-treatment can be life-threatening and result in chronic disability. The British Orthopaedic Association Standards for Trauma include critical steps in the timely diagnosis and management of acute musculoskeletal infection in children, the principles of acute clinical care and the service delivery requirements to appropriately manage this cohort of patients. Orthopaedic and paediatric services are likely to encounter cases of acute musculoskeletal infection in children and thus an awareness and thorough understanding of the British Orthopaedic Association Standards for Trauma guidelines is essential. This article reviews these guidelines and associated published evidence for the management of children with acute musculoskeletal infection.

Assessing the cost-effectiveness of integrated case management of Neglected Tropical Diseases in Liberia.

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated. CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.

OBJECTIVES: The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities. METHODS: Using patients with RA in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 and ≤22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, and low and moderate disease activity, and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSMs). RESULTS: A total of 3,254 patients with RA were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person-years for patients in remission, 6.6 for low disease activity, and 8.0 for moderate disease activity. Using MSMs and compared with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13-2.28) and with moderate disease activity was 1.83 (95% CI 1.30-2.64). CONCLUSION: The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.

Intervenções psicológicas necessárias: a prática como residente no serviço de medicina fetal / Necessary psychological interventions: the practice as a resident in the fetal medicine service / Intervenciones psicológicas necesarias: la práctica como residente en el servicio de medicina fetal

Com os avanços tecnológicos e o aprimoramento da prática médica via ultrassonografia, já é possível detectar possíveis problemas no feto desde a gestação. O objetivo deste estudo foi analisar a prática do psicólogo no contexto de gestações que envolvem riscos fetais. Trata-se de um estudo qualitativo sob formato de relato de experiência como psicólogo residente no Serviço de Medicina Fetal da Maternidade Escola da Universidade Federal do Rio de Janeiro (UFRJ). Os registros, feitos por observação participante e diário de campo, foram analisados em dois eixos temáticos: 1) intervenções psicológicas no trabalho em equipe em consulta de pré-natal, exame de ultrassonografia e procedimento de amniocentese; e 2) intervenções psicológicas em casos de bebês incompatíveis com a vida. Os resultados indicaram que o psicólogo nesse serviço é essencial para atuar de forma multiprofissional na assistência pré-natal para gravidezes de alto risco fetal. Ademais, a preceptoria do residente é relevante para sua formação e treinamento para atuação profissional no campo da psicologia perinatal.(AU)

Face to the technological advances and the improvement of medical practice via ultrasound, it is already possible to detect possible problems in the fetus since pregnancy. The objective of this study was to analyze the psychologist's practice in the context of pregnancies which involve fetal risks. It is a qualitative study based on an experience report as a psychologist trainee at the Fetal Medicine Service of the Maternity School of UFRJ. The records, based on the participant observation and field diary, were analyzed in two thematic axes: 1) psychological interventions in the teamwork in the prenatal attendance, ultrasound examination and amniocentesis procedure; and 2) psychological interventions in cases of babies incompatible to the life. The results indicated that the psychologist in this service is essential to work in a multidisciplinary way at the prenatal care for high fetal risk pregnancies. Furthermore, the resident's preceptorship is relevant to their education and training for professional performance in the field of Perinatal Psychology.(AU)

Con los avances tecnológicos y la mejora de la práctica médica a través de la ecografía, ya se puede detectar posibles problemas en el feto desde el embarazo. El objetivo de este estudio fue analizar la práctica del psicólogo en el contexto de embarazos de riesgos fetal. Es un estudio cualitativo basado en un relato de experiencia como residente de psicología en el Servicio de Medicina Fetal de la Escuela de Maternidad de la Universidade Federal do Rio de Janeiro (UFRJ). Los registros, realizados en la observación participante y el diario de campo, se analizaron en dos ejes temáticos: 1) intervenciones psicológicas en el trabajo en equipo, en la consulta prenatal, ecografía y los procedimientos de amniocentesis; y 2) intervenciones psicológicas en casos de bebés incompatibles con la vida. Los resultados señalaron como fundamental la presencia del psicólogo en este servicio trabajando de forma multidisciplinar en la atención prenatal en el contexto de embarazos de alto riesgo fetal. Además, la tutela del residente es relevante para su educación y formación para el desempeño profesional en el campo de la Psicología Perinatal.(AU)

Atendimento psicossocial à mulher que comete ofensa sexual / Psychosocial attention for women that commit sexual offenses / Atención psicosocial para mujeres que cometen delitos sexuales

Objetivamos apresentar uma proposta de atendimento psicossocial grupal oferecida para mulheres adultas que cometeram ofensa sexual, cuidadoras e mães. A experiência está sendo desenvolvida no Distrito Federal, Brasil, com pessoas do gênero feminino provenientes de encaminhamento judicial. Carece que os profissionais das áreas da justiça, saúde, serviço social e psicologia avancem no estudo e na compreensão desta temática, de modo a pensarem a atuação e o apoio terapêutico a essas mulheres. O modo de atendimento é focal e breve, com ênfase na criação de um ambiente lúdico como facilitador das interações grupais e da discussão sobre os temas: identidade; confiança nas relações afetivas e sociais; vivência pessoal com violência física e sexual; configuração de gênero; e expressão da sexualidade e futuro. A abordagem individual também se baseia no enfoque dos temas mencionados. O oferecimento de ajuda à mulher cuidadora ou à mãe tem participação ativa na interrupção do circuito abusivo sexual, pois essa violência é extremamente ocultada, ocasionando uma prolongada vulnerabilidade para as vítimas. Ressalta-se o valor do texto indicando a descrição de ação voltada para uma população permanentemente não estudada e evitada em seu reconhecimento. Os limites desta proposta encontram-se na falta de outras iniciativas que possibilitem uma discussão sobre essa experiência.(AU)

We aim to present a proposal of a group psychosocial intervention offered for adult female sexual offenders, caregivers, and mothers. The intervention is being developed at Federal District, Brazil, with female people coming from judicial referrals. Professionals in the areas of justice, health, social work, and psychology need to advance in the study and understanding this theme to think about action and therapeutic support for these women. The intervention is a focal and brief approach, with emphasis on the creation of a ludic environment as a facilitator of group interactions and discussion about the themes: identity; trust in affective and social relationships; personal experience with physical and sexual violence; gender configuration; and sexuality expression and future. The individual approach is also based on focusing on these themes. The offering of help to the female caregiver or the mother has an active participation in the interruption of the sexual offense circuit, since this violence is extremely hidden, bringing a prolonged condition of vulnerability to the victims. The value of this text is highlighted indicating the description of an action directed to a population that is permanently not studied and whose recognition is avoided. The limits of this proposal are found in the absence of other initiatives that would allow a discussion about this experience.(AU)

Este texto presenta una propuesta de atención psicosocial grupal destinada a mujeres adultas que han cometido delito sexual, a cuidadoras y madres. La intervención se está desarrollando en el Distrito Federal (Brasil), con personas del género femenino provenientes de remisiones judiciales. Es necesario que los profesionales de las áreas de justicia, salud, trabajo social y psicología avancen en el estudio y comprensión de esta temática para pensar en el desempeño y apoyo terapéutico de estas mujeres. El servicio es enfocado y breve, con énfasis en la creación de un ambiente lúdico como facilitador de interacciones grupales y discusión sobre los temas: identidad; confianza en las relaciones afectivas y sociales; experiencia personal con violencia física y sexual; configuración de género; y expresión de la sexualidad y el futuro. El enfoque individual también se centra en estos temas. La oferta de ayuda a la mujer cuidadora o a la madre es importante para la interrupción del circuito de abuso sexual, ya que esta violencia es extremadamente oculta y provoca una vulnerabilidad prolongada a las víctimas. Se destaca el valor del texto con la descripción de la acción dirigida a una población que no es objeto de estudios ni reconocida. Los límites de esta propuesta se encuentran en la ausencia de otras iniciativas que permitan un debate sobre esta experiencia.(AU)

Fever and hypothermia do not affect the all-cause 30-day hospital readmission.

BACKGROUND: One of the goals of the Affordable Care Act is to decrease hospital readmissions. While widely adhered to, there is no published research to support the practice of delaying discharge if patients exhibit fever or hypothermia in the preceding 24 h, which is the focus of our study. METHODS: Retrospective analysis of the minimal (Tmin) and maximal (Tmax) body temperatures collected during the last 24 h before discharge of 19,038 inpatients. Fever was defined as Tmax >99.5F (+1SD from the mean Tmax) or >100.2F (+2SDs), and hypothermia as Tmin <97.1F (-1SD from the mean Tmin) or <96.7F (-2SDs). RESULTS: The overall readmission rate was 10.2% (highest for General Medicine and Pediatrics). The rate of readmission was not different between normothermic patients and those with abnormal body temperature, except for higher readmission rate (12.2%) for patients with fever at 1SD from Tmax compared with normothermic patients (9.96%). Neither fever nor hypothermia was associated with shorter time to readmission, except for fever at 2 SDs from Tmax (10.6 days) compared with normothermic patients (12.6 days). Surprisingly, univariate analysis revealed that higher Tmax and older age were associated with lower readmission probability. Both uni- and multivariate analysis showed that the presence of fever is associated with lower readmission probability. Evaluating 200 individual cases, the most common explanation for body temperature abnormality was infection and 90% of the preventable readmissions were due to infection. CONCLUSIONS: Abnormal body temperature 24 h prior to discharge was not useful for predicting the probability of readmission.

Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers.

BACKGROUND: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs). METHODS: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring. RESULTS: Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response. CONCLUSIONS: HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Performance of the Universal Vital Assessment (UVA) mortality risk score in hospitalized adults with infection in Rwanda: A retrospective external validation study.

BACKGROUND: We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda. METHODS: We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure. RESULTS: We included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68-0.85); modified UVA, 0.77 (0.68-0.85); qSOFA, 0.66 (0.56-0.75), amalgamated qSOFA, 0.71 (0.61-0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15-0.59); modified UVA >4, 0.35 (0.15-0.59); qSOFA >1, 0.14 (0.07-0.24); amalgamated qSOFA >1, 0.44 (0.20-0.70); and MEWS >5, 0.14 (0.08-0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43-0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82). CONCLUSIONS: The admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.

There are no equal opportunity infectors: Epidemiological modelers must rethink our approach to inequality in infection risk.

Mathematical models have come to play a key role in global pandemic preparedness and outbreak response: helping to plan for disease burden, hospital capacity, and inform nonpharmaceutical interventions. Such models have played a pivotal role in the COVID-19 pandemic, with transmission models-and, by consequence, modelers-guiding global, national, and local responses to SARS-CoV-2. However, these models have largely not accounted for the social and structural factors, which lead to socioeconomic, racial, and geographic health disparities. In this piece, we raise and attempt to clarify several questions relating to this important gap in the research and practice of infectious disease modeling: Why do epidemiologic models of emerging infections typically ignore known structural drivers of disparate health outcomes? What have been the consequences of a framework focused primarily on aggregate outcomes on infection equity? What should be done to develop a more holistic approach to modeling-based decision-making during pandemics? In this review, we evaluate potential historical and political explanations for the exclusion of drivers of disparity in infectious disease models for emerging infections, which have often been characterized as "equal opportunity infectors" despite ample evidence to the contrary. We look to examples from other disease systems (HIV, STIs) and successes in including social inequity in models of acute infection transmission as a blueprint for how social connections, environmental, and structural factors can be integrated into a coherent, rigorous, and interpretable modeling framework. We conclude by outlining principles to guide modeling of emerging infections in ways that represent the causes of inequity in infection as central rather than peripheral mechanisms.

The association between socioeconomic status and the 30- and 90-day risk of infection after total hip arthroplasty : a registry-based cohort study of 103,901 patients with osteoarthritis.

AIMS: The aim of this study was to examine whether socioeconomic status (SES) is associated with a higher risk of infections following total hip arthroplasty (THA) at 30 and 90 days. METHODS: We obtained individual-based information on SES markers (cohabitation, education, income, and savings) on 103,901 THA patients from Danish health registries between 1 January 1995 and 31 December 2017. The primary outcome measure was any hospital-treated infection (i.e. all infections). The secondary outcomes were further specified to specific hospital-treated infections (pneumonia, urinary tract infection, and periprosthetic joint infection). The primary timepoint was within 90 days. In addition, the outcomes were further evaluated within 30 days. We calculated the cumulative incidence, and used the pseudo-observation method and generalized linear regression to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs) for each marker. RESULTS: The cumulative incidence of any infection at 90 days was highest in patients who lived alone (1.5% (95% CI 1.3 to 1.6)) versus cohabitant (0.7% (95% CI 0.7 to 0.8)), had the lowest educational achievement (1.1% (95% CI 1.0 to 1.2)) versus highest (0.7% (95% CI 0.5 to 0.8)), had the lowest income (1.6% (95% CI 1.5 to 1.70)) versus highest (0.4% (95% CI 0.3 to 0.5)), or had lowest savings (1.3% (95% CI 1.2 to 1.4)) versus highest (0.7% (95% CI 0.6 to 0.8)). Within 90 days, the RRs for any infection were 1.3 (95% CI 1.2 to 1.4) for patients living alone versus cohabiting, 1.2 (95% CI 1.0 to 1.3) for low education achievement versus high, 1.7 (95% CI 1.4 to 2.1) for low income versus high income, and 1.5 (95% CI 1.4 to 1.8) for low savings versus high savings. The same trends were also seen for any infections within the first 30 days. CONCLUSION: Our study provides evidence that socioeconomic inequality adversely influences the risk of infection after THA, thus contributing to healthcare disparities and inequalities. We found that living alone, low educational achievement, low income, or low savings were associated with higher risks of infections within the first 30 and 90 days after THA. Therefore, the development of targeted intervention strategies with the aim of increasing awareness of patients identified as being at greatest risk is needed to mitigate the impact of SES on the risk of infections following THA. Cite this article: Bone Joint J 2022;104-B(2):221-226.

Asociación de los resultados de dos pruebas diagnósticas de infección por Helicobacter pylori / Association of the results of two diagnostic tests for Helicobacter pylori infection

Helicobacter pylori es un microrganismo que se considera que afecta al 50% de la población. Se realizó un estudio con diseño no experimental, correlacional y transversal, con el objetivo de determinar la asociación de los resultados de pruebas diagnósticas de infección por H. pylori a través de biopsia obtenida por endoscopía superior y prueba de antígeno de la superficie en mues-tras de heces en 100 pacientes atendidos en el Servicio de Gastroenterología del Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López del Instituto Ecuatoriano de Seguridad Social (IESS), en la ciudad de Guayaquil, Ecuador, durante 2019. La media de la edad en la muestra de estudio fue 37,5 años, con un predominio del género femenino (78%). El 65% de las pruebas de antígeno para la detección de H. pylori en heces resultaron negativas. Los repor-tes de las pruebas de antígeno en heces e histopatología permitieron apreciar diferencias entre estos, pero con predominio de las coincidencias en los diagnósticos positivos. Existió una asocia-ción estadísticamente significativa entre las lesiones inflamatorias de la mucosa gástrica producto de la gastritis crónica atrófica y la infección por H. pylori. Los resultados de las dos pruebas diag-nósticas tuvieron una correlación lineal positiva y débil con significación estadística.

Helicobacter pylori is a microorganism that affects 50% of the population worldwide. A study with a non-experimental, correlational, and cross-sectional design was carried out in order to determine the association of the results of diagnostic tests for H. pylori infection through biopsy obtained by upper endoscopy and surface antigen test in samples of feces in 100 patients. These ones were treated at the Gastroenterology Service of the Ambulatory Surgical Clinic Center (Hospital del Día) Efrén Jurado López of the Ecuadorian Institute of Social Security (IESS), in the city of Guayaquil, Ecuador, during 2019. The mean age in the study sample was 37.5 years old, with a predominance of the female gender (78%). 65% of stool antigen tests for H. pyloriwere negative. The reports of the stool antigen test and histopathology allowed to appreciate differences between them, but with a predominance of the coincidences in the positive diagno-ses. There was a statistically significant association between the inflammatory lesions of the gastric mucosa because of chronic atrophic gastritis and the infection by H. pylori. The results of the two diagnostic tests had a positive and weak linear correlation with statistical significance

Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures. METHODS: We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses. RESULTS: We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates. CONCLUSIONS: The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.

Decision-tree derivation and external validation of a new clinical decision rule (DISCERN-FN) to predict the risk of severe infection during febrile neutropenia in children treated for cancer.

BACKGROUND: In 2017, international guidelines proposed new management of febrile neutropenia in children with cancer, adapted to the risk of severe infection by clinical decision rules (CDRs). Until now, none of the proposed CDRs has performed well enough in high-income countries for use in clinical practice. Our study aimed to build and validate a new CDR (DISCERN-FN) to predict the risk of severe infection in children with febrile neutropenia. METHODS: We did two prospective studies. First, a prospective derivation study included all episodes of febrile neutropenia in children (aged <18 years) with a cancer diagnosis and receiving treatment for it who were admitted for an episode of febrile neutropenia, excluding patients already treated with antibiotics for this episode, febrile neutropenia not induced by chemotherapy, those receiving palliative care, and those with a stem cell allograft for less than 1 year, from April 1, 2007, to Dec 31, 2011 from two paediatric cancer centres in France. We collected the children's medical history, and clinical and laboratory data, and analysed their associations with severe infection. Sipina software was used to derive the CDR as a decision tree. Second, a prospective, national, external validation study was done in 23 centres from Jan 1, 2012, to May 31, 2016. The primary outcome was severe infection, defined by bacteraemia, a positive bacterial culture from a usually sterile site, a local infection with a high potential for extension, or an invasive fungal infection. The CDR was applied a posteriori to all episodes to evaluate its sensitivity, specificity, and negative likelihood ratio. FINDINGS: The derivation set included 539 febrile neutropenia episodes (270 episodes in patients with blood cancer [median age 7·5 years, IQR 3·7-11·2; 158 (59 %) boys and 112 (41%) girls] and 269 in patients with solid tumours [median age 6·6 years, IQR 2·9-14·2; 140 (52 %) boys and 129 (48%) girls]). Significant variables introduced into the decision tree were cancer type (solid tumour vs blood cancer), age, high-risk chemotherapy, level of fever, C-reactive protein concentration (at 24-48 h after admission), and leucocyte and platelet counts and procalcitonin (at admission and at 24-48 h after admission). For the derivation set, the CDR sensitivity was 98% (95% CI 93-100), its specificity 56% (51-61), and the negative likelihood ratio 0·04 (0·01-0·15). 1806 febrile neutropenia episodes were analysed in the validation set (mean age 8·1 years [SD 4·8], 1014 (56%) boys and 792 (44%) girls), of which 332 (18%, 95% CI 17-20) were linked with severe infection. For the validation set, the CDR had a sensitivity of 95% (95% CI 91-97), a specificity of 38% (36-41), and a negative likelihood ratio of 0·13 (0·08-0·21). Our CDR reduced the risk of severe infection to a post-test probability of 0·8% (95% CI 0·2-2·9) in the derivation set and 2·4% (1·5-3·9) in the validation set. The validation study is registered at ClinicalTrials.gov, NCT03434795. INTERPRETATION: The use of our CDR substantially reduced the risk of severe infection after testing in both the derivation and validation groups, which suggests that this CDR would improve clinical practice enough to be introduced in appropriate settings. FUNDING: Ligue Nationale Contre le Cancer.

Multidrug-Resistant Infections in the Developing World.

Antimicrobials are essential in reducing morbidity and mortality from infectious diseases globally. However, due to the lack of effective surveillance measures and widespread overuse, there is an increasing threat to the effectiveness of antimicrobials. Although there is a global increase in antimicrobial resistance, low- and middle-income countries share a much higher burden. Antimicrobial stewardship efforts such as effective surveillance and reduction in overuse can help combat the increase in antimicrobial resistance.

Impactos da COVID-19 nos pacientes oncológicos: uma revisão sistemática / Impacts of COVID-19 on cancer patients: a systematic review

Introdução: Com a pandemia de coronavírus os pacientes oncológicos, que estão em tratamentos, nos quais a maioria são imunossupressores, se tornaram um grupo muito suscetível a formas graves da infecção. Logo, como forma de proteção e prevenção, a realização de exames de rastreio no ambiente hospitalar foi restringida, atrasando diversos diagnósticos e comprometendo a eficácia de tratamentos. Objetivos: Analisar a produção científica acerca do tema câncer e COVID-19, a fim de contribuir com informações sobre o assunto. Métodos: Revisão sistemática da literatura nas bases de dados SciELO, LILACS e PubMed. Os descritores utilizados foram "câncer" AND "COVID-19" de acordo com o Medical Subject Headings (MeSH) e seus equivalentes para a língua portuguesa, conforme os descritores de Ciências da Saúde (DeCS). Foram incluídos artigos originais em inglês e português, sem delimitação temporal. Resultados: Foram encontrados 1.606 artigos e, após utilizar os critérios de inclusão e exclusão, nove foram incluídos para análise na revisão. Dentre os temas centrais abordados pelos estudos selecionados estão o impacto da pandemia em algumas áreas de acompanhamento do paciente oncológico, como: tratamento, telemedicina, diminuição de funcionários no atendimento ao paciente com câncer, diminuição dos ensaios clínicos, redução dos recursos financeiros e apoio psicológico a essa população. Conclusão: A pandemia afetou diretamente o modo de vida desse grupo, que sofreu com uma redução no atendimento médico e nos recursos dispostos a eles. Portanto, nota-se a necessidade de prestar um cuidado mais específico a esses pacientes em situação tão delicada durante a pandemia.

Introduction: During the coronavirus pandemic, oncological patients, who are undergoing treatments in which the majority are immunosuppressant, have become a group very susceptible to severe forms of the infection. Therefore, as a form of protection, their going to hospital environments were restricted, delaying diagnosis and compromising the effectiveness of treatments. Objectives: This study aims to analyze the scientific about the production of the theme cancer and COVID-19 in order to contribute with informations on the subject. Methods: Systematic review of literature using the SciELO, LILACS and PubMed. The following keywords were used: "cancer" AND "COVID-19" according to the Medical Subject Headings (MeSH) and their translation to the Portuguese. Studies in English and Portuguese from inception were included. Results: 1,606 studies were screened and 9 were included in the systematic review after using the inclusion and exclusion criterias. Among the central themes addressed by the selected studies are the pandemic impacts in areas of monitoring oncological patients, such as: treatment, telemedicine, reduction of employees in the care of cancer patients, reduction of clinical trials, reduction of financial resources, and psychological support to that population. Conclusion: The pandemic directly affected the way of life of this group, which suffered from a reduction in medical care and the resources available to them. Therefore, there is a need to provide more specific care to these patients in such a delicate situation during the pandemic.

Extubation in the operating room results in fewer composite mechanical ventilation-related adverse outcomes in patients after liver transplantation: a retrospective cohort study.

BACKGROUND: To investigate the effect of extubation in the operating room (OR) on mechanical ventilation-related adverse outcomes in patients who undergo liver transplantation. METHODS: Patients who underwent liver transplantation between January 2016 and December 2019 were included. According to the timing of extubation, patients were divided into OR extubation group and intensive care unit (ICU) extubation group. The propensity score was used to match OR extubation group and ICU extubation group at a 1:2 ratio by demographical and clinical covariates. The primary outcome was a composite of mechanical ventilation-related adverse outcomes, including 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), and in-hospital moderate to severe pulmonary complications. Secondary outcomes included in-hospital moderate to severe infectious complications, unplanned reintubation rates, ICU and postoperative hospital lengths of stay, and total hospital cost. RESULTS: A total of 438 patients were enrolled. After propensity score matching, 94 patients were in OR extubation group and 148 patients were in ICU extubation group. Incidence of the composite mechanical ventilation-related adverse outcomes was significantly lower in OR extubation group than ICU extubation group, even after adjusting for confounding factors (19.1% vs. 31.8%; Odds Ratio, 0.509; 95% Confidence Index [CI], 0.274-0.946; P=0.031). The duration of ICU stay was much shorter in OR extubation group than ICU extubation group (median 4, Interquartile range [IQR] (3 ~ 6) vs. median 6, IQR (4 ~ 8); P<0.001). Meanwhile, extubation in the OR led to a significant reduction of total hospital cost compared with extubation in the ICU (median 3.9, IQR (3.5 ~ 4.6) 10000 US dollars vs. median 4.1, IQR (3.8 ~ 5.1) 10000 US dollars; P=0.021). However, there were no statistically significant differences in moderate to severe infectious complications, unplanned reintubation rates, and the length of postoperative hospital stay between groups. CONCLUSIONS: Among patients who underwent liver transplantation, extubation in the OR compared with extubation in the ICU, significantly reduced the primary composite outcome of 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), or in-hospital moderate to severe pulmonary complications. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT04261816. Retrospectively registered on 1st February 2020.

Age-adjusted quick Sequential Organ Failure Assessment score for predicting mortality and disease severity in children with infection: a systematic review and meta-analysis.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53-0.81), 0.71 (95% CI 0.36-0.91), and 6.57 (95% CI 4.46-9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66-0.79) and 0.63 (95% CI 0.21-0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21-0.97) and 0.72 (95% CI 0.11-0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Fevers and the social costs of acute infection in wild vervet monkeys.

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

A multi-approach and multi-scale platform to model CD4+ T cells responding to infections.

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. Such modularity improves computational performance and versatility and facilitates data integration. We validated our technology by reproducing known experimental results, including differentiation patterns of CD4+ T cells triggered by different combinations of cytokines, metabolic regulation by IL2 in these cells, and their response to influenza infection. In doing so, we added multi-scale insights to single-scale studies and demonstrated its predictive power by discovering switch-like and oscillatory behaviors of CD4+ T cells that arise from nonlinear dynamics interwoven across three scales. We identified the inflamed lymph node's ability to retain naive CD4+ T cells as a key mechanism in generating these emergent behaviors. We envision our model and the generic framework encompassing it to serve as a tool for understanding cellular and molecular immunological problems through the lens of systems immunology.