Developing rights-based standards for children having tests, treatments, examinations and interventions: using a collaborative, multi-phased, multi-method and multi-stakeholder approach to build consensus.

Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020-2022) informed the development of international rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.    Conclusion: This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child. What is Known: • Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. • Professionals report uncertainty and tensions in applying evidence-based practice to children's procedural care. What is New: • This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives. • The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.

Diagnostic Stewardship to Prevent Diagnostic Error.

This Viewpoint discusses the growth of diagnostic stewardship beyond infectious disease to reduce diagnostic errors in other fields.

Utilising Interview Methodology to Inform the Development of New Clinical Assessment Tools for Anxiety in Autistic Individuals Who Speak Few or no Words.

Autistic individuals with intellectual disability who speak few or no words are at high risk of anxiety but are underrepresented in research. This study aimed to describe the presentation of anxiety in this population and discuss implications for the development of assessments. Interviews were conducted with 21 parents/carers of autistic individuals and nine clinicians. Data were analysed using content analysis and interpretative phenomenological analysis. Anxiety behaviours described by parents/carers included increased vocalisation, avoidance and behaviours that challenge. Changes to routine were highlighted as triggering anxiety. Clinicians discussed the importance of identifying an individual's baseline of behaviour, knowing an individual well and ruling out other forms of distress. This study raises considerations for early identification of anxiety and for subsequent support.

Lactantes febriles menores de tres meses sin foco aparente: ¿es necesario cambiar la estrategia de evaluación?: probamos el step by step / Febrile infants of under three months of age without apparent focus: is it necessary to change the assessment strategy?: we tested the step-by-step approach / Lactentes febris com menos de três meses de idade e sem foco aparente: é necessário alterar a estratégia de avaliação?: tentamos o "passo a passo"

Introducción: la fiebre es un motivo muy frecuente de consulta y hasta en un 20% de los pacientes no se encuentra la causa. En el ámbito de la emergentología pediátrica clásicamente ha existido interés en homogeneizar la forma de evaluar los lactantes febriles menores de tres meses. Contar con un protocolo que permita detectar precozmente el niño que cursa una infección bacteriana invasiva (IBI) sin realizar conductas desproporcionadas es todo un desafío. Objetivo: evaluar y comparar la capacidad para identificar IBI en la pauta actual de fiebre sin foco (FSF) como en la estrategia step by step, en lactantes con FSF valorados en el DEP-CHPR. Material y métodos: estudio observacional, descriptivo, retrospectivo y de pruebas diagnósticas. Criterios de inclusión: lactantes menores de 90 días de vida que consultaron en 2017 y 2018 en DEP-CHPR con diagnóstico de FSF. Resultados: se incluyeron 261 lactantes evaluados con la pauta de FSF actual, en ellos se aplicó la estrategia step by step. El rango de edad fue de 84 días (4-88 días) con una media de 41 días. Sexo masculino 148 niños (56,7%). Se registraron 37 infecciones bacterianas (14,2%) de las cuales 3 fueron IBI (1,1%) y 34 fueron no-IBI (13,1%). La sensibilidad para step by step fue de 0,94% y de 0,89 para la pauta actual, con un VPN de 0,98 para ambas estrategias. Discusión: los lactantes menores de 3 meses son más susceptibles por características fisiológicas a infecciones bacterianas invasivas y cuanto más pequeño aumenta aún más la frecuencia. El step by step discrimina a menores de 1 mes en menores de 21 días y otro grupo de más de 21 días. Nuestra pauta no hace esta discriminación y realiza por igual laboratorio en sangre, orina y líquido cefalorraquídeo; realizando en ocasiones estudios cruentos no necesarios. Conclusiones: ambas estrategias aplicadas en esta población resultaron altamente sensibles para identificar infección bacteriana con un VPN elevado. La aplicación de step by step presenta como beneficio adicional evitar con seguridad la punción lumbar en recién nacidos entre los 21 y 28 días.

Introduction: fever is a very frequent reason for consultation and in up to 20% of patients the cause has not been found. In the field of pediatric emergentology, there has been a traditional interest in homogenizing the way of assessing febrile infants under three months of age. Having a protocol that enables early detection of children with IBIs without engaging in disproportionate procedures is a challenge. Objective: to evaluate and compare the ability to identify IBIs in the present FSF regimen as in the Step-by-Step strategy, in infants with FSF assessed at the Pereira Rossell Pediatric Hospital Center. Material and methods: observational, descriptive, retrospective study and diagnostic tests. Inclusion criteria: Infants under 90 days of age who consulted in 2017 and 2018 at the DEP-CHPR with a diagnosis of FSF. Results: 261 infants diagnosed with FSF regimen were included and they all received a Step-by-Step approach. The age range was 84 days (4 - 88) days with a mean of 41 days. Males 148 children (56.7%). There were 37 bacterial infections (14.2%), of which 3 were IBI (1.1%) and 34 were Non-IBI (13.1%). The sensitivity for the Step-by-Step approach was 0.94% and 0.89 for the current regimen, with a NPV of 0.98 for both strategies. Discussion: infants younger than 3 months-old are more susceptible due to physiological characteristics to invasive bacterial infections, and the younger they are, the higher the frequency. The Step-by-Step Approach splits children of under 1 month of age into those under or over 21 days of age. Our guideline does not make this discrimination and performs the same blood, urine and cerebrospinal fluid laboratory tests sometimes carrying out blood tests is not necessary. Conclusions: both approaches used in this population were highly sensitive to the identification of bacterial infections with a high NPV. The application of the "Step-by-Step" approach has the additional benefit of avoiding lumbar puncture to newborns of between 21 and 28 days of age.

Introdução: a febre é um motivo muito comum de consulta e em até 20% dos pacientes a causa não é encontrada. No campo da emergência pediátrica, tradicionalmente tem havido interesse em homogeneizar a forma de avaliação de lactentes febris menores de três meses de idade. Ter um protocolo que permita a detecção precoce de uma criança com IBI sem realizar procedimentos desproporcionais é um desafio. Objetivo: avaliar e comparar a capacidade de identificação de IBI na atual Diretriz da FSF e na estratégia Passo a Passo, em lactentes com FSF avaliados no DEP-CHPR. Material e métodos: estudo observacional, descritivo, retrospectivo e de testes diagnósticos. Critérios de inclusão: Lactentes com menos de 90 dias de idade que consultaram em 2017 e 2018 no Hospital Pediátrico Pereira Rossell do Uruguai com diagnóstico de FSF. Resultados: Foram incluídos 261 lactentes avaliados com a atual diretriz da FSF, nos quais foi aplicada a estratégia Passo a Passo. A faixa etária foi de 84 dias (4 - 88) dias com média de 41 dias. Sexo masculino 148 crianças (56,7%). Foram registradas 37 infecções bacterianas (14,2%), sendo 3 IBI (1,1%) e 34 Não IBI (13,1%). A sensibilidade para Passo a Passo foi de 0,94% e 0,89 para o esquema atual, com VPN de 0,98 para ambas estratégias. Discussão: crianças menores de 3 meses de idade são mais suscetíveis a infecções bacterianas invasivas devido às características fisiológicas e quanto menores, mais frequentes. O Passo a Passo separa crianças menores de 1 mês em dois grupos: menores de 21 dias e acima de 21 dias. Nossa diretriz não faz essa discriminação e realiza exames laboratoriais de sangue, urina e líquido cefalorraquidiano da mesma forma; às vezes realizando estudos de sangue que não são necessários. Conclusões: ambas as estratégias aplicadas nesta população foram altamente sensíveis para identificar infecção bacteriana com alto VPN. A aplicação do "Passo a Passo" apresenta como benefício adicional evitar a punção lombar em recém-nascidos entre 21 e 28 dias.

Eficacia y seguridad del equipo de aspiración de vacío extraoral para prevenir la infección por Sars-cov-2 en personal sanitario expuesto durante procedimientos estomatológicos / Efficacy and safety of extraoral vacuum aspiration equipment to prevent Sars-cov-2 infection in healthcare personnel exposed during stomatological procedures

ANTECEDENTES: El presente documento expone la evaluación de la eficacia y seguridad del equipo de aspiración de vacío extraoral en comparación con el eyector de saliva o el aspirador de secreción con flujo de succión no menor a 50 L/min (actualmente disponibles en la institución), para prevenir la infección por SARS-CoV-2 en personal sanitario expuesto durante procedimientos estomatológicos. ASPECTOS GENERALES: La pandemia por la enfermedad por coronavirus (COVID-19) ha tenido un impacto significativo en la atención odontológica (Abdelrahman et al. 2021; Cagetti et al. 2021). En diversos países, la atención odontológica ambulatoria fue interrumpida al inicio de la pandemia, a excepción de la atención de emergencia y urgencia dental (Abdelrahman et al. 2021; Cagetti et al. 2021). Esta interrupción de las atenciones odontológicas se debió a que 14,tc. 1 el cuidado dental implica un contacto cercano con el paciente durante periodos de tiempo "or prolongados, lo que genera preocupación sobre la transmisión del SARS-CoV-2 a través de la generación de aerosoles durante los procedimientos estomatológicos (Meng, Hua, and Bian 2020; Peng et al. 2020). De acuerdo con los Centers for Disease Control and Prevention (CDC), los dispositivos dentales que generan aerosoles y contaminan el aire incluyen al raspador ultrasónico, la pieza de mano dental de alta velocidad, jeringa de aire o agua, pulido y abrasión por aire (Centers for Disease Control and Prevention 2022). Estos procedimientos generan una mezcla de aerosoles y gotitas (miden 0.001 a 50 pm de diámetro) que contienen sangre y saliva con diversos patógenos (T. S. Singh and Mabe 2009), lo que genera un ambiente con alto potencial de transmisión de enfermedades como la COVID-19 (Peng et al. 2020). En base a este aumento del riesgo de transmisión de SARS-CoV-2 en los trabajadores de salud, los responsables de formular políticas y los equipos clínicos han optado por reevaluar y adaptar la atención odontológica en respuesta a los desafíos de la pandemia por COVID-19 (World Health Organization 2020b). METODOLOGÍA: La búsqueda sistemática se realizó en las bases de datos bibliográficas PubMed, The Cochrane Library, Web of Science y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). Asimismo, se realizó una búsqueda en las páginas web de grupos o instituciones que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), la Haute Authorité de Santé (HAS), el Institute for Quality and Efficiency in HealthCare (IQWiG), el Institute for Clinical and Economic Review (ICER) yen la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), y en las principales instituciones o sociedades especializadas en odontología: la American Dental Association y la British Dental Association. Adicionalmente, se llevó a cabo una búsqueda manual en el motor de búsqueda Google utilizando los términos: (("extra-oral" OR extraoral) AND (vacuum OR aspirator OR suction) AND (COVID-19 OR SARS-CoV-2)) y (("extra-oral" OR extraoral) AND (vacuum OR aspirator OR suction) AND (virus OR viral)); revisando en las diez primeras páginas de resultados, a fin de poder identificar otras publicaciones de relevancia que pudiesen haber sido omitidas por la estrategia de búsqueda o que no hayan sido publicadas en las bases de datos bibliográficas consideradas. Finalmente, se realizó una búsqueda manual de las referencias de los estudios que ingresaron a la fase de texto completo, así como una búsqueda manual en la plataforma ClinicalTrials.gov para identificar ensayos clínicos aleatorizados (ECA) en curso o que no hayan sido publicados aún. RESULTADOS: GPC: gula de práctica clínica; ETS: evaluación de tecnologías sanitarias; RS: revisión sistemática; ECA: ensayo clínico aleatorizado; EO: estudio observacional; LILACS: Literatura Latinoamericana y del Caribe en Ciencias de la Salud; BRISA: Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas; JDA: Japan Dental Association, NHS: National Health Service. Flujograma adaptado de: Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. CONCLUSIONES: El presente dictamen preliminar tuvo por objetivo realizar una evaluación sobre la eficacia y seguridad del equipo de aspiración de vacío extraoral en comparación con el eyector de saliva y el aspirador de secreción con flujo de succión no menor a 50 L/min (actualmente disponibles en la institución), para prevenir la infección por SARS-CoV-2 en personal sanitario expuesto durante procedimientos estomatológicos. Se identificaron una GPC (Hoshi et al.) y cinco documentos de recomendación realizados por Centers for Disease Control and Prevention, World Health Organization, Dental Council of India, Federal Ministry of Health of Nigeria y Government of Canada relevantes para el tema. La GPC emite una recomendación sobre la tecnología de interés; sin embargo, esta recomendación tuvo un muy bajo nivel de evidencia y recomendación débil debido a que se basó en un único estudio de simulación, lo cual no permite extrapolar los resultados a un entorno clínico de la vida real con pacientes o personal de salud. Ninguno de los documentos de recomendación incluidos emite recomendaciones sobre la intervención de interés (equipo de aspiración de vacío extraoral), sino que hacen referencia a los dispositivos evacuadores de alto volumen que son de uso intraoral, diferentes a lo solicitado. Asimismo, recomiendan otras medidas que se deben tomar en cuenta para mitigar la transmisión de enfermedades durante procedimientos generadores de aerosoles, donde destacan el uso de diques dentales, uso de equipo de protección personal adecuado, odontología a cuatro manos, y enjuagues bucales con clorhexidina. En el documento del MINSA, destacan una serie de disposiciones que deben instaurarse al momento de realizar una atención odontológica. Dentro de estas disposiciones destacan las medidas que debe utilizar el personal de salud dental antes, durante y después de la atención (principalmente, el uso del equipo de protección personal), en los establecimientos odontológicos (como una ventilación adecuada) y el esquema de vacunación completo del personal de salud. Las acciones combinadas tendrían un impacto positivo en la prevención de la infección por SARS-CoV-2. Por lo expuesto, el !ETS' no aprueba el uso del equipo de aspiración de vacío extraoral para prevenir la infección por SARS-CoV-2 en personal sanitario expuesto durante procedimientos estomatológicos.

Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022 / Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022

RESUMEN Objetivos. Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). Materiales y métodos. Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. Resultados. Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. Conclusiones. Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

ABSTRACT Objective. To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). Materials and methods. We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. Results. We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. Conclusions. We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

Pediatric Rome IV diagnosis agreement is greater than agreement on diagnostic testing.

BACKGROUND: Pediatric Rome IV criteria are used to diagnose childhood functional gastrointestinal disorders (FGIDs). This study of pediatric gastroenterology physicians measured their agreement in (1) Making a pediatric Rome IV FGID diagnosis; and (2) Diagnostic testing for patients with FGIDs. METHODS: Pediatric gastroenterologists and pediatric gastroenterology fellows at two medical centers completed a survey containing clinical FGID vignettes. For each vignette, raters identified the most likely Rome IV diagnosis(es) and selected which diagnostic test(s) (if any) they typically would obtain. The survey was re-administered within 3 months. Inter-rater and intra-rater weighted percent agreement was determined. Linear mixed modeling identified sources of variability in diagnostic testing. KEY RESULTS: Thirty-four raters completed the initial survey of whom thirty-one (91%) completed the repeat survey. Overall inter-rater agreement on Rome IV diagnoses was 68% for initial and repeat surveys whereas intra-rater agreement was 76%. In contrast, overall inter-rater agreement on diagnostic testing was <30% for both initial and repeat surveys and intra-rater agreement was only 57%. Between-physician differences accounted for 43% of the variability in the number of tests selected. Rater identified use of Rome criteria in clinical practice was associated with 1.1 fewer diagnostic tests on average (95% CI 0.2-2.0, p = 0.015). Higher intra-rater agreement was noted for diagnostic testing in faculty when compared to fellows (p = 0.009). CONCLUSIONS & INFERENCES: In a multicenter evaluation among pediatric gastroenterology physicians, pediatric Rome IV diagnostic agreement was higher than that reported for previous Rome versions, and higher than agreement on diagnostic testing.

Unbearable transepidermal water loss (TEWL) experimental variability: why?

Despite the wide breadth of research, much disparity exists in transepidermal water loss (TEWL) research data-possibly due to uncontrolled experimental variables. We determined whether such experimental variables significantly impact TEWL studies and cause this disparity. An initial literature search regarding TEWL was performed to determine potential confounding variables. A subsequent search procured relevant and representative studies investigating the impact of these variables on TEWL. Variables, such as age, anatomic site, and temperature, impact TEWL and should be controlled for in TEWL studies. Other variables, such as smoking and menstrual cycle, have inconclusive results or do not provide sufficient data breadth to make a conclusion regarding its effect, if such an effect exists, on TEWL metrics. Therefore, these variables require further research to determine their potential impact on TEWL. Matching for as many experimental variables as possible may reduce the disparity in TEWL data/conclusions.

Correlation between Computed Tomography Clinical Diagnosis and Findings in Pediatric Computed Tomography.

<b>Background and Objective:</b> Pediatric Computed Tomography (CT) is a fast, accurate imaging examination using ionizing radiation to create detailed images of pathological conditions. The radiation benefit should be outweighing the risk through the procure justification and dose optimization. The study aimed to investigate the correlation between the physician's initial diagnosis and the CT findings to build procedure justification for a pediatric patient's head scan. <b>Materials and Methods:</b> The study included 81 children examined clinically and by CT scan to diagnose cranial and cerebral pathology. Eighty-one pediatric patients were investigated by CT scan and clinical diagnosis. <b>Results:</b> The patient age ranged between 1-15 years old, (44%) were male and (56%) females. The patients referred to the CT scan from emergency department n = 10 (7%), outpatient clinics n = 66, (84%) and inpatients clinics n = 5, (9%). The study showed that 46% of patients were normal with no CT findings. Almost half of the cases were negative and did not confirm the clinical diagnosis. <b>Conclusion:</b> The study concluded that most head CT scans in children were not justified. An effort towards improving the refereeing physician's awareness about radiation dose and request justification should be conducted.

Development of a Molecular Assay for Detection and Quantification of the BRAF Variation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens.

Importance: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. Objective: To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. Design, Setting, and Participants: This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. Results: A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/µL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy. Conclusions and Relevance: This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

Epidemiology of serious bacterial infection in febrile infants under 3 months of age and diagnostic management in Mayotte.

OBJECTIVE: This study aimed to determine the prevalence of serious bacterial infections (SBIs) in infants less than 90 days old presenting with fever on arrival at the emergency department (ED), and to assess the diagnostic management of febrile infants. DESIGN: A retrospective study at Mamoudzou Hospital, Mayotte Island, French Department. SETTING: General ED in the only pediatric hospital throughout the territory PATIENTS: We included infants less than 90 days old with a history of fever and bacterial investigation evaluated in the ED between 2016 and 2018. We excluded preterm infants (gestational age < 37 weeks) and those with known immunodeficiency or previous administration of antibiotics. RESULTS: A total of 594 infants were included. In all, 105 infants (17.7%) were diagnosed with an SBI and 28 (4.7%) with an invasive bacterial infection of which 1.34% was meningitis. The most frequent SBI was pneumonia (n = 69, 11.6%) followed by urinary tract infection (UTI; n = 37, 6.2%). Predominant pathogens (excluding contaminants) were Escherichia coli (51.2% of the UTI cases), group B Streptococcus (62.5% of meningitis cases), and Staphylococcus aureus (61.5% of bacteremia cases). Seven infants presented with bacterial pneumonia due to Staphylococcus aureus with Panton-Valentine leucocidin (PVL) exotoxin production. Ill-appearing infants, clinical signs of SBI and complex chronic condition were associated with a risk of SBI (respective odds ratio [OR]: 4.6, 95% confidence interval [CI]: 3-6.9; OR: 4.2, 95% CI: 2.8-6.4; and OR: 3.2, 95% CI: 1.2-8.5). The median age for SBI was 42 days (5-90). Fever without source (FWS) occurred more often in infants under 21 days of age (48.5% vs. 31.3% in older infants, p < 0.001). The median duration of fever at home was 24 h (6-96). Concerning management, in infants aged under 21 days, there were more lumbar punctures (58.3% vs. 23% in older infants, p < 0.001) and more frequent initiation of empiric antibiotics (62.6% vs. 42.7%, p < 0.001). Length of stay was also longer in this age range (5 days vs. 3 days, p = 0.037). CONCLUSION: Delay in medical consultation in the case of fever, the risk of SBI regardless of age, and unusual epidemiology with many IBI due to Staphylococcus aureus with PVL exotoxin production are specific characteristics observed in our study. Knowledge of the current epidemiology of SBI in Mayotte would be useful for setting up a risk-stratified protocol in this population in the future.

Evaluation of alternative reagents on the performance of the modified Knott's test.

The aim of the present study was to evaluate the suitability of different reagents as safe alternatives to 2% formalin in the modified Knott's test for the diagnosis of subcutaneous (Dirofilaria repens) and cardiopulmonary (D. immitis) dirofilariosis. A total of 61 blood samples from dogs naturally infected with D. immitis and D. repens were collected and analysed in two different laboratories (Lab 1, University of Parma and Lab 2, University of Napoli). For each blood sample the modified Knott's method was performed to identify and measure the mean length and width of the microfilariae (mfs) using 2% formalin (A), 2% acetic acid (B), 2% glacial acetic acid (C), 10% saponin (D) and distilled water (E). When compared to 2% formalin, there was no significant difference (P > 0.05) among the mean length and width of either D. immitis or D. repens mfs with distilled water (E). The lengths and widths of mfs, however, were significantly reduced (P < 0.05) when using B, C, D likely due to more pronounced parasite dehydration. Despite differences in measurements, the morphological features of the head and tail of the two species were maintained, suggesting that all the solutions tested could be a suitable alternative to formalin. All alternative reagents caused more marked haemolysis compared to formalin, improving readability of slides. The values of the mean length and the mean width of D. immitis and the mean width of D. repens mfs obtained with formalin and distilled water were statistically different (P < 0.005) between the two laboratories. The difference in mf measurements between the two labs could be due to the use of reagents purchased from different manufacturing companies. Results suggest that distilled water could replace formalin in the modified Knott's test, as a safer reagent that allows morphology-based species differentiation of Dirofilaria spp.

Mycotoxin Biomarkers in Pigs-Current State of Knowledge and Analytics.

Farm animals are frequently exposed to mycotoxins, which have many adverse effects on their health and become a significant food safety issue. Pigs are highly exposed and particularly susceptible to mycotoxins, which can cause many adverse effects. For the above reasons, an appropriate diagnostic tool is needed to monitor pig' exposure to mycotoxins. The most popular tool is feed analysis, which has some disadvantages, e.g., it does not include individual exposure. In recent years, the determination of biomarkers as a method to assess the exposure to mycotoxins by using concentrations of the parent compounds and/or metabolites in biological matrices is becoming more and more popular. This review provides a comprehensive overview of reported in vivo mycotoxin absorption, distribution, metabolism and excretion (ADME) and toxicokinetic studies on pigs. Biomarkers of exposure for aflatoxins, deoxynivalenol, ochratoxin A, fumonisins, T-2 toxin and zearalenone are described to select the most promising compound for analysis of porcine plasma, urine and faeces. Biomarkers occur in biological matrices at trace levels, so a very sensitive technique-tandem mass spectrometry-is commonly used for multiple biomarkers quantification. However, the sample preparation for multi-mycotoxin methods remains a challenge. Therefore, a summary of different biological samples preparation strategies is included in that paper.

A guide to diagnosing and managing ascites in cirrhosis.

Combined serum and ascites fluid measurements point to the cause of ascites. For patients with modest edema, a reduced weight-loss target with diuresis may be acceptable.