Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis / Los tests de diagnóstico rápido para dengue reducirían las hospitalizaciones, los costes sanitarios y la prescripción de antibióticos en España: un análisis de coste-efectividad

Background: Current gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. Methods: We performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015–2020 dengue admissions at Hospital Clinic Barcelona (Spain). Results: Dengue RDTs were associated with 53.6% (95% CI: 33.9–72.5) reduction of hospital admissions and were estimated to save 289.08–389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5–66.1) of dengue patients. Discussion: Implementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.(AU)

Introducción: El actual gold standard para el diagnóstico de dengue se basa en técnicas caras y que requieren tiempo. Los tests de diagnóstico rápido (TDR) se han propuesto como una posible alternativa, aunque los datos sobre su posible impacto en áreas no endémicas son escasos. Métodos: Realizamos un análisis de coste-efectividad comparando los costes del uso de TDR para dengue con el manejo habitual de viajeros con fiebre en España. Para medir la efectividad se estimaron las hospitalizaciones potencialmente evitables y la reducción de antibióticos empíricos de acuerdo con las hospitalizaciones por dengue entre 2015-2020 en el Hospital Clínic Barcelona (España). Resultados: El uso de TDR para dengue se asoció con una reducción de 53.6% (IC 95%: 33.9–72.5) de las hospitalizaciones y un ahorro de 289.08-389.31€ por viajero testado. Además, el uso de TDR hubiese evitado el tratamiento de antibióticos en 46.4% (IC 95%: 27.5–66.1) de los casos de dengue. Discusión: La implementación de TDR de dengue para el manejo de viajeros con fiebre es una medida de reducción de gastos que disminuiría a la mitad los ingresos hospitalarios por dengue y supondría una reducción del uso inapropiado de antibióticos en España.(AU)

Hypothesis testing procedure for binary and multi-class F1 -scores in the paired design.

In modern medicine, medical tests are used for various purposes including diagnosis, disease screening, prognosis, and risk prediction. To quantify the performance of the binary medical test, we often use sensitivity, specificity, and negative and positive predictive values as measures. Additionally, the F 1 $$ {F}_1 $$ -score, which is defined as the harmonic mean of precision (positive predictive value) and recall (sensitivity), has come to be used in the medical field due to its favorable characteristics. The F 1 $$ {F}_1 $$ -score has been extended for multi-class classification, and two types of F 1 $$ {F}_1 $$ -scores have been proposed for multi-class classification: a micro-averaged F 1 $$ {F}_1 $$ -score and a macro-averaged F 1 $$ {F}_1 $$ -score. The micro-averaged F 1 $$ {F}_1 $$ -score pools per-sample classifications across classes and then calculates the overall F 1 $$ {F}_1 $$ -score, whereas the macro-averaged F 1 $$ {F}_1 $$ -score computes an arithmetic mean of the F 1 $$ {F}_1 $$ -scores for each class. Additionally, Sokolova and Lapalme 1 $$ {}^1 $$ gave an alternative definition of the macro-averaged F 1 $$ {F}_1 $$ -score as the harmonic mean of the arithmetic means of the precision and recall over classes. Although some statistical methods of inference for binary and multi-class F 1 $$ {F}_1 $$ -scores have been proposed, the methodology development of hypothesis testing procedure for them has not been fully progressing yet. Therefore, we aim to develop hypothesis testing procedure for comparing two F 1 $$ {F}_1 $$ -scores in paired study design based on the large sample multivariate central limit theorem.

Estimated Prevalence and Testing for Albuminuria in US Adults at Risk for Chronic Kidney Disease.

Importance: Albuminuria testing is crucial for guiding evidence-based treatments to mitigate chronic kidney disease (CKD) progression and cardiovascular morbidity, but it is widely underutilized among persons with or at risk for CKD. Objective: To estimate the extent of albuminuria underdetection from lack of testing and evaluate its association with CKD treatment in a large US cohort of patients with hypertension or diabetes. Design, Setting, and Participants: This cohort study examined adults with hypertension or diabetes, using data from the 2007 to 2018 National Health and Nutrition Examination Surveys (NHANES) and the Optum deidentified electronic health record (EHR) data set of diverse US health care organizations. Analyses were conducted from October 31, 2022, to May 19, 2023. Main Outcomes and Measures: Using NHANES as a nationally representative sample, a logistic regression model was developed to estimate albuminuria (urine albumin-creatinine ratio ≥30 mg/g). This model was then applied to active outpatients in the EHR from January 1, 2017, to December 31, 2018. The prevalence of albuminuria among those with and without albuminuria testing during this period was estimated. A multivariable logistic regression was used to examine associations between having albuminuria testing and CKD therapies within the subsequent year (prescription for angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB], prescription for sodium-glucose cotransporter 2 inhibitor [SGLT2i], and blood pressure control to less than 130/80 mm Hg or less than 140/90 mm Hg on the latest outpatient measure). Results: The total EHR study population included 192 108 patients (mean [SD] age, 60.3 [15.1] years; 185 589 [96.6%] with hypertension; 50 507 [26.2%] with diabetes; mean [SD] eGFR, 84 [21] mL/min/1.73 m2). There were 33 629 patients (17.5%) who had albuminuria testing; of whom 11 525 (34.3%) had albuminuria. Among 158 479 patients who were untested, the estimated albuminuria prevalence rate was 13.4% (n = 21 231). Thus, only 35.2% (11 525 of 32 756) of the projected population with albuminuria had been tested. Albuminuria testing was associated with higher adjusted odds of receiving ACEi or ARB treatment (OR, 2.39 [95% CI, 2.32-2.46]), SGLT2i treatment (OR, 8.22 [95% CI, 7.56-8.94]), and having blood pressure controlled to less than 140/90 mm Hg (OR, 1.20 [95% CI, 1.16-1.23]). Conclusions and Relevance: In this cohort study of patients with hypertension or diabetes, it was estimated that approximately two-thirds of patients with albuminuria were undetected due to lack of testing. These results suggest that improving detection of CKD with albuminuria testing represents a substantial opportunity to optimize care delivery for reducing CKD progression and cardiovascular complications.

Infecção materna por SARS-CoV-2: descrição das notificações em gestantes / Maternal infection by SARS-CoV-2: description of notifications in pregnant women

Objetivo: Caracterizar as notificações de infecção por SARS-CoV-2 em gestantes em um município do sul de Santa Catarina. Métodos: Estudo transversal que avaliou as notificações de casos suspeitos de infecção por SARS-CoV-2 em gestantes no município de Tubarão, Santa Catarina, de março de 2020 a outubro de 2021. Coletaram-se os dados das fichas de notificação de infecção por SARS-CoV-2 da Fundação Municipal de Saúde e no Prontuário Eletrônico do Cidadão (PEC) das gestantes notificadas. A comparação da prevalência de confirmação segundo sintomas apresentados e características maternas foi realizada pela razão de prevalência (RP), com intervalo de confiança (IC) de 95%. Resultados: Foram registradas 555 notificações de gestantes suspeitas para a COVID-19, correspondentes a 487 mulheres. A prevalência de confirmação para a doença foi de 27,3%. O sintoma mais frequente no momento da notificação foi cefaleia (53,0%), entretanto o mais associado à confirmação foi a anosmia (RP: 2,28; IC 95%: 1,68-3,09). Das notificações registradas, 35,0% foram realizadas por gestantes que tiveram contato com casos suspeitos ou confirmados de COVID-19. O contato prévio foi mais relatado por gestantes assintomáticas, em comparação às gestantes que apresentaram sintomas (RP: 1,46; IC 95%: 1,12-1,91). Mulheres que relataram contato prévio com suspeitos ou confirmados para a COVID-19 apresentaram maior frequência de doença confirmada, quando comparadas às gestantes não expostas (RP: 1,80; IC 95%: 1,35-2,39). Conclusão: As gestantes, por terem maior susceptibilidade a surtos de doenças e gravidade do quadro, podem ter adotado com mais atenção medidas como a realização de testes diagnósticos quando em contato prévio com casos de COVID-19, mesmo assintomáticas.

Objective: To characterize the notifications of SARS-CoV-2 infection in pregnant women in a city in the South of Santa Catarina. Methods: Cross-sectional study that evaluated notifications of suspected cases of SARS-CoV-2 infection in pregnant women in the municipality of Tubarão, Santa Catarina, from March 2020 to October 2021. Data were collected from the SARS-CoV-2 infection notification forms from the Municipal Health Foundation, and from the Citizen's Electronic Health Record of the notified pregnant women. The comparison of the prevalence of confirmation according to symptoms and maternal characteristics was performed using the Prevalence Ratio (PR), with a confidence interval (CI) of 95%. Results: 555 notifications of suspected pregnant women for COVID-19 were registered, corresponding to 487 women. The prevalence of confirmation for the disease was 27.3%. The most frequent symptom at the time of notification was headache (53.0%), however, the most associated with confirmation was anosmia (PR: 2.28; 95% CI: 1.68-3.09). Of the notifications registered, 35.0% were made by pregnant women who had contact with suspected or confirmed cases of COVID-19. The previous contact was more frequently reported by asymptomatic pregnant women compared to pregnant women who had symptoms (PR: 1.46; 95% CI: 1.12-1.91). Women who reported previous contact with suspected or confirmed COVID-19 had a higher frequency of confirmed disease when compared to unexposed pregnant women (PR: 1.80; 95% CI: 1.35-2.39). Conclusion: Pregnant women, due to their greater susceptibility to disease outbreaks and disease severity, may have adopted more attentive measures such as diagnostic testing in the face of previous contact with cases of COVID-19, even if asymptomatic.

Hepatitis C Virus Testing and Care Cascade Among Transgender and Gender Diverse Individuals.

INTRODUCTION: Hepatitis C virus (HCV) prevalence among transgender and gender-diverse individuals ranges from 1.8% to 15.7% versus 1% in the general population. Previous HCV studies inclusive of transgender and gender-diverse individuals primarily rely on convenience-based sampling methods or are geographically restricted. The purpose of this study is to compare the prevalence of HCV diagnoses, testing, and care engagement between transgender and gender-diverse and cisgender individuals. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database, in 2022, the unadjusted prevalence of HCV testing among all adults and people who inject drugs from January 2001 to December 2019 was measured. Multivariable logistic regression was used to compare the adjusted odds of HCV diagnoses and care engagement by gender subgroup. RESULTS: The overall unadjusted frequency of HCV diagnoses among transgender and gender-diverse individuals was approximately 3 times that of cisgender individuals (1.06% vs 0.38%, p<0.001), including among people who inject drugs (6.36% vs 2.36%, p=0.007). Compared with cisgender women, transfeminine/nonbinary individuals had over 5 times the adjusted odds of a HCV diagnosis and approximately 3.5 times the odds of being tested for HCV. In addition, compared with cisgender women, transfeminine/nonbinary individuals had significantly increased odds of having a HCV‒related procedure (e.g., abdominal ultrasounds, liver biopsies, Fibroscans). Cisgender men had significantly increased odds of receiving HCV medication compared with cisgender women. CONCLUSIONS: Although testing was higher among transgender and gender-diverse individuals, the higher overall frequency of HCV diagnoses among transgender and gender-diverse than among cisgender individuals signals persistent health disparities. Interventions are warranted to prevent HCV and increase ongoing testing and treatment uptake among transgender and gender-diverse populations.

Accuracy of the Number Needed to Treat Compared With Diagnostic Testing: Brief Critical Review.

CONTEXT.­: Number needed to treat (NNT) seems simple and is widely used. But its derivation from the absolute risk reduction is difficult to visualize. Like diagnostic sensitivity, absolute risk reduction is a measure of treatment accuracy. Thus, NNT is a measure of accuracy. NNT is inversely proportional to the relative risk reduction and the baseline risk that may be torturous when accuracy is poor. In order to better visualize the accuracy and weaknesses of NNT, NNT is compared with variables in diagnostic science that are often better understood, such as diagnostic sensitivity, specificity, and positive predictive value. OBJECTIVE.­: To better understand the accuracy of NNT. DATA SOURCES.­: Receiver operating characteristic curves are used to help visualize accuracy. It is shown that baseline risk and prevalence are highly correlated. Like positive predictive value, NNT is dependent on prevalence. Similar to diagnostic testing, symptoms and additional testing can increase prevalence and improve accuracy of the NNT. Examples are shown where changes in prevalence cause alterations in NNT. Moreover, data indicate that when accuracy of NNT is low, although the average NNT may be favorable, some subgroups may exhibit very poor response and even harm. It is shown that manipulations to increase prevalence can produce smaller, more selective groupings that can improve the accuracy and reduce the cost of expensive drugs. CONCLUSIONS.­: When the power of prediction is poor, the value of NNT must be carefully deliberated because it may be misleading. Indeed, the upper confidence interval may be a better reflection of NNT than the average.

Herramientas diagnostico-terapéuticas en síndromes mielodisplásicos en Uruguay / Diagnostic and therapeutic tools in myelodysplastic syndromes in Uruguay / Instrumentos diagnóstico-terapêuticos nas síndromes mielodisplásicas no Uruguai

Los Síndromes Mielodisplásicos (SMD) son un grupo heterogéneo de enfermedades mieloides. Esta heterogeneidad en la presentación clínica complejiza el diagnóstico requiriendo diversos estudios complementarios. El tratamiento debe ser individualizado y adaptado al riesgo, desde terapias de soporte hasta intervenciones de alto costo. Para conocer la accesibilidad a las herramientas diagnóstico y terapéuticas se realizó una encuesta online dirigida a los hematólogos que asisten pacientes con SMD en Uruguay en 2016 y 2019. Las encuestas fueron respondidas por 32.5% y 26.6% de los miembros de la Sociedad de Hematología del Uruguay. Más del 90% tienen acceso a estudios histológicos, citogenéticos, FISH y citometría de flujo. La posibilidad de realizar paneles de secuenciación masiva se encuentra restringida a menos de 10% derivando la muestra al exterior, siendo mayor en 2019 en comparación a 2016. Los sistemas de estratificación de riesgo más utilizados son el sistema internacional de puntuación de riesgo (IPSS) y su versión revisada (IPSS-R). La disponibilidad de tratamientos de soporte (transfusiones, eritropoyetina y G-CSF), de azacitidina y del trasplante alogénico de precursores hematopoyéticos es amplia. Existió un aumento en indicación de azacitidina en 2019 con respecto a 2016. Sin embargo, el acceso a decitabina, lenalidomida y fármacos quelantes de hierro es escaso y no se cuenta con ensayos clínicos donde incluir pacientes que fallan o no responden a los tratamientos convencionales. La presente encuesta, realizada en dos períodos, describe la realidad y su evolución en nuestro país en cuanto a accesibilidad a herramientas diagnósticas y terapéuticas extrapolables a otras patologías oncohematológicas. Los datos recabados permitirán plantear estrategias tendientes a mejorar el abordaje diagnóstico-terapéutico de los pacientes con SMD en Uruguay.

Myelodysplastic Syndromes (MDS) constitutes an heterogenous group of hematological malignancies. Reaching an accurate diagnosis, represents in an important number of cases, a major challenge that requires different diagnostic tools. In order to acknowledge the scope of access to those tools in our country, we performed a survey addressed to Uruguayan hematologists who care for MDS patients in their clinical practice. The survey was carried out in 2016 and 2019 among Uruguayan Hematology Society members. Response rate was 32.5% and 26.6% respectively. Access to bone marrow biopsy, cytogenetics, FISH and flow cytometry was accessible to more than 90% of physicians. Less than 10% of respondents were able to request next generation sequencing (NGS) studies and in that case, they have to send them abroad. IPSS and R-IPSS were the most frequently used risk scores. Support treatment such as growth factors and transfusions are widely accessible. Azacytidine and allogenic transplant are available as well. However, access to decitabine, lenalidomide and iron chelating drugs is scarce and there are no clinical trials to include patients who fail or do not respond to conventional treatments. This survey, carried out in two periods, describes the reality and its evolution in our country in terms of accessibility to diagnostic and therapeutic tools that can be extrapolated to other oncohematological pathologies. We were able to get to know our country reality regarding diagnostic and therapeutic tools for MDS patients. This, would represent an important input in order to design health strategies aiming to improve clinical care for our patients.

As Síndromes Mielodisplásicas (SMD) são um grupo heterogêneo de doenças mielóides. Essa heterogeneidade na apresentação clínica torna o diagnóstico mais complexo, exigindo vários estudos complementares. O tratamento deve ser individualizado e adaptado ao risco, desde terapias de suporte até intervenções de alto custo. Para conhecer a acessibilidade de ferramentas diagnósticas e terapêuticas, foi realizada uma pesquisa online dirigida aos hematologistas que atendem pacientes com SMD no Uruguai em 2016 e 2019. As pesquisas foram respondidas por 32,5% e 26,6% dos membros da Sociedad de Hematologia do Uruguai. Mais de 90% têm acesso a estudos histológicos, citogenéticos, FISH e citometria de fluxo. A possibilidade de realização de painéis de sequenciamento massivo está restrita a menos de 10% provenientes da amostra no exterior, sendo maior em 2019 em relação a 2016. Os sistemas de estratificação de risco mais utilizados são o sistema internacional de pontuação de risco (IPSS) e sua versão revisada (IPSS -R). Tratamentos de suporte (transfusões, eritropoietina e G-CSF), azacitidina e transplante alogênico de células-tronco hematopoiéticas estão amplamente disponíveis. Houve aumento da indicação de azacitidina em 2019 em relação a 2016. No entanto, o acesso a decitabina, lenalidomida e quelantes de ferro é escasso e não há ensaios clínicos para incluir pacientes que falham ou não respondem aos tratamentos convencionais. Este inquérito, realizado em dois períodos, descreve a realidade e a sua evolução no nosso país em termos de acessibilidade a instrumentos diagnósticos e terapêuticos que podem ser extrapolados para outras patologias onco-hematológicas. Os dados coletados permitirão propor estratégias destinadas a melhorar a abordagem diagnóstico-terapêutica de pacientes com SMD no Uruguai.

Rapid tests for HIV, syphilis, and chronic hepatitis in a prison population in a prison complex in Salvador (BA), Brazil. / Testes rápidos de HIV, sífilis e hepatites crônicas na população carcerária em um complexo penitenciário de Salvador (BA), Brasil.

This study aimed to quantitatively analyze the results of rapid tests for Human Immunodeficiency Virus (HIV), Syphilis, and Chronic Hepatitis in the prison population in a prison complex in Salvador (BA), Brazil. This cross-sectional study consisted of a sample of men incarcerated from August 2018 to August 2020 submitted to rapid tests. Descriptive statistics and prevalence ratios with respective 95% confidence intervals were employed to analyze data. A total of 6,160 men were studied. Most were black and brown (93.1%) and resided in Salvador (BA), Brazil (65.8%), with predominantly elementary schooling level (65.3%). Five hundred eighty-one (9.4%) people deprived of their liberty were positive for one or more STIs, and Syphilis was the most prevalent (80%). The variables age greater than 25 years [PR = 1.37 95%CI (1.17-1.61)] and schooling level without Higher Education [PR = 2.16 95%CI (1.04-4.49)] were associated with a higher positivity rate in tests, while not sharing drugs was a protective factor for test positivity [PR = 1.28 95%CI (1.07-1.53)]. We concluded that there was a low prevalence of STIs in the sample studied, and Syphilis was the most prevalent.

O objetivo do estudo foi analisar quantitativamente resultados de testes rápidos de vírus da imunodeficiência humana (HIV), sífilis e hepatites crônicas na população carcerária em complexo penitenciário de Salvador (BA). Trata-se de um estudo transversal. A amostra foi composta por homens privados de liberdade no período de agosto de 2018 a agosto de 2020, com testes rápidos sendo realizados. Para análise dos dados foi utilizada estatística descritiva e razão de prevalência com os respectivos intervalos de confiança de 95%. Foram estudados 6.160 homens, com maioria (93,1%) de pretos e pardos, residentes de Salvador (65,8%), com escolaridade predominante de ensino fundamental (65,3%). Das pessoas privadas de liberdade, 581 (9,4%) obtiveram resultado reagente para uma ou mais IST, sendo sífilis a mais prevalente (80%). As variáveis idade maior de 25 anos [RP = 1,37 IC95% (1,17-1,61)] e nível de escolaridade sem presença de ensino superior [RP = 2,16 IC95% (1,04-4,49)] se mostraram associadas à maior taxa de positividade nos testes, enquanto o não compartilhamento de drogas em algum momento da vida mostrou ser fator protetor à positividade nos testes [RP = 1,28 IC95% (1,07-1,53)]. Conclui-se que existiu uma baixa prevalência das IST na amostra estudada, sendo sífilis a mais prevalente.

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.

The DSM-5 introduction of the Social (Pragmatic) Communication Disorder as a new mental disorder: a philosophical review.

The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included the Social (Pragmatic) Communication Disorder (SPCD) as a new mental disorder characterized by deficits in pragmatic abilities. Although the introduction of SPCD in the psychiatry nosography depended on a variety of reasons-including bridging a nosological gap in the macro-category of Communication Disorders-in the last few years researchers have identified major issues in such revision. For instance, the symptomatology of SPCD is notably close to that of (some forms of) Autism Spectrum Disorder (ASD). This opens up the possibility that individuals with very similar symptoms can be diagnosed differently (with either ASD or SPCD) and receive different clinical treatments and social support. The aim of this paper is to review recent debates on SPCD, particularly as regards its independence from ASD. In the first part, we outline the major aspects of the DSM-5 nosological revision involving ASD and SPCD. In the second part, we focus on the validity and reliability of SPCD. First, we analyze literature on three potential validators of SPCD, i.e., etiology, response to treatment, and measurability. Then, we turn to reliability issues connected with the introduction of the grandfather clause and the use of the concepts of spectrum and threshold in the definition of ASD. In the conclusion, we evaluate whether SPCD could play any role in contemporary psychiatry other than that of an independent mental disorder and discuss the role that non-epistemic factors could play in the delineation of the future psychiatry nosography.

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.

Intractable lateral epicondilytis: A differential diagnosis algorithm for a correct clinical interpretation

The epicondylalgia is the most frequent upper extremity pathology in adults and it can become an “intractable lateral epicondylitis” when patients do not improve with the treatment received. This is a complex entity that includes several musculo-tendinous, articular and neural syndromes than can coexist and they can also be confused with each other. For this reason, it is necessary to do a systematized and exhaustive evaluation where all the dysfunctions capable of generating the symptoms are precisely and independently analyzed. On this basis, a 7 steps assessment algorithm is proposed on this paper to enable the clinician to perform a complete and organized evaluation of these patients, to achieve a correct clinical interpretation. (AU)

Pathways to diagnosis of pediatric TB patients: A mixed methods study from India.

BACKGROUND: A significant proportion of pediatric tuberculosis (TB) patients go unnotified due to the challenges in diagnosis of TB among children. The experiences of this vulnerable group while going through the TB care cascade remain largely undocumented. The aim of this study was to explore the experiences of pediatric TB patients and families along the pathway to TB diagnosis and appropriate treatment in four cities of India. METHODS: The study used a mixed methods, single phased, embedded design. The primary qualitative and secondary quantitative data were collected simultaneously by interviewing families of 100 randomly selected Xpert MTB/RIF positive pediatric TB patients, under the pediatric TB project, in 4 Indian cities using a semi-structured questionnaire. The qualitative component was analyzed to deduce patterns and themes on the patient and family experiences. Descriptive statistics were used to quantify various events along the TB care pathway including various delays (patient, diagnosis and total) and number of providers visited by patients during the diagnostic process. RESULTS: The median patient, diagnostic and total delays were 3 (IQR: 2,5), 39 (IQR: 23, 91) and 43 days (IQR: 28.5, 98.5), respectively. Patients visited a median of 3 (IQR: 2,4) providers before accessing Xpert MTB/RIF testing. On an average, 68.4% of physicians ordered any test most of them being irrelevant for TB diagnosis. Qualitative data showed considerable suffering for children and their families before and after TB diagnosis including serious concerns of stigma, disruption in education and social life and recurrence of the disease. CONCLUSION: Our study highlights the significant physical and social distress that the children with TB and their families undergo along the TB care pathway. It also shows diagnostic delay in excess of a month during which multiple providers were met and the patients underwent several diagnostic tests, most of them being inappropriate. Efforts to make Xpert MTB/RIF testing more accessible and part of physicians' toolkit will be of considerable value to ease the complexity of TB diagnosis in children. In addition, communication strategy needs to be developed and implemented to generate awareness among general population around pediatric TB and its management.

Provocative growth hormone testing in children: how did we get here and where do we go now?

OBJECTIVES: Provocative growth hormone (GH) tests are widely used for diagnosing pediatric GH deficiency (GHD). A thorough understanding of the evidence behind commonly used interpretations and the limitations of these tests is important for improving clinical practice. CONTENT: To place current practice into a historical context, the supporting evidence behind the use of provocative GH tests is presented. By reviewing GH measurement techniques and examining the early data supporting the most common tests and later studies that compared provocative agents to establish reference ranges, the low sensitivity and specificity of these tests become readily apparent. Studies that assess the effects of patient factors, such as obesity and sex steroids, on GH testing further bring the appropriateness of commonly used cutoffs for diagnosing GHD into question. SUMMARY AND OUTLOOK: Despite the widely recognized poor performance of provocative GH tests in distinguishing GH sufficiency from deficiency, limited progress has been made in improving them. New diagnostic modalities are needed, but until they become available, clinicians can improve the clinical application of provocative GH tests by taking into account the multiple factors that influence their results.

Abdominal investigations in the year preceding a diagnosis of abdominal cancer: A register-based cohort study in Denmark.

BACKGROUND: More than 11,500 abdominal cancers are yearly diagnosed in Denmark. Nevertheless, little is known about which investigations the patients undergo before a diagnosis of abdominal cancer. We aimed to investigate the frequency and timing of selected diagnostic investigations during the year preceding an abdominal cancer diagnosis. METHODS: We conducted a nationwide registry-based cohort study of patients aged ≥ 18 years who were diagnosed with a first-time abdominal cancer in 2014-2018. We included the following cancer types: oesophageal, gastric, colon, rectal, liver, gall bladder/biliary tract, pancreatic, endometrial, ovarian, kidney, and bladder cancer. Investigations of interest were transvaginal ultrasound, abdominal ultrasound, colonoscopy, gastroscopy, endoscopic retrograde cholangiopancreatography, cystoscopy, hysteroscopy, abdominal computed tomography and abdominal magnetic resonance imaging. Generalised linear models were used to calculate incidence rate ratios to enable comparison of monthly rates of investigations. RESULTS: All types of investigations were performed, with varying frequency, across the 11 abdominal cancer types in the year preceding the diagnosis. Increased use of investigations revealed that the timing of the onset differed for the different abdominal cancers, with increases seen 2-6 months before the diagnosis. Abdominal ultrasound, colonoscopy and computed tomography were the investigations with the earliest increase. CONCLUSION: In the year before a diagnosis of an abdominal cancer, some patients appear to undergo investigations typically used to detect another cancer type. This indicates that a window of opportunity exists to diagnose some abdominal cancers at an earlier time point. Future studies should explore an alternative clinical pathway to promote earlier diagnosis of abdominal cancers.

The Utility of Infectious and Neurodiagnostic Testing in Children With Complex Febrile Seizures Requiring Mechanical Ventilation.

A retrospective cohort analysis was performed on 79 consecutive patients between 6 months and 5 years admitted to a tertiary hospital with a diagnosis of complex febrile seizures requiring mechanical ventilation from 2011 to 2017 to determine the utility of infectious and neurologic diagnostics. Intubation was used as a proxy for severity of illness. The overall intensive care unit stay was short (95% intubated <24 hours, 88% admitted <3 days). No life-threatening infections were identified, and none required surgical interventions. Electroencephalogram (EEG) was obtained on 43%, 26% of which were abnormal. Sixty-six percent of patients were discharged on rescue benzodiazepine and 20% with maintenance antiseizure medications. Duration of follow-up averaged 4 years (range 1 month to 9 years); 8 patients (10%) were subsequently diagnosed with epilepsy. Our findings suggest that extensive diagnostic evaluations may not be necessary for children with complex febrile seizures requiring mechanical ventilation although the role of EEG is less understood.

Combined clinical and imaging features better predict the critical outcomes of patients with SARS-COV-2.

ABSTRACT: The purpose of this study was to investigate the predictive value of combined clinical and imaging features, compared with the clinical or radiological risk factors only. Moreover, the expected results aimed to improve the identification of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) patients who may have critical outcomes.This retrospective study included laboratory-confirmed SARS-COV-2 cases between January 18, 2020, and February 16, 2020. The patients were divided into 2 groups with noncritical illness and critical illness regarding severity status within the hospitalization. Univariable and multivariable logistic regression models were used to explore the risk factors associated with clinical and radiological outcomes in patients with SARS-COV-2. The ROC curves were performed to compare the prediction performance of different factors.A total of 180 adult patients in this study included 20 critical patients and 160 noncritical patients. In univariate logistic regression analysis, 15 risk factors were significantly associated with critical outcomes. Of importance, C-reactive protein (1.051, 95% confidence interval 1.024-1.078), D-dimer (1.911, 95% CI, 1.050-3.478), and CT score (1.29, 95% CI, 1.053-1.529) on admission were independent risk factors in multivariate analysis. The combined model achieved a better performance in disease severity prediction (P = .05).CRP, D-dimer, and CT score on admission were independent risk factors for critical illness in adults with SARS-COV-2. The combined clinical and radiological model achieved better predictive performance than clinical or radiological factors alone.