ABSTRACT
PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].
ABSTRACT
BACKGROUND: Delirium is an underdiagnosed clinical syndrome typified by an acute alteration of mental state. It is an important problem in critical care and intensive care units (ICU) due to its high prevalence and its association with adverse outcomes. Delirium is a very distressing condition for patients, with a huge impact on their well-being. Diagnosis of delirium in the critical care setting is challenging. This is especially true for patients who are mechanically ventilated and are therefore unable to engage in a verbal interview. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a tool specifically designed to assess for delirium in the context of ICU patients, including those on mechanical ventilation. CAM-ICU can be administered by non-specialists to give a dichotomous delirium present/absent result. OBJECTIVES: To determine the diagnostic accuracy of the CAM-ICU for the diagnosis of delirium in adult patients in critical care units. SEARCH METHODS: We searched MEDLINE (Ovid SP, 1946 to 8 July 2022), Embase (Ovid SP, 1982 to 8 July 2022), Web of Science Core Collection (ISI Web of Knowledge, 1945 to 8 July 2022), PsycINFO (Ovid SP, 1806 to 8 July 2022), and LILACS (BIREME, 1982 to 8 July 2022). We checked the reference lists of included studies and other resources for additional potentially relevant studies. We also searched the Health Technology Assessment database, the Cochrane Library, Aggressive Research Intelligence Facility database, WHO ICTRP, ClinicalTrials.gov, and websites of scientific associations to access any annual meetings and abstracts of conference proceedings in the field. SELECTION CRITERIA: We included diagnostic studies enrolling adult ICU patients assessed using the CAM-ICU tool, regardless of language or publication status and reporting sufficient data on delirium diagnosis for the construction of 2 x 2 tables. Eligible studies evaluated the diagnostic performance of the CAM-ICU versus a clinical reference standard based on any iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria applied by a clinical expert. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and collated study data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used two univariate fixed-effect or random-effects models to determine summary estimates of sensitivity and specificity. We performed sensitivity analyses that excluded studies considered to be at high risk of bias and high concerns in applicability, due mainly to the target population included (e.g. patients with traumatic brain injury). We also investigated potential sources of heterogeneity, assessing the effect of reference standard diagnosis and proportion of patients ventilated. MAIN RESULTS: We included 25 studies (2817 participants). The mean age of participants ranged from 48 to 69 years; 15 of the studies included critical care units admitting mixed populations (e.g. medical, trauma, surgery patients). The percentage of patients receiving mechanical ventilation ranged from 11.8% to 100%. The prevalence of delirium in the studies included ranged from 12.5% to 83.9%. Presence of delirium was determined by the application of DSM-IV criteria in 13 out of 25 included studies. We assessed 13 studies as at low risk of bias and low applicability concerns for all QUADAS-2 domains. The most common issue of concern was flow and timing of the tests, followed by patient selection. Overall, we estimated a pooled sensitivity of 0.78 (95% confidence interval (CI) 0.72 to 0.83) and a pooled specificity of 0.95 (95% CI 0.92 to 0.97). Sensitivity analysis restricted to studies at low risk of bias and without any applicability concerns (n = 13 studies) gave similar summary accuracy indices (sensitivity 0.80 (95% CI 0.72 to 0.86), specificity 0.95 (95% CI 0.93 to 0.97)). Subgroup analyses based on diagnostic assessment found summary estimates of sensitivity and specificity for studies using DSM-IV of 0.79 (95% CI 0.72 to 0.85) and 0.94 (95% CI 0.90 to 0.96). For studies that used DSM-5 criteria, summary estimates of sensitivity and specificity were 0.75 (95% CI 0.67 to 0.82) and 0.98 (95% CI 0.95 to 0.99). DSM criteria had no significant effect on sensitivity (P = 0.421), but the specificity for detection of delirium was higher when DSM-5 criteria were used (P = 0.024). The relative specificity comparing DSM-5 versus DSM-IV criteria was 1.05 (95% CI 1.02 to 1.08). Summary estimates of sensitivity and specificity for studies recruiting < 100% of patients with mechanical ventilation were 0.81 (95% CI 0.75 to 0.85) and 0.95 (95% CI 0.91 to 0.98). For studies that exclusively recruited patients with mechanical ventilation, summary estimates of sensitivity and specificity were 0.91 (95% CI 0.76 to 0.97) and 0.98 (95% CI 0.92 to 0.99). Although there was a suggestion of differential performance of CAM-ICU in ventilated patients, the differences were not significant in sensitivity (P = 0.316) or in specificity (P = 0.493). AUTHORS' CONCLUSIONS: The CAM-ICU tool may have a role in the early identification of delirium, in adult patients hospitalized in intensive care units, including those on mechanical ventilation, when non-specialized, properly trained clinical personnel apply the CAM-ICU. The test is most useful for exclusion of delirium. The test may miss a proportion of patients with incident delirium, therefore in situations where detection of all delirium cases is desirable, it may be best to repeat the test or combine CAM-ICU with another assessment. Future studies should compare different screening tests proposed for bedside assessment of delirium, as this approach will reveal which tool yields superior accuracy. In addition, future studies should consider and report the flow and timing of the tests and clearly report key characteristics related to patient selection. Finally, future research should focus on the impact of CAM-ICU screening on patient outcomes.
Subject(s)
Delirium , Intensive Care Units , Adult , Humans , Middle Aged , Aged , Sensitivity and Specificity , Delirium/diagnosis , Critical CareABSTRACT
Dada la relevancia del desarrollo temprano de los conocimientos o habilidades considerados precursores de la alfabetización, resulta fundamental, para la elaboración de propuestas pedagógicas, identificar aquellos aspectos en los que es necesario focalizar dichas propuestas. En este sentido, el estudio que se informa abordó la incidencia del medio en las habilidades tempranas de lectura y escritura en tres grupos de niños de diferente procedencia socioeconómica (niveles socioeconómicos medio urbano, bajo urbano y bajo rural). Los niños respondieron a 11 pruebas que evalúan las siguientes variables precursoras de la alfabetización: Habilidades de procesamiento fonológico, Conocimiento de las correspondencias, Habilidades de discriminación visual de letras y palabras, Habilidad de lectura de palabras en contexto, Capacidad de reconocimiento de acciones de lectura y escritura, Formas tempranas de escritura, Conocimiento de lenguaje técnico y Manejo de libro. Los resultados obtenidos señalan que existen diferencias entre los grupos en las tareas implicadas en el reconocimiento de lenguaje técnico, en las de conciencia fonológica y en las formas de escritura. Sin embargo, no se hallaron diferencias entre los niños de los distintos sectores socioeconómicos evaluados en las tareas de discriminación, manejo de libro y reconocimiento de acciones de lectura y escritura. En concordancia con el modelo evolutivo de Nelson (2007), los grupos muestran un desempeño similar en conocimientos que responden a procesos perceptivos básicos y difieren en aquellos que la investigación ha demostrado que requieren de la intervención de un adulto alfabetizado.(AU)
Due to the fact that early literacy skills are crucial for reading and writing learning process, it is important to identify them in order to design teaching activities. Most of the former literacy studies have been carried out with middle class children and show that reading and writing learning process begins very early at home. The rate and the way reading and writing are developed is highly related with parents educational level and the kind and frequency of the literacy activities they propose. There are differences between social groups with regard to these activities that may cause knowledge differences at early age that may explain reading and writing learning process failure in low income children. From a developmental perspective there have been numerous studies focused mainly on literacy learning before formal teaching of reading and writing in school. These researches tempt to explore and describe the concepts, knowledge, skills and early actions of reading and writing as well as the social context where these developments occur. In the framework of these observations, the aim of the present study was to compare early reading and writing skills in three groups of children from different socioeconomic environment. From theoretical and methodological point of view we have take in account a cognitive psychology perspective to explore those variables considered early literacy skills such as phonological awareness, early writing skills among others as well as we have adopted as teaching and learning process framework Vigotskys zone of proximal development as well as Bruners scaffolding. The groups were described according to different variables such us age (measured up to May, 30th), sex and socioeconomic level. In order to measure the last variable, parents education level and job were considered according Sartú (1992) occupational scale. Using this variables three groups were selected: Group A was formed by 20 children mean age 5.5-year-olds from middle urban income families who attended a public kindergarten school situated in a middle class neighborhood. Group B was formed by 19 kids mean age 5.3-year-olds from low income families who attended to a public kindergarten school in a low income urban neighborhood. Group C was formed by 17 children mean age 5.3-year-olds who attended a public kindergarten school from a low rural income area. Kids were assessed with 11 tasks: Phonological awareness, Letter-sound correspondences, Differences between letters, Words from pictures, Reading words in context, Recognition of writing and reading activities, Early reading and writing performance, Technical vocabulary knowledge, proper usage of books was tested. The results of this study provides empirical information on the early literacy pattern of learning process of Spanish-speaking children as well as differences in knowledge and skills involved in this process between children from different socioeconomic groups. Differences between the three groups were observed in technical vocabulary knowledge and phonological awareness tasks performance. There were no differences between socioeconomically groups in distinguishing letters and words from pictures, recognizing writing and reading activities and proper using of books. According to Nelson (2007), children have a similar performance in those activities based on basic cognitive skills and differ in the ones that involve adults instruction. The similar performances of the groups tested seems to indicate that the knowledge involved in early literacy process is develop in a sequence characterized by an emerging knowledge about writing in the social environment. The fact that children did not grasp a complete competence in one knowledge before reaching it in other later ability shows that literacy acquisition is characterized by an overlapping development of different abilities and knowledge.(AU)
ABSTRACT
Dada la relevancia del desarrollo temprano de los conocimientos o habilidades considerados precursores de la alfabetización, resulta fundamental, para la elaboración de propuestas pedagógicas, identificar aquellos aspectos en los que es necesario focalizar dichas propuestas. En este sentido, el estudio que se informa abordó la incidencia del medio en las habilidades tempranas de lectura y escritura en tres grupos de niños de diferente procedencia socioeconómica (niveles socioeconómicos medio urbano, bajo urbano y bajo rural). Los niños respondieron a 11 pruebas que evalúan las siguientes variables precursoras de la alfabetización: Habilidades de procesamiento fonológico, Conocimiento de las correspondencias, Habilidades de discriminación visual de letras y palabras, Habilidad de lectura de palabras en contexto, Capacidad de reconocimiento de acciones de lectura y escritura, Formas tempranas de escritura, Conocimiento de lenguaje técnico y Manejo de libro. Los resultados obtenidos señalan que existen diferencias entre los grupos en las tareas implicadas en el reconocimiento de lenguaje técnico, en las de conciencia fonológica y en las formas de escritura. Sin embargo, no se hallaron diferencias entre los niños de los distintos sectores socioeconómicos evaluados en las tareas de discriminación, manejo de libro y reconocimiento de acciones de lectura y escritura. En concordancia con el modelo evolutivo de Nelson (2007), los grupos muestran un desempeño similar en conocimientos que responden a procesos perceptivos básicos y difieren en aquellos que la investigación ha demostrado que requieren de la intervención de un adulto alfabetizado.
Due to the fact that early literacy skills are crucial for reading and writing learning process, it is important to identify them in order to design teaching activities. Most of the former literacy studies have been carried out with middle class children and show that reading and writing learning process begins very early at home. The rate and the way reading and writing are developed is highly related with parents educational level and the kind and frequency of the literacy activities they propose. There are differences between social groups with regard to these activities that may cause knowledge differences at early age that may explain reading and writing learning process failure in low income children. From a developmental perspective there have been numerous studies focused mainly on literacy learning before formal teaching of reading and writing in school. These researches tempt to explore and describe the concepts, knowledge, skills and early actions of reading and writing as well as the social context where these developments occur. In the framework of these observations, the aim of the present study was to compare early reading and writing skills in three groups of children from different socioeconomic environment. From theoretical and methodological point of view we have take in account a cognitive psychology perspective to explore those variables considered early literacy skills such as phonological awareness, early writing skills among others as well as we have adopted as teaching and learning process framework Vigotsky's zone of proximal development as well as Bruner's scaffolding. The groups were described according to different variables such us age (measured up to May, 30th), sex and socioeconomic level. In order to measure the last variable, parents education level and job were considered according Sartú (1992) occupational scale. Using this variables three groups were selected: Group A was formed by 20 children mean age 5.5-year-olds from middle urban income families who attended a public kindergarten school situated in a middle class neighborhood. Group B was formed by 19 kids mean age 5.3-year-olds from low income families who attended to a public kindergarten school in a low income urban neighborhood. Group C was formed by 17 children mean age 5.3-year-olds who attended a public kindergarten school from a low rural income area. Kids were assessed with 11 tasks: Phonological awareness, Letter-sound correspondences, Differences between letters, Words from pictures, Reading words in context, Recognition of writing and reading activities, Early reading and writing performance, Technical vocabulary knowledge, proper usage of books was tested. The results of this study provides empirical information on the early literacy pattern of learning process of Spanish-speaking children as well as differences in knowledge and skills involved in this process between children from different socioeconomic groups. Differences between the three groups were observed in technical vocabulary knowledge and phonological awareness tasks performance. There were no differences between socioeconomically groups in distinguishing letters and words from pictures, recognizing writing and reading activities and proper using of books. According to Nelson (2007), children have a similar performance in those activities based on basic cognitive skills and differ in the ones that involve adult's instruction. The similar performances of the groups tested seems to indicate that the knowledge involved in early literacy process is develop in a sequence characterized by an emerging knowledge about writing in the social environment. The fact that children did not grasp a complete competence in one knowledge before reaching it in other later ability shows that literacy acquisition is characterized by an overlapping development of different abilities and knowledge.