Cross-cultural adaptation, reliability and validity of the Spanish version of the long-term quality of life questionnaire.

Purpose: The aim of this study was to translate, culturally adapt, and evaluate the psychometric properties of the Spanish Long-Term Quality of Life (LTQL) questionnaire. Methods: The LTQL was initially translated into Spanish and cross-culturally adapted based on established guidelines. The Spanish LTQL was administered to patients with breast cancer who had completed their initial treatment 5 years earlier, along with other self-report measures: Quality of Life in Adult Cancer Survivors (QLACS), Hospital Anxiety and Depression Scale (HADS) and EORT-QLQ-BR23. Reliability was evaluated using internal consistency and test-retest. Convergent and known-groups validity were examined. Structural validity as determined by confirmatory factor analysis (CFA) and Rasch analyses was used to assess the unidimensionality and item-functioning of the LTQL domains. Results: Cronbach's alpha were above 0.7 in all domains. Test-retest coefficients were between 0.72 to 0.96 for LTQL domains. LTQL total score was correlated with others total scores of other measures: QLACS (r=-0.39), HADS depression (r=-0.57), HADS anxiety (-0.45) and EORTC-QLQ-BR23 (r=-0.50). CFA provided satisfactory fit indices, with RMSEA value of 0.077 and TLI and CFI values of 0.901 and 0.909, respectively. All factor loadings were higher than 0.40 and statistically significant (P<0.001). Rasch analysis showed that Somatic Concerns domain had 4 misfitting items, and Philosophical/Spiritual View of Life and social Support domains only 1 misfit item. However, unidimensionality was supported for the four domains. Conclusion: The findings support the validity and reliability of the Spanish version of LTQL questionnaire to be used in long-term cancer female survivors.

Percutaneous ethanol injection in thyroid nodular pathology and metastatic cervical adenopathies: A systematic review, meta-analysis and economic evaluation.

BACKGROUND: Percutaneous ethanol injection (PEI) has been shown to be a valuable treatment for thyroid nodular pathology and metastatic cervical adenopathies. OBJECTIVE: To evaluate the effectiveness, safety, and cost-effectiveness of PEI in thyroid nodular pathology and metastatic cervical adenopathies. METHODS: A systematic review (SR) using meta-analysis was conducted on the effectiveness and safety of PEI. A SR on cost-effectiveness was also performed. The SRs were conducted according to the methodology developed by the Cochrane Collaboration with reporting in accordance with the PRISMA statement. A cost-minimization analysis was carried out using a decision tree model. Assuming equal effectiveness between two minimally invasive techniques (PEI and radiofrequency ablation (RFA)), the model compared the costs of the alternatives with a horizon of six months and from the perspective of the Spanish National Health System. RESULTS: The search identified three RCTs (n=157) that evaluated PEI versus RFA in patients diagnosed with benign thyroid nodules: ninety-six patients with predominantly cystic nodules and sixty-one patients with solid nodules. No evidence was found on other techniques or thyroid nodular pathology. No statistically significant differences were observed between PEI and RFA in volume reduction (%), symptom score, cosmetic score, therapeutic success and major complications. No economic evaluations were identified. The cost-minimization analysis estimated the cost per patient of the PEI procedure at €326 compared to €4781 for RFA, which means an incremental difference of -€4455. CONCLUSIONS: There are no differences between PEI and RFA regarding their safety and effectiveness, but the economic evaluation determined that the former option is cheaper.

Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections.

BACKGROUND: Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. METHODS: Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. RESULTS: Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674). CONCLUSIONS: In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

Ethical, Legal, Organisational and Social Issues of Teleneurology: A Scoping Review.

BACKGROUND: Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. Teleneurology (TN) allows neurology to be applied when the doctor and patient are not present in the same place, and sometimes not at the same time. In February 2021, the Spanish Ministry of Health requested a health technology assessment report on the implementation of TN as a complement to face-to-face neurological care. METHODS: A scoping review was conducted to answer the question on the ethical, legal, social, organisational, patient (ELSI) and environmental impact of TN. The assessment of these aspects was carried out by adapting the EUnetHTA Core Model 3.0 framework, the criteria established by the Spanish Network of Health Technology Assessment Agencies and the analysis criteria of the European Validate (VALues In Doing Assessments of healthcare TEchnologies) project. Key stakeholders were invited to discuss their concerns about TN in an online meeting. Subsequently, the following electronic databases were consulted from 2016 to 10 June 2021: MEDLINE and EMBASE. RESULTS: 79 studies met the inclusion criteria. This scoping review includes 37 studies related to acceptability and equity, 15 studies developed during COVID and 1 study on environmental aspects. Overall, the reported results reaffirm the necessary complementarity of TN with the usual face-to-face care. CONCLUSIONS: This need for complementarity relates to factors such as acceptability, feasibility, risk of dehumanisation and aspects related to privacy and the confidentiality of sensitive data.

Telemedicine for neurological diseases: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases. METHODS: The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated. RESULTS: Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up. CONCLUSIONS: Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases.

Information needs and research priorities in long-term survivorship of breast cancer: Patients and health professionals' perspectives.

OBJECTIVE: The objective of this work is to identify unmet information needs of long-term-survivors of breast cancer (BC) and future research needs from the perspectives of patients and health care professionals. METHODS: Two online Delphi surveys were conducted. Participants in Survey 1 were patients. Participants in Survey 2 were health care professionals from both primary and secondary care involved in BC care. Both surveys included three successive rounds. The first round aimed to identify research and information needs; the second round aimed to rank the relative importance of those needs; the third round aimed to find consensus. RESULTS: The most important information needs were self-management recommendations of common health problems after treatment and complications of breast reconstruction after 5 years. The most important research priorities were related to interventions and tools to increase information provision by professionals about certain tests, diet, and coordinated action between primary and specialised care during follow-up, and indications and safety issues of pregnancy in survivors. CONCLUSIONS: Two fundamental ideas were identified: (1) Patients request information about self-management common health problems after treatment and breast reconstruction complications. (2) Health care professionals emphasise the need for a standardised approach based on protocols, recommendations, and coordinated actions in the provision of information. IMPLICATIONS FOR CANCER SURVIVORS: Given the increasing number of BC survivors, it is essential to identify information and research needs to improve their care and health outcomes.

Effectiveness of Mantra-Based Meditation on Mental Health: A Systematic Review and Meta-Analysis.

BACKGROUND: Meditation is defined as a form of cognitive training that aims to improve attentional and emotional self-regulation. This systematic review aims to evaluate the available scientific evidence on the effectiveness and safety of mantra-based meditation techniques (MBM), in comparison to passive or active controls, or other active treatment, for the management of mental health symptoms. METHODS: MEDLINE, EMBASE, Cochrane Library, and PsycINFO databases were consulted up to April 2021. Randomised controlled trials regarding meditation techniques mainly based on the repetition of mantras, such as transcendental meditation or others, were included. RESULTS: MBM, compared to control conditions, was found to produce significant small-to-moderate effect sizes in the reduction of anxiety (g = -0.46, IC95%: -0.60, -0.32; I2 = 33%), depression (g = -0.33, 95% CI: -0.48, -0.19; I2 = 12%), stress (g = -0.45, 95% CI: -0.65, -0.24; I2 = 46%), post-traumatic stress (g = -0.59, 95% CI: -0.79, -0.38; I2 = 0%), and mental health-related quality of life (g = 0.32, 95% CI: 0.15, 0.49; I2 = 0%). CONCLUSIONS: MBM appears to produce small-to-moderate significant reductions in mental health; however, this evidence is weakened by the risk of study bias and the paucity of studies with psychiatric samples and long-term follow-up.

[Content validation of the spanish version of the Long-term Quality of Life Instrument for long-term female breast cancer survivors.] / Validación de contenido de la versión en castellano del instrumento Long-term Quality of Life Instrument para mujeres supervivientes de cáncer de mama de larga duración.

OBJECTIVE: The quality of life of women affected by breast cancer diagnosed 5 or more years ago has been relatively unexplored in Spain; there are no instruments for its measurement validated. The objective of the study is to translate into Spanish, culturally adapt and examine the content validity of the Spanish version of the Long-Term Quality of Life Instrument (LTQL). METHODS: The initial translation was performed by two translators with Spanish as their mother tongue carried out the translation of the questionnaire, obtaining two initial versions in Spanish (T1 and T2). An analysis of the results and elaboration of a single preliminary version in Spanish (T-1-2) were performed. The retro-translation was performed by two translators with English as their mother tongue not familiar with the original version translated the joint version (T-1-2) back into the original language (RT1 and RT2) to identify inconsistencies. Finally, a final version of the questionnaire was obtained. For content validation a committee of experts (seven women affected by breast cancer) assessed the degree of clarity, accuracy and understanding of each of the items in the questionnaire translated into Spanish, and calculated the content validity index (CVI) of the questionnaire according to Lawshe and Tristán. RESULTS: The LTQL questionnaire was translated into Spanish with a low discrepancy between translators. An adequate CVI higher than 0.58 was obtained in clarity (0.95), precision (0.93), comprehension (0.91) and relevance (0.72). CONCLUSIONS: The LTQL is a useful questionnaire in the health field for the assessment of quality of life of women survivors of long-term breast cancer.

OBJETIVO: La calidad de vida de mujeres afectadas de cáncer de mama diagnosticadas hace 5 o más años ha sido relativamente poco explorada en España, no existen instrumentos para su medida validados. El objetivo del estudio fue traducir al castellano, adaptar culturalmente y examinar la validez de contenido del cuestionario Long-Term Quality of Life Instrument (LTQL). METODOS: La traducción inicial fue realizada por dos traductores con castellano como lengua materna que tradujeron independientemente el cuestionario (versiones T1 y T2). Se realizó un análisis de los resultados y se elaboró una única versión preliminar en castellano (T-1-2). La retrotraducción se realizó por dos traductores con inglés como lengua materna que tradujeron independientemente la versión conjunta (T-1-2) al idioma original (RT1 y RT2) para identificar inconsistencias. Finalmente, se obtuvo una versión final del cuestionario. Para la validación de contenido se constituyó un comité de expertas (siete mujeres afectadas de cáncer de mama) que valoró el grado de claridad, precisión, comprensión y relevancia de cada uno de los ítems del cuestionario traducido al castellano y se calculó el índice de validez de contenido (CVI) del cuestionario según Lawshe y Tristán. RESULTADOS: Se tradujo el cuestionario LTQL al castellano con una baja discrepancia entre los traductores. Se obtuvo un CVI adecuado mayor de 0,58 en claridad (0,95), precisión (0,93), comprensión (0,91) y relevancia (0,72). CONCLUSIONES: El LTQL en un cuestionario de utilidad en el campo de la salud para la evaluación de la calidad de vida de mujeres supervivientes de cáncer de mama de larga duración.

Validación de contenido de la versión en castellano del instrumento Long-term Quality of Life Instrument para mujeres supervivientes de cáncer de mama de larga duración / Content validation of the spanish version of the Long-term Quality of Life Instrument for long-term female breast cancer survivors

Fundamentos: La calidad de vida de mujeres afectadas de cáncer de mama diagnosticadas hace 5 o másaños ha sido relativamente poco explorada en España, no existen instrumentos para su medida validados. El objetivo del estudio fue traducir al castellano, adaptar culturalmente y examinar la validez de contenido del cuestionario Long-Term Quality of Life Instrument (LTQL Métodos: La traducción inicial fue realizada por dos traductores con castellano como lengua materna que tradujeron independientemente el cuestionario (versiones T1 y T2). Se realizó un análisis de los resultados y se elaboró una única versión preliminar en castellano (T-1-2). La retrotraducción se realizó por dos traductores con inglés como lengua materna que tradujeron independientemente la versión conjunta (T-1-2) al idioma original (RT1 y RT2) para identificar inconsistencias. Finalmente, se obtuvo una versión final del cuestionario. Para la validación de contenido se constituyó un comité de expertas (siete mujeres afectadas de cáncer de mama) que valoró el grado de claridad, precisión, comprensión y relevancia de cada uno de los ítems del cuestionario traducido al castellano y se calculó el índice de validez de contenido (CVI) del cuestionario según Lawshe y Tristán. Resultados: Se tradujo el cuestionario LTQL al castellano con una baja discrepancia entre los traductores. Se obtuvo un CVI adecuado mayor de 0,58 en claridad (0,95), precisión (0,93), comprensión (0,91) y relevancia (0,72). Conclusiones: El LTQL en un cuestionario de utilidad en el campo de la salud para la evaluación de la calidad de vida de mujeres supervivientes de cáncer de mama de larga duración.(AU)

Background: The quality of life of women affected by breast cancer diagnosed 5 or more years ago has been relatively unexplored in Spain; there are no instruments for its measurement validated. The objective of the study is to translate into Spanish, culturally adapt and examine the content validity of the Spanish version of the LongTerm Quality of Life Instrument (LTQL). Methods: The initial translation was performed by two translators with Spanish as their mother tongue carried out the translation of the questionnaire, obtaining two initial versions in Spanish (T1 and T2). An analysis of the results and elaboration of a single preliminary version in Spanish (T-1-2) were performed. The retro-translation wasperformed by two translators with English as their mother tongue not familiar with the original version translated the joint version (T-1-2) back into the original language (RT1and RT2) to identify inconsistencies. Finally, a final version of the questionnaire was obtained. For content validation a committee of experts (seven women affected by breast cancer) assessed the degree of clarity, accuracy and understanding of each of the items in the questionnaire translated into Spanish, and calculated the content validity index (CVI) of the questionnaire according to Lawshe and Tristán.Results: The LTQL questionnaire was translated into Spanish with a low discrepancy between translators. An adequate CVI higher than 0.58 was obtained in clarity (0.95), precision (0.93), comprehension (0.91) and relevance (0.72). Conclusions: The LTQL is a useful questionnaire in the health field for the assessment of quality of life of women survivors of long-term breast cancer.(AU)

Aplicaciones móviles para mejorar la adherencia a la medicación: revisión y análisis de calidad / Mobile applications to improve drug adherence: Review and quality analysis

Objetivo: Revisar las aplicaciones móviles en español para mejorar la adherencia farmacológica y evaluar sus características y calidad con el fin de identificar aplicaciones de alta calidad. Médoto: Se ha hecho una revisión siguiendo un procedimiento por pasos similar a una revisión sistemática de la literatura. La fuente de los datos han sido plataformas de distribución digital de aplicaciones móviles Apple Apps Store y Google Play Store. Se han seleccionado aquellas aplicaciones dirigidas a apoyar la autogestión de los medicamentos, capaces de generar recordatorios, en español, actualizadas en los últimos 2 años y gratuitas. Los análisis de las aplicaciones se han hecho según un conjunto de características consideradas deseables y evaluación de la calidad con la herramienta Mobile App Rating Scale. Resultados: De 708 aplicaciones, se seleccionaron 3. Las aplicaciones Medisafe y Mytherapy presentaron el 89% y el 78% de las características deseables, respectivamente. La aplicación de Sergio Licea presentó el 56%. La mayor puntuación global de calidad la obtuvo MyTherapy (3,79/5; RIQ: 3-4), seguida de Medisafe (3,72/5; RIQ: 3-4) y, por último, Sergio Licea (2,87/5; RIQ: 2-4). La valoración de la calidad es coincidente con la hecha por los usuarios. Hay muchas aplicaciones disponibles, sin embargo, la mayoría no cumplieron los criterios de selección establecidos. Conclusiones: Através de un proceso sistemático por pasos, identificamos la aplicación de mayor calidad en español para que sea probada en un estudio futuro, que proporcionará evidencia sobre el uso de una intervención multicomponente para mejorar la adherencia a la medicación.(AU)

Objective: To review the mobile apps in the Spanish market to improve adherence to medications and evaluate their characteristics and quality to identify high-quality applications. Method: A review was carried out following a stepwise procedure similar to a systematic review of the scientific literature. Apple Apps Store and Google Play Store mobile application digital distribution platforms. Applications aimed at supporting self-management of treatment, which generate reminders, in Spanish, updated in the last 2 years and free. We evaluate the applications according to a set of characteristics considered desirable and the quality with the Mobile App Rating Scale tool. Results: Out of 708 applications, 3 applications were selected. The Medisafe and Mytherapy applications had 89% and 78% of the desirable characteristics, respectively. Sergio Licea's application only had 56%. The highest global quality score was obtained by the MyTherapy application (3.79/5, IQR: 3-4), followed by Medisafe (3.72/5, (IQR: 3-4) and, finally, Sergio Licea (2.87/5, IQR: 2-4). The quality assessment coincides with the user assessment. There are many available applications, however, most did not meet the selection criteria. Conclusions: A systematic stepwise process was able to identify the quality application to be tested in a future study that will provide evidence on the use of a multicomponent inter.(AU)

Diffusible signal factor signaling controls bioleaching activity and niche protection in the acidophilic, mineral-oxidizing leptospirilli.

Bioleaching of metal sulfide ores involves acidophilic microbes that catalyze the chemical dissolution of the metal sulfide bond that is enhanced by attached and planktonic cell mediated oxidation of iron(II)-ions and inorganic sulfur compounds. Leptospirillum spp. often predominate in sulfide mineral-containing environments, including bioheaps for copper recovery from chalcopyrite, as they are effective primary mineral colonizers and oxidize iron(II)-ions efficiently. In this study, we demonstrated a functional diffusible signal factor interspecies quorum sensing signaling mechanism in Leptospirillum ferriphilum and Leptospirillum ferrooxidans that produces (Z)-11-methyl-2-dodecenoic acid when grown with pyrite as energy source. In addition, pure diffusible signal factor and extracts from supernatants of pyrite grown Leptospirillum spp. inhibited biological iron oxidation in various species, and that pyrite grown Leptospirillum cells were less affected than iron grown cells to self inhibition. Finally, transcriptional analyses for the inhibition of iron-grown L. ferriphilum cells due to diffusible signal factor was compared with the response to exposure of cells to N- acyl-homoserine-lactone type quorum sensing signal compounds. The data suggested that Leptospirillum spp. diffusible signal factor production is a strategy for niche protection and defense against other microbes and it is proposed that this may be exploited to inhibit unwanted acidophile species.

[Mobile applications to improve drug adherence: Review and quality analysis]. / Aplicaciones móviles para mejorar la adherencia a la medicación: revisión y análisis de calidad.

OBJECTIVE: To review the mobile apps in the Spanish market to improve adherence to medications and evaluate their characteristics and quality to identify high-quality applications. METHOD: A review was carried out following a stepwise procedure similar to a systematic review of the scientific literature. Apple Apps Store and Google Play Store mobile application digital distribution platforms. Applications aimed at supporting self-management of treatment, which generate reminders, in Spanish, updated in the last 2 years and free. We evaluate the applications according to a set of characteristics considered desirable and the quality with the Mobile App Rating Scale tool. RESULTS: Out of 708 applications, 3 applications were selected. The Medisafe and Mytherapy applications had 89% and 78% of the desirable characteristics, respectively. Sergio Licea's application only had 56%. The highest global quality score was obtained by the MyTherapy application (3.79/5, IQR: 3-4), followed by Medisafe (3.72/5, (IQR: 3-4) and, finally, Sergio Licea (2.87/5, IQR: 2-4). The quality assessment coincides with the user assessment. There are many available applications, however, most did not meet the selection criteria. CONCLUSIONS: A systematic stepwise process was able to identify the quality application to be tested in a future study that will provide evidence on the use of a multicomponent intervention to improve medication adherence.

Novel Template Plasmids pCyaA'-Kan and pCyaA'-Cam for Generation of Unmarked Chromosomal cyaA' Translational Fusion to T3SS Effectors in Salmonella.

The type III secretion systems (T3SS) encoded in pathogenicity islands SPI-1 and SPI-2 are key virulence factors of Salmonella. These systems translocate proteins known as effectors into eukaryotic cells during infection. To characterize the functionality of T3SS effectors, gene fusions to the CyaA' reporter of Bordetella pertussis are often used. CyaA' is a calmodulin-dependent adenylate cyclase that is only active within eukaryotic cells. Thus, the translocation of an effector fused to CyaA' can be evaluated by measuring cAMP levels in infected cells. Here, we report the construction of plasmids pCyaA'-Kan and pCyaA'-Cam, which contain the ORF encoding CyaA' adjacent to a cassette that confers resistance to kanamycin or chloramphenicol, respectively, flanked by Flp recombinase target (FRT) sites. A PCR product from pCyaA'-Kan or pCyaA'-Cam containing these genetic elements can be introduced into the bacterial chromosome to generate gene fusions by homologous recombination using the Red recombination system from bacteriophage λ. Subsequently, the resistance cassette can be removed by recombination between the FRT sites using the Flp recombinase. As a proof of concept, the plasmids pCyaA'-Kan and pCyaA'-Cam were used to generate unmarked chromosomal fusions of 10 T3SS effectors to CyaA' in S. Typhimurium. Each fusion protein was detected by Western blot using an anti-CyaA' monoclonal antibody when the corresponding mutant strain was grown under conditions that induce the expression of the native gene. In addition, T3SS-1-dependent secretion of fusion protein SipA-CyaA' during in vitro growth was verified by Western blot analysis of culture supernatants. Finally, efficient translocation of SipA-CyaA' into HeLa cells was evidenced by increased intracellular cAMP levels at different times of infection. Therefore, the plasmids pCyaA'-Kan and pCyaA'-Cam can be used to generate unmarked chromosomal cyaA' translational fusion to study regulated expression, secretion and translocation of Salmonella T3SS effectors into eukaryotic cells.

Acute myelitis and SARS-CoV-2 infection. A new etiology of myelitis?

The etiological agent of coronavirus disease-19 (COVID-19), SARS-coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and quickly spread worldwide leading the World Health Organization (WHO) to recognize it not only as a pandemic but also as an important thread to public health. Beyond respiratory symptoms, new neurological manifestations are being identified such as headache, ageusia, anosmia, encephalitis or acute cerebrovascular disease. Here we report the case of an acute transverse myelitis (TM) in a patient with SARS-CoV-2 infection detected by the nasopharyngeal swab technique but not in cerebrospinal fluid (CSF) analysis. Anti-herpes simplex virus (HSV) 1 and varicella-zoster IgM antibodies were not detected in serum samples and spinal and brain magnetic resonance imaging (MRI) showed no abnormal findings. This case remarks that COVID-19 nervous system damage could be caused by immune-mediated mechanisms.

Clinical, Genomic, and Pharmacological Study of MYCN-Amplified RB1 Wild-Type Metastatic Retinoblastoma.

An uncommon subgroup of unilateral retinoblastomas with highly aggressive histological features, lacking aberrations in RB1 gene with high-level amplification of MYCN (MCYNamplRB1+/+) has only been described as intra-ocular cases treated with initial enucleation. Here, we present a comprehensive clinical, genomic, and pharmacological analysis of two cases of MCYNamplRB1+/+ with orbital and cervical lymph node involvement, but no central nervous system spread, rapidly progressing to fatal disease due to chemoresistance. Both patients showed in common MYCN high amplification and chromosome 16q and 17p loss. A somatic mutation in TP53, in homozygosis by LOH, and high chromosomal instability leading to aneuploidy was identified in the primary ocular tumor and sites of dissemination of one patient. High-throughput pharmacological screening was performed in a primary cell line derived from the lymph node dissemination of one case. This cell line showed resistance to broad spectrum chemotherapy consistent with the patient's poor response but sensitivity to the synergistic effects of panobinostat-bortezomib and carboplatin-panobinostat associations. From these cells we established a cell line derived xenograft model that closely recapitulated the tumor dissemination pattern of the patient and served to evaluate whether triple chemotherapy significantly prolonged survival of the animals. We report novel genomic alterations in two cases of metastatic MCYNamplRB1+/+ that may be associated with chemotherapy resistance and in vitro/in vivo models that serve as basis for tailoring therapy in these cases.

Multicomponent Interventions for the Prevention of Delirium in Hospitalized Older People: A Meta-Analysis.

OBJECTIVES: To comprehensively assess the effects of multicomponent interventions for prevention of delirium in hospitalized older people. DESIGN: Systematic review with meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods. PARTICIPANTS: All randomized controlled trials were included. Included studies were conducted in hospitalized older people (aged ≥65 years). MEASUREMENTS: The electronic databases MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were consulted (search date: 2015 to March 2019). Predefined criteria were used to determine inclusion of studies and to assess their methodologic quality. RESULTS: From 1,250 records identified, 10 randomized controlled trials were included (n = 2,850: 1355 medical patients, 1,243 surgical, and 160 intensive care unit). The multicomponent interventions, compared with usual care, reduced the incidence of delirium (risk ratio (RR) = 0.62; 95% confidence interval (CI) = 0.54-0.72; I2 = 0%; k = 10; n = 2,758), duration of delirium (RR = -1.18; 95% CI = -1.95 to -0.40; I2 = 45%; k = 6; n = 276), severity of delirium (standard mean difference = -0.98; 95% CI = -1.46 to -0.49; I2 = 0%; k = 3; n = 82), and pressure ulcers (RR = 0.48; 95% CI = 0.26-0.88; I2 = 0%; k = 2; n = 457). CONCLUSIONS: This meta-analysis suggests that multicomponent interventions to prevent delirium are effective in decreasing its incidence, duration, and severity; as well as the incidence of pressure ulcers in hospitalized older people. Therefore, multicomponent interventions hold great promise to impact in the most important and prevalent conditions affecting fragile older people during hospitalization.

Health status, lifestyle habits, and perceived social support in long-term cancer survivors: a cross-sectional study.

OBJECTIVE: To compare the presence of comorbidities and self-perceived health and social support between long-term cancer survivors and people without a history of cancer from a clinical trial examining the effects of a multiple risk behavior intervention. RESULTS: Of the 4259 people studied, 190 (4.46%) were cancer survivors. They had a mean ± SD age of 62.8 ± 7 years vs. 58.7 ± 8 years (P < 0.01) for non-cancer people and were more likely to be on long-term sick leave (11.9 vs. 3.5%, P < 0.001). No differences were observed for smoking, adherence to the Mediterranean diet, physical activity, obesity, or social support. Cancer survivors were more likely to have worse self-perceived health (OR 1.82; 95% CI 1.02-2.75), more comorbidities (OR 1.68; 95% CI 1.18-2.39), COPD (OR 2.17; 95% CI 1.25-3.78), and depression (OR 1.65; 95% CI 1.06-2.57). Older age and worse self-perceived health were independent predictors of survivorship in the adjusted analysis.

Pharmacologic interventions for prevention of delirium in hospitalized older people: A meta-analysis.

INTRODUCTION: To comprehensively assess the effects of pharmacologic interventions for prevention of delirium in hospitalized older people. MATERIALS AND METHODS: A systematic review with meta-analysis following Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was performed. Hospitalized people aged 65 and older, recruited to randomized controlled clinical trials. The electronic databases MEDLINE, EMBASE, WOS and Cochrane Central Register of Controlled Trials were consulted (March 2019). Predefined criteria were used to determine inclusion of studies and to assess their methodologic quality. RESULTS: 1855 records were identified in the database, and after removing the duplicates, the titles and abstracts evaluated were 1250 records. Finally, 25 randomized controlled trials contributed to meta-analysis (n = 5820): 1 anti-epileptics (n = 697), 2 anti-inflammatories (n = 615), 4 antipsychotics (n = 1193), 2 cholinesterase inhibitors (n = 87), 13 hypnotics/sedatives (n = 2909), 1 opioids (n = 52), 1 psychostimulants/nootropics (n = 81), 1 yokukansan (n = 186). Olanzapine (RR = 0.36; 95 %CI: 0.24, 0.52; k = 1; n = 400), rivastigmine (RR = 0.36; 95 %CI: 0.15, 0.87; k = 1; n = 62), dexmedetomidine (RR = 0.52; 95 %CI: 0.38, 0.71; I²â€¯= 55 %; k = 6; n = 2084), and ramelteon (RR = 0.09; 95 %CI: 0.01, 0.64; k = 1; n = 65) reduced the incidence of delirium compared to placebo/usual care. Only dexmedetomidine was also associated with a shorter duration of delirium (0.70 days reduction) and a lower consumption of psychotropic drugs (48 %). No effect was found in mortality, adverse events, urinary tract infections or post-operative complications. CONCLUSIONS: This meta-analysis suggests that dexmedetomidine is effective in reducing the incidence and duration of delirium in hospitalized older patients. Individual studies reveal effects of ramelteon, olanzapine and rivastigmine on the incidence of delirium but the evidence is insufficient to draw a robust conclusion.

Effect of an intervention to improve the prescription of antifungals in pediatric hematology-oncology.

BACKGROUND: The use of antifungals has expanded in pediatric hematology-oncology, and the need to develop pediatric-based surveillance and education activities is becoming crucial. The aims of this study were to evaluate the impact of a multidisciplinary protocol on the adequacy of antifungal prescription in a pediatric hematology-oncology unit and to assess the effect of an educational intervention to improve the knowledge of prescribing pediatricians over time. METHODS: A multidisciplinary team established a protocol for the management of invasive fungal disease (IFD). The use of antifungals before (January 2012-May 2013) and after the protocol (June 2013-December 2015) was evaluated. Prescribing pediatricians attended a training course on IFD and were evaluated before 0, 6, and 12 months after the intervention. RESULTS: During the study period, antifungal agents were used in 185 episodes (56 children, 39.3% females), and were administered as prophylaxis (58.9%), empiric (34.6%), or targeted therapy (6.5%). Antifungal prescriptions were inadequate in 7% of the episodes, related to drug selection (53.8%), dosage (38.5%) and route of administration (7.7%). After protocol implementation, inadequate prescriptions decreased 9.9% (15.2% vs 5.3%; P = .04). Following the educational activity, the percentage of adequate responses to the questionnaire improved significantly compared to baseline, and persisted over time (19.7% improvement at 0 months [P < .0001]; 21.1% at 6 months [P < .0001]; 16.6% at 12 months [P = .002]). CONCLUSIONS: The establishment of multidisciplinary protocols and education activities improved the quality of antifungal prescription and the knowledge of prescribers regarding antifungal therapy. Therefore, these activities may be important for the implementation of antifungal stewardship programs in pediatrics.