Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach.

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples.

Validation of a sustainable internationally monitored cervical cancer screening system using a visual smartphone inspection in Kinshasa, Democratic Republic of Congo.

OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of a cervical cancer screening program based on visual inspection with acetic acid and Lugol's iodine using a smartphone in a sub-urban area of very low resources in Kinshasa (Democratic Republic of Congo). METHODS: This cross-sectional validation study was conducted at Monkole Hospital and it included women between the ages of 25-70 years after announcing a free cervical cancer screening campaign through posters placed in the region of our hospital. Questionnaires collected sociodemographic and behavioral patients characteristics. In the first consultation, we gathered liquid-based cytology samples from every woman. At that time, local health providers performed two combined visual inspection techniques (5% acetic acid and Lugol's iodine) while a photograph was taken with a smartphone. Two international specialists evaluated the results of the smartphone cervicography. When a visual inspection was considered suspicious, patients were offered immediate cryotherapy. Cytological samples were sent to the Pathology Department of the University of Navarra for cytological assessment and human papillomavirus (HPV) DNA genotyping. RESULTS: A total of 480 women participated in the study. The mean age was 44.6 years (range 25-65). Of all the patients, only 18.7% were infected with HPV (75% had high-risk genotypes). The most frequent high-risk genotype found was 16 (12.2%). The majority (88%) of women had normal cytology. After comparing combined visual inspection results with cytology, we found a sensitivity of 66.0%, a specificity of 87.8%, a positive predictive value of 40.7%, and a negative predictive value of 95.3% for any cytological lesion. The negative predictive value for high-grade lesions was 99.7%. CONCLUSIONS: Cervical cancer screening through combined visual inspection, conducted by non-specialized personnel and monitored by experts through smartphones, shows encouraging results, ruling out high-grade cytological lesions in most cases. This combined visual inspection test is a valid and affordable method for screening programs in low-income areas.

Pregestational BMI and higher offspring's risk of overweight/obesity in smoker and non-smoker mothers.

OBJECTIVE: To assess the association between pregestational BMI and offspring's risk of overweight/obesity after accounting for the most important confounders, especially maternal smoking habit. DESIGN: Prospective cohort study. SETTING: The Seguimiento Universidad de Navarra (SUN) study is a prospective cohort of Spanish graduates with more than 22 000 participants nationwide. Recruitment started in 1999, and it is permanently open. Data on diet, lifestyle and clinical diagnoses are collected at baseline and every 2 years. PARTICIPANTS: Women from the SUN cohort who reported at least one pregnancy during follow-up (n 3496) were invited to this study. Among them, 1527 agreed to participate and completed an additional more detailed online questionnaire on their pregnancy history and their offspring's nutritional status. RESULTS: After excluding 165 children, we analysed data of 2791 participants born to 1485 mothers and observed that each 5 kg/m2 increase in pregestational BMI was associated with a 0·22 (95 % CI 0·15, 0·29) higher z-score in offspring's BMI and higher risk of overweight/obesity (multivariable-adjusted relative risk (RR) 1·57 (95 % CI 1·39, 1·77)) in childhood or adolescence. Furthermore, we observed stronger association in children born to smoker mothers (RR 1·91; 95 % CI 1·48, 2·46) than from non-smoker mothers (RR 1·51; 95 % CI 1·31, 1·73) (Pfor interaction = 0·02). CONCLUSIONS: We found a synergistic interaction between pregestational BMI and maternal smoking habit on offspring's z-score of the BMI and in their risk of overweight/obesity. Although further research is needed to analyse dose-response relationships, these findings reinforce the importance of promoting healthy lifestyles in pregnant women in order to prevent childhood obesity.

Prevención, diagnóstico y tratamiento de la sepsis neonatal: Guía de práctica clínica basada en evidencias del Instituto Nacional Materno Perinatal del Perú / Prevention, diagnosis and treatment of the neonatal sepsis: Clinical practice guideline-based evidence in a peruvian institute specialized

RESUMEN Introducción. La sepsis neonatal es un conjunto de signos y síntomas clínicos causados por una infección sistémica, asociada a factores de riesgo de tipo materno, neonatal u hospitalario. Objetivo. Brindar recomendaciones informadas por la mejor evidencia disponible para la prevención, diagnóstico y tratamiento de la sepsis neonatal. Métodos. Se desarrolló una guía de práctica clínica (GPC) basada en evidencias, mediante un proceso de adaptación, a cargo de un equipo de metodólogos y médicos neonatólogos expertos en el manejo clínico de la sepsis neonatal. Se realizó la búsqueda y preselección de GPC que respondan al alcance y objetivos planteados, utilizando el instrumento AGREE-II se evalúo la calidad metodológica de las guías para decidir su adaptación. Se realizó una búsqueda sistemática en múltiples bases de datos: Medline/PubMed, Embase/Ovid, Cochrane Library y LILACS, para identificar la evidencia que responda a las preguntas de la guía. Estas fueron seleccionadas y analizadas críticamente por pares clínicos y metodológicos, las recomendaciones fueron elaboradas usando el enfoque GRADE. Resultados. Se formularon 16 preguntas clínicas y recomendaciones basadas en evidencia a las que se llegó, mediante un diálogo deliberativo de expertos clínicos de diferentes hospitales de referencia para el manejo de la sepsis neonatal en el Perú. Las recomendaciones abordan la identificación de factores de riesgo, el uso de métodos confirmatorios y el tratamiento antibiótico como profilaxis y durante manejo de la enfermedad. Conclusiones. La GPC permite estandarizar el manejo clínico de la sepsis neonatal, así como la identificación de necesidades de investigación a realizarse en el contexto peruano.

ABSTRACT Introduction. Neonatal sepsis is a set of clinical signs and symptoms caused by a systemic infection, associated with maternal, neonatal or hospital risk factors. Objective. Provide informed recommendations for the best available evidence for the prevention, diagnosis and treatment of neonatal sepsis. Methods an Evidence-based Clinical Practice Guide (CPG) was developed through an adaptation process, in charge of a team of methodologists and neonatologists who are experts in the clinical management of neonatal sepsis. The search and preselection of CPGs that respond to the scope and objectives set were carried out, using the AGREE-II instrument, the methodological qualityof the guides was evaluated and their adaptation decided. To identify the evidence that answers the questions in the guideline, a systematic search was carried out in multiple databases: Medline / PubMed, Embase / Ovid, Cochrane Library and LILACS. These were selected and critically analyzed by clinical and methodological peers, the recommendations were elaborated using the GRADE approach. Results. 16 clinical questions and recommendations based on evidence were formulated, which were reached, through a deliberative dialogue of clinical experts from different reference hospitals for the management of neonatal sepsis in Peru. The recommendations address the identification of risk factors, the use of confirmatory methods and antibiotic treatment as prophylaxis and during disease management. Conclusions. The CPG allows standardizing the clinical management of neonatal sepsis, as well as the identification of research needs to be carried out in the Peruvian context.

Caesarean delivery is associated with higher risk of overweight in the offspring: within-family analysis in the SUN cohort.

BACKGROUND: Most studies assessing the association between caesarean delivery (CD) and childhood overweight/obesity have failed to account for important confounders, such as maternal prepregnancy body mass index (BMI) or the indication of the CD. Furthermore, within-family analyses have reported contradictory results. We aimed at evaluating the association between CD and offspring's risk of overweight/obesity while adjusting for important confounders and accounting for correlations between siblings. METHODS: Women in the 'Seguimiento Universidad de Navarra' cohort provided structured information regarding their pregnancy history and their children's health through online cross-sectional questionnaires. We calculated adjusted differences in BMI z-score and risk ratios (RR) for offspring's overweight/obesity associated with CD, with hierarchical models to account for correlations between siblings. We also performed a within-family analysis in 341 siblings who were discordant in delivery mode, using conditional multivariable logistic regression. RESULTS: Among the 2791 children analysed, those born by CD had higher average BMI z-scores (difference: 0.17; 95% CI 0.07 to 0.27) and higher risk of overweight/obesity (RR: 1.32, 95% CI 1.05 to 1.65) than children born vaginally. The association did not differ by maternal characteristics or offspring's age strata, and the results were consistent in sensitivity analyses. Furthermore, within-family analysis showed that children born by CD had 2.67-fold higher risk of overweight/obesity (95% CI 1.10 to 5.12) than their peers born vaginally. CONCLUSION: Children born by CD have higher average BMI z-scores and higher risk of overweight/obesity than children born vaginally. The consistency of these findings across multiple approaches to address potential residual confounding likely suggests a true biological effect.