The presence of El Niño Southern Oscillation (ENSO) implies the presence of fluctuating rains in coastal areas and these changes influence the occurrence of febrile syndromes outbreaks. In Peru, Aedes aegypti is the vector responsible for various viruses such as the dengue, Zika, chikungunya, which is distributed in 18 Peruvian departments. These viruses cause similar clinical characteristics in the host and for this reason rapid, sensitive and specific diagnostic tests are needed so that the patient can receive timely treatment. / Revisión por pares

Introduction: There is uncertainty whether low-risk febrile neutropenia (FN) episodes in children with cancer are best managed in the inpatient or outpatient setting. Methods: A cost-utility model was created to compare four different treatment strategies for low-risk FN in pediatric cancer patients. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollar), and incremental cost-effectiveness ratios (ICER). Results: The most cost-effective strategy was outpatient treatment with intravenous antibiotics. It was cost saving ($2,732 versus $2,757) and more effective (0.66 QAFNE versus 0.55 QAFNE) as compared to outpatient treatment with oral antibiotics. An early discharge strategy after 48 hours in hospital was slightly more effective but significantly more expensive than outpatient treatment with intravenous antibiotics resulting in an unacceptably high ICER of more than $130,000 per QAFNE. Inpatient care was the least cost-effective strategy. Conclusions: Outpatient strategies for treatment of low-risk FN in children are more cost-effective than traditional inpatient care.

Introduction: There is uncertainty whether low-risk febrile neutropenia (FN) episodes in children with cancer are best managed in the inpatient or outpatient setting. Methods: A cost-utility model was created to compare four different treatment strategies for low-risk FN in pediatric cancer patients. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollar), and incremental cost-effectiveness ratios (ICER). Results: The most cost-effective strategy was outpatient treatment with intravenous antibiotics. It was cost saving ($2,732 versus $2,757) and more effective (0.66 QAFNE versus 0.55 QAFNE) as compared to outpatient treatment with oral antibiotics. An early discharge strategy after 48 hours in hospital was slightly more effective but significantly more expensive than outpatient treatment with intravenous antibiotics resulting in an unacceptably high ICER of more than $130,000 per QAFNE. Inpatient care was the least cost-effective strategy. Conclusions: Outpatient strategies for treatment of low-risk FN in children are more cost-effective than traditional inpatient care.

Les crises fébriles représentent l'évènement épileptique le plus fréquent dans l'espèce humaine et touchent 5 % de la population. Bien que la bénignité de leur pronostic ait été établie par de nombreuses études prospectives, une infime proportion de ces enfants va développer un syndrome d'épilepsie mésio-temporale avec sclérose de l'hippocampe. L'hypothèse de ce travail est que la crise fébrile serait nécessaire mais non suffisante au développement de ce type d'épilepsie, un second élément au potentiel épileptogène serait ainsi indispensable. Notre travail a montré que les crises hyperthermiques chez la souris constituent une bonne approche pour modéliser les crises fébriles de l'enfant. Nous avons ainsi montré que les conséquences des crises hyperthermiques étaient différentes selon la séquence de survenue par rapport au second évènement épileptogène. (i) Lorsque la crise hyperthermique précède l'injection de kaïnate dans l'hippocampe, elle accélère la phase d'épileptogenèse et majore la dispersion des cellules granulaires du gyrus denté, sans modifier la perte cellulaire des neurones pyramidaux de la corne d'Ammon. Elle entraine également une modification du pattern des décharges rythmiques hippocampiques lors de la phase chronique, sans modifier la fréquence ni la durée de ces décharges. (ii) Lorsque la crise hyperthermique succède à la présence d'une dysplasie de la partie CA3 de la corne d'Ammon d'origine génétique, elle semble diminuer le risque de crise chez les animaux KO pour le gène de la double cortine. Pourtant, l'augmentation de la fréquence d'une néo-expression du NPY par les cellules granulaires, chez les animaux Hz pour cette mutation, suggère que les crises hyperthermiques favoriseraient la route vers une épilepsie, tout en activant la mise en place de mécanismes protecteurs contre la survenue des crises. En conclusion, les crises hyperthermiques faciliteraient la route vers l'épilepsie, mais n'auraient pas d'effet facilitateur sur la route vers la crise. / Whereas febrile seizures are the most common seizure type in children and are reported in the history of mesial temporal lobe epilepsy, their role in its etiology remains controversial. They have been suggested to modify the functional organization of the hippocampus but to require another insult to induce epilepsy. To test this hypothesis, we developed a model of hyperthermic seizures in mice and examined their long-term consequences on a second insult induced either by (i) intra-hippocampal kaïnic acid injection in adult animals or by (ii) hippocampal dysplasia developed by double-cortin knock-out mice. (i) While adults, mice that were subjected to hyperthermic seizures developed epileptogenesis more rapidly than sham mice. The occurrence and duration of hippocampal paroxysmal discharges were not modified by hyperthermic seizures, as was their mean time-frequency. In this model, hyperthermic seizures increased the granular cells dispersion, but have no influence on the massif pyramidal cell loss. (ii) In preexisting hippocampal dysplasia, the occurrence of hyperthermic seizures did not increase the proportion of seizures in double-cortin knock-out mice after hyperthermic seizures, and suggest that hyperthermic seizures rather might decrease recurrent seizures via the neo-expression of NPY. In conclusion, hyperthermic seizures in immature mice might facilitate the route to epilepsy, but did not exacerbate the route to seizures.

No description available.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objective: This study was carried out to determine the prevalence of leptospirosis among febrile patients with a suspicious clinical diagnosis of dengue fever in northern Peru. Results: A total of 276 serum samples from patients with acute febrile illness (AFI) and suspected diagnosis for dengue virus (DENV) were analyzed. We identified an etiological agent in 121 (47.5%) patients, DENV was detected in 30.4% of the cases, leptospirosis in 11.2% and co-infection by both pathogens was observed in 5.9% of the patients. In this study the most common clinical symptoms reported by the patients were: headache 89.1%, myalgias 86.9% and arthralgias 82.9%. No differences in symptomatology was observed among the different study groups. / National Research Foundation of Korea / Revisión por pares

Thesis (M.Med. (Paediatrics and Child Health)) -- University of Limpopo, 2022 / BACKGROUND Febrile neutropenia is a medical emergency that complicates the clinical course and treatment of both hematological and solid malignancies, potentially worsening the overall outcome and increasing the financial burden. The epidemiology of pathogens is varied, and determines the selection of empiric antibiotic therapy for febrile neutropenia. Empirically piperacillin/tazobactam plus amikacin has been recommended as the most suitable antibiotic for management of febrile neutropenia. There is a lack of local studies to provide advice for antibiotic choice in our setting. OBJECTIVE To identify causative organisms of infection and antibiotic susceptibility patterns in childhood cancer patients with chemotherapy related febrile neutropenia in Pietersburg Hospital Oncology Ward Limpopo Province. METHODS This is a retrospective cross-sectional study that reviewed all the febrile neutropenic episodes in children with cancer and with a positive blood culture during the febrile neutropenia episode. Data collected included patient demographics (date of birth, sex, date of diagnosis) diagnosis, organisms cultured and the antibiotic sensitivity profile. RESULTS There were 152 records of positive blood cultures identified of 348 episodes of febrile neutropenia for 413 patients. The median age of study population is 6years (mean age of 6.8years; range 3 to 11years) with male predominance at (61.2%). The most common cancer diagnosis was Acute Lymphoblastic Leukemia (ALL) (33.6%) followed by Nephroblastoma (15.8%), Acute myeloid leukemia (11.2%), Non- Hodgkin’s lymphoma (9.9%), Hodgkin’s lymphoma (5.9%) and other cancers (15.3%). The majority of causative organisms were gram-positive bacteria (45%) followed by gram-negative bacteria (32.4%) and fungi (6.1%). Gram-positive organisms were statistically significant pathogens causing bacteraemia more often in neutropenic patients than gram-negative organisms with a p value=0.016. The majority (n=102; 67.10%) were sensitive organisms with the minority being multidrug resistant organisms (n=23; 15.1%) and 17.8% were contaminants n=27. The most common gram-positive pathogens were Coagulase negative staphylococcus n=37; (21.6%). The most common multidrug resistant organisms were Klebsiella pneumoniae CRE (10.7 %;), followed by Enterococcus faecium VRE (1.9%), Klebsiella oxytoca CRE (1.3%), Enterococcus faecalis VRE (0.6%), and Staphylococcus aureus MRSA (0.6%). No multidrug resistant fungal organisms were cultured. The majority of organisms were sensitive to the first line empiric therapy piperacillin/tazobactam plus Amikacin (67.10%). Thirty patients died during these febrile neutropenic episodes and case fatality rate was 8.6%. CONCLUSION This study confirmed that the causative bacteria of febrile neutropenia in this study were susceptible to the first line empiric therapy piperacillin/tazobactam plus amikacin, and this regimen is therefore appropriate for this paediatric oncology unit.

This article reports the findings of a grounded theory study of the processes involved in adherence and treatment seeking delay for febrile neutropenia in chemotherapy patients. Interviews were conducted with 12 patients. Six theoretical constructs were generated, namely ‘Recall of Treatment Advice’, ‘Impact of Emotions’, ‘Influence of Social Networks’, ‘Symptom Monitoring Behaviour’, ‘Symptom Interpretation’, and ‘Preparation and Journey Time’. A model was developed to reflect the complex interplay between these theoretical constructs. Data extracts are presented to illustrate the grounding of the model in patients’ accounts, and the model is discussed with reference to previous theory and research.

Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme with an important function in cell oxidative damage prevention. Erythrocytes have a predisposition towards oxidized environments due to their lack of mitochondria, giving G6PD a major role in its stability. G6PD deficiency (G6PDd) is the most common enzyme deficiency in humans; it affects approximately 400 million individuals worldwide. The overall G6PDd allele frequency across malaria endemic countries is estimated to be 8%, corresponding to approximately 220 million males and 133 million females. However, there are no reports on the prevalence of G6PDd in Andean communities where bartonellosis is prevalent.

New approaches quantifying the effect of treatment are needed in oncology to improve the drug development process and to enable treatment optimization for existing therapies. This thesis focuses on the development of pharmacometric models for biomarkers, side effects and efficacy in order to identify predictors of clinical response in anti-cancer drug therapy. The variability in myelosuppression was characterized in six different cytotoxic anticancer treatments to evaluate a model-based dose individualization approach utilizing neutrophil counts as a biomarker. The estimated impact of inter-occasion variability was relatively low in relation to the inter-individual variability, indicating that myelosuppression is predictable from one treatment course to another. The approach may thereby be useful for dose optimization within an individual. To further study and to identify predictors for the severe side effect febrile neutropenia (FN), the relationship between the shape of the myelosuppression time-course and the probability of FN was characterized. Patients with a rapid decline in neutrophil counts and high drug sensitivity were identified to have a higher probability of developing FN compared with other patients who experience grade 4 neutropenia. Predictors of clinical response in patients receiving sunitinib for the treatment of gastro-intestinal stromal tumor (GIST) were identified by the development of an integrated modeling framework. Drug exposure, biomarkers, tumor dynamics, side effects and overall survival (OS) were linked in a unified structure, and univariate and multivariate exposure variables were tested for their predictive capacities. The soluble biomarker, sVEGFR-3 and tumor size at start of treatment were found to be promising predictors of overall survival, with decreased sVEGFR-3 levels and smaller baseline tumor size being predictive of longer OS. Also hypertension and neutropenia was identified as predictors of OS. The developed modeling framework may be useful to monitor clinical response, optimize dosing in sunitinib and to facilitate dose individualization.