Leishmania Animal Models Used in Drug Discovery: A Systematic Review.

Many different animal models are in use for drug development for leishmaniasis, but a universal model does not exist. There is a plethora of models, and this review assesses their design, quality, and limitations, including the attention paid to animal welfare in the study design and execution. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines of available literature after the year 2000 describing animal models for leishmaniasis. The risk of bias was determined using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias assessment tool. A total of 10,980 records were initially identified after searching the databases PubMed, EMBASE, LILACS, and SciELO. Based on the application of predetermined exclusion and inclusion criteria, a total of 203 papers describing 216 animal experiments were available for full analysis. Major reasons for exclusion were a lack of essential study information or appropriate ethical review and approval. Mice (82.8%; an average of 35.9 animals per study) and hamsters (17.1%; an average of 7.4 animals per study) were the most frequently used animals, mostly commercially sourced, in the included studies. All studies lacked a formal sample size analysis. The promastigote stages of L. amazonensis or L. major were most frequently used to establish experimental infections (single inoculum). Animal welfare was poorly addressed in all included studies, as the definition of a human end-point or consideration of the 3Rs (Replacement, Reduction, Refinement) was hardly addressed. Most animals were euthanized at the termination of the experiment. The majority of the studies had an unknown or high risk of bias. Animal experiments for drug development for leishmaniasis mainly poorly designed and of low quality, lack appropriate ethical review, and are deficient in essential information needed to replicate and interpret the study. Importantly, aspects of animal welfare are hardly considered. This underpins the need to better consider and record the details of the study design and animal welfare.

Safety and efficacy of allylamines in the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review.

Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators-if any-included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.

Quality of life of children and adults following cardiac surgery for congenital heart disease: A Mexican cohort.

Objective: The real burden of (congenital heart defects [CHD]) and the improvement after surgical correction or palliation is both reflected in the quality of life (QoL). There are few studies in Latin-America that evaluate QoL in the CHD population. The purpose of this study was to measure the QoL after corrective or palliative surgery for CHD. Materials and methods: An observational, cross-sectional, and comparative study was carried out at the Miguel Hidalgo Centennial Hospital. Patients from 8 to 18 years old who underwent surgery for CHD were included during a period of 8 months. A total of 40 patients were included, together with a group of 80 healthy controls. From all participants, a KIDSCREEN-52 questionnaire was taken. A comparative analysis of the results was performed. Results: Overall, patients with cardiac surgery had better QoL indexes than healthy controls (p < 0.0001). The difference was greatest in moods and emotions, autonomy, and parent relations. Conclusions: Self-perception of QoL in post-operative patients for congenital heart disease is similar and in certain dimensions higher than the healthy population, possibly due to socioeconomic differences, parental care, and styles of coping with their disease. Higher complexity studies that include psychosocial variables and parental perception are required, and a better understanding of the QoL determinants will improve the attention provided to the patient and their families. Objetivo: Los efectos de las cardiopatías congénitas en los pacientes, así como la mejoría después de la paliación o la corrección quirúrgica, se reflejan en la calidad de vida (CV). Hay pocos estudios en Latinoamérica que evalúen la CV en esta población. El objetivo de este artículo es notificar la CV posterior a la operación paliativa o correctiva para defectos cardíacos congénitos. Material y métodos: Se llevó a cabo un estudio observacional, transversal y comparativo en el Centenario Hospital Miguel Hidalgo. Durante un período de ocho meses se incluyó a pacientes de 8 a 18 años sometidos a una intervención para cardiopatías congénitas. Se reunió a dos grupos de 40 pacientes y 80 controles sanos, pareados por edad y sexo. A cada participante se le aplicó el cuestionario KIDSCREEN-52 y se realizó un análisis comparativo de los resultados. Resultados: Los pacientes sometidos a operación cardíaca tuvieron mejores índices de CV que los controles sanos (p < 0.0001). La mayor diferencia se obtuvo en los aspectos de estado de ánimo y emociones, autonomía y relación con los padres. Conclusiones: La autopercepción de la CV después de una intervención para cardiopatías congénitas es similar y, en ciertas dimensiones, mejor que la de la población sana, tal vez por diferencias socioeconómicas, atención de los padres y modelos de adaptación a la enfermedad. Se requieren estudios más extensos que incluyan variables psicosociales y percepción parental. Una mayor comprensión de los determinantes de la CV podría mejorar la atención ofrecida al paciente y su familia.

Quality of life of children and adults following cardiac surgery for congenital heart disease: A Mexican cohort / Calidad de vida en niños y adultos después de cirugía para cardiopatías congénitas: primera cohorte mexicana

Abstract Objective: The real burden of (congenital heart defects [CHD]) and the improvement after surgical correction or palliation is both reflected in the quality of life (QoL). There are few studies in Latin-America that evaluate QoL in the CHD population. The purpose of this study was to measure the QoL after corrective or palliative surgery for CHD. Materials and methods: An observational, cross-sectional, and comparative study was carried out at the Miguel Hidalgo Centennial Hospital. Patients from 8 to 18 years old who underwent surgery for CHD were included during a period of 8 months. A total of 40 patients were included, together with a group of 80 healthy controls. From all participants, a KIDSCREEN-52 questionnaire was taken. A comparative analysis of the results was performed. Results: Overall, patients with cardiac surgery had better QoL indexes than healthy controls (p < 0.0001). The difference was greatest in moods and emotions, autonomy, and parent relations. Conclusions: Self-perception of QoL in post-operative patients for congenital heart disease is similar and in certain dimensions higher than the healthy population, possibly due to socioeconomic differences, parental care, and styles of coping with their disease. Higher complexity studies that include psychosocial variables and parental perception are required, and a better understanding of the QoL determinants will improve the attention provided to the patient and their families.

Resumen Objetivo: Los efectos de las cardiopatías congénitas en los pacientes, así como la mejoría después de la paliación o la corrección quirúrgica, se reflejan en la calidad de vida (CV). Hay pocos estudios en Latinoamérica que evalúen la CV en esta población. El objetivo de este artículo es notificar la CV posterior a la operación paliativa o correctiva para defectos cardíacos congénitos. Material y métodos: Se llevó a cabo un estudio observacional, transversal y comparativo en el Centenario Hospital Miguel Hidalgo. Durante un período de ocho meses se incluyó a pacientes de 8 a 18 años sometidos a una intervención para cardiopatías congénitas. Se reunió a dos grupos de 40 pacientes y 80 controles sanos, pareados por edad y sexo. A cada participante se le aplicó el cuestionario KIDSCREEN-52 y se realizó un análisis comparativo de los resultados. Resultados: Los pacientes sometidos a operación cardíaca tuvieron mejores índices de CV que los controles sanos (p < 0.0001). La mayor diferencia se obtuvo en los aspectos de estado de ánimo y emociones, autonomía y relación con los padres. Conclusiones: La autopercepción de la CV después de una intervención para cardiopatías congénitas es similar y, en ciertas dimensiones, mejor que la de la población sana, tal vez por diferencias socioeconómicas, atención de los padres y modelos de adaptación a la enfermedad. Se requieren estudios más extensos que incluyan variables psicosociales y percepción parental. Una mayor comprensión de los determinantes de la CV podría mejorar la atención ofrecida al paciente y su familia.

A Modified Case Definition to Facilitate Essential Hospital Care During Ebola Outbreaks.

During the late phase of the large West-African Ebola virus disease (EVD) outbreak, the majority of patients were cared for in designated treatment centers. However, the preexisting healthcare infrastructure was already overwhelmed by the outbreak. This had a huge impact on other, non-EVD-related diseases, causing an unprecedented increase in morbidity and mortality, which most likely exceeded the toll due to EVD directly. Consequently, a crucial question is how to provide appropriate healthcare and safeguard functionality of a healthcare system that also serves patients not suspected or diagnosed to have EVD. Here, we report on the Lion Heart Medical Center's experience in Sierra Leone and note that a case definition of Ebola that is broader than those commonly applied may be better suited when it is necessary to identify atypically presenting, pauci-symptomatic cases.

Circulating bone morphogenetic protein levels and delayed fracture healing.

OBJECTIVE: Despite adequate treatment 5-30% of bone fracture patients experience delayed union. During normal fracture union, bone morphogenetic proteins (BMPs) induce healing through a sequential cascade of events. Improved fracture healing after BMP-2 or -7 supplementation in patients with impaired fracture union suggests a deficiency of one or more of these factors. We postulated that low levels of circulating BMPs may result in delayed bone healing. The aim of this study was to quantify differences in levels of circulating BMP-2, -4, -6, -7, and -9 in patients that have demonstrated normal or delayed fracture healing. PATIENTS AND METHODS: Blood samples were collected from an unselected cohort of 65 patients that had been treated for a diaphyseal tibia or femur fracture. Patients were divided into a group with fracture healing within nine months after injury and a group with delayed fracture union. BMP plasma concentrations were quantified using ELISAs and compared between these two groups. RESULTS: Circulating plasma levels of BMP-2, -4, -6, and -7 did not differ between 34 patients with normal fracture healing and 31 patients with delayed fracture healing. Also the median BMP-9 plasma levels were not statistically different between the two groups of patients. However, the distribution in the patients with normal union showed a wider range (72-2496 pg/ml) compared with the delayed union group (120-816 pg/ml). CONCLUSION: In general, circulating BMP concentrations are not statistically different between patients who demonstrated normal or delayed fracture healing. High circulating BMP-9 levels seem to be associated with faster fracture healing, but are apparently not decisive.