Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis

Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization

Cost-effectiveness analysis of five pharmacological strategies for the first-line treatment of patients with neuropathic pain in Colombia

ABSTRACT: Materials and methods: A decision tree was constructed comparing amitriptyline, duloxetine, gabapentin, oxcarbazepine, pregabalin, tramadol and no treatment. The transition probabilities were obtained from a study identified in a systematic review of clinical literature. Costs were measured by expert consensus using the standard case methodology, and resource valuation was carried out using national-level pricing manuals. Deterministic sensitivity, of scenarios, and probabilistic analyses were carried out. Results: pregabalin proved to be the strategy with the best cost-effectiveness relationship, followed by gabapentin and amitriptyline. This result stands in almost all the sensitivity analyses performed, and only changes when the probability of pain reduction of more than 30 % was less than 14 % for pregabalin. Conclusions: pregabalin is a cost-effective alternative, and could be considered as the first-line treatment of patients with neuropathic pain in Colombia. Gabapentin and amitriptyline obtained a similar costeffectiveness relationship, and could be considered as alternatives according to the particular characteristics of each patient and the physician judgement and experience.RESUMEN: Determinar la relación de costo-efectividad de cinco estrategias farmacológicas para el tratamiento de primera línea de pacientes con dolor neuropático en Colombia. Materiales y métodos: se construyó un árbol de decisiones que compara amitriptilina, duloxetina, gabapentina, oxcarbazepina, pregabalina, tramadol y la opción de no tratamiento. Las probabilidades de transición se extrajeron de un estudio identificado en una revisión sistemática de la literatura clínica. Los costos se identificaron con la metodología caso tipo, mediante consenso de expertos, y la valoración de los recursos se llevó a cabo con manuales tarifarios de alcance nacional. Se hicieron análisis de sensibilidad determinísticos, de escenarios y probabilísticos. Resultados: pregabalina resultó ser la estrategia con la mejor relación de costo-efectividad, seguida de gabapentina y amitriptilina. Este resultado se mantiene en la mayoría de los análisis de sensibilidad, y solo se modifica cuando la probabilidad de disminuir el dolor en más del 30 % es inferior al 14 % para pregabalina. Conclusiones: la pregabalina es una alternativa costo-efectiva, por lo que puede ser considerada como tratamiento de primera línea de pacientes con dolor neuropático en Colombia. Gabapentina y amitriptilina obtuvieron una relación similar de costos y beneficios, y también podrían considerarse como alternativas de acuerdo con las características particulares de cada paciente y con el criterio y la experiencia del médico tratante

Isolation of human bone marrow mesenchymal stem cells and evaluation of their osteogenic potential

Las células madre mesenquimatosas de médula ósea humana (abreviadas hBMSCs) constituyen una fuente de células auto-renovables con alto potencial de diferenciación, comúnmente aisladas a partir de los aspirados medulares en huesos largos. Su diferenciación hacia el linaje osteogénico, por ejemplo, ha sido ampliamente utilizada para la evaluación biológica de biomateriales o matrices con aplicaciones en la ingeniería de tejidos óseos. El objetivo de este trabajo consistió en aislar hBMSCs a partir de la cabeza femoral de pacientes sometidos a artroplastia total de cadera, así como evaluar su potencial osteogénico. Brevemente, se extrajo el hueso esponjoso y se disgregó mecánicamente; las células desprendidas se cultivaron y las células no adherentes se eliminaron luego de 4 días. El potencial osteogénico se evaluó en la quinta generación de cultivo, mediante ensayos de diferenciación a 14 y 20 días donde se compararon cultivos con y sin suplementos osteogénicos. La evaluación se realizó mediante tinción con Alizarina Roja y la cuantificación de los niveles de expresión génica de los marcadores osteogénicos colágeno tipo I, osteonectinca y sialoprotiena ósea mediante RT-PCR en tiempo real. Las hBMSCs obtenidas presentaron un fenotipo no-diferenciado estable, así como la capacidad de mineralizar la matriz extracelular y expresar un fenotipo similar al osteoblasto durante la inducción osteogénica. Los tres marcadores evaluados se sobre-expresaron en los cultivos en condiciones osteogénicas, y se encontró que cambios hasta de 2X en sus niveles de expresión son relevantes para el desarrollo del proceso de diferenciación. El modelo de hBMSCS presentado podría ser utilizado para la evaluación in vitro de la osteoinductividad de diferentes biomateriales, moléculas bioactivas o matrices para ingeniería de tejidos.Human bone marrow mesenchymal stem cells (hBMSCs) comprise a cell population capable of self-renewal and multilineage differentiation commonly isolated from bone marrow aspirates of large bones. Their osteogenic potential has been extensively exploited for the biological evaluation of scaffolds or biomaterials with applications in bone tissue engineering. This work aimed to isolate hBMSCs from femoral heads of patients undergoing total hip arthroplasty and to evaluate their osteogenic potential. Briefly, the trabecular bone was extracted and mechanically disaggregated; the released cells were cultured and non-adherent cells were removed after 4 days. The osteogenic potential was evaluated at the fifth passage after 14 and 20 days of induction, comparing cultures with and without osteogenic supplements, via Alizarin red staining and the quantification of the gene expression levels of the osteogenic markers collagen type I, osteonectin and bone sialoprotein through real-time RT-PCR. The obtained hBMSCs presented a stable undifferentiated phenotype after prolonged cell culture, matrix mineralization capabilities and expression of osteoblast phenotype upon osteogenic induction. The three markers were up-regulated in cultures under osteogenic conditions and 2 fold differences in their expression levels were found to be significant for the onset of the differentiation process. The obtained hBMSCs may have applications on the in vitro evaluation of the osteoinductivity of different biomaterials, bioactive molecules or tissue engineering scaffolds

Self-Rated Health Status and Cardiorespiratory Fitness in a Sample of Schoolchildren from Bogotá, Colombia. The FUPRECOL Study

To evaluate the relationship between Self-Rated Health (SRH) and cardiorespiratory fitness (CRF) in a sample of children and adolescents enrolled in official schools in Bogotá, Colombia. A cross-sectional study was performed with 7402 children and adolescents between 9 and 17 years of age. Participants were asked to rate their health based on eight validated questions, addressing the participants propensity for headache, stomach-ache, backache, feeling-low, irritability/bad mood, nervousness, sleeping-difficulties, and dizziness. The choices were “rarely or never”, “almost every month”, “almost every week”, and “more than once a week/about every day”. Participants performed the international course-navette shuttle run test to estimate CRF, and cut-off points for age and gender were used to categorize the healthy/unhealthy fitness zone according to the FITNESSGRAM® criteria. Overall, 16.4% of those surveyed reported a perception of irritability/bad mood “more than once a week/about every day”, followed by feeling-low and nervousness (both with 9.9%). Dizziness had the lowest prevalence with a percentage of 6.9%. Unhealthy CRF in boys increased the likelihood of headaches by 1.20 times, stomach aches by 1.31 times, feeling-low by 1.29 times, nervousness by 1.24 times, and dizziness by 1.29 times. In girls, unhealthy CRF increased the likelihood of headaches by 1.19 times, backache by 1.26 times, feeling-low by 1.28 times, irritability/bad mood by 1.17 times, sleeping-difficulties by 1.20 times, and dizziness by 1.27 times. SRH was associated with CRF in both genders. Early identification of children and adolescents with low CRF levels will permit interventions to promote healthy behaviors and prevent future diseases during adulthood.The FUPRECOL Study was possible due to the financial support provided by the Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología “Francisco José de Caldas” COLCIENCIAS (Contract No. 671-2014 Code 122265743978)

Condição periodontal e qualidade de vida relacionada à saúde bucal em um grupo de pacientes com doença de Parkinson

Introduction: there is a relationship between some neurodegenerative conditions such as Parkinson's disease and the presence of periodontitis. Identify its specific situation allows establishing prevention and treatment strategies.Objective: to determine the periodontal condition and the oral health-related quality of life (OHRQoL) in a group of patients with Parkinson's disease in the city of Medellín- Colombia.Methods: a descriptive study was conducted on 25 patients from a Foundation in the city. A survey and a clinical examination were conducted with information on sociodemographic and clinical variables, and the application of the OHIP-14P was carried out. The periodontal condition and the OHRQoL were determined according to different variables. The ethical requirements for health research were met.Results: 76% have localized Periodontitis. There were statistically significant differences (p <0.05) in terms of variables such as probing depth ≥ 4 mm by sex (greater in men) and greater dental loss in> 65 years. A greater impact of oral and periodontal health was identified on the quality of life in men, those people > 65 years, with a higher level of academic training, those with low social support, and a shorter time with a diagnosis of Parkinson's disease. Similarly, a relationship in the OHRQoL was observed in case of people with negative indicators of general and oral health and those using dental prostheses.Conclusions: no subject evaluated was healthy and the majority had localized Periodontitis. Differences in the periodontal status and the OHRQoL in patients with Parkinson´s disease according to sociodemographic and clinical variables.Introducción: existe relación entre condiciones neurodegenerativas como la enfermedad de Parkinson y la presencia de periodontitis. Identificar su situación específica permitirá establecer estrategias de prevención y tratamiento.Objetivo: determinar la condición periodontal y la calidad de vida relacionada con la salud bucal (CVRSB) en un grupo de pacientes con Enfermedad de Parkinson en la ciudad de Medellín- Colombia.Métodos: estudio descriptivo realizado en 25 pacientes de una Fundación de la ciudad. Se realizó encuesta y examen clínico con información de variables sociodemográficas y clínicas, y aplicación del OHIP-14P. Se determinó la condición periodontal y la CVRSB de acuerdo a diferentes variables. Se cumplieron los requisitos éticos para investigación en salud.Resultados: el 76% tienen Periodontitis localizada. Existen diferencias estadísticamente significativas (p<0,05) en términos de variables como profundidad sondeable ≥ 4mm por sexo (mayor en hombres) y mayor pérdida dental en personas ≥ 65 años. Se identificó mayor impacto de la salud bucal y periodontal en la calidad de vida en los hombres, y en personas mayores de 65 años, con un mayor nivel de formación académica, con bajo apoyo social, y menor tiempo con diagnóstico de enfermedad de Parkinson. De igual forma existe relación de la CVRSB en personas con indicadores negativos de salud general y bucal y en aquellas que usaban prótesis dentales.Conclusiones: ningún sujeto evaluado estaba sano periodontalmente, en su mayoría con enfermedad periodontal localizada. Se encontraron diferencias en el estado periodontal de los pacientes con Parkinson y su CVRSB de acuerdo a factores sociodemográficos y clínicos.Introdução: existe uma relação entre condições neurodegenerativas como a doença de Parkinson e a presença de periodontite. Identificar sua situação específica permitirá que você estabeleça estratégias de prevenção e tratamento. Objetivo: determinar a condição periodontal e a qualidade de vida relacionada à saúde bucal (QVRS) em um grupo de pacientes com doença de Parkinson na cidade de Medellín-Colômbia. Métodos: estudo descritivo realizado com 25 pacientes de uma Fundação municipal. Realizou-se levantamen-to e exame clínico com informações sobre variáveis sociodemográficas e clínicas, e aplicação do OHIP-14P. A condição periodontal e a QVRS foram determinadas de acordo com diferentes variáveis. Os requisitos éticos para pesquisa em saúde foram atendidos. Resultados: 76% têm periodontite localizada. Existem diferenças estatisticamente significativas (p<0,05) em termos de variáveis como profundidade probável ≥ 4mm por sexo (maior em homens) e maior perda dentária em pessoas ≥ 65 anos. Identificou-se maior impacto da saúde bucal e periodontal na qualidade de vida em homens e em pessoas com mais de 65 anos, com maior nível de formação acadêmica, com baixo suporte social e menor tempo de diagnóstico da doença de Parkinson. Da mesma forma, há relação entre QVRS em pessoas com indicadores negativos de saúde geral e bucal e naqueles que usaram próteses dentárias. Conclusões: nenhum dos indivíduos avaliados era periodontalmente saudável, a maioria com doença peri-odontal localizada. Foram encontradas diferenças no estado periodontal de pacientes com Parkinson e sua QVRS de acordo com fatores sociodemográficos e clínicos

Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis

Background Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. Methods We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). Findings Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4–20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals. Interpretation Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries

Rapid health evaluation in migrant peoples in transit through Darien, Panama: protocol for a multimethod qualitative and quantitative study.

BACKGROUND: The world is currently unprepared to deal with the drastic increase in global migration. There is an urgent need to develop programs to protect the well-being and health of migrant peoples. Increased population movement is already evident throughout the Americas as exemplified by the rising number of migrant peoples who pass through the Darien neotropical moist broadleaf forest along the border region between Panama and Colombia. The transit of migrant peoples through this area has an increase in the last years. In 2021, an average of 9400 people entered the region per month compared with 2000-3500 people monthly in 2019. Along this trail, there is no access to health care, food provision, potable water, or housing. To date, much of what is known about health needs and barriers to health care within this population is based on journalistic reports and anecdotes. There is a need for a comprehensive approach to assess the health care needs of migrant peoples in transit. This study aims to describe demographic characteristics, mental and physical health status and needs, and experiences of host communities, and to identify opportunities to improve health care provision to migrant peoples in transit in Panama. STUDY DESIGN AND METHODS: This multimethod study will include qualitative (n = 70) and quantitative (n = 520) components. The qualitative component includes interviews with migrant peoples in transit, national and international nongovernmental organizations and agencies based in Panama. The quantitative component is a rapid epidemiological study which includes a questionnaire and four clinical screenings: mental health, sexual and reproductive health, general and tropical medicine, and nutrition. CONCLUSION: This study will contribute to a better understanding of the health status and needs of migrant peoples in transit through the region. Findings will be used to allocate resources and provide targeted health care interventions for migrant peoples in transit through Darien, Panama