Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially underrepresented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past 2 decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES: RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION: Each trial was reviewed and extracted independently by 2 investigators with disagreements settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described, and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843 of 255,237) were from LMICs. According to the RI, 6 LMICs were overrepresented (>1.25), 7 were adequately represented (0.75-1.25), and 26 were underrepresented (<0.75). Most global CKD RCTs (80.2%) included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71of 310) in 2003-2007 to 45.5% (n=140of 308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of nonrandomized studies of intervention, and studies identified in 1 database. CONCLUSIONS: Despite an increase in participation over the past 2 decades, individuals with CKD from LMICs remain significantly underrepresented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) substantially affects people from low- and middle-income countries (LMICs). However, the participation of these countries in randomized controlled trials (RCTs) remains uncertain. To assess the global distribution and representation of these countries in kidney disease research, we reviewed 1,366 CKD drug RCTs published from 2003-2023, conducted in 84 countries involving more than 300,000 participants. LMICs were included in approximately a third of these studies, with their participants making up approximately one-quarter of the total; lower-middle-income countries were poorly represented, and low-income countries were absent. LMICs constituted a third of participants in multinational RCTs. Most LMICs were underrepresented relative to the prevalence of CKD. We observed an increasing inclusion of LMICs, particularly in the last decade. Nonetheless, individuals with CKD from LMICs remain underrepresented in drug RCTs, suggesting that increased efforts are warranted to include representation of these populations in these studies.

Training in Transplantation and Cellular Therapy in Latin America: A Cross-Sectional Study of the LABMT: Cell Therapy and Transplantation Training in Latin America: A LABMT Survey.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a complex and resource-intensive procedure that has become a critical treatment for certain hematologic conditions. However, in Latin America, access to HCT is limited compared to high-income countries, in part due to a lack of standardized training programs for HCT professionals. To address this gap, the Latin-American Bone Marrow Transplantation Group (LABMT) conducted a cross-sectional study to assess the current state of training programs in HCT and cellular therapy across the region. OBJECTIVE(S): This study aimed to describe and analyze the availability, characteristics, and challenges of HCT training programs in Latin America, with a focus on identifying barriers and proposing solutions for improvement. STUDY DESIGN: A cross-sectional survey was sent to 127 recognized HCT centers across 14 Latin American countries in December 2022. The survey collected data on institutional characteristics, training program structure, costs, and barriers to program development. Descriptive statistics were used to summarize the data, and comparative analyses were performed using Chi-square and Mann-Whitney tests. RESULTS: Of the 127 centers surveyed, 50 (39%) responded, with the majority located in Brazil (34%) and Mexico (30%). Among the respondents, 64% (n=32) offered formal training programs lasting six months or longer. The most significant barriers reported were lack of funding (n=21), limited number of transplant procedures (n=15), and a shortage of qualified professors (n=11). Proposed solutions included increasing student mobility opportunities (n=28), enhancing program quality (n=27), and improving access to funding (n=15). Only 6% of programs offered exposure to CAR-T therapy, and fewer than half of the centers provided international rotations. CONCLUSIONS: This study highlights significant disparities in HCT training programs across Latin America, with most countries lacking access to formalized training. While Brazil and Mexico serve as regional hubs, other nations have limited or no training opportunities. Addressing these gaps through increased funding, international collaborations, and standardized curricula is essential to improving HCT training and ultimately patient care in the region.

[Epidemiological profile of allergic respiratory disease in Mexican children]. / Perfil epidemiológico de la enfermedad respiratoria alérgica en niños mexicanos.

OBJECTIVE: Report the prevalence and severity of the most common allergic diseases in children living in Monterrey, México. METHODS: Cross-sectional multi-center survey on the most common allergic diseases, completed by parents of 6-7-year-old children and by 13-14- year-old adolescents in the Monterrey metropolitan area, between January 2018 and December 2019. RESULTS: A total of 3,044 questionnaires were eligible for the analysis. Among children between 6-7 years old, 30.2% (n = 143/473) presented wheezing at any time in their life; with a higher prevalence in the male population. In the adolescent group, 26.4% reported having experienced wheezing at some point in their life, with a slight predominance in the female group (54.9%). CONCLUSIONS: Knowing the prevalence of allergic diseases in our population gives us tools to generate strategies that allow us to provide the best quality healthcare to our patients.

OBJETIVO: Reportar la prevalencia y gravedad de las enfermedades alérgicas más comunes en niños residentes en Monterrey, México. MÉTODOS: Encuesta multicéntrica transversal, acerca de las enfermedades alérgicas más comunes, completada por padres de niños de 6 aa 7 años y por adolescentes de 13 a 14 años del área metropolitana de Monterrey, entre enero de 2018 y diciembre de 2019. RESULTADOS: Un total de 3044 cuestionarios fueron elegibles para el análisis. Entre los niños de 6-7 años, 30.2% (n = 143/473) manifestaron sibilancias en algún momento de su vida; con mayor prevalencia en la población masculina. En el grupo de adolescentes el 26.4% refirió haber tenido sibilancias alguna vez en su vida, con un ligero predominio en el grupo femenino (54.9%). CONCLUSIONES: Conocer la prevalencia de las enfermedades alérgicas en la población brinda herramientas para generar estrategias para la mejor calidad asistencial en los pacientes.

Patient-important outcomes in clinical trials of atopic diseases and asthma in the last decade: A systematic review.

Background: Randomized Clinical Trials (RCTs) are important tools to establish the effects of a given intervention. Investigators should focus on outcomes that patients perceive: patient-important outcomes (PIOs), clinical endpoints that patients value directly and reflect how they feel, function, or survive. However, it is easier to consider surrogated outcomes to reduce costs and achieve better-looking results. The problem with these outcomes is that they indirectly measure PIOs, which might not correlate linearly or translate reliably into a positive PIO. Methods: We systematically searched MEDLINE for atopic disease RCTs rated among the top 10 allergic diseases and general internal medicine journals from the last 10 years. Two independent reviewers worked in duplicate and independently to collect data from all eligible articles. We gathered information regarding the type of study, title, author information, journal, intervention type, atopic disease, and primary and secondary outcomes. We assessed the outcomes investigators used in RCTs of atopic diseases and asthma. Results: This quantitative analysis included n = 135 randomized clinical trials. The most studied atopic disease during the period selected was asthma (n = 69), followed by allergic rhinitis (n = 51). When divided by atopic disease, primary outcomes in RCTs valuing allergic rhinitis had the most significant proportion of PIOs (76.7), asthma surrogated outcomes (38), and asthma/allergic rhinitis laboratory outcomes (42.9). PIOs in allergic rhinitis trials had the most significant proportion of PIOs favoring the intervention (81.4), asthma had the greatest proportion of surrogated outcomes (33.3), and asthma/allergic rhinitis laboratory outcomes (40). When divided by atopic disease, trials studying atopic dermatitis and urticaria had the same proportion of PIOs (64.7) as their secondary outcomes. Asthma had the highest (37.5) surrogate outcomes. Journals of general/internal medicine had a greater proportion of PIOs, and a post hoc analysis showed a significant difference in the proportion and secondary outcomes that favored the intervention between PIOs and laboratory outcomes. Conclusion: Approximately 7.5 out of 10 primary outcomes in RCTs published in general/internal medicine are PIOs compared to 5 out of 10 primary outcomes in atopic disease journals. Investigators should focus on selecting patient-important outcomes in their clinical trials to establish clinical guidelines with better-quality recommendations that impact patients' life and values. Registration: International Prospective Register of Systematic Reviews (PROSPERO, NIHR) ID: CRD42021259256.

Psychological impact of the COVID-19 pandemic on patients with allergic diseases.

BACKGROUND: On March 2020, World Health Organization (WHO) declared COVID-19 to be a pandemic disease. Interactions between allergy-related inflammatory and psychiatric disorders including depression, anxiety, and post-traumatic stress disorder (PTSD) have been documented. Therefore, those who have pre-existing allergic conditions may have an increased psychiatric reaction to the stresses of the COVID-19 pandemic. OBJECTIVE: Identify the psychological impact of COVID-19 in patients with allergic diseases and determine if these individuals have a greater risk of presenting with post-traumatic stress disorder (PTSD). METHODS: It is a cross-sectional, survey-based study designed to assess the degree of symptoms of depression and the risk of PTSD using the Patient Health Questionnaire (PHQ-9) and the Impact of Event Scale-Revised (IES-R), respectively, in allergic patients. RESULTS: A total of 4106 surveys were evaluated; 1656 (40.3%) were patients with allergic disease, and 2450 (59.7%) were non-allergic (control) individuals. Of those with allergies, 76.6% had respiratory allergic disease including asthma and allergic rhinitis. Individuals with allergic disease reported higher scores regarding symptoms of PTSD on the IES-R scale (p = 0.052, OR 1.24 CI 0.99-1.55) as well as a higher depression risk score in the PHQ-9 questionnaire (mean 6.82 vs. 5.28) p = 0.000 z = -8.76.The allergy group presented a higher score in the IES-R questionnaire (mean 25.42 vs. 20.59), being more susceptible to presenting PTSD (p = 0.000, z = -7.774).The individuals with allergic conditions were further divided into subgroups of those with respiratory allergies such as allergic rhinitis and asthma vs those with non-respiratory allergies such as drug and food allergy, urticaria and atopic dermatitis. This subgroup analysis compares respiratory versus non-respiratory allergic patients, with similar results on the IES-R (mean 25.87 vs 23.9) p = 0.0124, z = -1.539. There was no significant difference on intrusion (p = 0.061, z = -1.873) and avoidance (p = 0.767, z = -0.297), but in the hyperarousal subscale, patients with respiratory allergy had higher scores (mean 1.15 vs. 0.99) p = 0.013 z = -2.486. CONCLUSIONS: Psychological consequences such as depression and reported PTSD are present during the COVID-19 pandemic causing an impact particularly in individuals with allergic diseases. If we acknowledge the impact and how it is affecting our patients, we are able to implement interventions, follow up, and contribute to their overall well-being.