El reto del envejecimiento y la complejidad farmacoterapéutica en el paciente VIH+

Objective: To describe the current knowledge and management of aging and pharmacotherapeutic complexity in HIV + patients. Method: A review of literature was carried out, including articles, originals or reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms «Polypharmacy»/«Polifarmacia», «Aging»/«Envejecimiento», «Frailty»/«Fragilidad», «Complejidad Farmacotera péutica»/«Medication Regimen Complexity» and «HIV»/«VIH» were combined. The review was carried out independently by two authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An aging of the population and an increase in associated comorbidities have been identified, especially over 50 years-old. Immunological changes similar to those that are generated in a non-infected elderly population have been described. These conditions influencing the prescription of antiretroviral treatment, according to studies identified. In parallel, polypharmacy is increasingly present, being defined exclusively by the concomitant use of five drugs. Pharmacotherapeutic complexity, through the Medication Regimen Complexity Index, has begun to analyse and relate to health outcomes. There has been a need to know and apply concepts already known in non-HIV-aged population, such as deprescription, potentially inappropriate medication, cholinergic risk, although few results are available. Conclusions: There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new concepts that help pharmacotherapeutic optimization in this population

Salud oral de los escolares de Ceuta. Influencias de la edad, el género, la etnia y el nivel socioeconómico

Background: The objective of this study is that of gauging the prevalence of dental caries, periodontal disease and malocclusion among the school-age population of Ceuta and the spread thereof by age, sex, ethnic background and father�s occupation. Methods: Prevalence survey of a multistage, stratified, random sample of schoolchildren 7, 12 and 14 years of age (n=347) in order to calculate DMFT and dmft indexes �permanent and deciduous dentition�, CPITN and malocclusion. Assessment of the statistical significance of the differences encountered according to age, sex, ethnic background and socioeconomic status using the Chi-Square, Student T and Snedecor F tests. To calculate, among schoolchildren ages 12 and 14, the odds ratios of showing a DMFT index over 4 and their 95% confidence intervals by gender, ethnic background and the socioeconomic status. Results: Dmft (decayed, filled and missing teeth) was 3.02 at 7 and DMFT was 3.91 at 12 and 4.46 at 14. Odds ratios of DMFT> 4 were 2.26 by gender (95% CI=1,27-4,05), 2.17 by ethnic group (95% CI= 1,18-3,99) and 1.8 by SES (95% CI=0,85-3,81). In schoolchildren of low SES �unemployed father�s� OR by ethnic group was 1,37 (95% CI=0,28-7,0). No statistically significant differences were found in the distribution of malocclusion and periodontal disease � except by age. Conclusions: Dmft and DMFT values are in Ceuta higher than the mean national values and the proposed value of the WHO for the year 2000. Risk of DMFT higher than the median is 2.3 in girls compared with boys, 2.17 in Moslem compared with non Moslem and 1.8 in low SES schoolchildren �unemployed father�s� compared to other SES schoolchildren. The increased risk related to ethnic background is influenced by SES.Fundamento: La caries dental tiene una etiología multifactorial en la que intervienen características del huésped (saliva y esmalte dental), de la flora bucal (placa bacteriana) y del substrato sobre el que ésta se desarrolla (higiene oral y dieta). El objetivo de este trabajo es medir la prevalencia de caries, enfermedad periodontal y maloclusión en la población escolar de Ceuta, y su distribución según edad, género, etnia y nivel socioeconómico (NSE) �medido a través de la ocupación paterna�. Métodos: Se realizó una exploración física de la cavidad bucal a una muestra de escolares de 7, 12 y 14 años (n=347) del distrito sanitario de Ceuta con el fin de calcular los índices cao �dentición temporal�, CAO �dentición definitiva�, CPITN y de maloclusión. La selección de la muestra se realizó de forma aleatoria, estratificada polietápica. Se valoró la significación estadística de las diferencias encontradas aplicando las pruebas de Chi-cuadrado, T de Student. y F de Snedecor. Se calcularon las razones de ventaja (Odds Ratio), según sexo, etnia y NSE, de un índice CAO superior a la mediana de la distribución en escolares de 12 y 14 años. Resultados: El índice cao (piezas cariadas, ausentes y obturadas en dentición temporal) es 3,02 a los 7 años y el índice CAO (piezas cariadas, ausentes y obturadas en dentición definitiva) es 3,91 a los 12 años y 4,46 a los 14 años. Las razones de ventaja (OR) de un índice CAO> 4 a los 12-14 años y sus intervalos de confianza (IC) son los siguientes: 2,26 según género (IC95%= 1,27-4,05), 2,17 según etnia (IC95%=1,18-3,99) y 1,80 según NSE (IC95%=0,85-3,81). En el estrato de bajo NSE la OR por etnia es 1,38 (IC95%= 0,28-7,0). No se observan diferencias significativas en la distribución de maloclusión ni de enfermedad periodontal �excepto por edad�. Conclusiones: Los valores del índice CAO en escolares de Ceuta son más elevados que el promedio nacional y superiores al objetivo marcado por la OMS para el año 2000. El riesgo de índice CAO superior a la mediana es en niñas 2,3 veces mayor que en niños, en musulmanes 2,17 veces mayor que en no musulmanes y en escolares con bajo nivel socioeconómico �padres desempleados� 1,8 veces mayor que en escolares con padres activos. El aumento de riesgo asociado a etnia está influenciado por el nivel socioeconómico

Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin’s lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy

Correction: Smartphone Apps for Patients With Hematologic Malignancies: Systematic Review and Evaluation of Content

[This corrects the article DOI: 10.2196/35851.]

Salud oral de los escolares de Ceuta: influencias de la edad, el género, la etnia y el nivel socioeconómico

Fundamento: La caries dental tiene una etiología multifactorial en la que intervienen características del huésped (saliva y esmalte dental), de la flora bucal (placa bacteriana) y del substrato sobre el que ésta se desarrolla (higiene oral y dieta). El objetivo de este trabajo es medir la prevalencia de caries, enfermedad periodontal y maloclusión en la población escolar de Ceuta, y su distribución según edad, género, etnia y nivel socioeconómico (NSE) -medido a través de la ocupación paterna-. Métodos: Se realizó una exploración física de la cavidad bucal a una muestra de escolares de 7, 12 y 14 años (n=347) del distrito sanitario de Ceuta con el fin de calcular los índices cao -dentición temporal-, CAO -dentición definitiva-, CPITN y de maloclusión. La selección de la muestra se realizó de forma aleatoria, estratificada polietápica. Se valoró la significación estadística de las diferencias encontradas aplicando las pruebas de Chi-cuadrado, T de Student. y F de Snedecor. Se calcularon las razones de ventaja (Odds Ratio), según sexo, etnia y NSE, de un índice CAO superior a la mediana de la distribución en escolares de 12 y 14 años. Resultados: El índice cao (piezas cariadas, ausentes y obturadas en dentición temporal) es 3,02 a los 7 años y el índice CAO (piezas cariadas, ausentes y obturadas en dentición definitiva) es 3,91 a los 12 años y 4,46 a los 14 años. Las razones de ventaja (OR) de un índice CAO> 4 a los 12-14 años y sus intervalos de confianza (IC) son los siguientes: 2,26 según género (IC95%= 1,27-4,05), 2,17 según etnia (IC95%=1,18-3,99) y 1,80 según NSE (IC95%=0,85-3,81). En el estrato de bajo NSE la OR por etnia es 1,38 (IC95%= 0,28-7,0). No se observan diferencias significativas en la distribución de maloclusión ni de enfermedad periodontal -excepto por edad-. Conclusiones: Los valores del índice CAO en escolares de Ceuta son más elevados que el promedio nacional y superiores al objetivo marcado por la OMS para el año 2000. El riesgo de índice CAO superior a la mediana es en niñas 2,3 veces mayor que en niños, en musulmanes 2,17 veces mayor que en no musulmanes y en escolares con bajo nivel socioeconómico -padres desempleados- 1,8 veces mayor que en escolares con padres activos. El aumento de riesgo asociado a etnia está influenciado por el nivel socioeconómico

Venetoclax combination therapy with hypomethylating agents in young adults with relapsed/refractory acute myeloid leukaemia

In recent years, one of the most successful advances in treating acute myeloid leukaemia (AML) has been the combination of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax with hypomethylating agents (decitabine or azacytidine). This combination treatment has an accelerated approval by the Food and Drug Administration for newly diagnosed AML adults who are 75 years of age or older or who have comorbidities and are not eligible to receive intensive induction chemotherapy. AML is the most common form of acute leukaemia in adults, with a median age at diagnosis of 68 years. Consequently, most of the patients included in the studies are elderly. Traditionally, young patients achieve higher remission rates compared with the elderly AML population. Although venetoclax combination therapy could become a treatment option for treating young patients with relapsed/refractory AML, this regimen has not been systematically tested in this setting. In this study, we summarize the currently available evidence on the treatment of venetoclax in combination with hypomethylating agents for the treatment of young relapsed/refractory AML patients, in addition to our experience in clinical practice with two case reports. Venetoclax, combined with hypomethylating agents, seems to be an effective option for young relapsed/refractory AML patients. However, due to the poor quality of the evidence, additional well-designed studies with greater numbers of patients are needed to confirm the effectiveness and safety of venetoclax combination regimens for this population

Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin’s lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy.Peer reviewe

Checklist for clinical applicability of subgroup analysis

[What is known and objective] Subgroup analysis plays an important role in clinical decision‐making. Correct management of subgroup analysis is necessary to optimize effectiveness, safety and efficiency of treatments. No homogeneous criteria have been developed for interpretation of subgroup analysis. In this study, the researcher develops a checklist to evaluate the reliability and applicability of the results of subset analyses.[Methods] With a review of previous literature, three main criteria were included in the checklist: statistical association, biological plausibility and consistency among studies. Statistical association considered interaction probability, prespecification of analysis, number of subgroups analysed, sample size and positive/negative result in global analysis. Each item was given an indicative score. Total score was related to a level of applicability for the results in clinical practice. Checklist validation included interinvestigator concordance and assessment about utility. Three drug examples were used to validate the tool.[Results and discussion] Twenty‐six evaluators showed adequate interinvestigator concordance (kappa 0.79, 1 and 0.83 for each drug example regarding applicability). Kappa values increased to 0.94, 1 and 1 after group discussion. Checklist utility score was greater than 4.7/5 in three drug examples. In pre‐analysis, inter‐researcher agreement on global applicability recommendation of subgroup results to practice was 92.3% (ramucirumab), 96% (nivolumab) and 100% (mepolizumab). In post‐analysis, inter‐researcher agreement on applicability recommendation of subgroup results was 100%, 94.45% and 100%, respectively. The checklist validation shows a high interindividual agreement of the results, both with respect to the evaluation of the applicability of subgroup analysis and concerning clinical decision‐making.[What is new and conclusion] We have developed the first validated tool for interpretation of subgroup analyses. The checklist contributes to the adoption of homogeneous criteria for subgroup analyses, thereby allowing discussion and evaluation of the effects of a health intervention.The translation of this research was funded by the Group for Drug Evaluation, Standardization, and Research in Drug Selection (GENESIS, for its acronym in Spanish) of the Spanish Society of Hospital Pharmacy, Madrid, Spain