RESUMEN
The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug versus the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend 1) avoiding the use of grace periods when specifying object drug exposure episodes; and 2) including a washout period following each precipitant exposed period.
RESUMEN
Pulmonary artery aneurysm (PAA) is a rare pulmonary vascular disease with nonspecific symptoms and various etiologies. As the disease progresses, in addition to the dilation of the pulmonary arteries, it may be accompanied by remodeling of the cardiac structure and changes in the morphology of the aorta. Recognizing the cause of PAA is therefore a clinically challenging task. In this review article, we provide an overview of various causes of PAA with the support of corresponding imaging findings on computed tomography pulmonary angiography (CTPA) examination. Firstly, from the perspective of hemodynamics, a logical diagnosis is provided according to whether the main pulmonary artery (MPA) is dilated, and whether the PA is dilated locally or diffusely. Secondly, for the imaging examination of vascular wall lesions, due to the limitations of ultrasound examination and interventional procedures, the irreplaceability of dual-phase CTPA examination in disease assessment is especially emphasized. Finally, for highly suspected disorders, it is necessary to comprehensively check with the patient whether there is a family history or past medical history. For patients with PAA, especially those with Marfan syndrome (MFS) or arteritis, adequate preoperative imaging evaluation, regular postoperative radiographic follow-up, and concurrent treatment of the underlying disease (if necessary) are crucial, which are related to the prognosis and long-term quality of life of such patients. Despite the nonspecific features of PAA presentation, a thorough examination of the patient's clinical history and imaging characteristics will play an important role in diagnosing PAA and planning patient management strategies.
RESUMEN
Alveolar echinococcosis (AE) may affect the composition of the host's gut microbiota, potentially disrupting the balance between the gut microbiota and metabolites. Metagenomics and untargeted metabolomics were employed to characterize changes in the gut microbiota and metabolites in mouse models infected with E. multilocularis. Pearson correlation coefficients were calculated to compare the distribution of microbiota and metabolites, revealing synergistic or mutually exclusive relationships. Functional outputs of the gut microbiota were explored using the CAZy database and six enzymes involved in carbohydrate metabolism were identified with statistically significant differential expression between infected and control groups. The resistome was characterized by identifying antibiotic resistance genes annotated in the Comprehensive Antibiotic Resistance Database from the metagenomes of the groups. Firmicutes are the main carrier of ARGs in the host gut with tetQ being most prevalent. Antibiotic efflux, inactivation and target modification were the principal mechanisms of resistance. Comparison and analysis of two sets of antibiotic metabolic pathways allowed the identification of enzyme reactions unique to infected mice. KEGG pathway overview shows phenazine biosynthesis involving phzG to be one of them. In conclusion, infection with AE in mice leads to an overall disruption of gut microbiota and metabolites with the involvement of enzymes related to carbohydrate metabolism. Furthermore, antibiotic-resistance genes may play a role in disease progression, offering potential insights into the relationship between antibiotic use in AE and treatment outcomes.
RESUMEN
Introduction: Highly active antiretroviral therapy (HAART) was piloted in 2002 and was scaled up in 2003 in mainland China. The aim of this study was to evaluate the mortality and its possible predictors based on the long-term initial antiretroviral therapy (ART) cohort among HIV positive children and adolescents. Methods: This prospective open-labeled multicenter cohort study was conducted from January 2008 to July 2021. The participants were recruited from six representative sites in mainland China. A total of 609 participants with an HIV-positive serostatus and <18 years old were recruited and each participant was informed consent at the time of enrollment. Mortality and annual hazard were calculated, and predictors for death were analyzed using Cox regression models generating hazard ratios (HR). Results: The results showed that the mortality was 0.721 per hundred person-years, and the annual hazard was less than 0.10 over time. Both CD4+T cell count and CD4+T cell percentage declined in the death group during the follow-up. The Cox regression model showed that the baseline low CD4+T cell count level (Low vs. High: aHR = 8.309, 95% CI: (1.093, 63.135)) and age >5 years old at HIV diagnosis (6-12 vs. 0-5: aHR = 3.140, 95%CI: (1.331, 27.411)); 13-18 vs. 0-5: aHR = 5.451, 95%CI: (1.434, 20.724)) were possible risk factors for death. Conclusion: The longitudinal cohort study demonstrated the efficacy of China's ART program among HIV-positive children and adolescents which could be beneficial to other countries with limited resources.
RESUMEN
Accurate outcome and exposure ascertainment in electronic health record (EHR) data, referred to as EHR phenotyping, relies on the completeness and accuracy of EHR data for each individual. However, some individuals, such as those with a greater comorbidity burden, visit the health care system more frequently and thus have more complete data, compared with others. Ignoring such dependence of exposure and outcome misclassification on visit frequency can bias estimates of associations in EHR analysis. We developed a framework for describing the structure of outcome and exposure misclassification due to informative visit processes in EHR data and assessed the utility of a quantitative bias analysis approach to adjusting for bias induced by informative visit patterns. Using simulations, we found that this method produced unbiased estimates across all informative visit structures, if the phenotype sensitivity and specificity were correctly specified. We applied this method in an example where the association between diabetes and progression-free survival in metastatic breast cancer patients may be subject to informative presence bias. The quantitative bias analysis approach allowed us to evaluate robustness of results to informative presence bias and indicated that findings were unlikely to change across a range of plausible values for phenotype sensitivity and specificity. Researchers using EHR data should carefully consider the informative visit structure reflected in their data and use appropriate approaches such as the quantitative bias analysis approach described here to evaluate robustness of study findings.
Asunto(s)
Neoplasias de la Mama , Registros Electrónicos de Salud , Humanos , Femenino , Proyectos de Investigación , Sesgo , CogniciónRESUMEN
The potential distribution range and management strategies for P. viburni are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa, i.e., the south of the Sahara Desert, and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.
RESUMEN
Mental health problems leads to serious disease burden among people living with HIV/AIDS (PLHIV). The study aimed at measuring the mental disorders-caused burden of disease based on PLHIV in mainland China. The data used was from the national HIV/AIDS case reporting system, life expectancy (LE) and LE-eliminated suicide were evaluated by the life-table method. The total YLLs and YLLs caused by suicide in each age group were calculated. The disability weights were estimated by the scale of depression symptoms (CES-D) from the multi-center cross-sectional survey, then calculated the corresponding YLDs as a burden of mental illness among PLHIV. Results showed that the LE had been prolonged by implementing antiviral therapy for PLHIV. The proportion of YLLs caused by suicide was the highest (5·46%) in the 15-24 age group. The YLDs in the 25-34 age group were the highest. The YLLs caused by suicide in males were higher than those in the same age group of females. The YLDs and YLLs were higher in heterosexual-infected PLHIV than in homosexual-infected PLHIV, except for YLLs in the 25-34 age group. In summary, this study first provided localized data on the disease burden caused by mental health problems among PLHIV.
Asunto(s)
Costo de Enfermedad , Infecciones por VIH , Esperanza de Vida , Trastornos Mentales , Suicidio , Humanos , Masculino , Femenino , Adulto , China/epidemiología , Persona de Mediana Edad , Estudios Transversales , Infecciones por VIH/psicología , Infecciones por VIH/complicaciones , Suicidio/psicología , Suicidio/estadística & datos numéricos , Adolescente , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Adulto Joven , Anciano , Síndrome de Inmunodeficiencia Adquirida/psicología , Depresión/psicología , Depresión/epidemiologíaRESUMEN
The National surveillance data showed that homosexual transmission played a considerable role in new HIV infections in China. The emphasis on antiretroviral therapy and prevention of mother-to-child transmission provided chances for reproduction among people living with HIV/AIDS. Issues of fertility desire have a paucity of data among HIV-positive men who have sex with men (MSM). This cross-sectional study has assessed fertility attitudes and associated factors, as well as the reproductive knowledge among HIV-positive MSM. Analysis was mainly based on the multinomial regression model. The study included 129 participants, and almost all of the participants (96.1%) were between 18 and 30 years old and 82.2% of them were single. About 35.6% expressed a fertility desire. MSM without siblings tended to have fertility desire (OR = 0.236, 95%CI: 0.078â¼0.712, p = 0.010). Surrogacy (36.4%) was the most desired method among the 86 respondents who had the desire or did not make a decision. While the accuracy of the reproductive knowledge was only 69.6%. In summary, we recommend that providers offer much more professional information and develop assisted reproductive technology to meet the reproductive aspirations of HIV-positive MSM.
Asunto(s)
Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina , Humanos , Masculino , Adulto , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Estudios Transversales , Infecciones por VIH/psicología , Infecciones por VIH/epidemiología , China/epidemiología , Adolescente , Prevalencia , Adulto Joven , Fertilidad , Encuestas y Cuestionarios , Persona de Mediana EdadRESUMEN
BACKGROUND: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. METHODS: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50-999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. RESULTS: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137-0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. CONCLUSION: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Estudios Longitudinales , Incidencia , Viremia/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Insuficiencia del Tratamiento , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Estudios de Cohortes , Carga Viral , Inhibidores de Integrasa , Integrasas/farmacología , Integrasas/uso terapéuticoRESUMEN
Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Animales , Ratones , Sistemas de Liberación de Medicamentos/métodos , Hipertermia Inducida/métodos , Fototerapia/métodos , Doxorrubicina , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , ADN/uso terapéutico , Concentración de Iones de Hidrógeno , Nanopartículas/uso terapéutico , Liberación de Fármacos , Línea Celular TumoralRESUMEN
Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H2 O2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn2+ enables T1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.
Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia/métodos , Biomimética , Preparaciones de Acción Retardada , Neoplasias/patología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
This cohort study compares the proportion of patients with urothelual cancer who initiated first-line chemotherapy and immune checkpoint inhibitors during the periods before and after avelumab approval.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Carcinoma de Células Transicionales/terapia , InmunoterapiaRESUMEN
Chemotherapy remains the mainstay of cancer treatment, and doxorubicin (DOX) is recommended as a first-line chemotherapy drug against cancer. However, systemic adverse drug reactions and multidrug resistance limit its clinical applications. Here, a tumor-specific reactive oxygen species (ROS) self-supply enhanced cascade responsive prodrug activation nanosystem (denoted as PPHI@B/L) was developed to optimize multidrug resistance tumor chemotherapy efficacy while minimizing the side effects. PPHI@B/L was constructed by encapsulating the ROS-generating agent ß-lapachone (Lap) and the ROS-responsive doxorubicin prodrug (BDOX) in acidic pH-sensitive heterogeneous nanomicelles. PPHI@B/L exhibited particle size decrease and charge increase when it reached the tumor microenvironment due to acid-triggered PEG detachment, to favor its endocytosis efficiency and deep tumor penetration. Furthermore, after PPHI@B/L internalization, rapidly released Lap was catalyzed by the overexpressed quinone oxidoreductase-1 (NQO1) enzyme NAD(P)H in tumor cells to selectively raise intracellular ROS levels. Subsequently, ROS generation further promoted the specific cascade activation of the prodrug BDOX to exert the chemotherapy effects. Simultaneously, Lap-induced ATP depletion reduced drug efflux, synergizing with increased intracellular DOX concentrations to assist in overcoming multidrug resistance. This tumor microenvironment-triggered cascade responsive prodrug activation nanosystem potentiates antitumor effects with satisfactory biosafety, breaking the chemotherapy limitation of multidrug resistance and significantly improving therapy efficiency. STATEMENT OF SIGNIFICANCE: Chemotherapy remains the mainstay of cancer treatment, and doxorubicin (DOX) is recommended as a first-line chemotherapy drug against cancer. However, systemic adverse drug reactions and multidrug resistance limit its clinical applications. Here, a tumor-specific reactive oxygen species (ROS) self-supply enhanced cascade responsive prodrug activation nanosystem (denoted as PPHI@B/L) was developed to optimize multidrug resistance tumor chemotherapy efficacy while minimizing the side effects. The work provides a new sight for simultaneously addressing the molecular mechanisms and physio-pathological disorders to overcome MDR in cancer treatment.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Nanopartículas , Neoplasias , Profármacos , Humanos , Profármacos/farmacología , Profármacos/uso terapéutico , Especies Reactivas de Oxígeno , Nanopartículas/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Neoplasias/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: This study aimed to compare survival outcomes of neoadjuvant (NAC) and adjuvant chemotherapy (AdC) within each breast cancer subtype and stage among older women. METHODS: Older (≥ 66 years) women newly diagnosed with stage I-III invasive ductal breast cancer during 2010-2017 and treated with both chemotherapy and surgery within one year were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Analyses were performed within each of six groups, jointly defined based on subtype (hormone receptor [HR]-positive/human epidermal growth factor receptor 2 [HER2]-negative, HER2 + , and triple-negative) and stage (I-II and III). Kaplan-Meier curves and multivariable Cox models were used to compare overall and recurrence-free survival between NAC and AdC, with optimal full matching performed for confounding adjustment. RESULTS: Among 8,495 included patients, 8,329 (20.6% received NAC) remained after matching. Before multiple testing adjustment, Cox models showed that NAC was associated with a lower hazard for death among stage III HER2 + patients (hazard ratio = 0.347, 95% confidence interval CI 0.161-0.745) but a higher hazard for death among triple-negative patients (stage I-II: hazard ratio = 1.558, 95% CI 1.024-2.370; stage III: hazard ratio = 2.453; 95% CI 1.254-4.797). A higher hazard for death/recurrence was associated with NAC among stage I-II HR + /HER2- patients (hazard ratio = 1.305, 95% CI 1.007-1.693). No significant difference remained after multiple testing adjustment. CONCLUSIONS: The opposite trends (before multiple testing adjustment) of survival comparisons for advanced HER2 + and triple-negative disease warrant further research. Caution is needed due to study limitations such as cancer stage validity.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Anciano , Estados Unidos/epidemiología , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Medicare , Receptor ErbB-2/metabolismo , Estadificación de Neoplasias , Quimioterapia Adyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Antioxidant-defense systems of tumor cells protect them from oxidative damage and is strongly associated with tumor metastasis. In this work, a mussel-inspired multifunctional nanomedicine (ZS-MB@P) has been designed for inhibiting tumor growth and metastasis through amplified oxidative stress and photothermal/magnetothermal/photodynamic triple-combination therapy. This nanomedicine was fabricated via loading a silica shell on the magnetic nano-octahedrons [zinc-doped magnetic Fe3O4 nano-octahedrons] by encapsulating photosensitizer methylene blue (MB) and subsequently coating polydopamine (PDA) shells as "gatekeeper." The nanomedicine could realize photothermal therapy, photodynamic therapy, and magnetic hyperthermia after treatment with near-infrared (NIR) irradiation and applied magnetic field. Under pH and NIR stimulation, controlled amount of MB was released to produced exogenous reactive oxygen species. Noteworthy, PDA can amplify intracellular oxidative stress by depleting glutathione, thus inhibiting breast cancer metastasis effectively since oxidative stress is an important barrier to tumor metastasis. The outstanding ability to suppress tumor growth and metastasis was comprehensively assessed and validated both in vitro and in vivo. Moreover, the nanomedicine showed outstanding T2 magnetic resonance imaging for tracking the treatment process. Taken together, this work offers an innovative approach in the synergistic treatment of recalcitrant breast cancer.
Asunto(s)
Neoplasias de la Mama , Hipertermia Inducida , Nanopartículas , Fotoquimioterapia , Humanos , Femenino , Fotoquimioterapia/métodos , Fototerapia , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Estrés Oxidativo , Línea Celular Tumoral , Nanomedicina TeranósticaRESUMEN
In recent years, researchers are developing novel nanoparticles for diagnostic applications using imaging techniques and for therapeutic purposes through drug delivery techniques. The unique physical and chemical properties of mesoporous silica nanoparticles (MSNs) make it possible to integrate a variety of commonly used therapeutic and imaging agents to construct a multimodal synergistic anticancer drug delivery system. Herein, recent advances in MSNs synthesis for drug delivery and smart response applications are reviewed. First, synthetic strategies for the fabrication of ordered MSNs, hollow MSNs, core-shell structured MSNs, dendritic MSNs, and biodegradable MSNs are outlined. Then, the recent research progress in designing functional MSN materials with various controlled release mechanisms in anticancer therapy is discussed, and new properties are introduced to suggest the latest design requirements as drug delivery materials. The review also highlights significant achievements in bioimaging using MSNs and their multifunctional counterparts as delivery vehicles. Finally, personal views on key directions for future work in this area are presented.
Asunto(s)
Antineoplásicos , Nanopartículas , Dióxido de Silicio/química , Porosidad , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Nanopartículas/uso terapéutico , Nanopartículas/química , Portadores de Fármacos/químicaRESUMEN
INTRODUCTION: The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP). METHODS: Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. RESULTS: In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. CONCLUSIONS: These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Adulto , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inducido químicamente , Receptores de Trombopoyetina/agonistas , Incidencia , Metaanálisis en Red , Trombocitopenia/tratamiento farmacológico , Hidrazinas/efectos adversos , Benzoatos/efectos adversos , Proteínas Recombinantes de Fusión/efectos adversos , Receptores Fc/uso terapéutico , Trombopoyetina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
[This corrects the article DOI: 10.1016/j.bioactmat.2022.03.008.].
RESUMEN
Background: Antiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children. Methods: From January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2-4 adverse events and abnormal laboratory test results. Results: A total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5-10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3-4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5-6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108-4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004-3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299-5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238-0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2-4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children. Conclusion: Our research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.
RESUMEN
Background: Anaemia (low haemoglobin [Hb]) is well known to be associated with high mortality and adverse cardiac events following surgical treatment of abdominal aortic aneurysm (AAA). However, little is known about the relationship of AAA volume and Hb level alterations with endovascular repair of AAA. This study aimed to examine the changes in the Hb level and aneurysm volume before and after endovascular aneurysm repair (EVAR) for AAA and determine the relationship between the post-operative Hb level and the volume loss of AAA. Methods: This retrospective study reviewed patients with AAA who underwent EVAR between January 2020 and February 2021 at a tertiary medical centre. The clinical features and medical history of the patients were analysed. Alterations in the Hb level were recorded, and the AAA volume was calculated from computed tomography angiography images before and after EVAR to infer the association between the post-operative Hb level and alterations in AAA volume. Moreover, AAA volume, pre-operative Hb level and medical history were studied to identify the risk factors for anaemia 24 h after EVAR. Results: A total of 74 patients (mean age, 67 ± 7.9 years) were included in this study. The Hb level decreased significantly 24 h after EVAR, and the post-operative Hb level was negatively correlated with AAA volume loss (r = -0.252, p = 0.041). No relationship was observed between AAA volume loss and decrease in the Hb level (r = 0.072, p = 0.571) or between pre-operative AAA volume and decrease in the Hb level (r = 0.072, p = 0.566). Furthermore, 59.5% of the patients (n = 44) developed anaemia 24 h after EVAR. The odds ratio (OR) of anaemia 24 h after EVAR was 5.3 times higher in those with hypertension (OR, 5.304; 95% confidence interval [CI], 1.024-27.424) than in those without the condition. The pre-operative Hb level (or normal Hb level) was a protective factor (OR = 0.909; 95% CI, 0.853-0.969). The area under the receiver operating characteristic curve was 0.840. The post-operative Hb level declined significantly, and AAA volume loss contributed to it. Moreover, hypertension was identified to be a risk factor for anaemia 24 h after EVAR, and pre-operative Hb level was discerned to be a protective factor. Conclusions: The findings suggest that decrease in the Hb level in the early post-EVAR stage warrants the attention of surgeons, especially in patients with a history of hypertension or a low pre-operative Hb level.