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OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.
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Teorema de Bayes , Metanálise em Rede , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Ftalazinas/uso terapêutico , Feniltioidantoína/uso terapêutico , Feniltioidantoína/análogos & derivados , Benzamidas/uso terapêutico , Acetato de Abiraterona/uso terapêutico , Piperazinas/uso terapêutico , NitrilasRESUMO
Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.
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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic neoplasm that exhibits myelodysplastic and myeloproliferative characteristics with heterogeneous clinical and pathological features. There are limited publications on the ethnic and racial disparity of cytogenetics and genomics in CMML patients. This study aims to define the cytogenetic and molecular landscape in Hispanic CMML patients from Puerto Rico and explore its possible clinical significance. One hundred and eleven (111) Hispanic CMML patients from Puerto Rico were diagnosed in our institute from 2009 to 2018. Karyotypes were available in one hundred and seven (107) patients. Seventeen (17) patients had abnormal karyotypes (17/107, 16%). Compared to previously published data, Hispanic CMML patients in this study had significantly lower rates of overall cytogenetic abnormalities (16% vs 27-28%, p < 0.05) and trisomy 8 (2% vs 7%, p < 0.05). Among one hundred and eleven (111) Hispanic CMML patients, 40-gene myeloid molecular profile tests were performed in fifty-six (56) CMML patients. Gene mutations were identified in fifty-four (54) patients (96%). The most frequent mutated genes were: TET2, SRSF2, ASXL1, ZRSR2, DNMT3A, NRAS, CBL, and RUNX1. Twenty-nine (29) out of fifty-six (56) patients (29/56, 52%) had mutated TET2/wild type ASXL1 (muTET2/wtASXL1). Previous studies indicated that mutated ASXL1, DNMT3A, NRAS, RUNX1, and SETBP1 may associate with an unfavorable prognosis and muTET2/wtASXL1 may associate with a favorable prognosis in CMML patients. Compared to previously published data, Hispanic CMML patients from Puerto Rico in this study had significantly lower mutation rates in ASXL1 and SETBP1, and a higher rate of muTET2/wtASXL1. The findings raise the possibility of a favorable prognosis in Hispanic CMML patients.
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Klebsiella pneumoniae is one of the main pathogenic bacteria that causes nosocomial infections, such as pneumonia, urinary tract infection, and sepsis. Therefore, the rapid and accurate detection of K. pneumoniae is important for the timely treatment of infectious patients. This study aimed to establish a loop-mediated isothermal amplification (LAMP) method for the rapid and sensitive detection of K. pneumoniae-specific gene ureR_1 (Gene ID: 11847803). The ureR_1 gene was obtained through local and online BLAST, and the specific primers were designed for its detection. Positive reactions were observed on all 140 K. pneumoniae clinical isolates while all the 82 non-K. pneumoniae clinical isolates were negative. Plasmids with the specific gene and the mouse blood with K. pneumoniae were used for sensitivity analysis. The detection limit of the LAMP was 1 bacterium/reaction. The results showed that the LAMP targeted to ureR_1 is a fast, specific, sensitive, inexpensive, and suitable method for the detection of K. pneumoniae.
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Genes Bacterianos , Klebsiella pneumoniae/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Primers do DNA/genética , Primers do DNA/isolamento & purificação , Klebsiella pneumoniae/isolamento & purificação , Limite de Detecção , Plasmídeos/genética , Plasmídeos/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Temperatura , Fatores de TempoRESUMO
Klebsiella pneumoniae is one of the main pathogenic bacteria that causes nosocomial infections, such as pneumonia, urinary tract infection, and sepsis. Therefore, the rapid and accurate detection of K. pneumoniae is important for the timely treatment of infectious patients. This study aimed to establish a loop-mediated isothermal amplification (LAMP) method for the rapid and sensitive detection of K. pneumoniae-specific gene ureR_1 (Gene ID: 11847803). The ureR_1 gene was obtained through local and online BLAST, and the specific primers were designed for its detection. Positive reactions were observed on all 140 K. pneumoniae clinical isolates while all the 82 non-K. pneumoniae clinical isolates were negative. Plasmids with the specific gene and the mouse blood with K. pneumoniae were used for sensitivity analysis. The detection limit of the LAMP was 1 bacterium/reaction. The results showed that the LAMP targeted to ureR_1 is a fast, specific, sensitive, inexpensive, and suitable method for the detection of K. pneumoniae.
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Técnicas de Amplificação de Ácido Nucleico/métodos , Genes Bacterianos , Klebsiella pneumoniae/genética , Plasmídeos/isolamento & purificação , Plasmídeos/genética , Temperatura , Fatores de Tempo , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Primers do DNA/isolamento & purificação , Primers do DNA/genética , Limite de Detecção , Klebsiella pneumoniae/isolamento & purificaçãoRESUMO
BACKGROUND: Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. METHODS: This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. FINDINGS: 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8-12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8-14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67-6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23-0·99; log-rank p value=0·0434). INTERPRETATION: A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. FUNDING: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.
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Fibrilação Atrial/tratamento farmacológico , Uso de Medicamentos/tendências , Educação Médica Continuada , Educação de Pacientes como Assunto , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Anticoagulantes , Argentina/epidemiologia , Fibrilação Atrial/epidemiologia , Brasil/epidemiologia , China/epidemiologia , Retroalimentação , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Romênia/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVE: To detect the snail habitats from the marshland of Eastern Dongting Lake Area, using the Remote Sensing (RS) and Geographic Information System (GIS) technology based on the China-Brazil Earth Resources Satellite-02B (CBERS-02B) CCD images. METHODS: According to the two typical traits of snail habitats in marshland including "water in summer and land in winter" and "no grass, no snails", the "water in summer and land in winter" region and the vegetation coverage region were calculated by RS image processing respectively. The two regions mentioned above were then overlapped to confirm the snail habitats through comparing with the data from field survey under spatial overlapping of Arcgis as the last step. RESULTS: In Eastern Dongting Lake area, the "water in summer and land in winter" region and vegetation coverage region were predicted based on the formula normalized difference water index (NDWI) > 0.01 and normalized difference vegetation index (NDVI) > 0.36, respectively. The snail habitat was determined by theme overlay of the two regions said above. The agreement rate between the prediction and the geospatial data of field survey was 93.55%, which demonstrated the final results were credible and reliable. CONCLUSION: CBERS-02B image could be used to detect the snail habitats and to monitor the changes of them, so as to find out the characteristics of distribution and the trends of diffusion. The snail index (discriminant 1 and 2) seemed to be suitable for the detection of snail habitats in the marshland of Lake area and used for the programs of snail control.