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INTRODUCTION: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS). RESULTS: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies. CONCLUSION: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used.
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Cabozantinib plus nivolumab was approved as a first-line (1L) treatment for advanced renal cell carcinoma (aRCC) following the CheckMate 9ER trial. CaboCombo (ClinicalTrials.gov identifier: NCT05361434) is a non-interventional study designed to evaluate the effectiveness and tolerability of cabozantinib plus nivolumab in a real-world setting. Overall, 311 patients with clear-cell aRCC receiving 1L cabozantinib plus nivolumab will be recruited from at least 70 centers in seven countries worldwide. The primary end point is overall survival at 18 months. Secondary end points include progression-free survival, objective response rate, safety, patterns of treatment, subsequent anticancer therapies and quality of life. CaboCombo will provide real-world evidence on the characteristics, treatment sequences, and outcomes of patients with aRCC receiving 1L cabozantinib plus nivolumab.
Renal cell carcinomas (RCC) are cancers that grow in the kidneys. Clear-cell RCC is the most common type reported in almost three quarters of patients. RCC tumors become advanced if they grow and spread to other parts of the body. In a clinical trial called CheckMate 9ER, a combination of two drugs called cabozantinib and nivolumab improved survival compared with a drug called sunitinib in patients with advanced clear-cell RCC who had not received any previous treatments. In CheckMate 9ER, cabozantinib plus nivolumab also reduced the size and slowed the spread of tumors compared with sunitinib. However, clinical trials only allow certain patients to participate under strict treatment conditions and so do not provide information on how a treatment will work in all patients. Researchers therefore carry out additional studies to gather extra information from real-world clinical practice. CaboCombo is a study that will look at how well cabozantinib plus nivolumab stops tumors from growing and spreading, the side effects of the drugs, and also how the drugs are used by doctors. It is an observational study, which means that researchers will observe all patients and doctors using the treatment but they will not intervene. The aim of the study is to gather information that will help doctors make treatment decisions for their patients. This article describes how the CaboCombo study will be carried out and the information it will give the researchers. The results will help physicians make decisions on the best treatment option for patients. Clinical Trial Registration: NCT05361434 (ClinicalTrials.gov).
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Anilidas , Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Piridinas , Humanos , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/patología , Ensayos Clínicos Fase IV como Asunto , Neoplasias Renales/patología , Nivolumab/uso terapéutico , Estudios Prospectivos , Calidad de VidaRESUMEN
CONTEXT: The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD). OBJECTIVE: This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1. METHODS: Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor. RESULTS: In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01. CONCLUSION: Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.
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Hipoglucemia , Síndrome de Laron , Niño , Adolescente , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Estudios Longitudinales , Factor I del Crecimiento Similar a la Insulina , Proteínas Recombinantes/efectos adversos , Bases de Datos Factuales , Modelos LogísticosRESUMEN
OBJECTIVES: Many protocols and preparations are used for bowel cleansing before pediatric colonoscopy but few are based on scientific evidence. We evaluated efficacy, safety, tolerability, and patient preference of oral sulfate solution (OSS) at 75% of the adult dose versus polyethylene glycol (PEG)-electrolyte solution in adolescents presenting for diagnostic colonoscopy. METHODS: Phase III, randomized, evaluator-blinded, non-inferiority study of OSS and PEG in adolescents aged 12-17 years. OSS and PEG were administered in 2 doses on the day before colonoscopy. Primary endpoint included proportion of patients with successful overall preparation (4-point scale). Secondary endpoints included overall and segmental bowel cleansing (Boston Bowel Preparation Scale; BBPS), completed colonoscopies, duration of examination, time to cecal intubation, proportion of nasogastric tubes (NGTs), adverse events (AEs) and acceptability. RESULTS: Successful cleansing was achieved in 71.4% and 79.0% of patients receiving OSS and PEG, respectively [adjusted difference -7.61 (95% confidence interval, CI, -18.45 to 3.24); P = 0.0907]. Segmental BBPS score for the left and transverse colon were similar between treatment groups, but better for the right colon with PEG than OSS [2.2 (95% CI, 2.0-2.4) and 1.9 (95% CI, 1.7-2.1), respectively; P = 0.0015]. Significantly fewer OSS patients needed NGT placement to ingest the whole solution [9/125 (7.2%)] than PEG patients [36/116 (31.0%); P < 0.0001]. Treatment acceptability was significantly higher with OSS than PEG ( P < 0.0001). Duration of examination, completed colonoscopies, and time to cecal intubation were similar between preparations. Gastrointestinal AEs including nausea, vomiting, abdominal pain, and distension were similar in both groups but more patients receiving PEG had AEs assessed as incapacitating. CONCLUSIONS: Non-inferiority of OSS to PEG was not demonstrated, but OSS was associated with a lower requirement for NGT, better acceptability, and less frequent severe AEs than with PEG.
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Catárticos , Colonoscopía , Adolescente , Adulto , Niño , Humanos , Catárticos/efectos adversos , Ciego , Colonoscopía/métodos , Polietilenglicoles/efectos adversos , SulfatosRESUMEN
AIMS: To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms. METHODS: Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment. Subanalyses were performed according to age and concomitant treatment (radiotherapy, alpha-blockers, and antiandrogens). RESULTS: A total of 354 patients were treated with LHRH analogs for 48 weeks. The percentage of patients with moderate/severe LUTS (IPSS > 7) decreased from 60.2% (n = 213/354) at baseline to 52.8% (n = 187/354) at Week 48. Among patients with moderate/severe LUTS at baseline: 73.7% (n = 157/213) still had moderate/severe LUTS at Week 48; percentage reductions of patients with LUTS at Week 48 were statistically significant (p < 0.05) overall and by age or concomitant treatment, except for alpha-blockers (84.2% patients receiving them still had moderate/severe LUTS at Week 48). All IPSS items, including quality of life for urinary symptoms, improved throughout the study. The only predictor of response to treatment with LHRH analogs that improved IPSS by 3 points after 48 weeks was baseline testosterone levels. Lower baseline testosterone levels were associated with greater improvement in IPSS after treatment with LHRH analogs (odds ratio 0.998, 95% confidence interval 0.996-1.000, p = 0.0277). CONCLUSION: LHRH analogs have a positive effect in patients with locally advanced or metastatic prostate cancer presenting moderate/severe LUTS regardless of age or concomitant treatment received (radiotherapy, antiandrogens, or alpha-blockers).
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Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Andrógenos/uso terapéutico , Hormona Liberadora de Gonadotropina/uso terapéutico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/diagnóstico , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Calidad de Vida , Testosterona/uso terapéuticoRESUMEN
Objectives: To measure the effect of dyadic adjustment on changes in patients' quality of life when initiating treatment with gonadotropin-releasing hormone (GnRH) agonist. Patients and methods: A prospective, multicenter, longitudinal, and non-interventional study (NCT02630641) that included patients with prostate cancer starting GnRH agonist therapy, and their partners, in 157 centers in France. Data were collected at inclusion and after 6 months of treatment on quality of life (WHOQOL-BREF), disease perception (B-IPQ), disease symptoms (QLQ-PR25), and perception of cohesion within the couple (dyadic adjustment, DAS-16). Results: The Full Analysis Set included 492 patients (median age [Q1;Q3]: 74 [68;80] years). An improvement of the quality of life (defined as the improvement of at least one of the four dimensions of WHOQOL-BREF) was reported in 290/434 (67%) patients between baseline and follow-up. Quality of life was better at baseline and follow-up in patients with good cohesion within the couple than in those with medium or poor cohesion. Factors associated with improvement in quality of life of patients were the following: initial presence of QLQ-PR25 hormonal treatment-related symptoms (OR [95% CI]: 3.00 [1.46, 6.17]) suggesting testosterone deficiency symptoms at baseline and initial low level (2.04 [1.12, 3.72]) or absence of sexual activity (2.23 [1.11, 4.50]) before GnRH agonist initiation. Conclusion: Men with the greatest improvement in quality of life after initiating hormone therapy were those with, at baseline, testosterone deficiency symptoms (identified by QLQ-PR25 treatment-related symptoms score) or no/low sexual activity. Cohesion within the couple was not confirmed as an influence on the evolution of quality of life.
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BACKGROUND: Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex® Growth Forum Database (Eu-IGFD) Registry (NCT00903110). METHODS: The Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019. RESULTS: This analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1. CONCLUSION: Children and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.
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Factor I del Crecimiento Similar a la Insulina , Adolescente , Niño , Estudios Clínicos como Asunto , Femenino , Trastornos del Crecimiento , Pérdida Auditiva Sensorineural , Humanos , Factor I del Crecimiento Similar a la Insulina/deficiencia , Masculino , Proteínas Recombinantes , Sistema de RegistrosRESUMEN
ABSTRACT: Triptorelin is one of the most commonly used gonadotropin-releasing hormone agonists and has been used in the treatment of deep infiltrating endometriosis (DIE). This study aimed to evaluate the efficacy and safety of up to 24âweeks of triptorelin treatment after conservative surgery for DIE.This prospective, non-interventional study was performed in 18 tertiary hospitals in China. Premenopausal women aged ≥18âyears treated with triptorelin 3.75âmg once every 28âdays for up to 24âweeks after conservative surgery for DIE were included. Endometriosis symptoms were assessed, using a visual analogue scale (0-10âcm) or numerical range (0-10), at baseline (pre-surgery) and routine visits 3, 6, 9, 12, 18, and 24âmonths after surgery. Changes in symptom intensity over time were primary outcome measures.A total of 384 women (mean [standard deviation] age, 33.4 [6.2] years) were analyzed. Scores for all symptoms (pelvic pain, dysmenorrhea, ovulation pain, dyspareunia, menorrhagia, metrorrhagia, and gastrointestinal and urinary symptoms) assessed decreased from baseline over 24âmonths. Cumulative improvement rates in pelvic pain, dysmenorrhoa, ovulation pain, and dyspareunia were 74.4%, 83.6%, 55.1%, and 66.9%, respectively. The 24-month cumulative recurrence rate (≥1 symptom) was 22.2%. The risk of symptom recurrence was higher in patients with ≥2 versus 1 lesion (odds ratio [OR] 2.539; 95% CI: 1.458-4.423; Pâ=â.001) and patients with moderate (OR 5.733; 95% CI: 1.623-20.248; Pâ=â.007) or severe (OR 8.259; 95% CI: 2.449-27.851; Pâ=â.001) pain versus none/mild pain. Triptorelin was well tolerated without serious adverse events.Triptorelin after conservative surgery for DIE improved symptoms over 24âmonths of follow up. The recurrence rate of symptoms was low and triptorelin was generally well tolerated.Trial registration number: ClinicalTrials.gov, NCT01942369.
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Endometriosis , Pamoato de Triptorelina/uso terapéutico , Adulto , China , Dispareunia/tratamiento farmacológico , Dispareunia/etiología , Endometriosis/tratamiento farmacológico , Endometriosis/cirugía , Femenino , Humanos , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Estudios Prospectivos , Pamoato de Triptorelina/efectos adversosRESUMEN
BACKGROUND: Cabozantinib monotherapy is approved in the UK for patients with treatment-naïve intermediate- or poor-risk advanced renal cell carcinoma (aRCC), or patients who received prior vascular endothelial growth factor-targeted therapy. Data are limited on the real-world use of cabozantinib for aRCC. PATIENTS AND METHODS: CERES (NCT03696407) was a retrospective study of patients with aRCC who received cabozantinib through the UK managed access programme (MAP; August 2016-July 2017), at which time cabozantinib had European regulatory approval for second- or later-line use only. The study objectives were to characterize aRCC treatment patterns and evaluate cabozantinib effectiveness. Outcomes were stratified by cabozantinib treatment line, MAP treatment date (months 0-7 vs. 8-12) and (post hoc) Charlson Comorbidity Index (CCI; ≥ 6 vs. < 6). RESULTS: Of 100 patients included, 99% had stage IV disease, 63% had a CCI ≥ 6 and 81% had an Eastern Cooperative Oncology Group Performance Status 0-1. Median (range) duration of follow-up was 10.8 (0.4-33.5) months. Cabozantinib was administered as second-line, third-line and fourth- or later-line in 41%, 31% and 28% of patients, respectively. Most patients (84%) initiated cabozantinib at 60 mg. Average (range) cabozantinib dose was 45.5 (19.6-59.8) mg/day; 66% of patients had ≥ 1 dose reduction. Disease progression was the most common reason for discontinuation (65.1%). Median (95% confidence interval) progression-free survival (PFS) and overall survival (OS) were 6.01 (5.16-7.85) and 10.84 (7.92-16.85) months, respectively. Overall response rate was 34.5%; disease control rate 70.1% and duration of response 6.9 (1.8-26.9) months. No significant differences in survival estimates were observed between treatment line or treatment date subgroups. Total CCI score ≤ 6 (vs. > 6) was associated with prolonged median PFS and OS. CONCLUSION: Cabozantinib demonstrated clinical activity in this UK real-world aRCC population. The results provide a benchmark for future real-world studies in aRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Anilidas , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Piridinas , Estudios Retrospectivos , Reino Unido , Factor A de Crecimiento Endotelial VascularRESUMEN
ABSTRACT: Triptorelin has been used after surgery in deep infiltrating endometriosis. This post-hoc analysis aimed to evaluate symptom control between patients receiving 1-3 triptorelin injections and those receiving 4-6 injections within 24âmonths of conservative surgery for deep infiltrating endometriosis, in the real-world.Included patients were divided into two groups (received up to 3âmonths injections in group A, 4-6 injections in group B) based on the numbers of triptorelin (Diphereline, 3.75 mg intramuscular injection once every 28âdays for up to 24âweeks) administration. Evolution in score of pain intensity at 3, 6, 9, 12, 18, and 24âmonths after primary triptorelin administration and symptom improvement/recurrence rates between two groups were compared. Symptoms of pain intensity were assessed using a visual analogue scale (VAS) with a range from 0 to 10âcm. An improvement in symptoms was defined as a reduction of at least 3âcm or 3 units from pre-surgery levels.156 patients in group A and 228 in group B. Pain symptom score (meanâ±âstandard deviation) diminished to a nadir at 3-months for group A and 6-months for group B; at 6-months nadir scores were significantly lower in group B (0.9â±â1.7 vs 0.4â±â1.2 respectively, Pâ=â.002). No significant difference for pain symptom scores between both groups at 24-months (Pâ=â.269). The 6-month and 24-month cumulative improvement rates of pain (80.6% vs 89.8%, Pâ=â.014 and 82.6% vs 90.7%, Pâ=â.025) and gastro-intestinal symptoms (61.0% vs 80.8%, Pâ=â.022 and 61.0% vs 83.3%, Pâ=â.008) were significantly higher in group B, whereas there was no significant difference in rates of menstrual disorders and urinary symptoms. There is no significant difference for 12-months and 24-months cumulative recurrence rates of total symptoms between both groups (11.3% vs 13.8%, Pâ=â.568 and 16.1% vs 26.0%, Pâ=â.094).In women with deep infiltrating endometriosis, longer treatment with triptorelin following conservative surgery was associated with a decrease in symptom intensity and greater improvement of pain symptoms in the short-term and greater improvement of gastro-intestinal symptoms in the long-term.Trial registration number: ClinicalTrials.gov, NCT01942369.
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Endometriosis/tratamiento farmacológico , Luteolíticos/administración & dosificación , Índice de Severidad de la Enfermedad , Pamoato de Triptorelina/administración & dosificación , Adulto , Terapia Combinada , Endometriosis/cirugía , Femenino , Humanos , Estudios ProspectivosRESUMEN
Objective: The International Cooperative Growth Study, NutropinAq® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq® [somatropin]) in paediatric growth disorders. Methods: Open-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs). Results: 2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events). Conclusions: There was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.
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Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Vigilancia de Productos Comercializados/estadística & datos numéricos , Proteínas Recombinantes/uso terapéutico , Sistema de Registros/estadística & datos numéricos , Insuficiencia Renal Crónica/tratamiento farmacológico , Síndrome de Turner/tratamiento farmacológico , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/patología , Hormona de Crecimiento Humana/deficiencia , Humanos , Lactante , Agencias Internacionales , Masculino , Pronóstico , Insuficiencia Renal Crónica/patología , Síndrome de Turner/patologíaRESUMEN
INTRODUCTION: To evaluate the effectiveness and safety of long-acting GnRH agonist follicular and GnRH antagonist protocols among women undergoing in vitro fertilization (IVF) using data published in both English-language and Chinese studies. METHODS: We systematically searched the PubMed, Embase, Cochrane, CNKI, and Wanfang databases up to March 2019 for studies comparing long-acting GnRH agonist follicular and GnRH antagonist protocols in women undergoing IVF. The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and implantation rate; safety outcomes were ovarian hyperstimulation syndrome (OHSS) and miscarriage rate in fresh cycle. Statistical analysis was done using R software. The study protocol was registered with PROSPERO (CRD42019139396). RESULTS: In 11 studies that met the inclusion criteria, 1994 women belonged to the long-acting GnRH agonist follicular protocol group and 1678 to the GnRH antagonist protocol group. Live birth rate (relative risk (RR) 1.61; 95% confidence interval (CI) 1.27, 2.05; P < 0.001), clinical pregnancy rate (RR 1.44; 95% CI 1.32, 1.58; P < 0.001), and implantation rate (RR 1.58; 95% CI 1.44, 1.73; P = 0.001) were higher in the long-acting GnRH agonist follicular protocol compared with the antagonist protocol group. There was no difference in miscarriage rate (RR 0.98; 95% CI 0.58, 1.64; P = 0.98) between the long-acting GnRH agonist follicular and antagonist protocols. However, OHSS rate (RR 1.63; 95% CI 1.15, 2.32; P = 0.0058) was lower in the GnRH antagonist protocol compared to the long-acting GnRH agonist protocol group. CONCLUSION: The long-acting GnRH agonist follicular protocol was beneficial in improving live birth rate, clinical pregnancy rate, and implantation rate whereas the incidence of OHSS was significantly lower in women undergoing the GnRH antagonist protocol.
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Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Femenino , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Humanos , Metaanálisis como Asunto , Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Ginkgo biloba is a common symptomatic treatment for cognitive impairment, although data on its efficacy are controversial. OBJECTIVE: The aim of the current study was to evaluate the effectiveness of standardized Ginkgo biloba extract EGb761® (Tanakan®) for the improvements of cognitive functions over 24 months in a local cohort of patients diagnosed with amnestic mild cognitive impairment (aMCI). METHODS: This multicentre non-interventional study included 500 eligible patients with a MCI treated with 120 mg/day standardized Ginkgo biloba extract EGb761® (Tanakan®). Patients were evaluated using several scales for assessment of cognition, memory, activities of daily living, and depression (MMSE, FAQ, CGI, HAM-D) at baseline and every 6 months after that for a 24-month period. The median change in MMSE at the 24-month follow-up was the primary outcome of the study. RESULTS: A statistically significant increase of 2 points in the median MMSE score was obtained. In patients with other concomitant cognitive disorders, the improvement in MMSE was less significant. Tanakan® improved memory impairment (using the delayed recall test) and the ability to accomplish activities of daily living (mean FAQ score, 1.7); it also decreased the severity of depression (mean HAM-D score, 2.4) at the end of the study. More than 80% of the patients showed minimal improvement of their condition as assessed by the CGI-Improvement Scale. CONCLUSION: The administration of EGb761® (Tanakan®) led to a significant improvement of cognitive decline, memory, activities of daily living, and depression in subjects with aMCI over 24 months.
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Disfunción Cognitiva/tratamiento farmacológico , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Cognición/efectos de los fármacos , Femenino , Ginkgo biloba , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RumaníaRESUMEN
OBJECTIVE: The European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS). DESIGN: Ongoing, open-label, observational registry (NCT00903110). METHODS: Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008-2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs). RESULTS: Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years' treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common. CONCLUSIONS: In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.
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Trastornos del Crecimiento/tratamiento farmacológico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/deficiencia , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Síndrome de Laron/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Adolescente , Estatura , Peso Corporal/efectos de los fármacos , Niño , Femenino , Crecimiento/efectos de los fármacos , Humanos , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Síndrome de Laron/genética , Estudios Longitudinales , Masculino , Seguridad del Paciente , Pubertad , Resultado del Tratamiento , Adulto JovenRESUMEN
Acinetobacter baumannii has emerged as one of the most problematic bacterial pathogens responsible for hospital-acquired and community infections worldwide. Besides its high capacity to acquire antibiotic resistance mechanisms, it also presents high adhesion abilities on inert and living surfaces leading to biofilm development. This lifestyle confers additional protection against various treatments and allows it to persist for long periods in various hospital niches. Due to their remarkable antimicrobial tolerance, A. baumannii biofilms are difficult to control and ultimately eradicate. Further insights into the mechanism of biofilm development will help to overcome this challenge and to develop novel antibiofilm strategies. To unravel critical determinants of this sessile lifestyle, the proteomic profiles of two A. baumannii strains (ATTC17978 and SDF) grown in planktonic stationary phase or in mature solid-liquid (S-L) biofilm were compared using a semiquantitative proteomic study. Of interest, among the 69 common proteins determinants accumulated in the two strains at the S-L interface, we sorted out the MacAB-TolC system. This tripartite efflux pump played a role in A. baumannii biofilm formation as demonstrated by using ΔmacAB-tolC deletion mutant. Complementary approaches allowed us to get an overview of the impact of macAB-tolC deletion in A. baumannii physiology. Indeed, this efflux pump appeared to be involved in the envelope stress response occurring in mature biofilm. It contributes to maintain wild type (WT) membrane rigidity and provides tolerance to high osmolarity conditions. In addition, this system is probably involved in the maintenance of iron and sulfur homeostasis. MacAB-TolC might help this pathogen face and adapt to deleterious conditions occurring in mature biofilms. Increasing our knowledge of A. baumannii biofilm formation will undoubtedly help us develop new therapeutic strategies to tackle this emerging threat to human health.
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BACKGROUND: Real-world data on cabozantinib in metastatic renal cell carcinoma (mRCC) is limited. This study (CABOREAL) reports treatment patterns and outcomes for patients treated with cabozantinib through the French Early Access Program. PATIENTS AND METHODS: This multicentre (n = 26), observational, retrospective study enrolled patients with mRCC who had received ≥1 dose of cabozantinib. Overall survival (OS) was estimated using the Kaplan-Meier method; subgroups were compared using the log-rank test. A multiple Cox regression model assessed predictive factors of OS after cabozantinib initiation. RESULTS: Four hundred and ten recruited patients started treatment between September 2016 and February 2018: the Eastern Cooperative Oncology Group Performance Status ≥2, 39.3%; poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 31.7%; 0-1, 2 and ≥3 previous treatment lines, 25.3%, 33.4% and 41.2%, respectively; bone metastases, 55.9%; brain metastases, 16.8%. Median (min-max) follow-up was 14.4 (0-30) months. Overall, 57.0% of patients had a dose reduction, 15.6% an alternative dose schedule. The median average daily dose was 40.0 mg. Median (quartile [Q]1-Q3) treatment duration was 7.6 (0.1-29.1) months, median OS was 14.4 months, and the 12-month OS rate was 56.5% (95% confidence interval: 51.5-61.2). Most patients (54.4%) received subsequent treatment. Predictive factors associated with longer OS were body mass index ≥25 kg/m2 (p = 0.0021), prior nephrectomy (p = 0.0109), favourable or intermediate IMDC risk (p < 0.0001) and cabozantinib initiation at 60 mg/day (p = 0.0486). CONCLUSIONS: In the largest real-world study to date, cabozantinib was effective in unselected, heavily pretreated patients with mRCC. Initiation at 60 mg/day was associated with improved outcomes. CLINICALTRIALS. GOV IDENTIFIER: NCT03744585.
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Anilidas/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Piridinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/uso terapéutico , Anciano , Anilidas/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Piridinas/farmacología , Proteínas Tirosina Quinasas Receptoras/farmacología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background and study aims Oral sulphate solution (OSS) is a sulphate-based, low-volume bowel cleansing preparation taken in two doses of 500âmL, each followed by 1000mL of water or clear liquid. The primary objective of this observational study was to document compliance with the recommended hydration guidelines in a representative sample of the European population. Patients and methods Prospective, non-interventional, multicentre study (NCT02630680, EUPAS9361) in patients prescribed OSS for colonoscopy preparation in routine clinical practice in Europe. Patients were included according to pre-agreed consecutive enrolment rules. Patients recorded the volume of OSS and water or clear liquid intake, and occurrence of adverse events (AEs). Compliance with hydration was calculated as a ratio of actual volume of water/clear liquid taken versus prescribed 2,000âmL, and non-compliance defined as <â75â% intake. Colon cleansing level was assessed on a 4-point scale. Results Between October 2015 and January 2017, 1,281 patients were recruited in 16 centres in four European countries (safety population nâ=â1,206; registry population nâ=â1,177). Of patients, 94.5â% were ≥â75â% and 86.8â% 100â% compliant with hydration guidelines. Patients took an average of 96.8â% of the recommended OSS volume; 46 patients (3.9â%) were non-compliant. Colon cleansing levels were good-to-excellent in 87.6â% of patients. Three hundred and twenty-nine patients (27.3â%) experienced 758 treatment-related AEs, mostly gastrointestinal (82.9â%), all were mild-to-moderate. Non-compliant patients had no AEs suggestive of dehydration. Conclusion In this non-interventional study in a real-life setting, treatment compliance with hydration guidelines was good-to-excellent in 94.5â% of patients receiving OSS.âThe safety profile of OSS was similar to the prescribing information.
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BACKGROUND: No published studies have specifically assessed whether treatment modifications to androgen deprivation therapy (ADT) for prostate cancer (PCa) are frequently carried out in routine clinical practice. The current study was conducted to determine what proportion of patients who had initiated hormone therapy with a gonadotropin-releasing hormone (GnRH) analogue then had their treatment regimen modified during the first 24 months. METHODS: A prospective, noninterventional study was carried out in routine clinical practice in France. Patients with locally advanced or metastatic PCa were followed up for 2 years after treatment initiation with a GnRH analogue. The primary endpoint was the proportion of patients with a modification to their initial hormone therapy. RESULTS: In total, 1301 patients were enrolled into the study by 204 physicians, and the primary endpoint could be evaluated for 891 patients. The GnRH analogue treatment was initiated for metastatic PCa (24.2%), locally advanced PCa without planned local treatment (20.6%), locally advanced PCa in association with radiotherapy (31.6%), and biochemical recurrence after local treatment (21.4%). Hormonal treatment was modified in 43.8% (390/891) of patients during the 24-month follow-up period after GnRH analogue initiation. In 61.3% of cases (239/390), the type of modification involved a change of GnRH analogue formulation or switch to another GnRH analogue. A total of five significant predictive factors for GnRH analogue treatment modification were identified: metastatic stage; physician sector; physician speciality; presence or absence of urinary symptoms; and intermittent versus continuous ADT. CONCLUSIONS: This study shows that in 43.8% of the patients with advanced PCa, ADT is modified in the first 2 years after initiation in routine clinical practice. Predictive factors for alteration of ADT were metastatic stage and the choice of an intermittent schedule.
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BACKGROUND: Lower urinary tract symptoms (LUTSs) may develop in men with prostate cancer (PCa) and can impact quality of life (QoL). Gonadotropin-releasing hormone (GnRH) agonists as androgen deprivation therapy are standard treatment for PCa, however, data are limited on their effects on LUTSs. A grouped analysis of national observational, non-interventional studies initiated in clinical practice was performed to assess the effectiveness of triptorelin in reducing moderate or severe LUTSs, measured using the International Prostate Symptom Score (IPSS) in men with advanced or metastatic PCa. METHODS: Men with PCa and LUTSs scheduled to receive triptorelin (3-month or 1-month extended release formulation) were recruited into prospective, non-interventional studies at centres in Algeria, Australia, Belgium, China, Hungary, Romania and South Korea. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTSs, assessed by IPSS, after 48 weeks. Secondary endpoints included: total IPSS, QoL due to urinary symptoms (IPSS Question 8) and prostate-specific antigen (PSA) levels at 24 and 48 weeks. RESULTS: A total of 2701 patients were recruited; 1851 patients with moderate or severe LUTSs at baseline (IPSS > 7), received triptorelin and had follow-up IPSS (efficacy population). The proportion of patients with moderate or severe LUTSs was reduced to 67.2% from baseline at week 48, following a reduction to 75.9% at week 24: the overall time effect was significant (p < 0.001). QoL due to urinary symptoms significantly improved from a mean score of 3.7 at baseline, to adjusted means of 2.5 and 2.1, at weeks 24 and 48, respectively (p < 0.001 versus baseline). Mean PSA levels were reduced from 158.8 ng/ml at baseline to 11.5 and 16.0 ng/ml at weeks 24 and 48, respectively. CONCLUSIONS: Within the limitations of these observational studies, improvements in LUTSs and QoL observed after 24 weeks and maintained at 48 weeks indicate that triptorelin-induced effects improve LUTSs in patients with advanced PCa.
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Bevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells.