Risk factors for non-response and discontinuation of Dienogest in endometriosis patients: A cohort study.
- 作者列表："Nirgianakis K","Vaineau C","Agliati L","McKinnon B","Gasparri ML","Mueller MD
INTRODUCTION:Progestins are commonly prescribed first-line drugs for endometriosis. High rates of non-response and intolerance to these drugs have been previously reported. However, no study to date has investigated the characteristics and comorbidities of patients taking progestins in relation to treatment outcomes, so identifying which patients will respond to or tolerate the treatment is currently impossible. The purpose of this study, therefore, was to identify risk factors for non-response and discontinuation of Dienogest (DNG) in women with endometriosis. MATERIAL AND METHODS:This is a retrospective cohort study including women currently taking, or newly prescribed, DNG for endometriosis-associated pain presenting in the Endometriosis Clinic of the University Hospital of Bern between January 2017 and May 2018. Women with initiation of treatment directly after surgery for endometriosis were excluded. For all participants the symptoms and comorbidities were documented. Effectiveness, tolerability and discontinuation of DNG were the primary end points. Univariate and multivariate binary logistic regression models were carried out to identify risk factors for non-response, intolerance and discontinuation of DNG. RESULTS:A sufficient or excellent treatment response was reported by 85/125 (68%) participants. Genital bleeding during the DNG treatment was negatively (OR 0.185, 95% CI 0.056-0.610, P = .006) and rASRM endometriosis stages III and IV were positively (OR 3.876, 95% CI 1.202-12.498, P = .023) correlated with the DNG response. When accounting for exclusively pretreatment factors, primary dysmenorrhea (OR 0.236, 95% CI 0.090-0.615, P = .003) and suspicion of adenomyosis (OR 0.347, 95% CI 0.135-0.894, P = .028) were inversely correlated with DNG response, and the latter was also correlated with treatment discontinuation (OR 3.189, 95% CI 1.247-8.153, P = .015). CONCLUSIONS:Genital bleeding during the DNG treatment and low rASRM stages are independent risk factors for DNG non-response. Before treatment initiation, primary dysmenorrhea and suspicion of adenomyosis correlate with DNG non-response. The results could assist the clinician first to provide detailed information to women before treatment initiation, second to identify and possibly modify in-therapy factors correlated to treatment effectiveness and lastly to switch treatment on time if needed.
介绍: 孕激素是常用的子宫内膜异位症的一线药物。以前曾报道过对这些药物无反应和不耐受的高发生率。然而，迄今为止，还没有研究调查服用孕激素的患者的特征和合并症与治疗结果的关系，因此确定哪些患者对治疗有反应或耐受治疗目前是不可能的。因此，本研究的目的是确定子宫内膜异位症女性患者无反应和停用Dienogest (DNG) 的危险因素。 材料和方法: 这是一项回顾性队列研究，包括2017年1月至2018年5月间在伯ber大学医院的子宫内膜异位症门诊中出现的目前服用或新处方的DNG治疗子宫内膜异位症相关疼痛的女性。子宫内膜异位症手术后直接开始治疗的妇女被排除在外。记录所有参与者的症状和合并症。DNG的有效性、耐受性和停药是主要终点。进行单因素和多因素二元logistic回归模型，以确定无反应，不耐受和停止DNG的危险因素。 结果: 85/125名 (68%) 参与者报告了充分或极好的治疗反应。DNG治疗期间生殖器出血呈负相关 (OR 0.185，95% CI 0.056-0.610，P = .006)，rASRM子宫内膜异位症III期和IV期与DNG反应呈正相关 (OR 3.876，95% CI 1.202-12.498，P = .023)。当仅考虑治疗前因素时，原发性痛经 (OR 0.236，95% CI 0.090-0.615，P = .003) 和怀疑子宫腺肌病 (OR 0.347，95% CI 0.135-0.894，P = .028) 与DNG反应呈负相关，而后者也与治疗中止相关 (OR 3.189，95% CI 1.247-8.153，P = .015)。 结论: DNG治疗期间生殖器出血和低rASRM分期是DNG无反应的独立危险因素。治疗开始前，原发性痛经和怀疑子宫腺肌病与DNG无反应相关。结果可以帮助临床医生首先在治疗开始前向女性提供详细信息，其次确定并可能修改与治疗有效性相关的治疗中因素，最后在需要时及时切换治疗。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.