How is safety of dermatology drugs assessed: trials,registries, and spontaneous reporting

ABSTRACT

Introduction: Skin conditions are common and highly varied in their etiology; therefore, a diverse array of therapeutics are utilized. Drug safety studies in dermatology can be challenging as there are over 3000 diagnoses to consider. As a result, dermatologists rely on data from multiple sources including clinical trials and real-world evidence.

Areas covered: In this review, we cover the main sources of safety data available, their strengths and weaknesses and how dermatologists should utilize such data. We use real-world examples of the different types of adverse events reported and how they are best captured by either randomized controlled trials or post-marketing pharmacovigilance methods. With multiple new therapies in dermatology, such as dupilumab for atopic dermatitis and janus-kinase inhibitors for alopecia areata the specialty is awash with evolving high-level evidence for their use. It is important to understand the optimal way to assess safety from trials but also appreciate the need for ongoing capture of safety data in clinical practice.

Expert opinion: In dermatology, there is a plethora of conditions to treat and clinical trials, post-marketing surveillance, such as drug registries and spontaneous reporting, all enable dermatologists to gain a more comprehensive understanding of the safety profiles of drugs being used.     

IKBKE enhances TMZ-chemoresistance through upregulation of MGMT expression in glioblastoma

Glioblastoma multiforme (GBM) is the most common and aggressive malignant type of brain tumor. Despite advances in diagnosis and therapy, the prognosis of     

Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent

Benzophenone-3 is a putative endocrine disrupting chemical and common ingredient in sunscreens. The potential of endocrine disrupting chemicals to act as agonists or antagonists in critical hormonally regulated processes, such as mammary gland development and mammary tumorigenesis, demands evaluation of its potential in promoting breast cancer. This study identifies the effects of BP-3 on mammary tumorigenesis with high-fat diet during puberty versus adulthood in Trp53-null transplant BALB/c mice. Benzophenone-3 exposure yielded levels in urine similar to humans subjected to heavy topical sunscreen exposure. Benzophenone-3 was protective for epithelial tumorigenesis in mice fed lifelong low-fat diet, while promotional for epithelial tumorigenesis in mice fed adult high-fat diet. Benzophenone-3 increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity dependent on specific dietary regimen and tumor histopathology. Even in instances of an ostensibly protective effect, other parameters suggest greater risk. Although benzophenone-3 seemed protective on low-fat diet, spindle cell tumors arising in these mice showed increased proliferation and decreased apoptosis. This points to a need for further studies of benzophenone-3 in both animal models and humans as a potential breast cancer risk factor, as well as a more general need to evaluate endocrine disrupting chemicals in varying dietary contexts.     

丙戊酸钠通过EGFR下调CD44表达抑制胶质瘤细胞生长

目的:探讨丙戊酸钠通过抑制A172胶质瘤细胞表皮生长因子受体（epidermal growth factor receptor，EGFR）的活化，下调CD44表达，进而调节细胞生长的机制。方法:实时荧光定量PCR和Western blot检测A172胶质瘤细胞中CD44以及siRNA下调CD44表达的情况，MTT检测CD44和丙戊酸钠对细胞生长的影响，Western blot检测丙戊酸钠对细胞中p-EGFR、EGFR和CD44表达影响。结果:丙戊酸钠抑制A172胶质瘤细胞生长，并具有浓度依赖性。A172胶质瘤细胞表达CD44，siRNA下调CD44表达后，细胞生长较正常组显著减缓。活化EGFR促进A172胶质瘤CD44蛋白表达，而EGFR的抑制剂Lapatinib可显著抑制上述效应。丙戊酸钠抑制EGFR磷酸化，下调CD44蛋白表达。结论:丙戊酸钠抑制A172胶质瘤细胞的生长。抑制A172胶质瘤细胞中EGFR的活化，下调CD44的表达，是丙戊酸钠抑制胶质瘤细胞生长的其中一个机制。     

局部晚期食管鳞癌新辅助放疗剂量与病理完全缓解关系分析

目的 探讨接受新辅助放化疗的局部晚期食管鳞癌患者新辅助放疗剂量与病理完全缓解(pCR)的关系。方法 收集2017-2019年间在四川大学华西医院肿瘤中心经病理确诊为食管鳞癌并接受新辅助放化疗和手术的 116例局部晚期患者临床资料。116例患者中 40~45Gy组 80例,≥45Gy组 36例,分析两组术后pCR率。结果 全组患者的pCR率为38.8%(45/116),40~45Gy组与≥45Gy组的pCR率分别为44%(35/80)和28%(10/36)(P=0.105)。结论 术前新辅助采用较高的放疗剂量不增加局部晚期食管鳞癌的pCR率,有必要进行前瞻性的临床研究确定合适的新辅助放疗剂量。     

A Last Gift

Here at the Center, we had the privilege of seeing how Dan Callahan lived out his last days and weeks. True to his nature, Dan never stopped thinking or writing. Indeed, his wife Sidney told me that he finished his last essay one day before his death, on July 16th, insisting that she help him get to the computer so he could discuss it with a colleague. “It's my last one,” he told her with his characteristic self‐awareness. Dan also chose the last topic he would focus on: climate change. At a December 2018 board meeting, Dan presented his desire to develop a workshop to explore the ways in which bioethics in general, and The Hastings Center in particular, might be able to make a valuable contribution to addressing the problem of global warming.     

Altered pharmacokinetics of combined oral contraceptives in obesity — multistudy assessment

Objective

The objective was to evaluate the pharmacokinetics (PKs) of levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in obese women.

The Dark Side of Addiction Support Forums: Impacts of Poor Quality and Insufficient Emotional Support on Perceived Support Availability and Health Efficacy

Research has identified many benefits of participating in online social support forums; however, the potential negative impacts of these communities have rarely been examined. This study explored the negative impacts of low quality (i.e., low person-centered) and insufficient (i.e., under-benefitted) emotional support on online support seekers. Health stigma and perceived support availability were also examined as mediating and moderating variables, respectively, in the model. An online survey of addiction support forum users (N = 321) was conducted. Results showed that for participants with low health stigma, low person-centered support decreased health self-efficacy through reducing perceived online emotional support availability, but under-benefitted support did not impact them. For those with high health stigma, low person-centered emotional support had positive effects on health self-efficacy through increasing perceived support availability, whereas under-benefitted support reduced health self-efficacy through decreasing perceived support availability. Importantly, a considerable proportion of participants (44.86%) reported under-benefitted emotional support. These findings suggest support forum participation can have negative impacts, but not all participants are adversely impacted equally. Instead, moderating variables, such as health stigma, can play an important role. Implications for future research and health care practitioners are discussed.