Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.     

聚甲酚磺醛溶液治疗外阴硬化性苔藓病变的临床分析

目的观察使用聚甲酚磺醛溶液治疗外阴硬化性苔藓病变的临床疗效。方法对经临床诊断确诊为外阴硬化性苔藓病变且自愿接受本次研究的36例患者使用聚甲酚磺醛溶液,观察其疗效。结果36例外阴硬化性苔藓病变患者经过聚甲酚磺醛溶液3个月疗程治疗,痊愈率达76.9%,显效率为15.4%,有效率为7.7%。结论聚甲酚磺醛溶液能有效治疗外阴硬化性苔藓病变,无论是缓解瘙痒症状,还是改善病灶皮肤病变效果均较好,为广大临床医生提供了治疗此疾患的新思路。     

医院信息化平台住院陪护人员管理功能的开发与应用

目的 探讨医院信息系统中增加住院陪护管理功能的应用效果。方法 基于互联网医院、智慧医院等信息系统，开发信息化住院陪护管理功能，包括流行病学史调查、免费核酸申请、电子陪护证办理、体温监测登记及上报和统计查询。该功能与医院智慧护理链接后全院应用。比较功能应用前和应用后的遵医嘱一患一陪达标率、有效陪护证达标率、体温监测并登记日上报达标率和陪护证使用追溯率，评价护士和管理者疫情防控管理的人均耗时以及对该管理功能的满意度。结果 应用信息化陪护管理功能后，一患一陪达标率、有效陪护证达标率、体温监测并登记日上报达标率和陪护证使用追溯率显著高于应用前（均P＜0.05）；护士陪护管理人均耗时从（554.13±30.77）s降至（311.67±21.54）s（P＜0.05）；护士和管理者对该信息化陪护管理功能的满意度显著提高（均P＜0.05）。结论 信息化住院陪护管理功能的应用有效提升了疫情期间陪护的管理质量和管理效率，提高了一线护士和管理者的满意度。     

ICU转科患者家属迁移应激的过渡期护理研究进展

以过渡期护理内涵为基础对文献进行干预措施内容提取，以干预时间点为标准对ICU转科患者家属迁移应激的过渡期护理措施进行综述，护理干预措施包括干预前准备、转科前干预、转科中干预、转科后干预，并总结护理干预效果评价，以期为临床护理人员开展相关实践提供具体参考，推进以家庭为中心的护理工作，改善临床护理质量。     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

CNS Maturation Process in Children and Adolescents in the Northern Region of the Russian Federation and Its Reflection in the Dynamics of Integral EEG Parameters

Neuroscience and Behavioral Physiology - We present here results from analysis of the formation of brain bioelectrical activity in children and adolescents living in the northern region of Russia...