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.     

Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

核医学学科新增医疗服务项目定价方法研究

目的：基于以价值为基础的定价方法，计算核医学学科新增医疗服务项目镭[²²³ Ra]骨转移瘤治疗的医疗服务价格。为相关新增医疗服务项目的申报和定价打下循证基础，为合理补偿医务人员劳动价值、提升患者服务项目可及性提供依据。方法：采集2021年3—12月使用“镭核素[²²³ Ra]骨转移瘤治疗资源投入及费用数据采集表”相关数据，开展专家访谈进行系数赋值和基线对照项目确定，得到镭[²²³ Ra]骨转移瘤治疗服务各个环节的成本和新增服务的价值。结果：镭[²²³ Ra]骨转移瘤治疗服务按服务特点分为注射前评估、治疗计划、给药、给药后监测、废弃物处理与监测等环节，各环节3地平均人力耗时分别为104分钟、39分钟、25分钟、72分钟和56分钟，中位物耗成本为48.20元，3地总成本(平均人力成本+中位物耗成本)为763.68元。结合系数赋值结果和基线对比项目，得到新增项目的价值为810.19元。结论：运用基于技术难度和风险程度的价值定价理论，计算镭[²²³ Ra]骨转移瘤治疗新增医疗服务项目的服务价值，建议以价值作为服务定价依据。该定价公式和研究方法不仅可用于其他核医学学科新增服务项目的定价，还适用于现行医疗服务项目的价格动态调整，为未来学科价格工作提供方法学参考。     

基于动脉自旋标记技术的麻痹性痴呆患者脑血流量特点及其与认知障碍相关性

目的探讨麻痹性痴呆（GPI）患者脑血流量（CBF）特点及其与认知障碍的相关性。 方法纳入2018年1月至2019年12月于首都医科大学附属北京地坛医院就诊的GPI患者18例和健康体检者18例（健康对照组），采用蒙特利尔认知评估量表评定认知功能。采用磁共振动脉自旋标记技术扫描评估其各个脑区CBF，并进一步应用Spearman相关分析CBF异常区域与认知功能的相关性。 结果GPI患者蒙特利尔认知评估量表评分低于健康对照组[（16.00 ± 7.19）vs. （27.90 ± 1.21）：t =－7.853、P < 0.001）]。18例GPI患者中，头颅MRI正常5例，脑白质病变1例，脑萎缩9例，3例患者同时存在脑萎缩和脑白质病变。健康对照组头颅MRI均未见异常。GPI患者脑13、14、28、37、38、41、42、43、44、46、48、49、50、51、52、69、70、77、78、83、84、88、109、117、165、166、167、168、169、177、178、179、187、188、211、212、213、214、215、216、219、223、227、237和238区CBF显著高于健康对照组（P均< 0.001）。GPI患者认知障碍中的注意力障碍与脑69、70、77、78、166和168区CBF异常有一定的负相关性（r =－0.476、P = 0.046，r =－0.487、P = 0.034，r =－0.604、P = 0.008，r = －0.545、P = 0.019，r =－0.544、P = 0.02，r =－0.522、P = 0.026）。 结论GPI患者存在全脑血流量升高。GPI患者认知功能障碍中的注意力障碍可能与局部脑区血流量升高有一定相关性。局部CBF越高，注意力障碍越严重。这可能也是GPI发病机制之一。     

Ex vivo porcine model for eye,eyelid, and orbit movement analysis of 4-mm ferromagnetic foreign bodies in MRI

Graefe's Archive for Clinical and Experimental Ophthalmology - Ferromagnetic foreign bodies (FFB) present during magnetic resonance imaging (MRI) explorations can lead to tissue injury due to...     

Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...