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.     

Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

Increased alpha suppression with age during involuntary memory retrieval

Recent work suggests that while voluntary episodic memory declines with age, involuntary episodic memory, which comes to mind spontaneously without intention, remains relatively intact. However, the neurophysiology underlying these differences has yet to be established. The current study used electroencephalography (EEG) to investigate voluntary and involuntary retrieval in older and younger adults. Participants first encoded sounds, half of which were paired with pictures, the other half unpaired. EEG was then recorded as they listened to the sounds, with participants in the involuntary group performing a sound localization cover task, and those in the voluntary group additionally attempting to recall the associated pictures. Participants later reported which sounds brought the paired picture to mind during the localization task. Reaction times on the localization task were slower for voluntary than involuntary retrieval and for paired than unpaired sounds, possibly reflecting increased attentional demands of voluntary retrieval and interference from reactivation of the associated pictures respectively. For the EEG analyses, young adults showed greater alpha event-related desynchronization (ERD) during voluntary than involuntary retrieval at frontal and occipital sites, while older adults showed pronounced alpha ERD regardless of intention. Additionally, older adults showed greater ERD for paired than unpaired sounds at occipital sites, likely reflecting visual reactivation of the associated pictures. Young adults did not show this alpha ERD memory effect. Taken together, these data suggest that involuntary memory is largely preserved with age, but this may be due to older adults' greater recruitment of top-down control even when demand for such control is limited.     

Brief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications

PURPOSE: Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. However, angioedema as a complication of ACEI therapy is under-recognized. As there are important implications for anesthesiologists and emergency medicine physicians, a review was undertaken to document the scope of the problem of ACEI-induced angioedema.. METHODS: A review of the published literature (identified by searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical uses of ACEIs and the incidence, risk factors, pathophysiology, clinical presentation and management of angioedema associated with the use of these drugs. PRINCIPAL FINDINGS: The incidence of ACEI related angioedema has increased from 0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are predisposed to developing angioedema which may be triggered by trauma, airway instrumentation, infection, and irritant fumes, particularly in those who are at increased risk. Cases of acute facial and airway oedema, due to ACEI drug administration, may be misdiagnosed as an anaphylactic reaction, and the association with ACEIs may be ignored. Some cases of intraoperative and postoperative airway edema may be precipitated by airway instrumentation in patients receiving ACEI drugs. The severity of airway compromise ranges from mild facial edema to severe laryngeal or subglottic edema which may prove life-threatening. CONCLUSION: In view of the widespread clinical indications and ever-increasing use of ACEI drugs, the potentially life-threatening adverse reaction of ACEI-associated angioedema, and its treatment, must be recognized by anesthesiologists and all clinicians involved in airway management.     

Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.     

全膝关节置换术后的骨溶解：胫骨盘表面的修饰及聚乙烯衬垫灭菌方法对其的影响术 后5至10年的报告

背景：从关节和胫骨假体聚乙烯衬垫后表面转移磨损碎屑，是全膝关节置换术后假体周围骨溶解的主要原因。全膝人工关节假体设计随时问而发生变化，例如对胫骨盘近端表面的粗糙度和聚乙烯衬垫的灭菌方法。我们假设胫骨盘表面抛光和采用空气中γ射线照射之外的其他方法对衬垫灭菌，可降低骨溶解的发生率。方法：从1987年至1998年，我们采用后十字韧带保留型的解剖型组配式全膝人工关节假体系列。对300名患者施行365例全膝关节置换术。术后5至10年，对这些患者的膝关节摄正、侧位X线片。由两位关节置换专家对X线片上的骨溶解状况进行单独评定（骨溶解的界定标准为假体周围存在边缘清晰的非线性松质骨丢失区）。结果：在粗糙表面的胫骨盘的242例膝关节中，使用空气中γ射线照射灭菌的衬垫固定，有34％（82例）骨溶解阳性。用惰性气体中γ射线照射或没有照射的衬垫与抛光表面连接的98例膝关节中，有9％（9例）骨溶解阳性。骨溶解与六项因素相关，这些因素为：一项与患者（男性）相关、一项与胫骨盘（近端表面抛光）相关、三项与聚乙烯衬垫（加工的原材料、灭菌方法及存放时间）相关及一项与手术技术（股骨假体与胫骨假体间的过伸）相关。结论：在这类假体设计中，胫骨盘近端表面采用抛光及衬垫采用更为先进的灭菌方法（不用空气中γ射线照射灭菌）能显著减少骨溶解的发生率，但不能避免骨溶解。     

The expression of emotion through nonverbal behavior in medical visits

Relationship-centered care reflects both knowing and feeling: the knowledge that physician and patient bring from their respective domains of expertise, and the physician’s and patient’s experience, expression, and perception of emotions during the medical encounter. These processes are conveyed and reciprocated in the care process through verbal and nonverbal communication. We suggest that the emotional context of care is especially related to nonverbal communication and that emotion-related communication skills, including sending and receiving nonverbal messages and emotional self-awareness, are critical elements of high-quality care. Although nonverbal behavior has received far less study than other care processes, the current review argues that it holds significance for the therapeutic relationship and influences important outcomes including satisfaction, adherence, and clinical outcomes of care.     

Mild traumatic brain injury in an insured population: subjective complaints and return to employment

The great majority of traumatic brain injury (TBI) is of mild severity, with Glasgow Coma Scores (GCS) of 13-15, post-traumatic amnesia of less than 48 hours and brief, if any, hospitalization. All mild TBI admissions to hospital were provided with education in the form of a brief interview and a brochure on minor head trauma from the National Head Injury Foundation. Seventy-seven insured individuals with mild TBI were contacted by phone between 1 and 3 months post-injury to determine the frequency and severity of post-traumatic symptoms and the rate of return to work (RTW). Twenty-six per cent of those contacted had subjective complaints; 88% had returned to work or school; 16% of those returning did so with some symptoms. Only 45% of symptomatic individuals sought medical consultation for their condition when offered. Education about post-traumatic symptoms from the onset may provide sufficient reassurance to most individuals that future use of medical services is seen as unnecessary. Rate of RTW is relatively higher than reported in previous studies of mild TBI.