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1.
Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.  相似文献   
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Although classified by the Joint Monitoring Programme (JMP) as unimproved sanitation facilities, public toilets still play a critical role in eliminating open defecation in informal settlements. We explored perspectives of toilet operators on opportunities and barriers to operation and maintenance (O&M) of public toilets in informal settlements. A cross-sectional study design was used. Up to 20 in-depth interviews were used to obtain data on the experiences of public toilet operators. Thematic content analysis was used.

Ressults show that opportunities for improving O&M include; operation of public toilets is a source of livelihood; operators are knowledgeable on occupational risks, and the community is involvedin sanitation activities. Barriers to effective O&M include; high operation costs, failure to break even and a lack of investments in occupational health Therefore, there is need to recognise the significance of public toilets as a viable alternative to open defecation in areas where ownership of private sanitation facilities is difficult. Failure to observe the health and safety of toilet operators may further compromise O&M.  相似文献   

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Background

Although suggested by practice guidelines, the need for pre-exercise stress testing in asymptomatic people with diabetes remains controversial. We examined the utility of screening with pre-exercise stress testing in patients with diabetes.

Methods

We completed a cohort study, evaluating patients with diabetes who attended an exercise program intake session between 2007 and 2012. The exposure of interest was referral for pre-exercise stress testing determined by an algorithm requiring sedentary patients with diabetes and ≥ 1 cardiac risk factor to undergo testing. Outcomes included cardiac catheterization, revascularization, cardiovascular-related admissions, mortality, and change in care.

Results

Among 1705 people with diabetes, 676 (40%) were referred for pre-exercise stress testing. In patients who were referred for stress testing compared with those who were not, there was no difference in the composite of cardiovascular outcomes (revascularization, cardiovascular-related admissions, and cardiovascular-related death) within 1 year (2.8% vs 1.9%, P = 0.250), or subsequent to the first year (3.1% vs 4.6%, P = 0.164). Within 1 year, more revascularizations were performed in patients referred for stress testing compared with those who were not (2.1% vs 0.8%, P = 0.027) but not during longer-term follow-up (mean 3.4 years).

Conclusions

The rates of cardiovascular outcomes in both tested and untested patients were low. Patients undergoing stress testing had no difference in adverse cardiovascular outcomes over the follow-up periods. Referral for stress testing did not result in a change in care for most patients. Our findings suggest stress testing before beginning an exercise program is not necessary for most asymptomatic patients with diabetes.  相似文献   
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PURPOSE: To evaluate the influence of various bleaching systems on subsurface microhardness of enamel and dentin. METHODS: 60 bovine crowns were distributed among seven groups (A: Opalescence Xtra Boost, B: Opalescence Quick, C: Rapid White, D: Whitestrips, E: Opalescence 10%, F: Opalescence PF 15%). The crowns were sectioned and baseline hardness (Knoop) of enamel and dentin was assessed on the sectioned surface at various distances from the enamel surface. The sectioned surface was covered with wax and the enamel was treated for 10 days with the bleaching agents A-F according to manufacturers' instructions. Bleaching with C-F was conducted each day (C: twice per day for 10 minutes, D: twice per day for 30 minutes, E: 8 hours, F: 4 hours), systems A-B were applied on first and fifth days (A: twice for 10 minutes, B: 1 hour). Finally, hardness was re-assessed. Data were statistically analyzed to compare baseline hardness and final hardness in the respective groups (P< 0.05). RESULTS: Analysis showed that in Group C, hardness was significantly reduced in both enamel and dentin. In the remaining groups, significant reduction of hardness was observed up to the following depths [microm] in enamel; A: 250, B: 700, D: 300, E: 150, F: 150. In these groups no significant hardness changes were recorded in subsurface dentin.  相似文献   
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Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left‐sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S‐DIBH) with prone free breathing (P‐FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S‐DIBH and P‐FB plans was compared using paired two‐tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%‐0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%‐0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%‐15.4%) for S‐DIBH and 1.0% (range 0.4%‐9.8%) for P‐FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%‐6.0%) with S‐DIBH and 0.0% (range 0.0%‐0.4%) with P‐FB (P = .008). Both S‐DIBH and P‐FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S‐DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI.  相似文献   
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