What the Pandemic Experience Taught Us About STEM Higher Education-School Partnerships.

The move to virtual schooling and other measures to reduce the spread of SARS-CoV-2 infection dramatically changed the educational experience for grades K-12 populations during the years 2020 and 2021. STEM teaching and learning, and community partnerships focused on STEM education, were not exempt from the changes. Universities and other community partners had to adapt their STEM partnership programming to address new needs and assist students, teachers, families, and schools throughout periods of at-home learning and the re-reintroduction of in-person classes. Some of the changes included developing new programs, providing health-related guidance to school leaders, and converting student-focused programs to virtual formats. Through these experiences, new approaches emerged and lessons were learned that can be applied to partnership activities during normal times. These lessons included recognizing the importance of addressing inequities in students' access to technology; development of strategies to redesign enrichment programs and classroom instruction for effective online delivery; and identifying and adapting to the range of technologies available to support virtual teaching in differing schools. The increased familiarity by all partners with virtual formats has opened the door to greater participation by students in STEM enrichment programs, online partnerships with STEM professionals and mentoring opportunities.

Baseline Screening MRI Uptake and Findings in Women with ≥ 20% Lifetime Risk of Breast Cancer.

BACKGROUND: The American Cancer Society recommends screening magnetic resonance imaging (MRI) for patients with a ≥ 20% lifetime breast cancer risk. This study assesses the outcomes of baseline MRI screens in women from a high-risk breast clinic (HRBC). METHODS: We retrospectively reviewed patients from our institution's HRBC, excluding those with prior breast cancer and predisposing genetic mutations. Screening MRI was recommended for a lifetime risk of ≥ 20% using the Tyrer-Cuzick model. We determined baseline MRI results, biopsy rates, and frequency of MRI-detected high-risk lesions (HRLs) and breast cancers. RESULTS: Overall, 319 women attended our HRBC; median age was 48 years and 4.7% had prior atypia/lobular carcinoma in situ. Screening MRI was recommended for 282 patients, of whom 196 (69.5%) completed a baseline screen. A Breast Imaging-Reporting and Data System (BIRADS) 3 or 4 finding occurred in 19.6% of patients; 23 (12.3%) required 6-month follow-up MRI, 16 (8.6%) underwent core biopsy, and 4 (2.1%) underwent excisional biopsy after initial core. An additional 7 (3.7%) patients had a non-breast incidental finding. An HRL was identified in 2 (1.1%) patients (atypical ductal and lobular hyperplasia, respectively), and 2 (1.1%) were diagnosed with T1N0 breast cancers. CONCLUSIONS: In the setting of an HRBC, 70% of women with a ≥ 20% lifetime risk of breast cancer pursued screening MRI when recommended. On baseline screen, the rate of MRI-detected breast cancer was low (1%); however, malignancies were mammographically occult and identified at an early stage. Despite a low cancer rate, nearly one in four women required additional diagnostic investigation. Prescreening counselling should include a discussion of this possibility, and longer-term follow-up of screening MRI is needed in this high-risk population.

Outcomes at 6 months for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularisation with stent placement: the TARGET follow-up study.

BACKGROUND: Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown. METHODS: In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously. FINDINGS: At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14.8%) patients who received tirofiban and 345 (14.3%) patients who received abciximab (hazard ratio 1.04, 95% CI 0.90-1.21; p=0.591). The rates for the individual endpoints were 191 (8.0%) versus 159 (6.6%) for myocardial infarction (hazard ratio 1.21, 95% CI 0.98-1.50; p=0.074), 26 (1.1%) versus 25 (1.0%) for death (1.04, 0.60-1.80; p=0.893), and 194 (8.1%) versus 208 (8.6%) for target-vessel revascularisation (0.93, 0.77-1.14; p=0.495). INTERPRETATION: At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation.

Secondary hormonal manipulation of prostate cancer.

Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone-resistant prostate cancer (HRPC) have a median survival of approximately 18 months, and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease, and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone.

Low dose ketoconazole with replacement doses of hydrocortisone in patients with progressive androgen independent prostate cancer.

PURPOSE: High-dose (400 mg.) oral ketoconazole 3 times daily with replacement doses of hydrocortisone has become a standard treatment option for patients with advanced prostate cancer which progresses after androgen deprivation. However, toxicity can hinder the ability to deliver treatment and the cost of the regimen can be substantial. Therefore, a prospective phase II study was conducted to assess the efficacy and safety of a regimen of low dose (200 mg.) oral ketoconazole 3 times daily with replacement doses of hydrocortisone in men with androgen independent prostate cancer. MATERIALS AND METHODS: The study included 28 patients with progressive prostate cancer despite anorchid levels of testosterone and ongoing testicular androgen suppression. Treatment consisted of low dose ketoconazole and replacement doses of oral hydrocortisone (20 mg. every morning and 10 mg. at bedtime). At the time of disease progression patients were treated with high dose ketoconazole and continued on the same dose of hydrocortisone. Adrenal androgen levels were measured, and baseline and followup levels correlated with clinical outcome. RESULTS: Overall, 13 (46%) of 28 patients had a prostate specific antigen decrease of more than 50% (95% confidence interval 27.5% to 66.1%). Median duration of prostate specific antigen decrease for all responders was 30+ weeks and 5 patients continue to exhibit a response, ranging from 36+ to 53+ weeks. In general, therapy was well tolerated. There were no grade 4 toxicities. Grade 3 toxicities included hepatotoxicity in 1 patient and depression in 2. The most common toxicities were nausea (29% grades 1 and 2), dry skin (18% grade 1) and fatigue (14% grade 1). Four (14%) patients discontinued low dose ketoconazole due to toxicities. Of the 16 patients who received high dose ketoconazole after disease progression with low dose ketoconazole, 3 were removed from treatment due to toxicity and no patient responded to high dose ketoconazole. There was no difference in the distribution of pretreatment endocrine values between responders and nonresponders, and the magnitude of change in adrenal androgen levels was not associated with response to therapy, although a potential association could easily have been missed due to small sample size. CONCLUSIONS: The regimen of low dose ketoconazole with replacement doses of hydrocortisone is well tolerated and has moderate activity in patients with progressive androgen independent prostate cancer.

Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer.

There is a pressing need for new agents to treat hormone-refractory prostate cancer (HRPC). Doxorubicin has shown modest activity in this setting, but its use is limited by its toxicities. Liposomal encapsulation of doxorubicin appears to promote enhanced tumor accumulation in some tumor types, and toxicity appears to be reduced. A phase II trial of liposomal doxorubicin was therefore conducted in patients with HRPC. Fourteen patients with progressive HRPC were treated. For the first dose only, patients were randomized to receive either doxorubicin 50 mg/m2 or liposomal doxorubicin 50 mg/m2 in order to evaluate exploratory pharmacokinetics. For all subsequent cycles, all patients received liposomal doxorubicin 50 mg/m2. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. All 14 patients were evaluable for response and toxicity. Two patients (14%) had declines in serum PSA of > or = 50%. The first patient had a baseline PSA of 34.7 ng/mL and a nadir of 17.0 ng/mL. The second patient had a baseline PSA of 5580.0 ng/mL and a nadir of 200.7 ng/mL. The latter of these 2 patients had an unambiguous improvement in bone scan and a reduction in pain. Treatment was well tolerated overall. One patient was removed from treatment after the development of a grade 3 infusion reaction with the first cycle of liposomal doxorubicin. Neutropenia was the most common toxicity; in only 1 case was it grade 3, and no cases of grade 4 were seen. Doxorubicin plasma concentrations were best fit by a linear, two-compartment model. Liposomal doxorubicin plasma concentrations were best fit by a linear, one-compartment model. Treatment with liposomal doxorubicin was well tolerated overall. While monotherapy with liposomal doxorubicin has only modest activity in the treatment of HRPC, it may be of interest to study this agent as part of combination chemotherapy.