Making informed choices on incorporating chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development.

BACKGROUND & OBJECTIVES: Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 "transcriptome" is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer's disease and type-2 diabetes. CONCLUSION: Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

Ultrasound-guided core biopsy in the diagnosis of lymphoma of the head and neck. A 9 year experience.

OBJECTIVES: This retrospective study aimed to evaluate the diagnostic utility of ultrasound-guided core biopsy (USCB) in lymphoma of the head and neck, in particular whether core biopsy can provide sufficient diagnostic information for definitive treatment. METHODS: All lymphomas diagnosed in the head and neck at Eastbourne General Hospital between January 2000 and June 2009 were identified. Radiology and pathology reports were reviewed and the diagnostic techniques recorded. The type of biopsy (fine needle aspiration, needle core, surgical excision biopsy) used to establish a diagnosis sufficient to allow treatment, i.e. the "index" diagnostic technique, was identified. Previous inconclusive or inadequate biopsies were noted. Pathology reports based on USCB were graded 0-3 according to diagnostic completeness and ability to provide treatment information. RESULTS: Of 691 overall cases of lymphoma diagnosed over the 9 year period, 171 different patients presented with lymphoma in the head and neck. Of these 171, 83 had USCB biopsy during diagnostic work up. 60 were regarded as grade 3 where a confident diagnosis of lymphoma was made. In seven patients, clinical management proceeded on the basis of a suggestive (grade 2) pathology report without surgical excision, and these were therefore also included as "index" biopsies. Overall therefore, 67/83 core biopsies (81%) provided adequate information to allow treatment. Surgical excision biopsy was the index modality in 104 cases. CONCLUSION: In the majority of cases USCB is adequate for confident histopathological diagnosis avoiding the need for surgical excision biopsy in cases of suspected head and neck lymphoma.

Illegal immigration to Hong Kong.

"Illegal migration from China is contrasted to that from Vietnam to highlight Hong Kong's unique place in such flows.... The key difference in Hong Kong's effectiveness at stemming these two illegal migrant streams has been bilateral cooperation, which has been achieved with China but lacking in the case of Vietnam.... This paper seeks to outline the dimensions of the illegal migration problem from China and Indochina, the different attitudes taken by the Hong Kong authorities to the problems, and some theoretical issues for consideration."

Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure.

To investigate the determinants of mortality in patients with chronic congestive heart failure, we prospectively evaluated 84 patients with this disorder who underwent detailed biochemical, clinical, and functional tests at the time of initial evaluation and were then followed for 12 to 52 months (mean 31). During this period of follow-up, 58% of the patients died, of whom 71% died suddenly. The most important pretreatment predictor of mortality in these patients was the frequency of ventricular extrasystoles, followed by echocardiographic fractional shortening, a diagnosis of coronary artery disease, and duration of treadmill exercise. The finding of hypokalemia and hyponatremia in these patients at the time of entry into the study was associated with a poor prognosis by univariate analytical methods, but these electrolyte abnormalities did not provide independent prognostic information. The presence of ventricular arrhythmias was related to the severity of left ventricular dysfunction, exercise intolerance, and neurohormonal activation, suggesting that such arrhythmias are multifactorial in origin and may not simply be related to electrolyte abnormalities.