A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.

https://www.jstor.org/stable/pdf/3765916.pdf

The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.

Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.

/pdf/gene-expression-profiling-predicts-clinical-outcome-of-5bu8dmnf6h.pdf

Gene expression profiling predicts clinical outcome of breast cancer

Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

/pdf/guidelines-for-the-early-management-of-patients-with-acute-19udbft6e7.pdf

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

https://vascular.stanford.edu/content/dam/sm/vascular/documents/endovasc/guidelines/PIIS0741521406022968.pdf

Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)

Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a...

/pdf/a-gene-expression-signature-as-a-predictor-of-survival-in-1f6irz2ok6.pdf

A Gene-Expression Signature as a Predictor of Survival in Breast Cancer

The randomized clinical trial is accepted as the most reliable method of determining the relative merits of different therapies. At best it is a scientific experiment in the clinical setting, and demands all the rigours of experimental methods to produce valid data from which inference may be drawn. Randomization ensures the highest probability that the only difference between treated patient groups is the treatment given, and it is the component of clinical trials that produces the greatest ethical problems. It has three essential features. First, it eliminates investigator bias; second, it tends to balance known and unknown prognostic parameters in treatment groups; and, third, it forms the basis for the validity of statistical tests of significance.

Highlights in development of randomized clinical trials

Randomized clinical trials evaluating local treatments for early breast cancer have provided new data on the long-term morbidity and cause-specific mortality associated with radiotherapy combined with different types of mastectomy. The difficulty surgeons have in determining optimal integration of surgery and radiotherapy for breast preservation is demonstrated by the wide variation of radiotherapy schedules, lack of interpretable data to justify a radiotherapy "boost," and data from a randomized trial suggesting that radiotherapy applied only to the excision site might be sufficient. The use of cytology aspirates for tumor grading, the prognostic importance of vascular invasion, and new tumor markers and cancer cells in bone marrow at diagnosis are all reported. New data came from attempts to identify an axillary sentinel node at surgery for breast cancer. Studies of connective tissue disorders in women with silicone implants failed to find evidence of increased risk, but 3-year follow-ups confirmed that surgeons who preferred mastectomy are more likely to have anxious, depressed patients.

Surgery of early breast cancer.

Background: The prognostic abilities of most gene expression signatures in breast cancer are often due to detection of proliferative activity measured from expression of genes regulated as a function of cell cycle progression. Cell Cycle Progression (CCP) score is an important prognostic factor in prostate cancer, and has shown promising results for renal and lung cancer; its role in ductal carcinoma in situ (DCIS) has not been explored. We investigated the prognostic and predictive relevance of CCP Score in DCIS using material from UK/ANZ DCIS trial. Methods: Formalin-fixed paraffin embedded tissues were collected from patients enrolled in the UK/ANZ DCIS trial, a randomised 2X2 factorial design trial investigating role of tamoxifen, radiotherapy (RT) or both as adjuvant treatment in DCIS. mRNA expression of 25 S- and M-phase CCP genes was evaluated by reverse transcription followed by PCR on customized Taqman low-density arrays. CCP score is an un-weighted average of the expression values of CCP genes after normalisation with 14 housekeeping genes. CCP score was analysed as a continuous variable and also as an ordinal variable using tertile-based cut-offs. Exploratory analyses with subgroups defined by HER2 status by immunohistochemistry were performed. Results: CCP scores were evaluable in 521 (134 recurrence events) of 704 available samples (DCIS absent or insufficient RNA in 51, assay failure in 132). Increase in CCP score (median 1.15; IQR 0.71-1.74) was associated with increased risk of ipsilateral breast event (IBE) [Hazard ratio (HR) = 1.28; 95% Confidence Interval (95%CI) 1.08-1.51; p = 0.0049]. CCP score however was not an independent predictor in multivariate analyses [HR = 1.16; 95%CI 0.95-1.42; p = 0.14]. CCP scores were categorised as CCP low ( /= 0.87 to /= 1.52) by tertiles. The benefit of RT in reducing IBE was significant when CCP score was low [HR = 0.35; 95%CI 0.14-0.87; p = 0.024] or intermediate [HR = 0.23; 95%CI 0.09-0.59; p = 0.0023], however, those with high CCP score did not derive significant RT benefit [HR = 0.59; 95%CI 0.31-1.13; p = 0.11]. In exploratory subgroup analyses, HER2 negative DCIS with high CCP score (20.9% of all DCIS cases) did not derive RT benefit and the largest RT benefit was seen for DCIS that expressed HER2 and did not have a high CCP score (23.2% of all DCIS cases). Conclusions: CCP score is not independently associated with the risk of IBE but appears to be a predictor of RT benefit. Exploratory analyses suggest that combined with HER2 status, it may help in identifying a large DCIS subgroup where RT is highly indicated and another large subgroup where mastectomy may be merited. Citation Format: Thorat MA, Wagner S, Jones LJ, Levey PM, Bulka K, Hoff R, Sangale Z, Flake II DD, Bundred NJ, Fentiman IS, Forbes JF, Lanchbury JS, Cuzick J. Prognostic and predictive relevance of cell cycle progression (CCP) score in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-06.

Abstract P1-09-06: Prognostic and predictive relevance of cell cycle progression (CCP) score in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial

Management of breast cancer risk Screening versus prophylaxis

This article presents a systematic approach to analysing linear integer multi-objective optimization problems with uncertainty in the input data. The goal of this approach is to provide decision makers with meaningful information to facilitate the selection of a solution that meets performance expectations and is robust to input parameter uncertainty. Standard regularization techniques often deal with global stability concepts. The concept presented here is based on local quasi-stability and includes a local regularization technique that may be used to increase the robustness of any given efficient solution or to transform efficient solutions that are not robust (i.e. unstable), into robust solutions. An application to a multi-objective problem drawn from the mining industry is also presented.

John F. Forbes

Papers

Highlights in development of randomized clinical trials

Surgery of early breast cancer.

Abstract P1-09-06: Prognostic and predictive relevance of cell cycle progression (CCP) score in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial

Management of breast cancer risk Screening versus prophylaxis

Stability analysis and regularization of uncertain linear multi-objective integer optimization problems