M E Beth Smith

Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. PURPOSE To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer. DATA SOURCES MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists. STUDY SELECTION English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. DATA EXTRACTION Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria. DATA SYNTHESIS Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer. LIMITATION Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. CONCLUSION Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Systematic Review: Comparative Effectiveness of Medications to Reduce Risk for Primary Breast Cancer

Nelson and colleagues reviewed trials and observational studies to summarize the benefits and harms of tamoxifen citrate, raloxifene, and tibolone in reducing the risk for primary breast cancer in ...

Early Warning System Scores for Clinical Deterioration in Hospitalized Patients: A Systematic Review

RATIONALE Early warning system (EWS) scores are used by hospital care teams to recognize early signs of clinical deterioration and trigger more intensive care. OBJECTIVE To systematically review the evidence on the ability of early warning system scores to predict a patients risk of clinical deterioration and the impact of early warning system implementation on health outcomes and resource utilization. METHODS We searched the MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases through May 2014. We included English-language studies of early warning system scores used with adults admitted to medical or surgical wards. We abstracted study characteristics, including population, setting, sample size, duration, and criteria used for early warning system scoring. For predictive ability, the primary outcomes were modeled for discrimination on 48-hour mortality, cardiac arrest, or pulmonary arrest. Outcomes for the impact of early warning system implementation included 30-day mortality, cardiovascular events, use of vasopressors, respiratory failure, days on ventilator, and resource utilization. We assessed study quality using a modified Quality in Prognosis Studies assessment tool where applicable. MEASUREMENTS AND MAIN RESULTS Of 11,183 citations studies reviewed, one controlled trial and 20 observational studies of 13 unique models met our inclusion criteria. In eight studies, researchers addressed the predictive ability of early warning system tools and found a strong predictive value for death (area under the receiver operating characteristic curve [AUROC], 0.88-0.93) and cardiac arrest (AUROC, 0.74-0.86) within 48 hours. In 13 studies (one controlled trial and 12 pre-post observational studies), researchers addressed the impact on health outcomes and resource utilization and had mixed results. The one controlled trial was of good quality, and the researchers found no difference in mortality, transfers to the ICU, or length of hospital stay. The pre-post designs of the remaining studies have significant methodological limitations, resulting in insufficient evidence to draw conclusions. CONCLUSIONS Early warning system scores perform well for prediction of cardiac arrest and death within 48 hours, although the impact on health outcomes and resource utilization remains uncertain, owing to methodological limitations. Efforts to assess performance and effectiveness more rigorously will be needed as early warning system use becomes more widespread.

Quality varies across clinical practice guidelines for mammography screening in women aged 40–49 years as assessed by AGREE and AMSTAR instruments

OBJECTIVE To assess the quality of clinical practice guidelines providing recommendations on the frequency of mammography screening in asymptomatic, average-risk women 40-49 years of age. STUDY DESIGN AND SETTING We searched the National Guideline Clearinghouse and MEDLINE for guidelines published from 2005 to 2010. Five independent assessors rated the quality of each guideline and its underlying evidence review using the Appraisal of Guidelines for Research and Evaluation (AGREE) and Assessment of Multiple Systematic Reviews (AMSTAR) instruments, respectively. RESULTS Eleven guidelines were appraised. Ten referenced an underlying evidence review; two referenced the same review. Three reviews were rated good, one was moderate, and five were rated poor quality. On overall assessment of the quality of the guidelines, two were strongly recommended, two were recommended with provisos, and seven were either not recommended or the assessors were unsure whether to recommend it. Most guidelines clearly presented their recommendations, but the rigor of development, applicability, and stakeholder involvement varied. Seven guidelines recommended mammography screening as part of a periodic health examination and four recommended individualized screening in the target population. The latter four guidelines were based on good-quality reviews and three were recommended by the assessors. CONCLUSION Guideline users need to be aware of the variability in quality and identify the high-quality guidelines that meet their needs.