For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Background Recent changes to the Food and Drug Administration boxed warning for metformin will increase use in individuals with historical contraindications or precautions. Prescribers must understand clinical outcomes of metformin use in these populations. Purpose To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate-to-severe chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment. Data Sources MEDLINE (via PubMed) from January 1994 to September 2016; Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection English-language studies that examined adults with type 2 diabetes and chronic kidney disease with eGFR <60 mL/min/1.73m2, congestive heart failure, or chronic liver disease with hepatic impairment; compared diabetes regimens that included metformin to regimens that did not; and reported all-cause mortality, major adverse cardiovascular events and other outcomes of interest. Data Extraction Two reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis Based on quantitative/qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, and chronic liver disease with hepatic impairment, and reduced heart failure readmission in patients with chronic kidney disease and congestive heart failure. Limitations We identified low strength of evidence and sparse data on multiple outcomes of interest. Available studies were observational and had varying follow-up durations. Conclusions Metformin use in patients with moderate chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support recent changes in metformin labeling. Registration PROSPERO CRD42016027708 Funding Source U.S. Department of Veterans Affairs

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