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71.
Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice.  相似文献   
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Background  

Both violence and depression during pregnancy have been linked to adverse neonatal outcomes, particularly low birth weight. The aim of this study was to investigate the independent and interactive effects of these maternal exposures upon neonatal outcomes among pregnant adolescents in a disadvantaged population from Sao Paulo, Brazil.  相似文献   
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Background  

Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes.  相似文献   
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