A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders

PurposeUnderstanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.MethodsWe searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.ResultsAcross the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.ConclusionWe describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.     

PAMAM versus PEI complexation for siRNA delivery: interaction with model lipid membranes and cellular uptake

Pharmaceutical Research - Cationic polymers have many advantages as vectors for mediated cellular entry and delivery of siRNA. However, toxicity related to their cationic charge has compromised...     

American Cancer Society nutrition and physical activity guideline for cancer survivors

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.     

Part II: presentation,diagnosis, classification,treatment, and prevention of stress fractures in female athletes

ABSTRACT

Objectives: Stress fractures (SFx) occur as the result of repetitive loads over short periods of time, which leads to micro-damage of the bone through cortical resorption, ultimately leading to fracture. They are a common injury in female athletes and often cause significant morbidity. The goal of this study is to review the presentation, diagnosis, classification, treatment, and prevention of SFx in female athletes.

Results: A thorough history, physical exam, and appropriate imaging can facilitate early diagnosis of stress fracture (SFx) and faster resolution of symptoms with more conservative management. The female athlete triad is an especially important factor that contributes to the increased risk of SFx in females. The continuum of stress injuries ranges from mild microfailure to complete fracture, which has resulted in the development of newer grading schemas through MRI and radiographic findings. Stress fractures are also classified as low- or high-risk according to anatomic location, as blood supply and applied forces at different locations affect the likelihood of fracture propagation, displacement, delayed union, or non-union.

Conclusions: The ability to screen for at-risk athletes is paramount in preventing SFx. Recognition and prompt treatment of the female athlete triad requires a multidisciplinary approach in order to restore energy balance, correct menstrual irregularities, and improve bone health. This review provides a basis for understanding how to identify and treat stress fractures, which may allow treating physicians to diagnose this condition earlier and minimize any associated morbidity.