Publications

The American College of Medical Genetics and Genomics (ACMG) recommends that mutations in 56 genes for 24 conditions are clinically actionable and should be reported as secondary findings after whole-genome sequencing (WGS). Our aim was to identify published economic evaluations of detecting mutations in these genes among the general population or among targeted/high-risk populations and conditions and identify gaps in knowledge. A targeted PubMed search from 1994 through November 2014 was performed, and we included original, English-language articles reporting cost-effectiveness or a cost-to-utility ratio or net benefits/benefit-cost focused on screening (not treatment) for conditions and genes listed by the ACMG. Articles were screened, classified as targeting a high-risk or general population, and abstracted by two reviewers. General population studies were evaluated for actual cost-effectiveness measures (e.g., incremental cost-effectiveness ratios (ICER)), whereas studies of targeted populations were evaluated for whether at least one scenario proposed was cost-effective (e.g., ICER of ≤$100,000 per life-year or quality-adjusted life-year gained). A total of 607 studies were identified, and 32 relevant studies were included. Identified studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The cost-effectiveness of screening in the general population was examined for only 2 of 24 conditions (8%). The cost-effectiveness of most genetic findings that the ACMG recommends for return has not been evaluated in economic studies or in the context of screening in the general population. The individual studies do not directly address the cost-effectiveness of WGS.

BACKGROUND

It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury.

METHODS

Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance.

RESULTS

Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04).

CONCLUSIONS

CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

OBJECTIVE

Surgical site infections (SSIs) are a leading cause of morbidity and mortality among women undergoing cesarean section (C-section), a common procedure in North America. While risk factors for SSI are often modifiable, wide variation in clinical practice exists. With this review, we provide a comprehensive overview of the results and quality of systematic reviews and meta-analyses on interventions to reduce surgical site infections among women undergoing C-section.

METHODS

We searched PubMed and the Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses published between January 2000 and May 2014 on interventions to reduce the occurrence of SSIs (incisional infections and endometritis), among women undergoing C-section. We extracted data on the interventions, outcomes, and strength of evidence as determined by the original article authors, and assessed the quality of each article based on a modified Assessment of Multiple Systematic Reviews tool.

RESULTS

A total of 30 review articles met inclusion criteria and were reviewed. Among these articles, 77 distinct interventions were evaluated: 29% were supported with strong evidence as assessed by the original article authors, and 83% of the reviews articles were classified as good quality based on our assessment. Ten interventions were classified as being effective in reducing SSI with strong evidence in a good-quality article, including preoperative vaginal cleansing, the use of perioperative antibiotic prophylaxis, and several surgical techniques.

CONCLUSION

Efforts to reduce SSI rates among women undergoing C-section should include interventions such as preoperative vaginal cleansing and the use of perioperative antibiotics because compelling evidence exists to support their effectiveness.