Publications

Human pluripotent stem cells (hPS cells) are rapidly emerging as a powerful tool for biomedical discovery. The advent of human induced pluripotent stem cells (hiPS cells) with human embryonic stem (hES)-cell-like properties has led to hPS cells with disease-specific genetic backgrounds for in vitro disease modeling and drug discovery as well as mechanistic and developmental studies. To fully realize this potential, it will be necessary to modify the genome of hPS cells with precision and flexibility. Pioneering experiments utilizing site-specific double-strand break (DSB)-mediated genome engineering tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have paved the way to genome engineering in previously recalcitrant systems such as hPS cells. However, these methods are technically cumbersome and require significant expertise, which has limited adoption. A major recent advance involving the clustered regularly interspaced short palindromic repeats (CRISPR) endonuclease has dramatically simplified the effort required for genome engineering and will likely be adopted widely as the most rapid and flexible system for genome editing in hPS cells. In this unit, we describe commonly practiced methods for CRISPR endonuclease genomic editing of hPS cells into cell lines containing genomes altered by insertion/deletion (indel) mutagenesis or insertion of recombinant genomic DNA.

Despite improvements in overall health of the American population, disparities persist, particularly for minority women. The Affordable Care Act (ACA) offers the potential to reduce disparities through expanded insurance coverage, greater access to high-quality care, and bolstered prevention efforts in the context of new models of care such as the patient-centered medical home (PCMH). We use case studies representing three clinical conditions (breast cancer, HIV, and coronary heart disease) to present strategies for how a PCMH could reduce disparities for minority women. The case studies highlight the opportunity that further implementation of the ACA provides to improve screening, risk assessment, and prevention for a range of conditions that impact the health of minority women, as well as areas ripe for future investigation.

BACKGROUND

Patients with chronic noncancer pain treated with higher doses of opioids or concurrent substance use are at increased risk of adverse events. Although several national guidelines recommend maximum dosing thresholds and urine drug testing, adherence to these guidelines is inconsistent.

METHODS

To identify predictors of higher-risk opioid prescriptions in 2 academic primary care clinics, the authors developed a retrospective cohort of 842 patients who were prescribed ≥5 opioid prescriptions for noncancer pain between March 2012 and March 2013. The authors evaluated odds of higher-dose opioid prescriptions and urine drug testing using multivariate logistic models.

RESULTS

Among study subjects, 47% received prescriptions for the equivalent of ≥50 mg morphine per day. After adjustment for confounders, patients with a resident primary care provider were less likely to receive higher-dose prescriptions compared with faculty providers (odds ratio = 0.66, 95% confidence interval [CI]: 0.46-0.94), whereas patients with a nonlocal home address were more likely to be prescribed higher doses (odds ratio = 2.1, 95% CI: 1.5-2.9). Hispanic, Asian, and older patients were also less likely to be prescribed higher doses. Urine drug testing was not regularly completed (35% over 2 years), but odds of testing were higher for patients who self-identified as black, had resident primary care providers, lived locally, or were prescribed higher opioid doses.

CONCLUSIONS

In this academic clinical setting, patients with a resident primary care provider are less likely to receive higher-risk opioid prescriptions, as are Hispanic, Asian, and older patients. Black patients complete urine drug tests more frequently independent of other patient and provider characteristics. Additional studies are needed to assess why patients who travel larger distances to their primary care clinic are prescribed higher doses of opioids for chronic noncancer pain.