Aartik Sarma

The state of health policy education in U.S. medical schools.

A survey of deans of medical education in the United States reveals both progress and challenges in incorporating health policy education into medical school curricula.

A Systematic Review of Reported Cost for Smear and Culture Tests during Multidrug-Resistant Tuberculosis Treatment

Background In 2011, World Health Organization revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB) by increasing the frequency of culture examination from quarterly to monthly after culture conversion. Implementing the recommendation requires substantial additional investment in laboratory infrastructure. The objective of this review is to provide cost evidence that is needed for national TB programs to budget for optimal monitoring strategies. Methods and Findings We conducted the first systematic literature review on unit cost estimates of three monitoring strategies: 1) smear only; 2) culture only; 3) combined smear and culture. 26 peer-reviewed studies were selected by searching 10 databases in English and Chinese for literature published between 1995 and 2012. Cost estimates were converted into 2010 constant USD and international dollars. We assessed the quality of the estimates using a matrix with five essential elements and provided a cost projection for the combined smear and culture tests where the data were available. The 26 studies reported the cost estimates in 16 predominantly high- or middle-income countries from 1993 to 2009. The estimated unit cost for smear, culture, and combined tests ranges from

A Simple Method for Amplifying RNA Targets (SMART)

0.26 to

Ligation with Nucleic Acid Sequence–Based Amplification

10.50,

A Novel Subtyping Assay for Detection of Clostridium difficile Virulence Genes

1.63 to

Early In Vitro Transcription Termination in Human H5 Influenza Viral RNA Synthesis

62.01, and

A Systems Approach to Healthcare Innovation Using the MIT Hacking Medicine Model

26.73 to

SIMULTANEOUS QUANTITATIVE MULTIPLE PRIMER DETECTION OF CLOSTRIDIUM DIFFICILE

39.57, respectively. The ratio of culture to smear costs varies from 1.35 to 11.98. The wide range of estimates is likely attributable to using different laboratory methods in different regions and years and differing practices in collecting and reporting cost data. Most studies did not report information critical for generalizing their conclusions. Conclusion The paucity and low quality of unit cost estimates for TB monitoring in resource-poor settings impose technical challenges in predicting the resources needed for strengthening microbiological monitoring. To improve the validity and comparability of the cost data, we strongly advocate the data collection, estimation, and reporting follow protocols proposed by WHO.

DETECTION OF SHORT RNA SEQUENCES

We present a novel and simple method for amplifying RNA targets (named by its acronym, SMART), and for detection, using engineered amplification probes that overcome existing limitations of current RNA-based technologies. This system amplifies and detects optimal engineered ssDNA probes that hybridize to target RNA. The amplifiable probe-target RNA complex is captured on magnetic beads using a sequence-specific capture probe and is separated from unbound probe using a novel microfluidic technique. Hybridization sequences are not constrained as they are in conventional target-amplification reactions such as nucleic acid sequence amplification (NASBA). Our engineered ssDNA probe was amplified both off-chip and in a microchip reservoir at the end of the separation microchannel using isothermal NASBA. Optimal solution conditions for ssDNA amplification were investigated. Although KCl and MgCl(2) are typically found in NASBA reactions, replacing 70 mmol/L of the 82 mmol/L total chloride ions with acetate resulted in optimal reaction conditions, particularly for low but clinically relevant probe concentrations (≤100 fmol/L). With the optimal probe design and solution conditions, we also successfully removed the initial heating step of NASBA, thus achieving a true isothermal reaction. The SMART assay using a synthetic model influenza DNA target sequence served as a fundamental demonstration of the efficacy of the capture and microfluidic separation system, thus bridging our system to a clinically relevant detection problem.

THE LEARNING CURVE FOR MEDICAL DEVICES: EXPERIENCE WITH VASCULAR CLOSURE DEVICES IN MASSACHUSETTS

This work presents a novel method for detecting nucleic acid targets using a ligation step along with an isothermal, exponential amplification step. We use an engineered ssDNA with two variable regions on the ends, allowing us to design the probe for optimal reaction kinetics and primer binding. This two-part probe is ligated by T4 DNA Ligase only when both parts bind adjacently to the target. The assay demonstrates that the expected 72-nt RNA product appears only when the synthetic target, T4 ligase, and both probe fragments are present during the ligation step. An extraneous 38-nt RNA product also appears due to linear amplification of unligated probe (P3), but its presence does not cause a false-positive result. In addition, 40 mmol/L KCl in the final amplification mix was found to be optimal. It was also found that increasing P5 in excess of P3 helped with ligation and reduced the extraneous 38-nt RNA product. The assay was also tested with a single nucleotide polymorphism target, changing one base at the ligation site. The assay was able to yield a negative signal despite only a single-base change. Finally, using P3 and P5 with longer binding sites results in increased overall sensitivity of the reaction, showing that increasing ligation efficiency can improve the assay overall. We believe that this method can be used effectively for a number of diagnostic assays.