BACKGROUND: There is a well-documented lack of rapid, low-cost tuberculosis (TB) drug resistance diagnostics in low-income settings across the globe. It is these areas that are plagued with a disproportionately high disease burden and in greatest need of these diagnostics. METHODS: In this study, we compared the performance of Light Forge, a microfluidic high-resolution melting analysis (HRMA) prototype for rapid low-cost detection of TB drug resistance with a commercial HRMA device, a predictive "nearest-neighbor" thermodynamic model, DNA sequencing, and phenotypic drug susceptibility testing (DST). The initial development and assessment of the Light Forge assay was performed with 7 phenotypically drug resistant strains of Mycobacterium tuberculosis (M.tb) that had their rpoB gene subsequently sequenced to confirm resistance to Rifampin. These isolates of M.tb were then compared against a drug-susceptible standard, H37Rv. Seven strains of M.tb were isolated from clinical specimens and individually analyzed to characterize the unique melting profile of each strain. RESULTS: Light Forge was able to detect drug-resistance linked mutations with 100% concordance to the sequencing, phenotypic DST and the "nearest neighbor" thermodynamic model. Researchers were then blinded to the resistance profile of the seven M.tb strains. In this experiment, Light Forge correctly classified 7 out of 9 strains as either drug resistant or drug susceptible. CONCLUSIONS: Light Forge represents a promising prototype for a fast, low-cost diagnostic alternative for detection of drug resistant strains of TB in resource constrained settings.

Background: Multiple studies have been published that attempt to examine relevant outcomes of utilizing helicopter transport over traditional ground-based emergency medical services (EMS). Unfortunately, these studies suffer from poor methodology and are confounded by substantial differences in training and expertise of the personnel involved in the medical transfer. The EMS system in Central Massachusetts is unique in that when a physician from an outside hospital calls for an HEMS transport, the pilot determines if weather conditions permit to fly without having any further knowledge about the patient. If flying is deemed unsafe, the helicopter personnel will retrieve the patient by traditional ground ambulance. This allowed us to compare these two transfer modalities while eliminating the confounder of crew expertise. We hypothesize that the overall mortality of these inter-facility transfers is comparable, regardless of mode of transport and diagnoses, if accompanied by highly-trained and experienced personnel. Purpose: This study aimed to delineate the advantages of helicopter transport (HEMS) over ground transport (GEMS) of critically ill patients undergoing inter-facility transfers. Methods: We performed a retrospective chart review of 2,129 patients that were transferred from an outside hospital to our tertiary care center in Central Massachusetts by a Helicopter EMS (HEMS) crew between January of 2010 and April of 2017. These patients were either transferred by ground ambulance or helicopter ambulance. Transfers occurred by ground ambulance in limited cases where HEMS was grounded due to poor weather. In these instances, the Helicopter crew, consisting of a paramedic and flight nurse, staffed a ground ambulance to complete the transfer. Furthermore, we identified 655 patients that were transferred directly from the scene of the emergency, but these patients were excluded due to inability to standardize for transport distance. After categorizing 1,323 patients that were transferred by HEMS and 151 patients that were transferred by GEMS, patients were matched to their respective All Patients Refined Diagnosis Related Group (APR-DRG) and In-Hospital Mortality data. Scalar and categorical outcomes were analyzed T-Test or Fishers exact test respectively. Sub-group analyses were completed by categorizing patients by diagnosis or APR-DRG severity level. Results: The use of Helicopter EMS significantly reduced the time to definitive care over Ground EMS by at least twenty-one minutes, but no-more than one hour and seventeen minutes depending on the location of the requesting hospital. We found no statistical difference in the age or gender of the population transferred by either HEMS or GEMS. However, the population transferred by GEMS had significantly increased APR-DRG Severity and Risk of Mortality scores over the population transferred by HEMS. Despite this finding, there was no difference in in-hospital mortality between the two transfer modalities. Subgroup analysis did not show any significant difference in mortality based on diagnosis or APR- DRG classification. Conclusions: Despite the significant reduction in the time to definitive care through the utilization of HEMS, there was no statistically significant survival benefit conferred to critically ill patients undergoing inter-facility transfers. This suggests that the transport methodology may be of secondary importance to the level of training of the providers who are delivering the care en route.