Investigation of False Positive Results with an Oral Fluid Rapid HIV-1/2 Antibody Test

BACKGROUND: In March 2004, the OraQuick® rapid HIV antibody test became the first rapid HIV test approved by the US Food and Drug Administration for use on oral fluid specimens. Test results are available in 20 minutes, and the oral fluid test is non-invasive. From August 2004–June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick® oral-fluid rapid HIV tests in Minnesota. METHODOLOGY/PRINCIPAL FINDINGS: In a field investigation, we reviewed performance study data on oral-fluid and whole-blood OraQuick® rapid HIV test device lots and expiration dates and assessed test performance and interpretation with oral-fluid and whole-blood specimens by operators who reported false-positive results. We used multivariate logistic regression to evaluate client demographic and risk characteristics associated with false-positive results. Next, we conducted an incidence study of false-positive OraQuick rapid HIV tests in nine US cities and tested both oral-fluid and finger-stick whole-blood specimens from clients; reactive tests were confirmed with Western blot. Sixteen (4.1%) false-positive oral-fluid results occurred in the performance study from April 15, 2004 through August 31, 2004 with unexpired devices from six test lots among 388 HIV-uninfected clients (specificity, 95.9%; 95% CI: 93.4–97.6). Three test operators who had reported false-positive results performed and interpreted the test according to package-insert instructions. In multivariate analysis, only older age was significantly associated with false-positive results (adjusted odds ratio = 4.5, 95% CI: 1.2–25.7). In the incidence study, all valid oral-fluid and whole-blood results from 2,268 clients were concordant and no false-positive results occurred (100% specificity). CONCLUSIONS/SIGNIFICANCE: The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results. The findings suggest this was an isolated cluster; the test's overall performance was as specified by the manufacturer

Developing a decision instrument to guide abdominal-pelvic imaging of blunt trauma patients: Methodology and protocol of the NEXUS abdominal-pelvic imaging study

Although computed tomography (CT) of the abdomen and pelvis (A/P) can provide crucial information for managing blunt trauma patients, liberal and indiscriminant imaging is expensive, can delay critical interventions, and unnecessarily exposes patients to ionizing radiation. Currently no definitive recommendations exist detailing which adult blunt trauma patients should receive A/P CT imaging and which patients may safely forego CT. Considerable benefit could be realized by identifying clinical criteria that reliably classify the risk of abdominal and pelvic injuries in blunt trauma patients. Patients identified as “very low risk” by such criteria would be free of significant injury, receive no benefit from imaging and therefore could be safely spared the expense and radiation exposure associated with A/P CT. The goal of this two-phase nationwide multicenter observational study is to derive and validate the use of clinical criteria to stratify the risk of injuries to the abdomen and pelvis among adult blunt trauma patients. We estimate that nation-wide implementation of a rigorously developed decision instrument could safely reduce CT imaging of adult blunt trauma patients by more than 20%, and reduce annual radiographic charges by $180 million, while simultaneously expediting trauma care and decreasing radiation exposure with its attendant risk of radiation-induced malignancy. Prior to enrollment we convened an expert panel of trauma surgeons, radiologists and emergency medicine physicians to develop a consensus definition for clinically significant abdominal and pelvic injury. In the first derivation phase of the study, we will document the presence or absence of preselected candidate criteria, as well as the presence or absence of significant abdominal or pelvic injuries in a cohort of blunt trauma victims. Using recursive partitioning, we will examine combinations of these criteria to identify an optimal “very low risk” subset that identifies injuries with a sensitivity exceeding 98%, excludes injury with a negative predictive value (NPV) greater than 98%, and retains the highest possible specificity and potential to decrease imaging. In Phase 2 of the study we will validate the performance of a decision rule based on these criteria among a new cohort of patients to ensure that the criteria retain high sensitivity, NPV and optimal specificity. Validating the sensitivity of the decision instrument with high statistical precision requires evaluations on 317 blunt trauma patients who have significant abdominal-pelvic injuries, which will in turn require evaluations on approximately 6,340 blunt trauma patients. We will estimate potential reductions in CT imaging by counting the number of abdominal-pelvic CT scans performed on “very low risk” patients. Reductions in charges and radiation exposure will be determined by respectively summing radiographic charges and lifetime decreases in radiation morbidity and mortality for all “very low risk” cases. Trial registration: Clinicaltrials.gov trial registration number: NCT04937868

Developing a decision instrument to guide abdominal-pelvic imaging of blunt trauma patients: Methodology and protocol of the NEXUS abdominal-pelvic imaging study.

Although computed tomography (CT) of the abdomen and pelvis (A/P) can provide crucial information for managing blunt trauma patients, liberal and indiscriminant imaging is expensive, can delay critical interventions, and unnecessarily exposes patients to ionizing radiation. Currently no definitive recommendations exist detailing which adult blunt trauma patients should receive A/P CT imaging and which patients may safely forego CT. Considerable benefit could be realized by identifying clinical criteria that reliably classify the risk of abdominal and pelvic injuries in blunt trauma patients. Patients identified as "very low risk" by such criteria would be free of significant injury, receive no benefit from imaging and therefore could be safely spared the expense and radiation exposure associated with A/P CT. The goal of this two-phase nationwide multicenter observational study is to derive and validate the use of clinical criteria to stratify the risk of injuries to the abdomen and pelvis among adult blunt trauma patients. We estimate that nation-wide implementation of a rigorously developed decision instrument could safely reduce CT imaging of adult blunt trauma patients by more than 20%, and reduce annual radiographic charges by $180 million, while simultaneously expediting trauma care and decreasing radiation exposure with its attendant risk of radiation-induced malignancy. Prior to enrollment we convened an expert panel of trauma surgeons, radiologists and emergency medicine physicians to develop a consensus definition for clinically significant abdominal and pelvic injury. In the first derivation phase of the study, we will document the presence or absence of preselected candidate criteria, as well as the presence or absence of significant abdominal or pelvic injuries in a cohort of blunt trauma victims. Using recursive partitioning, we will examine combinations of these criteria to identify an optimal "very low risk" subset that identifies injuries with a sensitivity exceeding 98%, excludes injury with a negative predictive value (NPV) greater than 98%, and retains the highest possible specificity and potential to decrease imaging. In Phase 2 of the study we will validate the performance of a decision rule based on these criteria among a new cohort of patients to ensure that the criteria retain high sensitivity, NPV and optimal specificity. Validating the sensitivity of the decision instrument with high statistical precision requires evaluations on 317 blunt trauma patients who have significant abdominal-pelvic injuries, which will in turn require evaluations on approximately 6,340 blunt trauma patients. We will estimate potential reductions in CT imaging by counting the number of abdominal-pelvic CT scans performed on "very low risk" patients. Reductions in charges and radiation exposure will be determined by respectively summing radiographic charges and lifetime decreases in radiation morbidity and mortality for all "very low risk" cases. Trial registration: Clinicaltrials.gov trial registration number: NCT04937868

The living interface between synthetic biology and biomaterial design

Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to 'living' materials that sense and respond based on the reciprocal interactions between materials and embedded cells