Loss of Receptor on Tuberculin-Reactive T-Cells Marks Active Pulmonary Tuberculosis

BACKGROUND: Tuberculin-specific T-cell responses have low diagnostic specificity in BCG vaccinated populations. While subunit-antigen (e.g. ESAT-6, CFP-10) based tests are useful for diagnosing latent tuberculosis infection, there is no reliable immunological test for active pulmonary tuberculosis. Notably, all existing immunological tuberculosis-tests are based on T-cell response size, whereas the diagnostic potential of T-cell response quality has never been explored. This includes surface marker expression and functionality of mycobacterial antigen specific T-cells. METHODOLOGY/PRINCIPAL FINDINGS: Flow-cytometry was used to examine over-night antigen-stimulated T-cells from tuberculosis patients and controls. Tuberculin and/or the relatively M. tuberculosis specific ESAT-6 protein were used as stimulants. A set of classic surface markers of T-cell naive/memory differentiation was selected and IFN-gamma production was used to identify T-cells recognizing these antigens. The percentage of tuberculin-specific T-helper-cells lacking the surface receptor CD27, a state associated with advanced differentiation, varied considerably between individuals (from less than 5% to more than 95%). Healthy BCG vaccinated individuals had significantly fewer CD27-negative tuberculin-reactive CD4 T-cells than patients with smear and/or culture positive pulmonary tuberculosis, discriminating these groups with high sensitivity and specificity, whereas individuals with latent tuberculosis infection exhibited levels in between. CONCLUSIONS/SIGNIFICANCE: Smear and/or culture positive pulmonary tuberculosis can be diagnosed by a rapid and reliable immunological test based on the distribution of CD27 expression on peripheral blood tuberculin specific T-cells. This test works very well even in a BCG vaccinated population. It is simple and will be of great utility in situations where sputum specimens are difficult to obtain or sputum-smear is negative. It will also help avoid unnecessary hospitalization and patient isolation

A Quality Improvement Initiative to Reduce Underdosing of Rectal Diazepam as Home Seizure Rescue Medication After Hospitalization.

BACKGROUND AND OBJECTIVES: Seizure rescue medications are commonly prescribed to patients with epilepsy to treat and prevent clusters of seizures or status epilepticus. Underdosing of rescue medications decreases their efficacy, which may lead to status epilepticus and potentially avoidable emergency department (ED) visits or hospitalizations. In this quality improvement initiative, we aimed to reduce the rate of underdosed rectal diazepam prescriptions for children discharged from the inpatient neurology service at our institution from a baseline of 6% to 3% by July 2023. METHODS: The primary intervention was an order panel in the electronic health record that automated selection of correct dosing for age-based and weight-based seizure rescue medications including rectal diazepam, intranasal diazepam, and intranasal midazolam. A statistical process control p-chart was used to analyze our primary outcome measure, the monthly rate of underdosed rectal diazepam prescriptions for patients discharged from the inpatient neurology service. The process measure was use of the new order panel. Balancing measures included the dispense rate, cost for seizure rescue medications, and provider satisfaction. RESULTS: During the baseline period, July 2020-August 2022, rectal diazepam was underdosed for 6% of patients discharged from the neurology service. After intervention, we achieved and sustained 0% underdosing of rectal diazepam. We observed no concerning changes in the dispense rate for the medications, the average copay cost remained low, and surveys of ordering providers showed overall high rates of satisfaction. By spreading the intervention, we reduced underdosing from 21% to 0.6% in the ED and from 12% to 4% across the health care system. DISCUSSION: An order panel that automated selection of correct dosing effectively and sustainably reduced underdosing of seizure rescue medications and is transferrable across care settings. We expect that proper dosing of seizure rescue medications should reduce the occurrence of status epilepticus and associated complications

Singapore 1994-1996: Bibliographies

10.1177/002200949803300306The Journal of Commonwealth Literature333134-15