• Adherence with tobramycin inhaled solution and health care utilization

      Briesacher, Becky A.; Quittner, Alexandra L.; Saiman, Lisa; Sacco, Patricia; Fouayzi, Hassan; Quittell, Lynne M. (2011-01-22)
      BACKGROUND: Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization. METHODS: We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories. RESULTS: Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received 4 or more cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving 2 or less cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768). CONCLUSIONS: Use of TIS did not reflect recommended guidelines and may impact other health care utilization.
    • Controlling gene expression in living cells through small molecule-RNA interactions

      Werstuck, Geoffrey; Green, Michael R. (1998-10-09)
      Short RNA aptamers that specifically bind to a wide variety of ligands in vitro can be isolated from randomized pools of RNA. Here it is shown that small molecule aptamers also bound their ligand in vivo, enabling development of a method for controlling gene expression in living cells. Insertion of a small molecule aptamer into the 5' untranslated region of a messenger RNA allowed its translation to be repressible by ligand addition in vitro as well as in mammalian cells. The ability of small molecules to control expression of specific genes could facilitate studies in many areas of biology and medicine.
    • Prevention of descending pneumonia in rts with perflubron-delivered tobramycin

      Dickson, Eric W.; Doern, Gary V.; Trevino, Leo; Mazzoni, Michelle; Heard, Stephen O. (2003-10-01)
      OBJECTIVES: Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia. METHODS: Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons. RESULTS: All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05). CONCLUSIONS: Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP.