Browsing by Author "Strother, Robert M."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Modeling Sitagliptin Effect on Dipeptidyl Peptidase 4 (DPP4) Activity in Adults with Hematological Malignancies After Umbilical Cord Blood (UCB) Hematopoietic Cell Transplant (HCT)
    (Springer International Publishing, 2014-03) Vélez de Mendizábal, Nieves; Strother, Robert M.; Farag, Sherif S.; Broxmeyer, Hal E.; Messina-Graham, Steven; Chitnis, Shripad D.; Bies, Robert R.; Department of Medicine, IU School of Medicine
    Background and Objectives— Dipeptidyl peptidase-4 (DPP4) inhibition is a potential strategy to increase the engraftment rate of hematopoietic stem/progenitor cells. A recent clinical trial using sitagliptin, a DPP4 inhibitor approved for type 2 diabetes mellitus, has shown to be a promising approach in adults with hematological malignancies after umbilical cord blood (UCB) hematopoietic cell transplant (HCT). Based on data from this clinical trial, a semi-mechanistic model was developed to simultaneously describe DPP4 activity after multiple doses of sitagliptin in subjects with hematological malignancies after a single-unit UCB HCT. Methods— The clinical study included 24 patients that received myeloablative conditioning followed by 4 oral sitagliptin 600mg with single-unit UCB HCT. Using a nonlinear mixed effects approach, a semi-mechanistic pharmacokinetic/pharmacodynamic model was developed to describe DPP4 activity from this trial data using NONMEM 7.2. The model was used to drive Monte-Carlo simulations to probe various dosage schedules and the attendant DPP4 response. Results— The disposition of sitagliptin in plasma was best described by a 2-compartment model. The relationship between sitagliptin concentration and DPP4 activity was best described by an indirect response model with a negative feedback loop. Simulations showed that twice a day or three times a day dosage schedules were superior to once daily schedule for maximal DPP4 inhibition at the lowest sitagliptin exposure. Conclusion— This study provides the first pharmacokinetic/pharmacodynamic model of sitagliptin in the context of HCT, and provides a valuable tool for exploration of optimal dosing regimens, critical for improving time to engraftment in patients after UCB HCT.
  • Thumbnail Image
    Item
    Prevalence and correlates of pain and pain treatment in a western Kenya referral hospital
    (Mary Ann Liebert, Inc., 2013-10) Huang, Kristin T. L.; Owino, Claudio; Gramelspacher, Gregory P.; Monahan, Patrick O.; Tabbey, Rebeka; Hagembe, Mildred; Strother, Robert M.; Njuguna, Festus; Vreeman, Rachel C.; Department of Medicine, IU School of Medicine
    BACKGROUND: Pain is often inadequately evaluated and treated in sub-Saharan Africa (SSA). OBJECTIVE: We sought to assess pain levels and pain treatment in 400 hospitalized patients at a national referral hospital in western Kenya, and to identify factors associated with pain and pain treatment. DESIGN: Using face-validated Kiswahili versions of two single-item pain assessment tools, the Numerical Rating Scale (NRS) and the Faces Pain Scale-Revised (FPS-R), we determined patients' pain levels. Additional data collected included patient demographics, prescribed analgesics, and administered analgesics. We calculated mean pain ratings and pain management index (PMI) scores. RESULTS: Averaged between the NRS and FPS-R, 80.5% of patients endorsed a nonzero level of pain and 30% of patients reported moderate to severe pain. Older patients, patients with HIV, and cancer patients had higher pain ratings. Sixty-six percent of patients had been prescribed analgesics at some point during their hospitalization, the majority of which were nonopioids. A majority of patients (66%) had undertreated pain (negative scores on the PMI). CONCLUSION: This study shows that hospitalized patients in Kenya are experiencing pain and that this pain is often undertreated.
  • Thumbnail Image
    Item
    Prevalence and Correlates of Pain and Pain Treatment in a Western Kenya Referral Hospital
    (2013-10) Huang, Kristin TL.; Owino, Claudio; Gramelspacher, Gregory P.; Monahan, Patrick O.; Tabbey, Rebeka; Hagembe, Mildred; Strother, Robert M.; Njuguna, Festus; Vreeman, Rachel C.
    Background: Pain is often inadequately evaluated and treated in sub-Saharan Africa (SSA). Objective: We sought to assess pain levels and pain treatment in 400 hospitalized patients at a national referral hospital in western Kenya, and to identify factors associated with pain and pain treatment. Design: Using face-validated Kiswahili versions of two single-item pain assessment tools, the Numerical Rating Scale (NRS) and the Faces Pain Scale–Revised (FPS-R), we determined patients' pain levels. Additional data collected included patient demographics, prescribed analgesics, and administered analgesics. We calculated mean pain ratings and pain management index (PMI) scores. Results: Averaged between the NRS and FPS-R, 80.5% of patients endorsed a nonzero level of pain and 30% of patients reported moderate to severe pain. Older patients, patients with HIV, and cancer patients had higher pain ratings. Sixty-six percent of patients had been prescribed analgesics at some point during their hospitalization, the majority of which were nonopioids. A majority of patients (66%) had undertreated pain (negative scores on the PMI). Conclusion: This study shows that hospitalized patients in Kenya are experiencing pain and that this pain is often undertreated.