Browsing by Subject "Efficacy"
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Item Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics(American Association for Cancer Research, 2016-05) Arpin, Carolynn C.; Mac, Stephen; Jiang, Yanlin; Cheng, Huiwen; Grimard, Michelle; Page, Brent D. G.; Kamocka, Malgorzata M.; Haftchenary, Sina; Su, Han; Ball, Daniel; Rosa, David A.; Lai, Ping-Shan; Gómez-Biagi, Rodolfo F.; Ali, Ahmed M.; Rana, Rahul; Hanenberg, Helmut; Kerman, Kagan; McElyea, Kyle C.; Sandusky, George E.; Gunning, Patrick T.; Fishel, Melissa L.; Pediatrics, School of MedicineConstitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells.Item Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis(Taylor & Francis, 2021) Nikolaou, Andreas; Ambavane, Apoorva; Shah, Anshul; Ma, Wenkang; Tosh, Jon; Kapetanakis, Venediktos; Willson, Jenny; Wang, Feng; Hogea, Cosmina; Gorsh, Boris; Gutierrez, Ben; Sapra, Sandhya; Suvannasankha, Attaya; Samyshkin, Yevgeniy; Medicine, School of MedicineBackground: Patients with relapsed/refractory multiple myeloma (RRMM) require several lines of therapy, with typically shorter remission duration with each additional line. Research design and methods: The cost-effectiveness of belantamab mafodotin (belamaf; DREAMM-2; NCT03525678) was compared with selinexor plus dexamethasone (SEL+DEX; STORM Part 2; NCT02336815) among patients with RRMM who have received at least four prior therapies. The base case used a US commercial payer's perspective over a 10-year time horizon. Efficacy data were based on parametric survival analysis of DREAMM-2 and matching-adjusted indirect treatment comparison between DREAMM-2 and STORM Part 2, which assessed relative treatment effects between belamaf and SEL+DEX. Cost inputs included drug treatment, concomitant medications, adverse event management, subsequent treatments, and disease management. Results: Belamaf decreased total treatment costs per patient by $14,267 and increased patient life years by 0.74 and quality-adjusted life years (QALYs) by 0.49 versus SEL+DEX. Patients receiving belamaf accrued 0.12 fewer progression-free life years versus patients on SEL+DEX. Conclusions: From a US commercial payer's perspective, belamaf had lower costs, and increased QALYs and life-year gain, compared with SEL+DEX. Belamaf is therefore likely to be a cost-effective treatment option for patients with RRMM who have received four or more prior lines of therapy.Item Impact of allogeneic feline uterine-derived mesenchymal stromal cell intravenous treatment on renal function of nephrectomized cats with chronic kidney disease(Elsevier, 2021) Zacharias, Shelly; Welty, Matthew B.; Sand, Theodore T.; Black, Linda L.; Medical and Molecular Genetics, School of MedicineChronic kidney disease (CKD) is a common condition and leading cause of mortality in cats. Mesenchymal stromal cells (MSCs) may have a therapeutic effect on CKD. The aim of this pilot study was to determine efficacy of systemically-administered allogeneic uterine tissue-derived MSCs (UMSCs) in cats with CKD. Eighteen renal-compromised, unilaterally nephrectomized cats received two doses of 3 × 107 allogeneic UMSCs given intravenously (IV) with a 2-week dose interval. The primary endpoint was renal function, with treatment success defined by a 20% increase in glomerular filtration rate (GFR; iohexol clearance) and/or a 20% decrease in plasma creatinine in 50% of the cats. Secondary endpoints included diet and water consumption, body weight, urine characteristics, and adverse events. Treatment was well tolerated and associated with a statistically meaningful increase in GFR on Days 13, 28, 57, 99, 121 and 182, compared with baseline (P < 0.0001 for Days 13 to 99 inclusive; P = 0.0029 and P = 0.0225 for Days 121 and 182, respectively). Greater than 50% of the cats demonstrated a 20% increase in GFR on all days except Day 150, at which point GFR measurements were consistently above baseline. Statistically meaningful increases in diet and water consumption were observed. Substantial improvements in GFR were observed throughout the six-month evaluation period (excluding Day 150) in more than 50% of cats, thereby meeting the primary endpoint. Therefore, this IV-administered, allogeneic cellular therapy may support both renal function and clinical status of cats with CKD.Item Investigating the Efficacy and Sustainability of Instructional Coaching on Teacher Pedagogy(Office of the Vice Chancellor for Research, 2011-04-08) Teemant, AnnelaIdentifying value-added models and measures of instructional coaching are increasingly important with renewed focus on improving teacher quality. This longitudinal and quasiexperimental study investigates the efficacy and sustainability of instructional coaching outcomes with urban elementary teachers (N = 36). The instructional coaching intervention targets use of five research-based practices—the Standards for Effective Pedagogy—known to benefit culturally, linguistically, and economically diverse learners. Quantitative preintervention, post-intervention, and one-year-after intervention data were collected across two years. The intervention consisted of a 30-hour workshop and seven individual coaching sessions across the school year. Findings demonstrate instructional coaching led to statistically significant teacher change against a performance standard. Teachers were able to sustain these changes, albeit at a slightly lower level of fidelity, one year following the intervention. The pattern of attrition reveals that teachers struggle to sustain a commitment to providing teacher assistance to students in the process of learning.Item Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers—Improvements in Clinical Efficacy and Safety(MDPI, 2023-07-15) Hassan, Md Sazzad; Awasthi, Niranjan; Ponna, Saisantosh; von Holzen, Urs; Surgery, School of MedicineTaxanes (paclitaxel and docetaxel) are one of the most useful classes of anticancer drugs. Taxanes are highly hydrophobic; therefore, these drugs must be dissolved in organic solvents (polysorbate or Cremophor EL), which contribute to their toxicities. To reduce this toxicity and to enhance their efficacy, novel formulations have been developed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an albumin-stabilized, Cremophor-free, and water-soluble nanoparticle formulation of paclitaxel. Nab-paclitaxel has better solubility and less infusion-associated toxicity compared to solvent-based paclitaxel. Additionally, nab-paclitaxel can be given at higher doses and concentrations compared with solvent-based paclitaxel. Based on its superior clinical efficacy and safety profile, nab-paclitaxel received FDA approval for metastatic breast cancer (2008) and NSCLC (2011). Among gastrointestinal cancers, it is now approved in the USA for treating patients with metastatic adenocarcinoma of the pancreas as first-line therapy in combination with gemcitabine. Furthermore, several clinical trials have suggested the potential efficacy of nab-paclitaxel as a single agent or in combination with other agents for the treatment of metastatic esophageal, gastric, bowel, and biliary tract cancers. Nab-paclitaxel has been demonstrated to have greater overall response rates (ORR) with enhanced progression-free survival (PFS), overall survival (OS) and a superior safety profile with fewer adverse effects in patients with gastrointestinal tract cancers. This review summarizes the advantages associated with nab-paclitaxel-based regimens in terms of improving clinical efficacy and the safety profile in upper gastrointestinal cancer.Item Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3–11 Years with Hepatitis C Genotype 1a(Springer, 2020-05-25) Rosenthal, Philip; Narkewicz, Michael R.; Yao, Betty B.; Jolley, Christopher D.; Lobritto, Steven J.; Wen, Jessica; Molleston, Jean P.; Hsu, Evelyn K.; Jonas, Maureen M.; Zha, Jiuhong; Liu, Li; Leung, Daniel H.; Pediatrics, School of MedicineIntroduction To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1. Methods This is an ongoing, open-label, Phase 2/3 study in children 3–11 years old infected with HCV GT1 who were HCV treatment-naïve and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters. Results Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3–8 years old and 12 were 9–11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1–99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade ≥ 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation. Conclusion The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3–11 years of age.Item Remimazolam for sedation in gastrointestinal endoscopy: A comprehensive review(Baishideng, 2024) Dahiya, Dushyant Singh; Kumar, Ganesh; Parsa, Syeda; Gangwani, Manesh Kumar; Ali, Hassam; Sohail, Amir Humza; Alsakarneh, Saqr; Hayat, Umar; Malik, Sheza; Shah, Yash R.; Mohan Pinnam, Bhanu Siva; Singh, Sahib; Mohamed, Islam; Rao, Adishwar; Chandan, Saurabh; Al-Haddad, Mohammad; Medicine, School of MedicineWorldwide, a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient comfort. Propofol, benzodiazepines and opioids continue to be widely used. However, in recent years, Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal (GI) endoscopy. It is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural sedation. Remimazolam has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase, volume of distribution, total body clearance, and negligible drug-drug interactions. It also has satisfactory efficacy and has achieved high rates of successful sedation in GI endoscopy. Furthermore, studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol, which is currently a gold standard for procedural sedation in most parts of the world. However, the use of Propofol is associated with hemodynamic instability and respiratory depression. In contrast, Remimazolam has lower incidence of these adverse effects intra-procedurally and hence, may provide a safer alternative to Propofol in procedural sedation. In this comprehensive narrative review, highlight the pharmacologic characteristics, efficacy, and safety of Remimazolam for procedural sedation. We also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.Item Risk reduction and adventure tourism safety: An extension of the risk perception attitude framework (RPAF)(Elsevier, 2019-10-01) Wang, Jie; Liu-Lastres, Bingjie; Ritchie, Brent W.; Pan, Dong-ZiVisitor safety is an important topic in adventure tourism but remains underexplored. Using a psychological approach, this study applies and extends Rimal and Real's risk perception attitude framework to include personality traits and emotions to understand adventure tourists' safety behaviours on site. Focusing on tidal-bore watching activities in China, this study consists of two phases: interviews with nine local stakeholders followed by a field survey involving 302 visitors. Cluster analyses were conducted and three visitors' groups were identified that varied in risk perception attitudes and safety behaviours. Mediation analyses were conducted to explore the role played by worry during visitors' decision-making related to safety behaviours. Based on the findings, this study provided managerial insight for developing risk communication strategies to engage visitors in self-protective behavior. This study also provided recommendations on how to improve visitors' safety and to protect their lives in adventure-tourism sites in China.Item Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Adult Patients With X-Linked Hypophosphatemia(Oxford University Press, 2025) Ali, Dalal S.; Mirza, Reza D.; Alsarraf, Farah; Hussein, Salma; Alrob, Hajar Abu; Appelman-Dijkstra, Natasha M.; Beck-Nielsen, Signe Sparre; Biosse-Duplan, Martin; Brandi, Maria Luisa; Carpenter, Thomas O.; Chaussain, Catherine; Cohen-Solal, Martine; Crowley, Rachel K.; Dandurand, Karel; Florenzano, Pablo; Fukumoto, Seiji; Gagnon, Claudia; Goodyer, Paul; Grasemann, Corinna; Imel, Erik A.; Jan de Beur, Suzanne M.; Lehman, Anna; Lewiecki, E. Michael; Morgante, Emmett; Ward, Leanne M.; Khan, Aliya A.; Guyatt, Gordon; Medicine, School of MedicineContext: Understanding the effects of burosumab compared to conventional therapy or no treatment on patient-important outcomes in adults with X-linked hypophosphatemia (XLH) is essential to guide evidence-based treatment recommendations. Objective: To examine the highest certainty evidence addressing the management of XLH in adults to inform treatment recommendations. Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included randomized controlled trials (RCTs) and observational studies of individuals aged 18+ with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to no treatment or conventional therapy (phosphate and active vitamin D) and conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty. Results: We screened 4114 records, after removing duplicates, and assessed 254 full texts. One RCT and 2 observational studies were eligible. The RCT of burosumab vs no treatment had low RoB. Burosumab probably improves pain from fracture/pseudofracture healing (moderate certainty) but has little or no impact on direct pain measures (moderate certainty). Burosumab may reduce the need for parathyroidectomy (low certainty) but has little or no impact on fatigue (high certainty), stiffness (moderate certainty), and mobility (low certainty) over 24 weeks. Burosumab may increase dental abscess risk (low certainty). Indirect evidence comparing burosumab to conventional therapy provided low certainty regarding burosumab vs conventional therapy. Two observational studies on conventional therapy vs no treatment had high RoB and very low certainty regarding the impact of conventional therapy on patient-important outcomes. Conclusion: No formal comparisons between burosumab and conventional therapy in adults exist. Evidence for conventional therapy vs no treatment is very uncertain. Our review highlights the need for more data on the long-term effects of burosumab and conventional therapy on patient-important outcomes in adult patients with XLH.Item Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia(Oxford University Press, 2025) Ali, Dalal S.; Mirza, Reza D.; Hussein, Salma; Alsarraf, Farah; Alexander, R. Todd; Alrob, Hajar Abu; Appelman-Dijkstra, Natasha M.; Biosse-Duplan, Martin; Brandi, Maria Luisa; Carpenter, Thomas O.; Chaussain, Catherine; Dandurand, Karel; Filler, Guido; Florenzano, Pablo; Fukumoto, Seiji; Grasemann, Corinna; Imel, Erik A.; Jan de Beur, Suzanne M.; Morgante, Emmett; Ward, Leanne M.; Khan, Aliya A.; Guyatt, Gordon; Medicine, School of MedicineObjective: To examine the evidence addressing the management of X-linked hypophosphatemia (XLH) in children to inform treatment recommendations. Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included randomized controlled trials (RCTs) and observational studies of individuals younger than 18 years with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to either no treatment or conventional therapy (phosphate and active vitamin D) or evaluating conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty. Results: We screened 4114 records and assessed 254 full texts. One RCT and one post hoc study proved eligible when comparing burosumab to conventional therapy or no treatment. The open-label RCT was at high RoB, with certainty of evidence ranging from moderate to very low. Burosumab, compared to conventional therapy, probably prevents lower limb deformity and improves physical health quality of life (QoL) (moderate certainty). Burosumab may increase height and enhance the burden of symptoms related to chronic hypophosphatemia (low certainty). Burosumab probably increases treatment-emergent adverse events (moderate certainty) and may increase dental abscesses (low certainty). One observational study assessing conventional therapy vs no treatment was at high RoB, providing very low certainty evidence regarding the impact of conventional therapy on final height. Conclusion: Our review indicates that burosumab likely provides benefits to children by preventing lower limb deformity and improving physical health QoL while potentially increasing height. However, burosumab may also increase adverse events. Our review found limited evidence regarding the impact of conventional therapy compared to no treatment on final height. Further research is required to understand the long-term effect of medical therapy in children.