Clinical Trials Commons^™

Utility Of Inflammatory Markers To Predict Adverse Outcome In Acute Pancreatitis: A Retrospective Study In A Single Academic Center, Mohamad Mubder, Banreet Dhindsa, Danny Nguyen, Syed Saghir, Chad Cross, Ranjit Makar, Gordon Ohning

School of Medicine Faculty Research

Background/Aim: Acute pancreatitis (AP) is a commonly encountered emergency where early identification of complicated cases is important. Inflammatory markers like lymphocyte to monocyte ratio (LMR) and neutrophil to lymphocyte ratio (NLR) are simple and readily available markers. In this study, we evaluated the utility of these markers in the early identification of patients with complicated AP. Patients and Methods: All patients with a diagnosis of AP admitted to the University Medical Center in Las Vegas/Nevada between August 2015 and September 2018 were identified using ICD-10 codes. Medical records were reviewed retrospectively. Epidemiological measures and their associated confidence intervals were calculated …

Novel Inference Methods For Generalized Linear Models Using Shrinkage Priors And Data Augmentation., Arinjita Bhattacharyya

Electronic Theses and Dissertations

Generalized linear models have broad applications in biostatistics and sociology. In a regression setup, the main target is to find a relevant set of predictors out of a large collection of covariates. Sparsity is the assumption that only a few of these covariates in a regression setup have a meaningful correlation with an outcome variate of interest. Sparsity is incorporated by regularizing the irrelevant slopes towards zero without changing the relevant predictors and keeping the resulting inferences intact. Frequentist variable selection and sparsity are addressed by popular techniques like Lasso, Elastic Net. Bayesian penalized regression can tackle the curse of …

A Modular Framework For Early-Phase Seamless Oncology Trials, Philip S. Boonstra, Thomas M. Braun, Elizabeth C. Chase

The University of Michigan Department of Biostatistics Working Paper Series

Background: As our understanding of the etiology and mechanisms of cancer becomes more sophisticated and the number of therapeutic options increases, phase I oncology trials today have multiple primary objectives. Many such designs are now 'seamless', meaning that the trial estimates both the maximum tolerated dose and the efficacy at this dose level. Sponsors often proceed with further study only with this additional efficacy evidence. However, with this increasing complexity in trial design, it becomes challenging to articulate fundamental operating characteristics of these trials, such as (i) what is the probability that the design will identify an acceptable, i.e. safe …

Three Essays On Health Economics And Policy Evaluation, Shishir Shakya

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation consists of three essays on the U.S. Health care policy. Each paragraph below refers to the three abstracts for the three chapters in this dissertation, respectively. I provide quantitative evidence on how much Prescription Drug Monitoring Programs (PDMPs) affects the retail opioid prescribing behaviors. Using the American Community Survey (ACS), I retrieve county-level high dimensional panel data set from 2010 to 2017. I employ three separate identification strategies: difference-in-difference, double selection post-LASSO, and spatial difference-in-difference. I compare how the retail opioid prescribing behaviors of counties, that are mandatory for prescribers to check the PDMP before prescribing controlled substances …

A Signature Enrichment Design With Bayesian Adaptive Randomization For Cancer Clinical Trials, Fang Xia

Dissertations and Theses (Open Access)

Clinical trials in the era of precision medicine demand more flexible and efficient trial designs. Adaptive clinical trial designs allow pre-specified modifications of an on-going clinical trial and could shorten the trial duration. We reviewed five common types of adaptive clinical trials based on adaptation methods. In particular, outcome-randomization becomes more popular as it can assign more patients to the promising treatments based on the accumulated trial data. This data-driven allocation allows more patients to benefit from the trial, which is especially important for cancer patients. We compared different Bayesian outcome-adaptive randomization methods and discussed them from both methodological and …

Phase Iv Clinical Trials: Postmarketing Surveillance Of Prescription Drugs, Morgan Belling, Jacquline Nunner, Jessica Stemen

Pharmacy and Wellness Review

No abstract provided.

Toxoplasma Gondii Igg Associations With Sleepwake Problems, Sleep Duration And Timing, Celine C. Corona, Ma Zhang, Abhishek Wadhawan, Melanie L. Daue, Maureen W. Groer, Aline Dagang, Christopher A. Lowry, Kathleen A. Ryan, Andrew J. Hoisington, John W. Stiller, Dietmar Fuchs, Braxton D. Mitchell, Teodor T. Postolache

Faculty Publications

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family …

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …

The Potential Of Organ On Chip Technology For Replacing Animal Testing, Malcolm Wilkinson

Human Clinical Trials Collection

The term organ on a chip is used to describe the latest stage of development of in vitro cell culture technology. Figure 26.1 shows its steady development since the 1960s. Each step forward has improved our ability to model human-clinical response to new drugs or therapies and has enabled safety risk assessment of existing cosmetics, personal care products, or other chemicals in the environment. Scientific evidence that the predictive power of in vitro tests is superior to the use of animals will trigger a major shift in the way that medical research, in many areas, is carried out. In this …

Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu

College of Graduate Studies: Theses & Dissertations

In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …

Variations In Institutional Review Board Processes And Consent Requirements For Trauma Research: An East Multicenter Survey, Jeffry Nahmias, Areg Grigorian, Scott Brakenridge, Randeep S. Jawa, Daniel N. Holena, John Varujan Agapian, Brandon Bruns, Paul J. Chestovich, Bruce Chung, Jonathan Nguyen, Carl I. Schulman, Kristan Staudenmayer, Rachel Dixon, Jason W. Smith, Andrew C. Bernard, Jose L. Pascual

School of Medicine Faculty Research

Oversight of human subject research has evolved considerably since its inception. However, previous studies identified a lack of consistency of institutional review board (IRB) determination for the type of review required and whether informed consent is necessary, especially for prospective observational studies, which pose minimal risk of harm. We hypothesized that there is significant inter-institution variation in IRB requirements for the type of review and necessity of informed consent, especially for prospective observational trials without blood/tissue utilization. We also sought to describe investigators’ and IRB members’ attitudes toward the type of review and need for consent. Eastern Association for the …

Low-Fat Abiraterone Food Effect Is Of Little Consequence, Jill M. Kolesar, Glenn X. Liu

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Quality Of Life During Treatment With Chemohormonal Therapy: Analysis Of E3805 Chemohormonal Androgen Ablation Randomized Trial In Prostate Cancer, Alicia K. Morgans, Yu-Hui Chen, Christopher J. Sweeney, David F. Jarrard, Elizabeth R. Plimack, Benjamin A. Gartrell, Michael A. Carducci, Maha Hussain, Jorge A. Garcia, David Cella, Robert S. Dipaola, Linda J. Patrick-Miller

Internal Medicine Faculty Publications

Purpose

Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone.

Methods

Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months. The …

Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …

Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha

Graduate Center for Gerontology Faculty Publications

Background

Alzheimer’s disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations.

Methods

Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators.

Results

The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free …

Systematic Review And Meta-Analysis: Tuberculosis, Tnfα Inhibitors, And Crohn's Disease, Brent L. Cao

Honors Undergraduate Theses

Inflammation is often a protective reaction against harmful foreign agents. However, in many disease conditions, the mechanisms behind the inflammatory response are poorly understood. Often times, the inflammation causes adverse effects, such as joint pain, abdominal pain, fever, fatigue, and loss of appetite. Thus, many treatments aim to inhibit the inflammatory response in order to control adverse symptoms. Such treatments include TNFα inhibitors. However, a major risk associated with drugs inhibiting tumor necrosis factor alpha (TNFα) is serious infection, including tuberculosis (TB).

Anti-TNFα therapy is used to treat patients with Crohn’s disease, for which the risk of tuberculosis may be …

A Checklist For Clinical Trials In Rare Disease: Obstacles And Anticipatory Actions-Lessons Learned From The For-Dmd Trial, R Crow, K Hart, M Mcdermott, R Tawil, W Martens, Mathula Thangarajh, +Several Additional Authors

Neurology Faculty Publications

Background: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) …

Simulations For Designing And Interpreting Intervention Trials In Infectious Diseases., M Elizabeth Halloran, Kari Auranen, Sarah Baird, Nicole E Basta, Steven E Bellan, +Several Additional Authors

Global Health Faculty Publications

BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods.

DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, …

Long-Term Follow-Up Of Cardiac Function And Quality Of Life For Patients In Nsabp Protocol B-31/Nrg Oncology: A Randomized Trial Comparing The Safety And Efficacy Of Doxorubicin And Cyclophosphamide (Ac) Followed By Paclitaxel With Ac Followed By Paclitaxel And Trastuzumab In Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2, Patricia A. Ganz, Edward H. Romond, Reena S. Cecchini, Priya Rastogi, Charles E. Geyer Jr., Sandra M. Swain, Jong-Hyeon Jeong, Louis Fehrenbacher, Howard M. Gross, Adam M. Brufsky, Patrick J. Flynn, Tanya A. Wahl, Thomas E. Seay, James L. Wade Iii, David D. Biggs, James N. Atkins, Jonathan Polikoff, John L. Zapas, Eleftherios P. Mamounas, Norman Wolmark

Markey Cancer Center Faculty Publications

Purpose

Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment.

Patients and Methods

Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported …

Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah

Health and Clinical Sciences Faculty Publications

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.

Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as …

First-In-Human Clinical Trial Of Oral Onc201 In Patients With Refractory Solid Tumors, Mark N. Stein, Joseph R. Bertino, Howard L. Kaufman, Tina M. Mayer, Rebecca A. Moss, Ann W. Silk, Nancy Chan, Jyoti Malhotra, Loma Rodriguez, Joseph Aisner, Robert Aiken, Bruce G. Haffty, Robert S. Dipaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Sioghan Dickerson, Ling Zheng, Wafik S. El-Deiry, Joshua E. Allen, Martin Stogniew, Wolfgang Oster, Janice M. Mehnert

Internal Medicine Faculty Publications

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D).

Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, …

Novel Bayesian Adaptive Clinical Trial Designs In Early Phases, Haitao Pan

Dissertations and Theses (Open Access)

Early phase, or phase I and phase II, trials are the first step in testing new medicines that have been developed in the lab. The main goal of phase I clinical trials is to establish the recommended dose of new drugs for phase II trials. For the cytotoxic drugs, the goal is to find maximum tolerated dose (MTD). The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Therefore, dose escalation methods, especially Bayesian designs, are recommended to be used in phase I …

A Phase Iii, Randomized, Multi-Center, Double Blind, Placebo Controlled Study Of Safety And Efficacy Of Lofexidine For Relief Of Symptoms In Individuals Undergoing Inpatient Opioid Withdrawal, Charles W. Gorodetzky, Sharon L. Walsh, Peter R. Martin, Andrew J. Saxon, Kristen L. Gullo, Kousick Biswas

Center on Drug and Alcohol Research Faculty Publications

Background: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine.

Methods: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; …

Treatment Pathway Of Bone Sarcoma In Children, Adolescents, And Young Adults, Damon R. Reed, Masanori Hayashi, Lars M. Wagner, Odion Binitie, Diana A. Steppan, Andrew S. Brohl, Eric T. Shinohara, Julia A. Bridge, David M. Loeb, Scott C. Borinstein, Michael S. Isakoff

Pediatrics Faculty Publications

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Phase Iii Prospective Randomized Comparison Trial Of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab In Patients With Advanced Carcinoid Tumors: Swog S0518, James C. Yao, Katherine A. Guthrie, Cesar Moran, Jonathan R. Strosberg, Matthew H. Kulke, Jennifer A. Chan, Noelle Loconte, Robert R. Mcwilliams, Edward M. Wolin, Bassam Mattar, Shannon Mcdonough, Helen Chen, Charles D. Blanke, Howard S. Hochster

Markey Cancer Center Faculty Publications

Purpose

Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs.

Patients and Methods

Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary …

Safety And Immunogenicity Of An Inactivated Whole Cell Tuberculosis Vaccine Booster In Adults Primed With Bcg: A Randomized, Controlled Trial Of Dar-901, C. Fordham Von Reyn, Timothy Lahey, Robert D. Arbeit, Bernard Landry, Leway Kailani, Lisa Adams, Brenda Haynes, Todd Mackenzie, Wendy Wieland-Alter, Ruth Connor, Sue Tvaroha, David Hokey, Ann Ginsberg, Richard Waddell

Dartmouth Scholarship

Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic.

Polymer Micelle Formulation For The Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy And Pharmacokinetic Studies In Mice, Ji Eun Park, Se-Eun Chun, Derek Alexander Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee

Pharmaceutical Sciences Faculty Publications

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic …

Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.

METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells …