A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered.
View Article and Find Full Text PDFThis paper reports results of a hybrid effectiveness-implementation randomized trial that systematically varied levels of human oversight required to support implementation of a digital medicine intervention for persons with mild to moderate alcohol use disorder (AUD). Participants were randomly assigned to three groups representing possible digital health support models within a health system: self-monitored use ( = 185), peer-supported use ( = 186), or a clinically integrated model ( = 187). Across all three groups, percentage of risky drinking days dropped from 38.
View Article and Find Full Text PDFBackground: The clinical narrative in electronic health records (EHRs) carries valuable information for predictive analytics; however, its free-text form is difficult to mine and analyze for clinical decision support (CDS). Large-scale clinical natural language processing (NLP) pipelines have focused on data warehouse applications for retrospective research efforts. There remains a paucity of evidence for implementing NLP pipelines at the bedside for health care delivery.
View Article and Find Full Text PDFIntroduction: Physicians are a critical clinical resource for patient care. Yet physician recruitment has been considerably understudied, particularly in substance use disorder (SUD) settings. This study proposes a conceptual model called the "Physician Recruitment Descriptive Factors Framework" to investigate the role of environmental, organizational, and individual factors in the use of physician recruitment strategies.
View Article and Find Full Text PDFBorealization is a type of community reorganization where Arctic specialists are replaced by species with more boreal distributions in response to climatic warming. The process of borealization is often exemplified by the northward range expansions and subsequent proliferation of boreal species on the Pacific and Atlantic inflow Arctic shelves (i.e.
View Article and Find Full Text PDFObjective: This randomized controlled trial tested whether external coaching influences addiction treatment providers' utilization of medications to treat opioid use disorder (MOUDs).
Methods: This study recruited 75 unique clinical sites in Florida, Ohio, and Wisconsin, including 61 sites in specialty treatment agencies and 14 behavioral health sites within health systems. The trial used external coaching to increase use of MOUDs in the context of a learning collaborative and compared it with no coaching and no learning collaborative (control condition).
Administering myelosuppressive chemotherapy to patients with aggressive malignant hematologic disorders typically poses serious infectious complications, which can be exacerbated by the presence of active COVID-19 infection. We report on a case of a successfully treated fit elderly woman with refractory acute myeloid leukemia (AML) who also had mild COVID-19 infection and detectable viral load at the time she was found to have recurrent disease. Prior to initiation of reinduction treatment with cytarabine/idarubicin, this 2-dose COVID-19-vaccinated patient received antiviral therapy with remdesivir with resolution of upper respiratory symptoms.
View Article and Find Full Text PDFVariation among populations in life history and intrinsic population characteristics (i.e., population diversity) helps maintain resilience to environmental change and dampen interannual variability in ecosystem services.
View Article and Find Full Text PDFBackground: E2027 is a novel, highly selective and potent inhibitor of phosphodiesterase 9 in development for dementia with Lewy bodies. Cardiac safety assessments for emerging agents are essential to avoid drug-induced QT interval prolongation, which may predispose individuals to potentially fatal ventricular arrhythmias. To evaluate the cardiac safety of E2027 and to inform dose selection for the phase 2 study of E2027 in dementia with Lewy bodies, we evaluated concentration-response modeling of pooled electrocardiogram data.
View Article and Find Full Text PDFConservation of Arctic fish species is challenging partly due to our limited ability to track fish through time and space, which constrains our understanding of life history diversity and lifelong habitat use. Broad Whitefish (Coregonus nasus) is an important subsistence species for Alaska's Arctic Indigenous communities, yet little is known about life history diversity, migration patterns, and freshwater habitat use. Using laser ablation Sr isotope otolith microchemistry, we analyzed Colville River Broad Whitefish 87Sr/86Sr chronologies (n = 61) to reconstruct movements and habitat use across the lives of individual fish.
View Article and Find Full Text PDFSubst Abuse Treat Prev Policy
October 2021
Background: Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment.
Methods: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey.
Chinook salmon () declines are widespread and may be attributed, at least in part, to warming river temperatures. Water temperatures in the Yukon River and tributaries often exceed 18°C, a threshold commonly associated with heat stress and elevated mortality in Pacific salmon. Untangling the complex web of direct and indirect physiological effects of heat stress on salmon is difficult in a natural setting with innumerable system challenges but is necessary to increase our understanding of both lethal and sublethal impacts of heat stress on populations.
View Article and Find Full Text PDFBackground: Interval duration measurements (IDMs) were compared between standard 12-lead electrocardiograms (ECGs) and 6-lead ECGs recorded with AliveCor's KardiaMobile 6L, a hand-held mobile device designed for use by patients at home.
Methods: Electrocardiograms were recorded within, on average, 15 min from 705 patients in Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic. Interpretable 12-lead and 6-lead recordings were available for 685 out of 705 (97%) eligible patients.
Manipulative experiments provide stronger evidence for identifying cause-and-effect relationships than correlative studies, but protocols for implementing temperature manipulations are lacking for large species in remote settings. We developed an experimental protocol for holding adult Chinook salmon () and exposing them to elevated temperature treatments. The goal of the experimental protocol was to validate heat stress biomarkers by increasing river water temperature from ambient (~14°C) to a treatment temperature of 18°C or 21°C and then maintain the treatment temperature over 4 hours within a range of ±1.
View Article and Find Full Text PDFMedication for opioid use disorder (MOUD) is a key strategy for addressing the opioid use disorder crisis, yet gaps in MOUD provision impede this strategy's benefits. The research reported here sought to understand what distinguishes low- and high-performing organizations in building and using capacity to provide MOUD. As part of a mixed methods MOUD implementation trial, semi-structured telephone interviews were conducted with personnel from low- and high-performing MOUD-providing organizations.
View Article and Find Full Text PDFBiol Blood Marrow Transplant
June 2020
Hematopoietic stem cell transplantation (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications that may result in chronic illness.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
June 2020
Background: OLZ/SAM is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, and is in development for the treatment of schizophrenia and bipolar I disorder. OLZ/SAM is under development with the intent to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This thorough QT study assessed the effects of therapeutic and supratherapeutic doses of OLZ/SAM on cardiac repolarization in patients with schizophrenia.
View Article and Find Full Text PDFBackground: Buprenorphine is a critically important treatment for addressing the opioid epidemic, but there are virtually no studies of physicians' job satisfaction with providing buprenorphine. Physicians' job satisfaction has been linked to burnout and turnover as well as patients' adherence to treatment recommendations, so it is important to understand how physicians' satisfaction with providing buprenorphine treatment compares to their overall job satisfaction.
Methods: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 55 physicians working in 38 organizations in Florida, Ohio, and Wisconsin completed a baseline web-based survey.
The JTpeak interval has been proposed as a new biomarker to demonstrate mixed ion channel effects, potentially leading to reduced late-stage electrocardiogram (ECG) monitoring for mildly QT-prolonging drugs. ECG waveforms from the IQ-CSRC study were used. Twenty healthy subjects were enrolled with 6 subjects on placebo and 9 subjects on each of 5 mildly QT-prolonging drugs - moxifloxacin, dofetilide, ondansetron, dolasetron, and quinine - and 1 negative drug, levocetirizine.
View Article and Find Full Text PDFPatients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients.
View Article and Find Full Text PDFIntensive Care Med
May 2019
Purpose: Enteral feeding intolerance (EFI) is a frequent problem in the intensive care unit (ICU), but current prokinetic agents have uncertain efficacy and safety profiles. The current study compared the efficacy and safety of ulimorelin, a ghrelin agonist, with metoclopramide in the treatment of EFI.
Methods: One hundred twenty ICU patients were randomized 1:1 to ulimorelin or metoclopramide for 5 days.
Objectives: Effective pharmacological treatments for opioid use disorder (OUD) continue to be underutilized, particularly within specialty substance use disorder (SUD) treatment organizations. Few studies have examined whether specific practices to recruit prescribers, financial needs, and human resource needs facilitate or impede the implementation of pharmacotherapy.
Methods: Surveys were completed by administrators from 160 treatment programs in Florida, Ohio, and Wisconsin.
Nonclinical assays with JNJ-54861911, a β-secretase 1 inhibitor have indicated that at high concentrations, it may delay cardiac repolarization. A 4-way crossover thorough QT (TQT) study was performed in 64 healthy subjects with 50 and 150 mg JNJ-54861911 once daily for 7 days, placebo, and 400 mg moxifloxacin. Retrospective high-precision QT (HPQT) analysis was performed on serial elecrocardiograms extracted from first-in-human single-ascending dose (SAD) and multiple-ascending dose (MAD) studies to evaluate if early studies could detect and predict QT effect.
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