Impulsivity in amphetamine use disorder: Examination of sex differences.

Aims: This study aimed to test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP).

Design: A naturalistic cross-sectional design was used.

Setting: The Tulsa 1000 study was held in Tulsa, OK, USA.

Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics.

Research Question: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status?

Study Design And Methods: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data.

Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer.

Section Head: Clinical/translational cancer immunotherapy.

Background: The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC).

Methods: Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored.

Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection.

Methods: In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021-11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization.

The Intersection of Telemedicine and Wilderness Care: Past, Present, and Future.

Wilderness medicine and telemedicine seemingly exist at opposite ends of the clinical continuum. However, these 2 specialties share a common history and the literature abounds with examples of successful deployment of telemedicine to resource limited settings. The recent widespread adoption of telemedicine has important ramifications for wilderness providers.

Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is effective against the SARS-CoV-2 Delta variant to prevent progression to severe disease and mortality.

Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1 2021 - December 11 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment.

Who Cares More about Chemical Defenses - the Macroalgal Producer or Its Main Grazer?

The consequences of defensive secondary metabolite concentrations and interspecific metabolite diversity on grazers have been extensively investigated. Grazers which prefer certain food sources are often found in high abundance on their host and as a result, understanding the interaction between the two is important to understand community structure. The effects of intraspecific diversity, however, on the grazer are not well understood.

Temporal associations between emergency department and telehealth volumes during the COVID-19 pandemic: A time-series analysis from 2 academic medical centers.

Background: The COVID-19 pandemic compelled healthcare systems to rapidly adapt to changing healthcare needs as well as identify ways to reduce COVID transmission. The relationship between pandemic-related trends in emergency department (ED) visits and telehealth urgent care visits have not been studied.

Methods: We performed an interrupted time series analysis to evaluate trends between ED visits and telehealth urgent medical care visits at two urban healthcare system in Colorado.

Real World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: Neutralizing monoclonal antibodies (mAbs) are authorized for early symptomatic COVID-19 patients. Whether mAbs are effective against the SARS-CoV-2 Delta variant, among vaccinated patients, or for prevention of mortality remains unknown.

Objective: To evaluate the effectiveness of mAb treatment in preventing progression to severe disease during the Delta phase of the pandemic and based on key baseline risk factors.

Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial.

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States.

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the prevention and management of tick-borne illness (TBI). Recommendations are graded based on quality of supporting evidence according to criteria put forth by the American College of Chest Physicians. The guidelines include a brief review of the clinical presentation, epidemiology, prevention, and management of TBI in the United States, with a primary focus on interventions that are appropriate for resource-limited settings.

Early Skin-to-Skin Care with a Polyethylene Bag for Neonatal Hypothermia: A Randomized Clinical Trial.

Objective: To determine whether early polyethylene bag use with skin-to-skin care compared with skin-to skin care alone reduce hypothermia among infants born at term in resource-limited settings.

Study Design: Infants born at term in the tertiary referral center in Lusaka, Zambia, were randomized using sequentially numbered sealed opaque envelopes in 2 phases: after birth (phase 1) and at 1 hour after birth (phase 2) to either skin-to-skin care with polyethylene bags or skin-to-skin care alone. Infant and maternal temperatures were recorded at birth, 1 hour, and every 4 hours until discharge or 24 hours.

Optimizing the Therapeutic Window of Targeted Drugs in Oncology: Potency-Guided First-in-Human Studies.

Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design.

Validating in vivo hyperpolarized Xe diffusion MRI and diffusion morphometry in the mouse lung.

Purpose: Diffusion and lung morphometry imaging using hyperpolarized gases are promising tools to quantify pulmonary microstructure noninvasively in humans and in animal models. These techniques assume the motion encoded is exclusively diffusive gas displacement, but the impact of cardiac motion on measurements has never been explored. Furthermore, although diffusion morphometry has been validated against histology in humans and mice using He, it has never been validated in mice for Xe.

Effort Thrombosis Presenting as Unilateral "Pumped" Arm in a Climber.

Upper extremity injuries are common among the growing population of climbers. Although conditions affecting musculoskeletal structures are the most common causes of symptoms, a comprehensive differential diagnosis is necessary to avoid the misdiagnosis of high-morbidity conditions in this patient population. We present a case of a climber with acute edema, erythema, and pain of the entire right upper extremity.

Alloderm and Cortiva Have Similar Perioperative Wound Complications in Abdominal Wall Reconstruction.

Background: Although controversial, the use of acellular dermal matrices (ADMs) for abdominal wall reconstruction (AWR) is increasing. There are now many different ADMs available, but there is a lack of studies directly comparing ADMs in terms of outcomes.

Materials And Methods: A retrospective chart review was performed to compare perioperative wound complications (up to 120 d postoperatively) between patients who underwent AWR with the human noncrosslinked ADMs Alloderm or Cortiva from January 2012 to March 2020.

Standard machine learning approaches outperform deep representation learning on phenotype prediction from transcriptomics data.

Background: The ability to confidently predict health outcomes from gene expression would catalyze a revolution in molecular diagnostics. Yet, the goal of developing actionable, robust, and reproducible predictive signatures of phenotypes such as clinical outcome has not been attained in almost any disease area. Here, we report a comprehensive analysis spanning prediction tasks from ulcerative colitis, atopic dermatitis, diabetes, to many cancer subtypes for a total of 24 binary and multiclass prediction problems and 26 survival analysis tasks.

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 Non-Hodgkin Lymphomas.

Purpose: In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20 non-Hodgkin lymphomas (NHL).

Patients And Methods: Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D).

Results: Sixty-seven patients received utomilumab (0.

A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors.

Background: Expressed on activated T and natural killer cells, 4-1BB/CD137 is a costimulatory receptor that signals a series of events resulting in cytokine secretion and enhanced effector function. Targeting 4-1BB/CD137 with agonist antibodies has been associated with tumor reduction and antitumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed in various solid tumor indications and associated with poor prognosis.

Operating characteristics of stepwise covariate selection in pharmacometric modeling.

Stepwise covariate modeling (SCM) is a widely used tool in pharmacometric analyses to identify covariates that explain between-subject variability (BSV) in exposure and exposure-response relationships. However, this approach has several potential weaknesses, including over-estimated covariate effect and incorrect selection of covariates due to collinearity. In this work, we investigated the operating characteristics (i.

Antibiotic Prescribing Patterns for Sinusitis Within a Direct-to-Consumer Virtual Urgent Care.

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Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer.

Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.

A New Proposal for Management of Severe Frostbite in the Austere Environment.

Despite advances in outdoor clothing and medical management of frostbite, individuals still experience catastrophic amputations. This is a particular risk for those in austere environments, due to resource limitations and delayed definitive treatment. The emerging best therapies for severe frostbite are thrombolytics and iloprost.