Finding Long-COVID: temporal topic modeling of electronic health records from the N3C and RECOVER programs.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection.

A Case Demonstration of the Open Health Natural Language Processing Toolkit From the National COVID-19 Cohort Collaborative and the Researching COVID to Enhance Recovery Programs for a Natural Language Processing System for COVID-19 or Postacute Sequelae of SARS CoV-2 Infection: Algorithm Development and Validation.

Background: A wealth of clinically relevant information is only obtainable within unstructured clinical narratives, leading to great interest in clinical natural language processing (NLP). While a multitude of approaches to NLP exist, current algorithm development approaches have limitations that can slow the development process. These limitations are exacerbated when the task is emergent, as is the case currently for NLP extraction of signs and symptoms of COVID-19 and postacute sequelae of SARS-CoV-2 infection (PASC).

Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program.

Long COVID, or complications arising from COVID-19 weeks after infection, has become a central concern for public health experts. The United States National Institutes of Health founded the RECOVER initiative to better understand long COVID. We used electronic health records available through the National COVID Cohort Collaborative to characterize the association between SARS-CoV-2 vaccination and long COVID diagnosis.

Clinical encounter heterogeneity and methods for resolving in networked EHR data: a study from N3C and RECOVER programs.

Objective: Clinical encounter data are heterogeneous and vary greatly from institution to institution. These problems of variance affect interpretability and usability of clinical encounter data for analysis. These problems are magnified when multisite electronic health record (EHR) data are networked together.

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program.

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations.

Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design Settings And Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C).

Using Electronic Medical Records to Identify Enhanced Recovery After Surgery Cases.

Context: Enhanced recovery after surgery (ERAS) aims to improve surgical outcomes by integrating evidence-based practices across preoperative, intraoperative, and postoperative care. Data in electronic medical records (EMRs) provide insight on how ERAS is implemented and its impact on surgical outcomes. Because ERAS is a multimodal pathway provided by multiple physicians and health care providers over time, identifying ERAS cases in EMRs is not a trivial task.

In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.

Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design.

Effects of Fostamatinib on the Pharmacokinetics of the CYP2C8 Substrate Pioglitazone: Results From In Vitro and Phase 1 Clinical Studies.

Fostamatinib is a prodrug that undergoes gastrointestinal tract dephosphorylation to form the active metabolite, R406. Here we report its cytochrome P450-inducing potential. In vitro, R406 3 and 10 μM induced CYP2C8 to levels representing 53% and 75%, respectively, of the level achieved by the positive control, rifampicin.

Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies.

Purpose: Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure.

Methods: AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC.

An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.

Purpose: To assess the effect of age and gender on the pharmacokinetics (PK) of the ghrelin receptor agonist anamorelin.

Methods: Three demographic cohorts of healthy subjects were enrolled in this single-center, open-label study. Subjects received a single oral dose (25 mg) of anamorelin HCl.

Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine.

Background And Objective: Vandetanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) signalling, indicated for the treatment of medullary thyroid cancer. We investigated potential drug-drug interactions between vandetanib and metformin [organic cation transporter 2 (OCT2) substrate; NCT01551615]; digoxin [P-glycoprotein (P-gp) substrate; NCT01561781]; midazolam [cytochrome P450 (CYP) 3A4 substrate; NCT01544140]; omeprazole (proton pump inhibitor) or ranitidine (histamine H2-receptor antagonist; both NCT01539655).

Methods: Four open-label, phase I studies were conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17 (midazolam), n = 16 (omeprazole), n = 18 (ranitidine).

Oral alitretinoin: a review of the clinical pharmacokinetics and pharmacodynamics.

Alitretinoin is an endogenous retinoid related to vitamin A. Studies have shown that oral alitretinoin is effective and well tolerated in the treatment of severe chronic hand eczema. This review summarizes the clinical pharmacokinetic and pharmacodynamic data from a number of studies involving alitretinoin.

Method to determine allocation of clinical pharmacist resources.

Purpose: An objective methodology to guide decisions by hospital pharmacy departments on the best use of clinical pharmacist personnel is described.

Summary: To help determine the optimal deployment of state-licensed Clinical Pharmacist Specialist (CPS) staff, a task force led by the pharmacy department at University of North Carolina (UNC) Hospitals developed an objective approach to evaluating the relative need for and potential impact of CPS expertise within the medical center's many service units. After analyzing several years of patient census and medication-use data and using information from proprietary databases (Thomson Reuters) to calculate a "service-specific pharmacy intensity score" for each hospital service, the task force identified five staff-allocation metrics best suited to the medical center's service-based pharmacy coverage model.

Phase I study evaluating the safety and pharmacokinetics of MDX-1303, a fully human monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers.

MDX-1303 (Valortim) is a fully human monoclonal antibody (hMAb) with a high affinity for Bacillus anthracis protective antigen (PA). MDX-1303 binds to PA and interferes with the activity of the anthrax toxin; it was selected based on its superior functional activity in the toxin neutralization activity (TNA) assay. MDX-1303 has demonstrated efficacy in the postexposure and therapeutic settings in New Zealand White rabbits, cynomolgus monkeys, and African green monkeys.

Influence of alitretinoin on the pharmacokinetics of the oral contraceptive ethinyl estradiol/norgestimate.

Background: Alitretinoin (9-cis retinoic acid) is currently registered in many European countries and in Canada as the only licensed treatment for severe chronic hand eczema unresponsive to potent topical corticosteroids. Alitretinoin, like all retinoids, is teratogenic, and women of child-bearing potential must strictly adhere to pregnancy-prevention measures.

Aim: To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28(®)), a commonly prescribed combination oral contraceptive.

Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam.

Purpose: Brivaracetam (BRV) is a new anticonvulsant under development. Although BRV is an analog of levetiracetam (LEV), in addition to being an SV2A ligand, it also inhibits sodium channels in a voltage-dependent manner. The cognitive effects of BRV are uncertain.

Cost-effectiveness of electrocardiography vs. electrocardiography plus limited echocardiography to diagnose LVH in young, newly identified, hypertensives.

Background: In the United States, screening for left ventricular hypertrophy (LVH) in a newly diagnosed hypertensive patient is typically performed using electrocardiography (ECG). Echocardiography (echo) is a more accurate but also more expensive procedure. However, the introduction of limited echo within the past decade has made sonographic imaging of the heart less expensive and more available for routine screening.

A longitudinal study on the relationship between weight loss, medical expenditures, and absenteeism among overweight employees in the WAY to Health study.

Objective: To quantify the extent to which successful weight loss among overweight/obese employees translates into subsequent savings in medical expenditures and absenteeism.

Methods: This analysis relied on medical claims and absenteeism data collected from overweight/obese employees at 17 community colleges in North Carolina.

Results: We find no evidence that participants achieving at least a 5% weight loss experienced reduced medical expenditures or lower absenteeism during the 12-month weight loss intervention or in the subsequent 2 years.

Community-based hepatitis B screening programs in the United States in 2008.

The Centers for Disease Control and Prevention (CDC) recommends hepatitis B surface antigen (HBsAg) testing to identify hepatitis B virus (HBV) infection for foreign-born persons from areas with HBsAg prevalence of > or = 2%. Currently, most HBsAg screening in the United States is performed by independent community organizations. For these HBsAg screening programs, we collected information about the location, number of people screened, other services beyond screening provided, the population/ethnicity groups targeted for screening, and the prevalence of HBsAg among those screened.

Population PK-PD model for Fc-osteoprotegerin in healthy postmenopausal women.

Osteoporosis is a metabolic bone disease resulting from increased bone resorption and characterized by low bone mass that leads to increased bone fragility and risk of fracture, particularly of the hip, spine and wrist. Bone resorption is dependent on receptor activator of NF-kappa B ligand (RANKL), which binds to RANK receptor on preosteoclasts to initiate osteoclastogenesis and maintains osteoclast function and survival. To neutralize the effects of RANKL, the body naturally produces the protein osteoprotegerin (OPG), which acts as a decoy receptor for RANKL and contributes to bone homeostasis.

Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist.

Unlabelled: CPG 10101 (ACTILON) is a novel potent and selective unmethylated cytidine-phosphate-guanosine (CpG)-containing oligodeoxynucleotide agonist of Toll-like receptor 9 (TLR9) being developed for the treatment of chronic infections such as HCV.

Objectives And Methods: In this randomized, double-blind, placebo-controlled Phase I study in 48 normal volunteers, we investigated the safety, pharmacokinetic parameters and immune effects of subcutaneous administration of CPG 10101. Five sequential escalating doses from 0.

The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate.

The effects of supratherapeutic dosages of duloxetine, a serotonin and norepinephrine reuptake inhibitor, on blood pressure and pulse rate were assessed in a multicenter, double-blind, randomized, placebo-controlled, crossover study in 117 healthy women aged 19 to 74 years. Dosages were escalated from 60 mg twice daily (BID) to 200 mg BID over 16 days. Vital signs were monitored at baseline, before morning dosing, and sequentially at steady state.

Phase 1 study of two merozoite surface protein 1 (MSP1(42)) vaccines for Plasmodium falciparum malaria.

Objectives: To assess the safety and immunogenicity of two vaccines, MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel, targeting blood-stage Plasmodium falciparum parasites.

Design: A Phase 1 open-label, dose-escalating study.

Setting: Quintiles Phase 1 Services, Lenexa, Kansas between July 2004 and November 2005.