Background Immune checkpoint inhibitors have been demonstrated to improve overall survival. Atypical patterns of response have been reported, including dissociated response (DR). We evaluated the prevalence of DR. Patients and methods Patients had to have a baseline computed tomography (CT) scan and at least one follow-up CT scan and two target lesions (TLs). Three types of DR were evaluated using

Background and Objective Fabry disease, an X-linked lysosomal storage disorder characterized by absent or reduced alpha-galactosidase activity, is a lifelong disease that impairs patients’ quality of life. Patients with Fabry disease have a considerably shortened lifespan, with mortality being mainly due to renal failure, cardiovascular disease, or cerebrovascular disease. Enzyme replacement therapy

Intranasal drug administration is a commonly used route for therapeutic formulations, but there may be challenges associated with a lack of absorption and bioavailability, as well as damage to mucosal tissue. To address these issues, potential absorption enhancers that are generally nonirritating to nasal mucosal tissue have been investigated as excipients in intranasal formulations. Among those studied

Background and Objectives Osteoarthritis (OA) is a major public health burden. While knee and hip joints are most commonly affected, the glenohumoral (shoulder) joint is also frequently involved. We evaluated the pharmacokinetics and safety/tolerability of triamcinolone acetonide extended-release (TA-ER) and triamcinolone acetonide crystalline suspension (TAcs) in patients with shoulder OA. Methods

BACKGROUND Hepatic impairment can impact apixaban pharmacokinetics and pharmacodynamics by decreasing cytochrome P450-mediated metabolism and factor X production. OBJECTIVE This study evaluated the effect of mild or moderate (Child-Pugh A and B) hepatic impairment on apixaban pharmacokinetics, pharmacodynamics, and safety. METHODS This open-label, parallel-group, single-dose study included eight mildly

Recently, an increasing number of cases with delayed cutaneous reaction after immunization with mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This adverse reaction, which is considered a delayed-type or T cell-mediated hypersensitivity reaction, has been described for the Moderna (mRNA-1273) and Comirnaty (Pfizer/BioNTech, BNT162b2) vaccines

Background and Objective Coronavirus disease 2019 is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus. It was first detected in December 2019 and has since been declared a pandemic causing millions of deaths worldwide. Therefore, there is an urgent need to develop effective therapeutics against coronavirus disease 2019. A critical step in the crosstalk

Background Gastroesophageal reflux frequently occurs in infants from birth to 2 years and is characterised by reflux and regurgitation often occurring during or immediately after feeds. These reflux events can range in both frequency and severity, and as the reflux events increase, they become increasingly distressing for both the infant and the parent. The study aimed to characterise the properties

Introduction Intravenous lipid emulsions (ILE) have been credited for successful resuscitation in drug intoxication cases where other cardiac life-support methods have failed. However, inter-individual variability can function as a confounder that challenges our ability to define the scope of efficacy for lipid interventions, particularly as relevant data are scarce. To address this challenge, we developed

Background Golimumab (GLM) has been reported to have lower immunogenicity than do other TNF inhibitors used for treating rheumatoid arthritis (RA). We previously found a prolonged effect of and improvement similar to that associated with infliximab (IFX) after switching to subcutaneous GLM (GLM-SC) for control of RA activity or adverse events. Thus, this study aimed to evaluate the continued maintenance

Introduction HTL0018318 is a selective muscarinic M1 receptor partial agonist under development for the symptomatic treatment of dementias, including Alzheimer’s disease. Clinically, HTL0018318 would likely be used alone or in conjunction with cholinesterase inhibitors (e.g. donepezil). Objective We investigated the safety, tolerability, and pharmacokinetics of HTL0018318 given alone and in combination

Several adamantanes have established actions against coronaviruses. Amantadine, rimantadine, bananins and the structurally related memantine are effective against human respiratory coronavirus HCoV-OC43, bovine coronavirus and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and a spiroadamantane amine is effective against the coronavirus strain 229E. Molecular docking studies suggest that

Background and Objective Anaphylactic shock is a serious adverse drug reaction that can occur in response to contrast media used during coronary computed tomography angiography. The imaging quality of coronary computed tomography angiography is improved by β-blockers, which decrease heart rate. In this study, we sought to analyze anaphylactic shock treatment in patients receiving short-acting β1-blockers

Large-scale vaccination strategies are currently being deployed against severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2). Whether systemic medication for skin diseases affects the efficacy of vaccination and whether temporary interruption or extension of the dosing interval is necessary is under debate. Most immunomodulating/immunosuppressive drugs only affect vaccine-induced immune responses

Background and Objective In end-stage kidney disease, high urea levels promote the carbamylation of lysine side chains on a variety of proteins, including albumin. Albumin carbamylation has been identified as a risk factor for mortality and sevelamer led to a decrease in urea levels in dialysis patients. In the present secondary analysis of the NICOREN trial, we investigated the putative impacts of

A correction to this paper has been published: https://doi.org/10.1007/s40268-021-00347-2

Background Sickle cell disease is an inherited blood disorder with reduced blood-carrying capacity. It is associated with a tendency to form microclots in blood vessels, leading to painful episodes known as a vaso-occlusive crisis. Rivipansel is a pan-selectin inhibitor being studied for the treatment of a vaso-occlusive crisis in patients with sickle cell disease. Methods A population pharmacokinetic

Background GNE myopathy is a rare genetic muscle disease resulting from deficiency in an enzyme critical for the biosynthesis of N-acetylneuraminic acid (Neu5Ac, sialic acid). The uncharged Neu5Ac precursor, N-acetylmannosamine (ManNAc), is under development as an orphan drug for treating GNE myopathy. Methods A semi-mechanistic population pharmacokinetic model was developed to simultaneously characterize

Effective lowering of circulating ammonia is the mainstay strategy in the prevention and treatment of hepatic encephalopathy in cirrhosis and there is increasing interest in agents with the metabolic potential for the active removal of ammonia by the liver and skeletal muscle by agents including l-ornithine l-aspartate, branched-chain amino acids, as well as the re-purposing of benzoate and phenylacetate

Introduction Opioids are potent painkillers but can have severe adverse effects in the intensive care unit (ICU). The aim of this study was to compare the outcomes of fentanyl and morphine use among patients at risk for and with acute respiratory distress syndrome (ARDS). Methods We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of opioids and the associated

Background Selenite is a radiosensitizer and inhibitor of androgen receptor expression and function. In a phase I study (NCT02184533) in 15 subjects with metastatic cancer receiving daily oral sodium selenite with palliative radiation therapy, disease stabilization was observed, as evidenced by tumor regression, marked reduction in pain symptoms, and decreased prostate-specific antigen levels (only

Background Even though nebulised administration of amikacin can achieve high epithelial lining fluid concentrations, this has not translated into improved patient outcomes in clinical trials. One possible reason is that the cellular and chemical composition of the epithelial lining fluid may inhibit amikacin-mediated bacterial killing. Objective The objective of this study was to identify whether the

Introduction Gallstones are a known adverse effect of somatostatin analogs, but the exact incidence and clinical implications are unknown. Objectives The aim of this study was to investigate the incidence of gallstones on imaging and related complications in unbiased trial data. Methods Data from the DIPAK 1 trial, in which 305 polycystic kidney disease patients were randomized to standard of care

There are numerous treatment options currently available for patients with type 2 diabetes mellitus; however, a multitude of patients continue to have inadequately controlled glycemic levels with their current antihyperglycemic regimen. Furthermore, the American Diabetes Association guidelines increasingly highlight the importance of multifactorial management and optimizing medication regimens that

Background Monoclonal antibodies (mAbs) have proved to be a valuable tool for the treatment of different cancer types. However, clinical use of an increasing number of mAbs, have also highlighted limitations with monotherapy for cancers, in particular for such with more complex mechanisms, requiring action on additional molecules or pathways, or for cancers quickly acquiring resistance following monotherapy

Background Hereditary angioedema (HAE) with C1-esterase inhibitor (C1-INH) deficiency is a rare disease associated with painful, potentially fatal swelling episodes affecting subcutaneous or submucosal tissues. HAE attacks recur with unpredictable severity and frequency throughout patients’ lives; long-term prophylaxis is essential for some patients. In the absence of head-to-head studies, indirect

Introduction ModraDoc006 is a novel docetaxel tablet formulation that is co-administrated with the cytochrome P450 3A4 and P-glycoprotein inhibitor ritonavir (r): ModraDoc006/r. Objectives This study evaluated the effect of food consumed prior to administration of ModraDoc006/r on the pharmacokinetics of docetaxel and ritonavir. Methods Patients with advanced solid tumours were enrolled in this randomized

Background and Objectives We demonstrated that the mRNA induction of S100s in rat peripheral leukocytes by severe hyperglycemia was reduced by inhibiting postprandial hyperglycemia. Here, we compared inflammatory gene expression in peripheral leukocytes between type 2 diabetes mellitus (T2DM) patients undergoing dietary therapy alone and healthy volunteers, and between T2DM patients undergoing dietary

Background and Objective Dissecting cellulitis of the scalp is a primary scarring alopecia. Isotretinoin is commonly referenced in the literature as a treatment for dissecting cellulitis. The objective of this article was to conduct a review and meta-analysis to assess the efficacy of isotretinoin for treating dissecting cellulitis of the scalp. Methods The following databases were searched for articles

Objective The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients’ cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass. Methods In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for

Background Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of these problems. Aim The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature

Introduction In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as

Background and Objective Anaplastic lymphoma kinase gene rearrangements (ALKr) resulting in EML4–ALK proteins occur in a subset of solid tumors and are targeted by ALK inhibitors. Given the development of drug resistance to ALK inhibitors, ALK inhibitors with different kinase selectivity are required. Methods This phase I, non-randomized, open-label study evaluated the dose-limiting toxicity (DLT)

At present, no cure is available for COVID-19 but vaccines, antiviral drugs, immunoglobulins, or the combination of immunoglobulins with antiviral drugs have been suggested and are in clinical trials. The purpose of this paper is to discuss the role of a pharmacokinetic and viral load analysis as a basis for adjusting immunoglobulin dosing to treat COVID-19. We reviewed the pre-clinical and clinical

Background Pancreatic enzyme-replacement therapy (PERT), provided as pancreatin to patients with pancreatic exocrine insufficiency (PEI), is considered an essential substitute for the pivotal physiological function the pancreas fulfills in digestion. PEI involves a reduction in the synthesis and secretion of pancreatic enzymes (lipase, protease, amylase), which leads to an inadequate enzymatic response

Objective The objective of this study was to compare the predictive performances of a glomerular filtration rate (GFR) model with a physiologically based pharmacokinetic (PBPK) model to predict total or renal clearance or area under the curve of renally excreted drugs in subjects with varying degrees of renal impairment. Methods From the literature, 11 studies were randomly selected in which total

Background and Objectives Currently, there are no US FDA-approved therapies for eosinophilic esophagitis (EoE). Budesonide oral suspension (BOS; SHP621, TAK-721) is a viscous, muco-adherent, oral formulation of budesonide that is in phase III development for the treatment of EoE. BOS 2 mg twice daily was studied in 12- and 36-week phase III studies for the induction and maintenance of clinical remission

Background and objective Phenytoin is extensively protein bound with a narrow therapeutic range. The unbound phenytoin is pharmacologically active, but total concentrations are routinely measured in clinical practice. The relationship between free and total phenytoin has been described by various binding models with inconsistent findings. Systematic comparison of these binding models in a single experimental

Background and Objective Mycophenolate mofetil is widely used in kidney transplant recipients. Mycophenolate mofetil is hydrolysed by blood esterases to mycophenolic acid (MPA), the active drug. Although MPA therapeutic drug monitoring has been recommended to optimise the treatment efficacy by the area under the plasma concentration vs time curve, little is known regarding MPA concentrations in peripheral

Background Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. Methods We devised a set of diagnostic criteria for SCLE in collaboration with a

Expedited development programs for biological products to be used in the treatment of serious conditions bring about challenges because of the compressed clinical development timeframes. As expedited development does not lessen the quality expectations, one challenge is providing adequate chemistry, manufacturing, and control (CMC) information required to support approval of a biological product. In

Nimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral nimodipine for 21 days. However, pharmacokinetic studies have suggested variability of nimodipine pharmacokinetics in subarachnoid hemorrhage and in other patient populations. The clinical relevance of such variability is unknown. Therefore

Background and Objectives Remimazolam is a new ultra-short-acting benzodiazepine currently being developed for intravenous use in procedural sedation, general anaesthesia, and intensive care unit sedation. Benzodiazepines represent a drug class associated with drug-facilitated sexual assaults, especially in combination with alcohol. Two clinical trials were designed to evaluate the oral bioavailability

Background Endothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, l-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage. Objective This study examined the hemodynamic safety and effect profiles of the combined

Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation

Background and Objective The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect

Tenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or

Background and objective Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and

Background In 2006, the National Malaria Control Program in Mali recommended artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. Since the introduction of artemisinin-based combination therapy, few reports are available on the level of resistance of Plasmodium falciparum to the most common anti-malarial drugs in Mali. Methods From 2016 to 2017, we assessed the

The prevalence of cutaneous adverse events attributable to newly approved anti-cancer drugs has been well reviewed in the dermatologic literature. In contrast, over 75% of US Food and Drug Administration approvals in the past 5 years have been for non-cancer drugs and indications. This represents multiple other categories of approved medications associated with cutaneous adverse reactions. To investigate

Introduction Ibuprofen and acetaminophen provide analgesia via different mechanisms of action and do not exhibit drug–drug interactions; therefore, combining low doses of each may provide greater efficacy without compromising safety. Objectives The present study assessed the analgesic efficacy of fixed-dose combinations (FDCs) of ibuprofen/acetaminophen (IBU/APAP) compared with ibuprofen 400 mg and

Background and Objective Based on previous experience of sorbent-mediated ticagrelor, dabigatran, and radiocontrast agent removal, we set out in this study to test the effect of two sorbents on the removal of edoxaban, a factor Xa antagonist direct oral anticoagulant. Methods We circulated 100 mL of edoxaban solution during six first-pass cycles through 40-mL sorbent columns (containing either CytoSorb

Background and Objective Oral tramadol, an atypical opioid approved in the United States (US) since 1995 and a Schedule IV controlled substance, has less abuse liability compared to Schedule II conventional opioids. Intravenous (IV) tramadol is not available in the US, but has the potential to fill a gap between non-opioid medications and conventional opioids for treatment of acute pain. This study

Background Clostridium difficile infection is the leading cause of hospital-acquired gastrointestinal infection and incidence rates continue to rise. Clostridium difficile infection is becoming increasingly complex to treat owing to the rise in treatment failures and recurrent infections. There is a clear need for new therapeutic options for the management of this disease. Objective This study aimed

Background It is unclear whether generics are as safe as brand-name drugs in cardiology. For public health surveillance purposes, we evaluated if switching from the brand-name losartan, valsartan, or candesartan impacted the occurrence of the following outcomes: emergency room (ER) consultations, hospitalizations, or death. Study Design This was a retrospective cohort study. Methods This study was

Background and objective Beyond its application for diagnostics in patients, esophagogastroduodenoscopy (EGD) is used to assess gastrointestinal drug effects in clinical trials, where the interpretation of any pathological findings depends on the respective background variability. The objective of this analysis was to characterize the occurrence of pathological findings in the upper gastrointestinal

Background Cenobamate is a new, Food and Drug Administration (FDA)-approved oral antiepileptic drug for treatment of focal seizures in adults. This study examined recovery of cenobamate from suspensions administered through ex vivo enteral feeding tubes. Methods Suspensions containing 100 and 200 mg of cenobamate were prepared (five duplicates for each dose), passed through five vertically standing