Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women.

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (n = 14).

Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis.

With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD.

Consensus guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury occurring during clinical trials in adults with chronic cholestatic liver disease.

Background: Improved knowledge of the molecular pathophysiology and immunopathogenesis of cholestatic liver diseases in recent years has led to an increased interest in developing novel therapies. Patients with cholestatic liver disease often require different approaches to assessment and management of suspected drug-induced liver injury (DILI) compared to those with healthy livers and those with parenchymal liver diseases. At present, there are no regulatory guidelines or society position papers, that systematically address best practices pertaining to detection of DILI in these patients.

Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis.

Background: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials.

Correction to: Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience.

In the original publication of the article, the ALT and AST values in Fig. 5a-e were capped at 10× ULN, which did not accurately reflect the narrative provided for each case. In this correction, the original Fig.

Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience.

Introduction: Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical trials due to liver safety concerns.

Methods: The liver safety of fasiglifam was assessed from data based on six phase II and nine phase III double-blind studies and two open-label studies with emphasis on pooled data from 15 double-blind studies from both global and Japanese development programs.

Combining the G-protein-coupled receptor 40 agonist fasiglifam with sitagliptin improves glycaemic control in patients with type 2 diabetes with or without metformin: A randomized, 12-week trial.

Aims: To evaluate the efficacy and safety of fasiglifam, an orally active G-protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin).

Materials And Methods: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg. The primary endpoint was change from baseline glycated haemoglobin (HbA1c) at 12 weeks; a key secondary endpoint was change in fasting plasma glucose (FPG).

Clinical malaria and sickle cell disease among multiple family members in Chicago, Illinois.

Malaria is a disease of global importance and accounts for up to 500 million cases per year. Nearly all malaria cases in the United States occur among persons who have traveled to areas with ongoing malaria transmission. Among the cases of malaria reported in the United States in 2000-2005, 695 were in US residents under the age of 18 years.

Hospital-based directly observed therapy for HIV-infected children and adolescents to assess adherence to antiretroviral medications.

Background: The introduction of highly active antiretroviral therapy for HIV led to significant declines in HIV-associated morbidity and mortality in children. Nonadherence to antiretroviral therapy is the leading cause of treatment failure in HIV-infected patients. The ability to recognize nonadherence is suboptimal, and differentiating it from other causes of inadequate viral suppression may be difficult.

Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy.

Background: The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART).

Methods: Children 2 to <19 years, receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA.

Epidemiology and treatment of community-associated methicillin-resistant Staphylococcus aureus in children.

Similar to the epidemiology of methicillin-sensitive Staphylococcus aureus, community-associated methicillin-resistant S. aureus infections occur in children in different regions of the USA and throughout the world. Although minor skin and soft-tissue infections predominate, life-threatening invasive disease and death can result.

Treatment of community-acquired methicillin-resistant Staphylococcus aureus in children.

Purpose Of Review: The concept of methicillin-resistant Staphylococcus aureus (MRSA) associated with broad resistance, nosocomial acquisition, and known risk factors has recently been expanded. A new type of MRSA that is resistant to fewer antibiotics has emerged in pediatric practice since the mid-1990s. These isolates are community acquired and have been reported from diverse geographic regions.

Clindamycin treatment of methicillin-resistant Staphylococcus aureus infections in children.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) with a narrower antibiotic resistance pattern have emerged. There is a risk for the appearance of resistance during clindamycin therapy of erythromycin-resistant MRSA infections because of the linked resistance mechanisms.

Methods: We analyzed clindamycin-susceptible MRSA organisms from children (1987 to 2000) along with clinical data.

Chronic vulvovaginitis caused by antibiotic-resistant Shigella flexneri in a prepubertal child.

A 7-year 8-month-old girl was diagnosed with a prolonged course of vulvovaginitis caused by Shigella flexneri. The child was symptomatic with intermittent vaginal bleeding, dysuria and foul smelling vaginal discharge for a 3-year period. Initial attempts to resolve the infection with successive courses of antibiotic therapy using ampicillin, trimethoprim-sulfamethoxazole, cefixime and amoxicillin/clavulanic acid failed.