Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Impact of the COVID‐19 pandemic on the glycemic control in people with diabetes mellitus: A retrospective cohort study

ABSTRACT Aim To investigate the impact of the COVID‐19 pandemic and its preventive measures on the glycemic and lipid control in people with diabetes mellitus (DM). Materials and methods We conducted this retrospective cohort study from April 2019 to March 2021; we termed the period from April 2019 to March 2020 as the pre‐COVID‐19 period, and the period from April 2020 to March 2021 as the COVID‐19 period, and divided each of these two periods into four quarters. Results In the 1st quarter of the COVID period, when the Japanese government declared the first public health emergency, 3,465 people with diabetes mellitus were receiving treatment, which was 10.4% lower than that in the pre‐COVID period. The annual mean HbA1c level was significantly elevated in the COVID‐19 period. The annual mean total cholesterol (TC) and triglyceride (TG) levels were also significantly higher in the COVID‐19 period. Although there were no significant differences in the glycemic control or annual medication between the two periods in people with type 1 diabetes mellitus, the annual mean HbA1c, TC, and TG levels were significantly higher in the COVID‐19 period in people with type 2 diabetes mellitus. Furthermore, a significant increase in the percentage of prescriptions for glinides, biguanides, sodium‐glucose cotransporter 2 inhibitors, and glucagon‐like peptide‐1 receptor agonists for people with type 2 diabetes mellitus was observed in the COVID period. Conclusions It appears from our study that COVID‐19 and its preventive measures had a negative impact on the glycemic and lipid control in people with diabetes mellitus

Effect of age and sex on bone markers in Chlorocebus aethiops raised in captivity

National Primate Center (CENP); Coordination for the Improvement of Higher Level Personnel (CAPES – Procad-NF No. 21/2009; Procad/ Casadinho No. 06/2011); Brazilian National Council for Scientific and Technological Development (CNPq – Chamada Universal Faixa A No. 14/2012).Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil / Universidade Federal Rural da Amazônia. Programa de Pós-graduação de Saúde e Produção Animal da Amazônia. Belém, PA, Brazil.Universidade Estadual Paulista. Faculdade de Medicina Veterinária de Zootecnia. Departamento de Cirurgia Veterinária e Anestesiologia. Botucatu, SP, Brazil.Universidade Federal Rural da Amazônia. Programa de Pós-graduação de Saúde e Produção Animal da Amazônia. Belém, PA, Brazil.Universidade Federal Rural da Amazônia. Programa de Pós-graduação de Saúde e Produção Animal da Amazônia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil / Universidade Federal Rural da Amazônia. Programa de Pós-graduação de Saúde e Produção Animal da Amazônia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Universidade Federal Rural da Amazônia. Programa de Pós-graduação de Saúde e Produção Animal da Amazônia. Belém, PA, Brazil.The objective was to evaluate the procollagen type I N-propeptide (PINP), osteocalcin (OC), β-crosslaps (β-CTX), and parathyroid hormone (PTH) in relation to age and sex of Chlorocebus aethiops in captivity. METHODS: Seventy-three monkeys were divided into four age groups: AG1 (juvenile); AG2 (young adult); AG3 (adult); and AG4 (senile). An electrochemiluminescence immunoassay with an Elecsys 2010 analyzer was used to determine the serum markers of bone. RESULTS AND CONCLUSIONS: Sex did not influence the results of the markers. However, the variables PINP, OC, and β-CTX were negatively correlated with age (r = -0.643; r = -0.711; r = -0.488; P < 0.001, respectively), and PTH was correlated positively with age (r = 0.418, P < 0.001). The data obtained can be used as biomarkers of bone metabolism reference intervals in healthy C. aethiops in captivity