Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated Plasmodium falciparum malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.     

Transgenerational sublethal effects of abamectin and pyridaben on demographic traits of Phytonemus pallidus (Banks) (Acari: Tarsonemidae)

In addition to determining the lethal effects, identifying sublethal effects of a pesticide is crucial to understanding the total impact a pesticide may have on a pest population. We determined the sublethal effects the two pesticides, abamectin and pyridaben, have on the cyclamen mite, Phytonemus pallidus (Banks) (Acari: Tarsonemidae)—a major pest of strawberry. Demographic traits of the P. pallidus progeny (F1 generation) produced by parents (F0 generation) treated with a low lethal concentration (LC₁₅) of abamectin and pyridaben were assessed using the age-stage, two-sex life table theory. The total longevity of the F1 generation (males = 10.78 days; female = 14.35 days) was the shortest in the progeny of the abamectin treated parents, differing significantly from the progeny of mites treated with pyridaben (males = 11.50 days, females = 15.63 days), and the control population (males = 13.50 days, females = 17.81 days). The intrinsic rates of increase (r) and the finite rates of increase (λ) of the progeny of abamectin (r = 0.0854 day⁻¹, λ = 1.0891 day⁻¹) and pyridaben (r = 0.0951 day⁻¹, λ = 1.0997 day⁻¹) treated parents were significantly lower than in the control mites (r = 0.1455 day⁻¹, λ = 1.1567 day⁻¹). The lowest fecundity (5.35 eggs/female), occurred in F1 female offspring of parents treated with LC₁₅ concentrations of abamectin, which was significantly lower than in the pyridaben (6.11 eggs/female) and control treatments (11.45 eggs/female). Transgenerational sublethal effects of abamectin and pyridaben in P. pallidus can be effectively used to for optimizing IPM programs against this pest on strawberries.