Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience

<p>Abstract</p> <p>Background</p> <p>This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field.</p> <p>Case description</p> <p>In 2002, DND<it>i </it>created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DND<it>i </it>and sanofi-aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam^®/Artesunate Amodiaquine Winthrop^®("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DND<it>i </it>and sanofi-aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan.</p> <p>Discussion and evaluation</p> <p>The partnership between DND<it>i </it>and sanofi-aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan.</p> <p>Conclusions</p> <p>The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases.</p

CASA-Mot technology: how results are affected by the frame rate and counting chamber

For over 30 years, CASA-Mot technology has been used for kinematic analysis of sperm motility in different mammalian species, but insufficient attention has been paid to the technical limitations of commercial computer-aided sperm analysis (CASA) systems. Counting chamber type and frame rate are two of the most important aspects to be taken into account. Counting chambers can be disposable or reusable, with different depths. In human semen analysis, reusable chambers with a depth of 10 mm are the most frequently used, whereas for most farm animal species it is more common to use disposable chambers with a depth of 20 mm. The frame rate was previously limited by the hardware, although changes in the number of images collected could lead to significant variations in some kinematic parameters, mainly in curvilinear velocity (VCL). A frame rate of 60 frames s(-1) is widely considered to be the minimum necessary for satisfactory results. However, the frame rate is species specific and must be defined in each experimental condition. In conclusion, we show that the optimal combination of frame rate and counting chamber type and depth should be defined for each species and experimental condition in order to obtain reliable results

Subthalamic and pallidal deep brain stimulation for Parkinson's disease-meta-analysis of outcomes.

Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation

Aim and shoot: molecule-imprinting polymer coated MoO3 for selective SERS detection and photocatalytic destruction of low-level organic contaminants

A sensitive and selective SERS sensor with easy and excellent recyclability is highly demanded because of its great potential application in complex detection environments. Here, using methylene blue (MB) as a model target, a semiconductor-based SERS substrate composed of a MoO3 nanorod core and a uniform molecule-imprinting polymethacrylic acid shell (MIP) with a thickness of 4 nm was designed and fabricated (MoO3@MIP) to achieve selective detection. The key to the successful coating of the ultrathin uniform MIP shell lies in the pretreatment of a MoO3 core with nitric acid, providing sufficient surficial hydroxyls for the anchoring of a polymer precursor. The molecule-imprinted voids for MB were formed simply via light irradiation as a result of photocatalytic degradation by a MoO3 semiconductor. This core–shell MIP composite shows a high SERS selectivity towards low-level MB in a mixed MB/CV solution. The enhanced factor (EF) is high, at 1.6 × 104. More importantly, the selective detection allows the further photocatalytic recycling of MoO3@MIP in an “aim-and-shoot” way, which well preserves the detection selectivity and sensitivity towards MB at least for 4 cycles. Based on decreased sensitivity with the increasing shell thickness (10–24 nm), a MIP-gating charge transfer mechanism is proposed to demonstrate the high EF instead of the molecule-enrichment effect. This “aim-and-shoot” strategy is expected to push forward the prosperous application of selective SERS for trace detection in versatile environments

Design of a flight control architecture using a non-convex bundle method

We design a feedback control architecture for longitudinal flight of an aircraft. The multi-level architecture includes the flight control loop to govern the short term dynamics of the aircraft, and the autopilot to control the long term modes. Using H1 performance and robustness criteria, the problem is cast as a non-convex and non-smooth optimization program. We present a non-convex bundle method, prove its convergence, and show that it is apt to solve the longitudinal flight control problem

Dolphin morbillivirus infection in different parts of the Mediterranean Sea

Morbillivirus were isolated from Mediterranean striped dolphins (Stenella coeruleoalba) dying along the coasts of Italy and Greece in 1991. They were antigenically identical to the morbilliviruses isolated from striped dolphins in Spain in 1990