Model-informed target product profiles of long-acting-injectables for use as seasonal malaria prevention

Seasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine (SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, show LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimising LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process

Cricoid Pressure During Intubation: Review of Research and Survey of Nurse Anesthetists

This project assessed the knowledge of certified registered nurse anesthetists and student registered nurse anesthetists at a Premier Clinical Research University Medical Center regarding the effectiveness, value, and alternatives to the cricoid pressure technique during intubation, and possible alternatives that would safely achieve the same goal as this technique

Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria

Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We propose using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability

Theory of reactive interventions in the elimination and control of malaria

Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission. However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted.; Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics. Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections.; RCD proved most effective at low prevalence. Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case. Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases. However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions).; RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range. In other settings, it is likely to reduce disease burden. RCD may also help maintain the disease-free state in the face of imported infections. Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and Sao Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in Sao Paulo (from 12.3% to 31.2%) and Dakar (from 6.7% to 19.4%) and increased six-fold in Ulaanbaatar (from 3.1% to 19.7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries

Intraspecific phenotypic variability of the herbaceous species Daucus carota (Apiaceae) used for restoration purposes

For restoration purposes nature conservation preferably requests the use of local seed sources based on the “local-is-best” (LIB) approach. However, counter-arguments against this usage are potential benefits by increased variation, which could be beneficial especially in times of global change. We here investigate intraspecific morphological variability of one of the most common herbaceous, insect pollinated and zoochorous plants from seed mixtures used for landscape restoration processes in central Europe, the wild carrot, Daucus carota L. (Apiaceae). Our results show that D. carota features no vegetative but two generative characters that significantly differed among plants originating from seeds of natural (I) and restored (R) sites. We could show that effects of mowing always overlay origin-specific characteristics. The earlier genetic analysis did not support a regional provenance concept for restoration purposes, while slight differences in phenological parameters related to fitness pinpoint to ‘mix and match-admixture provenancing’ as a compromise strategy.</jats:p