Herry Consult (Austria)

Soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) infect about one-fifth of the world’s population. The currently available drugs are all highly efficacious against A. lumbricoides. However, they are only moderately efficacious against hookworm and poorly efficacious against T. trichiura. Oxantel, a tetrahydropyrimidine derivative discovered in the 1970s, has recently been brought back to our attention given its high efficacy against T. trichiura infections (estimated 76% cure rate and 85% egg reduction rate at a 20 mg/kg dose). This review summarizes the current knowledge on oxantel pamoate and its use against T. trichiura infections in humans. Oxantel pamoate acts locally in the human gastrointestinal tract and binds to the parasite’s nicotinic acetylcholine receptor (nAChR), leading to a spastic paralysis of the worm and subsequent expulsion. The drug is metabolically stable, shows low permeability and low systemic bioavailability after oral use. Oxantel pamoate was found to be safe in humans, with only a few mild adverse events reported. Several clinical trials have investigated the efficacy of this drug against T. trichiura and suggest that oxantel pamoate is more efficacious against T. trichiura than the currently recommended drugs, which makes it a strong asset to the depleted drug armamentarium and could help delay or even prevent the development of resistance to existing drugs. We highlight existing data to support the use of oxantel pamoate against T. trichiura infections.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01505-1.

Summary This paper presents an upgraded workflow to address direct geostatistical simulations on unstructured grids. Comparing to previous approaches, this algorithm is based on a recently proposed spectral decomposition applicable to a wide class of variograms and allowing for non-stationarity. The method is encapsulated in a workflow dedicated to unstructured grids including facies modeling and hydrocarbon in place computations. The proposed methodology is able to treat any kind of grid; it takes into account the support effect and it decreases drastically the computation time compared to previous approaches based on Sequential Gaussian Simulations. The method is illustrated on a synthetic example and some results on a true case study are also provided.

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.

Large tunnel cross-sections in soft ground require a design methodology that can adequately deal with the complex stress state surrounding the underground opening and the associated excavation stages; this is especially the case at bifurcations where adjacent tunnels merge to create a transition zone of a larger cross-section. Vertical profile design constraints may further lead to shallow overburden conditions that add to the risks that have to be addressed as part of the tunnel design. This paper presents an advanced NATM design methodology that is integrated with design and construction risk management schemes to meet major risk-bearing aspects; namely, large tunnel cross-section (area of up to 470 m²), a shallow overburden (as low as 10.5 m), soft-ground conditions (cemented sands and gravels), and the location of the tunnel inside an urban area. Special emphasis was paid to controlling the settlement risks associated with tunneling via an oriented risk triggers and alarm plan.

Background and Aims: Walking and cycling are increasingly recognized as effective forms of physical activity, an important public health priority. Urban and transport planning are more influential ...

Pharmacogenomics--the application of genomic technologies such as gene sequencing and gene expression analysis to drugs--is beginning to make its impact on central nervous system drug development. The mapping of genes (including their polymorphisms) and their expression in normal and disease states to discover new drug targets will also change the scenery of dementia therapeutics' development completely because it uses a "bottom-up" strategy, identifying genes whose expression is changed in dementia or by drug therapy. Drugs identified this way should be mechanistically novel, more potent and specific, and probably quicker to develop. Pharmacogenomics can however also greatly contribute to the improvement of drugs targeting currently known receptors and enzymes.