Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

The equity dimension in evaluations of the quality and outcomes framework: A systematic review

<p>Abstract</p> <p>Background</p> <p>Pay-for-performance systems raise concerns regarding inequity in health care because providers might select patients for whom targets can easily be reached. This paper aims to describe the evolution of pre-existing (in)equity in health care in the period after the introduction of the Quality and Outcomes Framework (QOF) in the UK and to describe (in)equities in exception reporting. In this evaluation, a theory-based framework conceptualising equity in terms of equal access, equal treatment and equal treatment outcomes for people in equal need is used to guide the work.</p> <p>Methods</p> <p>A systematic MEDLINE and Econlit search identified 317 studies. Of these, 290 were excluded because they were not related to the evaluation of QOF, they lacked an equity dimension in the evaluation, their qualitative research focused on experiences or on the nature of the consultation, or unsuitable methodology was used to pronounce upon equity after the introduction of QOF.</p> <p>Results</p> <p>None of the publications (n = 27) assessed equity in access to health care. Concerning equity in treatment and (intermediate) treatment outcomes, overall quality scores generally improved. For the majority of the observed indicators, all citizens benefit from this improvement, yet the extent to which different patient groups benefit tends to vary and to be highly dependent on the type and complexity of the indicator(s) under study, the observed patient group(s) and the characteristics of the study. In general, the introduction of QOF was favourable for the aged and for males. Total QOF scores did not seem to vary according to ethnicity. For deprivation, small but significant residual differences were observed after the introduction of QOF favouring less deprived groups. These differences are mainly due to differences at the practice level. The variance in exception reporting according to gender and socio-economic position is low.</p> <p>Conclusions</p> <p>Although QOF seems not to be socially selective at first glance, this does not mean QOF does not contribute to the inverse care law. Introducing different targets for specific patient groups and including appropriate, non-disease specific and patient-centred indicators that grasp the complexity of primary care might refine the equity dimension of the evaluation of QOF. Also, information on the actual uptake of care, information at the patient level and monitoring of individuals' health care utilisation tracks could make large contributions to an in-depth evaluation. Finally, evaluating pay-for-quality initiatives in a broader health systems impact assessment strategy with equity as a full assessment criterion is of utmost importance.</p

Root Canal Anatomy of Maxillary and Mandibular Teeth

It is a common knowledge that a comprehensive understanding of the complexity of the internal anatomy of teeth is imperative to ensure successful root canal treatment. The significance of canal anatomy has been emphasized by studies demonstrating that variations in canal geometry before cleaning, shaping, and obturation procedures had a greater effect on the outcome than the techniques themselves. In recent years, significant technological advances for imaging teeth, such as CBCT and micro-CT, respectively, have been introduced. Their noninvasive nature allows to perform in vivo anatomical studies using large populations to address the influence of several variables such as ethnicity, aging, gender, and others, on the root canal anatomy, as well as to evaluate, quantitatively and/or qualitatively, specific and fine anatomical features of a tooth group. The purpose of this chapter is to summarize the morphological aspects of the root canal anatomy published in the literature of all groups of teeth and illustrate with three-dimensional images acquired from micro-CT technology.info:eu-repo/semantics/publishedVersio

Inheritance and relationships of flowering time and seed size in kabuli chickpea

Flowering time and seed size are the important traits for adaptation in chickpea. Early phenology (time of flowering, podding and maturity) enhance chickpea adaptation to short season environments. Along with a trait of consumer preference, seed size has also been considered as an important factor for subsequent plant growth parameters including germination, seedling vigour and seedling mass. Small seeded kabuli genotype ICC 16644 was crossed with four genotypes (JGK 2, KAK 2, KRIPA and ICC 17109) to study inheritance of flowering time and seed size. The relationships of phenology with seed size, grain yield and its component traits were studied. The study included parents, F1, F2 and F3 of four crosses. The segregation data of F2 indicated flowering time in chickpea was governed by two genes with duplicate recessive epistasis and lateness was dominant to earliness. Two genes were controlling 100-seed weight where small seed size was dominant over large seed size. Early phenology had significant negative or no association (ICC 16644 × ICC 17109) with 100-seed weight. Yield per plant had significant positive association with number of seeds per plant, number of pods per plant, biological yield per plant, 100-seed weight, harvest index and plant height and hence could be considered as factors for seed yield improvement. Phenology had no correlation with yield per se (seed yield per plant) in any of the crosses studied. Thus, present study shows that in certain genetic background it might be possible to breed early flowering genotypes with large seed size in chickpea and selection of early flowering genotypes may not essentially have a yield penalty

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients