A probabilistic method to estimate the burden of maternal morbidity in resource-poor settings: preliminary development and evaluation

Background

Maternal morbidity is more common than maternal death, and population-based estimates of the burden of maternal morbidity could provide important indicators for monitoring trends, priority setting and evaluating the health impact of interventions. Methods based on lay reporting of obstetric events have been shown to lack specificity and there is a need for new approaches to measure the population burden of maternal morbidity. A computer-based probabilistic tool was developed to estimate the likelihood of maternal morbidity and its causes based on self-reported symptoms and pregnancy/delivery experiences. Development involved the use of training datasets of signs, symptoms and causes of morbidity from 1734 facility-based deliveries in Benin and Burkina Faso, as well as expert review. Preliminary evaluation of the method compared the burden of maternal morbidity and specific causes from the probabilistic tool with clinical classifications of 489 recently-delivered women from Benin, Bangladesh and India.

Results

Using training datasets, it was possible to create a probabilistic tool that handled uncertainty of women’s self reports of pregnancy and delivery experiences in a unique way to estimate population-level burdens of maternal morbidity and specific causes that compared well with clinical classifications of the same data. When applied to test datasets, the method overestimated the burden of morbidity compared with clinical review, although possible conceptual and methodological reasons for this were identified.

Conclusion

The probabilistic method shows promise and may offer opportunities for standardised measurement of maternal morbidity that allows for the uncertainty of women’s self-reported symptoms in retrospective interviews. However, important discrepancies with clinical classifications were observed and the method requires further development, refinement and evaluation in a range of settings.

     

Replication Kinetics of B.1.351 and B.1.1.7 SARS-CoV-2 Variants of Concern Including Assessment of a B.1.1.7 Mutant Carrying a Defective ORF7a Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is a readily transmissible and potentially deadly pathogen which is currently re-defining human susceptibility to pandemic viruses in the modern world. The recent emergence of several genetically distinct descendants known as variants of concern (VOCs) is further challenging public health disease management, due to increased rates of virus transmission and potential constraints on vaccine effectiveness. We report the isolation of SARS-CoV-2 VOCs imported into Australia belonging to the B.1.351 lineage, first described in the Republic of South Africa (RSA), and the B.1.1.7 lineage originally reported in the United Kingdom, and directly compare the replication kinetics of these two VOCs in Vero E6 cells. In this analysis, we also investigated a B.1.1.7 VOC (QLD1516/2021) carrying a 7-nucleotide deletion in the open reading frame 7a (ORF7a) gene, likely truncating and rendering the ORF7a protein of this virus defective. We demonstrate that the replication of the B.1.351 VOC (QLD1520/2020) in Vero E6 cells can be detected earlier than the B.1.1.7 VOCs (QLD1516/2021 and QLD1517/2021), before peaking at 48 h post infection (p.i.), with significantly higher levels of virus progeny. Whilst replication of the ORF7a defective isolate QLD1516/2021 was delayed longer than the other viruses, slightly more viral progeny was produced by the mutant compared to the unmutated isolate QLD1517/2021 at 72 h p.i. Collectively, these findings contribute to our understanding of SARS-CoV-2 replication and evolutionary dynamics, which have important implications in the development of future vaccination, antiviral therapies, and epidemiological control strategies for COVID-19.     

Interesting case of narrow QRS tachycardia. What is the mechanism?

A 67‐year‐old female presented with history of recurrent palpitations. During one of the episodes of palpitation, a narrow QRS tachycardia was recorded and it was reported to be terminated with intravenous adenosine. The 12‐lead electrocardiogram (ECG) showed no manifest ventricular preexcitation. ECG was within normal limits. The patient underwent an electrophysiology study after informed consent. She was taking calcium channel blockers and that was stopped five half‐lives prior to the procedure. As catheters were being placed, a narrow QRS tachycardia got induced. During the study, there was development of right bundle branch block during the tachycardia. What is the mechanism of the tachycardia?     

Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity

Induction of potent and sustained antiviral or antitumor immunity is dependent on the efficient activation of CD8+ and CD4+ T cells. While dendritic cells constitute a powerful platform for stimulating cellular immunity, presentation of endogenous antigens by dendritic cells transfected with nucleic acid-encoded antigens favors the stimulation of CD8+ T cells over that of CD4+ T cells. A short incubation of mRNA-transfected dendritic cells with antisense oligonucleotides directed against the invariant chain enhances the presentation of mRNA-encoded class II epitopes and activation of CD4+ T-cell responses in vitro and in vivo. Immunization of mice with the antisense oligonucleotide-treated dendritic cells stimulates a more potent and longer lasting CD8+ cytotoxic T-cell (CTL) response and enhances the antitumor efficacy of dendritic cell-based tumor vaccination protocols. Transient inhibition of invariant chain expression represents a simple and general method to enhance the stimulation of CD4+ T-cell responses from endogenous antigens.     

Purification of human immunoglobulin G: a new approach to plasma fractionation

BACKGROUND AND OBJECTIVES: Currently, plasma fractionation involves multiple processing steps using established methods such as ethanol precipitation and column chromatography. The known limitations associated with conventional purification techniques, combined with strict regulations on safety and high demand for particular plasma proteins, have resulted in a shortage of plasma-derived therapeutics such as intravenous immunoglobulin G (IgG). MATERIALS AND METHODS: In this study, IgG was purified from human plasma using Gradiflow technology, an electrophoresis-based separation technology. RESULTS: IgG was isolated from plasma to high purity, with 94 +/- 5% recovery in a short processing time. CONCLUSIONS: The technology has been shown to be linearly scalable and has the capacity to contribute to increased production of important plasma fraction therapeutics.     

Extraventricular neurocytoma, a comprehensive review

Aims and objective

Extra ventricular neurocytoms (EVN) are a rare parenchymal brain tumour distinct from central neurocytomas. This review attempts to analyze a series of seven cases of EVN from a single institute against the background of available literature.

Method

Retrospective analysis of the clinical manifestation, pathological features, imaging findings, microsurgical treatment effectiveness and progression free survival of seven cases of EVN operated between 2000–2012.

Results

The study group included five females and two males in the age group 7–65 years (mean 30.71 yrs). The distribution of the lesion was as follows Lobar 4, Cerebellum 1, Pineal 1, spinal 1. The duration of clinical symptoms ranged from three months to seven years and the presentation was site and size specific. Cystic Changes (71 %), perilesional oedema (57 %) and heterogeneous contrast enhancement (85.7 %), and calcification (42 %) were a few distinct imaging characteristics. Increased perfusion correlated with atypical histology in two patients. Surgical resection remains the main management strategy for longer outcome and patients with STR + RT and GTR had comparable follow-up. Extremes of age and atypical histological features were adverse prognostic factors.

Conclusion

EVN are rare tumors with either glial or neuronal differentiation or a potential for atypical changes. Both, GTR and STR combined with RT, offer reasonably good outcome with overall comparable survival. The available literature of EVN is limited, larger series with long term follow-ups are needed to dictate the management protocol. The role of adjuvant therapy is still debatable and needs further validation.