Elimination of mother- to - child transmission of HIV in South Africa : Rapid scale- up using quality improvement

PKBackground: South Africa (SA) is committed to achieving the goal of eliminating mother-to-child transmission (MTCT) of HIV by 2015. To achieve this, universal coverage of quality antenatal, labour, delivery and postnatal services for all women has to be attained. Over the past decade, the prevention of mother-to-child transmission (PMTCT) programme has been scaled up to reach all healthcare facilities in the country. However, challenges persist in achieving 100% coverage and access to the programme. Objectives: We describe the process undertaken by the National Department of Health (NDoH), in collaboration with partners, to develop, implement and monitor a data-driven intervention to improve facility, district, provincial and national PMTCT-related performance. Methods: Between 2011 and 2013, the NDoH developed and implemented an intervention using data-driven participatory processes to understand facility-level bottlenecks to optimise PMTCT implementation and to scale up priority PMTCT actions nationally. Results: There was remarkable improvement across all key indicators in the PMTCT cascade over the 3 years 2011 - 2013. Simple monitoring tools such as a visual dashboard and data for action reports were successfully used to improve the performance of the PMTCT programme across SA. MTCT has shown a significant downward trend. Conclusions: It is feasible to implement district-level, data-driven quality improvement processes at a national scale to improve the performance of the PMTCT programme at the local level

Returning to work after stroke: perspectives of employer stakeholders, a qualitative study.

Purpose: More than 40 % of working age adults with stroke fail to return to work. The work context is a key factor in return to work, but little is known about the experiences of employers in supporting employees with stroke. The aim of this study was to explore return to work after stroke from the employer perspective, to identify key features associated with success and to seek participants’ views regarding the role of healthcare in return to work. Methods: Data was gathered through 18 semi-structured interviews with employer stakeholders and included small business owners, line managers, human resources and occupational health staff. Data was analysed thematically. Results: The main themes identified were: the impact of stroke on the employer, characteristics of the employee, communication, knowledge and information, experience of other stakeholders, integrating healthcare in return to work. Conclusion: Employers face complex emotional and practical issues when helping an employee return to work after stroke, for which many lack knowledge and experience. The range and quality of support networks that they access is variable and advice and support from clinicians is welcomed. Further research is necessary to investigate how such support could be funded and integrated within existing service provision

Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy

Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias 1–4 remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment

Predicting discharge to institutional long-term care after stroke: a systematic review & meta-analysis

Background/Objectives: Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. Design: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. Setting: Acute and rehabilitation hospitals. Participants: Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. Measurements: Factors associated with new institutionalization. Results: From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. Conclusion: Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting

Analysis of interactions between ribosomal proteins and RNA structural motifs

<p>Abstract</p> <p>Background</p> <p>One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in <it>T. thermophilus </it>and <it>E. coli</it>, supporting the idea of a core made by both RNA and proteins, conserved by evolution. Recent work showed also that ribosomal RNA is modularly composed. Motifs are generally single-stranded sequences of consecutive nucleotides (ssRNA) with characteristic folding. The role of these motifs in protein-RNA interactions has been so far only sparsely investigated.</p> <p>Results</p> <p>This work explores the role of RNA structural motifs in the interaction of proteins with ribosomal RNA (rRNA). We analyze composition, local geometries and conformation of interface regions involving motifs such as tetraloops, kink turns and single extruded nucleotides. We construct an interaction map of protein binding sites that allows us to identify the common types of shared 3-D physicochemical binding patterns for tetraloops. Furthermore, we investigate the protein binding pockets that accommodate single extruded nucleotides either involved in kink-turns or in arbitrary RNA strands. This analysis reveals a new structural motif, called <it>tripod</it>.</p> <p>It corresponds to small pockets consisting of three aminoacids arranged at the vertices of an almost equilateral triangle. We developed a search procedure for the recognition of tripods, based on an empirical tripod fingerprint.</p> <p>Conclusion</p> <p>A comparative analysis with the overall RNA surface and interfaces shows that contact surfaces involving RNA motifs have distinctive features that may be useful for the recognition and prediction of interactions.</p

Wilms tumor characteristics in children with heterozygous germline <i>DIS3L2 </i>variants

Purpose: Heterozygous germline DIS3L2 pathogenic variants were recently linked to Wilms tumor (WT) predisposition. Limited data on cancer penetrance and characteristics complicate surveillance/management recommendations. This study aims to describe an extended cohort of children with WTs and heterozygous germline DIS3L2 (likely) pathogenic variants ([L]PVs). Methods: Clinical and tumor data of children with WT and heterozygous germline DIS3L2 (L)PVs were retrospectively collected. Results: Thirty-four children were identified, including 4 familial cases. Germline (L)PVs included exon 9 deletions (n = 28) and other (n = 6) (L)PVs. Seventeen parents were confirmed to have the DIS3L2 (L)PV, of whom 1 had a past WT. Median age at WT diagnosis was 41 months (range: 8-101). A somatic second hit in DIS3L2 was found in 19 of 20 children with genetic tumor data. Five children had bilateral WTs and 11 had metastases (32%). Eight children had high-risk tumor histology (24%, of which 7 post-chemotherapy blastemal). Three children relapsed or developed a second primary tumor; 4 children were deceased. Recurring clinical features were lacking. Conclusion: Children with WTs and heterozygous germline DIS3L2 (L)PVs lack a recognizable phenotype. DIS3L2 (L)PVs are a cause for familial WT, but WT penetrance is likely low. This cohort exhibits a high percentage of metastases and high-risk blastemal tumors, which need further study.</p

Income and education as predictors of return to working life among younger stroke patients

<p>Abstract</p> <p>Background</p> <p>Socioeconomic conditions are not only related to poor health outcomes, they also contribute to the chances of recovery from stroke. This study examines whether income and education were predictors of return to work after a first stroke among persons aged 40-59.</p> <p>Methods</p> <p>All first-stroke survivors aged 40-59 who were discharged from a hospital in 1996-2000 and who had received income from work during the year prior to the stroke were sampled from the Swedish national register of in-patient care (n = 7,081). Income and education variables were included in hazard regressions, modelling the probability of returning to work from one to four years after discharge. Adjustments for age, sex, stroke subtype, and length of in-patient care were included in the models.</p> <p>Results</p> <p>Both higher income and higher education were associated with higher probability of returning to work. While the association between education and return to work was attenuated by income, individuals with university education were 13 percent more likely to return than those who had completed only compulsory education, and individuals in the highest income quartile were about twice as likely to return as those in the lowest. The association between socioeconomic position and return to work was similar for different stroke subtypes. Income differences between men and women also accounted for women's lower probability of returning to work.</p> <p>Conclusions</p> <p>The study demonstrates that education and income were independent predictors of returning to work among stroke patients during the first post-stroke years. Taking the relative risk of return to work among those in the higher socioeconomic positions as the benchmark, there may be considerable room for improvement among patients in lower socioeconomic strata.</p

Computational Structural Analysis: Multiple Proteins Bound to DNA

BACKGROUND: With increasing numbers of crystal structures of proteinratioDNA and proteinratioproteinratioDNA complexes publically available, it is now possible to extract sufficient structural, physical-chemical and thermodynamic parameters to make general observations and predictions about their interactions. In particular, the properties of macromolecular assemblies of multiple proteins bound to DNA have not previously been investigated in detail. METHODOLOGY/PRINCIPAL FINDINGS: We have performed computational structural analyses on macromolecular assemblies of multiple proteins bound to DNA using a variety of different computational tools: PISA; PROMOTIF; X3DNA; ReadOut; DDNA and DCOMPLEX. Additionally, we have developed and employed an algorithm for approximate collision detection and overlapping volume estimation of two macromolecules. An implementation of this algorithm is available at http://promoterplot.fmi.ch/Collision1/. The results obtained are compared with structural, physical-chemical and thermodynamic parameters from proteinratioprotein and single proteinratioDNA complexes. Many of interface properties of multiple proteinratioDNA complexes were found to be very similar to those observed in binary proteinratioDNA and proteinratioprotein complexes. However, the conformational change of the DNA upon protein binding is significantly higher when multiple proteins bind to it than is observed when single proteins bind. The water mediated contacts are less important (found in less quantity) between the interfaces of components in ternary (proteinratioproteinratioDNA) complexes than in those of binary complexes (proteinratioprotein and proteinratioDNA).The thermodynamic stability of ternary complexes is also higher than in the binary interactions. Greater specificity and affinity of multiple proteins binding to DNA in comparison with binary protein-DNA interactions were observed. However, protein-protein binding affinities are stronger in complexes without the presence of DNA. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the interface properties: interface area; number of interface residues/atoms and hydrogen bonds; and the distribution of interface residues, hydrogen bonds, van der Walls contacts and secondary structure motifs are independent of whether or not a protein is in a binary or ternary complex with DNA. However, changes in the shape of the DNA reduce the off-rate of the proteins which greatly enhances the stability and specificity of ternary complexes compared to binary ones