Splitting It Up: The spduration Split-Population Duration Regression Package for Time-Varying Covariates

We present an implementation of split-population duration regression in the spduration (Beger et al., 2017) package for R that allows for time-varying covariates. The statistical model accounts for units that are immune to a certain outcome and are not part of the duration process the researcher is primarily interested in. We provide insights for when immune units exist, that can significantly increase the predictive performance compared to standard duration models. The package includes estimation and several post-estimation methods for split-populationWeibull and log-logistic models. We provide an empirical application to data on military coups

In vitro interaction of chronic wound bacteria in biofilms

Objective: To use in vitro biofilm models of wound bacterial isolates and compare the biofilms produced for different combinations of wound bacterial species. Method: In vitro biofilms, generated by Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus oralis and Micrococcus luteus in microtitre plates and a constant depth film fermentor (CDFF), were studied. The tested isolates all originated from chronic venous leg ulcers. Biofilms of individual and dual combinations of these species were generated in microtitre plate wells at 37°C for 24-96 hours and also in the CDFF for 7 days. The extent of biofilm formation from these systems was then measured using crystal violet staining and/or total viable counts. Results: All the chronic wound bacteria formed biofilms (both individually and in mixed culture) in these models. In mixed species microtitre plate biofilms, both P. aeruginosa and S. aureus appeared to antagonise biofilm formation by S. oralis and M. luteus, with P. aeruginosa completely inhibiting the growth of these organisms. Similar effects were evident in the CDFF model, when all four bacterial species were added simultaneously, with M. luteus being 'out-competed' by the other organisms present and occurring at numbers at the limits of detection; however, there was an apparent increase in the numbers of S. oralis compared with its single culture equivalent. Conclusion: The study highlighted differences in biofilm formation ability for the tested species in both closed and open model systems. Using dual species biofilms, distinct species antagonism was observed with apparent antagonism of pathogenic species over 'commensal' ones. Such a finding provides insight into possible bacterial interactions during development of 'non-healing' wound biofilms

“Quality teaches you how to use water. It doesn’t provide a water pump”: a qualitative study of context and mechanisms of action in an Ethiopian quality improvement program

Background Quality improvement collaboratives are a common approach to bridging the quality-of-care gap, but little is known about implementation in low-income settings. Implementers rarely consider mechanisms of change or the role of context, which may explain collaboratives’ varied impacts. Methods To understand mechanisms and contextual influences we conducted 55 in-depth interviews with staff from four health centres and two hospitals involved in quality improvement collaboratives in Ethiopia. We also generated control charts for selected indicators to explore any impacts of the collaboratives. Results The cross facility learning sessions increased the prominence and focus on quality, allowed learning from experts and peers and were motivational through public recognition of success or a desire to emulate peers. Within facilities, new structures and processes were created. These were fragile and sometimes alienating to those outside the improvement team. The trusted and respected mentors were important for support, motivation and accountability. Where mentor visits were infrequent or mentors less skilled, team function was impacted. These mechanisms were more prominent, and quality improvement more functional, in facilities with strong leadership and pre-existing good teamwork; as staff had shared goals, an active approach to problems and were more willing and able to be flexible to implement change ideas. Quality improvement structures and processes were more likely to be internally driven and knowledge transferred to other staff in these facilities, which reduced the impact of staff turnover and increased buy-in. In facilities which lacked essential inputs, staff struggled to see how the collaborative could meaningfully improve quality and were less likely to have functioning quality improvement. The unexpected civil unrest in one region strongly disrupted the health system and the collaborative. These contextual issues were fluid, with multiple interactions and linkages. Conclusions The study confirms the need to carefully consider context in the implementation of quality improvement collaboratives. Facilities that implement quality improvement successfully may be those that already have characteristics that foster quality. Quality improvement may be alienating to those outside of the improvement team and implementers should not assume the organic spread or transfer of quality improvement knowledge

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Changes in health worker knowledge and motivation in the context of a quality improvement programme in Ethiopia

A knowledgeable and motivated workforce is critical for health systems to provide high-quality services. Many low- and middle-income countries face shortages in human resources and low health worker motivation but are also home to a burgeoning number of quality improvement (QI) programmes. This study evaluates whether and how motivation and clinical knowledge in three cadres of health workers changed in the context of a QI programme for maternal and newborn health in Ethiopia. This mixed-methods study used a pre-post comparison group design with matched comparison areas. We interviewed 395 health workers at baseline in April 2018 and 404 at endline in June 2019 from seven districts (woredas) with QI and seven comparison woredas. Three cadres were interviewed: health extension workers, facility-based skilled midlevel maternal and newborn care providers, and non-patient-facing staff. A qualitative component sought to triangulate and further elucidate quantitative findings using in-depth interviews with 22 health workers. Motivation was assessed quantitatively, exploratory factor analysis was used to categorize motivation dimensions, and regression-based difference-in-difference analyses were conducted. Knowledge was assessed through a clinical vignette. Qualitative data were analysed in a deductive process based on a framework derived from quantitative results. Although knowledge of the QI programme was high (79%) among participants from QI woreda at endline, participation in QI teams was lower (56%). There was strong evidence that health worker knowledge increased more in areas with QI than comparison areas. Three motivation dimensions emerged from the data: (1) 'helping others', (2) 'pride and satisfaction' and (3) 'external recognition and support'. We found strong evidence that motivation across these factors improved in both QI and comparison areas, with weak evidence of greater increases in comparison areas. Qualitative data suggested the QI programme may have improved motivation by allowing staff to provide better care. This study suggests that although QI programmes can increase health worker knowledge, there may be little effect on motivation. Programme evaluations should measure a wide range of outcomes to fully understand their impact

Cell-Cell Communication between Malaria-Infected Red Blood Cells via Exosome-like Vesicles

Cell-cell communication is an important mechanism for information exchange promoting cell survival for the control of features such as population density and differentiation. We determined that Plasmodium falciparum-infected red blood cells directly communicate between parasites within a population using exosome-like vesicles that are capable of delivering genes. Importantly, communication via exosome-like vesicles promotes differentiation to sexual forms at a rate that suggests that signaling is involved. Furthermore, we have identified a P. falciparum protein, PfPTP2, that plays a key role in efficient communication. This study reveals a previously unidentified pathway of P. falciparum biology critical for survival in the host and transmission to mosquitoes. This identifies a pathway for the development of agents to block parasite transmission from the human host to the mosquito.Neta Regev-Rudzki, Danny W. Wilson, Teresa G. Carvalho, Xavier Sisquella, Bradley M. Coleman, Melanie Rug, Dejan Bursac, Fiona Angrisano, Michelle Gee, Andrew F. Hill, Jake Baum, Alan F. Cowma

Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC-Kpn), are an increasing threat to patient safety. Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013–14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI. Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC-Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn4401a), except one KPC-Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC-Kpn (ST491) with Tn4401a-carrying pKpQILD2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC-Kpn (ST14,ST661) including clonal spread of KPC-Kpn (ST661) from a symptomatic case to nine ward contacts. Conclusions: WGS of outbreak KPC isolates demonstrated blaKPC dissemination via horizontal transposition (Tn4401a), plasmid spread (pKpQIL-D2) and clonal spread (K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of blaKPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts

RhierBAPS: An R implementation of the population clustering algorithm hierBAPS.

Identifying structure in collections of sequence data sets remains a common problem in genomics. hierBAPS, a popular algorithm for identifying population structure in haploid genomes, has previously only been available as a MATLAB binary. We provide an R implementation which is both easier to install and use, automating the entire pipeline. Additionally, we allow for the use of multiple processors, improve on the default settings of the algorithm, and provide an interface with the ggtree library to enable informative illustration of the clustering results. Our aim is that this package aids in the understanding and dissemination of the method, as well as enhancing the reproducibility of population structure analyses

Decision-making and referral processes for patients with motor neurone disease: a qualitative study of GP experiences and evaluation of a new decision-support tool

Background The diagnosis of motor neurone disease (MND) is known to be challenging and there may be delay in patients receiving a correct diagnosis. This study investigated the referral process for patients who had been diagnosed with MND, and whether a newly-developed tool (The Red Flags checklist) might help General Practitioners (GPs) in making referral decisions. Methods We carried out interviews with GPs who had recently referred a patient diagnosed with MND, and interviews/surveys with GPs who had not recently referred a patient with suspected MND. We collected data before the Red Flags checklist was introduced; and again one year later. We analysed the data to identify key recurring themes. Results Forty two GPs took part in the study. The presence of fasciculation was the clinical feature that most commonly led to consideration of a potential MND diagnosis. GPs perceived that their role was to make onward referrals rather than attempting to make a diagnosis, and delays in correct diagnosis tended to occur at the specialist level. A quarter of participants had some awareness of the newly-developed tool; most considered it useful, if incorporated into existing systems. Conclusions While fasciculation is the most common symptom associated with MND, other bulbar, limb or respiratory features, together with progression should be considered. There is a need for further research into how decision-support tools should be designed and provided, in order to best assist GPs with referral decisions. There is also a need for further work at the level of secondary care, in order that referrals made are re-directed appropriately