Effect of case management on neonatal mortality due to sepsis and pneumonia.

BACKGROUND: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST). METHODS: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness. RESULTS: Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR = 0.56, 95% CI 0.41-0.77) and 34% (RR = 0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively. CONCLUSION: Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US

Learning and Matching Multi-View Descriptors for Registration of Point Clouds

Critical to the registration of point clouds is the establishment of a set of accurate correspondences between points in 3D space. The correspondence problem is generally addressed by the design of discriminative 3D local descriptors on the one hand, and the development of robust matching strategies on the other hand. In this work, we first propose a multi-view local descriptor, which is learned from the images of multiple views, for the description of 3D keypoints. Then, we develop a robust matching approach, aiming at rejecting outlier matches based on the efficient inference via belief propagation on the defined graphical model. We have demonstrated the boost of our approaches to registration on the public scanning and multi-view stereo datasets. The superior performance has been verified by the intensive comparisons against a variety of descriptors and matching methods

Determining weight-bearing tissue condition using peak reactive hyperemia response trend and ultrasonographic features: implications for pressure ulcer prevention

Frequent repositioning is important to prevent pressure ulcer (PU) development, by relieving pressure and recovering damages on skin areas induced by repetitive loading. Although repositioning is the gold standard to prevent PU, there is currently no strategy for determining tissue condition under preventive approaches. In this study, the peak reactive hyperemia (RH) trends and ultrasonographic (US) features are compared with the tissue condition under histopathological examination to determine the potential use of these features in determining the tissue condition noninvasively. Twenty-one male Sprague–Dawley rats (seven per group), with body weight of 385–485 g, were categorized into three groups and subjected to different recovery times, each with three repetitive loading cycles at skin tissues above of right trochanter area. The first, second, and third groups were subjected to short (3 minutes), moderate (10 minutes), and prolonged (40 minutes) recovery, respectively, while applying fixed loading time and pressure (10 minutes and 50 mmHg, respectively), to provide different degree of recovery and tissue conditions (tissue damage and tissue recovery). Peak RH was measured in the three cycles to determine RH trend (increasing, decreasing, and inconsistent). All rat tissues were evaluated using ultrasound at pre- and post-experiment and rated by two raters to categorize the severity of tissue changes (no, mild, moderate, and severe). The tissue condition was also evaluated using histopathological examination to distinguish between normal and abnormal tissues. Most of the samples with increasing RH trend is related to abnormal tissue (71%); while inconsistent RH trends is more related to normal tissue (82%). There is no relationship between the tissue conditions evaluated under ultrasonographic and histopathological examination. Peak RH trend over repetitive loading may serve as a new feature for determining the tissue condition that leading to pressure ulcer

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors

Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

BACKGROUND: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. METHODS: In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD) when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. RESULTS: The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC) was high (1.61 μg/ml). The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. CONCLUSION: The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines

Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p

Investigating and learning lessons from early experiences of implementing ePrescribing systems into NHS hospitals:a questionnaire study

Background: ePrescribing systems have significant potential to improve the safety and efficiency of healthcare, but they need to be carefully selected and implemented to maximise benefits. Implementations in English hospitals are in the early stages and there is a lack of standards guiding the procurement, functional specifications, and expected benefits. We sought to provide an updated overview of the current picture in relation to implementation of ePrescribing systems, explore existing strategies, and identify early lessons learned.Methods: a descriptive questionnaire-based study, which included closed and free text questions and involved both quantitative and qualitative analysis of the data generated.Results: we obtained responses from 85 of 108 NHS staff (78.7% response rate). At least 6% (n = 10) of the 168 English NHS Trusts have already implemented ePrescribing systems, 2% (n = 4) have no plans of implementing, and 34% (n = 55) are planning to implement with intended rapid implementation timelines driven by high expectations surrounding improved safety and efficiency of care. The majority are unclear as to which system to choose, but integration with existing systems and sophisticated decision support functionality are important decisive factors. Participants highlighted the need for increased guidance in relation to implementation strategy, system choice and standards, as well as the need for top-level management support to adequately resource the project. Although some early benefits were reported by hospitals that had already implemented, the hoped for benefits relating to improved efficiency and cost-savings remain elusive due to a lack of system maturity.Conclusions: whilst few have begun implementation, there is considerable interest in ePrescribing systems with ambitious timelines amongst those hospitals that are planning implementations. In order to ensure maximum chances of realising benefits, there is a need for increased guidance in relation to implementation strategy, system choice and standards, as well as increased financial resources to fund local activitie

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Optical and near-infrared observations of the Fried Egg Nebula

Context. The fate of a massive star during the latest stages of its evolution is highly dependent on its mass-loss rate and geometry and therefore knowing the geometry of the circumstellar material close to the star and its surroundings is crucial. Aims. We aim to provide insight into the nature (i.e. geometry, rates) of mass-loss episodes, and in particular, the connection between the observed asymmetries due to the mass lost in a fast wind or during a previous, prodigious mass-losing phase. In this context, yellow hypergiants offer a good opportunity to study mass-loss events. Methods. We analysed a large set of optical and near-infrared data in spectroscopic and photometric, spectropolarimetric, and interferometric (GRAVITY/VLTI) modes, towards the yellow hypergiant IRAS 17163−3907. We used X-shooter optical observations to determine the spectral type of this yellow hypergiant and we present the first model-independent, reconstructed images of IRAS 17163−3907 at these wavelengths tracing milli-arcsecond scales. Lastly, we applied a 2D radiative transfer model to fit the dereddened photometry and the radial profiles of published diffraction-limited VISIR images at 8.59 μm, 11.85 μm, and 12.81 μm simultaneously, adopting a revised distance determination using Gaia Data Release 2 measurements. Results. We constrain the spectral type of IRAS 17163−3907 to be slightly earlier than A6Ia (Teff ∼ 8500 K). The interferometric observables around the 2 μm window towards IRAS 17163−3907 show that the Brγ emission appears to be more extended and asymmetric than the Na I and the continuum emission. Interestingly, the spectrum of IRAS 17163−3907 around 2 μm shows Mg II emission that is not previously seen in other objects of its class. In addition, Brγ shows variability in a time interval of four months that is not seen towards Na I. Lastly, in addition to the two known shells surrounding IRAS 17163−3907, we report on the existence of a third hot inner shell with a maximum dynamical age of only 30 yr. Conclusions. The 2 μm continuum originates directly from the star and not from hot dust surrounding the stellar object. The observed spectroscopic variability of Brγ could be a result of variability in the mass-loss rate. The interpretation of the presence of Na I emission at closer distances to the star compared to Brγ has been a challenge in various studies. To address this, we examine several scenarios. We argue that the presence of a pseudo-photosphere, which was traditionally considered to be the prominent explanation, is not needed and that it is rather an optical depth effect. The three observed distinct mass-loss episodes are characterised by different mass-loss rates and can inform theories of mass-loss mechanisms, which is a topic still under debate both in theory and observations. We discuss these in the context of photospheric pulsations and wind bi-stability mechanisms