Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data

Background: Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods: In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings: 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23–0.96). Interpretation: Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. Funding: The NIHR Health Technology Assessment Programme

Long-term monitoring in primary care for chronic kidney disease and chronic heart failure: a multi-method research programme

Background: Long-term monitoring is important in chronic condition management. Despite considerable costs of monitoring, there is no or poor evidence on how, what and when to monitor. The aim of this study was to improve understanding, methods, evidence base and practice of clinical monitoring in primary care, focusing on two areas: chronic kidney disease and chronic heart failure. Objectives: The research questions were as follows: does the choice of test affect better care while being affordable to the NHS? Can the number of tests used to manage individuals with early-stage kidney disease, and hence the costs, be reduced? Is it possible to monitor heart failure using a simple blood test? Can this be done using a rapid test in a general practitioner consultation? Would changes in the management of these conditions be acceptable to patients and carers? Design: Various study designs were employed, including cohort, feasibility study, Clinical Practice Research Datalink analysis, seven systematic reviews, two qualitative studies, one cost-effectiveness analysis and one cost recommendation. Setting: This study was set in UK primary care. Data sources: Data were collected from study participants and sourced from UK general practice and hospital electronic health records, and worldwide literature. Participant: The participants were NHS patients (Clinical Practice Research Datalink: 4.5 million patients), chronic kidney disease and chronic heart failure patients managed in primary care (including 750 participants in the cohort study) and primary care health professionals. Interventions: The interventions were monitoring with blood and urine tests (for chronic kidney disease) and monitoring with blood tests and weight measurement (for chronic heart failure). Main outcome measures: The main outcomes were the frequency, accuracy, utility, acceptability, costs and cost-effectiveness of monitoring. Results: Chronic kidney disease: serum creatinine testing has increased steadily since 1997, with most results being normal (83% in 2013). Increases in tests of creatinine and proteinuria correspond to their introduction as indicators in the Quality and Outcomes Framework. The Chronic Kidney Disease Epidemiology Collaboration equation had 2.7% greater accuracy (95% confidence interval 1.6% to 3.8%) than the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate. Estimated annual transition rates to the next chronic kidney disease stage are ≈ 2% for people with normal urine albumin, 3–5% for people with microalbuminuria (3–30 mg/mmol) and 3–12% for people with macroalbuminuria (> 30 mg/mmol). Variability in estimated glomerular filtration rate-creatinine leads to misclassification of chronic kidney disease stage in 12–15% of tests in primary care. Glycaemic-control and lipid-modifying drugs are associated with a 6% (95% confidence interval 2% to 10%) and 4% (95% confidence interval 0% to 8%) improvement in renal function, respectively. Neither estimated glomerular filtration rate-creatinine nor estimated glomerular filtration rate-Cystatin C have utility in predicting rate of kidney function change. Patients viewed phrases such as ‘kidney damage’ or ‘kidney failure’ as frightening, and the term ‘chronic’ was misinterpreted as serious. Diagnosis of asymptomatic conditions (chronic kidney disease) was difficult to understand, and primary care professionals often did not use ‘chronic kidney disease’ when managing patients at early stages. General practitioners relied on Clinical Commissioning Group or Quality and Outcomes Framework alerts rather than National Institute for Health and Care Excellence guidance for information. Cost-effectiveness modelling did not demonstrate a tangible benefit of monitoring kidney function to guide preventative treatments, except for individuals with an estimated glomerular filtration rate of 60–90 ml/minute/1.73 m2, aged < 70 years and without cardiovascular disease, where monitoring every 3–4 years to guide cardiovascular prevention may be cost-effective. Chronic heart failure: natriuretic peptide-guided treatment could reduce all-cause mortality by 13% and heart failure admission by 20%. Implementing natriuretic peptide-guided treatment is likely to require predefined protocols, stringent natriuretic peptide targets, relative targets and being located in a specialist heart failure setting. Remote monitoring can reduce all-cause mortality and heart failure hospitalisation, and could improve quality of life. Diagnostic accuracy of point-of-care N-terminal prohormone of B-type natriuretic peptide (sensitivity, 0.99; specificity, 0.60) was better than point-of-care B-type natriuretic peptide (sensitivity, 0.95; specificity, 0.57). Within-person variation estimates for B-type natriuretic peptide and weight were as follows: coefficient of variation, 46% and coefficient of variation, 1.2%, respectively. Point-of-care N-terminal prohormone of B-type natriuretic peptide within-person variability over 12 months was 881 pg/ml (95% confidence interval 380 to 1382 pg/ml), whereas between-person variability was 1972 pg/ml (95% confidence interval 1525 to 2791 pg/ml). For individuals, monitoring provided reassurance; future changes, such as increased testing, would be acceptable. Point-of-care testing in general practice surgeries was perceived positively, reducing waiting time and anxiety. Community heart failure nurses had greater knowledge of National Institute for Health and Care Excellence guidance than general practitioners and practice nurses. Health-care professionals believed that the cost of natriuretic peptide tests in routine monitoring would outweigh potential benefits. The review of cost-effectiveness studies suggests that natriuretic peptide-guided treatment is cost-effective in specialist settings, but with no evidence for its value in primary care settings. Limitations: No randomised controlled trial evidence was generated. The pathways to the benefit of monitoring chronic kidney disease were unclear. Conclusions: It is difficult to ascribe quantifiable benefits to monitoring chronic kidney disease, because monitoring is unlikely to change treatment, especially in chronic kidney disease stages G3 and G4. New approaches to monitoring chronic heart failure, such as point-of-care natriuretic peptide tests in general practice, show promise if high within-test variability can be overcome

Tribological performance and tribochemical processes in a DLC/steel system when lubricated in a fully formulated oil and base oil

Diamond-like carbon (DLC) coatings show extremely good promise for a number of applications in automotive components as they exhibit excellent tribological properties such as low friction and good wear resistance. This can impact on improved fuel economy and durability of the engine components. Much work has been reported on the dry sliding of DLC coatings with less so in lubricated contacts and, as such, there is a need to further understand the tribochemistry of lubricated DLC contacts. Commercially-available oils are normally optimised to work on ferrous surfaces. Previous studies on DLC lubricated contacts have tended to use model oil systems rather than fully formulated lubricants and from this an interesting picture of lubrication mechanisms is emerging. Optimising compatibility between a surface and a set of lubricant additives may lead to excellent durability (wear) as well as increased fuel economy (low friction). In this work, the friction and wear properties of a DLC coating under boundary lubrication conditions have been investigated and the tribological performance compared with that of an uncoated steel system. A pin-on-plate tribotester was used to run the experiments using High speed steel (HSS) M2 grade plates coated with 15 at.% hydrogenated DLC (a-C:15H) sliding against cast iron pins. A Group III mineral base oil, fully synthetic Group IV PAO and four different fully formulated oils were used in this study. Furthermore optical and scanning electron microscopes (SEM) were used to observe the wear scar and to assess the durability of the coatings. Energy-Dispersive X-ray analysis (EDX), X-ray Photoelectron Spectroscopy (XPS) and Raman spectroscopy analyses were performed on the tribofilms to understand the tribochemical interactions between oil additives and the a-C:15H coating. This study show that the durability of the a-C:15H coating strongly depends on the selected additive package in the oils. In addition the effect of detergent, dispersant and antioxidants on the performance of the molybdenum-based friction modifier (Mo-FM) and ZDDP anti-wear additive was investigated and results are reported in this paper

La evolución del derecho a la educación en Colombia entre 1820 a 1876, como un derecho económico, social y cultural

In examining the evolution of the right to education in New Granada, Gran Colombia and the United States of Colombia, a major effort is evidenced by Francisco de Paula Santander, Mariano Ospina Rodriguez to promote the development of education as a right which should be free and compulsory.However, the project initiated by Santander Ospina Rodriguez and other presidents of the period covered from 1820 to 1876, is to prevent the social, political, cultural and civil wars that were designed to search for autonomy, freedom and independence.Al examinar la evolución del derecho a la educación en la Nueva Granada, la Gran Colombia y los Estados Unidos de Colombia, se evidencia un importante esfuerzo por parte de Francisco de Paula Santander y Mariano Ospina Rodríguez de promover el desarrollo de la educación como un derecho que debía ser gratuito y obligatorio.Sin embargo, el proyecto iniciado por Santander y Ospina Rodríguez y demás presidentes de la época comprendida entre 1820 a 1876, tiene como obstáculo los problemas sociales, políticos, culturales y las guerras civiles que tenían como fin la búsqueda de la autonomía, libertad e independencia

Multiscale friction in lubricant-surface systems for high performance transmissions under mild wear

The lubricant-surface system is complex in nature and can significantly affect the frictional performance of high-performance transmission systems. The complexity stems from the coupled mechanical and chemical phenomena that occur at the interfacial tooth conjunctions. A combined analytical and precision experimental approach is presented to analyse the salient parameters of the lubricant-surface system. A multiscale procedure comprising topographical measurement, pin-on-disc tribometry, atomic force microscopy in lateral force mode, X-ray photo-electron spectroscopy and continuum contact mechanics analysis under mixed non-Newtonian thermo-elastohydrodynamics is used to describe the formation of a tribo-film, as well as wear and frictional characteristics of the lubricant-surface system. The contribution of chemisorbed and physisorbed bonded tribo-film on the boundary coefficient of friction is ascertained at different physical scales. Therefore, the paper presents a novel multiscale analysis, promoting improved understanding of the complex interactions between mechanisms of friction, wear and surface chemistry

A neutron scattering study of water sorbed on silica

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