Challenges to estimating vaccine impact using hospitalization data.

Because the real-world impact of new vaccines cannot be known before they are implemented in national programs, post-implementation studies at the population level are critical. Studies based on analysis of hospitalization rates of vaccine-preventable outcomes are typically used for this purpose. However, estimates of vaccine impact based on hospitalization data are particularly prone to confounding, as hospitalization rates are tightly linked to changes in the quality, access and use of the healthcare system, which often occur simultaneously with introduction of new vaccines. Here we illustrate how changes in healthcare delivery coincident with vaccine introduction can influence estimates of vaccine impact, using as an example reductions in infant pneumonia hospitalizations after introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. To this end, we explore the effect of changes in several metrics of quality and access to public healthcare on trends in hospitalization rates before (2008-09) and after (2011-12) PCV10 introduction in 2010. Changes in infant pneumonia hospitalization rates following vaccine introduction were significantly associated with concomitant changes in hospital capacity and the fraction of the population using public hospitals. Importantly, reduction of pneumonia hospitalization rates after PCV10 were also associated with the expansion of outpatient services in several Brazilian states, falling more sharply where primary care coverage and the number of health units offering basic and emergency care increased more. We show that adjustments for unrelated (non-vaccine) trends commonly employed by impact studies, such as use of single control outcomes, are not always sufficient for accurate impact assessment. We discuss several ways to identify and overcome such biases, including sensitivity analyses using different denominators to calculate hospitalizations rates and methods that track changes in the outpatient setting. Employing these practices can improve the accuracy of vaccine impact estimates, particularly in evolving healthcare settings typical of low- and middle-income countries

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

Soft 3D printing of thermoplastic polyurethane: Preliminary study

Thermoplastic polyurethane (TPU) is a highly elastic linear polymer composed of soft segments, usually flexible polyester or polyethers. It is widely used in 3D printing technologies using FFF (Fused Filament Fabrication), SLS (Selective Laser Sintering) or inkjet printing. Among these options, FFF is the most common. However, stiffness and hardness values of 3D printed TPU in filament form are higher that it would be desirable for some applications, which require softer materials. Therefore, it was seen necessary to find a new methodology for 3D printing soft TPU. In this way, the present study seeks to be first research study which focuses on the possibility of 3D printing TPU using DIW (Direct Ink Writing) technology with UV light. Firstly, the optimal 3D printing and curing parameters to print soft TPU are determined and then two different TPU formulations are 3D printed. It was concluded that the 3D printing of this TPU is challenging due to several points: (1) the viscosity of the TPU; (2) their main issue is their sticky behavior; and (3) shrinkage which takes place after the thermal treatment and for some applications, it might be problem. Despite that ,TPU appears to be a promising material to be used in different industrial applications.Peer ReviewedPostprint (author's final draft

3D printed surgical planning prototype manufactured by a hybrid multi-material 3D printer

Surgical planning is a preoperative method of pre-visualization that is carried out before or during a surgical intervention in order to achieve the best outcome. This can be done either image-based or hands-on. Regarding the first strategy, it is based on the use of medical images. However, it has a huge limitation, which is the difficulty of identifying anatomical structures (crucial for surgeons to make correct decisions) and distances between tissues without any physical support. This problem is overcome with the use of 3D models. Despite this important development, until nowadays most of the surgical planning prototypes were 3D printed either using the moulding technique, which might take several days, or high-cost technologies as is material jetting. That is why, the present manuscript seeks to solve the problems arose by the use of a hybrid-multi material 3D printer which can not only use several materials at the time, but also two 3D printing technologies. The prototype introduced in this study is a neuroblastoma, a common cancer among children.Peer ReviewedPostprint (published version

Control of telomere length by a trimming mechanism that involves generation of t-circles

Telomere lengths are maintained in many cancer cells by the ribonucleoprotein enzyme telomerase but can be further elongated by increasing telomerase activity through the overexpression of telomerase components. We report here that increased telomerase activity results in increased telomere length that eventually reaches a plateau, accompanied by the generation of telomere length heterogeneity and the accumulation of extrachromosomal telomeric repeat DNA, principally in the form of telomeric circles (t-circles). Telomeric DNA was observed in promyelocytic leukemia bodies, but no intertelomeric copying or telomere exchange events were identified, and there was no increase in telomere dysfunction-induced foci. These data indicate that human cells possess a mechanism to negatively regulate telomere length by trimming telomeric DNA from the chromosome ends, most likely by t-loop resolution to form t-circles. Additionally, these results indicate that some phenotypic characteristics attributed to alternative lengthening of telomeres (ALT) result from increased mean telomere length, rather than from the ALT mechanism itself

Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study

Background: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. Methods and Findings: We obtained weekly virology and underlying cause-of-death mortality time series for 2005–2009 for 20 countries covering ,35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%–85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000–249,000 respiratory deaths to influenza in an average prepandemic season, with only 19% in persons ,65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010–2012). Conclusions: We estimate that 2009 global pandemic respiratory mortality was ,10-fold higher than the World Health Organization’s laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons ,65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics

The commissioning of a hybrid multi-material 3D printer

Additive Manufacturing (AM) has rapidly become an important technology in both research and industry. This development has allowed the evolution of 3D printers which are able to print complex geometries at low costs and faster than traditional methods. Despite this, most of these printers are either only for using one material or one technology. This limits a lot its use in different sectors such as aeronautics, automotive or health, because multi-material prototypes are needed. For example, surgeons need surgical planning prototypes for preoperative planning. These 3D printed prototypes have mainly been manufactured using just one technology. As a result, the prototypes have some main limitations: (1) do not actually mimic the anatomical structures of the human body, (2) high costs specially for Material Jetting and Powder Bed Fusion AM technologies. Therefore, the aim of present manuscript is the design, development, and commissioning of a hybrid multi-material 3D printer.Peer ReviewedObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i InfraestructuraObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Specialist laboratory networks as preparedness and response tool - The emerging viral diseases-expert laboratory network and the chikungunya outbreak, Thailand, 2019

We illustrate the potential for specialist laboratory networks to be used as preparedness and response tool through rapid collection and sharing of data. Here, the Emerging Viral Diseases-Expert Laboratory Network (EVD-LabNet) and a laboratory assessment of chikungunya virus (CHIKV) in returning European travellers related to an ongoing outbreak in Thailand was used for this purpose. EVD-LabNet rapidly collected data on laboratory requests, diagnosed CHIKV imported cases and sequences generated, and shared among its members and with the European Centre for Disease Prevention and Control. Data across the network showed an increase in CHIKV imported cases during 1 October 2018-30 April 2019 vs the same period in 2018 (172 vs 50), particularly an increase in cases known to be related to travel to Thailand (72 vs 1). Moreover, EVD-LabNet showed that strains were imported from Thailand that cluster with strains of the ECSA-IOL E1 A226 variant emerging in Pakistan in 2016 and involved in the 2017 outbreaks in Italy. CHIKV diagnostic requests increased by 23.6% between the two periods. The impact of using EVD-LabNet or similar networks as preparedness and response tool could be improved by standardisation of the collection, quality and mining of data in routine laboratory management systems