The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations

Background: The UK guideline recommends 3-yearly surveillance for patients with intermediate-risk (IR) adenomas. No study has examined whether or not this group has heterogeneity in surveillance needs. Objectives To examine the effect of surveillance on colorectal cancer (CRC) incidence; assess heterogeneity in risk; and identify the optimum frequency of surveillance, the psychological impact of surveillance, and the cost-effectiveness of alternative follow-up strategies. Design: Retrospective multicentre cohort study. Setting: Routine endoscopy and pathology data from 17 UK hospitals (n = 11,944), and a screening data set comprising three pooled cohorts (n = 2352), followed up using cancer registries. Subjects: Patients with IR adenoma(s) (three or four small adenomas or one or two large adenomas). Primary outcomes: Advanced adenoma (AA) and CRC detected at follow-up visits, and CRC incidence after baseline and first follow-up. Methods: The effects of surveillance on long-term CRC incidence and of interval length on findings at follow-up were examined using proportional hazards and logistic regression, adjusting for patient, procedural and polyp characteristics. Lower-intermediate-risk (LIR) subgroups and higher-intermediate-risk (HIR) subgroups were defined, based on predictors of CRC risk. A model-based cost–utility analysis compared 13 surveillance strategies. Between-group analyses of variance were used to test for differences in bowel cancer worry between screening outcome groups (n = 35,700). A limitation of using routine hospital data is the potential for missed examinations and underestimation of the effect of interval and surveillance. Results: In the hospital data set, 168 CRCs occurred during 81,442 person-years (pys) of follow-up [206 per 100,000 pys, 95% confidence interval (CI) 177 to 240 pys]. One surveillance significantly lowered CRC incidence, both overall [hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77] and in the HIR subgroup (n = 9265; HR 0.50, 95% CI 0.34 to 0.76). In the LIR subgroup (n = 2679) the benefit of surveillance was less clear (HR 0.62, 95% CI 0.16 to 2.43). Additional surveillance lowered CRC risk in the HIR subgroup by a further 15% (HR 0.36, 95% CI 0.20 to 0.62). The odds of detecting AA and CRC at first follow-up (FUV1) increased by 18% [odds ratio (OR) 1.18, 95% CI 1.12 to 1.24] and 32% (OR 1.32, 95% CI 1.20 to 1.46) per year increase in interval, respectively, and the odds of advanced neoplasia at second follow-up increased by 22% (OR 1.22, 95% CI 1.09 to 1.36), after adjustment. Detection rates of AA and CRC remained below 10% and 1%, respectively, with intervals to 3 years. In the screening data set, 32 CRCs occurred during 25,745 pys of follow-up (124 per 100,000 pys, 95% CI 88 to 176 pys). One follow-up conferred a significant 73% reduction in CRC incidence (HR 0.27, 95% CI 0.10 to 0.71). Owing to the small number of end points in this data set, no other outcome was significant. Although post-screening bowel cancer worry was higher in people who were offered surveillance, worry was due to polyp detection rather than surveillance. The economic evaluation, using data from the hospital data set, suggested that 3-yearly colonoscopic surveillance without an age cut-off would produce the greatest health gain. Conclusions: A single surveillance benefited all IR patients by lowering their CRC risk. We identified a higher-risk subgroup that benefited from further surveillance, and a lower-risk subgroup that may require only one follow-up. A surveillance interval of 3 years seems suitable for most IR patients. These findings should be validated in other studies to confirm whether or not one surveillance visit provides adequate protection for the lower-risk subgroup of intermediate-risk patients

Effect of thong style flip-flops on children’s barefoot walking and jogging kinematics

BACKGROUND: Thong style flip-flops are a popular form of footwear for children. Health professionals relate the wearing of thongs to foot pathology and deformity despite the lack of quantitative evidence to support or refute the benefits or disadvantages of children wearing thongs. The purpose of this study was to compare the effect of thong footwear on children’s barefoot three dimensional foot kinematics during walking and jogging. METHODS: Thirteen healthy children (age 10.3 ± 1.6 SD years) were recruited from the metropolitan area of Sydney Australia following a national press release. Kinematic data were recorded at 200 Hz using a 14 camera motion analysis system (Cortex, Motion Analysis Corporation, Santa Rosa, USA) and simultaneous ground reaction force were measured using a force platform (Model 9281B, Kistler, Winterthur, Switzerland). A three-segment foot model was used to describe three dimensional ankle, midfoot and one dimensional hallux kinematics during the stance sub-phases of contact, midstance and propulsion. RESULTS: Thongs resulted in increased ankle dorsiflexion during contact (by 10.9°, p; = 0.005 walk and by 8.1°, p; = 0.005 jog); increased midfoot plantarflexion during midstance (by 5.0°, p; = 0.037 jog) and propulsion (by 6.7°, p; = 0.044 walk and by 5.4°, p;= 0.020 jog); increased midfoot inversion during contact (by 3.8°, p;= 0.042 jog) and reduced hallux dorsiflexion during walking 10% prior to heel strike (by 6.5°, p; = 0.005) at heel strike (by 4.9°, p; = 0.031) and 10% post toe-off (by 10.7°, p; = 0.001). CONCLUSIONS: Ankle dorsiflexion during the contact phase of walking and jogging, combined with reduced hallux dorsiflexion during walking, suggests a mechanism to retain the thong during weight acceptance. Greater midfoot plantarflexion throughout midstance while walking and throughout midstance and propulsion while jogging may indicate a gripping action to sustain the thong during stance. While these compensations exist, the overall findings suggest that foot motion whilst wearing thongs may be more replicable of barefoot motion than originally thought

cGMP-Dependent Protein Kinase I Is Crucial for Angiogenesis and Postnatal Vasculogenesis

Background Endothelium-derived nitric oxide plays an important role for the bone marrow microenvironment. Since several important effects of nitric oxide are mediated by cGMP-dependent pathways, we investigated the role of the cGMP downstream effector cGMP-dependent protein kinase I (cGKI) on postnatal neovascularization. Methodology/Principal Findings In a disc neovascularization model, cGKI -/- mice showed an impaired neovascularization as compared to their wild-type (WT) littermates. Infusion of WT, but not cGKI -/- bone marrow progenitors rescued the impaired ingrowth of new vessels in cGKI-deficient mice. Bone marrow progenitors from cGKI -/- mice showed reduced proliferation and survival rates. In addition, we used cGKI alpha leucine zipper mutant (LZM) mice as model for cGKI deficiency. LZM mice harbor a mutation in the cGKI alpha leucine zipper that prevents interaction with downstream signaling molecules. Consistently, LZM mice exhibited reduced numbers of vasculogenic progenitors and impaired neovascularization following hindlimb ischemia compared to WT mice. Conclusions/Significance Our findings demonstrate that the cGMP-cGKI pathway is critical for postnatal neovascularization and establish a new role for cGKI in vasculogenesis, which is mediated by bone marrow-derived progenitors

Rede de suporte tecnológico domiciliar à criança dependente de tecnologia egressa de um hospital de saúde pública

A tecnologia aplicada à manutenção da vida cresceu muito nos últimos anos, com a incorporação de grandes avanços. A pesquisa e desenvolvimento aplicados às áreas de terapia intensiva pediátrica e neonatal favoreceram o surgimento da criança dependente de tecnologia (CDT), subordinada a artefatos tecnológicos e/ou farmacológicos necessários à sobrevivência. No Rio de Janeiro, o Instituto Fernandes Figueira (IFF) absorve essa clientela, estendendo o cuidado após a alta, atendendo-a em casa através do Programa de Atendimento Domiciliar Interdisciplinar (PADI), quando aplicável. O presente artigo apresenta a rede institucional envolvida com o atendimento da CDT, a forma com que a família assimila a tecnologia e torna-se gerente do cuidado, bem como a rede criada para aquisição de equipamento de apoio ao mesmo. Destacam-se também suas formas de obtenção e modos com que os diversos elementos articulam-se em função do fornecimento e manutenção do suporte tecnológico domiciliar necessário à sobrevivência desta criança dependente de tecnologia egressa do IFF.Due to major advances, life maintenance technology has improved remarkably over the past few years. Research and development in the field of intensive pediatric and neonatal care has prompted the appearance of a new type of patient: the Technologically-Dependent Child (TDC), a heterogeneous and loosely-defined group whose survival is dependent on technological and pharmacological artifacts. A Government pediatric hospital in Rio de Janeiro, the Instituto Fernandes Figueira (IFF/FIOCRUZ) cares for this group. When eligible patients return home, they are enrolled in the Interdisciplinary Home Care Program (PADI) run by this Institution. This paper discusses the life maintenance equipment purchase and maintenance network, analyzing how families absorb technology so as to become homecare givers and take decisions. Finally, it also examines how families, hospitals and funding agencies must cooperate in order to care for the TDC at home and at this Institution. This qualitative research project is based on observations and interviews conducted at hospital facilities and children being treated in their homes through the Interdisciplinary Home Care Program

Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin

Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*β1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA*β1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA*β1 cells and upregulation of the ECM protein Decorin in the neighbouring non-expressing cells. Experiments using inhibitors in explant models and genetic knock-downs in vivo reveal an integrin-Wnt7a-Decorin pathway that promotes proliferation and differentiation of neuroepithelial cells, and identify Decorin as a novel neurogenic factor in the central nervous system

System dynamics urban sustainability model for Puerto Aura in Puebla, Mexico

This paper reports on an on-going project on urban sustainability, the Puerto Aura in the region of the Valsequillo Lake in Puebla, Mexico. As part of the project, a simulation model was built to explore the dynamic interaction of the dimensions inherent in sustainable urban development. After reviewing literature on sustainable urban development (SUD) frameworks and tools, we identify key variables that intervene in SUD. We propose a System Dynamics model to simulate the dimensions that intervene in a sustainable development and to anticipate the consequences of the decision making process. The structure and inter-relationships of four sectors in the proposed model are described, the sustainability indicators in each sector explained. Preliminary conclusions are drawn stating that a complete run of the model simulating a 20 years horizon in monthly periods is expected when the full data from the Puerto Aura master plan becomes available