Effects of "10,000 steps Ghent": a whole-community intervention

BACKGROUND: Currently there is a great deal of interest in multistrategy community-based approaches to changing physical activity or health behaviors. The aim of this article is to describe the effectiveness of the physical activity promotion project "10,000 Steps Ghent" after 1 year of intervention. METHODS: A multistrategy community-based intervention was implemented in 2005 with follow-up measurements in 2006 to promote physical activity to adults. A local media campaign, environmental approaches, the sale and loan of pedometers, and several local physical activity projects were concurrently implemented. In 2005, 872 randomly selected subjects (aged 25 to 75), from the intervention community Ghent and 810 from a comparison community, participated in the baseline measurements. Of these, 660 intervention subjects and 634 comparison subjects completed the follow-up measurements in 2006. Statistical analyses were performed in 2006. RESULTS: After one year there was an increase of 8% in the number of people reaching the "10,000 steps" standard in Ghent, compared with no increase in the comparison community. Average daily steps increased by 896 (95% CI=599-1192) in the intervention community, but there was no increase in the comparison community (mean change -135 [95% CI= -432 to 162]) (F time x community=22.8, p<0.001). Results are supported by self-reported International Physical Activity Questionnaire (IPAQ) data. CONCLUSIONS: The "10,000 steps/day" message reached the Ghent population and the project succeeded in increasing pedometer-determined physical activity levels in Ghent, after 1 year of intervention.     

Association of thyroid hormone concentrations with levels of organochlorine compounds in cord blood of neonates

BACKGROUND: Thyroid hormones are important regulators of brain development. During critical periods of development, even transient disorders in thyroid hormone availability may lead to profound neurologic impairment. Animal experiments have shown that certain environmental pollutants, including heavy metals and organochlorine compounds such as polychlorinated biphenyls (PCBs) and dioxins, can interfere with thyroid hormone homeostasis. Whether these contaminants can affect circulating levels of thyroid hormones in humans is unclear, however, because the results of available studies are inconsistent. OBJECTIVES: The aim of the present study is to examine the possible relationships between concentrations of environmental pollutants and thyroid hormone levels in human umbilical cord blood. METHODS: We measured concentrations of environmental pollutants [including selected PCBs, dioxin-like compounds, hexachlorobenzene, p,p'-DDE (dichlorodiphenyldichloroethylene), cadmium, lead] and thyroid hormones in the cord blood of 198 neonates. RESULTS: A statistically significant inverse relationship between concentrations of organochlorine compounds and levels of both free triiodothyronine (fT3) and free thyroxine (fT4), but not thyroid-stimulating hormone, was observed. We found no association between concentrations of heavy metals and thyroid hormone levels. CONCLUSIONS: Our results suggest that environmental chemicals may affect the thyroid system of human neonates. Although the differences in fT3 and fT4 levels associated with the organochlorine compounds were within the normal range, the observed interferences may still have detrimental effects on the neurologic development of the individual children, given the importance of thyroid hormones in brain development.     

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

Objective

To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.

Participants

A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.

Design/methods

The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.

Results

The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO₂/FiO₂ < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).

Conclusions

Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

     

Functional Evaluation of an <Emphasis Type="Italic">IKBKG</Emphasis> Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia

Hypomorphic IKBKG mutations in males are typically associated with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Some mutations cause immunodeficiency without EDA (NEMO-ID). The immunological profile associated with these NEMO-ID variants is not fully documented. We present a 2-year-old patient with suspected immunodeficiency in which a hemizygous p.Glu57Lys IKBKG variant was identified. At the age of 1 year, he had an episode of otitis media that evolved into a bilateral mastoiditis (Pseudomonas spp). Hypogammaglobulinemia, specific (polysaccharide) antibody deficiency, and low switched memory B cell subsets were noticed. The mother was heterozygous for the variant but had no signs of incontinentia pigmenti. Patient peripheral blood mononuclear cells produced low amounts of IL-6 after stimulation with IL-1β, Pam₃CSK_4, and FSL-1. In patient fibroblasts, IκB-α was degraded normally upon stimulation with IL-1β or TNF-α. Transduction of wild-type and variant NEMO in NEMO^?/? deficient SV40 fibroblasts revealed a slight but significant reduction of IL-6 production upon stimulation with IL-1β and TNF-α. In conclusion, we demonstrated that p.Glu57Lys leads to specific immunological defects in vitro. No other pathogenic PID variants were identified through whole exome sequencing. As rare polymorphisms have been described in IKBKG and polygenic inheritance remains an option in the presented case, this study emphasizes the need for thorough functional and genetic evaluation when encountering and interpreting suspected disease-causing NEMO-ID variants.     

Gender, educational and age differences in meanings that underlie global self-rated health

Objectives

The single-item question on self-rated health has been widely used in surveys. This study aims to explore which frames of reference are used by respondents when answering this question, to describe differences in the used frame of reference according to gender, educational background and age, and to determine whether subgroup differences can be explained by differences in prior health experiences.

Methods

Face-to-face interviews were conducted in a sample of 310 adults who were asked to rate their health using a single-item question with closed-ended answering categories and to explain the reasons for the rating they gave with open-ended probes. Different indicators of prior health experiences were taken into account.

Results

Physical health problems were the most utilized referents. However, participants also mentioned reasons that go beyond the physical dimension of health. Subgroup differences were found. Prior health experiences partly explained subgroup differences for some referents, but not for others.

Conclusions

Investigators using the single question on self-rated health for comparing health across different population groups should be aware that the meaning of the question varies across different socio-demographic groups.     

Physical activity promotion in schools: which strategies do schools (not) implement and which socioecological factors are associated with implementation?

We studied the implementation and associated factors of strategies (e.g. sports after school and during lunch break, active schoolyards, active school commuting) and organizational principles (e.g. safe bike racks, pupil involvement) that facilitate the physical activity (PA)-promoting role of schools. Key representatives of 111 elementary and 125 secondary schools filled out an online survey. Less than half of the elementary schools organized sports during lunch-break or after school. In secondary schools the least implemented strategies were the promotion of active school commuting and after-school sports. In general pupil, parental and community involvement scored low. Better knowledge of community schools and having attended in-service training were associated with higher implementation scores in elementary and secondary schools. Better implementation of the strategies was found in larger schools. Participation in activities from the School Sports Association and more perceived interest from parents and the school board were also associated with higher implementation scores. In conclusion, knowledge of community schools and in-service training next to sufficient human resources are potential key factors to promote PA. Efforts are needed to convince and help schools to increase parental and pupil involvement and to build a policy on school-community partnerships.     

Regulation of the somatotropic axis by intensive insulin therapy during protracted critical illness

The catabolic state of critical illness has been linked to the suppressed somatotropic GH-IGF-binding protein (IGFBP) axis. In critically ill patients it has been demonstrated that, compared with the conventional approach, which only recommended insulin therapy when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood glucose levels below 6.1 mmol/liter with intensive insulin therapy almost halved intensive care mortality, acute renal failure, critical illness polyneuropathy, and bloodstream infections. Poor blood glucose control in diabetes mellitus has also been associated with low serum IGF-I levels, which can be increased by insulin therapy. We hypothesized that intensive insulin therapy would improve the IGF-I axis, possibly contributing to the clinical correlates of anabolism. Therefore, this study of 363 patients, requiring intensive care for more than 7 d and randomly assigned to either conventional or intensive insulin therapy, examines the effects of intensive insulin therapy on the somatotropic axis. Contrary to expectation, intensive insulin therapy suppressed serum IGF-I, IGFBP-3, and acid-labile subunit concentrations. This effect was independent of survival of the critically ill patient. Concomitantly, serum GH levels were increased by intensive insulin therapy. The suppression of IGF-I in association with the increased GH levels suggests GH resistance induced by intensive insulin therapy, which was reflected by the decreased serum GH-binding protein levels. Intensive insulin therapy did not affect IGFBP-3 proteolysis, which was markedly higher in protracted critically ill patients compared with healthy controls. Also, intensive insulin therapy did not suppress the urea/creatinine ratio, a clinical correlate of catabolism. In conclusion, our data suggest that intensive insulin therapy surprisingly suppressed the somatotropic axis despite its beneficial effects on patient outcome. GH resistance accompanied this suppression of the IGF-I axis. To what extent and through which mechanisms the changes in the GH-IGF-IGFBP axis contributed to the survival benefit under intensive insulin therapy remain elusive.     

Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities

Critically ill patients are at increased risk of fractures during rehabilitation, and can experience impaired healing of traumatic and surgical bone fractures. In addition, markers of bone resorption are markedly increased in critically ill patients, while markers of bone formation are decreased. In the current study, we have directly investigated the effect of critical illness on bone metabolism and repair. In a human in vitro model of critical illness, Fluorescence-activated cell sorting (FACS) analysis revealed an increase in circulating CD14+/CD11b+ osteoclast precursors in critically ill patient peripheral blood compared to healthy controls. In addition, the formation of osteoclasts was increased in patient peripheral blood mononuclear cell (PBMC) cultures compared to healthy controls, both in the presence and absence of osteoclastogenic factors receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Culturing PBMCs with 10% critically ill patient serum further increased osteoclast formation and activity in patient PBMCs only, and neutralization studies revealed that immunoglobulin G (IgG) antibody signaling through the immunoreceptor Fc receptor common γ chain III (FcRγIII) played an important role. When analyzing bone formation, no differences in osteogenic differentiation were observed using human periosteal-derived cells (hPDCs) treated with patient serum in vitro, but a decrease in the expression of vascular endothelial growth factor receptor 1 (VEGF-R1) suggested impaired vascularization. This was confirmed using serum-treated hPDCs implanted onto calcium phosphate scaffolds in a murine in vivo model of bone formation, where decreased vascularization and increased osteoclast activity led to a decrease in bone formation in scaffolds with patient serum-treated hPDCs. Together, these findings may help to define novel therapeutic targets to prevent bone loss and optimize fracture healing in critically ill patients.