Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.

OBJECTIVE: Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. STUDY DESIGN: To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. RESULTS: After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. CONCLUSIONS: It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included

D-cycloserine-augmented one-session treatment of specific phobias in children and adolescents.

BACKGROUND: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7-14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7-10 years) would have greater benefits than adolescents (11-14 years), and that DCS effects would be stronger for participants with the greater within-session fear reduction during the OST. METHODS: Thirty-five children and adolescents were randomized to either OST combined with DCS (n = 17), or OST combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month following treatment. RESULTS: There were no significant pre- to post-treatment or follow-up benefits of DCS relative to placebo. Secondary analyses of age indicated that relative to PBO, DCS was associated with greater improvements for children (but not adolescents) on measures of severity at 1-month follow-up. Children in the DCS condition also showed significantly greater improvement to 1 month on global functioning relative to other groups. Conversely, adolescents had significant post-treatment benefits in the PBO condition on symptom severity measures relative to DCS, and adolescents in the DCS condition had significantly poorer functioning at 3 months relative to all other groups. Finally, there was a trend for within-session fear reduction to be associated with moderating effects of DCS, whereby greater reduction in fear was associated with greater functioning at one-month follow-up for children who received DCS, relative to PBO. LIMITATIONS: The study sample was small and therefore conclusions are tentative and require replication. CONCLUSIONS: Age and within-session fear reduction may be important moderators of DCS-augmented one-session exposure therapy, which requires testing in a fully powered randomized controlled trial

Relative fat oxidation is higher in children than adults

Background: Prepubescent children may oxidize fatty acids more readily than adults. Therefore, dietary fat needs would be higher for children compared with adults. The dietary fat recommendations are higher for children 4 to 18 yrs (i.e., 25 to 35% of energy) compared with adults (i.e., 20 to 35% of energy). Despite this, many parents and children restrict dietary fat for health reasons. Methods: This study assessed whether rates of fat oxidation are similar between prepubescent children and adults. Ten children (8.7 ± 1.4 yr, 33 ± 13 kg mean ± SD) in Tanner stage 1 and 10 adults (41.6 ± 8 yr, 74 ± 13 kg) were fed a weight maintenance diet for three days to maintain body weight and to establish a consistent background for metabolic rate measurements (all foods provided). Metabolic rate was measured on three separate occasions before and immediately after breakfast and for 9 hrs using a hood system (twice) or a room calorimeter (once) where continuous metabolic measurements were taken. Results: During all three sessions whole body fat oxidation was higher in children (lower RQ) compared to adults (mean RQ= 0.84 ± .016 for children and 0.87 ± .02, for adults, p < 0.02). Although, total grams of fat oxidized was similar in children (62.7 ± 20 g/24 hrs) compared to adults (51.4 ± 19 g/24 hrs), the grams of fat oxidized relative to calorie expenditure was higher in children (0.047 ± .01 g/kcal, compared to adults (0.032 ± .01 p < 0.02). Females oxidized more fat relative to calorie expenditure than males of a similar age. A two way ANOVA showed no interaction between gender and age in terms of fax oxidation. Conclusion: These data suggest that fat oxidation relative to total calorie expenditure is higher in prepubescent children than in adults. Consistent with current dietary guidelines, a moderate fat diet is appropriate for children within the context of a diet that meets their energy and nutrient needs. Originally published Nutrition Journal, Vol. 6, No. 19, Aug 200

Verticalization of bacterial biofilms

Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms of rod-shaped bacteria were observed at single-cell resolution and shown to develop from a disordered, two-dimensional layer of founder cells into a three-dimensional structure with a vertically-aligned core. Here, we elucidate the physical mechanism underpinning this transition using a combination of agent-based and continuum modeling. We find that verticalization proceeds through a series of localized mechanical instabilities on the cellular scale. For short cells, these instabilities are primarily triggered by cell division, whereas long cells are more likely to be peeled off the surface by nearby vertical cells, creating an "inverse domino effect". The interplay between cell growth and cell verticalization gives rise to an exotic mechanical state in which the effective surface pressure becomes constant throughout the growing core of the biofilm surface layer. This dynamical isobaricity determines the expansion speed of a biofilm cluster and thereby governs how cells access the third dimension. In particular, theory predicts that a longer average cell length yields more rapidly expanding, flatter biofilms. We experimentally show that such changes in biofilm development occur by exploiting chemicals that modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15 figure

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points

Interaction among general practitioners age and patient load in the prediction of job strain, decision latitude and perception of job demands. A Cross-sectional study

BACKGROUND: It is widely recognized and accepted that job strain adversely impacts the workforce. Individual responses to stressful situations can vary greatly and it has been shown that certain people are more likely to experience high levels of stress in their job than others. Studies highlighted that there can be age differences in job strain perception. METHODS: Cross-sectional postal survey of 300 Lithuanian general practitioners. Psychosocial stress was investigated with a questionnaire based on the Reeder scale. Job demands were investigated with the Karasek scale. The analysis included descriptive statistics; logistic regression beta coefficients to find out predictors and interactions between characteristics and predictors. RESULTS: Response rate was 66% (N = 197). Logistic regression as significant predictors for job strain assigned – duration of work in primary care; for job demands- age and duration of working in primary care; for decision latitude- age and patient load. The interactions with regard to job strain showed that GP's age and job strain are negatively associated to a low patient load. Lower decision latitude for older GP age is strongly related to higher patient load. Job demands and GP age are slightly positively related at low patient load. CONCLUSIONS: Lithuanian GP's have high patient load and are at risk of stress, they have high job demands and low decision latitude. Older GP's perceive less strain, lower job demands and higher decision latitude in case of low patient load. Young GP's decision latitude has week association to patient load. Regarding to the changes in patient load younger GP's perceive it more sensitively as changes in job demands

Protocol: developing a conceptual framework of patient mediated knowledge translation, systematic review using a realist approach

<p>Abstract</p> <p>Background</p> <p>Patient involvement in healthcare represents the means by which to achieve a healthcare system that is responsive to patient needs and values. Characterization and evaluation of strategies for involving patients in their healthcare may benefit from a knowledge translation (KT) approach. The purpose of this knowledge synthesis is to develop a conceptual framework for patient-mediated KT interventions.</p> <p>Methods</p> <p>A preliminary conceptual framework for patient-mediated KT interventions was compiled to describe intended purpose, recipients, delivery context, intervention, and outcomes. A realist review will be conducted in consultation with stakeholders from the arthritis and cancer fields to explore how these interventions work, for whom, and in what contexts. To identify patient-mediated KT interventions in these fields, we will search MEDLINE, the Cochrane Library, and EMBASE from 1995 to 2010; scan references of all eligible studies; and examine five years of tables of contents for journals likely to publish quantitative or qualitative studies that focus on developing, implementing, or evaluating patient-mediated KT interventions. Screening and data collection will be performed independently by two individuals.</p> <p>Conclusions</p> <p>The conceptual framework of patient-mediated KT options and outcomes could be used by healthcare providers, managers, educationalists, patient advocates, and policy makers to guide program planning, service delivery, and quality improvement and by us and other researchers to evaluate existing interventions or develop new interventions. By raising awareness of options for involving patients in improving their own care, outcomes based on using a KT approach may lead to greater patient-centred care delivery and improved healthcare outcomes.</p

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total