Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test the hypothesis that mfBIA can be used to assess the anatomical, physiological, and metabolic state of skeletal muscles. mfBIA measurements focusing on impedance, resistance, reactance, phase angle, center frequency, membrane capacitance, and both extracellular and intracellular resistance were carried out. Eight healthy human control subjects and three selected cases were examined to demonstrate the extent to which this method may be used clinically, and in relation to training in sport. The electrode setup is shown to affect the mfBIA parameters recorded. Our recommendation is the use of noble metal electrodes in connection with a conductance paste to accommodate the typical BIA frequencies, and to facilitate accurate impedance and resistance measurements. The use of mfBIA parameters, often in conjunction with each other, can be used to reveal indications of contralateral muscle loss, extracellular fluid differences, contracted state, and cell transport/metabolic activity, which relate to muscle performance. Our findings indicate that mfBIA provides a noninvasive, easily measurable and very precise momentary assessment of skeletal muscles.

BACKGROUND: The identification of detrimental dietary patterns early in life may contribute to reducing the high incidence of fracture among healthy children. However, information based on a systematic review of the effect of various dietary foods and nutrients on fracture risk is lacking.

OBJECTIVE: We conducted a systematic review and meta-analysis of observational studies that examined the association between dietary intake or serum nutritional concentrations and childhood fractures.

DESIGN: Studies published up until June 2015 were identified on the basis of a literature search in Medline, Web of Science, and Scopus databases and by hand searching references by first author based on predefined inclusion criteria. A meta-analysis was carried out for case-control studies that examined differences in mean calcium intake in the case compared with the control group. Random-effects analysis was performed on the basis of the effect estimates derived as the differences in mean calcium intakes between cases and controls.

RESULTS: From a total of 1960 articles, we identified 18 observational studies, which were primarily case-control in design. Randomized controlled trials were absent, potentially because of unethical aspects related to the enrollment of children randomly assigned to certain dietary exposures and later fracture rates. Overall, fracture risk seemed to be associated with milk avoidance, high energy intake, high cheese intake, high intake of sugar-sweetened beverages, and no breastfeeding. The pooled effect size of the 9 case-control studies that examined mean calcium intake, which had appropriate data for the meta-analysis, showed no association (P = 0.99) with fair heterogeneity (I(2) = 69.3%, P = 0.001) with the use of the random-effects model.

CONCLUSIONS: On the basis of a systematic review of studies that were judged to be of high or medium quality, there is an indication that some nutritional factors seem to be associated with an increased fracture risk among children. The results may be inflated by selection bias, bias in diet reporting, or residual confounding. More high-quality longitudinal observational or intervention studies are needed on the subject.

BACKGROUND/AIM: To recommend Patient-Reported Outcome (PRO) questionnaires to measure hip and groin disability in young-aged to middle-aged adults.

METHODS: A systematic review was performed in June 2014. The methodological quality of the studies included was determined using the COnsensus-based Standards for the selection of health Measurement INstruments list (COSMIN) together with standardised evaluations of measurement properties of each PRO.

RESULTS: Twenty studies were included. Nine different questionnaires for patients with hip disability, and one for hip and groin disability, were identified. Hip And Groin Outcome Score (HAGOS), Hip Outcome Score (HOS), International Hip Outcome Tool-12 (IHOT-12) and IHOT-33 were the most thoroughly investigated PROs and studies including these PROs reported key aspects of the COSMIN checklist. HAGOS and IHOT-12 were based on studies with the least ratings of poor study methodology (23% and 31%, respectively), whereas IHOT-33 and HOS had a somewhat larger distribution (46%). These PROs all contain adequate measurement qualities for content validity (except HOS), test-retest reliability, construct validity, responsiveness and interpretability. No information or poor quality rating on methodological aspects made it impossible to fully evaluate the remaining PROs at present.

CONCLUSIONS: HAGOS, HOS, IHOT-12 and IHOT-33 can be recommended for assessment of young-aged to middle-aged adults with pain related to the hip joint, undergoing non-surgical treatment or hip arthroscopy. At present, HAGOS is the only PRO also aimed for young-aged to middle-aged adults presenting with groin pain and is recommended for use in this population.

TRIAL REGISTRATION NUMBER: CRD42014009995.

BACKGROUND: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC.

METHODS: Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.

RESULTS: The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59-6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64-5.32, p = 0.005).

CONCLUSION: Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC.

OBJECTIVE: To determine how settings for power and color Doppler ultrasound sensitivity vary on different high- and intermediate-range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints.

METHODS: Six different types of ultrasound machines were used. On each machine, the factory setting for superficial musculoskeletal scanning was used unchanged for both color and power Doppler modalities. The settings were then adjusted for increased Doppler sensitivity, and these settings were designated study settings. Eleven patients with rheumatoid arthritis (RA) with wrist involvement were scanned on the 6 machines, each with 4 settings, generating 264 Doppler images for scoring and color quantification. Doppler sensitivity was measured with a quantitative assessment of Doppler activity: color fraction. Higher color fraction indicated higher sensitivity.

RESULTS: Power Doppler was more sensitive on half of the machines, whereas color Doppler was more sensitive on the other half, using both factory settings and study settings. There was an average increase in Doppler sensitivity, despite modality, of 78% when study settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings, the grades for each of 7 of the patients varied between 0 and 3, while the grades for each of the other 4 patients varied between 0 and 2.

CONCLUSION: The effect of using different machines, Doppler modalities, and settings has a considerable influence on the quantification of inflammation by ultrasound in RA patients, and this must be taken into account in multicenter studies.

BACKGROUND: Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal POP exposures and increased BMI, waist circumference and change in BMI from 5 to 7 years of age, though only among girls with overweight mothers.

OBJECTIVES: In the same birth cohort, we investigated whether prenatal POP exposure was associated with serum concentrations of insulin and leptin among 5-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age.

METHODS: The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB), were measured in maternal pregnancy serum and breast milk. Children were followed-up at the age of 5 years where a non-fasting blood sample was drawn; 520 children (273 boys and 247 girls) had adequate serum amounts available for biomarker analyses by Luminex® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age 5 while taking into account confounders.

RESULTS: Girls with highest prenatal POP exposure were more likely to have high non-fasting insulin levels (PCBs 4th quartile: OR=3.71; 95% CI: 1.36, 10.01. DDE 4th quartile: OR=2.75; 95% CI: 1.09, 6.90. HCB 4th quartile: OR=1.98; 95% CI: 1.06, 3.69) compared to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed.

CONCLUSION: These findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic diseases by affecting the level of insulin.

OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare the efficacy and safety of reduced frequency dosing for aflibercept, relative to other approved and marketed vascular endothelial growth factor inhibitors for wet AMD, over 12 months.

RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed according to a pre-specified protocol, a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5 mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard NMA models were used to analyze change at 3 months, and fractional polynomial regression over 12 months. Safety data were analyzed using binomial models with a logistic link function.

RESULTS: Five trials formed a complete evidence network. At 3 months, all posologies of aflibercept and ranibizumab resulted in similar changes in BCVA. Over 12 months, approved posologies of aflibercept and ranibizumab resulted in similar changes from baseline, between 6.7 (95% credible interval [CrI], 5.5, 7.8) and 9.1 (8.1, 10.1) ETDRS letters; however, reduced frequency aflibercept was associated with a smaller change (1.8 letters, [-25.9, 29.2]). There was a trend towards a greater change in BCVA, with increasing frequency of dosing. All posologies performed similarly with respect to safety, and CrIs were wide.

CONCLUSIONS: Approved posologies of ranibizumab and aflibercept are similarly effective treatments for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.