A survey of fecal samples found enterococcal excretion in 82% of 388 bank voles (Clethrionomys glareolus), 92% of 131 woodmice (Apodemus sylvaticus), and 75% of 165 badgers (Meles meles). ...Vancomycin-resistant enterococci, all Enterococcus faecium of vanA genotype, were excreted by 4.6% of the woodmice and 1.2% of the badgers, but by none of the bank voles.
Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn's disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ...ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1 year of treatment.
Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index CDAI reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.
Results: Thirteen RCTs were identified. Ustekinumab 90 mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300 mg. For clinical remission, ustekinumab 90 mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300 mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.
Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1 year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.
BackgroundPreterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk ...factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.Methods and findingsWe conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 95% CI: 0.97; 1.00, p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 95% CI: 1.03; 2.08, p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.ConclusionsThis study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.
Radiotherapy treatment planning calculations of the chest wall are complex due to missing tissue, the thin chest wall and the presence of lung. The accuracy of calculated dose is dependent on the ...type of algorithm employed. This work evaluates a collapsed cone (CC) and a pencil beam (PB) convolution model for radiotherapy planning of the chest wall. Various irradiation geometries simulating the chest wall have been examined and calculations were compared with measurements with an ionization chamber in epoxy resin water substitute and in low-density lung substitute blocks. A retrospective treatment planning study comprising 6 patients was carried out to evaluate the differences in the dose distributions and monitor units predicted by the two algorithms. The calculated dose in unit density medium was within +/-1% for the CC model and up to +/-2% for PB. In low density medium and under full scatter conditions, CC overestimated the dose by 1% whereas PB overestimated the dose by 9%. In the tangential irradiation geometry with water and lung media, the PB overestimated dose to the isocentre by up to 10%, whereas the dose from CC was within 3%. From the treatment planning study calculated monitor units (MU) and doses were consistent with the experimental findings. The CC model is more accurate for radiotherapy treatment planning of the chest wall and especially when there is significant involvement of lung tissue.
Background & Aims: Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease ...and compared them with characteristics of adult-onset disease in patients in Scotland. Methods: Anatomic locations and behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease CD, 99 ulcerative colitis UC, 41 IBD type unclassified IBDU diagnosed before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC) IBD using the Montreal classification. Results: At the time of diagnosis in children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in 36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral characteristics progressed; 24% of children developed stricturing or penetrating complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio OR, 3.32; 95% confidence interval CI, 1.86–5.92). Compared with adults, childhood-onset disease was characterized by a “panenteric” phenotype (ileocolonic plus upper GI L3+L4; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45–40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03–0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21–0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults ( P < .0001; OR, 5.08; 95% CI, 2.73–9.45); 46% of the children progressed to develop extensive colitis during follow-up. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true for UC. Conclusions: Childhood-onset IBD is characterized by extensive intestinal involvement and rapid early progression.
Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial ...hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.
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