Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

Objective To examine the presence and extent of small study effects in clinical osteoarthritis research. Design Meta-epidemiological study. Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome. Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials. Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates. Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.

[Evaluation of a preschool program to promote phonological awareness and letter-sound correspondence--long-term effects in the prevention of dyslexia at the end of the 3rd and 4th grades]

The present study evaluates the long-term effects of a preschool training in phonological awareness and letter- sound correspondence.

Falcarinol is a covalent cannabinoid CB1 receptor antagonist and induces pro-allergic effects in skin

The skin irritant polyyne falcarinol (panaxynol, carotatoxin) is found in carrots, parsley, celery, and in the medicinal plant Panax ginseng. In our ongoing search for new cannabinoid (CB) receptor ligands we have isolated falcarinol from the endemic Sardinian plant Seseli praecox. We show that falcarinol exhibits binding affinity to both human CB receptors but selectively alkylates the anandamide binding site in the CB(1) receptor (K(i)=594nM), acting as covalent inverse agonist in CB(1) receptor-transfected CHO cells. Given the inherent instability of purified falcarinol we repeatedly isolated this compound for biological characterization and one new polyyne was characterized. In human HaCaT keratinocytes falcarinol increased the expression of the pro-allergic chemokines IL-8 and CCL2/MCP-1 in a CB(1) receptor-dependent manner. Moreover, falcarinol inhibited the effects of anandamide on TNF-alpha stimulated keratinocytes. In vivo, falcarinol strongly aggravated histamine-induced oedema reactions in skin prick tests. Both effects were also obtained with the CB(1) receptor inverse agonist rimonabant, thus indicating the potential role of the CB(1) receptor in skin immunopharmacology. Our data suggest anti-allergic effects of anandamide and that falcarinol-associated dermatitis is due to antagonism of the CB(1) receptor in keratinocytes, leading to increased chemokine expression and aggravation of histamine action.

Autologous stem cell transplantation: leukapheresis product has anti-angiogenic effects in vivo correlating with neutrophil-derived VEGFR1

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is used for the treatment of hemato-oncologic malignancies. In this study, we measured the effect of HDC/ASCT on plasma concentrations of antiangiogenic soluble vascular endothelial growth factor receptor 1 (sVEGFR1) and of leukapheresis products (LP) and patient serum on chick chorioallantoic (CAM) angiogenesis.

Cardiometabolic effects in caregivers of nursing home placement and death of their spouse with Alzheimer's disease

To test the hypothesis that cardiometabolic risk is attenuated when caregivers are relieved of caregiving stress when the caregiving recipient transitions out of the home.

Prospective ex-vivo study on thermal effects in human skin phototypes II, IV and VI: a comparison between the 808, 1064, 1210 and 1320-nm diode laser

Laser Assisted Skin Healing (LASH) was first introduced in 2001 by Capon and Mordon to prevent keloids and hypertrophic scars. LASH requires homogenous heating throughout the full thickness of the skin around the wound. However, LASH therapy with 808-nm diode laser is deemed to be only applicable for phototype I-IV due to melanin absorption. This prospective ex-vivo study aims to evaluate the thermal effects of different wavelengths (808, 1064, 1210 and 1320 nm) on human skin phototype II, IV and VI.