Anti-tumor necrosis factor (TNF) therapy has revolutionized the medical treatment of the inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis. Twenty years ago, infliximab became the first anti-TNF agent approved for IBD. Data from randomized controlled trials, large observational cohort studies, postmarketing registries, and meta-analyses show that infliximab is a very effective treatment for moderate to severe IBD with a good safety profile. Infliximab has been also used to treat pouchitis following an ileal pouch–anal anastomosis (IPAA) after restorative proctocolectomy and to prevent postoperative recurrence following an ileocolonic resection for CD with good results. Nevertheless, up to 30% of patients show no clinical benefit following induction and up to 50% lose response over time. Both these unwanted outcomes can be largely explained by inadequate drug concentrations and frequently by the development of antibodies to infliximab. Loss of response can be managed efficiently and often prevented by applying therapeutic drug monitoring. Recently, the first biosimilars of infliximab have been approved and are utilized in clinical practice with comparable efficacy and safety with the originator. This review will mainly focus on the efficacy of infliximab in IBD.

This cover sheet may not be removed from the document.Please scroll down to view the document. Methods: Patients about to undergo orthodontic treatment using upper and lower fixed appliances were recruited into this 2-arm parallel design RCT in 9 trial sites in the South West of England. They were randomly allocated to one of two groups, namely the experimental chewing gum group or control ibuprofen group. Eligibility criteria included patients undergoing upper and lower fixed appliance therapy, aged 11-17 years, who were able to use ibuprofen and chewing gum. The primary outcome measure was pain experienced using a mean of three recordings on a scale of 0-10. Secondary outcome measures were pain experienced in the subsequent three days, again after the first archwire change, the use of ibuprofen and appliance breakages. Pain scores were recorded using a questionnaire and posted to a collection centre by the patient. Randomisation was by means of a central telephone service and comprised computer-generated pseudo-random numbers used to generate a sequential allocation list, with permuted blocks of variable size (two and four) and stratified by centre. Neither clinicians nor the patients were blinded to the intervention. Patients in the control group were only permitted to use ibuprofen whilst patients in the experimental group were allowed to use ibuprofen only if they didn't get sufficient analgesia from using chewing gum.Data were analysed using the principle of Intention to Treat with multilevel modelling to reflect the structured nature of the data (scores within patient within site).Results: 1000 patients were recruited and randomised in a ratio of 1:1 to either the chewing gum or ibuprofen (control) groups. The male to female ratio was similar in both groups 3 (chewing gum 35.6%: 64.4%, ibuprofen 38.4%: 61.6%). The pain questionnaire response rates were good at approximately 84% and 83% following appliance placement (chewing gum group 419: ibuprofen group 407) and 70% and 71% following the first archwire change (chewing gum group 343: ibuprofen group 341). The primary outcome was similar for the two groups: mean pain 4.31 in the experimental (chewing gum) group and 4.17 in the control (ibuprofen) group, difference 0.14 (95% confidence interval -0.13 to 0.41). There was a suggestion that the relative pain scores for the two groups changed over time, with the chewing gum group experiencing slightly more pain on the day of bond-up and less on the subsequent three days; however, the differences were not of clinical importance. There were no significant differences for the period following archwire change. The reported use of ibuprofen was less in the chewing gum group than in the control ibuprofen group:following appliance placement the mean number of occasions ibuprofen was used was 2.1 in the chewing gum group and 3.0 in the ibuprofen group (adjusted difference -0.96 (95%CI -0.75 to -1.17, p<0.001)); following archwire change the analogous figures were 0.8 and 1.5 occasions (difference -0.65 (-0.44 to -0.86,...

The aim of this study was to determine which of two occlusal indices were the most appropriate for use in the assessment of orthognathic outcome. The indices used were the Peer Assessment Rating (PAR) Index and the Index of Treatment Complexity, Outcome, and Need (ICON). These indices were validated against the subjective assessments of treatment outcome and treatment improvement obtained from a panel of experienced orthodontic consultants. For the subjective assessment, intraexaminer agreement for ranking treatment outcome, from patient study models (30 models), was good. Interexaminer agreement for ranking treatment outcome, in the same way, was good or moderate. Intraexaminer agreement for ranking treatment improvement (30 start and finish pairs of models) was very good or good. Interexaminer agreement for ranking treatment improvement ranged from good to fair. All the patient study models were scored using PAR and ICON. The level of correlation between PAR and ICON scores of treatment outcome and the subjective ranking of treatment outcome was significant (P < 0.001). The level of correlation between PAR and ICON scores of treatment improvement and the subjective ranking of treatment improvement was also significant (P < 0.001). It is concluded that both PAR and ICON are suitable indices for assessing the clinical outcome of combined orthodontic treatment and orthognathic surgery.

Persistent digit sucking habits are an important aetiological factor for malocclusion, and patients with persistent habits are frequently referred for orthodontic treatment. The present study investigated the effects of digit sucking habits on vertical and anteroposterior dentofacial characteristics by employing a cephalometric analysis of patients with persistent digit sucking habits compared with patients without such habits. Significant differences were seen in maxillary prognathism, relative prognathism, maxillary incisor angulation, interincisal angle, maxillary length and maxillary plane angulation. No significant differences were observed for mandibular prognathism or length, maxillary mandibular plane angle, cranial base measurements nor any measurement of facial height. The digit sucking group were also found to have a larger variation of lower incisor angulation than the controls, although no significant difference in the mean value for this variable was detected. It is concluded that persistent digit sucking may cause largely dentoalveolar change, together with some minor effects on the skeletal pattern.

e13006 Background: The 5-year survival for patients (pts) with glioblastoma (GBM) is low at approximately 3%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remain the standard of care. The optimal duration of therapy with TMZ is unknown, though treatment periods of 6 months (mo), 12 mo and longer have been utilized. Whether or not there is a benefit with longer treatment duration is controversial. Methods: A retrospective chart review of all pts diagnosed with GBM who were treated at a regional referral center was conducted with data obtained from their electronic medical records. These pts were treated with TMZ for up to 2 years between January 1, 2002 and December 31, 2011. Survival was calculated as the time from initial surgical diagnosis until death. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) as well as the overall survival (OS) distribution of pts after treatment. The results were compared to historical controls and data from previous clinical trials of pts treated up to 1 year. Results: Data from 56 pts were evaluated, the majority of whom had gross total resection and had external pathology review confirming the diagnosis of GBM. The OS probability was 55.4% (SE = 0.068) at 1 year, 26.9% (SE = 0.067) at 2 years and 20.1% (SE = 0.065) at 3 years. The median PFS time in this study group was 8 mo (95% CI = 4.0 – 9.0 mo). The probability of no progression at 2 years was 8.6% (SE = 0.05). Seven pts (12.5%) were treated with TMZ for 2 years. The probability of disease progression at 2 years among these pts was 33.3% with a median time-to-progression of 20 mo (95% CI = 5.0-28.0). These patients showed an increased survival probability at 3 years compared to pts who did not receive the 2 year treatment of TMZ (log-rank test Chi-square = 12.4, p = 0.0004). Conclusions: This analysis suggests that there may be an advantage for a longer duration of TMZ therapy in pts with GBM. In this review, treatment with TMZ for 2 years was associated with an increased survival benefit. While we consider the sample size to be too small for generalization, a prospective/multicenter study with a larger sample size might better evaluate the question of duration of TMZ therapy, particularly if both clinical and basic science data are paired.