469 research outputs found

    Optimization and de-escalation of biologicals in patients with crohn’s disease

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    The role of affective teacher–student relationships in bullying and peer victimization: A multilevel meta-analysis

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    This meta-analysis synthesizes evidence about the associations of affective teacher–student relationships with bullying perpetration and peer victimization. A systematic database search resulted in 65 primary studies (k) that met the inclusion criteria. The final sample included 185,881 students from preschool to high school. Separate multilevel analyses were conducted for bullying perpetration (k = 25, N = 97,627) and peer victimization (k = 57, N = 151,653). Results showed small to medium, negative overall correlations between teacher-student relationship quality and both bullying perpetration (r = −.17, 95% CI [−.21, −.14]) and peer victimization (r = −.14, 95% CI [−.17, −.11]). Teacher-student relationship quality was also related to less subsequent peer victimization (b = −0.05, 95% CI [−0.08, −0.02]). Associations between teacher-student relationship quality and bullying were stronger for ethnic minority students and when the same informant reported about both variables. Associations with peer victimization were stronger for negative (e.g., conflict) than for positive (e.g., closeness) relationship indicators and when the same informant was used for both variables. Generally, findings demonstrate that higher-quality teacher-student relationships are related to less bullying perpetration and less peer victimization. Hence, promoting positive and minimizing negative teacher-student relationships may help to tackle school-based bullying and peer victimization

    Early fecal calprotectin levels at week 8 may guide therapeutic decisions on Ustekinumab therapy in patients with Crohn’s disease

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    Background: Response evaluation after induction therapy with ustekinumab (UST) in Crohn’s disease (CD) is important for decisions on maintenance therapy. We aimed to assess the potential of fecal calprotectin (FC) levels to predict endoscopic response at week 16. Methods: CD patients with FC &gt;100 µg/g and endoscopic active disease (SES-CD&gt; 2, Rutgeerts’ score ≥ i2) at initiation of UST therapy were enrolled. FC was determined at weeks 0, 2, 4, 8 and 16 and patients underwent a colonoscopy at week 16. The primary outcome was an endoscopic response at week 16 (SES-CD score ≥50% decrease or a decrease of ≥1 points in Rutgeerts’ score). The optimal cut-off levels of FC and change in FC to predict endoscopic response were determined using ROC statistics. Results: 59 CD patients were included. Endoscopic response was observed in 21/59 (36%) patients. The diagnostic accuracy for FC levels at week 8 to predict endoscopic response at week 16 showed a predictive value of 0.71. A decrease in FC levels ≥500 µg/g between baseline at week 8 indicates endoscopic response (PPV = 89%), whereas absence of any decrease indicates endoscopic non-response after induction (NPV = 81%). Conclusions: Continuation of UST therapy without endoscopic response evaluation may be considered in patients with a decrease in FC levels of ≥500 µg/g at week 8. The decision on continuation of UST therapy or therapy optimization needs reconsideration in patients without a decrease of FC level. In all other patients, endoscopic response evaluation of induction therapy remains essential for therapeutic decisions.</p

    Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours.

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    Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 micrograms/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed. Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhIL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 micrograms/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated. In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent

    The impact of trial stage, developer involvement and international transferability on universal social and emotional learning programme outcomes: a meta-analysis

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    This study expands upon the extant prior meta-analytic literature by exploring previously theorised reasons for the failure of schoolbased, universal social and emotional learning (SEL) programmes to produce expected results. Eighty-nine studies reporting the effects of school-based, universal SEL programmes were examined for differential effects on the basis of: (1) stage of evaluation (efficacy or effectiveness); (2) involvement from the programme developer in the evaluation (led, involved, independent); and (3) whether the programme was implemented in its country of origin (home or away). A range of outcomes were assessed including: social-emotional competence, attitudes towards self, pro-social behaviour, conduct problems, emotional distress, academic achievement and emotional competence. Differential gains across all three factors were shown, although not always in the direction hypothesised. The findings from the current study demonstrate a revised and more complex relationship between identified factors and dictate major new directions for the field

    Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients

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    Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocker cyclosporin A (CsA). Now we tested the potent alternative orally applicable non-immunosuppressive P-gp blocker GF120918. Six patients received one course of oral paclitaxel of 120 mg/m2 in combination with 1000 mg oral GF120918 (GG918, GW0918). Patients received intravenous (i.v.) paclitaxel 175 mg/m2 as a 3-hour infusion during subsequent courses. The mean area under the plasma concentration–time curve (AUC) of paclitaxel after oral drug administration in combination with GF120918 was 3.27 ± 1.67 μM.h. In our previously performed study of 120 mg/m2 oral paclitaxel in combination with CsA the mean AUC of paclitaxel was 2.55 ± 2.29 μM.h. After i.v. administration of paclitaxel the mean AUC was 15.92 ± 2.46 μM.h. The oral combination of paclitaxel with GF120918 was well tolerated. The increase in systemic exposure to paclitaxel in combination with GF120918 is of the same magnitude as in combination with CsA. GF120918 is a good and safe alternative for CsA and may enable chronic oral therapy with paclitaxel. © 2001 Cancer Research Campaign http://www.bjcancer.co

    A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma

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    Advanced adenocarcinoma of the pancreas has a very poor prognosis. The aim of this study was to assess the efficacy and tolerability of a combination of the chemotherapeutic agents gemcitabine and raltitrexed. Chemonaïve patients with advanced adenocarcinoma of the pancreas were treated with a combination of raltitrexed (3.5 mg m−2 on day 1 of a 21-day treatment cycle) and gemcitabine (800 mg m−2 intravenously (i.v.) on days 1 and 8 of a 21-day cycle). Between April 2000 and February 2003, 27 patients were enrolled onto the study. The mean duration of treatment was 11 weeks. Four of 27 patients experienced at least one episode of grade 3 or 4 neutropenia. One patient with grade 4 neutropenia died due to sepsis. Four of 27 patients experienced grade 4 diarrhoea. There was one partial remission (4%) and 12 patients experienced disease stabilisation (44%). The 6-month and 1-year survival rates were 37 and 11%, respectively. Symptomatic benefit occurred in seven (26%) patients. We conclude that a combination of raltitrexed and gemcitabine, using the schedule and doses in this study, cannot be recommended for patients with advanced pancreatic cancer
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