Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy

BACKGROUND: We describe the risk indicators for oral mucositis (OM) in paediatric oncology patients hospitalised in the Institut Gustave Roussy (Villejuif-Paris) and treated with alkylant chemotherapy with autologous peripheral blood progenitor cells. METHODS: The sample was selected using PIGAS software. Three groups of subjects received different chemotherapy regimens: A. Melphalan, B. Busulfan and C. other alkylant protocols. The degree of mucositis was recorded by CTC version 2.0 (Common Toxicity Criteria). Descriptive statistics were performed. The association between mucositis and risk indicator variables was tested using a χ(2 )test. The association between case status and covariates was tested using unconditional logistic regression analysis. RESULTS: Of the 337 children enrolled, 241 showed mucositis (group 1) and 96 did not show mucositis (group 2) during alkylant chemotherapy. There was a higher prevalence of male patients in both groups. The three different chemotherapy regimen groups are correlated with the appearance of oral mucositis (χ(2 )= 22.42, p < 0.01). Weight loss was higher in group 1 (χ(2 )= 6.31, p = 0.01). The duration of aplasia was lower in the Busulfan protocol (7.5 days) than in the Melphalan group (9.3 days) or the other regimens (8.6 days). The use of Bufulfan(® )was directly associated with case status (presence of oral mucositis): odds ratio [OR] = 2.1 and confidence interval [95%CI] = 1.3–3.0. Also, occurrences of germinal tumours and secondary bacterial infections were directly linked with case status: [OR] = 1.4 and 1.8, confidence interval [95%CI] = 1.2 – 1.7 and 1.1 – 2.5, respectively. CONCLUSION: The presence of OM was associated with the three different chemotherapy regimens considered; in particularly patients treated with Busulfan had the highest prevalence

A qualitative investigation of lived experiences of long-term health condition management with people who are food insecure.

Background: As more people are living with one or more chronic health conditions, supporting patients to become activated, self-managers of their conditions has become a key health policy focus both in the UK and internationally. There is also growing evidence in the UK that those with long term health conditions have an increased risk of being food insecure. While international evidence indicates that food insecurity adversely affects individual's health condition management capability, little is known about how those so affected manage their condition(s) in this context. An investigation of lived experience of health condition management was undertaken with food insecure people living in north east Scotland. The study aimed to explore the challenges facing food insecure people in terms of, i. their self-care condition management practices, and ii. disclosing and discussing the experience of managing their condition with a health care professional, and iii. Notions of the support they might wish to receive from them. Methods: Twenty in-depth interviews were conducted with individuals attending a food bank and food pantry in north east Scotland. Interview audio recordings were fully transcribed and thematically analysed. Results: Individuals reporting multiple physical and mental health conditions, took part in the study. Four main themes were identified i.e.: 1. food practices, trade-offs and compromises, that relate to economic constraints and lack of choice; 2. illness experiences and food as they relate to physical and mental ill-health; 3. (in) visibility of participants' economic vulnerability within health care consultations; and 4. perceptions and expectations of the health care system. Conclusions: This study, the first of its kind in the UK, indicated that participants' health condition management aspirations were undermined by the experience of food insecurity, and that their health care consultations in were, on the whole, devoid of discussions of those challenges. As such, the study indicated practical and ethical implications for health care policy, practice and research associated with the risk of intervention-generated health inequalities that were suggested by this study. Better understanding is needed about the impact of household food insecurity on existing ill health, wellbeing and health care use across the UK

Entering and Exiting the Medicare Part D Coverage Gap: Role of Comorbidities and Demographics

Background: Some Medicare Part D enrollees whose drug expenditures exceed a threshold enter a coverage gap with full cost-sharing, increasing their risk for reduced adherence and adverse outcomes. Objective: To examine comorbidities and demographic characteristics associated with gap entry and exit. Design: We linked 2005-2006 pharmacy, outpatient, and inpatient claims to enrollment and Census data. We used logistic regression to estimate associations of 2006 gap entry and exit with 2005 medical comorbidities, demographics, and Census block characteristics. We expressed all results as predicted percentages. PATIENTS: 287,713 patients without gap coverage, continuously enrolled in a Medicare Advantage Part D (MAPD) plan serving eight states. Patients who received a low-income subsidy, could not be geocoded, or had no 2006 drug fills were excluded. Results: Of enrollees, 15.9% entered the gap, 2.6% within the first 180 days; among gap enterers, only 6.7% exited again. Gap entry was significantly associated with female gender and all comorbidities, particularly dementia (39.5% gap entry rate) and diabetes (28.0%). Among dementia patients entering the gap, anti-dementia drugs (donepezil, memantine, rivastigmine, and galantamine) and atypical antipsychoticmedications (risperidone, quetiapine, and olanzapine) together accounted for 40% of pre-gap expenditures. Among diabetic patients, rosiglitazone accounted for 7.2% of pre-gap expenditures. Having dementia was associated with twice the risk of gap exit. Conclusions: Certain chronically ill MAPD enrollees are at high risk of gap entry and exposure to unsubsidized medication costs. Clinically vulnerable populations should be counseled on how to best manage costs through drug substitution or discontinuation of specific, non-essential medications. © 2010 Society of General Internal Medicine

Preconceptional factors associated with very low birthweight delivery in East and West Berlin: a case control study

BACKGROUND: Very low birthweight, i.e. a birthweight < 1500 g, is among the strongest determinants of infant mortality and childhood morbidity. To develop primary prevention approaches to VLBW birth and its sequelae, information is needed on the causes of preterm birth, their personal and social antecedents, and on conditions associated with very low birthweight. Despite the growing body of evidence linking sociodemographic variables with preterm delivery, little is known as to how this may be extrapolated to the risk of very low birthweight. METHODS: In 1992, two years after the German unification, we started to recruit two cohorts of very low birthweight infants and controls in East and West Berlin for a long-term neurodevelopmental study. The present analysis was undertaken to compare potential preconceptional risk factors for very low birthweight delivery in a case-control design including 166 mothers (82 East vs. 84 West Berlin) with very low birthweight delivery and 341 control mothers (166 East vs. 175 West). RESULTS: Multivariate logistic regression analysis was used to assess the effects of various dichotomous parental covariates and their interaction with living in East or West Berlin. After backward variable selection, short maternal school education, maternal unemployment, single-room apartment, smoking, previous preterm delivery, and fetal loss emerged as significant main effect variables, together with living in West Berlin as positive effect modificator for single-mother status. CONCLUSION: Very low birthweight has been differentially associated with obstetrical history and indicators of maternal socioeconomic status in East and West Berlin. The ranking of these risk factors is under the influence of the political framework

Effect of Anti-Obesity Drug on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45) for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors

Sexual Priming, Gender Stereotyping, and Likelihood to Sexually Harass: Examining the Cognitive Effects of Playing a Sexually-Explicit Video Game

The present study examines the short-term cognitive effects of playing a sexually explicit video game with female “objectification” content on male players. Seventy-four male students from a university in California, U.S. participated in a laboratory experiment. They were randomly assigned to play either a sexually-explicit game or one of two control games. Participants’ cognitive accessibility to sexual and sexually objectifying thoughts was measured in a lexical decision task. A likelihood-to-sexually-harass scale was also administered. Results show that playing a video game with the theme of female “objectification” may prime thoughts related to sex, encourage men to view women as sex objects, and lead to self-reported tendencies to behave inappropriately towards women in social situations

Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells

Although it is well known that RET gene is strongly activated by retinoic acid (RA) in neuroblastoma cells, the mechanisms underlying such activation are still poorly understood. Here we show that a complex series of molecular events, that include modifications of both chromatin and DNA methylation state, accompany RA-mediated RET activation. Our results indicate that the primary epigenetic determinants of RA-induced RET activation differ between enhancer and promoter regions. At promoter region, the main mark of RET activation was the increase of H3K4me3 levels while no significant changes of the methylation state of H3K27 and H3K9 were observed. At RET enhancer region a bipartite chromatin domain was detected in unstimulated cells and a prompt demethylation of H3K27me3 marked RET gene activation upon RA exposure. Moreover, ChIP experiments demonstrated that EZH2 and MeCP2 repressor complexes were associated to the heavily methylated enhancer region in the absence of RA while both complexes were displaced during RA stimulation. Finally, our data show that a demethylation of a specific CpG site at the enhancer region could favor the displacement of MeCP2 from the heavily methylated RET enhancer region providing a novel potential mechanism for transcriptional regulation of methylated RA-regulated loci

Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis

BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-–mediated mode of action was specifically explored. RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe