Improvement in medication education in a pediatric subspecialty practice

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA).</p> <p>Methods</p> <p>This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired <it>t</it>-test (critical <it>P </it>value < 0.05) was performed on individuals who answered both questionnaires.</p> <p>Results</p> <p>There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (<it>P </it>< 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility.</p> <p>Conclusions</p> <p>MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.</p

Gastroesophageal reflux disease in 2006: The imperfect diagnosis

There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.&lt;p&gt;&lt;/p&gt; Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).&lt;p&gt;&lt;/p&gt; Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.&lt;p&gt;&lt;/p&gt; Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Aromatase expression is increased in BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression <it>in vitro</it>. Our objective was to characterise aromatase gene <it>(CYP19A1) </it>and its promoter expression in breast adipose and ovarian tissue in <it>BRCA1 </it>mutation carriers and unaffected controls.</p> <p>Methods</p> <p>We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.</p> <p>Results</p> <p>We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of <it>BRCA1 </it>mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.</p> <p>Conclusion</p> <p>Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in <it>BRCA1 </it>mutation carriers.</p

Establishing a follow-up of the Swiss MONICA participants (1984-1993): record linkage with census and mortality data

BACKGROUND: To assess the feasibility and quality of an anonymous linkage of 1) MONICA (MONItoring of trends and determinants in CArdiovscular disease, three waves between 1984 and 1993) data with 2) census and mortality records of the Swiss National Cohort in order to establish a mortality follow-up until 2008. Many countries feature the defect of lacking general population cohorts because they have missed to provide for follow-up information of health surveys. METHODS: Record linkage procedures were used in a multi-step approach. Kaplan-Meier curves from our data were contrasted with the survival probabilities expected from life tables for the general population, age-standardized mortality rates from our data with those derived from official cross-sectional mortality data. Cox regression models were fit to investigate the influence of covariates on survival. RESULTS: 97.8% of the eligible 10,160 participants (25-74y at baseline) could be linked to a census (1990: 9,737; 2000: 8,749), mortality (1,526, 1984-2008) and/or emigration record (320, 1990-2008). Linkage success did not differ by any key study characteristic. Results of survival analyses were robust to linkage step or certainty of a correct link. Loss to follow-up between 1990 and 2000 amounted to 4.7%. MONICA participants had lower mortality than the general population, but similar mortality patterns, (e.g. variation by educational level, marital status or region). CONCLUSIONS: Using anonymized census and death records allowed an almost complete mortality follow-up of MONICA study participants of up to 25 years. Lower mortality compared to the general population was in line with a presumable 'healthy participant' selection in the original MONICA study. Apart from that, the derived data set reproduced known mortality patterns and showed only negligible potential for selection bias introduced by the linkage process. Anonymous record linkage was feasible and provided robust results. It can thus provide valuable information, when no cohort study is available

Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

<p>Abstract</p> <p>Background</p> <p>Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT.</p> <p>Methods</p> <p>We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN.</p> <p>Results</p> <p>We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months.</p> <p>Conclusions</p> <p>LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence.</p

Molecular biology of breast cancer metastasis: Inflammatory breast cancer: clinical syndrome and molecular determinants

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer (LABC) that effects approximately 5% of women with breast cancer annually in the USA. It is a clinically and pathologically distinct form of LABC that is particularly fast growing, invasive, and angiogenic. Nearly all women have lymph node involvement at the time of diagnosis, and approximately 36% have gross distant metastases. Despite recent advances in multimodality treatments, the prognosis of patients with IBC is poor, with a median disease-free survival of less than 2.5 years. Recent work on the genetic determinants that underlie the IBC phenotype has led to the identification of genes that are involved in the development and progression of this disease. This work has been aided by the establishment of primary human cell lines and animal models. These advances suggest novel targets for future interventions in the diagnosis and treatment of IBC

The Fate of Porous Hydroxyapatite Granules Used in Facial Skeletal Augmentation

Facial appearance is largely determined by the morphology of the underlying skeleton. Hydroxyapatite is one of several materials available to enhance projection of the facial skeleton. This study evaluated the long-term maintenance of augmented bony projection when porous hydroxyapatite granules are used on the facial skeleton. Ten female patients aged 28–58 years were studied following aesthetic augmentation of the facial skeleton at 24 sites using porous hydroxyapatite granules. Postoperative CT scans at 3 months served as the baseline measurement and compared with scans taken at 1 and 2 years, with the thickness of the hydroxyapatite measured in axial and coronal planes. Thickness of original bone plus overlay of hydroxyapatite, thickness of the overlying soft tissue, and the overall projection (bone plus soft tissue) were recorded. It was found that 99.7% of the hydroxyapatite was maintained at 2 years, with no statistical difference (t test) from the baseline measurement. The overall projection (bony and soft tissue) was maintained as there was no evidence of native bone resorption or soft tissue atrophy. Radiographic results confirmed that the use of porous hydroxyapatite granules for enhancement of the facial skeleton is not only a predictable procedure, but maintains full bony projection at 2 years

Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported.</p> <p>Methods</p> <p>Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation.</p> <p>Results</p> <p>In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (<it>P </it>< 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC).</p> <p>Conclusion</p> <p>Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms.</p