Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2^−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2^−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.     

Antibiotics for nasopharyngitis are associated with a lower risk of office-based physician visit for acute otitis media within 14 days for 3- to 6-year-old children

Objectives  This study was designed to analyse factors potentially influencing children's return visits to physicians for symptoms of acute otitis media (AOM) within 14 days after being diagnosed with nasopharyngitis (NP), and the impact of recent antibiotic use.
Design  A controlled population-based pharmaco-epidemiological trial in 3- to 6-year-old children conducted from January to May 2000.
Setting  Three different geographical regions in France.
Participants  Among 2507 eligible children, 2456 could be analysed and 505 children had 634 office-based physician visits (OBPV) for NP symptoms.
Interventions  The statistical associations between antibiotics prescribed for NP and an OBPV for AOM within 14 days in a population-based study were analysed along with risk factors of AOM.
Main outcomes measure  Clinical events and antibiotic use.
Results  During the 2 weeks following physician-diagnosed NP, antibiotic use, especially a beta-lactam, significantly decreased the risk of OBPV for AOM in children (odds ratio = 0.2; 95% confidence interval = 0.09–0.7; P  = 0.002).
Conclusion  Antibiotics prescribed to children for NP seem to protect during the following 2 weeks against the risk of OBPV for AOM. It remains to be determined whether a subgroup at high risk of developing AOM after a viral infection exists and what might be the best strategy to adopt for NP in a national programme of optimal antibiotic use.     

Language skills of adolescents with Tourette Syndrome

A multiple single‐case study investigated language characteristics of adolescents with Tourette Syndrome (TS). Ten adolescent subjects with diagnosed TS were evaluated on a test battery sensitive to high level language and discourse impairment. Results were compared to established norms or, where no norms have been established, with results obtained by 15 non‐neurologically impaired adolescent subjects. Five subjects were differentiated from normal communicative performance by their test results. Although language profiles were variable, disorganized output, concreteness of language and poor language formulation abilities were apparent in these subjects. This symptomatology may reflect prefrontal disturbance and can possibly be explained by the pathogenesis of the disorder. This finding adds to literature regarding subcortical and frontal cortex language involvement and indicates further research.     

The ethics of gene therapy: balancing the risks

Gene therapy research is characterized by heightened uncertainty about the risks associated with the complex products involved, particularly the risk of genotoxicity. Recognizing that uncertainty concerning risks is inescapable in first-in-human clinical trials of gene therapy, decisions on how to balance the risks nevertheless must be made. Ethics can facilitate translational progress by, first, evaluating decision-making processes during risk assessment; and second, focusing on questions that require a degree of subjective judgement. Such assessments include determining the level of risk that is acceptable in trials, the category of patients that should be exposed to the risks, and the level of certainty with respect to risk that is required for both researchers and participants to make decisions. Analysis of these issues is affected by the burden of illness, existing treatment alternatives and the possible benefits of gene therapy. Patients' attitudes and experiences in this regard can reasonably inform the decision-making of researchers. Reflecting upon the approaches used to balance risks and possible benefits in gene therapy trials may improve decision-making processes across the spectrum of decisions that are made from the initial conception of a study up to decisions by research participants about consent. This manner of reflection facilitates the advancement of science, while protecting the welfare of research participants.     

An examination of associations between the inability to taste phenylthiocarbamide (PTC) and clinical characteristics and trait markers in first-episode,nonaffective psychotic disorders

Research findings are mixed as to whether or not the inability to taste phenylthiocarbamide (PTC) might represent an endophenotypic trait marker for schizophrenia. We hypothesized associations between PTC-tasting status and select clinical characteristics and trait markers in patients with psychotic disorders that, if present, would provide support for the inability to taste PTC as a trait marker. In a first-episode psychosis sample (n=93), we measured PTC tasting, family history of psychosis, age at onset of prodrome and psychosis, severity of positive and negative symptoms, global impairment in functioning, neurological soft signs, and four neurocognitive domains (verbal learning/memory, visual learning/memory, verbal working memory, and spatial working memory). Associations between PTC-non-tasting and clinical/neurocognitive variables were examined with χ² tests and independent samples t tests. Among participants, 67.7% tasted PTC in comparison to a strip of control paper, and 25.8% were non-tasters. Tasters and non-tasters did not show statistically significant differences with respect to family history, age at onset, severity of symptoms, neurological soft signs, or the four neurocognitive domains. In conjunction with other findings, it is unlikely that PTC-non-tasting is a trait marker of schizophrenia, though a conclusive study is warranted.     

Electrocardiographic ST-segment elevation in the trauma patient: acute myocardial infarction vs myocardial contusion

The diagnosis of myocardial contusion in the setting of blunt trauma engenders much discussion and controversy-partly because of the lack of a gold standard for its identification other than histologic findings at autopsy. Furthermore, blunt cardiac trauma represents a spectrum of disorders ranging from transient electrocardiographic change to sudden death from myocardial rupture; hence, no single terminology exists to define such a wide range of scenarios. Here, we present 2 cases of electrocardiographic ST-segment elevation after high-speed motor vehicle crashes resulting in numerous injuries, including blunt chest trauma. Both patients demonstrated electrocardiographic ST-segment elevation, resulting from myocardial contusion and acute myocardial infarction.     

Direct Observation of Clinical Skills Feedback Scale: Development and Validity Evidence

Construct: This article describes the development and validity evidence behind a new rating scale to assess feedback quality in the clinical workplace. Background: Competency-based medical education has mandated a shift to learner-centeredness, authentic observation, and frequent formative assessments with a focus on the delivery of effective feedback. Because feedback has been shown to be of variable quality and effectiveness, an assessment of feedback quality in the workplace is important to ensure we are providing trainees with optimal learning opportunities. The purposes of this project were to develop a rating scale for the quality of verbal feedback in the workplace (the Direct Observation of Clinical Skills Feedback Scale [DOCS-FBS]) and to gather validity evidence for its use. Approach: Two panels of experts (local and national) took part in a nominal group technique to identify features of high-quality feedback. Through multiple iterations and review, 9 features were developed into the DOCS-FBS. Four rater types (residents n = 21, medical students n = 8, faculty n = 12, and educators n = 12) used the DOCS-FBS to rate videotaped feedback encounters of variable quality. The psychometric properties of the scale were determined using a generalizability analysis. Participants also completed a survey to gather data on a 5-point Likert scale to inform the ease of use, clarity, knowledge acquisition, and acceptability of the scale. Results: Mean video ratings ranged from 1.38 to 2.96 out of 3 and followed the intended pattern suggesting that the tool allowed raters to distinguish between examples of higher and lower quality feedback. There were no significant differences between rater type (range = 2.36–2.49), suggesting that all groups of raters used the tool in the same way. The generalizability coefficients for the scale ranged from 0.97 to 0.99. Item-total correlations were all above 0.80, suggesting some redundancy in items. Participants found the scale easy to use (M = 4.31/5) and clear (M = 4.23/5), and most would recommend its use (M = 4.15/5). Use of DOCS-FBS was acceptable to both trainees (M = 4.34/5) and supervisors (M = 4.22/5). Conclusions: The DOCS-FBS can reliably differentiate between feedback encounters of higher and lower quality. The scale has been shown to have excellent internal consistency. We foresee the DOCS-FBS being used as a means to provide objective evidence that faculty development efforts aimed at improving feedback skills can yield results through formal assessment of feedback quality.