Lung function development in the first 2 yr of life is independent of allergic diseases by 2 yr

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.     

Attempts to isolate virus from human trigeminal and facial ganglions

Herpes virus hominis type 1 was isolated from the trigeminal ganglion (ganglion semilunare, gasservian) in three out of 20 randomly selected autopsies. Two of the three patients had been treated with immunosuppressive or cytostatic agents. Clinical signs of herpes infection were not observed during the previous 6 months. No virus was isolated from the facial ganglion (geniculate ganglion) in the same 20 cases. The findings are discussed in relation to the viral etiology of acute peripheral facial palsy.     

Association between food patterns and difficulties in falling asleep among adolescents in Norway — a descriptive Young-Hunt3 study

Journal of Public Health - Adolescents’ sleep duration has decreased over the past century; this is mainly caused by problems with falling asleep. Short sleep duration, poor sleep quality,...     

Determining drug dose in the era of targeted therapies: playing it (un)safe?

Targeted therapies against phosphatidylinositol 3-kinase (PI3K), Bruton’s tyrosine kinase (BTK), and B-cell lymphoma-2 (BCL-2) are approved for chronic lymphocytic leukemia (CLL). Since approval of the first-in-class drugs, next-generation agents have become available and are continuously under development. While these therapies act on well-characterized molecular targets, this knowledge is only to some extent taken into consideration when determining their dose in phase I trials. For example, BTK occupancy has been assessed in dose-finding studies of various BTK inhibitors, but the minimum doses that result in full BTK occupancy were not determined. Although targeted agents have a different dose–response relationship than cytotoxic agents, which are more effective near the maximum tolerated dose, the traditional 3 + 3 toxicity-driven trial design remains heavily used in the era of targeted therapies. If pharmacodynamic biomarkers were more stringently used to guide dose selection, the recommended phase II dose would likely be lower as compared to the toxicity-driven selection. Reduced drug doses may lower toxicity, which in some cases is severe for these agents, and are supported by retrospective studies demonstrating non-inferior outcomes for patients with clinically indicated dose reductions. Here, we review strategies that were used for dose selection in phase I studies of currently approved and select investigational targeted therapies in CLL, and discuss how our initial clinical experience with targeted therapies have pointed to dose reductions, intermittent dosing, and drug combinations as strategies to overcome treatment intolerance and resistance.Subject terms: Targeted therapies, Targeted therapies     

“The median isn't the message”: How to communicate the uncertainties of survival prognoses to cancer patients in a realistic and hopeful way

This study investigated how doctors communicate the uncertainties of survival prognoses to patients recently diagnosed with life‐threatening cancer, and suggests ways to improve this communication. Two hundred thirty‐eight Norwegian oncologists and general practitioners (GPs) participated in Study 1. The study included both a scenario and a survey. The scenario asked participants to respond to a hypothetical patient who wanted to know how long (s)he could be expected to live. There were marked differences in responses within both groups, but few differences between the GPs and oncologists. There was a strong reluctance among doctors to provide patients with a prognosis. Even when they were presented with a statistically well‐founded right‐skewed survival curve, only a small minority provided hope by communicating the variation in survival time. In Study 2, 177 healthy students rated their preferences for different ways of receiving information regarding the uncertainty of a survival prognosis. Participants who received an explicitly described right‐skewed survival curve believed that they would feel more hopeful. These participants also obtained a more realistic understanding of the variation in survival than those who did not receive this information. Based on the findings of the two studies and on extant psychological research, the author suggests much‐needed guidelines for communicating survival prognoses in a realistic and optimistic way to patients recently diagnosed with life‐threatening cancer. In particular, the guidelines emphasise that the doctor explains the often strongly right‐skewed variation in survival time, and thereby providing the patient with realistic hope.     

Freehand real-time elastography: impact of scanning parameters on image quality and in vitro intra- and interobserver validations

Real-time elastography is a method for visualization of the elastic properties of soft tissue and may potentially enable differentiation between malignant and benign pathologic lesions. Our aim was to validate the method on a tissue-mimicking (TM) phantom and to evaluate the influence of different scanning parameters and investigator variability. A TM-phantom containing eight spherical inclusions with known storage modulus was examined using two different transducers on an ultrasound (US) scanner equipped with software for real-time elasticity imaging. The ultrasound transducers were moved vertically in a repetitive manner to induce strain. Two investigators performed series of standardized elastography scans applying a 0-4 categorical quality scale to evaluate the influence of seven parameters: dynamic range of elasticity, region-of-interest, frequency of transducer movement, rejection of elastogram noise, frame rate, persistence and smoothing. Subsequently, repeated examinations of four selected inclusions were performed using a visual analog scale (VAS) where investigators marked a 100 mm horizontal line representing the span in image quality based on experience from the first examination. The hardest and softest inclusions were imaged more clearly than the inclusions with elasticity more similar to the background material. Intraobserver agreement on elastogram quality was good (kappa: 0.67 - 0.75) and interobserver agreement average (kappa: 0.55 - 0.56) when using the categorical scale. The subsequent VAS evaluation gave intraclass-correlation coefficients for the two observers of 0.98 and 0.93, respectively, and an interclass-correlation coefficient of 0.93. Real-time elastography adequately visualized isoechoic inclusions with different elastic properties in a TM-phantom with acceptable intra- and interobserver agreement. Dynamic range of elasticity was the parameter with most impact on the elastographic visualization of inclusions.     

Psychiatric and behavioural symptoms and the use of psychotropic medication in Special Care Units and Regular Units in Norwegian nursing homes

Background: In a number of countries Special Care Units (SCUs) have been established to meet the particular needs of patients with dementia. The criteria for SCUs are poorly defined and often not met. Aim: To assess the frequency distributions of dementia, psychiatric and behavioural symptoms and the use of psychotropic medication in SCUs and Regular Units (RUs) across different regions. Methods and material: By means of a structured interview, comprising the Neuropsychiatric Inventory, the Clinical Dementia Rating Scale and Lawton’s Physical Self‐maintenance scale, a representative sample of 1163 nonselected nursing home patients was assessed. In addition, information was collected from the patients’ records. Results: Overall SCU patients were significantly more likely to be younger, to have higher level of functioning, to have dementia, to exhibit clinically significant psychiatric and behavioural symptoms and to receive psychotropic medication. There were significant differences across regions in terms of psychiatric and behavioural symptoms and the use of psychotropic medication. The ratio of accommodation in SCUs to that in RUs varied across the regions. Conclusion: Patients in SCUs and patients in RUs are distinct nursing home populations. Regional differences, which might be due to diverse ratios of SCUs, are evident.     

Anxiety and depression among subjects attending genetic counseling for hereditary cancer

OBJECTIVES: The main aims of the study were to investigate changes in anxiety and depression over time in subjects attending genetic counseling (GC) for hereditary cancer, and secondly, to identify psychological, social, and medical variables associated with the course and outcome of anxiety and depression. METHODS: Of 275 eligible individuals, 221 consented to participate, 214 returned the baseline questionnaire, and were included in a prospective multi-center study. Questionnaires were mailed to the subjects before and after the GC. RESULTS: The mean values for anxiety and depression were quite low at all assessments. Mixed linear analyzes revealed that both anxiety and depression declined over time. Higher age, GC-related self-efficacy, and social support were associated with lower levels of anxiety. More social support, satisfaction with GC, self-rated physical function, and GC-related self-efficacy were associated with lower levels of depression. The effects of social support on both anxiety and depression had a significant interaction with time. CONCLUSION: The results support the buffer theory, which proposes that social support acts as a buffer, protecting people from the potentially pathogenic influence of stressful life events, such as GC. PRACTICE IMPLICATIONS: Subjects with less social support and less GC-related self-efficacy seem to be more vulnerable to anxiety and depression and should be offered extra attention by counselors.