Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis

Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis

Dying at home or in an institution: perspectives of Dutch physicians and bereaved relatives

Introduction Previous studies have shown that most people prefer to die at their own home. We investigated whether physicians or bereaved relatives in retrospect differently appreciate the dying of patients in an institution or at home. Materials and methods Of 128 patients with incurable cancer who were followed in the last phase of their lives, 103 passed away during follow-up. After death, physicians filled out a written questionnaire for 102 of these patients, and 63 bereaved relatives were personally interviewed. Results Of 103 patients, 49 died in an institution (mostly a hospital), and 54 died at home (or in two cases in a home-like situation). Patients who had been living with a partner relatively often died at home. Bereaved relatives knew of the patient’s wish to die at home in 25 out of 63 cases; 20 of these patients actually died at home. Thirty-one patients had no known preference concerning their place of dying. Most symptoms and the care provided to address them were equally prevalent in patients dying in an institution and patients dying at home. Bereaved relatives were in general quite satisfied about the provision of medical and nursing care in both settings. Conclusion We conclude that most patients’ preferences concerning the place of dying can be met. In about half of all cases, patients do not seem to have a clear preference concerning their place of dying, which is apparently not a major concern for many people. We found no indication that dying in an institution or at home involves major differences in the process and quality of dying

Intra-observer and interobserver variability of biventricular function, volumes and mass in patients with congenital heart disease measured by CMR imaging

Cardiovascular magnetic resonance (CMR) imaging provides highly accurate measurements of biventricular volumes and mass and is frequently used in the follow-up of patients with acquired and congenital heart disease (CHD). Data on reproducibility are limited in patients with CHD, while measurements should be reproducible, since CMR imaging has a main contribution to decision making and timing of (re)interventions. The aim of this study was to assess intra-observer and interobserver variability of biventricular function, volumes and mass in a heterogeneous group of patients with CHD using CMR imaging. Thirty-five patients with CHD (7–62 years) were included in this study. A short axis set was acquired using a steady-state free precession pulse sequence. Intra-observer and interobserver variability was assessed for left ventricular (LV) and right ventricular (RV) volumes, function and mass by calculating the coefficient of variability. Intra-observer variability was between 2.9 and 6.8% and interobserver variability was between 3.9 and 10.2%. Overall, variations were smallest for biventricular end-diastolic volume and highest for biventricular end-systolic volume. Intra-observer and interobserver variability of biventricular parameters assessed by CMR imaging is good for a heterogeneous group of patients with CHD. CMR imaging is an accurate and reproducible method and should allow adequate assessment of changes in ventricular size and global ventricular function

Mapping and characterization of novel parthenocarpy QTLs in tomato

Parthenocarpy is the development of the fruit in absence of pollination and/or fertilization. In tomato, parthenocarpy is considered as an attractive trait to solve the problems of fruit setting under unfavorable conditions. We studied the genetics of parthenocarpy in two different lines, IL5-1 and IVT-line 1, both carrying Solanum habrochaites chromosome segments. Parthenocarpy in IL5-1 is under the control of two QTLs, one on chromosome 4 (pat4.1) and one on chromosome 5 (pat5.1). IVT-line 1 also contains two parthenocarpy QTLs, one on chromosome 4 (pat4.2) and one on chromosome 9 (pat9.1). In addition, we identified one stigma exsertion locus in IL5-1, located on the long arm of chromosome 5 (se5.1). It is likely that pat4.1, from IL5-1 and pat4.2, from IVT-line 1, both located near the centromere of chromosome 4 are allelic. By making use of the microsynteny between tomato and Arabidopsis in this genetic region, we identified ARF8 as a potential candidate gene for these two QTLs. ARF8 is known to act as an inhibitor for further carpel development in Arabidopsis, in absence of pollination/fertilization. Expression of an aberrant form of the ArabidopsisARF8 gene, in tomato, has been found to cause parthenocarpy. This candidate gene approach may lead to the first isolation of a parthenocarpy gene in tomato and will allow further use in several crop species

Assessing Amyloid Pathology in Cognitively Normal Subjects Using F-18-Flutemetamol PET: Comparing Visual Reads and Quantitative Methods

Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffeebreak protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ 5 0.57) and good for BPND images (κ 5 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population

Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis

IMPORTANCE: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes. DATA SOURCES: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies. STUDY SELECTION: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data. DATA EXTRACTION AND SYNTHESIS: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy). MAIN OUTCOMES AND MEASURES: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method. RESULTS: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years. CONCLUSIONS AND RELEVANCE: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years

Secondary prevention of Alzheimer's dementia: neuroimaging contributions

BACKGROUND: In Alzheimer's disease (AD), pathological changes may arise up to 20 years before the onset of dementia. This pre-dementia window provides a unique opportunity for secondary prevention. However, exposing non-demented subjects to putative therapies requires reliable biomarkers for subject selection, stratification, and monitoring of treatment. Neuroimaging allows the detection of early pathological changes, and longitudinal imaging can assess the effect of interventions on markers of molecular pathology and rates of neurodegeneration. This is of particular importance in pre-dementia AD trials, where clinical outcomes have a limited ability to detect treatment effects within the typical time frame of a clinical trial. We review available evidence for the use of neuroimaging in clinical trials in pre-dementia AD. We appraise currently available imaging markers for subject selection, stratification, outcome measures, and safety in the context of such populations. MAIN BODY: Amyloid positron emission tomography (PET) is a validated in-vivo marker of fibrillar amyloid plaques. It is appropriate for inclusion in trials targeting the amyloid pathway, as well as to monitor treatment target engagement. Amyloid PET, however, has limited ability to stage the disease and does not perform well as a prognostic marker within the time frame of a pre-dementia AD trial. Structural magnetic resonance imaging (MRI), providing markers of neurodegeneration, can improve the identification of subjects at risk of imminent decline and hence play a role in subject inclusion. Atrophy rates (either hippocampal or whole brain), which can be reliably derived from structural MRI, are useful in tracking disease progression and have the potential to serve as outcome measures. MRI can also be used to assess comorbid vascular pathology and define homogeneous groups for inclusion or for subject stratification. Finally, MRI also plays an important role in trial safety monitoring, particularly the identification of amyloid-related imaging abnormalities (ARIA). Tau PET to measure neurofibrillary tangle burden is currently under development. Evidence to support the use of advanced MRI markers such as resting-state functional MRI, arterial spin labelling, and diffusion tensor imaging in pre-dementia AD is preliminary and requires further validation. CONCLUSION: We propose a strategy for longitudinal imaging to track early signs of AD including quantitative amyloid PET and yearly multiparametric MRI

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information