Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation?

GOALS OF WORK: In patients with locally advanced esophageal cancer, only those responding to the treatment ultimately benefit from preoperative chemoradiation. We investigated whether changes in subjective dysphagia or eating restrictions after two cycles of induction chemotherapy can predict histopathological tumor response observed after chemoradiation. In addition, we examined general long-term quality of life (QoL) and, in particular, eating restrictions after esophagectomy. MATERIALS AND METHODS: Patients with resectable, locally advanced squamous cell- or adenocarcinoma of the esophagus were treated with two cycles of chemotherapy followed by chemoradiation and surgery. They were asked to complete the EORTC oesophageal-specific QoL module (EORTC QLQ-OES24), and linear analogue self-assessment QoL indicators, before and during neoadjuvant therapy and quarterly until 1 year postoperatively. A median change of at least eight points was considered as clinically meaningful. MAIN RESULTS: Clinically meaningful improvements in the median scores for dysphagia and eating restrictions were found during induction chemotherapy. These improvements were not associated with a histopathological response observed after chemoradiation, but enhanced treatment compliance. Postoperatively, dysphagia scores remained low at 1 year, while eating restrictions persisted more frequently in patients with extended transthoracic resection compared to those with limited transhiatal resection. CONCLUSIONS: The improvement of dysphagia and eating restrictions after induction chemotherapy did not predict tumor response observed after chemoradiation. One year after esophagectomy, dysphagia was a minor problem, and global QoL was rather good. Eating restrictions persisted depending on the surgical technique used.

The importance of glacier and forest change in hydrological climate-impact studies

Changes in land cover alter the water balance components of a catchment, due to strong interactions between soils, vegetation and the atmosphere. Therefore, hydrological climate impact studies should also integrate scenarios of associated land cover change. To reflect two severe climate-induced changes in land cover, we applied scenarios of glacier retreat and forest cover increase that were derived from the temperature signals of the climate scenarios used in this study. The climate scenarios were derived from ten regional climate models from the ENSEMBLES project. Their respective temperature and precipitation changes between the scenario period (2074–2095) and the control period (1984–2005) were used to run a hydrological model. The relative importance of each of the three types of scenarios (climate, glacier, forest) was assessed through an analysis of variance (ANOVA). Altogether, 15 mountainous catchments in Switzerland were analysed, exhibiting different degrees of glaciation during the control period (0–51%) and different degrees of forest cover increase under scenarios of change (12–55% of the catchment area). The results show that even an extreme change in forest cover is negligible with respect to changes in runoff, but it is crucial as soon as changes in evaporation or soil moisture are concerned. For the latter two variables, the relative impact of forest change is proportional to the magnitude of its change. For changes that concern 35% of the catchment area or more, the effect of forest change on summer evapotranspiration is equally or even more important than the climate signal. For catchments with a glaciation of 10% or more in the control period, the glacier retreat significantly determines summer and annual runoff. The most important source of uncertainty in this study, though, is the climate scenario and it is highly recommended to apply an ensemble of climate scenarios in the impact studies. The results presented here are valid for the climatic region they were tested for, i.e., a humid, mid-latitude mountainous environment. They might be different for regions where the evaporation is a major component of the water balance, for example. Nevertheless, a hydrological climate-impact study that assesses the additional impacts of forest and glacier change is new so far and provides insight into the question whether or not it is necessary to account for land cover changes as part of climate change impacts on hydrological systems.

Who stays, who benefits? Predicting dropout and change in cognitive behaviour therapy for psychosis

This study investigates predictors of outcome in a secondary analysis of dropout and completer data from a randomized controlled effectiveness trial comparing CBTp to a wait-list group (Lincoln et al., 2012). Eighty patients with DSM-IV psychotic disorders seeking outpatient treatment were included. Predictors were assessed at baseline. Symptom outcome was assessed at post-treatment and at one-year follow-up. The predictor x group interactions indicate that a longer duration of disorder predicted less improvement in negative symptoms in the CBTp but not in the wait-list group whereas jumping-to-conclusions was associated with poorer outcome only in the wait-list group. There were no CBTp specific predictors of improvement in positive symptoms. However, in the combined sample (immediate CBTp+the delayed CBTp group) baseline variables predicted significant amounts of positive and negative symptom variance at post-therapy and one-year follow-up after controlling for pre-treatment symptoms. Lack of insight and low social functioning were the main predictors of drop-out, contributing to a prediction accuracy of 87%. The findings indicate that higher baseline symptom severity, poorer functioning, neurocognitive deficits, reasoning biases and comorbidity pose no barrier to improvement during CBTp. However, in line with previous predictor-research, the findings imply that patients need to receive treatment earlier.

Change in perfusion, hallucinations and fluctuations in consciousness in dementia with Lewy bodies.

Fluctuations in consciousness and visual hallucinations are common neuropsychiatric features of dementia with Lewy bodies and Parkinson's disease dementia. To investigate potential neural correlates, we compared how changes in brain perfusion over a 1-year period were related to changes in the severity of these key clinical features. We recruited 29 subjects with either Parkinson's disease with dementia (15 subjects) or dementia with Lewy bodies (14 subjects). Cerebral perfusion was measured using HMPAO SPECT at baseline, and repeated 1 year later. The presence of hallucinations (Neuropsychiatric Inventory), severity of fluctuations in consciousness (fluctuation assessment scale) and cognitive ability (CAMCOG) were assessed at both time points. After controlling for changes in cognitive ability and effect of cholinesterase medication, we found a significant correlation between an increase in perfusion in midline posterior cingulate and decrease in hallucination severity. There was also a significant correlation between increased fluctuations of consciousness and increased thalamic and decreased inferior occipital perfusion. We have identified important neural correlates of key clinical features in Lewy body dementia and postulate that the associations can be understood through the influence of the cholinergic system on attention.