The importance of social relationships in the process of cognitive ageing

Due to ageing populations worldwide, the number of people with cognitive impairments and dementia is increasing rapidly. Insight in the risk factors is crucial in order to develop interventions that prevent or delay the development of the disease. We investigated to what extent social functioning is associated with cognitive decline. Three stages of cognitive decline are considered, including subjective memory complaints, cognitive decline and dementia.The findings in this PhD thesis show that multiple aspects of social functioning are associated with different stages of cognitive decline. Better feelings of affection and behavioral confirmation protect against the development of subjective memory complaints and contribute to the recovery thereof. In addition, people recovered more often from subjective memory complaints if they were in a relationship, had a larger family composition, and had better feelings of status. Poor social relationships were also associated with cognitive decline. This was found for both the structure (e.g. small social network or low frequency of social contact), and the function (e.g. low social support and feelings of loneliness) of social relations. Particularly a lack of social interaction is associated with incident dementia. This effect is of comparable strength as other well-established risk factors for dementia, such as physical inactivity, smoking, and depression.It is well-known that non-smoking, a healthy diet and physical activity reduce the risk of cognitive decline. Our findings show that better social functioning should be added to this list. This is an important fact for GPs, geriatricians or policymakers who may still wonder whether promoting social interaction could be beneficial. We therefore advocate that more attention is paid to social functioning in the prevention of dementia

On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study

Introduction: Patients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting. Methods: A prospective study compared a baseline period with an intervention period. During the intervention period, an ICU hospital pharmacist reviewed medication orders for patients admitted to the ICU, noted issues related to prescribing, formulated recommendations and discussed those during patient review meetings with the attending ICU physicians. Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians. Results: During the 8.5-month study period, medication orders for 1,173 patients were reviewed. The ICU hospital pharmacist made a total of 659 recommendations. During the intervention period, the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74%. The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period: 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days, respectively (P < 0.001). Preventable ADEs (patient harm, National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period (P = 0.25). Per monitored patient-day, the intervention itself cost (sic)3, but might have saved (sic)26 to (sic)40 by preventing ADEs. Conclusions: On-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm (preventable ADEs) at acceptable costs per monitored patient-da

Retrospective methods to estimate radiation dose at the site of breast cancer development after Hodgkin lymphoma radiotherapy.

BACKGROUND: An increased risk of breast cancer following radiotherapy for Hodgkin lymphoma (HL) has now been robustly established. In order to estimate the dose-response relationship more accurately, and to aid clinical decision making, a retrospective estimation of the radiation dose delivered to the site of the subsequent breast cancer is required. METHODS: For 174 Dutch and 170 UK female patients with breast cancer following HL treatment, the 3-dimensional position of the breast cancer in the affected breast was determined and transferred onto a CT-based anthropomorphic phantom. Using a radiotherapy treatment planning system the dose distribution on the CT-based phantom was calculated for the 46 different radiation treatment field set-ups used in the study population. The estimated dose at the centre of the breast cancer, and a margin to reflect dose uncertainty were determined on the basis of the location of the tumour and the isodose lines from the treatment planning. We assessed inter-observer variation and for 47 patients we compared the results with a previously applied dosimetry method. RESULTS: The estimated median point dose at the centre of the breast cancer location was 29.75 Gy (IQR 5.8-37.2), or about 75% of the prescribed radiotherapy dose. The median dose uncertainty range was 5.97 Gy. We observed an excellent inter-observer variation (ICC 0.89 (95% CI: 0.74-0.95)). The absolute agreement intra-class correlation coefficient (ICC) for inter-method variation was 0.59 (95% CI: 0.37-0.75), indicating (nearly) good agreement. There were no systematic differences in the dose estimates between observers or methods. CONCLUSION: Estimates of the dose at the point of a subsequent breast cancer show good correlation between methods, but the retrospective nature of the estimates means that there is always some uncertainty to be accounted for

Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.

A plethora of functional and genetic studies have suggested a key role for the IL-23 pathway in chronic intestinal inflammation. Currently, pathogenic actions of IL-23 have been ascribed to specific effects on immune cells. Herein, we unveil a protective role of IL-23R signaling. Mice deficient in IL-23R expression in intestinal epithelial cells (Il23R(ΔIEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(ΔIEC) mice show impaired mucosal IL-22 induction in response to IL-23. αThy-1 treatment significantly deteriorates colitis in Il23R(ΔIEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(ΔIEC) mice by recruiting neutrophils as IL-22-producing cells, thereby restoring mucosal IL-22 levels. The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells.This work was supported by DFG Excellence Cluster Inflammation at Interfaces; the SFB877 B9, the SFB 1182 C2 project, and the BMBF IHEC DEEP project TP2.3 and 5.2 (to P.R.); the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement 260961 (to A.K.); the National Institute for Health Research Cambridge Biomedical Research Centre, ERC CoG GA 648889, and WTIA 106260-Z-14-Z (to A.K.); NIH DK53056, DK44319, and DK088199 (to R.S.B.); and the Fondation pour la Recherche Medicale (to M.C.).This is the final version of the article. It first appeared from Cell/Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.07.05

Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

Background: Patients with longstanding ulcerative colitis (UC) undergo regular dysplasia surveillance because of increased colorectal cancer risk. Previous studies demonstrated that autofluorescence imaging (AFI) and chromoendoscopy (CE) increased dysplasia detection. The aim of this study was to determine whether AFI should be further studied as an alternative method for dysplasia surveillance in patients with longstanding UC. Methods: In this prospective international, randomised trial, 210 patients undergoing colonoscopy surveillance for longstanding UC were randomised between 1 August 2013 and 10 March 2017 for inspection with either AFI or CE (105:105). Randomisation was minimised for a previous history of dysplasia and a previous history of primary sclerosing cholangitis. The main outcome was the relative dysplasia detection rate calculated by the ratio of AFI versus CE. This relative dysplasia detection rate was determined for the proportion of UC patients in which at least one dysplastic lesion was detected and for the mean number of dysplastic lesions per patient. The relative dysplasia detection rate needed to be above 0·67 for both outcomes to support performing a subsequent large non-inferiority trial, using an 80% confidence interval. Analysis was performed per protocol. The trial is registered at Netherlands Trial Register (NTR4062). Findings: AFI detected dysplasia in 13 (12·4%) patients, compared to 20 patients (19·1%) with CE. The relative dysplasia detection rate of CE versus AFI for the proportion of UC patients with at least one dysplastic lesion was 0·65 (80% CI; 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 for AFI compared to 0·37 for CE (relative dysplasia detection rate 0·36, 80% CI; 0·21-0·61). Two patients experienced an adverse event (intraprocedural mild bleeding = 1, abdominal pain = 1) in the AFI-arm and three patients (intraprocedural mild bleeding = 2, perforation = 1) in the CE-arm. Interpretation: In this randomised study comparing AFI with CE for dysplasia surveillance in patients with longstanding UC, AFI did not meet criteria for proceeding to a large non-inferiority trial. Therefore, current AFI technology should not be further investigated as an alternative dysplasia surveillance method. Funding: Olympus Europe and Olympus Keymed, Oxford and Nottingham NIHR biomedical research centres

The Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe