Large Sample Size Fallacy in Trials About Antipsychotics for Neuropsychiatric Symptoms in Dementia

Background: A typical antipsychotics for neuropsychiatric symptoms in dementia have been tested in much larger trials than the older conventional drugs. The advantage of larger sample sizes is that negative findings become less likely and the effect estimates more precise. However, as sample sizes increase, the trials also get more expensive and time consuming while exposing more patients to drugs with unknown safety profiles. Moreover, a large sample size might yield a statistically significant effect that is not necessarily clinically relevant. Objective: To assess (1) the variation in sample size and sample size calculations of antipsychotic trials in dementia, (2) the size of reported treatment effects and related statistical significance, and (3) general study characteristics that might be related to sample size. Study Design and Setting: We performed a meta-epidemiological study of randomized trials that tested antipsychotics for neuropsychiatric symptoms in dementia. The trials compared conventional or atypical antipsychotics with placebo or another antipsychotic. Two reviewers independently extracted sample size, sample size calculations, reported treatment effects with p-values, and general study characteristics (drug type, trial duration, type of funding). We calculated a reference sample size of 83 and 433 per study group for the placebo-controlled and head-to-head trials respectively. Results: We identified 33 placebo-controlled trials, and 18 head-to-head trials. Only 14 (42%) and 2 (11%), respectively, reported a sample size calculation. The average sample size per arm was 34 (range 6-179) in placebo-controlled trials testing conventional drugs, 107 (8-237) in such trials testing atypical drugs, and 104 (95-115) in such trials testing both drug types; it was 31 (10-88) in head-to-head trials. Thirteen out of 18 trials with sample sizes larger than required (72%) reported a statistically significant treatment effect, of which two (15%) were clinically relevant. None of the head-to-head trials reported a statistically significant treatment effect, even though some suggested non-inferiority. In placebo-controlled trials of atypical drugs, longer trial duration (>6 weeks) and commercial funding were associated with higher sample size. Conclusion: Sample size calculations were poorly reported in antipsychotic trials for dementia. Placebo-controlled trials of atypical antipsychotics showed large sample size fallacy while head-to-head trials were massively underpowered

Density and molecular epidemiology of Aspergillus in air and relationship to outbreaks of Aspergillus infection

After five patients were diagnosed with nosocomial invasive aspergillosis caused by Aspergillus fumigatus and A. flavus, a 14-month surveillance program for pathogenic and nonpathogenic fungal conidia in the air within and outside the University Hospital in Rotterdam (The Netherlands) was begun. A. fumigatus isolates obtained from the Department of Hematology were studied for genetic relatedness by randomly amplified polymorphic DNA (RAPD) analysis. This was repeated with A. fumigatus isolates contaminating culture media in the microbiology laboratory. The density of the conidia of nonpathogenic fungi in the outside air showed a seasonal variation: higher densities were measured during the summer, while lower densities were determined during the fall and winter. Hardly any variation was found in the numbers of Aspergillus conidia. We found decreasing numbers of conidia when comparing air from outside the hospital to that inside the hospital and when comparing open areas within the hospital to the closed department of hematology. The increase in the number of patients with invasive aspergillosis could not be explained by an increase in the number of Aspergillus conidia in the outside air. The short-term presence of A. flavus can only be explained by the presence of a point source, which was probably patient related. Genotyping A. fumigatus isolates from the department of hematology showed that clonally related isolates were persistently present for more than 1 year. Clinical isolates of A. fumigatus obtained during the outbreak period were different from these persistent clones. A. fumigatus isolates contaminating culture media were all genotypically identical, indicating a causative point source. Kn

The grey – green spectrum: a review of coastal protection interventions

In the face of uncertainties around coastal management and climate change, coastal engineering interventions need to be able to adapt to changing conditions. Nature-based solutions and other non-traditional, integrated interventions are gaining traction. However, system-based views are not yet embedded into coastal management strategies. Moreover, the differences in coastal interventions, ranging from hard (‘grey’) to nature-based (‘green’) infrastructure remain understudied. In coastal management it is therefore challenging to work with the grey-green spectrum of interventions with clarity and focus, and to produce results that can be evaluated. The objective of this paper was to examine whether there is a common understanding of: the characteristics and differences between grey and green infrastructure, where interventions sit on this spectrum, and the resilience of grey versus green infrastructure. We conducted an integrative literature review of the grey-green spectrum of coastal infrastructure. We examined 105 coastal protection case studies and expanded the double-insurance framework to ensure an integrative approach, looking at both external and internal factors of resilience. Our review showed that external factors are typically used to characterise the grey-green spectrum. However, although useful, they do not facilitate a holistic comparison of alternative interventions. The additional consideration of internal factors (response diversity, multifunctionality, modularity and adaptive, participatory governance) bridges this gap. The review showed that dikes, reefs, saltmarshes, sand nourishment and dunes span a wider segment of the grey-green spectrum than they are generally categorised in. Furthermore, resilient solutions for adaptation are unlikely to be exclusively engineered or natural, but tend to be a mix of the two at different spatial scales (micro, meso, macro and mega). Our review therefore suggests that coastal planners benefit from a more diverse range of options when they consider the incorporation of grey and green interventions in the context of each spatial scale. We propose that internal resilience should be accounted for when infrastructure options are comparatively evaluated. This consideration brings attention to the ways in which the grey-hybrid-green spectrum of infrastructure enhances value for people.NWO17595Environmental BiologyIndustrial Ecolog

Rapid detection of methicillin resistance in Staphylococcus aureus isolates by the MRSA-screen latex agglutination test

The slide agglutination test MRSA-Screen (Denka Seiken Co., Niigata, Japan) was compared with the mecA PCR ("gold standard") for the detection of methicillin resistance in Staphylococcus aureus. The MRSA-Screen test detected the penicillin-binding protein 2a (PBP2a) antigen in 87 of 90 genetically diverse methicillin-resistant S. aureus (MRSA) stock culture strains, leading to a sensitivity of 97%. The three discrepant MRSA strains displayed positive results only after induction of the mecA gene by exposure to methicillin. Both mecA PCR and MRSA-Screen displayed negative results among the methicillin-susceptible S. aureus strains (n = 106), as well as for Micrococcus spp. (n = 10), members of the family Enterobacteriaceae (n = 10), Streptococcus pneumoniae (n = 10), and Enterococcus spp. (n = 10) (specificity = 100%). Producing the same PBP2a antigen, all 10 methicillin-resistant Staphylococcus epidermidis strains score positived in both the latex test and the mecA PCR. Consequently, the MRSA-Screen test should be applied only after identification of the MRSA strain to the species level to rule out coagulase-negative staphylococci. In conclusion, due to excellent specificity and sensitivity the MRSA-Screen latex test has the potential to be successfully used for routine applications in the microbiology laboratory

Soundscape Optimization in Nursing Homes Through Raising Awareness in Nursing Staff With MoSART+

Introduction: Soundscapes in nursing homes are often suboptimal for residents. This can cause them feeling anxious and unsafe, or develop behavioral and psychological problems. Residents with dementia cannot adapt nursing home environments to their needs due to cognitive and physical limitations. It is up to the staff of psycho-geriatric wards to improve the soundscape. We evaluated the effect of the sound awareness intervention Mobile Soundscape Appraisal and Recording Technology (MoSART+) on soundscapes in nursing homes. Methods: The MoSART+ intervention was carried out in four nursing homes and took three months in each home. The MoSART+ intervention involved training ambassadors, assessing the soundscape with the MoSART application by the nursing staff to raise their sound awareness on random time points, discussing the measurements, and implementing micro-interventions. Soundscapes were assessed from 0 to 100 on four attributes: pleasantness, eventfulness, complexity, and range of affordances. Based on these scores, soundscapes were classified in four dimensions: calm, lively, boring, and chaotic. Nursing staff graded the environment on a scale of 0 to 10. T-test and Z-tests were used to analyze data. Results: Staff recorded 1882 measurements with the MoSART app. "People," "music, TV, and radio," and "machines and appliances" were the most prevalent sound sources before and after the implementation of micro-interventions. Post-implementation of micro-interventions, soundscapes were pleasant (median 69.0; IQR 54.0-81.0), of low complexity (33.0; 18.0-47.0), uneventful (27.0; 14.0-46.5), and gave moderate affordances (50.0; 35.0-67.0). Changes in attributes were statistically significant (p < 0.01). The proportion of the dimension calm increased (z = 12.7, p < 0.01), the proportion of chaotic decreased (z = 15.0, p < 0.01), and the proportion of lively decreased not statically significant (z = 0.68, p = 0.79). The proportion of boring was unchanged. The proportion of grades ≥6 increased after implementation of the micro-interventions (z = 15.3, p < 0.01). The micro-interventions focused on removing or reducing disturbing sounds and were unique for each nursing home. Discussion: The MoSART+ intervention resulted in a statistically significantly improvement of soundscapes, and more favorable evaluations of the nursing staff. The intervention empowered staff to adapt soundscapes. Nursing homes can improve soundscapes by raising sound awareness among staff. Trial Registration: Netherlands National Trial Register (NL6831)

Sounds in nursing homes and their effect on health in dementia:A systematic review

OBJECTIVES: Nursing home residents with dementia are sensitive to detrimental auditory environments. This paper presents the first literature review of empirical research investigating (1) the (perceived) intensity and sources of sounds in nursing homes, and (2) the influence of sounds on health of residents with dementia and staff. DESIGN: A systematic review was conducted in PubMed, Web of Science and Scopus. Study quality was assessed with the Mixed Methods Appraisal Tool. We used a narrative approach to present the results. RESULTS: We included 35 studies. Nine studies investigated sound intensity and reported high noise intensity with an average of 55-68 dB(A) (during daytime). In four studies about sound sources, human voices and electronic devices were the most dominant sources. Five cross-sectional studies focused on music interventions and reported positives effects on agitated behaviors. Four randomized controlled trials tested noise reduction as part of an intervention. In two studies, high-intensity sounds were associated with decreased nighttime sleep and increased agitation. The third study found an association between music and less agitation compared to other stimuli. The fourth study did not find an effect of noise on agitation. Two studies reported that a noisy environment had negative effects on staff. CONCLUSIONS: The need for appropriate auditory environments that are responsive to residents' cognitive abilities and functioning is not yet recognized widely. Future research needs to place greater emphasis on intervention-based and longitudinal study design