Distancing Measures and Challenges Discussed by COVID-19 Outbreak Teams of Dutch Nursing Homes:The COVID-19 MINUTES Study

The most severe COVID-19 infections and highest mortality rates are seen among long-term care residents. To reduce the risk of infection, physical distancing is important. This study investigates what physical distancing measures were discussed by COVID-19 outbreak teams of Dutch long-term care organizations and what challenges they encountered. The COVID-19 MINUTES study is a qualitative multi-center study (n = 41) that collected minutes of COVID-19 outbreak teams from March 2020 to October 2021. Textual units about distancing measures were selected and analyzed using manifest content analysis for the first wave: early March-early May 2020; the intermediate period of 2020: mid-May-mid-September 2020; and the second wave: late September 2020-mid-June 2021. During all periods, COVID-19 outbreak teams often discussed distancing visitors from residents. Moreover, during the first wave they often discussed isolation measures, during the intermediate period they often discussed distancing staff and volunteers from residents, and during both the intermediate period and the second wave they often discussed distancing among residents. During all periods, less often admission measures were discussed. Challenges persisted and included unrest among and conflicts between visitors and staff, visitors violating measures, resident non-adherence to measures, and staffing issues. The discussed distancing measures and corresponding challenges may guide local long-term care and (inter)national policymakers during the further course of the COVID-19 pandemic, outbreaks of other infectious diseases, and long-term care innovations

COVID-19 management in nursing homes by outbreak teams (MINUTES)-study description and data characteristics:A qualitative study

OBJECTIVES: Nursing homes are hit relatively hard by the COVID-19 pandemic. Dutch long-term care (LTC) organisations installed outbreak teams (OTs) to coordinate COVID-19 infection prevention and control. LTC organisations and relevant national policy organisations expressed the need to share experiences from these OTs that can be applied directly in COVID-19 policy. The aim of the ‘COVID-19 management in nursing homes by outbreak teams’ (MINUTES) study is to describe the challenges, responses and the impact of the COVID-19 pandemic in Dutch nursing homes. In this first article, we describe the MINUTES Study and present data characteristics. DESIGN: This large-scale multicentre study has a qualitative design using manifest content analysis. The participating organisations shared their OT minutes and other meeting documents on a weekly basis. Data from week 16 (April) to week 53 (December) 2020 included the first two waves of COVID-19. SETTING: National study with 41 large Dutch LTC organisations. PARTICIPANTS: The LTC organisations represented 563 nursing home locations and almost 43 000 residents. RESULTS: At least 36 of the 41 organisations had one or more SARS-CoV-2 infections among their residents. Most OTs were composed of management, medical staff, support services staff, policy advisors and communication specialists. Topics that emerged from the documents were: crisis management, isolation of residents, personal protective equipment and hygiene, staff, residents’ well-being, visitor policies, testing and vaccination. CONCLUSIONS: OT meeting minutes are a valuable data source to monitor the impact of and responses to COVID-19 in nursing homes. Depending on the course of the COVID-19 pandemic, data collection and analysis will continue until November 2021. The results are used directly in national and organisational COVID-19 policy

Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

<p>Abstract</p> <p>Background</p> <p>White matter hyperintensities (WMH) can lead to dementia but the underlying physiological mechanisms are unclear. We compared relative oscillatory power from electroencephalographic studies (EEGs) of 17 patients with subcortical ischemic vascular dementia, based on extensive white matter hyperintensities (SIVD-WMH) with 17 controls to investigate physiological changes underlying this diagnosis.</p> <p>Results</p> <p>Differences between the groups were large, with a decrease of relative power of fast activity in patients (alpha power 0.25 ± 0.12 versus 0.38 ± 0.13, p = 0.01; beta power 0.08 ± 0.04 versus 0.19 ± 0.07; p<0.001) and an increase in relative powers of slow activity in patients (theta power 0.32 ± 0.11 versus 0.14 ± 0.09; p<0.001 and delta power 0.31 ± 0.14 versus 0.23 ± 0.09; p<0.05). Lower relative beta power was related to worse cognitive performance in a linear regression analysis (standardized beta = 0.67, p<0.01).</p> <p>Conclusions</p> <p>This pattern of disturbance in oscillatory brain activity indicate loss of connections between neurons, providing a first step in the understanding of cognitive dysfunction in SIVD-WMH.</p

Reproducibility of EEG functional connectivity in Alzheimer's disease

BACKGROUND: Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer's disease (AD) compared to healthy subjects, there is no general consensus on the methodology of estimating functional connectivity in AD. Inconsistent results are reported due to multiple methodological factors such as diagnostic criteria, small sample sizes and the use of functional connectivity measures sensitive to volume conduction. We aimed to investigate the reproducibility of the disease-associated effects described by commonly used functional connectivity measures with respect to the amyloid, tau and neurodegeneration (A/T/N) criteria. METHODS: Eyes-closed task-free 21-channel EEG was used from patients with probable AD and subjective cognitive decline (SCD), to form two cohorts. Artefact-free epochs were visually selected and several functional connectivity measures (AEC(-c), coherence, imaginary coherence, PLV, PLI, wPLI) were estimated in five frequency bands. Functional connectivity was compared between diagnoses using AN(C)OVA models correcting for sex, age and, additionally, relative power of the frequency band. Another model predicted the Mini-Mental State Exam (MMSE) score of AD patients by functional connectivity estimates. The analysis was repeated in a subpopulation fulfilling the A/T/N criteria, after correction for influencing factors. The analyses were repeated in the second cohort. RESULTS: Two large cohorts were formed (SCD/AD; n = 197/214 and n = 202/196). Reproducible effects were found for the AEC-c in the alpha and beta frequency bands (p = 6.20 × 10-7, Cohen's d = - 0.53; p = 5.78 × 10-4, d = - 0.37) and PLI and wPLI in the theta band (p = 3.81 × 10-8, d = 0.59; p = 1.62 × 10-8, d = 0.60, respectively). Only effects of the AEC-c remained significant after statistical correction for the relative power of the selected bandwidth. In addition, alpha band AEC-c correlated with disease severity represented by MMSE score. CONCLUSION: The choice of functional connectivity measure and frequency band can have a large impact on the outcome of EEG studies in AD. Our results indicate that in the alpha and beta frequency bands, the effects measured by the AEC-c are reproducible and the most valid in terms of influencing factors, correlation with disease severity and preferable properties such as correction for volume conduction. Phase-based measures with correction for volume conduction, such as the PLI, showed reproducible effects in the theta frequency band

Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in HER2-positive advanced esophagogastric cancer: A meta-analysis

According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2-positive advanced esophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive esophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in-situ-hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N=557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS=20.7 months) versus ToGA (16.0 months, HR=0.75, 95%CI=0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered. This article is protected by copyright. All rights reserve

The Phenomenology of Primary Orthostatic Tremor

Background: The presence and prevalence of several neurological signs in patients with primary orthostatic tremor have not been systematically studied. Objectives: To assess the prevalence of clinical features of primary orthostatic tremor. Methods: Video-based assessment by four raters of standardized neurological examination of 11 patients with primary orthostatic tremor. Results: On standing, bent knees (7/11), hem sign (6/10), and a broad base of support (6/11) were the three most prevalent signs. Examination of gait revealed abnormal tandem gait (9/11) and bent knees (6/11) as the most prevalent clinical signs. In the arms, none of the patients displayed bradykinesia, ataxia, or dystonia. In the legs, ataxia was absent in all patients and bradykinesia was present in only one patient. Conclusions: Abnormal tandem gait, bent knees, hem sign, and broad base on standing are the most prevalent clinical signs in primary orthostatic tremor. We did not encounter clear extrapyramidal or unequivocal cerebellar signs

Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis

Introduction: After progression on first-line trastuzumab-based therapy, no HER2-targeted agent is available for patients with HER2-positive esophagogastric cancer. However, continuation of trastuzumab after progression is an established strategy in HER2-positive breast cancer. We conducted a meta-analysis to investigate whether continuation of trastuzumab beyond first-line therapy in combination with chemotherapy is more effective compared to chemotherapy-alone. Methods: PubMed, EMBASE, CENTRAL and meeting abstracts from ASCO and ESMO were searched up to June 2018 for studies (any design) investigating second-line trastuzumab plus chemotherapy compared to chemotherapy-alone for patients with HER2-positive esophagogastric cancer that progressed on first-line trastuzumab-based therapy. Meta-analysis was performed on the primary outcome, overall survival (OS), and on secondary outcomes progression-free survival (PFS), objective-response rate (ORR), and adverse events. Results: Four cohort studies and one randomized controlled trial (RCT) were included with n = 200 patients who received second-line trastuzumab plus chemotherapy and n = 183 who received chemotherapy-alone. Meta-analysis showed that trastuzumab plus chemotherapy did not prolonged OS [HR = 0.72, 95% confidence interval (95% CI) = 0.47–1.08, p=.11). PFS was longer with trastzumab plus chemotherapy compared to chemotherapy-alone (HR = 0.64, 95% CI = 0.45–0.91, p<.05). There was no significant difference in ORR between the trastuzumab plus chemotherapy-group and the chemotherapy-alone group (ORR = 19.1% versus ORR = 13.4%, p=.13) and no significant differences in grade 3/4 and grade 1/2 adverse events. Conclusions: This meta-analysis showed that patients who progressed on first-line trastuzumab-based therapy but of whom trastuzumab was continued in second-line and added to chemotherapy did not show longer OS or a higher ORR compared to patients receiving second-line chemotherapy-alone. However, PFS was prolonged and trastuzumab was not associated with additional safety concerns. In absence of available second-line HER2-targeted agents, a large prospective RCT should investigate if continuation of trastuzumab might be an attractive strategy, as this meta-analysis was mostly based on non-randomized studies and a RCT with a small sample size

Magnetoencephalography for the detection of intervention effects of a specific nutrient combination in patients with mild Alzheimer’s disease: Results from an exploratory double blind randomised controlled study

Synaptic loss is an early pathological finding in Alzheimer’s disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity and – networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity and graph theoretical aspects of MEG from the exploratory 24-week, double blind, randomized controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug-naïve patients with mild AD were compared between a test group (n=27), receiving Souvenaid, and a control group (n=28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination (MMSE). Peak frequencies of MEG were compared to EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared to EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further

Additional file 1: of Declining functional connectivity and changing hub locations in Alzheimer’s disease: an EEG study

The influence of the number of epochs. The number of epochs used for analyses influences the PLI outcomes. This supplement, including 1 figureand 1 table show that the PLI values become stable after 4 epochs of 8.192 seconds (4096 samples). (ZIP 66 kb