Use, failure, and non-compliance of respiratory personal protective equipment and risk of upper respiratory tract infections-A longitudinal repeated measurement study during the COVID-19 pandemic among healthcare workers in Denmark.

INTRODUCTION: Upper respiratory tract infections (URTI) are common and a common cause of sick-leave for healthcare workers, and furthermore pose a threat especially for patients susceptible to other diseases. Sufficient use of respiratory protective equipment (RPE) may protect both the workers and the patients. The COVID-19 pandemic provided a unique opportunity to study the association between use of RPE and URTI in a real-life setting. The aim of this study was to examine if failure of RPE or non-compliance with RPE guidelines increases the risk of non-COVID-19 URTI symptoms among healthcare workers. METHODS: In a longitudinal cohort study, we collected self-reported data daily on work tasks, use of RPE, and URTI symptoms among healthcare workers with patient contact in 2 Danish Regions in 2 time periods during the COVID-19 pandemic. The association between failure of RPE or non-compliance with RPE guidelines and URTI symptoms was analyzed separately by generalized linear models. Persons tested positive for severe acute respiratory syndrome coronavirus 2 were censored from the analyses. The 2 waves of data collection were analyzed separately, as there were differences in recommendations of RPE during the 2 waves. RESULTS: We found that for healthcare workers performing work tasks with a risk of transmission of viruses or bacteria, failure of RPE was associated with an increased risk of URTI symptoms, RR: 1.65[0.53-5.14] in wave 1 and RR: 1.30[0.56-3.03] in wave 2. Also non-compliance with RPE guidelines was associated with an increased risk of URTI symptoms compared to the use of RPE in wave 1, RR: 1.28[0.87-1.87] and wave 2, RR: 1.39[1.01-1.91]. Stratifying on high- versus low-risk tasks showed that the risk related to failure and non-compliance was primarily associated with high-risk tasks, although not statistically significant. DISCUSSION: The study was conducted during the COVID-19 pandemic and thus may be affected by other preventive measures in society. However, this gave the opportunity to study the use of RPE in a real-life setting, also in departments that did not previously use RPE. The circumstances in the 2 time periods of data collection differed and were analyzed separately and thus the sample size was limited and affected the precision of the estimates. CONCLUSION: Failures of RPE and non-compliance with RPE guidelines may increase the risk of URTI, compared to those who reported use of RPE as recommended. The implications of these findings are that the use of RPE to prevent URTI could be considered, especially while performing high-risk tasks where other prevention strategies are not achievable.

EEG Frequency Correlates with α2-Receptor Density in Parkinson's Disease.

INTRODUCTION: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson's disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We claim that the loss of noradrenaline may explain cognitive impairment and the pathological slowing of EEG waves. Here, we test the relationship between the number of noradrenergic α2 adrenoceptors and changes in the spectral EEG ratio in patients with PD. METHODS: We included nineteen patients with PD and thirteen healthy control (HC) subjects in the study. We used positron emission tomography (PET) with [11C]yohimbine to quantify α2 adrenoceptor density. We used EEG power in the delta (δ, 1.5-3.9 Hz), theta (θ, 4-7.9 Hz), alpha (α, 8-12.9 Hz) and beta (ß, 13-30 Hz) bands in regression analyses to test the relationships between α2 adrenoceptor density and EEG band power. RESULTS: PD patients had higher power in the theta and delta bands compared to the HC volunteers. Patients' theta band power was inversely correlated with α2 adrenoceptor density in the frontal cortex. In the HC subjects, age was correlated with, and occipital background rhythm frequency (BRF) was inversely correlated with, α2 adrenoceptor density in the frontal cortex, while occipital BRF was inversely correlated with α2 adrenoceptor density in the thalamus. CONCLUSIONS: The findings support the claim that the loss or dysfunction of noradrenergic neurotransmission may relate to the parallel processes of cognitive decline and EEG slowing.

Occupational exposure to epoxy components and risk of dermatitis: A registry-based follow-up study of the wind turbine industry.

BACKGROUND: Allergic contact allergy and dermatitis are frequently reported among epoxy-exposed workers. OBJECTIVES: To determine the risk of dermatitis associated with epoxy exposure. METHODS: We followed 825 epoxy-exposed and 1091 non-exposed blue-collar workers, and 493 white-collar workers of a Danish wind turbine blade factory during 2017-2022 with linked data from national health registers on diagnoses, patch testing, or fillings of prescriptions for topical corticosteroids. Incidence rate ratios of dermatitis or a first-time topical corticosteroid prescription were estimated with Poisson regression using non-exposed blue-collar workers as reference. We similarly estimated incidence rate ratios for the duration of epoxy exposure and current epoxy exposure. RESULTS: Epoxy-exposed blue-collar workers showed a dermatitis incidence rate of 2.1 per 100 000 person days, a two-fold increased risk of dermatitis and a 20% increased risk of filling a prescription for topical corticosteroids. Incidence rate ratios were higher during early exposure and declined with further exposure for both outcomes. White-collar workers had generally lower risks. CONCLUSION: We observed an increased risk of dermatitis following epoxy exposure confirming previous case reports and cross-sectional studies emphasizing the need for intensified focus on preventive efforts for this group of workers.

Use of Personal Protective Equipment Among Healthcare Workers During the First and the Second Wave of the COVID-19 Pandemic.

INTRODUCTION: To treat and properly care for COVID-19 patients it is vital to have healthy healthcare workers to ensure the continued function of the healthcare system and to prevent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to patients, co-workers, and the community. Personal protective equipment (PPE) can prevent healthcare workers from being infected with and transmitting SARS-CoV-2. Experience and training are pivotal to ensure optimal protection. This study aims to examine the use and failure of PPE and compliance with PPE guidelines during the first and the second wave of the COVID-19 pandemic among Danish healthcare workers. METHODS: Healthcare workers from the Central Denmark Region and the Capital Region of Denmark were invited to participate April-June 2020 during the first wave and November 2020-April 2021 during the second wave. Day-by-day, participants reported work procedures, use and failure of PPE, and compliance with PPE guidelines. Register-based information on sex, age, department, and profession was available for all participants. RESULTS: In total, 21 684 and 10 097 healthcare workers participated during the first and the second wave, respectively. During the first wave, 1.7% used filtering face piece-2 or -3 (FFP2 or FFP3) respirators and 8.2% used face masks [fluid resistant (type IIR) masks, masks with visor (typically type IIR), and other unspecified face masks] during physical contact with patients. During the second wave, the corresponding figures increased to 17.8% and 80.7%. During respiratory procedures, the use of FFP2 or FFP3 respirators increased from 5.6 to 24.3%, and the use of face masks from 14.7 to 77.8%. The no PPE use decreased from 21.3% during the first wave to 0.4% in the second wave, during respiratory procedures. Total PPE failures decreased from 0.7 to 0.4% from the first to second wave. The proportion not complying with PPE guidelines declined from 3.6 to 2.2% during physical contact with patients and from 6.5 to 4.6% during respiratory procedures. PPE failure and non-compliance varied by age, sex and type of department. Frequent reasons for non-compliance were forgetfulness and lack of time, and during the first but not during the second wave, limited availability of PPE. CONCLUSION: We found a substantial increase in the use of PPE and a substantial decrease in PPE failures from the first to the second wave of COVID-19 in Denmark. However, there is still a need for continuous focus on compliance in use of PPE among healthcare workers.

Risk of myocardial infarction among pigeon breeders: A follow-up study.

Pigeon breeders are exposed to high levels of fine particulate organic matter in the pigeon lofts. A total of 6,704 pigeon breeders and their 1:30 sex and age-matched referents from the general Danish population were followed from 1980 or first year of membership in the Danish Racing Pigeon Association, until first event of myocardial infarction, emigration, death, or end of study, on December 31, 2013. Information on outcomes and covariates was obtained by record linkage with national registers. Stratified Cox regression models estimated the hazard ratio of myocardial infarction, adjusted for occupation and residence at the start of follow-up. Compared with referents, pigeon breeders had an adjusted hazard ratio of 1.14 (95% CI: 1.05-1.22) for myocardial infarction. Exposure to pigeon-derived organic dust may increase the risk of myocardial infarction, but this finding needs to be corroborated.

Disruption of Sleep Microarchitecture Is a Sensitive and Early Marker of Parkinson's Disease.

BACKGROUND: Although sleep disturbances are highly prevalent in patients with Parkinson's disease, sleep macroarchitecture metrics show only minor changes. OBJECTIVE: To assess alterations of the cyclic alternating pattern (CAP) as a critical feature of sleep microarchitecture in patients with prodromal, recent, and established Parkinson's disease. METHODS: We evaluated overnight polysomnography for classic sleep macroarchitecture and CAP metrics in 68 patients at various disease stages and compared results to 22 age- and sex-matched controls. RESULTS: Already at the prodromal stage, patients showed a significantly reduced CAP rate as a central characteristic of sleep microarchitecture. Temporal characteristics of CAP showed a gradual change over disease stages and correlated with motor performance. In contrast, the sleep macroarchitecture metrics did not differ between groups. CONCLUSION: Data suggest that alterations of sleep microarchitecture are an early and more sensitive characteristic of Parkinson's disease than changes in sleep macroarchitecture.

Intestinal Transit in Early Moderate Parkinson's Disease Correlates with Probable RBD: Subclinical Esophageal Dysmotility Does Not Correlate.

Background: Nonmotor symptoms, including constipation and dysphagia, are very common in Parkinson's disease (PD) and Lewy pathology is widespread in the gastrointestinal tract, particularly in the lower esophagus. Constipation and REM sleep behavior disorder (RBD) may present prior to clinical diagnosis. Yet, little is known about esophageal dysfunction and its connection to constipation in early PD. Objective: This study aimed to investigate esophageal and colonic transit in early moderate PD and to study correlations between symptoms and objective measures. Methods: Thirty early moderate PD patients and 28 healthy controls (HC) were included in this cross-sectional study. Esophageal transit times were determined by esophageal scintigraphy and colonic transit times by CT after radio-opaque marker ingestion. Olfaction tests, clinical evaluation, and nonmotor questionnaires were also performed. Results: Distal esophageal transit times and colonic transit times were both significantly prolonged in the PD group compared to HC (p < 0.05 andp < 0.01, respectively) and a moderate-strong positive correlation was found between colonic transit time (CTT) and RBDSQ score (r = 0.61,p < 0.001). Significant correlations were also found between CTT and SCOPA-AUT scores as well as between CTT and ROME III functional constipation scores. Conclusion: Colonic transit correlates with probable RBD and is more severely prolonged in early moderate PD than is the distal esophageal transit time.

Healthcare workers' SARS-CoV-2 infection rates during the second wave of the pandemic: follow-up study.

OBJECTIVES: This study aimed to assess if, during the second wave of the COVID-19 pandemic, healthcare workers had increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, following close contact with patients, co-workers and persons outside work with COVID-19. METHODS: A follow-up study of 5985 healthcare workers from Denmark was conducted between November 2020 and April 2021 and provided day-to-day information on COVID-19 contacts. SARS-CoV-2 infection was defined by the first positive polymerase chain reaction (PCR) test ever. Data was analyzed in multivariable Poisson regression models. RESULTS: The SARS-CoV-2 infection rates following close contact 3-7 days earlier with patients, co-workers and persons outside work with COVID-19 were 153.7, 240.8, and 728.1 per 100 000 person-days, respectively. This corresponded with age, sex, month, number of PCR tests and mutually adjusted incidence rate ratios of 3.17 [40 cases, 95% confidence interval (CI) 2.15-4.66], 2.54 (10 cases, 95% CI 1.30-4.96) and 17.79 (35 cases, 95% CI 12.05-26.28). The risk of SARS-CoV-2 infection was thus lower, but the absolute numbers affected was higher following COVID-19 contact at work than COVID-19 contact off work. CONCLUSIONS: Despite strong focus on preventive measures during the second wave of the pandemic, healthcare workers were still at increased risk of SARS-CoV-2 infection when in close contact with patients or co-workers with COVID-19. There is a need for increased focus on infection control measures in order to secure healthcare workers' health and reduce transmission into the community during ongoing and future waves of SARS-CoV-2 and other infections.

Functional connectivity of spoken language processing in early-stage Parkinson's disease: An MEG study.

Parkinson's disease (PD) is a neurodegenerative disorder, well-known for its motor symptoms; however, it also adversely affects cognitive functions, including language, a highly important human ability. PD pathology is associated, even in the early stage of the disease, with alterations in the functional connectivity within cortico-subcortical circuitry of the basal ganglia as well as within cortical networks. Here, we investigated functional cortical connectivity related to spoken language processing in early-stage PD patients. We employed a patient-friendly passive attention-free paradigm to probe neurophysiological correlates of language processing in PD patients without confounds related to active attention and overt motor responses. MEG data were recorded from a group of newly diagnosed PD patients and age-matched healthy controls who were passively presented with spoken word stimuli (action and abstract verbs, as well as grammatically correct and incorrect inflectional forms) while focussing on watching a silent movie. For each of the examined linguistic aspects, a logistic regression classifier was used to classify participants as either PD patients or healthy controls based on functional connectivity within the temporo-fronto-parietal cortical language networks. Classification was successful for action verbs (accuracy = 0.781, p-value = 0.003) and, with lower accuracy, for abstract verbs (accuracy = 0.688, p-value = 0.041) and incorrectly inflected forms (accuracy = 0.648, p-value = 0.021), but not for correctly inflected forms (accuracy = 0.523, p-value = 0.384). Our findings point to quantifiable differences in functional connectivity within the cortical systems underpinning language processing in newly diagnosed PD patients compared to healthy controls, which arise early, in the absence of clinical evidence of deficits in cognitive or general language functions. The techniques presented here may aid future work on establishing neurolinguistic markers to objectively and noninvasively identify functional changes in the brain's language networks even before clinical symptoms emerge.

Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson's disease.

Previous studies have reported substantial involvement of the noradrenergic system in Parkinson's disease. Neuromelanin-sensitive MRI sequences and PET tracers have become available to visualize the cell bodies in the locus coeruleus and the density of noradrenergic terminal transporters. Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson's disease. We examined 93 subjects (40 healthy controls and 53 Parkinson's disease patients) with neuromelanin-sensitive turbo spin-echo MRI and calculated locus coeruleus-to-pons signal contrasts. Voxels with the highest intensities were extracted from published locus coeruleus coordinates transformed to individual MRI. To also investigate a potential spatial pattern of locus coeruleus degeneration, we extracted the highest signal intensities from the rostral, middle, and caudal third of the locus coeruleus. Additionally, a study-specific probabilistic map of the locus coeruleus was created and used to extract mean MRI contrast from the entire locus coeruleus and each rostro-caudal subdivision. Locus coeruleus volumes were measured using manual segmentations. A subset of 73 subjects had 11C-MeNER PET to determine noradrenaline transporter density, and distribution volume ratios of noradrenaline transporter-rich regions were computed. Patients with Parkinson's disease showed reduced locus coeruleus MRI contrast independently of the selected method (voxel approaches: P < 0.0001, P < 0.001; probabilistic map: P < 0.05), specifically on the clinically-defined most affected side (P < 0.05), and reduced locus coeruleus volume (P < 0.0001). Reduced MRI contrast was confined to the middle and caudal locus coeruleus (voxel approach, rostral: P = 0.48, middle: P < 0.0001, and caudal: P < 0.05; probabilistic map, rostral: P = 0.90, middle: P < 0.01, and caudal: P < 0.05). The noradrenaline transporter density was lower in patients with Parkinson's diseasein all examined regions (group effect P < 0.0001). No significant correlation was observed between locus coeruleus MRI contrast and noradrenaline transporter density. In contrast, the individual ratios of noradrenaline transporter density and locus coeruleus MRI contrast were lower in Parkinson's disease patients in all examined regions (group effect P < 0.001). Our multimodal imaging approach revealed pronounced noradrenergic terminal loss relative to cellular locus coeruleus degeneration in Parkinson's disease; the latter followed a distinct spatial pattern with the middle-caudal portion being more affected than the rostral part. The data shed first light on the interaction between the axonal and cell body compartments and their differential susceptibility to neurodegeneration in Parkinson's disease, which may eventually direct research towards potential novel treatment approaches.

Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease.

STUDY OBJECTIVES: Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients. METHODS: We analyzed 27 PD patients and 13 healthy control (HC) subjects who underwent overnight polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters, as well as CAP metrics, were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density. RESULTS: PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex. CONCLUSIONS: Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.

Preserved noradrenergic function in Parkinson's disease patients with rest tremor.

Noradrenergic neurotransmission may play an important role in tremor modulation through its innervation of key structures of the central tremor circuits. Here, Parkinson's disease (PD) patients with (PDT+) or without (PDT-) rest tremor had 11C-methylreboxetine(11C-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PDT+ compared to PDT-. METHODS: Sixty-five PD patients and 28 healthy controls (HC) were scanned with 11C-MeNER PET. Patients were categorized as PDT+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was ≥2; remaining were categorized as PDT-. Simplified reference tissue model 2 distribution volume ratios (DVR) for 11C-MeNER were calculated for thalamus, dorsal and median raphe, locus coeruleus (LC) and red nucleus using time activity curves (TACs) obtained from volumes of interest (VOI). Data were statistically interrogated with a general linear mixed model using 'region', and 'group' as factors and the interaction of 'region x group' was examined. RESULTS: Tremor positive PD patients had a significantly higher mean 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-MeNER DVR across all regions compared to HC. CONCLUSION: While both PD T+ and PD T- groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PDT+ in LC and thalamus. The greater loss of noradrenergic transporters in PDT- in LC and thalamus compared with PDT+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.

Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder - A PET study.

INTRODUCTION: Noradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand 11C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using 11C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether 11C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with 18F-DOPA PET were correlated. METHODS: 17 iRBD patients, 16 PD patients with (PDRBD+) and 14 without RBD (PDRBD-), and 25 control subjects underwent 11C-MeNER PET. iRBD patients also had 18F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed. RESULTS: Partial-volume corrected 11C-MeNER binding potential (BPND) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PDRBD+ groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PDRBD+P = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 11C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal 18F-DOPA uptake and thalamic 11C-MeNER binding in iRBD patients (r2 = 0.343, P = 0.013). CONCLUSIONS: This study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 11C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic 11C-MeNER binding and putaminal 18F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.

Molecular Imaging of the Noradrenergic System in Idiopathic Parkinson's Disease.

Noradrenergic neurons in both the peripheral nervous system and in the central nervous system (CNS) undergo severe degeneration in patients with Parkinson's disease (PD). This loss of noradrenaline may play essential roles in the occurrence of a wide range of prevalent non-motor symptoms and can further complicate the lives of PD patients. In vivo molecular imaging of noradrenaline may provide insights into to the extent of degeneration of noradrenergic neurons and subsequent depletion of noradrenergic projections. Molecular imaging methods exist to quantify the noradrenergic deficiency in peripheral autonomic terminals, such as [123I]-meta-iodobenzylguanidin scintigraphy of the heart. However, the degeneration of noradrenergic nuclei in the brainstem and their projections to the CNS has only been quantified with non-selective positron emission tomography ligands in previous studies. Here, we review recent advances in in vivo molecular imaging techniques that evaluate the role of deficits of noradrenaline in PD patients in the manifestation of motor and non-motor symptoms.

Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER.

Degeneration of noradrenergic neurons may underlie the disabling nonmotor symptoms in patients with Parkinson disease (PD). Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand (S,S)-11C-2-(α-(2-methoxyphenoxy)benzyl)morpholine (11C-MeNER) is a highly selective inhibitor of noradrenaline transporters, and PET studies suggest that this radioligand is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo. In the present investigation, we used PET with 11C-MeNER to map the density of noradrenaline transporters in groups of patients with PD and age-matched healthy controls. Methods: After administration of 11C-MeNER, 15 nondemented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) by multilinear analysis, simplified reference tissue model 2, and multilinear reference tissue model 2. Results: Metabolism of 11C-MeNER did not differ between groups. The simplified reference tissue model 2 and the multilinear reference tissue model 2 were used to determine 11C-MeNER BPND11C-MeNER BPND was reduced in the PD group compared with the control subjects, with regionally significant declines in the thalamus and nucleus ruber. Tremor was associated with higher tracer binding in the PD group on multivariate regression analysis. Conclusion: To our knowledge, this was the first specific quantification of noradrenergic denervation in PD patients in vivo. In agreement with predictions from determinations in vitro, we discovered a decline of noradrenergic projections in vivo in brain of PD patients.