COVID-19 government measures and their impact on mental health: a cross-sectional study of older primary care patients in Germany.

Background: With the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany. Methods: Data were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support. Results: We analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p < 0.001). The association was no longer significant when adding stress and covariates (b = 0.04; p = 0.43), while stress was linked to increased depressive symptoms (b = 0.22; p < 0.001). A final model confirms the assumption that the feeling of restriction is mediated by stress (total effect: b = 0.26; p < 0.001). Conclusion: We found evidence that feeling restricted due to COVID-19 government measures is associated with higher levels of depressive symptoms in older adults at increased risk for dementia. The association is mediated by perceived stress. Furthermore, social support was significantly associated with less depressive symptoms. Thus, it is of high relevance to consider possible adverse effects of government measures related to COVID-19 on mental health of older people.

Routine Implementation of Patient-Reported Outcomes Assessment Into Thoracic Surgery Practice.

BACKGROUND: Patient-reported outcomes (PROs) assessment is a necessary component of surgical outcome assessment and patient care. This study examined the success of routine PROs assessment in an academic-based thoracic surgery practice. METHODS: PROs, measuring pain intensity, physical function, and dyspnea, were routinely obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System (PROMIS) on all thoracic surgery patients beginning in April 2018 through January 2021. Questionnaires were administered electronically through a web-based platform at home or during the office visit. Completion rates and barriers were measured. RESULTS: A total of 9725 thoracic surgery office visits occurred during this time frame. PROs data were obtained in 6899 visits from a total of 3551 patients. The mean number of questions answered per survey was 22.4 ± 2.2. Overall questionnaire completion rate was 65.7%. A significant decline in survey completion was noted in April 2020, after which adjustments were made to allow for questionnaire completion through a mobile health platform. Overall monthly questionnaire completion rates ranged from 20% (April 2020) to 90% (October 2018). Mean T scores were dyspnea, 41.6 ± 12.3; physical function, 42.7 ± 10.5; and pain intensity, 52.8 ± 10.3. CONCLUSIONS: PROs can be assessed effectively in a thoracic surgery clinic setting, with minimal disruption of clinical activities. Future efforts should focus on facilitating PROs collection from disadvantaged patient populations and scaling implementation across programs.

Dark-field chest X-ray imaging for the assessment of COVID-19-pneumonia.

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging. METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski's method with a 0.05 level of significance. RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients. CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.

Computed tomography (CT) imaging uses X-rays to obtain images of the inside of the body. It is used to look at lung damage in patients with COVID-19. However, CT imaging exposes the patient to a considerable amount of radiation. As radiation exposure can lead to the development of cancer, exposure should be minimised. Conventional plain X-ray imaging uses lower amounts of radiation but lacks sensitivity. We used dark-field chest X-ray imaging, which also uses low amounts of radiation, to assess the lungs of patients with COVID-19. Radiologists identified pneumonia in patients more easily from dark-field images than from usual plain X-ray images. We anticipate dark-field X-ray imaging will be useful to follow-up patients suspected of having lung damage.

Fact boxes that inform individual decisions may contribute to a more positive evaluation of COVID-19 vaccinations at the population level.

OBJECTIVE: For an effective control of the SARS-CoV-2 pandemic with vaccines, most people in a population need to be vaccinated. It is thus important to know how to inform the public with reference to individual preferences-while also acknowledging the societal preference to encourage vaccinations. According to the health care standard of informed decision-making, a comparison of the benefits and harms of (not) having the vaccination would be required to inform undecided and skeptical people. To test evidence-based fact boxes, an established risk communication format, and to inform their development, we investigated their contribution to knowledge and evaluations of COVID-19 vaccines. METHODS: We conducted four studies (1, 2, and 4 were population-wide surveys with N = 1,942 to N = 6,056): Study 1 assessed the relationship between vaccination knowledge and intentions in Germany over three months. Study 2 assessed respective information gaps and needs of the population in Germany. In parallel, an experiment (Study 3) with a mixed design (presentation formats; pre-post-comparison) assessed the effect of fact boxes on risk perceptions and fear, using a convenience sample (N = 719). Study 4 examined how effective two fact box formats are for informing vaccination intentions, with a mixed experimental design: between-subjects (presentation formats) and within-subjects (pre-post-comparison). RESULTS: Study 1 showed that vaccination knowledge and vaccination intentions increased between November 2020 and February 2021. Study 2 revealed objective information requirements and subjective information needs. Study 3 showed that the fact box format is effective in adjusting risk perceptions concerning COVID-19. Based on those results, fact boxes were revised and implemented with the help of a national health authority in Germany. Study 4 showed that simple fact boxes increase vaccination knowledge and positive evaluations in skeptics and undecideds. CONCLUSION: Fact boxes can inform COVID-19 vaccination intentions of undecided and skeptical people without threatening societal vaccination goals of the population.

Learning Agroecology Online During COVID-19

Since March 2020, the COVID-19 pandemic propelled the "stay-at-home" policy worldwide under public health uncertainty, resulting in increased individualization, as well as an increased reliance or dependency on digital communication technology. Based on a review of existing literature alongside a reflection on personal fieldwork experiences, we aim to: (1) describe major elements of agroecological pedagogy, (2) explore adaptation pathways to combine digitalization and participatory action-learning, and (3) briefly discuss opportunities and challenges for agroecologists beyond COVID-19. Agroecological pedagogy is deeply embedded in the praxis, the scientific knowledge and ways of knowing (academic or not), and in the politics and agency of food movements. In line with Freire's liberation pedagogy, seeing what already exists (e.g., in: ecosystems, home-gardens, fields, farms, and watersheds) through participation and volunteering. Alongside a critical analysis to explain and explore certain phenomena, causes and consequences will likely result in the act leading to the implementation of transformative practices and novel designs that improve the state of any situation being addressed. Participatory action research/learning methods are strategic in agroecological pedagogy. Overall, the lockdown period led to increased societal digitalization of human interactions. During lockdown, however, the implementation of strategies for remote agroecology participatory action-learning were hampered, but not vanquished. Key changes to agroecology education projects "before" and "during" lockdown include an increased reliance on digital and remote strategies. Creative adaptations in the virtual classrooms were designed to nurture, deepen, and foster alternatives in favor of diverse knowledges and ways of knowing for food system transformations.

Nopp140-chaperoned 2'-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity.

Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.

Nopp140-chaperoned 2’-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity (preprint)

ABSTRACT Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB) specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at some 80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2’-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.

Patterns of sedation and narcotic utilization for critically ill patients with COVID-19

INTRODUCTION: The COVID-19 pandemic has proliferated since the start of this year and has strained ICU resources globally. Far from an isolated respiratory illness, COVID-19 has multisystem effects, including pronounced neurological effects. Very little is known about critically ill patients and their sedation/analgesia requirements. We sought to quantify the sedation requirements for critically ill patients with COVID-19. METHODS: A prospective registry from 03/2020 to 06/2020 with COVID-19 at an urban tertiary care hospital was analyzed for intubated COVID-19 patients. Sedation data was abstracted for days 1,3,5,7,10,13,16,19,22,25, and 28 from the EMR, and infusion information was recorded as weighted average doses over a 24-hour period. Narcotics were reported as oral morphine equivalents (OMEs) and benzodiazepine doses were reported as midazolam equivalents (ME). A comparison was made to the placebo group of patients from the MIND-USA study as the median of the means. RESULTS: A total of 62 patients were analyzed with 55% African American, 33% Hispanic, 65% male, mean age of 58.5 years old, BMI of 33, and APACHE II score on ICU admission of 18.6. The median duration of mechanical ventilation was 9.5 days and an in-hospital mortality of 80.6%. Compared to the control arm of the MIND-USA study, the COVID-19 cohort had 2.89x higher propofol dose (TDD 4032 mg vs. 1391 mg), 5.5x higher precedex dose (TDD 3400mcg vs. 617mcg), 8.8x higher benzodiazepine dose (35 mg ME vs. 4 mg ME) and 1.79x higher OME dose (363 mg vs. 203 mg). The average infusions per patients was 2.42 and the most used infusions used were propofol (30% of patients per day) and precedex (25.8%). Approximately 17.6% of patients per day were receiving a paralytic infusion;however, a considerably greater share of patients (46.6% per day) were demonstrating quadriplegic paralysis. CONCLUSIONS: Critically ill patients with COVID-19 infection have significantly higher sedation/narcotic requirements than patients without COVID-19. This may be related to the underlying neurological effects of the virus and a potentially synergistic effect with sedation causing a high rate of quadriplegic paralysis. Further prospective trials are required to evaluate this hypothesis.