Evaluating a multimodal, clinical and work-directed intervention (RTW-PIA) to support sustainable return to work among employees with mental disorders: study protocol of a multicentre, randomised controlled trial.

BACKGROUND: Mental disorders (MDs) are one of the leading causes for workforce sickness absence and disability worldwide. The burden, costs and challenges are enormous for the individuals concerned, employers and society at large. Although most MDs are characterised by a high risk of relapse after treatment or by chronic courses, interventions that link medical-psychotherapeutic approaches with work-directed components to facilitate a sustainable return to work (RTW) are rare. This protocol describes the design of a study to evaluate the (cost-)effectiveness and implementation process of a multimodal, clinical and work-directed intervention, called RTW-PIA, aimed at employees with MDs to achieve sustainable RTW in Germany. METHODS: The study consists of an effectiveness, a health-economic and a process evaluation, designed as a two-armed, multicentre, randomised controlled trial, conducted in German psychiatric outpatient clinics. Sick-listed employees with MDs will receive either the 18-month RTW-PIA treatment in conjunction with care as usual, or care as usual only. RTW-PIA consists of a face-to-face individual RTW support, RTW aftercare group meetings, and web-based aftercare. Assessments will be conducted at baseline and 6, 12, 18 and 24 months after completion of baseline survey. The primary outcome is the employees´ achievement of sustainable RTW, defined as reporting less than six weeks of working days missed out due to sickness absence within 12 months after first RTW. Secondary outcomes include health-related quality of life, mental functioning, RTW self-efficacy, overall job satisfaction, severity of mental illness and work ability. The health-economic evaluation will be conducted from a societal and public health care perspective, as well as from the employer's perspective in a cost-benefit analysis. The design will be supplemented by a qualitative effect evaluation using pre- and post-interviews, and a multimethod process evaluation examining various predefined key process indicators from different stakeholder perspectives. DISCUSSION: By applying a comprehensive, multimethodological evaluation design, this study captures various facets of RTW-PIA. In case of promising results for sustainable RTW, RTW-PIA may be integrated into standard care within German psychiatric outpatient clinics. TRIAL REGISTRATION: The study was prospectively registered with the German Clinical Trials Register ( DRKS00026232 , 1 September 2021).

First responder communication in CBRN environments: FIRCOM-CBRN study.

INTRODUCTION: Recent terror attacks and assassinations involving highly toxic chemical weapons have stressed the importance of sufficient respiratory protection of medical first responders and receivers. As full-face respirators cause perceptual-motor impairment, they not only impair vision but also significantly reduce speech intelligibility. The recent introduction of electronic voice projection units (VPUs), attached to a respirator, may improve communication while wearing personal respiratory protection. OBJECTIVE: To determine the influence of currently used respirators and VPUs on medical communication and speech intelligibility. METHODS: 37 trauma anaesthetists carried out an evaluation exercise of six different respirators and VPUs including one control. Participants had to listen to audio clips of a variety of sentences dealing with scenarios of emergency triage and medical history taking. RESULTS: In the questionnaire, operators stated that speech intelligibility of the Avon C50 respirator scored the highest (mean 3.9, ±SD 1.0) and that the Respirex Powered Respiratory Protective Suit (PRPS) NHS-suit scored lowest (1.6, 0.9). Regarding loudness the C50 plus the Avon VPU scored highest (4.1, 0.7), followed by the Draeger FPS-7000-com-plus (3.4, 1.0) and the Respirex PRPS NHS-suit scored lowest (2.3, 0.8). CONCLUSIONS: We found that the Avon C50 is the preferred model among the tested respirators. In our model, electronic voice projection modules improved loudness but not speech intelligibility. The Respirex PRPS NHS-suit was rated significantly less favourably in respect of medical communication and speech intelligibility.

Survey of UK Health Care First Responders' Knowledge of Personal Protective Equipment Requirements.

INTRODUCTION: An adequate level of personal protective equipment (PPE) is necessary when treating patients with highly infectious diseases or those contaminated with hazardous substances. METHODS: Following National Institute for Health Research's Research Centre (London, United Kingdom) approval, the authors of this study conducted a survey of specialist registrars' knowledge of the respiratory and skin protection requirements needed during a resuscitation scenario with Advanced Life Support. Participant responses were compared to UK national recommendations and to a previous survey in 2009. RESULTS: A total of 98 specialist registrars (in Anesthesiology, n=51; in Emergency Medicine (EM), n=21; and in Intensive Care Medicine (ICM) n=26) completed hand-delivered surveys. The best knowledge of PPE requirements (76%) was found for severe acute respiratory syndrome (SARS), with less knowledge about PPE requirements for anthrax, plague, Ebola virus disease (EVD), and smallpox (60%). The results show limited knowledge of PPE requirements (20%-30%) for various chemical warfare agents. Personal protective equipment knowledge regarding treatment of sarin-contaminated casualties was over-rated by 80%, and for patients with EVD, it was over-rated by up to 67% of participants. CONCLUSION: The results of the tested cohort indicate that current knowledge regarding PPE for chemical warfare agents remains very limited.

Automatic segmentation of odor maps in the mouse olfactory bulb using regularized non-negative matrix factorization.

Segmentation of functional parts in image series of functional activity is a common problem in neuroscience. Here we apply regularized non-negative matrix factorization (rNMF) to extract glomeruli in intrinsic optical signal (IOS) images of the olfactory bulb. Regularization allows us to incorporate prior knowledge about the spatio-temporal characteristics of glomerular signals. We demonstrate how to identify suitable regularization parameters on a surrogate dataset. With appropriate regularization segmentation by rNMF is more resilient to noise and requires fewer observations than conventional spatial independent component analysis (sICA). We validate our approach in experimental data using anatomical outlines of glomeruli obtained by 2-photon imaging of resting synapto-pHluorin fluorescence. Taken together, we show that rNMF provides a straightforward method for problem tailored source separation that enables reliable automatic segmentation of functional neural images, with particular benefit in situations with low signal-to-noise ratio as in IOS imaging.

Hepatic sinusoidal obstruction syndrome after immune-checkpoint-inhibitor therapy: when the liver sends SOS.

A woman in her 50s presented to the hospital with new-onset jaundice and ascites. Her medical history included a melanoma of the right shoulder, diagnosed 8 months before, for which she had received four cycles of ipilimumab and nivolumab. Due to the oncological history and previous immunotherapy, an immune-checkpoint-inhibitor (ICI)-induced hepatitis was suspected, and a high-dose corticosteroid treatment was initiated. However, as there was no improvement in the liver function tests, a percutaneous liver biopsy was performed for further diagnostic clarification. Histological analysis ultimately identified a hepatic sinusoidal obstruction syndrome (SOS) as the underlying cause of liver dysfunction and portal hypertension. ICI-related hepatic SOS represents an extremely rare adverse event related to immunotherapy that should be considered in all patients with treatment-refractory ICI-related hepatotoxicity and clinical signs of portal hypertension.

Magneto-optical assessment of Plasmodium parasite growth via hemozoin crystal size.

Hemozoin is a natural biomarker formed during the hemoglobin metabolism of Plasmodium parasites, the causative agents of malaria. The rotating-crystal magneto-optical detection (RMOD) has been developed for its rapid and sensitive detection both in cell cultures and patient samples. In the current article we demonstrate that, besides quantifying the overall concentration of hemozoin produced by the parasites, RMOD can also track the size distribution of the hemozoin crystals. We establish the relations between the magneto-optical signal, the mean parasite age and the median crystal size throughout one erythrocytic cycle of Plasmodium falciparum parasites, where the latter two are determined by optical and scanning electron microscopy, respectively. The significant correlation between the magneto-optical signal and the stage distribution of the parasites indicates that the RMOD method can be utilized for species-specific malaria diagnosis and for the quick assessment of drug efficacy.

Respiratory protection during simulated emergency pediatric life support: a randomized, controlled, crossover study.

INTRODUCTION: Emergency pediatric life support (EPLS) of children infected with transmissible respiratory diseases requires adequate respiratory protection for medical first responders. Conventional air-purifying respirators (APR) and modern loose-fitting powered air-purifying respirator-hoods (PAPR-hood) may have a different impact during pediatric resuscitation and therefore require evaluation. OBJECTIVE: This study investigated the influence of APRs and PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. METHODS: Study design was a randomized, controlled, crossover study. Sixteen paramedics carried out a standardized EPLS scenario inside an ambulance, either unprotected (control) or wearing a conventional APR or a PAPR-hood. Treatment times and wearer comfort were determined and compared. RESULTS: All paramedics completed the treatment objectives of the study arms without adverse events. Study subjects reported that communication, dexterity and mobility were significantly better in the APR group, whereas the heat-build-up was significantly less in the PAPR-hood group. Treatment times compared to the control group did not significantly differ for the APR group but did with the PAPR-hood group (261±12 seconds for the controls, 275±9 seconds for the conventional APR and 286±13 seconds for the PAPR-hood group, P < .05. CONCLUSIONS: APRs showed a trend to better treatment times compared to PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. Study participants rated mobility, ease of communication and dexterity with the tight-fitting APR system significantly better compared to the loose-fitting PAPR-hood.

3D Bioprinting of Prevascularized Full-Thickness Gelatin-Alginate Structures with Embedded Co-Cultures.

The use of bioprinting allows the creation of complex three-dimensional cell laden grafts with spatial placements of different cell lines. However, a major challenge is insufficient nutrient transfer, especially with the increased size of the graft causing necrosis and reduced proliferation. A possibility to improve nutrient support is the integration of tubular structures for reducing diffusion paths. In this study the influence of prevascularization in full-thickness grafts on cell growth with a variation of cultivation style and cellular composition was investigated. To perform this, the rheological properties of the used gelatin-alginate hydrogel as well as possibilities to improve growth conditions in the hydrogel were assessed. Prevascularized grafts were manufactured using a pneumatic extrusion-based bioprinter with a coaxial extrusion tool. The prevascularized grafts were statically and dynamically cultured with a monoculture of HepG2 cells. Additionally, a co-culture of HepG2 cells, fibroblasts and HUVEC-TERT2 was created while HUVEC-TERT2s were concentrically placed around the hollow channels. A static culture of prevascularized grafts showed short-term improvements in cell proliferation compared to avascular grafts, while a perfusion-based culture showed improvements in mid-term cultivation times. The cultivation of the co-culture indicated the formation of vascular structures from the hollow channels toward avascular areas. According to these results, the integration of prevascular structures show beneficial effects for the in vitro cultivation of bioprinted grafts for which its impact can be increased in larger grafts.

A crossover study assessing the protective efficacy of improvised snorkel-based improvised respirators.

Introduction: This study was designed to determine whether improvised respirators based on modified full-face snorkel masks are able to pass a standard qualitative fit test. Methods: This is a prospective crossover study conducted in 16 staff. Fit-tests were conducted on masks mated to (1) an anaesthetic breathing circuit heat and moisture exchange filter and (2) a CE-marked P3 grade filter. P3 filters were mounted using both epoxy-coated and uncoated adaptors. Results: None of the tests using anaesthetic filters passed. Only one overall pass was observed using the P3-rated filter mated to the snorkel mask. Conclusions: These data suggest that improvised PPE designs cannot provide reliable protection against aerosols. Failures are likely due to poor fit, but the suitability of 3D printed materials is also uncertain as fused-filament manufacturing yields parts that are not reliably gas-tight. Improvised PPE cannot be recommended as a substitute for purpose designed systems.

Participative human-factor evaluation in the context of digital work (re-)design.

BACKGROUND: Challenged by digital transformation, organizations increasingly integrate information and communication technologies into work designs. Often focal points of such digital reengineering initiatives are technical and economic aspects. Yet, as integration of new technologies affects how employee work and interact, there is a need to evaluate human-centered criteria (human-factor evaluation), optimally by involving employees as situational experts. OBJECTIVE: The present study develops an integrative and persona-based evaluation approach of human-centered criteria for application in participative digital (re-)design of work to support the joint optimization of the technical and social system. METHODS: Drawing on methods from usability evaluation, a persona-based approach is developed to facilitate comprehension and application of human-centered evaluation by employees. To that end, human-centered criteria from existing evaluation models are systemized with specific reference to digital transformation of work processes. The developed approach is tested in pilot runs of three German small and medium-sized enterprises (SMEs). RESULTS: The initial overview shows a divergence of specific human-centered criteria at the detailed level. Simultaneously, a high convergence is found for overarching dimensions and categories. The Integrative Socio-Digital Evaluation Model (ISDEM) is developed to balance complexity and abstraction of criteria. The derived persona-based approach (persISDEM) shows a good applicability in the pilot runs. CONCLUSIONS: The present study provides an amendment to existing work design approaches with an emphasis on employee participation, enabling organizations to foster employees' comprehension and motivation to engage in evaluations of digital (re-)design of work and to create motivating and healthy jobs for successful digital transformation.

Advantages of virtual reality for the participative design of work processes: An integrative perspective.

BACKGROUND: The participative design of work processes is hampered by as-yet unresolved challenges. A root cause is seen in high information-pass-on-barriers. Virtual Reality (VR) may have a significant potential to overcome these challenges. Yet, there is no systematic understanding of which advantages provided by VR can support the participative design of work processes. OBJECTIVE: The present study aims to assess the potential of VR to support the participative design of work processes by conducting an integrative literature review identifying the advantages of VR in general work contexts and mapping them to known challenges in participative design of work processes. METHODS: The integrative literature review was conducted based on 268 sources of which 52 were considered for an in-depth analysis of the advantages offered by VR. RESULTS: The resulting conceptual framework consisted of 13 characteristic-related advantages (e.g., immersion, interactivity, flexibility) and 10 effect-related advantages (e.g., attractivity, involvement, cost efficiency) which readily address known challenges in the participative design of work processes. CONCLUSION: Mapping the advantages of VR to the challenges in participative design of work processes revealed a substantial potential of VR to overcome high information-pass-on-barriers. As such, employing VR in work process design initiatives represents a fruitful avenue for the promotion of prevention and employee health.

A crossover trial investigating the atmospheric content of improvised respirators.

Introduction: This study was designed to determine the respiratory safety of improvised respirators based on modified full-face snorkel masks, making comparisons with a purpose-designed mask. Methods: This is a prospective crossover study conducted on ten recruits. Volunteers wore snorkel masks mated to an anaesthetic heat and moisture exchange filter. The system was worn at rest then during exercise. Gases were sampled from the mask at 5-min intervals. Results: The modified snorkel was satisfactory in seven participants. For three carbon dioxide concentrations were >1%. Two participants exposed to excessive CO2 also experienced oxygen concentrations <19%. All participants exposed to unsatisfactory gas mixtures were non-white. Conclusions: Modifying snorkel masks changes the way that gases circulate through the system. These modifications increase the risk of rebreathing in some users, which may yield an unsafe gas mixture. These improvised masks cannot be recommended as a substitute for purpose-designed equipment.

Inflammation induces pro-NETotic neutrophils via TNFR2 signaling.

Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases intracellular neutrophil elastase (ELANE) abundance and induces neutrophil extracellular traps formation (NETosis) in CCR5+ PMNs, and triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, known activators of NETosis. In vivo, we find an increased number of CCR5+ PMNs in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ PMNs. In conclusion, we identify a phenotype of pro-NETotic, CCR5+ PMNs present in inflamed tissue in vivo and inducible in vitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.

Influence of respiratory protective equipment on simulated advanced airway skills by specialist tracheal intubation teams during the COVID-19 pandemic.

Background: The COVID-19 pandemic has highlighted the importance of respiratory protective equipment for clinicians performing airway management. Aim: To evaluate the impact of powered air-purifying respirators, full-face air-purifying respirators and filtering facepieces on specially trained anaesthesiologists performing difficult airway procedures. Methods: All our COVID-19 intubation team members carried out various difficult intubation drills: unprotected, wearing a full-face respirator, a filtering facepiece or a powered respirator. Airway management times and wearer comfort were evaluated and analysed. Results: Total mean (SD) intubation times did not show significant differences between the control, the powered, the full-face respirator and the filtering facepiece groups: Airtraq 6.1 (4.4) vs. 5.4 (3.1) vs. 6.1 (5.6) vs. 7.7 (7.6) s; videolaryngoscopy 11.4 (9.0) vs. 7.7 (4.3) vs. 9.8 (8.4) vs. 12.7 (9.8) s; fibreoptic intubation 16.6 (7.8) vs.13.8 (6.7) vs. 13.6 (8.1) vs. 16.9 (9.2) s; and standard endotracheal intubation by direct laryngoscopy 8.1 (3.5) vs. 6.5 (5.6) vs. 6.2 (4.2) vs. 8.0 (4.4) s, respectively. Use of the Airtraq achieved the shortest intubation times. Anaesthesiologists rated temperature and vision significantly better in the powered respirator group. Conclusions: Advanced airway management remains unaffected by the respiratory protective equipment used if performed by a specially trained, designated team. We conclude that when advanced airway skills are performed by a designated, specially trained team, airway management times remain unaffected by the respiratory protective equipment used.

Prospective observational study of gender and ethnicity biases in respiratory protective equipment for healthcare workers in the COVID-19 pandemic.

OBJECTIVE: To describe success rates of respiratory protective equipment (RPE) fit testing and factors associated with achieving suitable fit. DESIGN: Prospective observational study of RPE fit testing according to health and safety, and occupational health requirements. SETTING: A large tertiary referral UK healthcare facility. POPULATION: 1443 healthcare workers undergoing quantitative fit testing. MAIN OUTCOME MEASURES: Quantitative fit test success (pass/fail) and the count of tests each participant required before successful fit. RESULTS: Healthcare workers were fit tested a median (IQR) 2 (1-3) times before successful fit was obtained. Males were tested a median 1 (1-2) times, while females were tested a median 2 (1-2) times before a successful fit was found. This difference was statistically significant (p<0.001). Modelling each fit test as its own independent trial (n=2359) using multivariable logistic regression, male healthcare workers were significantly more likely to find a well-fitting respirator and achieve a successful fit on first attempt in comparison to females, after adjusting for other factors (adjusted OR=2.07, 95% CI): 1.66 to 2.60, p<0.001). Staff who described their ethnicity as White were also more likely to achieve a successful fit compared with staff who described their ethnicity as Asian (OR=0.47, 95% CI: 0.38 to 0.58, p<0.001), Black (OR=0.54, 95% CI: 0.41 to 0.71, p<0.001), mixed (OR=0.50 95% CI: 0.31 to 0.80, p=0.004) or other (OR=0.53, 95% CI: 0.29 to 0.99, p=0.043). CONCLUSIONS: Male and White ethnicity healthcare workers are more likely to achieve RPE fit test success. This has broad operational implications to healthcare services with a large female and Black, Asian and minority ethnic group population. Fit testing is imperative in ensuring RPE effectiveness in protecting healthcare workers during the COVID-19 pandemic and beyond.

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map.

Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.

Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.

INTRODUCTION: The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. METHODS: After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. RESULTS: The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. CONCLUSIONS: The results highlight the need to improve training and education regarding personal protection measures for medical first receivers.