Measures to prevent and treat Nipah virus disease: research priorities for 2024-29.

Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses.

Fulvenallenyl Radical (C7H5·)-Mediated Gas-Phase Synthesis of Bicyclic Aromatic C10H8 Isomers: Can Fulvenallenyl Efficiently React with Closed-Shell Hydrocarbons?

To understand the reactivity of resonantly stabilized radicals, often found in relevant concentrations in gaseous environments, it is important to determine their main reaction pathways. Here, it is investigated whether the fulvenallenyl radical (C7H5·) reacts preferentially with closed-shell molecules or radicals. Electronic structure calculations on the C10H9 potential energy surface accessed by the reactions of C7H5· with methylacetylene (CH3CCH) and allene (H2CCCH2) were combined with RRKM-ME calculations of temperature- and pressure-dependent rate constants using the automated EStokTP software suite and kinetic modeling to assess the reactivity of C7H5· with closed-shell unsaturated hydrocarbons. Experimentally, the reactions were attempted in a chemical microreactor heated to 998 ± 10 K by preparing fulvenallenyl radicals via pyrolysis of trichloromethylbenzene (C7H5Cl3) and seeding the radicals in methylacetylene or allene carrier gas, with product identification by means of photoionization mass spectrometry. The measured photoionization efficiency curve of m/z = 128 was assigned to a linear combination of the reference curves of two C10H8 isomers, azulene (minor) and naphthalene (major), presumably resulting from the C7H5· plus C3H4 reactions. However, the calculations demonstrated that these reactions are too slow, and kinetic modeling of processes in the reactor allowed us to conclude that the observation of naphthalene and azulene is due to the C7H5· plus C3H3· reaction, where propargyl is produced by direct hydrogen atom abstraction by chlorine (Cl) atoms from allene or methylacetylene and Cl stem from the pyrolysis of C7H5Cl3. Modeling results under the copyrolysis conditions of toluene and methylacetylene in high-temperature shock tube experiments confirmed the prevalence of the fulvenallenyl reaction with propargyl over its reactions with C3H4 even when the concentrations of allene and methylacetylene largely exceed that of propargyl. Overall, the reactions of fulvenallenyl with both allene and methylacetylene were found to be noncompetitive in the formation of naphthalene and azulene thus attesting the inefficiency of the fulvenallenyl radical reactions with the prototype closed-shell hydrocarbon species. In the meantime, the new reaction pathways revealed, including H-assisted isomerizations between C10H8 isomers and decomposition reactions of various C10H9 isomers, emerge as relevant and are recommended for inclusion in combustion kinetic models for naphthalene formation.

Efficacy of axitinib in a US cohort of patients with programmed cell death protein 1-resistant mucosal melanoma.

Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ±â€…anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021. Radiologic response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Twenty-three patients were included in this study. In all, 78% were females with a median age of 62 years. The originating site of mucosal melanoma was the sinonasal (35%), genitourinary (35%), and gastrointestinal (30%) tracts. Sixty-five percent of patients had M1c or M1d disease and 0% had BRAF V600 mutations detected. The majority (96%) had prior treatment inclusive of anti-PD-1, with a median of 2 prior lines, and 78% of patients received a combination of axitinib and PD-1 and the median duration of treatment was 3.2 months. The overall response rate was 13% and the disease control rate was 26%. The median progression-free survival was 3.2 months, and the median overall survival was 8.2 months. Overall, the regimen was well tolerated with 39% of patients requiring dose reduction and 9% requiring treatment cessation. Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.

Microbiome-informed study of the mechanistic basis of methane inhibition by Asparagopsis taxiformis in dairy cattle.

Copious amounts of methane, a major constituent of greenhouse gases currently driving climate change, are emitted by livestock, and efficient methods that curb such emissions are urgently needed to reduce global warming. When fed to cows, the red seaweed Asparagopsis taxiformis (AT) can reduce enteric methane emissions by up to 80%, but the achieved results can vary widely. Livestock produce methane as a byproduct of methanogenesis, which occurs during the breakdown of feed by microbes in the rumen. The ruminant microbiome is a diverse ecosystem comprising bacteria, protozoa, fungi, and archaea, and methanogenic archaea work synergistically with bacteria to produce methane. Here, we find that an effective reduction in methane emission by high-dose AT (0.5% dry matter intake) was associated with a reduction in methanol-utilizing Methanosphaera within the rumen, suggesting that they may play a greater role in methane formation than previously thought. However, a later spike in Methanosphaera suggested an acquired resistance, possibly via the reductive dehalogenation of bromoform. While we found that AT inhibition of methanogenesis indirectly impacted ruminal bacteria and fermentation pathways due to an increase in spared H2, we also found that an increase in butyrate synthesis was due to a direct effect of AT on butyrate-producing bacteria such as Butyrivibrio, Moryella, and Eubacterium. Together, our findings provide several novel insights into the impact of AT on both methane emissions and the microbiome, thereby elucidating additional pathways that may need to be targeted to maintain its inhibitory effects while preserving microbiome health and animal productivity. IMPORTANCE: Livestock emits copious quantities of methane, a major constituent of the greenhouse gases currently driving climate change. Methanogens within the bovine rumen produce methane during the breakdown of feed. While the red seaweed Asparagopsis taxiformis (AT) can significantly reduce methane emissions when fed to cows, its effects appear short-lived. This study revealed that the effective reduction of methane emissions by AT was accompanied by the near-total elimination of methane-generating Methanosphaera. However, Methanosphaera populations subsequently rebounded due to their ability to inactivate bromoform, a major inhibitor of methane formation found in AT. This study presents novel findings on the contribution of Methanosphaera to ruminal methanogenesis, the mode of action of AT, and the possibility for complementing different strategies to effectively curb methane emissions.

Durable complete response in a patient with leptomeningeal melanoma after treatment with dabrafenib, trametinib, and nivolumab.

Leptomeningeal disease (LMD) is a devastating complication of melanoma with a dismal prognosis. We present the case of a young man with stage IV BRAF V600E mutant melanoma with lung, lymph node, and brain metastases initially treated with ipilimumab and nivolumab, who subsequently developed LMD. Upon change to BRAF/MEK targeted therapy with nivolumab, a durable complete response was achieved and remains ongoing, off treatment, 7 years from diagnosis. Management of symptomatic LMD remains a critical unmet clinical challenge, with limited clinical trial data. This exceptional case is instructive, as the first published case of the use of the triplet, and the first durable response with therapy discontinuation, in melanoma LMD. The triple-drug regimen may be considered a viable option in fit patients. This case highlights the potential for long-term disease control and the critical and urgent need to develop clinical trials inclusive of patients with LMD to define the best treatment strategies.

Upper Limb Function in People With Upper and Lower Limb Loss 8 Years Postinjury: The Armed Services Trauma Outcome Study (ADVANCE) Cohort Study.

OBJECTIVE: Upper limb (UL) disability in people with UL amputation/s is well reported in the literature, less so for people with lower limb amputation/s. This study aimed to compare UL disability in injured (major trauma) and uninjured UK military personnel, with particular focus on people with upper and lower limb amputation/s. METHODS: A volunteer sample of injured (n = 579) and uninjured (n = 566) UK military personnel who served in a combat role in the Afghanistan war were frequency matched on age, sex, service, rank, regiment, role, and deployment period and recruited to the Armed Services Trauma Rehabilitation Outcome (ADVANCE) longitudinal cohort study. Participants completed the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire, scored from 0 (no disability) to 100 (maximum disability) 8 years postinjury. Mann-Whitney U and Kruskal Wallis tests were used to compared DASH scores between groups. An ordinal model was used to assess the effect of injury and amputation on DASH scores. RESULTS: DASH scores were higher in the group with injuries compared to the group without injuries (3.33 vs 0.00) and higher in people with lower limb loss compared to the group without injuries (0.83 vs 0.00), although this was not statistically significant. In the adjusted ordinal model, the odds of having a higher DASH score was 1.70 (95% CI = 1.18-2.47) times higher for people with lower limb loss compared to the group without injuries. DASH score was not significantly different between people with major and partial UL loss (15.42 vs 12.92). The odds of having a higher DASH score was 8.30 (95% CI = 5.07-13.60) times higher for people with UL loss compared to the uninjured group. CONCLUSION: People with lower limb loss have increased odds of having more UL disability than the uninjured population 8 years postinjury. People with major and partial UL loss have similar UL disability. The ADVANCE study will continue to follow this population for the next 20 years. IMPACT: For the first time, potential for greater upper limb disability has been shown in people with lower limb loss long-term, likely resulting from daily biomechanical compensations such as weight-bearing, balance, and power generation. This population may benefit from prophylactic upper limb rehabilitation, strength, and technique.

A KIF1C-CNBP motor-adaptor complex for trafficking mRNAs to cell protrusions.

mRNA localization to subcellular compartments is a widely used mechanism that functionally contributes to numerous processes. mRNA targeting can be achieved upon recognition of RNA cargo by molecular motors. However, our molecular understanding of how this is accomplished is limited, especially in higher organisms. We focus on a pathway that targets mRNAs to peripheral protrusions of mammalian cells and is important for cell migration. Trafficking occurs through active transport on microtubules, mediated by the KIF1C kinesin. Here, we identify the RNA-binding protein CNBP, as a factor required for mRNA localization to protrusions. CNBP binds directly to GA-rich sequences in the 3'UTR of protrusion targeted mRNAs. CNBP also interacts with KIF1C and is required for KIF1C recruitment to mRNAs and for their trafficking on microtubules to the periphery. This work provides a molecular mechanism for KIF1C recruitment to mRNA cargo and reveals a motor-adaptor complex for mRNA transport to cell protrusions.

Evaluating Outcomes Following Nerve Repair: Beyond the Medical Research Council.

Peripheral nerve injuries are common and remain a significant health challenge. Outcome measurements are used to evaluate injury, monitor recovery after nerve repair, and compare scientific advances. Clinical judgement is required to determine which available tools are most applicable, which requires a vast understanding of the available outcome measurements. In this article we discuss the highest yield tools available for clinical application.

Emerging 2D Ferromagnetism in Graphenized GdAlSi.

2D magnets are expected to give new insights into the fundamentals of magnetism, host novel quantum phases, and foster development of ultra-compact spintronics. However, the scarcity of 2D magnets often makes a bottleneck in the research efforts, prompting the search for new magnetic systems and synthetic routes. Here, an unconventional approach is adopted to the problem, graphenization - stabilization of layered honeycomb materials in the 2D limit. Tetragonal GdAlSi, stable in the bulk, in ultrathin films gives way to its layered counterpart - graphene-like anionic AlSi layers coupled to Gd cations. A series of inch-scale films of layered GdAlSi on silicon is synthesized, down to a single monolayer, by molecular beam epitaxy. Graphenization induces an easy-plane ferromagnetic order in GdAlSi. The magnetism is controlled by low magnetic fields, revealing its 2D nature. Remarkably, it exhibits a non-monotonic evolution with the number of monolayers. The results provide a fresh platform for research on 2D magnets by design.

TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication.

SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 -/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

Reading language of the eyes in female depression.

Aberrations in non-verbal social cognition have been reported to coincide with major depressive disorder. Yet little is known about the role of the eyes. To fill this gap, the present study explores whether and, if so, how reading language of the eyes is altered in depression. For this purpose, patients and person-by-person matched typically developing individuals were administered the Emotions in Masked Faces task and Reading the Mind in the Eyes Test, modified, both of which contained a comparable amount of visual information available. For achieving group homogeneity, we set a focus on females as major depressive disorder displays a gender-specific profile. The findings show that facial masks selectively affect inferring emotions: recognition of sadness and anger are more heavily compromised in major depressive disorder as compared with typically developing controls, whereas the recognition of fear, happiness, and neutral expressions remains unhindered. Disgust, the forgotten emotion of psychiatry, is the least recognizable emotion in both groups. On the Reading the Mind in the Eyes Test patients exhibit lower accuracy on positive expressions than their typically developing peers, but do not differ on negative items. In both depressive and typically developing individuals, the ability to recognize emotions behind a mask and performance on the Reading the Mind in the Eyes Test are linked to each other in processing speed, but not recognition accuracy. The outcome provides a blueprint for understanding the complexities of reading language of the eyes within and beyond the COVID-19 pandemic.

Synergistic Bactericidal Effect of Zn2+ Ions and Reactive Oxygen Species Generated in Response to Either UV or X-ray Irradiation of Zn-Doped Plasma Electrolytic Oxidation TiO2 Coatings.

Zn-containing TiO2-based coatings with Na, Ca, Si, and K additives were obtained by plasma electrolytic oxidation (PEO) of Ti in order to achieve an effective and broad bactericidal protection without compromising biocompatibility. A protocol has been developed for cleaning the coating surface from electrolyte residues, ensuring the preservation of the microstructure and composition of the surface layer. Using high-resolution transmission electron microscopy, three characteristic microstructural zones in the PEO-Zn coating are well documented: zone 1 with a TiO2-based nanocrystalline structure, zone 2 with an amorphous structure, and zone 3 around pores with an amorphous-nanocrystalline structure. The excellent cytocompatibility of PEO-Zn samples was confirmed by three different methods: monitoring the proliferation of MC3T3-E1 cells, assessing the viability of sheep osteoblast cells using calcein-AM staining and fluorescence microscopy, and incubation with spheroids based on primary osteoblast cells and mouse embryonic fibroblast NIH3T3 cells. The PEO-Zn coatings absorb >60% of the incident light over the UV and Vis-NIR spectral ranges. After 24 h, the PEO-Zn coatings completely inactivate four types of strains: Gram-positive Staphylococcus aureus CSA154 and ATCC29213 and Gram-negative Escherichia coli K261 and U20, and also prevent E. coli U20 and K261 biofilm formation. The superior antibacterial activity is associated with the synergistic effect of Zn2+ ions in safe concentration and reactive oxygen species (ROS) generated in response to either UV irradiation or soft short-term X-ray irradiation. The X-ray irradiation-induced ROS formation by a PEO coating is reported for the first time. The enhanced bactericidal activity after X-ray irradiation compared to UV illumination is attributed to the more intense ROS generation in the first few hours. The results obtained significantly expand the possibilities of using PEO coatings on the surfaces of titanium implants.

Factors affecting shared decision-making concerning menopausal hormone therapy.

Menopausal hormone therapy (MHT) is an effective treatment for menopause-related symptoms. Menopause management guidelines recommend a personalized approach to menopause care, including MHT use. Decision-making around menopause care is a complex, iterative process influenced by multiple factors framed by perspectives from both women and healthcare providers (HCPs). This narrative review aims to summarize evidence around factors affecting decision-making regarding menopause-related care. For HCPs, the provision of individualized risk estimates is challenging in practice given the number of potential benefits and risks to consider, and the complexity of the data available, especially within time-limited consultations. Women seeking menopause care have the difficult task of making sense of the benefit versus risk profiles to make choices in line with their decisional needs influenced by sociocultural/economic, educational, demographic, and personal characteristics. The press, social media, and influential celebrities also impact the perception of menopause and decision-making around it. Understanding these factors can lead to improved participation in shared decision-making, satisfaction with the decision and decision-making process, adherence to treatment, reduced decisional regret, efficient use of resources, and ultimately long-term satisfaction with care.

Reversed Corneal Fibroblasts Therapy Restores Transparency of Mouse Cornea after Injury.

Cell-based therapies using corneal stromal stem cells (CSSC), corneal keratocytes, or a combination of both suppress corneal scarring. The number of quiescent keratocytes in the cornea is small; it is difficult to expand them in vitro in quantities suitable for transplantation. This study examined the therapeutic effect of corneal fibroblasts reversed into keratocytes (rCF) in a mouse model of mechanical corneal injury. The therapeutic effect of rCF was studied in vivo (slit lamp, optical coherence tomography) and ex vivo (transmission electron microscopy and immunofluorescence staining). Injection of rCF into the injured cornea was accompanied by recovery of corneal thickness, improvement of corneal transparency, reduction of type III collagen in the stroma, absence of myofibroblasts, and the improvement in the structural organization of collagen fibers. TEM results showed that 2 months after intrastromal injection of cells, there was a decrease in the fibril density and an increase in the fibril diameter and the average distance between collagen fibrils. The fibrils were well ordered and maintained the short-range order and the number of nearest-neighbor fibrils, although the averaged distance between them increased. Our results demonstrated that the cell therapy of rCF from ReLEx SMILe lenticules promotes the recovery of transparent corneal stroma after injury.

Cancer fatalism, social media informational awareness, and education.

OBJECTIVE: Understand if cancer fatalism among adult social media users in the United States is linked to social media informational awareness and if the relationship varies by education level. METHODS: Cross-sectional data from the 2022 Health Information National Trends Survey (n = 3,948) were analyzed using multivariable linear probability models. The study population was defined as social media users active within the past year. The outcome variable was cancer fatalism and the predictor variables were social media informational awareness and education level. RESULTS: Participants with low social media informational awareness were 9% (95% CI = 3, 15), 6% (95% CI = 1, 11), and 21% (95% CI = 14, 27) percentage points more likely to agree that it seems like everything causes cancer, you cannot lower your chances of getting cancer, and there are too many cancer prevention recommendations to follow, respectively. Participants with a college degree or higher level of education and who reported high social media informational awareness were the least likely to agree that everything causes cancer (60%; 95% CI = 54, 66), you cannot lower your chances of getting cancer (14%; 95% CI = 10, 19), and there are too many cancer prevention recommendations to follow (52%; 95% CI = 46, 59). CONCLUSION: Social media informational awareness was associated with lower levels of cancer fatalism among adult social media users. College graduates with high social media informational awareness were the least likely to report cancer fatalism.

Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation.

Aims: The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease. Methods and results: Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner. Conclusion: Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease.

High repetition-rate foam targetry for laser-plasma interaction experiments: Concept and preliminary results.

Foam targets have gained considerable importance over the last decade in laser-matter interaction. They find widespread applications such as in inertial confinement fusion and secondary sources for particles and radiation. At the same time, the advent of high repetition-rate laser systems, be they short-pulse in the tens of femtosecond regime or in the kilo-Joule nanosecond regime, calls for equally high repetition rate targetry systems. A well-established repetition-rate targetry system is the tape target. In this article, we present the successful marriage of a tape target delivery system with 3D-printed foam targets produced by two photon polymerization.

Molecular Aspects of Inflammation and Lipid Metabolism in Health and Disease: The Role of the Mitochondria.

Inflammation and lipid metabolism are two deeply interconnected and reciprocally regulated major physiological processes [...].

Return to work in persons with persistent postconcussion symptoms: a survey study examining the perspectives of employees and managers.

OBJECTIVE: To examine challenges in return to work (RTW) for persons with persistent postconcussion symptoms (PPCS) experienced by the affected employees and their managers. METHODS: A survey of employees (S-E) and two surveys of managers (S-M1, S-M2) executed 4 months apart to capture the time perspective. Inclusion: Adults aged 18-66 with PPCS > 4 weeks, employed at the time of mTBI who returned to work within the previous year. Managers involved in their RTW process. OUTCOME MEASURES: Work status, working hours, work functioning (Work Role Functioning Questionnaire, WRFQ), work productivity. RESULTS: Ninety-two employees and 66 managers were recruited. Three-fourths of the employees had returned to work but only one-third worked under similar conditions. Weekly working hours decreased from 36,3 hours (SD = 10,5) before mTBI to 17,6 hours (SD = 9,7). Employees had difficulties with tasks 43% of time (WRFQ). They needed more breaks, struggled with multitasking and work speed. About 65.9% experienced affected work productivity. Managers reported lack of knowledge and difficulties assessing the number of working hours and suitable tasks. CONCLUSIONS: Most employees returned to work but only a minority worked under similar conditions as before mTBI. Employees and managers struggled to estimate workload. The affected employees and their workplaces need a long-term RTW support.