Frailty assessment for COVID-19 follow-up: a prospective cohort study.

BACKGROUND The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19. OBJECTIVES To investigate frailty and the CFS for post-COVID-19 follow-up. METHODS This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively. RESULTS Of the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2-3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=-0.48, p<0.001) (criterion validity) and with the St George's Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=-0.25, p<0.001), 6 min walk distance (r=-0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02). CONCLUSIONS The CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly

Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study.

BACKGROUND Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. OBJECTIVES We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. METHODS 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. RESULTS At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. CONCLUSIONS In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group

Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control

YesIt has long been known that Tissue Factor (TF) plays a role in blood coagulation and has a direct thrombotic action that is closely related to cardiovascular risk, but it is becoming increasingly clear that it has a much wider range of biological functions that range from inflammation to immunity. It is also involved in maintaining heart haemostasis and structure, and the observation that it is down-regulated in the myocardium of patients with dilated cardiomyopathy suggests that it influences cell-to-cell contact stability and contractility, and thus contributes to cardiac dysfunction. However, the molecular mechanisms underlying these coagulation-independent functions have not yet been fully elucidated. In order to analyse the influence of TF on the cardiomyocitic proteome, we used functional biochemical approaches incorporating label-free quantitative proteomics and gene silencing, and found that this provided a powerful means of identifying a new role for TF in regulating splicing machinery together with the expression of several proteins of the spliceosome, and mRNA metabolism with a considerable impact on cell viability

Intención de retorno, permanencia o reubicación de las víctimas del conflicto armado residentes en Bogotá análisis cualitativo

Forced displacement has been one of the most dramatic expressions of the internal armed conflict in Colombia being the most representative victimized with more than 7 million victims (UARIV, 2017). Bogotá, for its part, is the second receiving city of this population, implying a greater effort on the part of the financial institutions, which must make an effort in the coverage of policies and programs that aim to provide integral attention to the victims of the residents In the city The governmental entities under the law 1448 of 2011 have made a great effort for the people who suffered the displacement and were stripped of their land by the cause of the armed conflict, they return to their place of origin, the work that Has been difficult because of the presence of armed groups in the national territory.In the years 2012 formally initiated the peace agreements between the National Government and the Revolutionary Armed Forces of Colombia (FARC) being this one of the illegal armed groups with greater presence in the national territory, in the year 2016 It generates a great expectation in the referent to the restitution of lands and the possible return in the post-conflict state of the displaced population, the time that has elapsed since the date of displacement to the present, the development of families, social dynamics and the various functions.Taking into account the above, the District Secretary together with the High Council of Bogotá has seen the need to study the personal characteristics that facilitate the return to their place of origin, their relocation to another place of the victims that are in the city. Due to this the work is carried out with the perception that the victims of forced displacement, the residents in the city of Bogota against the peace agreements and their intention of return, through a qualitative investigation applying semi structured interviews to the population of study Which in turn contribute to quantitative studies based on the databases of the victim information system - SIVIC and the Single Registry of Victims - RUV.Some of the most important results are that the decision to return, stay or relocate the victims of the armed conflict is mainly linked to their safety precept in the territories where they have been involved, employment and education opportunities and relationships with Your family and safety in terms of well-being. Finally, it was possible to conclude that people who are in the range between 18 and 36 years prefer to stay in the city because of the job opportunities they find there, on the other hand, people who are in the range of 40 to 63 years of age do not find work opportunities that facilitate their stay in Bogota, so they prefer to return to their place of origi

A mixed-methods assessment of the feasibility of conducting neurosurgical clinical research in Uganda

Background: Clinical research is necessary to evaluate neurosurgical interventions, yet clinical trials are conducted less frequently in low- and middle-income countries. Because specific barriers, facilitating factors, and strategies for neurosurgical clinical research in Uganda have not been previously identified, this study evaluated neurosurgical providers\u27 perspectives on clinical research and documentation patterns of neurosurgical variables at [BLINDED FOR REVIEW, INSTITUTION A].Methods: Retrospective review of 166 neurosurgical patient charts assessed the frequency of documentation of key variables. Twenty-two providers working in neurosurgery participated in 6 focus group discussions (FGDs) with qualitative analysis utilizing the framework method.Results: Chart review showed that primary diagnosis (99.4%), pupil light response (97.6%), and CT scan results (93.3%) were documented for most patients. Cranial nerve exam (61.5%), pupil size (69.9%), and time to neurosurgical intervention (45%) were documented less frequently. On average, Glasgow Coma Scale was documented for 86.6% of days hospitalized, while vital signs were documented for 12.3%. In most FGDs, participants identified follow-up, financing, recruitment, time, approval, and sociocultural factors as research barriers. Participants described how the current health workforce facilitates successful research. To improve research capacity, suggested strategies focused on research networks, data collection, leadership, participant recruitment, infrastructure, and implementation.Conclusion: At [BLINDED FOR REVIEW, INSTITUTION A ABBREVIATION], there was variability in the frequency of documentation of neurosurgical variables, which may impact data collection for future studies. While multiple barriers were identified, sociocultural, financing, and time barriers greatly impacted neurosurgical clinical research. Despite that, identified facilitating factors and strategies could be utilized to support neurosurgical research capacity growth

DNA repair processes target transcribed region in multiple myeloma

Background: Multiple myeloma (MM) is a plasma cells malignancy charac- terized by a complex and heterogeneous genomic landscape. Using whole- exome and targeted sequencing, two main active mutational processes have been identified in MM provide initial insight into both initial pathogenic mechanisms and the processes affecting disease progression. However, lim- ited numbers of mutations identified using WES does not allow interrogation of question whether different parts of the genome are targeted by different mutational processes. Aims: Here we interrogate various genomic regions and mutation types such as non-coding regions and protein coding regions with missense mutations, to understand activated processes that cause DNA alteration in MM. Methods: We have processed 39 purified CD138+ MM cells samples with Whole Genome Sequencing; ten samples also have RNA and ATAC sequenc- ing. Public WES data from 999 samples were collected from dbGaP and CoMMpass study. Mutational processes were analyzed using non-negative matrix factorization and multiple linear regression model. Results: We identified an average >5000 SNVs per patient sample with a total of over 200K SNVs from WGS and additional >170K SNVs from pub- lic WES data. Overall C>T mutations constituted 30% of all detected muta- tions across the genome, including a small fraction of C>T mutations within CpG islands. Majority of the mutations were observed in the intergenic (IGR), introns and non-coding RNAs regions (lincRNAs and ncRNA). Tran- scribed strand of the genome showed enrichment in C>A and C>T muta- tions. With non-negative matrix factorization we were able to identify 8 mutational processes in MM genome six of which were not described before. Although APOBEC/AID processes were the majority for the non coding genome, DNA repair related processes were highly active in the coding genome. We have integrated WGS, ATACseq and RNAseq data from same patients and identified that DNA damage activity increased in the expressed genes and sub clonal populations. We have confirmed our results using pub- licly available WES data from 999 samples. Summary and Conclusions: C>A and C>T enrichment on the transcribed strand has been connected to high transcriptional activities and different mechanisms such as single versus double-strand DNA repair functions. Tar- geting of non-coding regions by APOBEC/AID could be part of ongoing somatic hypermutation in MM. However, missense mutations may be driven by DNA double-strand break-repair by homologous recombination and DNA mismatch repair processes. Increased intensity for DNA repair signa- tures in subclonal missense mutations may indicate that these processes may occur late during the MM progression. Future studies that can compare paired samples from early stage to relapsed and refractory myeloma can help us understand if DNA repair processes become dominant during the MM development

Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study

Background The infectious coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge. Up to one-third of hospitalised patients develop severe pulmonary complications and acute respiratory distress syndrome. Pulmonary outcomes following COVID-19 are unknown. Methods The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequelae of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the World Health Organization severity classification. Results 113 COVID-19 survivors were included (mild/moderate n=47, severe/critical n=66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function, i.e. diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, reduced 6-min walk distance (6MWD) and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex and body mass index (BMI), patients after severe/critical COVID-19 had a DLCO 20.9% pred (95% CI 12.4–29.4% pred, p=0.01) lower at follow-up. DLCO % pred was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD and minimal peripheral oxygen saturation at exercise were included in the multivariable model (adjusted odds ratio per 10% predicted 0.59, 95% CI 0. 37–0.87; p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7, 95% CI 1.7–239; p=0.03). Conclusions 4 months after severe acute respiratory syndrome coronavirus 2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small-airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19

Exploring the feasibility of pupillometry training and perceptions of potential use for intracranial pressure monitoring in Uganda: A mixed methods study

Introduction: Traumatic brain injury (TBI) accounts for the majority of Uganda\u27s neurosurgical disease burden; however, invasive intracranial pressure (ICP) monitoring is infrequently used. Noninvasive monitoring could change the care of patients in such a setting through quick detection of elevated ICP.Purpose: Given the novelty of pupillometry in Uganda, this mixed methods study assessed the feasibility of pupillometry for noninvasive ICP monitoring for patients with TBI.Methods: Twenty-two healthcare workers in Kampala, Uganda received education on pupillometry, practiced using the device on healthy volunteers, and completed interviews discussing pupillometry and its implementation. Interviews were assessed with qualitative analysis, while quantitative analysis evaluated learning time, measurement time, and accuracy of measurements by participants compared to a trainer\u27s measurements.Results: Most participants (79%) reported a positive perception of pupillometry. Participants described the value of pupillometry in the care of patients during examination, monitoring, and intervention delivery. Commonly discussed concerns included pupillometry\u27s cost, understanding, and maintenance needs. Perceived implementation challenges included device availability and contraindications for use. Participants suggested offering continued education and engaging hospital leadership as implementation strategies. During training, the average learning time was 13.5 minutes (IQR 3.5), and the measurement time was 50.6 seconds (IQR 11.8). Paired t-tests to evaluate accuracy showed no statistically significant difference in comparison measurements.Conclusion: Pupillometry was considered acceptable for noninvasive ICP monitoring of patients with TBI, and pupillometer use was shown to be feasible during training. However, key concerns would need to be addressed during implementation to aid device utilization

Exploring the feasibility of pupillometry training and perceptions of potential use for intracranial pressure monitoring in Uganda: A mixed methods study

Introduction: Traumatic brain injury (TBI) accounts for the majority of Uganda’s neurosurgical disease burden; however, invasive intracranial pressure (ICP) monitoring is infrequently used. Noninvasive monitoring could change the care of patients in such a setting through quick detection of elevated ICP. Purpose: Given the novelty of pupillometry in Uganda, this mixed methods study assessed the feasibility of pupillometry for noninvasive ICP monitoring for patients with TBI. Methods: Twenty-two healthcare workers in Kampala, Uganda received education on pupillometry, practiced using the device on healthy volunteers, and completed interviews discussing pupillometry and its implementation. Interviews were assessed with qualitative analysis, while quantitative analysis evaluated learning time, measurement time, and accuracy of measurements by participants compared to a trainer’s measurements. Results: Most participants (79%) reported a positive perception of pupillometry. Participants described the value of pupillometry in the care of patients during examination, monitoring, and intervention delivery. Commonly discussed concerns included pupillometry’s cost, understanding, and maintenance needs. Perceived implementation challenges included device availability and contraindications for use. Participants suggested offering continued education and engaging hospital leadership as implementation strategies. During training, the average learning time was 13.5 minutes (IQR 3.5), and the measurement time was 50.6 seconds (IQR 11.8). Paired t-tests to evaluate accuracy showed no statistically significant difference in comparison measurements. Conclusion: Pupillometry was considered acceptable for noninvasive ICP monitoring of patients with TBI, and pupillometer use was shown to be feasible during training. However, key concerns would need to be addressed during implementation to aid device utilization.</p