BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.

BACKGROUND: The COVID-19 pandemic had and still have a major impact on adolescent mental health and consequently on suicidal behavior. However, few studies have investigated whether the pandemic has changed the patterns and the triggers of suicidality peaks in adolescents, e.g., seasonal patterns or family conflicts. We hypothesized that the pandemic modified suicidality rates: an increment of suicide attempts would be observed in the first semester of the academic year during COVID-19 pandemic compared to the same period of previous academic year; and the precipitating factors would be more related to social stressors during the pandemic school year. METHODS: A retrospective cross-sectional study was conducted to assess the precipitating factors, also including school-related factors and cognitive skills, of adolescent suicide attempters occurred in the first and second semesters of the year before the pandemic lockdown (study periods 1 and 2) and the year after (study periods 3 and 4). RESULTS: The sample consisted of 85 adolescents aged between 12 and 17 recruited consecutively from March 2019 to March 2021 at emergency ward because of suicide attempt. Forty-eight adolescents (55.3% of the sample) were attended before the lockdown (pre-pandemic group) and 38 (44.7%) the year after. The results showed a higher proportion of female suicide attempters in period 4 (Sept 2020-Feb 2021) respect to period 3 (Mar 2020-Aug 2020), i.e., pandemic semesters compared with the increment observed between period 2 and 1 (prepandemic semesters; Fisher's exact test = 4.73; p = 0.026). The multinomial regression models showed a significant effect in the frequency of adolescents who attempted suicide (ratio χ2 = 15.19, p = 0.019), accounted by the differences between period 4 (Sept 2020-Feb 2021) and period 1 (Mar 2019-Aug 2019), with depressive symptoms being a significant contributing factor (Exp(b) = 0.93; p = 0.04). Additionally, social triggers and age were found to be significant risk factors for suicide attempts in the first semester of the pandemic academic year (period 4) compared to the same semester of the pre-pandemic year (period 2; Exp(b) = 0.16, p = 0.01, and Exp(b) = 1.88, p = 0.006, respectively). CONCLUSIONS: During the pandemic, the decrement between first and second semester of the number of females attempting suicide was more pronounced than in the prepandemic school year -though this findings lacked statistical power due to very limited sample size-. Change in the frequency of adolescent attempting suicide in the different school periods was associated with greater severity of depressive symptoms. Social relations in back-to-school after the lockdown were also associated with the number of adolescents attempting suicide.

Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics.

INTRODUCTION: Telehealth service provision and uptake has rapidly increased since the COVID-19 pandemic, allowing healthcare to be delivered safely and reducing non-essential face-to-face (F2F) contact. In Australia, the expansion of subsidisation of telehealth during COVID has led to its permanent installation within Australian primary care in 2022. However, little is known about consumer preferences and experiences with these services, particularly in relation to allied health practice (AHP). Previous studies on telehealth services have focused on general practice rather than allied health (AH) and broader primary care. Given that AH professionals make up a large proportion of the Australian healthcare workforce, the purpose of this study is to explore consumer preferences and experiences with telehealth AHP healthcare. METHODS AND ANALYSIS: This study uses a mixed methods research design that incorporates three independent but interrelated phases. Phase 2 of the study will use a focus group methodology to discuss consumer attitudes and experiences via a semistructured interview format. Phase 3 involves a discrete choice experiment (DCE) involving a large online survey conducted across the general population. The DCE will be informed by the qualitative findings from phases 1 and 2. The experiment aims to elicit consumer preferences in relation to AH services delivered through telehealth or F2F consultations, based on several hypothetical scenarios and preferences over several different dimensions. ETHICS AND DISSEMINATION: Ethics approval has been obtained from La Trobe University (approval number HEC23404). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.

Background Although there are many studies on violence against physicians in the literature, there are few studies on violence against physicians working in intensive care units (ICUs). We aimed to investigate the frequency, type and underlying factors of violence against physicians working in ICUs in Turkey in the past 1 year. Methods We collected data by sending a questionnaire about violence against physicians working in ICUs via e-mail and WhatsApp between 1 and 15 May 2022. IBM SPSS Statistics V.24.0 was used for data analysis. The chi-square test and Fisher precision test were used to compare categorical data. Results Over one-third (38.6%) of the 354 physicians participating in our study reported that they had been exposed to violence in the past year, while 20.7% reported that they had been exposed to violence more than once in the past year. There was a significant relationship between the frequency of exposure to violence, female gender, age group, title, subspecialization status, working style and duration of working in the ICU (p<0.05). There was no relationship between the working area, type of hospital and ICU and exposure to violence (p>0.05). The presence of restriction and control points at the entrance to ICUs prevented violence (p<0.05). Conclusion Physicians working in ICUs encounter violence against them. The frequency of violence increased after the Covid-19 pandemic. A significant relationship was found between the frequency of violence and female gender, age group, title, subspecialization status, working style and duration of working in ICUs.

BACKGROUND: Immunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic relapsed ovarian cancer. OBJECTIVE: To assess the effectiveness and safety of MVA-5T4 as treatment for asymptomatic relapsed ovarian cancer. METHODS: TRIOC was a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aim was to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. Eligible patients had International Federation of Gynecology and Obstetrics (FIGO) stage IC1-III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, Eastern Cooperative Oncology Group (ECOG) 0-1, with relapse defined by a rise in CA-125 to twice the upper limit of normal or low-volume disease on CT scan. The primary endpoint was disease progression (including deaths from ovarian cancer) at 25 weeks. Following a brief suspension, the trial restarted as a single-arm study. The revised single-arm design required 45 evaluable patients treated with MVA-5T4 to detect a 25-week progression rate of 50%, assuming an expected 70% rate without MVA-5T4; 85% power with one-sided 5% significance. RESULTS: A total of 94 eligible patients were recruited, median age was 65 years (range 42-82), median follow-up 34 months (range 2-46). Overall, 59 patients received MVA-5T4 and 35 patients received placebo. The median number of MVA-5T4 injections received was 7 (range 0-9), compared with a median of 6 (range 1-12) for patients receiving placebo. Median progression-free survival was the same in both arms (3.0 months). The 25-week progression rate was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference -5.7%, 95% CI -21.4% to 10.0%). Median time to clinical intervention was improved with MVA-5T4: 7.6 months (range 6.7-9.5) vs 5.6 (range 4.9-7.6), CONCLUSION: MVA-5T4 vaccination in patients with asymptomatic relapse was well-tolerated but did not improve the progression rate at 25 weeks. The majority of patients who received MVA-5T4 had clinical intervention later than those assigned to placebo. TRIAL REGISTRATION NUMBER: NCT01556841.

OBJECTIVE: To describe COVID-19 pandemic impact among mothers of young children (0-8 yrs.) and assess pre-pandemic factors associated with greater pandemic impact and psychosocial distress. METHODS: Mothers from three US birth cohorts (n=301, mean child age 2.4 years) reported on demographics and psychosocial distress (anxiety, perceived stress, financial stress) before the pandemic (2/2015-2/2020). During the pandemic (7/2020-6/2021), they completed a supplemental survey about the impact of the pandemic on their families (Coronavirus Impact Scale) and psychosocial distress. Multivariable linear and ordinal logistic regression were used to evaluate pre-pandemic factors associated with pandemic impact overall and by domain. RESULTS: Compared to pre-pandemic reports, maternal anxiety symptoms increased by 9.4%, perceived stress increased by 13.3%, and financial stress increased by 41.7%, of which all were statistically significant changes. Participants reported the most severe pandemic impact in family routines (72.4%), experiences of stress (40.2%), and social support (38.6%). Mothers with some college or a 4-year degree experienced higher overall pandemic impact compared to mothers with the least and highest education. Pre-pandemic distress was not associated with pandemic impact however, mid-pandemic, all three distress measures were significantly positively associated with overall CIS, with the largest effect size noted for perceived stress (B=1.36, 95% CI: 0.90,1.82). CONCLUSIONS: While, on average, mothers of young children experienced worsening psychosocial stress during the COVID-19 pandemic, pre-pandemic psychosocial stress alone was not prospectively associated with greater pandemic impact, suggesting that the COVID-19 pandemic may have both elaborated existing systemic social inequalities and created new burdens. WHAT'S NEW: While mothers of young children experienced worsening psychosocial distress during the pandemic, pre-pandemic psychosocial distress alone was not associated with greater family pandemic impact. The pandemic may have both exacerbated existing systemic social inequalities and created new burdens.

INTRODUCTION: Efforts to improve oxygen access have focused mainly on the supply side, but it is important to understand demand barriers, such as oxygen refusal among caregivers. We therefore aimed to understand caregiver, community and healthcare provider (HCP) perspectives and experiences of medical oxygen treatments and how these shape oxygen acceptance among caregivers of sick children in Lagos and Jigawa states, which are two contrasting settings in Nigeria. METHODS: Between April 2022 and January 2023, we conducted an exploratory qualitative study using reflexive thematic analysis, involving semistructured interviews with caregivers (Jigawa=18 and Lagos=7), HCPs (Jigawa=7 and Lagos=6) and community group discussions (Jigawa=4 and Lagos=5). We used an inductive-deductive approach to identify codes and themes through an iterative process using the theoretical framework of acceptability and the normalisation process theory as the analytic lens. RESULTS: Medical oxygen prescription was associated with tension, characterised by fear of death, hopelessness about a child's survival and financial distress. These were driven by community narratives around oxygen, past negative experiences and contextual differences between both settings. Caregiver acceptance of medical oxygen was a sense-making process from apprehension and scepticism about their child's survival chances to positioning prescribed oxygen as an 'appropriate' or 'needed' intervention. Achieving this transition occurred through various means, such as trust in HCPs, a perceived sense of urgency for care, previous positive experience of oxygen use and a symbolic perception of oxygen as a technology. Misconceptions and pervasive negative narratives were acknowledged in Jigawa, while in Lagos, the cost was a major reason for oxygen refusal. CONCLUSION: Non-acceptance of medical oxygen treatment for sick children is modifiable in the Nigerian context, with the root causes of refusal being contextually specific. Therefore, a one-size-fits-all policy is unlikely to work. Financial constraints and community attitudes should be addressed in addition to improving client-provider interactions.

In March 2020, universities in Zimbabwe temporarily closed and switched to remote learning to contain the spread of SARS Cov2 infections. The sudden change to distance learning gave autonomy to students to direct their own learning. To understand how the students at the University of Zimbabwe and Midlands State University adapted to emergency remote learning, focus group discussions and a self-administered questionnaire survey based on the self-regulated learning inventory were conducted to capture cognitive, motivational, and emotional aspects of anatomy learning during the COVID-19 pandemic. Thematic analysis was used to identify patterns among these students' lived experiences. Two coders analyzed the data independently and discussed the codes to reach a consensus. The results showed that students at the two medical schools cognitively and meta-cognitively planned, executed and evaluated self-regulated strategies in different ways that suited their environments during the COVID-19 lockdown. Several factors, such as demographic location, home setting/situation, socioeconomic background and expertise in using online platforms, affected the students' self-directed learning. Students generally adapted well to the constraints brought about by the lockdown on their anatomy learning in order to learn effectively. This study was able to highlight important self-regulated learning strategies that were implemented during COVID-19 by anatomy learners, especially those in low-income settings, and these strategies equip teachers and learners alike in preparation for similar future situations that may result in forced remote learning of anatomy.

BACKGROUND: COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management. OBJECTIVES: To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic. METHODS: We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment. RESULTS: In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea. CONCLUSIONS: Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.