Citations

Abstract Background: COVID-19 caused the worst international public health crisis, accompanied by major global economic downturns, mass-scale job losses, which impacted on the psychosocial wellbeing of the worldwide population. This study examined factors associated with psychosocial distress, fear of COVID-19 and coping strategies amongst the general population in Saudi Arabia.Methods: A cross-sectional study was conducted using an anonymous online questionnaire. Multivariate logistic regressions were used; Adjusted Odds Ratio (AOR) with 95% Confidence Intervals (CIs) was reported.Results: Among 803 participants, 70 %(n=556), were females and the median age was 27 years; 35% (n=278), were frontline or essential service workers; 24% (n=195), reported comorbid conditions including mental health illness. Factors associated with moderate to high levels of psychological distress were: youth (18 - 29 years) (AOR 3.35, 95% CIs 2.06 - 5.44), females (2.59, 1.60 - 4.19), non-Saudi nationals (2.17, 1.11 - 4.26), change in employment (2.9, 1.73 - 4.87), negative financial impact (2.14, 1.29-3.56), having comorbidities (2.67, 1.47 - 4.87), and current smoking (2.87, 1.55 - 5.33). Being ex-smokers (3.72, 1.14 - 12.14) and change in employment (3.42, 1.91 - 6.11) were associated with higher levels of fear of COVID-19. People whose financial situation was impacted and who had contact with known/suspected cases (1.63, 1.12-2.38) had low medium to high resilient coping.Conclusions: People in Saudi Arabia were at a higher risk of psychosocial distress and fear along with low resilience during the COVID-19 pandemic, warranting urgent attention from healthcare providers and policymakers, to provide specific mental health support strategies for their wellbeing currently and to avoid a post-pandemic mental health crisis.

Purpose of review The purpose of this review is to describe recent findings on the clinical presentation, pathogenesis, and management of fetal alcohol spectrum disorders (FASDs). Alcohol causes a range of physical, developmental, and cognitive impairments on the developing fetus. Individuals exposed to alcohol prenatally have a wide variability in dysmorphic and neurologic features. Hence, a greater understanding of the mechanisms through which alcohol induces defects in the developing fetus is imperative in developing therapies that prevent alcohol-induced effects. Recent findings Current research has focused on leveraging technology to developing tools that can aid in the diagnostic process, defining patterns of neurocognition and neuroimaging specific to FASD, developing neurobehavioral and pharmacologic interventions, and expanding access to care. Summary FASDs are a common cause of neurodevelopmental impairment in school-age children, and their recognition is essential to provide early interventions in order to optimize the outcome for these individuals when they reach adulthood. Although previously thought to be the result of irreversible neurologic injury from prenatal alcohol exposure, recent evidence points to the benefits of applying principles regarding neuroplasticity in improving the lives for patients and their families.

Abstract Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank. In addition, we provide a data-driven context with which to frame this discussion by analyzing key study design features of adult glioblastoma clinical trials listed on ClinicalTrials.gov as “recruiting” or “not yet recruiting” as of February 2021.

Abstract Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents.

Objective/background: Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal. Methods: We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy. Results: Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALC Leuk ) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6–14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3–5.1). Conclusion: The grade of CRS and ALC Leuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.

Abstract To discover lipidomic alterations during pregnancy in mothers who subsequently delivered small for gestational age (SGA) neonates and identify predictive lipid markers that can help recognize and manage these mothers, we carried out untargeted lipidomics on maternal serum samples collected between 24–28 weeks of gestation. We used a nested case-control study design and serum from mothers who delivered SGA and appropriate for gestational age babies. We applied untargeted lipidomics using mass spectrometry to characterize lipids and discover changes associated with SGA births during pregnancy. Multivariate pattern recognition software Collaborative Laboratory Integrated Reports (CLIR) was used for the post-analytical recognition of range differences in lipid ratios that could differentiate between SGA and control mothers and their integration for complete separation between the two groups. Here, we report changes in lipids from serum collected during pregnancy in mothers who delivered SGA neonates. In contrast to normal pregnancies where lysophosphatidic acid increased over the course of the pregnancy owing to increased activity of lysophospholipase D, we observed a decrease (32%; P = 0.05) of 20:4-lysophosphatidic acid in SGA mothers, which could potentially compromise fetal growth and development. Integration of lipid ratios in an interpretive tool (CLIR) could completely separate SGA mothers from controls demonstrating the power of untargeted lipidomic analyses for identifying novel predictive biomarkers. Additional studies are required for further assessment of the lipid biomarkers identified in this report.

Abstract Background The symptom burden associated with cancer and its treatment can negatively affect patients’ quality of life and survival. Symptom-focused collaborative care model (CCM) interventions can improve outcomes, but only if patients engage with them. We assessed the receptivity of severely symptomatic oncology patients to a remote nurse-led CCM intervention. Methods In a pragmatic, cluster-randomized, stepped-wedge trial conducted as part of the National Cancer Institute IMPACT Consortium (E2C2, NCT03892967), patients receiving cancer care were asked to rate their sleep disturbance, pain, anxiety, emotional distress, fatigue, and limitations in physical function. Patients reporting at least 1 severe symptom (≥7/10) were offered phone consultation with a nurse symptom care manager (RN SCM). Initially, patients had to “opt-in” to receive a call, but the protocol was later modified so they had to “opt-out” if they did not want a call. We assessed the impact of opt-in vs opt-out framing and patient characteristics on receptiveness to RN SCM calls. All statistical tests were 2-sided. Results Of the 1204 symptom assessments (from 864 patients) on which at least 1 severe symptom was documented, 469 (39.0%) indicated receptivity to an RN SCM phone call. The opt-out period (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.12 to 2.32, P = .01), receiving care at a tertiary care center (OR = 3.59, 95% CI = 2.18 to 5.91, P < .001), and having severe pain (OR = 1.80, 95% CI = 1.24 to 2.62, P = .002) were associated with statistically significantly greater willingness to receive a call. Conclusions Many severely symptomatic patients were not receptive to an RN SCM phone call. Better understanding of reasons for refusal and strategies for improving patient receptivity are needed.

Purpose To quantify the financial impact of an anterior cruciate ligament (ACL) injury on the remaining career earnings of National Basketball Association (NBA) players. Methods We performed a retrospective review of all NBA players who had an ACL rupture between 2000 and 2019. Players were matched to healthy controls by age, position, body mass index, and player efficiency rating at the time of injury (index year). Player information collected included demographic information, position, team role, draft pick, date of injury, contract length, and earnings during the 3 years before and 7 years after the index year, as well as new contract length and earnings after injury. Results A total of 12 players (22%) did not return to play (RTP). No statistically significant difference in annual earnings was present at any time point between cohorts. When we examined the mean difference in earnings between the first 3 post‐index seasons and the 3 pre‐index seasons, both the ACL and control cohorts showed increased salaries as players’ careers progressed, without a significant difference in earnings. When comparing cohorts, we found no significant difference in the length and earnings of contracts during the index year. Furthermore, there was no significant difference in the length or earnings of the first new contract signed after the index year between cohorts. Additionally, NBA players who were able to RTP after ACL reconstruction were more likely to experience increased earnings if they had greater experience and performance prior to their injury ( P < .01). Conclusions Our study found that NBA players did not experience diminished earnings after RTP from an ACL reconstruction when compared with matched controls. Furthermore, no differences were seen in lengths of new contracts or in contract earnings between cohorts. Players with greater experience and performance prior to injury were more likely to have increased earnings after ACL reconstruction. Level of Evidence Level III, retrospective case‐control study.

Abstract Background: The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. Objectives: We aimed to examine the extent and identify associated factors of psychological distress, fear of COVID-19, and coping.Methods: We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. Results: A total of 8,559 people participated; mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping; the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]); nurses had medium to high resilient coping (1.30 [1.03-1.65]). Conclusions: The extent of psychological distress, fear of COVID and coping varied by country; however, some groups were more vulnerable than others. There is an urgent need to prioritise health and well-being of these people through well-designed intervention that may need to be tailored to meet country specific requirements.