Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS). Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTS = 23) or <3 years (NSTS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTS = 23; NSTS = 74) and methylation analysis (NLTS = 18; NSTS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed. Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers. Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.

The Childhood Cancer Data Initiative: Using the Power of Data to Learn From and Improve Outcomes for Every Child and Young Adult With Pediatric Cancer.

Data-driven basic, translational, and clinical research has resulted in improved outcomes for children, adolescents, and young adults (AYAs) with pediatric cancers. However, challenges in sharing data between institutions, particularly in research, prevent addressing substantial unmet needs in children and AYA patients diagnosed with certain pediatric cancers. Systematically collecting and sharing data from every child and AYA can enable greater understanding of pediatric cancers, improve survivorship, and accelerate development of new and more effective therapies. To accomplish this goal, the Childhood Cancer Data Initiative (CCDI) was launched in 2019 at the National Cancer Institute. CCDI is a collaborative community endeavor supported by a 10-year, $50-million (in US dollars) annual federal investment. CCDI aims to learn from every patient diagnosed with a pediatric cancer by designing and building a data ecosystem that facilitates data collection, sharing, and analysis for researchers, clinicians, and patients across the cancer community. For example, CCDI's Molecular Characterization Initiative provides comprehensive clinical molecular characterization for children and AYAs with newly diagnosed cancers. Through these efforts, the CCDI strives to provide clinical benefit to patients and improvements in diagnosis and care through data-focused research support and to build expandable, sustainable data resources and workflows to advance research well past the planned 10 years of the initiative. Importantly, if CCDI demonstrates the success of this model for pediatric cancers, similar approaches can be applied to adults, transforming both clinical research and treatment to improve outcomes for all patients with cancer.

NCI intramural program approach to rare tumors: Natural history study of rare solid tumors in children and adults: A longitudinal, comprehensive data and biospecimen collection protocol.

Rare tumors across the world are lacking adequate knowledge, resources, and community. Through partnership with patients, advocacy organizations, researchers, and clinicians, we have developed a comprehensive, longitudinal, prospective, and retrospective natural history protocol to collect, analyze, and share data on patients with rare tumors. A strong collaborative effort is vital to ensure success of enrollment, patient engagement, data collection, and analysis to ultimately develop clinical trials to improve outcomes for patients with rare cancers.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

PURPOSE: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. METHODS: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. RESULTS: Fifty-five patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). CONCLUSION: This interim analysis supports feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. TRIAL REGISTRATION: NCT04301089 registered on 3/9/2020.

Heterogeneous clinicopathological findings and patient-reported outcomes in adults with MN1-altered CNS tumors: A case report and systematic literature review.

The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, "High-grade neuroepithelial tumor with MN1 alteration" (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with MN1-altered primary CNS tumors diagnosed via genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

Purpose: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. Methods: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. Results: 55 patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). Conclusion: This interim analysis confirmed feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. Trial Registration: NCT04301089 registered on 3/9/2020.

Association of Employment Status With Symptom Burden and Health-Related Quality of Life in People Living With Primary CNS Tumors.

BACKGROUND AND OBJECTIVES: Financial toxicity significantly affects many patients, especially cancer survivors. We evaluated the association of unemployment as a major contributor to financial toxicity with patient-reported outcomes (PROs) assessing multiple illness experience domains in a primary CNS tumor (PCNST) cohort. METHODS: Patient and disease characteristics and PROs measuring symptom burden, interference, psychologic distress, functional impairment, and health-related quality of life (HRQOL) from participants enrolled in an institutional review board-approved observational study at the US NIH's Neuro-Oncology Branch were collected between September 2016 and December 2019. Descriptive statistics, tests of association, and comparison of group mean values were used to describe and evaluate PROs. RESULTS: Of the 277 participants diagnosed with a PCNST, 57% were male and 43% were female. Participants reported their race as White, non-Hispanic (78%); White, Hispanic/Latino (9%); Asian (7%); Black (4%); Native Hawaiian/Pacific Islander (1%); and other (2%) with 8% missing. The median age of the overall cohort was 45 years (range 18-74). Hispanic participants in the overall sample were 2.3 times more likely, and in the brain tumor group 3.2 times more likely, to report unemployment (p = 0.043, odds ratio [OR] 2.3, 95% CI 1.0-5.4 and p = 0.008, OR 3.2, 95% CI 1.3-7.9, respectively). 77 (28%) individuals unemployed due to tumor reported more functional impairment with walking, washing, dressing, and performing usual activities and reduced HRQOL (p < 0.001). More unemployed participants in the total sample reported moderate-to-severe depressive symptoms (25%) than those employed (8%) (χ2(1) = 13.9, p < 0.001, OR 3.7, 95% CI 1.8-7.8) and more moderate-to-severe anxiety symptoms (30%) than those employed (15%) (χ2(1) = 7.8, p = 0.005, OR 2.4, 95% CI 1.3-4.5). Unemployed participants with brain tumor reported on average 3 more symptoms as moderate-to-severe compared with those employed (t(83) = -4.0, 95% CI [Formula: see text] difference -5 to -2, p < 0.001, Hedge g = 0.70). DISCUSSION: Being unemployed due to a PCNST strongly correlated with high symptom burden, functional impairment, psychological distress, and reduced HRQOL, which may be impediments to returning to work that warrant intervention. Lack of employer-based health insurance and reduced earnings are financial sequelae of unemployment superimposed on the physical, social, and cognitive effects of living with a PCNST. Innovations to screen for and address financial toxicity and its contributing factors are needed.

Relationship between RANO-PRO Working Group standardised priority constructs and disease progression among malignant glioma patients: A retrospective cohort study.

Background: Recognising the importance of clinical outcomes assessments (COAs), the Response Assessment in Neuro-Oncology-Patient Reported Outcome (RANO-PRO) Working Group recommended inclusion of core symptoms and functions in clinical care or research for malignant glioma patients. This study evaluated the association of the recommended symptoms (pain, perceived cognition, seizures, aphasia, symptomatic adverse events) and functions (weakness, walking, work, usual activities) with disease progression in these patients. Methods: In this retrospective cohort study, patients with malignant glioma were included from the US National Cancer Institute Neuro-Oncology Branch Natural History Study (NOB-NHS) which follows primary central nervous system tumour patients aged 18 years and older throughout their disease trajectory. The M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT), EQ-5D-3L, Karnofsky Performance Status (KPS), and Neurologic Function scores (NFS) were evaluated in relation to disease progression by chi-square tests, independent- and paired-samples t-tests, adjusted for multiple comparisons at first assessment and over time to a second assessment. Radiographic disease progression was determined on the interpretation of the imaging study by a radiologist and neuro-oncologist using standard criteria as part of clinical trial participation or routine standard of care. The priority constructs were evaluated to provide initial evidence of their relevance, relationship to disease status over time, and sensitivity to change in a diverse group of patients with malignant glioma. Findings: Seven hundred and sixty-five patients had enrolled into the NOB-NHS between September 1, 2016 and January 31, 2020. Three hundred and thirty-six patients had a diagnosis of a malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, and gliosarcoma) and were included in the current study. The sample was 64% male (n = 215), 36% female (n = 121), median age of 52 years (IQR = 18.75), 82% White (n = 276), and 65% had tumour recurrence (n = 219). One hundred and fifty-four (46%) had radiographic disease progression. Difficulty remembering, fatigue, and weakness were worse in the group whose imaging was interpreted as radiographic disease progression versus stable disease, as well as the functions of walking, work, activity, and self-care (1.1 < difference < 1.8). Patients with disease progression were four times more likely to have a poor KPS (≤80) and worse NFS. Among patients with disease progression at a second assessment (n = 112), all symptoms, except seizures, worsened between first assessment and disease progression and up to 22% of patients (n = 25) reported worsening mobility, self-care, and usual activity; 46% (n = 51) and 35% (n = 30) had worsened KPS and NFS, respectively. On average, 4 symptoms or functions (SD = 3) were reported as moderate-to-severe and 30% (n = 33) and 23% (n = 26) had a change to moderate-to-severe fatigue and walking, respectively, at time of disease progression. Over 7% of patients with worsening (n = 7 of 100) reported every symptom and function as having changed the most severely including seizures with fatigue and activity reported as the top symptom and function, respectively. Interpretation: The identified core symptoms and functions worsened at the time of progression, supporting the relevance and sensitivity of the priority constructs identified by the RANO-PRO Working Group for clinical care and clinical trials for malignant glioma patients. Funding: The Natural History Study is supported by Intramural Project 1ZIABC011786-03.

Exploring the acute cardiovascular effects of Floatation-REST.

The central nervous system (CNS) exerts a strong regulatory influence over the cardiovascular system in response to environmental demands. Floatation-REST (Reduced Environmental Stimulation Therapy) is an intervention that minimizes stimulation from the environment, yet little is known about the autonomic consequences of reducing external sensory input to the CNS. We recently found that Floatation-REST induces a strong anxiolytic effect in anxious patients while paradoxically enhancing their interoceptive awareness for cardiorespiratory sensations. To further investigate the physiologic nature of this anxiolytic effect, the present study measured acute cardiovascular changes during Floatation-REST using wireless and waterproof equipment that allowed for concurrent measurement of heart rate, heart rate variability (HRV), breathing rate, and blood pressure. Using a within-subjects crossover design, 37 clinically anxious participants with high levels of anxiety sensitivity and 20 non-anxious comparison participants were randomly assigned to undergo a 90-min session of either Floatation-REST or an exteroceptive comparison condition that entailed watching a relaxing nature film. Measures of state anxiety and serenity were collected before and after each session, while indices of autonomic activity were measured throughout each session. HRV was calculated using both time-series and frequency domain analyses. Linear mixed-effects modeling revealed a significant main effect of condition such that relative to the film condition, Floatation-REST elicited significant decreases (p < 0.001) in diastolic blood pressure, systolic blood pressure, breathing rate, and certain metrics of HRV including the standard deviation of the interbeat interval (SDNN), low-frequency HRV, and very low-frequency HRV. Heart rate showed a non-significant trend (p = 0.073) toward being lower in the float condition, especially toward the beginning of the session. The only metric that showed a significant increase during Floatation-REST was normalized high-frequency HRV (p < 0.001). The observed physiological changes were consistent across both anxious and non-anxious participants, and there were no significant group by condition interactions. Blood pressure was the only cardiac metric significantly associated with float-related reductions in state anxiety and increases in serenity. These findings suggest that Floatation-REST lowers sympathetic arousal and alters the balance of the autonomic nervous system toward a more parasympathetic state. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03051074], identifier [NCT03051074].

Glenoid bone augmentation: a contemporary and comprehensive systematic review of open procedures.

Introduction: There is a trend towards arthroscopically treating shoulder instability with glenoid deficiency. Despite this, there remains the option for treatment through an open technique. Multiple bone augmentation options are available for recurrent anterior shoulder instability. Objective: To provide a systematic review of recent studies for recurrent anterior shoulder instability necessitating glenoid bone augmentation specifically through open procedures using coracoid bone or free bone blocks [iliac crest bone autograft/allograft or distal tibia allograft (DTA)]. Methods: PubMed, Cochrane, EMBASE, and Google Scholar were searched for studies reporting open glenoid bone augmentation procedures with iliac crest, tibia, or coracoid bones within 10 years. Extracted data included study/patient characteristics, techniques, prior surgeries, prior dislocations, radiographic findings, range of motion (ROM), recurrent instability, patient-reported outcomes, and complications. Results: 92 met inclusion criteria (5693 total patients). Six were studies of iliac crest bone, four of DTA, and 84 using the coracoid bone. 29 studies measured postoperative arthritis showing no development or mild arthritis. 26 studies reported postoperative graft position. 62 studies reported ROM noting decline in internal/external rotation. 87 studies measured postoperative instability with low rates. Rowe Scores with noted improvement across 31/59 (52.5%) studies were seen. Common post operative complications included infection, hematoma, graft fracture, nerve injury, pain, and screw-related irritation. Conclusion: Despite a trend towards arthroscopic management of recurrent anterior shoulder instability with glenoid deficiency, open procedures continue to provide satisfactory outcomes. Additionally, studies have demonstrated safe and efficacious use of free bone block graft options in the primary and revision setting.

The Montreal Cognitive Assessment (MoCA) in neuro-oncology: A pilot study of feasibility and utility in telehealth and in-person clinical assessments.

Background: Cognitive impairments are a common burden for patients with primary CNS tumors. Neuropsychological assessment batteries can be too lengthy, which limits their use as an objective measure of cognition during routine care. The purpose of this study was to evaluate the feasibility and utility of the brief Montreal Cognitive Assessment (MoCA) in routine in-person and telehealth visits (as a result of the global COVID-19 pandemic) with neuro-oncology patients. Methods: Seventy-one adults with primary CNS tumors completed MoCA testing in person (n = 47) and via telehealth (n = 24). Correlation analysis and patient-reported outcomes (PROs), including symptom burden and interference, perceived cognition, general health status, and anxiety and depression, were included in this study. Feasibility was assessed through a provider satisfaction questionnaire. Results: Patients were primarily White (83%), college-educated (71%) males (54%) with high-grade tumors (66%). The average total score on the MoCA administered in person was 25 (range: 6-30), with 34% classified as abnormal, and the average total score via telehealth was 26 (range: 12-30), with 29% classified as abnormal. Providers reported satisfaction in using the MoCA during routine clinical care, both in person and via telehealth. Lower MoCA scores correlated with worse symptom severity, KPS, age, education, and previous treatment. Conclusions: The MoCA was feasible in clinical and telehealth settings, and its relationship to clinical characteristics and PROs highlights the need for both objective and patient-reported measures of cognition to understand the overall cognitive profile of a patient with a CNS tumor.

Return to play and performance in the National Basketball Association after undergoing operative or nonoperative treatment for foot fracture.

Background: The incidence of distal lower extremity fractures in National Basketball Association (NBA) athletes continues to increase. There is a paucity of data regarding return-to-play (RTP) rates and performance after sustaining foot fractures in these athletes. The purpose of this study is to quantify RTP rates and performance in NBA players after sustaining a foot fracture. Methods: Sixty-two NBA athletes suffered foot fractures between 2005 and 2021 according to publicly accessible online data. Each athlete was matched to a control player based on age at start of career, age at index injury year, body mass index (BMI), and position played. Performance statistics from 3 seasons prior and 3 seasons following the index injury season were recorded. Results: We found that players who suffered foot fracture injuries are expected to make a full recovery and reach their previous level of performance within three years. 100% of players treated nonoperatively returned to play; meanwhile only 90% of players who were treated operatively returned to play. This difference is statistically significant. Conclusion: NBA athletes have a high RTP rate after sustaining a foot fracture. Players may experience an initial decrease in playing time and performance when returning to play, however, these variables were found to return to baseline over time. After three seasons, player statistics returned to baseline in mostly every category, including player efficiency rating (PER). We found that players are expected to make a full recovery and return to their previous level of performance, regardless of whether they were treated operatively or not. Players treated nonoperatively returned to play at a rate of 100% meanwhile those treated operatively returned at a rate of 90%. Therefore, it is our recommendation that players opt for nonoperative treatment when possible.

Evaluation of the key geriatric assessment constructs in primary brain tumor population - a descriptive study.

INTRODUCTION: Despite an increasing aging population, older adults (≥ 65 years) with primary brain tumors (PBTs) are not routinely assessed for geriatric vulnerabilities. Recent reports of geriatric assessment (GA) in patients with glioblastomas demonstrated that GA may serve as a sensitive prognosticator of overall survival. Yet, current practice does not include routine evaluation of geriatric vulnerabilities and the relevance of GA has not been previously evaluated in broader cohorts of PBT patients. The objective of this descriptive study was to assess key GA constructs in adults with PBT dichotomized into older versus younger groups. MATERIALS AND METHODS: A cross-sectional analysis of data collected from 579 participants with PBT recruited between 2016 and 2020, dichotomized into older (≥ 65 years, n = 92) and younger (≤ 64 years, n = 487) from an ongoing observational trial. GA constructs were evaluated using socio-demographic characteristics, Charlson Comorbidity Index (CCI), polypharmacy (>5 daily medications), Karnofsky Performance Status (KPS), Neurologic Function Score (NFS), and patient-reported outcome assessments including general health, functional status, symptom burden and interference, and mood. Descriptive statistics, t-tests, chi-square tests, and Pearson correlations were used to evaluate differences between age groups. RESULTS: Older participants were more likely to have problems with mobility (58% vs. 44%), usual activities (64% vs 50%) and self-care (38% vs 26%) compared to the younger participants (odds ratios [ORs] = 1.3-1.4, ps < 0.05), while older participants were less likely to report feeling distressed (OR = 0.4, p < 0.05). Older participants also had higher CCI and were more likely to have polypharmacy (OR = 1.7, ps < 0.05). Increasing age strongly correlated with worse KPS score (r = -0.232, OR = 1.4, p < 0.001) and worse NFS (r = 0.210, OR = 1.5, p < 0.001). No differences were observed in overall symptom burden, symptom interference, and anxiety/depression scores. DISCUSSION: While commonly used GA tools were not available, the study employed patient- and clinician-reported outcomes to identify potential future research directions for the use of GA in the broader neuro-oncology population. Findings illustrate missed opportunities in neuro-oncology practice and underscore the need for incorporation of GA into routine care of this population. Future studies are warranted to further evaluate the prognostic utility of GA and to better understand functional aging outcomes in this patient population.

Hyperinsulinemia Associated Depression.

Hyperinsulinemia promotes fat accumulation, causing obesity. Being an inflammatory state, obesity can induce further inflammation and is a risk factor for HPA (hypothalamic pituitary axis) dysregulation through hypercortisolism-related hyperglycemia. In another hypothesis, the sympathetic nervous system (SNS) plays a significant role in the regulation of hormone secretion from the pancreas such as an increase in catecholamines and glucagon as well as a decrease in plasma insulin levels, a disruption on SNS activity increases insulin levels, and induces glycogenolysis in the liver and lipolysis in adipose tissue during hypoglycemia. Hyperglycemia-hyperinsulinemia exacerbates inflammation and increases the oxidative stress along with regulating the levels of norepinephrine in the brain sympathetic system. Increased inflammatory cytokines have also been shown to disrupt neurotransmitter metabolism and synaptic plasticity which play a role in the development of depression via inhibiting serotonin, dopamine, melatonin, and glutamate signaling. An increased level of plasma insulin over time in the absence of exercising causes accumulation of lipid droplets in hepatocytes and striated muscles thus preventing the movement of glucose transporters shown to result in an increase in insulin resistance due to obesity and further culminates into depression. Further hyperinsulinemia-hyperglycemia condition arising due to exogenous insulin supplementation for diabetes management may also lead to physiological hyperinsulinemia associated depression. Triple therapy with SSRI, bupropion, and cognitive behavioral therapy aids in improving glycemic control, lowering fasting blood glucose, decreasing the chances of relapse, as well as decreasing cortisol levels to improve cognition and the underlying depression. Restoring the gut microbiota has also been shown to restore insulin sensitivity and reduce anxiety and depression symptoms in patients.

Coping competence and hopelessness moderate the influence of perceived burdensomeness on suicidal ideation in undergraduate college students.

According to the interpersonal theory of suicide, the perception of imposing a burden on loved ones increases the risk for suicidal ideation. Little research, however, has examined the interaction of burdensomeness with cognitive variables in predicting suicidal ideation in college students even though the relationship between burdensomeness and ideation may be contingent on levels of cognitive risk factors. The present study thus examined the relationships between burdensomeness, hopelessness, coping competence, and suicidal ideation. Questionnaires were administered to 279 undergraduate students from a university in the Midwest United States. After controlling for depression, hopelessness, and coping competence, burdensomeness significantly predicted ideation and accounted for variance above and beyond the control variables. Moreover, the relationship between burdensomeness and suicidal ideation was significantly moderated by coping competence and hopelessness. The findings suggest that perceived burdensomeness plays a critical role in the risk for suicide in college students. More specifically, the findings suggest that coping competence and hopelessness can be ideal targets for interventions as changes in these variables may attenuate the association between perceived burdensomeness and suicidal ideation.

Applying fairness in labeling various types of internet use disorders. •.

We comment on arguments about internet and smartphone use disorders by Montag, Wegmann, Sariyska, Demetrovics, and Brand (2020). Although not currently official diagnoses, we emphasize that for some individuals, excessive internet/smartphone use can have dangerous consequences. We discuss the challenges with ICD-11 codifying only internet gaming as an internet use-related disorder, neglecting other types of excessive internet users. Montag et al.'s approach to classifying a broader range of internet use disorders seems more fair than the current system in aiding individuals needing treatment resources for excessive internet use.

Improved Efficacy of Topical Latanoprost 0.005% Demonstrated by Corneal Biomechanical Correcting Modified Goldmann Prism.

PURPOSE: To evaluate intraocular pressure (IOP) reduction measured by a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann (CATS) prism with the institution of a topical prostaglandin analog (PGA) or alternatively a topical beta blocker. DESIGN: Prospective, open-label, randomized, controlled, and reference device comparison. METHODS: Thirty-six (36) treatment naïve glaucoma patients (72 eyes) were randomized equally to treatment with latanoprost 0.005% or timolol maleate 0.5%. Each patient underwent IOP measurement with standard GAT and CATS prisms before and at 1, 3, and 6 months of treatment. Central corneal thickness (CCT) and corneal hysteresis (CH) were also measured. Medication response was defined as a 20% reduction in IOP from baseline. RESULTS: The CATS prism demonstrated the IOP reduction with topical latanoprost at a mean of 1.9 mmHg lower than the IOP measured with GAT (p=0.01). The CATS and GAT prisms detected no difference in IOP reduction with timolol (p=0.23). The number of latanoprost treatment non-responders was reduced from 36.1% measured with GAT to 13.8% when measured with the CATS prism (p=0.005). Timolol indicated no difference in the treatment non-response rate at 22.2% (p=0.999). CH increased significantly with latanoprost treatment by an average of 0.55 mmHg (p=0.014) and remained unchanged with timolol at -0.014 mmHg (p=0.68). DISCUSSION: IOP reduction and responder rates were increased when measured with a CATS prism in patients using latanoprost and not with timolol use. Latanoprost-induced alterations in corneal biomechanics may dampen the actual IOP reduction measured with a standard GAT prism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04178863.

Excessive reassurance seeking mediates relations between rumination and problematic smartphone use.

Aside from depression and anxiety, less is known about the relationship of problematic smartphone use (PSU) to other psychopathology- related variables. The authors' aim was to test previously neglected variables in relation to PSU: rumination and excessive reassurance seeking behavior (ERSB). The authors recruited 295 college students for a web-based survey of smartphone use frequency, PSU, depression and anxiety, ruminative thinking, and ERSB. The authors tested linear regression and mediation models, assessing rumination and ERSB as mediating associations between depression/anxiety severity with PSU, adjusting for age, sex, and smartphone use frequency. Results demonstrate that ERSB was significantly related to PSU severity, and ERSB mediated the association between rumination and PSU. Furthermore, the combination of rumination and ERSB mediated relations between both depression and anxiety severity with PSU. Results provide evidence for ERSB as an important variable in understanding relationships between psychopathology symptoms and PSU severity among college students.

Modified Goldmann prism intraocular pressure measurement accuracy and correlation to corneal biomechanical metrics: multicentre randomised clinical trial.

PURPOSE: Clinically evaluate intraocular pressure (IOP) measurements taken with a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann prism examining measurement differences correlated to central corneal thickness (CCT) and corneal hysteresis (CH) values. DESIGN: Prospective, open-label, randomised, controlled, multicentre reference device accuracy analysis. METHODS: A GAT and a modified surface GAT prism measured IOP on 243 unique eyes. The study design and methodology complied with International Standard Organization (ISO) tonometer evaluation guidelines, except the inclusion of thin (<500 µm) and thick (>600 µm) corneas. All eyes were randomised to IOP measurement by one of five standard Goldmann prisms and five modified prisms. Pressures were measured by six investigators, two times with each prism for a total of 1936 IOP measurements. Analysis included a multiple linear regression including CCT and CH correlation. RESULTS: The difference in IOP measurements of the standard and modified Goldmann prisms correlated well to CCT particularly in thin (<500 µm) and thick (>600 µm) corneas (R2=0.404, p=0.007). Corneal hysteresis (CH) also significantly correlated to the difference in prism measurements (R2=0.125, p=0.039). There was no significant overall mean IOP bias between the two prisms (+0.43 mm Hg in modified, p=0.19). DISCUSSION: The paired IOP measurement difference between GAT and a modified surface Goldmann replacement prism indicated a statistically significant correlation to CCT and CH. A simple modified replacement prism for any Goldmann-type tonometer may significantly improve IOP measurement accuracy by minimising corneal biomechanical errors associated with CCT and CH. TRIAL REGISTRATION NUMBER: NCT02990169 and NCT02989909.