Symptom Categories Research Articles

Patient With Parkinson Disease and Care Partner Perceptions of Key Domains Affecting Health-Related Quality of Life: Systematic Review

To effectively customize Parkinson disease (PD) programs, it is important to incorporate the "individual's voice" and have a thorough understanding of the symptom priorities of people with PD (PwP) and care partners (CP). In this convergent integrated mixed-method systematic review, we aimed to analyze qualitative and quantitative evidence of PD motor and nonmotor symptoms affecting health-related quality of life (HRQOL) in PwP and CP, comparing priorities across different levels of disease severity. We searched MEDLINE, PsycINFO, Web of Science, Embase, and Scopus; ProQuest Dissertations and Theses Global; and the Michael J. Fox Foundation Data Resources for studies published up to June 29, 2022. We included qualitative, quantitative, and mixed-method studies investigating PD symptom priorities among PwP and CP. We critically appraised eligible studies for methodological quality using the Mixed-Methods Appraisal Tool. Derived terms were mapped and coded according to thematic attribution. Independent syntheses of qualitative and quantitative evidence and transformation of quantitative data into qualitative formats were performed. Of the 7,716 identified studies, we included 70 that provided qualitative (n = 13), quantitative (n = 53), and mixed (n = 4) evidence. We included 604 mapped terms representing 11 PwP-identified and CP-identified motor and nonmotor symptom categories. Across all PD stages, both PwP and CP considered 5 domains more affecting their HRQOL, namely: "motor functionality," "mood," "cognition," "gait, balance, posture, and falls," and "nighttime sleep disorders." In early disease, PwP and CP considered "mood" the domain that most affected their HRQOL. In advanced PD, PwP considered "pain" the domain that most affects their HRQOL, while CP considered "psychiatric symptoms." The domain "gait, balance, posture, and falls" was equally considered by both PwP and CP as the second domain that most affects their HRQOL in the advanced stage of PD. The ranking of the priority of symptoms is largely shared by PwP and CP, and motor symptom priorities dominate the full disease spectrum. However, the nonmotor symptom priorities shift according to the disease severity stage. Tailored care and research require that providers consider these shifting priorities and incorporate the "individual's voice" into treatment decisions.

(071) Just Another Vaccine – VAERS Analysis Compares Genitourinary Symptoms of the COVID-19 Vaccine and Other Commonly Administered Vaccines

Abstract Introduction There has been a concern in mainstream media about adverse effects of the COVID-19 vaccine including those on the genitourinary system. Objective Our objective was to evaluate the rate of patient-reported genitourinary symptoms after the COVID-19 vaccine. We hypothesized rates of genitourinary side effects was not different compared to other commonly used vaccines. Methods We queried the Vaccine Adverse Events Reporting System (VAERS) database for all genitourinary symptoms reported after receiving the COVID-19, influenza, shingles, and pneumonia vaccines. Symptoms were placed into one of five categories – lower urinary tract symptoms (LUTS), sexual side effects, infectious, hematuria, or other disorders of the penis/scrotum/testis. Rates of genitourinary symptoms were compared between the vaccines. Data collection occurred 7-8/2022. Results Out of 13,568,650 symptoms reported after the COVID-19 vaccine, 9,022 were genitourinary (0.066%). Genitourinary symptoms included LUTS (39.71%), infectious (32.38%), hematuria (17.42%), disorders of the penis/scrotum/testis (5.99%), and sexual side effects (4.50%). Rates of genitourinary symptoms after the COVID-19 vaccine was significantly lower than the influenza (0.128%) (Table 1) but higher than the shingles (0.030%) and pneumonia (0.037%) vaccines (Table 2). There was no significant differences in the penis/scrotum/testis symptoms category. Rates of sexual side effects were overall low after the COVID vaccine (0.0030%) and not significantly different to rates of sexual side effects after the influenza vaccine (0.0036%) but were higher than after the pneumonia and shingles vaccines. Conclusions Genitourinary symptoms from the COVID-19 vaccine are rare. The rate of side effects is lower than the influenza vaccine, and while sexual and overall side effects are higher than the pneumonia and shingles vaccines, these rates are overall very low and unlikely to be clinically significant. Disclosure No.

Latent profile analysis of depressive symptoms in college students and its relationship with physical activity

ObjectiveTo explore the classification of depressive symptoms in college students and the relationship between those symptoms and physical activity. MethodsA convenience sampling method was employed to enlist college students from Songjiang University Town in Shanghai to complete in the General Information Questionnaire, Patient Health Questionnaire-9, and Physical Activity Scale-3. ResultsA total of 3541 students were analyzed, averaging 19.34 years of age with a male composition of 53 %. The participants can be classified into four categories, namely: Group 1, which exhibits the most severe depressive symptoms, including suicidal ideation and cognitive symptoms (11.07 %); Group 2, which only manifests cognitive symptoms without suicidal ideation (14.35 %); Group 3, which presents mild depressive symptoms (23.61 %); and Group 4, consisting of normal college students (50.97 %). Students with strained family and interpersonal relationships, high levels of academic stress, and low frequency of social activities were at higher risk for detecting suicidal intention and cognitive symptoms. The level of physical activity was significantly higher in the normal group than in the other groups (all P < 0.001), and only the frequency of exercise was significantly different among the remaining three groups (χ2 = 14.716, P = 0.005). The detection rate of cognitive symptoms was significantly lower when exercising >3 times per week for 30–59 min (OR = 0.740, 95 % CI: 0.590–0.928; OR = 0.596, 95 % CI: 0.427–0.831).The detection rate of suicidal thoughts was significantly lower when exercising 2 times per month to 2 times per week or >3 times per week (OR = 0.585, 95 % CI: 0.404–0.847; OR = 0.392, 95 % CI: 0.258–0.595). ConclusionSuicidal ideation and cognitive symptoms can differentiate between various categories of depressive symptoms among college students. Engaging in physical activity serves as a protective factor against depressive symptoms among college students.

Suicidal Thoughts and Trajectories of Psychopathological and Behavioral Symptoms in Adolescence

The suicidal risk of psychopathology in adolescence is suggested to differ based on its longitudinal trajectory, but the comorbidity of these symptom trajectories has not been well examined. This study comprehensively clustered trajectories of multiple psychopathological and behavioral symptoms and examined their associations with suicidal thoughts in adolescence. To determine which categories and trajectories of psychopathological and behavioral symptoms are associated with suicidal thoughts in adolescence, accounting for comorbid symptoms. This population-based cohort study in Japan used data from the Tokyo Teen Cohort (TTC) study, which was established in 2012 and is currently ongoing. Data from 3 waves of surveys conducted at ages 10, 12, and 16 years from October 2012 to September 2021 were used. Of the adolescents in the cohort, participants with at least 2 evaluations of psychopathological and behavioral symptoms were included. Data were analyzed from December 2022 to March 2023. Latent class growth analysis was used to cluster the trajectory of each psychopathological and behavioral symptom. The associations between symptom trajectories and suicidal thoughts at age 16 were examined. Suicidal thoughts were assessed using a self-report questionnaire. Psychopathological and behavioral symptoms were assessed using the 8 subscale scores of the caregiver-report Child Behavior Checklist. This study included 2780 adolescents (1306 female participants [47.0%]). Of the 1920 adolescents with data on suicidal thoughts, 158 (8.2%) had suicidal thoughts. The median (IQR) age was 10.2 (10.0-10.3) years at the first evaluation, 11.9 (11.8-12.1) years at the second evaluation, and 16.3 (16.1-16.5) years at the last evaluation. The clustering pattern of trajectories varied depending on symptom categories. After adjusting for each symptom trajectory and confounders, adolescents with persistent high withdrawn symptoms (odds ratio [OR], 1.88; 95% CI, 1.10-3.21) and those with increasing somatic symptoms (OR, 1.97; 95% CI, 1.16-3.34) had a significantly higher risk of suicidal thoughts than adolescents without these symptoms. There was no interaction between these symptom trajectories and the risk of suicidal thoughts. This cohort study found that persistent withdrawn symptoms and increasing somatic symptoms during early to midadolescence were associated with an increased risk of suicidal thoughts in midadolescence, even after accounting for comorbid symptoms and confounders. Attention should be paid to the suicidal risk associated with these symptoms, particularly when they persist or increase in the longitudinal follow-up.

Chronic Symptomatology Among Infants, Children, and Adolescents Within 12 Months After SARS-CoV-2 Infection.

Objective. The objective of this public health surveillance project was to estimate the proportion of persons under the age of 18 years with confirmed SARS-CoV-2 infection who developed chronic symptoms and to further characterize the symptoms and associated factors. Methods. Parents provided information during a telephone interview or through a web-based questionnaire. Results. Of 212 infants, children, and adolescents, 11 (5.2%) experienced a wide range of mild to severe chronic symptoms following SARS-CoV-2 infection, with 90% indicating inability to continue normal activities. Factors associated with chronic symptoms were pre-existing chronic medical conditions overall, certain categories of symptoms (eg, neurologic/psychiatric symptoms), and specific symptoms experienced with the acute SARS-CoV-2 infection (eg, fatigue, vomiting). Conclusion. Future research regarding chronic symptomatology among persons with confirmed SARS-CoV-2 infection would benefit from the use of standardized definitions of the timing and duration of chronic symptoms and from the enrollment of comparison groups.

Anxiety and Depression in Adults With Congenital Heart Disease

BackgroundA comprehensive understanding of adult congenital heart disease outcomes must include psychological functioning. Our multisite study offered the opportunity to explore depression and anxiety symptoms within a global sample. ObjectivesIn this substudy of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults With Congenital Heart Disease–International Study), the authors we investigated the prevalence of elevated depression and anxiety symptoms, explored associated sociodemographic and medical factors, and examined how quality of life (QOL) and health status (HS) differ according to the degree of psychological symptoms. MethodsParticipants completed the Hospital Anxiety and Depression Scale, which includes subscales for symptoms of anxiety (HADS-A) and depression (HADS-D). Subscale scores of 8 or higher indicate clinically elevated symptoms and can be further categorized as mild, moderate, or severe. Participants also completed analogue scales on a scale of 0 to 100 for QOL and HS. Analysis of variance was performed to investigate whether QOL and HS differed by symptom category. ResultsOf 3,815 participants from 15 countries (age 34.8 ± 12.9 years; 52.7% female), 1,148 (30.1%) had elevated symptoms in one or both subscales: elevated HADS-A only (18.3%), elevated HADS-D only (2.9%), or elevations on both subscales (8.9%). Percentages varied among countries. Both QOL and HS decreased in accordance with increasing HADS-A and HADS-D symptom categories (P < 0.001). ConclusionsIn this global sample of adults with congenital heart disease, almost one-third reported elevated symptoms of depression and/or anxiety, which in turn were associated with lower QOL and HS. We strongly advocate for the implementation of strategies to recognize and manage psychological distress in clinical settings. (Patient-Reported Outcomes in Adults With Congenital Heart Disease [APPROACH-IS]; NCT02150603)

Impact of Post-Acute Sequelae of COVID-19 on Lives of Patients Post-Intensive Care Unit Discharge: A Cross-Sectional Study

Objectives: Post-acute sequelae of SARS-CoV-2 (PASC) are known for their prolonged and persistent effects on patients. This study aimed to investigate the impact of the PASC on the quality of life (QOL) of patients, their levels of activity participation, and satisfaction with these levels, in addition to exploring whether the duration of post-intensive care unit (ICU) discharge is associated with the effects of PASC. Subject and Methods: This cross-sectional study included 134 patients with COVID-19 discharged from an ICU in Kuwait. Data were collected using two validated questionnaires: the World Health Organization Quality of Life-Brief (WHOQOL-BREF) and Satisfaction with Daily Occupations. Additionally, demographic information was collected, and 11 categories of related symptoms were investigated. Results: Most patients reported health issues post-ICU discharge. Furthermore, most PASC-related symptoms decreased over time, whereas a few increased. Notably, we observed a negative association between post-discharge duration and overall improvement in level of participation in activities of daily living. However, patients discharged from the ICU for more than 6 months demonstrated higher satisfaction with functional performance and improved QOL. Additionally, patients who received rehabilitation, and were vaccinated were less likely to have poor QOL. No significant sex differences were observed in the WHOQOL-BREF score. Conclusion: PASC adversely affected the daily functioning of patients, especially in leisure, social, and religious aspects. However, these effects lessened over time, with corresponding improvement in QOL. Additionally, patient satisfaction with functional performance increased over time. These findings shed light on the rehabilitation needs of patients with COVID-19.

The relationship between maladaptive health beliefs, pandemic-related stress, and health anxiety during the COVID-19 pandemic.

Research has demonstrated that people experience specific distress and anxiety regarding COVID-19. This distress may consist of interconnected symptom categories corresponding to a COVID stress syndrome. Susceptibility to COVID stress syndrome may be related to one's maladaptive health beliefs; however, no research has investigated the association between maladaptive health beliefs and COVID stress. The present study explored the impact of health beliefs on COVID stress, health anxiety, and associated psychological constructs. This cross-sectional survey study included 221 adults (M age = 20.59, SD = 2.28). Participants completed an online survey including demographic questionnaires and self-report measures of health beliefs, COVID stress, health anxiety, and related psychological constructs. Health anxiety, anxiety sensitivity, state/trait anxiety, intolerance of uncertainty, and depression accounted for significant variance in COVID stress (F(6, 214) = 11.18, R2 = .24, p < .001). Health beliefs (i.e., perceived likelihood of illness, medical service inadequacy, and difficulty coping) were associated with greater COVID stress, although health beliefs were not found to mediate the relationship between health anxiety and COVID stress. Health beliefs were associated with greater COVID stress, although health beliefs did not mediate the relationship between health anxiety and COVID stress. The relationship between health anxiety and COVID stress may be better explained by other COVID-related cognitions (e.g., vaccine efficacy, dangerousness of COVID-19). The findings highlight the importance of peoples' health beliefs during the pandemic. Given anxiety's influence on peoples' behavioural responses to the pandemic, further research should identify COVID-specific cognitions for prevention of COVID stress and health anxiety.

Fungi Associated with Post-harvest Losses of Multani Mango

The Multani mango, renowned for its exceptional taste and aromatic profile, is a cultivar thriving in the fertile soils of Multan, Pakistan, representing a cherished tropical delicacy. Despite its esteemed status in the region's mango-producing legacy, a formidable challenge arises from its limited shelf life. Fungal pathogens associated with the mango curtail its shelf life and detrimentally impact fruit yield and quality. This study aimed to isolate and identify fungal pathogens linked to Mango anthracnose, stem end rot, side rot, and fruit fly attack symptoms. Ten mango fruits exhibiting symptoms were systematically sampled from three distinct markets in Multan, totalling 30 fruits for each disease symptom category. Isolation and identification outcomes revealed that in mangoes displaying anthracnose symptoms, Colletotrichum gloeosporoides was present in 100% of fruit samples, followed by Aspergillus fumigatus (72.72%). For mango fruits with stem end rot, Botryodiplodia theobromae was identified in 90.90% of samples, followed by Colletotrichum gloeosporoides (70%). Fruits exhibiting symptoms of fruit fly attack and side rot contained Aspergillus flavus in 99.90% and 88.81% of samples, respectively. These findings underscore the pivotal role of fungal pathogens in the Multani mango's shelf-life predicament, necessitating strategic interventions in cultivation and post-harvest handling. The identification of specific pathogens provides valuable insights for targeted management practices aimed at preserving the quality and extending the shelf life of this esteemed mango cultivar.

The role of emotion beliefs in depression, anxiety, and stress

ABSTRACT Objective Beliefs about the controllability and usefulness of emotions may influence successful emotion regulation across multiple emotional disorders and could thus be influential mechanisms in long-term mental health outcomes. However, to date there has been little empirical work in this area. Our aim was to fill this gap, by examining the links between emotion beliefs and common emotional disorder symptoms. Specifically, we examined whether emotion beliefs can account for significant variance in depression, anxiety, and stress symptoms, and explored which profiles of emotion beliefs might characterise each of these symptom categories. Methods A sample of 948 Australian university students completed self-report measures of emotion beliefs and emotional disorder symptoms. Results A path analysis indicated that emotion beliefs accounted for a modest but significant 11%, 12%, and 9% of the variance in depression, anxiety, and stress symptoms, respectively (ps < .001). A latent profile analysis revealed six different profiles of combinations of emotion beliefs and emotional disorder symptom levels, collectively reinforcing the transdiagnostic relevance of emotion beliefs across each symptom category. Conclusions Overall, our results indicate the importance of considering emotion beliefs in conceptualisations of depression, anxiety, and stress, and suggest that emotion beliefs may be a useful assessment and treatment target.

Accuracy and reproducibility of ChatGPT's free version answers about endometriosis.

To evaluate the accuracy and reproducibility of ChatGPT's free version answers about endometriosis for the first time. Detailed internet searches to identify frequently asked questions (FAQs) about endometriosis have been performed. Scientific questions were prepared in accordance with the European Society of Human Reproduction and Embryology (ESHRE) endometriosis guidelines. An experienced gynecologist gave a score of 1-4 for each ChatGPT answer. The repeatability of ChatGPT answers about endometriosis was analyzed by asking each question twice, and the reproducibility of ChatGPT was accepted as scoring the answer to the same question in the same score category. A total of 91.4% (n = 71) of all FAQs were answered completely, accurately, and sufficiently. ChatGPT had the highest accuracy in the symptom and diagnosis category (94.1%, 16/17 questions) and the lowest accuracy in the treatment category (81.3%, 13/16 questions). Furthermore, of the 40 questions based on the ESHRE endometriosis guidelines, 27 (67.5%) were classified as grade 1, seven (17.5%) as grade 2, and six (15.0%) as grade 3. The reproducibility rate of FAQs in the prevention, symptoms, and diagnosis, and complications categories was the highest (100% for all categories). The reproducibility rate was the lowest for questions based on the ESHRE endometriosis guidelines (70.0%). ChatGPT accurately and satisfactorily responded to more than 90% of the questions about endometriosis, but to only 67.5% of questions based on the ESHRE endometriosis guidelines.

Prevalence of depression in junior and senior adolescents.

Depression affects the development of adolescents and makes it difficult for them to adapt to future life. The purpose of this study was to elucidate the population characteristics of adolescent depression. This study measured depression based on the Patient Health Questionnaire-9 items and sociodemographic questionnaire. A total of 8,235 valid questionnaires were collected from six schools in Haikou and Qionghai, Hainan Province, covering the ages of 13 to 18. The questionnaires included high schools with multiple levels, including general high schools, key high schools, and vocational high schools. Latent category analysis (LCA) was used to identify potential categories of depressive symptoms among adolescents. Latent Class Analysis (LCA) was used for determining depressive symptom latent categories and their proportional distribution among adolescents. LCA analysis divided the data into 3 categories, namely no depression, low depression, and high depression groups. The percentage of the high depression group was 10.1%, and that of the low depression group was 48.4%. The Jorden index was greatest for a PHQ-9 score of 14.5. The 1st grade of junior middle school students entered the high and low depression groups 1.72 and 1.33 times more often than seniors. The number of the 1st grade of high school students included in the high and low depression groups was 1.55 and 1.42 times of the 3rd grade of high school students group. The detection rate of the high depression group of vocational school adolescents was 13.5%, which was significantly higher than that of key high schools (9.6%) and general high schools (9.0%). This study found that 1st grade of junior middle school students and the 1st grade of high school students were more likely to fall into depressive conditions. Moreover, Adolescent girls require more attention than boys. Vocational school students need more psychological guidance.

The relationship between adolescent impulsivity, mental health, and internet addiction: a latent profile analysis

ABSTRACT This study aimed to identify group variations in adolescent impulsivity and explore the connections between latent categories of impulsivity and psychological symptoms, social anxiety, and internet addiction. The research involved 2,378 participants from three middle schools in Guangdong Province, China. We assessed the impact of impulsivity levels (measured by BBIS) on depression (measured by KADS-11), anxiety (measured by SCARED), social anxiety (measured by SASC), and internet addiction (measured by YDQ). Latent profile analysis was employed to examine the diversity in adolescent impulsivity, establish latent classifications, and investigate the variances in psychological symptoms, social anxiety, and internet addiction. The middle school students were categorized into five latent groups based on their BBIS scores. Statistical analysis revealed five impulsivity categories, strongly linked to psychological symptoms and social anxiety but less strongly associated with internet addiction. The high impulsivity group (C5) exhibited higher scores in psychological symptoms and social anxiety compared to other groups, whereas the poor self-regulation group (C3) displayed greater psychological symptoms, social anxiety scores, and internet addiction than the impulsive behavior group (C4). Future investigations should investigate the underlying factors contributing to the observed differences among these groups.

Association between severity of symptoms and minimum mental health treatment duration in humanitarian contexts: a retrospective observational study

Understanding and optimising mental health and psychosocial support (MHPSS) interventions in humanitarian crises is crucial, particularly for the most prevalent mental health conditions in conflict settings: anxiety, depression, and post-traumatic stress disorder. However, research on what is the most appropriate length of psychological intervention is lacking in this setting. We aimed to establish which factors are most closely related to improvement and to determine the required number of consultations needed to achieve this improvement. We retrospectively analysed records from 9028 patients allocated to treatment for anxiety, depression, and post-traumatic symptoms from the MHPSS programme in Borno State, Nigeria, from January 2018 to December 2019. Patient characteristics, severity (Clinical Global Impression of Severity Scale, CGI-S scale), and clinical improvement were assessed by an attending counsellor (CGI-I scale) and by the patient (Mental Health Global State, MHGS scale). Improvement was defined as scores 1, 2, and 3 in the Clinical Global Impression of Improvement (CGI-I) scale, and as a decrease of at least 4 points in the MHGS scale. We investigated the associations between the category of symptoms, the severity of illness, and improvement of symptoms using multivariable logistic regression. We used Kaplan-Meier (KM) curves to assess the number of consultations (i.e., time of treatment) needed to achieve improvement of symptoms, by symptom category and symptom severity. The patients included were referred to treatment for anxiety (n=3462), depression (n=3970), or post-traumatic symptoms (n=1596). Median age was 31 years (range 16-103), and 84.3% were female. Patients categorised as severe were less likely to present improvement according to the CGI-I scale (OR 0.11, 95% CI 0.05-0.25), while none of the other categories of symptoms showed significant results. Overall, three or more consultations were associated with improvement in both scales (OR 3.55, 95% CI 1.47-8.57 for CGI-I; and OR 3.04, 95% CI 2.36-3.90 for MHGS). KM curves for the category of symptoms showed that around 90% of patients with anxiety, depression, or post-traumatic symptoms, as well as those with mild or moderate severity, presented improvement after three consultations, compared with six consultations for those with severe symptoms. Classification by severity among patients with anxiety, depression, or post-traumatic symptoms could predict the probability of improvement, whereas classification by symptoms could not. Our study highlights the importance of classifying patient severity in MHPSS programmes to plan and implement the appropriate duration of care. A major limitation was the number of patients lost to follow up after the first consultation and excluded from the logistic regression and KM analysis. The study was funded and staffed entirely by Médicos Sin Fronteras (Médecins Sans Frontières), Spain.

Moya –Moya disease revealed by a subarachnoid hemorrhage: A case report

Background: Hemorrhage is a major category of the clinical symptoms of moyamoya disease (MMD). Intracerebral and intraventricular hemorrhages are the most common hemorrhages in MMD, and subarachnoid hemorrhages (SAHs) are notably rare. Case report: A 43 year old female patient, with no previous pathological history, admitted with a frank meningeal syndrome followed by a disorder of consciousness.She was admitted with a GCS at 15, which was subsequently reduced to 10. She was hemodynamically and respiratory stable with a BP of 12/8 cm/Hg, a respiratory rate of 16 cycles/min and a heart rate of 92 beats/min. Initial imaging showed subarachnoid hemorrhage Fisher IV. A cerebral angiography-CT showed vascular thrombosis of the internal carotid artery whitout aneurysm and arteriovenous malformation and dural fistulas. An EVD (external ventricular drain) was placed. After three days of hospitalization in the intensive care unit, a cerebral arteriogram was performed showing vascular arrest in the right internal carotid artery in its pre-cavernous portion with absence of visualization of the right sylvian artery and the presence of several perforating cerebral artery and external carotid artery bypass systems suggestive of Moya Moya. Conclusion: Moya Moya disease is a rare entity of unknown origin. Subarachnoid hemorrhage is a rare manifestation. It’s mainly occurs in a young adult. Cerebral angiography remains the gold standard for diagnosis.

An Updated Analysis of Ocular Adverse Events and Vision-Related Functioning in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. In this descriptive analysis, we evaluate the OAEs and their impact on daily functioning in transplant ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. The study is comprised of 2 Parts: Part 1 evaluates the safety/clinical activity of three different belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd and establishes the recommended phase 2 dose (RP2D). Part 2 further investigates the safety/efficacy of RP2D in two Groups and evaluates two different sets of guidelines for the management of OAEs. In Part 1, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events v5.0, while dry eye disease severity and vision-related functioning is assessed with the patient-reported questionnaire Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis presents the OAEs in all Part 1 pts over an extensive follow-up period (data cut-off: 05 June 2023). Results Thirty-six pts were included in this analysis, who were followed up for a median of 20.3 months (range 3.2-26.8). At baseline, all pts had ocular comorbidities. Among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4 mg/kg, a meaningful BCVA decline (BCVA &amp;lt;20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%) of the assessments, while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. The most frequently reported ≥Gr 3 ocular symptom was decreased vision, observed in 11 (5%)/ 8 (3%)/ 7 (3%) of the assessments, while ≥Gr3 keratopathy was noted in &amp;lt; 2% of assessments across all cohorts. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the Activities of Daily Living category (ADL) were 6 (3%)/4 (2%)/3 (2%). In terms of missed doses due to OAEs, among 129/138/119 planned belamaf infusions, the number of skipped doses were 53 (41%)/48 (35%)/32 (27%). The overall response rate was 100%, no disease progression was observed over a median follow-up of 20.3 months, and 30 (83%) patients achieved at least VGPR while 19 (53%) achieved at least CR, with a median time to first response of 1 month. Conclusions Over a prolonged follow-up period, the belamaf-Rd triplet, with the extended dosing schedule for belamaf, had a minimal impact in vision-related functioning, as the ‘all/most’ of the time worst answers in the ADL category of OSDI was ≤3% across all cohorts. Furthermore, the frequency of clinically relevant impairment in vision was low, as a meaningful BCVA decline was observed in &amp;lt;10% of assessments, with a rapid time to resolution. Finally, the treatment combination induced rapid, deep and durable responses across all dose levels, with no PD observed. In conclusion, this novel extended belamaf schedule nearly eradicates the risk for clinically relevant ocular toxicity and impact on ADL, without any compromise in clinical activity, suggesting it may be a valid option in the upfront treatment of this frail, elderly and difficult-to-treat pt population.

Transdiagnostic cognitive biases in psychiatric disorders: A systematic review and network meta-analysis

Psychiatric disorders are characterized by cognitive deficits, which have been proposed as a transdiagnostic feature of psychopathology (“C” factor). Similarly, cognitive biases (e.g., in attention, memory, and interpretation) represent common tendencies in information processing that are often associated with psychiatric symptoms. However, the question remains whether cognitive biases are also transdiagnostic or are specific to certain psychiatric disorders/symptoms. The current systematic review sought to address whether the proposed “C” factor of transdiagnostic cognitive dysfunction in psychopathology can be extended to cognitive biases. Overall, 31 studies comprising 4401 participants (2536 patients, 1865 non-clinical controls) met inclusion criteria, assessing 19 cognitive biases across 20 diagnostic categories, with most studies focusing on interpretation (k = 22) and attention (k = 11) biases and only 2 assessing memory biases. Traditional meta-analyses found a moderate effect size (g = 0.32) for more severe cognitive biases in all patients relative to non-clinical controls, as well as small but significant associations between interpretation biases and transdiagnostic symptom categories (general psychopathology: r = 0.20, emotion dysfunction: r = 0.17, psychotic symptoms: r = 0.25). Network meta-analyses revealed significant patient versus non-clinical control differences on attention and interpretation biases across diagnoses, as well as significant differences between diagnoses, with highest severity in panic disorder for attention biases and obsessive-compulsive disorder for interpretation biases. The current findings extend the big “C” interpretation of transdiagnostic cognitive dysfunction in psychiatric disorders to cognitive biases and transdiagnostic symptom dimensions. Results also suggest that while the presence of cognitive biases is transdiagnostic, bias severity differs across diagnoses, as in traditional neurocognitive deficits.

Impact of interleukin-1β single nucleotide polymorphisms and depressive symptoms in individuals with chronic viral hepatitis.

Elevated levels of interleukin 1β (IL-1β) have been identified in patients with chronic viral hepatitis and have been associated with depressive symptoms. Given the high prevalence of depression in this patient population, this study sought to explore the potential influence of IL-1β genetic variations on the severity of depressive symptoms. In a cohort of 181 Taiwanese patients with chronic viral hepatitis, we investigated the impact of five common IL-1β single nucleotide polymorphisms (SNPs), including rs16944, rs1143627, rs1143630, rs1143643, and rs3136558, on depressive symptoms using the Beck's Depression Inventory-II. Additionally, we analyzed the primary domains of IL-1β-related depressive symptoms according to Beck's six symptom categories of depression. Our analysis revealed significant associations between depressive symptoms and three intronic IL-1β SNPs. After controlling for age, sex, marital status, and education level, patients with the rs1143630 GG, rs1143643 CC, and rs3136558 AA genotypes demonstrated higher severity of depressive symptoms in the domains of indecision (p = 0.004), agitation (p = 0.001), and feelings of punishment (p = 0.005), respectively, compared to rs1143630 GA+AA, rs1143643 CT, and rs3136558 AG+GG genotypes. According to Beck's categorization, these symptoms can be classified into three dimensions: disturbances in emotion regulation, energy, and cognition. Our findings demonstrate the association between IL-1β polymorphisms and depressive symptoms and suggest a potential underlying mechanism for specific depressive symptoms within the chronic viral hepatitis population. These insights could improve our understanding and treatment of depressive symptoms in individuals with viral hepatitis.

The Additional Disease Burden Accompanying a Delayed Diagnosis of Multiple Myeloma: Utilising a Large Real-World Evidence Base

Background Multiple myeloma (MM) is one of the most difficult cancers to diagnose, leading to one of the longest delays in diagnosis of all cancers. Delays in diagnosis of MM can reduce survival and lead to complications; however, the extent of disease burden patients experience has not been fully explored from the patient perspective. Our large-scale real-world surveys explore the symptom profiles, disease burden, and the downstream impact on the quality of life (QoL) of MM patients with a delayed versus timely diagnosis. Methods MM patients participated in two national surveys in the UK. Patients were asked to provide demographics, information on their symptoms at diagnosis, and whether they received a timely (&amp;lt;3 months from initial symptoms) or delayed diagnosis (3 months or more from their initial symptoms). Patients subsequently completed the PROMIS-29 v2.0 Health-Related QoL Questionnaire where they were asked to reflect on their current experiences; having completed at least 1 line of treatment. The questionnaire assessed seven health domains (i.e. physical function, fatigue, pain interference, depression, anxiety, social activity participation, and sleep disturbance) alongside a 10-item pain intensity scale. Results 586 MM patients completed Survey 1 and 617 patients completed Survey 2. Overall, patients reported a wide range of symptoms at diagnosis with ‘pain’ reported most frequently overall (74% of cases). Patients with a delayed diagnosis had significantly more symptoms ( M = 5, SD = 4), compared to those with a timely diagnosis ( M = 3, SD = 3), p &amp;lt; .001. MM patients with a delayed diagnosis also reported significantly more symptoms in 9 of the categories of symptoms (see Figure 1) compared to patients with a timely diagnosis, p &amp;lt; .001. Moreover, patients with a delayed diagnosis perceived more of their symptoms as having a ‘high impact’ on their daily lives at the time of diagnosis compared to those with a timely diagnosis, p &amp;lt; .001. The next analysis assessed the likely order that symptoms manifest at diagnosis depending on whether patients had a delayed or timely diagnosis. The most frequently experienced first symptom in patients with a timely or delayed diagnosis was ‘pain’. Decision tree analysis showed that patients with a timely diagnosis who experienced ‘pain’ as their first symptom, were 57% more likely to experience spinal fractures as their next symptom. Conversely, those with a delayed diagnosis were 83% more likely to experience mobility issues as their second symptom. The downstream impact of a delayed diagnosis revealed MM patients with a delayed diagnosis had significantly higher pain interference ( M = 57 vs 53), pain intensity ( M = 4 vs 3), sleep disturbance ( M = 53 vs 51), anxiety ( M = 56 vs 53), depression ( M = 53 vs 50) and fatigue ( M = 57 vs 55), compared to MM patients with a timely diagnosis. MM patients with a delayed diagnosis reported significantly lower physical functioning scores ( M = 43 vs 45) than patients with a timely diagnosis. Scores measuring the ability of patients to carry out social roles and activities were also significantly lower in patients with a timely than delayed diagnosis ( M = 42 vs 44). Conclusions Patients in these large-scale and real-world surveys experienced considerable disease burden at diagnosis when they had a delayed versus timely diagnosis, both in terms of frequency and range of symptoms. The results show the considerable impact of individual symptoms on the daily lives of patients at diagnosis, as well as the downstream impact delayed diagnosis has on the QoL of MM patients. The results offer a potential model for disease progression based on the staging of symptoms and a method for identifying MM patients in clinical practice.

Long-Term Safety and Efficacy Results of Belantamab Mafodotin Plus Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: An Updated Part 1 Analysis from the Phase 1/2 Belard Trial

Introduction The preferred upfront treatment of transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM) consists of the combination of lenalidomide and dexamethasone (Rd) with a third antimyeloma agent of a different mechanism of action (e.g., proteasome inhibitors or anti-CD38 monoclonal antibodies). Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting BCMA, has shown efficacy in pretreated MM pts, while preclinical data demonstrate synergy between belamaf and lenalidomide, with no overlapping toxicities. Thus, there is a strong rationale for investigating the belamaf-Rd triplet in TI NDMM pts. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Eligible are adult pts with ECOG PS 0-2 and adequate organ function. Part 1 evaluates the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and establishes the recommended phase 2 dose (RP2D). In this part, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation. Ocular symptoms are classified by CTCAE v5.0, while the Ocular Surface Disease Index (OSDI) captures dry eye disease and activities of daily living (ADL).Herein, we present updated safety and efficacy results of all Part 1 pts with an extended follow-up time (cut-off date 05/06/2023). Results Of the 36 pts [median age: 72.5 years; male: 19 (53%)] in Part 1, 29 (81%) are still on treatment, while 7 (19%) have discontinued [6 pts due to belamaf-unrelated fatal events: (COVID-19: 1/1/2; Pneumonia: 1/1/0, for cohorts 2.5/1.9/1.4 respectively); 1 pt withdrew consent]. The median belamaf administrations and number of cycles reached were 6/7/7 and 20.0/22.5/20.0, for the respective cohorts. The most common (≥10% of pts) non-ocular ≥ Gr3 treatment-emergent adverse events were fatigue (21 pts, 58%; [7 (58%)/7 (58%)/7 (58%)]), diarrhoea (8 pts, 22%; 2 (17%)/3 (25%)/3 (25%)]), rash (6 pts, 17%; [2 (17%)/2 (17%)/2 (17%)]), COVID-19 (5 pts, 14%; [2 (17%)/1 (8%)/2 (17%)]) and insomnia (4 pts, 11%; 0/4 (33%)/0]) , while no ≥Gr3 thrombocytopenias and infusion-related reactions were reported. Regarding ≥Gr3 infections other than COVID-19, pneumonia was reported for 3 (8%) pts [1/1/1 (8%)] and lower respiratory tract infection for 1 (3%) pt [0/0/1(8%)]. Regarding ocular adverse events (OAEs), among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4, a meaningful BCVA decline (BCVA &amp;lt;20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%), while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. Across all cohorts, the most frequently reported ≥Gr 3 ocular symptom was decreased vision (26/665, 4%), while ≥Gr3 keratopathy was noted in &amp;lt;2% of assessments. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the ADL category were 6 (3%)/4 (2%)/3 (2%). The overall response rate was 100% across all cohorts: More specifically CR or better was achieved by 7 (58%)/6 (50%)/6 (50%), VGPR by 3 (25%)/5 (42%)/3 (25%) and PR by 2 (17%)/1 (8%)/3 (25%) pts in cohorts 2.5/1.9/1.4, with a median time to first response of 1 month. Finally, at a median follow-up of 20.3 months, no disease progression was observed, median PFS and median time to progression were not reached ( Figure 1) and responses continue to deepen across all cohorts. Conclusions Over an extended follow-up period, the belamaf-Rd triplet has proven a safe and effective combination for the upfront treatment of TI NDMM pts, with no long-term safety signals. Furthermore, the extended dosing schedule for belamaf had a minimal impact in vision-related functioning, as very low rates of meaningful BCVA decline and “most/all” OSDI responses were noted across all cohorts, with a rapid time to resolution. Meanwhile, a very promising clinical activity is observed, with rapid, deep and durable responses across all dose levels. Consequently, after validation with bigger pt numbers, this novel combination may well be a very attractive frontline option for this vulnerable and difficult-to-treat pt population.