Symptom Scale Research Articles

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

The Association of Central Sensitisation with Depression, Anxiety, and Somatic Symptoms: A Cross-Sectional Study of a Mental Health Outpatient Clinic in Japan

For patients with chronic pain and persistent physical symptoms, understanding the mechanism of central sensitisation may help in understanding how symptoms persist. This cross-sectional study investigated the association of central sensitisation with depression, anxiety, and somatic symptoms. Four hundred and fifteen adults attending an outpatient psychosomatic clinic were evaluated. Participants completed the Hospital Anxiety and Depression Scale, Somatic Symptom Scale 8, and the Central Sensitisation Inventory. The relationships between these factors were examined using descriptive statistics and multiple logistic regression analyses. The mean age was 42.3 years, and 59% were female. The disorders included adjustment disorders (n = 70), anxiety disorders (n = 63), depressive disorders (n = 103), feeding and eating disorders (n = 30), sleep–wake disorders (n = 37), somatic symptoms and related disorders (n = 84), and others (n = 28). In multiple logistic regression analyses, higher central sensitisation was associated with more severe anxiety, depression, and somatic symptoms after controlling for potential confounders. In the disease-specific analysis, somatic symptoms correlated more positively with central sensitisation than with depression or anxiety. Central sensitisation and depression, anxiety, and somatic symptoms were associated with patients attending an outpatient clinic. These findings highlight the importance of evaluating depression, anxiety, and somatic symptoms when assessing central sensitisation.

Classification of Neurocognition in Japanese Patients with Schizophrenia: A Cluster Analysis

Objectives. Cognitive functions in almost all domains are lower in patients with schizophrenia than those in healthy controls, with the severity of impairment differing between domains. Treatments are being developed to improve cognitive impairment in patients with schizophrenia. However, the pattern of cognitive impairment must be clarified to facilitate treatment. Therefore, this study aimed to classify the patterns of cognitive impairment in individuals and provide treatment suggestions. Methods. Patients with schizophrenia were recruited from two psychiatric hospitals in Japan. Demographic and psychopathological symptoms were assessed using the Positive and Negative Symptoms Scale for Schizophrenia and neurocognitive functions, using the CogHealth battery. The following domains were assessed: processing speed, visual attention, working memory, visual learning, and spatial attention. The scores were standardised and assigned as the same-aged average score. Hierarchical cluster analysis using Ward’s method was performed based on CogHealth scores. Subsequently, one-way analysis of variance (ANOVA) and Tukey’s multiple comparisons were performed to compare the variables in each cluster. Results. In total, 133 participants were classified into four clusters: Cluster 1 (n = 16), with severe cognitive impairment and psychiatric symptoms and the longest stay; Cluster 2 (n = 44), with moderate cognitive impairment and psychiatric symptoms; Cluster 3 (n = 42), with preserved cognitive function, except for spatial perception, and mild psychiatric symptoms; and Cluster 4 (n = 31), with only memory and spatial perception impairment and mild psychiatric symptoms. Implications. The clusters indicate that impairment may occur in all or selective domains. Selective domain impairments may be in spatial perception or in spatial perception and memory. Therefore, it is recommended that treatments for cognitive dysfunction are developed into four subsets considering an individual’s cognitive features.

Application of Patient-Reported Outcome Measurements in Adult Tumor Clinical Trials in China: Cross-Sectional Study.

International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.

Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Effects of transcranial direct current stimulation (tDCS) on positive and negative symptoms in patients with schizophrenia

&lt;strong data-sider-select-id="f4ff5758-cbc1-4488-b5a5-b99e557829a2"&gt;Introduction: The symptoms that patients with schizophrenia experience during schizophrenia are divided into two positive and negative symptoms. This study aims to evaluate the effectiveness of transcranial direct current stimulation (tDCS) on both positive and negative symptoms in patients with schizophrenia. &lt;strong data-sider-select-id="29511c21-03d5-4669-86b6-407f69f27fac"&gt;Method: This experimental study was a pretest-posttest plan consisting of patients with schizophrenia in Razi psychiatric hospital in Tabriz, of which 30 patients were selected in a targeted and available manner and randomly assigned to experimental and control groups. The experimental group underwent anodal tDCS treatment for ten sessions of 20 minutes at 72-hour intervals, while the control group underwent dummy treatment in the same manner. The research data were collected using The Positive and Negative Symptom Scale (PANSS) and analyzed using the covariance analysis method with SPSS software. &lt;strong data-sider-select-id="114a2ce6-9637-4a3f-9abf-a119f24c9f97"&gt;Results: The results of statistical analysis showed that tDCS has a significant effect on negative and general symptoms of schizophrenia (&lt;em data-sider-select-id="b29c5fe8-9cd3-403d-bb0d-5cb9687955c7"&gt;P=0.01) but has no significant effect on positive symptoms (&lt;em data-sider-select-id="d501a503-32d0-476d-bba9-74b786a54188"&gt;P≤0.05). &lt;strong data-sider-select-id="a10b5a5a-4d6d-42ac-ab49-c804ef982830"&gt;Conclusion: To the results of the present study, we concluded that tDCS is a suitable therapeutic tool in the treatment of pathological symptoms of schizophrenia.

Aberrant salience mediates the interplay between emotional abuse and positive symptoms in schizophrenia

IntroductionChildhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. MethodsWe approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. ResultsThe final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (β = 0.39; p < .001) and from ASI total score to PANSS positive (β = 0.17; p = .019). Finally, a statistically significant indirect association was found from emotional abuse to PANSS positive mediated by ASI total score (β = 0.06; p = .041; CI 95% [0.01, 0.13]). ConclusionEmotional abuse has an AS-mediated effect on positive psychotic symptomatology. AS evaluation could allow a better characterization of psychosis as well as explain the presence of positive symptoms in adults with SSDs who experienced CTA.

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Abstract PO5-04-14: Quality of Life (QoL) among metastatic hormone receptor positive, HER2 negative breast cancer patients during first line systemic treatment

Abstract Background Current international guidelines recommend endocrine therapy combined with a CDK4/6 inhibitor as the preferred first line systemic treatment in patients diagnosed with metastatic hormone receptor positive (HR), HER2 negative breast cancer (BC). Randomized controlled trials that led to the approval of these agents in the first line disease setting are derived from controlled environments and selected patients. We aimed to assess real-world patients’ characteristics, safety and health related quality of life in a non-select cohort of patients being managed in a Brazilian private Cancer Center. Methods: We performed a cross sectional study at Beneficencia Portuguesa de Sao Paulo evaluating quality of life among patients with metastatic HR+/HER2 negative treated in the first line disease setting. Inclusion criteria included patients that received the combination of a CDK4/6i with any endocrine therapy (ET) between January 2018 and April 2023. Primary endpoint was quality of life assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ-BR23, it is baseline, there is only one measurement for each patient. Results: We analyzed 72 patients who meet the inclusion criteria. Median age at diagnosis was 49 years old (ranging from 31 to 91). Approximately half of the population was premenopausal (51%). Palbociclib and abemaciclib were the most commonly used CDK4/6i, with 42 and 35% of patients, respectively. ECOG performance status was zero or one in almost the entire patient population analyzed (97%). 53% of the patients were diagnosed as de novo metastatic BC. Table 1 and 2 summarize the patients characteristics. Mean global health status was 75.4, with social and cognitive functioning scoring the highest (Mean 78.6 and 79.1, respectively). The most distressing symptom among the symptom scale was fatigue (Mean 27.2). Most symptoms and functioning scales did not meet the threshold for clinically meaningful differences between the different CDK4/6 inhibitors. Conclusion: Real-world data from our study is consistent with the historical expected health related quality of life among patients diagnosed with HR+/HER2 negative metastatic BC in the first line disease setting. Table. Citation Format: Débora Gagliato, Julio Antonio Araujo, Bianca Milena Verboski, Guilherme William Marcelino, Fabiana Nogueira Momberg, Gilmara Silveira da Silva, Rozana Mesquita Ciconelli, Antônio Buzaid. Quality of Life (QoL) among metastatic hormone receptor positive, HER2 negative breast cancer patients during first line systemic treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-14.

Incidence and assessment of delirium following open cardiac surgery; A systematic review and meta-analysis.

This systematic review and meta-analysis sought i) to provide an overview of the incidence of delirium following open cardiac surgery and ii) to investigate how incidences of delirium are associated with different assessment tools. A systematic search of studies investigating delirium following open cardiac surgery were conducted in Medline (Ovid), EMBASE, PsycINFO, CiNAHL and the Cochrane Database. Only studies with patients diagnosed or screened with a validated tool were included. Studies published from 2005 to 2021 were included in the meta-analysis.Of 7,126 individual studies retrieved, 106 met the inclusion criteria for the meta-analysis, hereof 31% of high quality. The weighted pooled incidence of delirium following open cardiac surgery across all studies was 23% (95% CI 20-26%), however we found a considerable heterogeneity (I2 = 99%), which could not be explained by subgroups or further sensitivity analyses. The most commonly applied screening tool for delirium is CAM/CAM-ICU. The lowest estimates of delirium were found by applying the Delirium Observation Scale (incidence 14%, 95% CI 8-20%), and the highest estimates in studies using "other" screening tools (Organic Brain Symptom Scale, Delirium Symptom Interview) pooled incidence of 43%, (95% CI 19 - 66%), however, only two studies applied these. Delirium following open cardiac surgery remains a complication with a high incidence of overall 23%, when applying a validated tool for screening or diagnosis. Nevertheless, this systematic review and meta-analyses highlight the significant inconsistency in current evidence regarding assessment tools and regimens. Prospero CRD42020215519.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks. Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed. Results: This analysis included 901 patients. Within 1–2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4–8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%–77.7% with upadacitinib 15 mg + TCS and 71.3%–83.6% with upadacitinib 30 mg + TCS. Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

Association of Sleep Quality with Physical and Psychological Health Indicators among Overweight and Obese, Middle-aged and Older Rural Indians

ObjectiveTo measure the association of sleep quality with physical (i.e., grip strength, functional mobility, balance) and psychological (depression, anxiety) health indicators in an overweight/obese population. MethodsBaseline data of 2,337 participants (1,382 overweight/obese and 955 normal weight) from an aging cohort in rural southern India (CBR-SANSCOG) was analyzed retrospectively. Assessment tools included the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, dynamometry for hand grip strength (HGS), timed up-and-go (TUG) for functional mobility, and chair stand test (CST) for lower limb strength, Geriatric Depression scale (GDS-30) for depressive symptoms and Generalized Anxiety Disorder scale (GAD-7) for anxiety symptoms. Linear regression models, adjusted for known confounders, were used to examine the association of sleep quality with the health parameters in overweight/obese and normal-weight groups. ResultsIn the fully adjusted model, higher total PSQI score was associated with higher TUG time (β= 0.06 95% CI: 0.004,0.12), higher scores on GDS (β= 1.08 95% CI: 0.96,1.20) and GAD (β= 0.71 95% CI: 0.62,0.79), and lower scores on CST (β= -0.12 95% CI: -0.19,-0.06) in overweight/obese. The sleep disturbance, sub-component of PSQI, was strongly associated with TUG, CST, GDS and GAD. Sleep duration and use of sleep medication showed no significant association with the health parameters in overweight/obese. ConclusionIn summary, concurrent presence of poor sleep quality and overweight/obesity can worsen physical and psychological health in middle-aged and older adults. We have addressed the importance of prevention of sleep problems and necessitate urgent attention towards assessment and treatment of sleep issues in overweight/obese.

The Correlates of Collective and Individual Trauma on Mental Health Outcomes Among Afghan Refugees: A Study of Sociodemographic Differences.

Following the U.S. military's departure from Afghanistan, a significant number of Afghan refugees have resettled in the United States, presenting complex mental health challenges exacerbated by extensive traumatic exposure. This demographic is particularly affected by collective trauma due to war, genocide, and the loss of homeland. However, detailed investigations into the correlations between collective trauma and mental health outcomes among Afghan refugees are limited. This study sought to explore the relationship between collective trauma and mental health outcomes within the Afghan refugee population in the United States, paying particular attention to the influence of sociodemographic factors. Identifying subgroups at greater risk allows for the development of more targeted mental health interventions. The study surveyed 173 Afghan refugees employing snowball sampling, utilizing a cross-sectional design. Data collection was facilitated through online and in-person surveys in English, Dari, and Pashto. Key measures included the Harvard Trauma Questionnaire for individual trauma experiences, the Historical Loss Scale for collective trauma, the Historical Loss Associated Symptoms Scale for collective trauma symptoms, the Afghan Symptom Checklist-22 for mental health symptoms, and the Post-Migration Living Difficulties Scale for post-migration stressors. Statistical analyses involved Pearson's correlation for variable associations, with nonparametric Mann-Whitney U and Kruskal-Wallis tests conducted to assess sociodemographic impacts due to data's non-normal distribution. The analysis revealed significant variations in collective trauma and mental health outcomes across subgroups. Afghan women, minoritized ethnic groups, those who experienced extended displacement, and refugees with uncertain visa statuses reported higher collective trauma levels and worse mental health outcomes. Statistical significance was noted in the correlations between collective trauma and mental health symptoms (r = .53, p < .01) and between post-migration difficulties and mental health (r = .33, p < .01). The disparities in mental health outcomes based on sociodemographic characteristics were significant, with nonparametric tests showing clear distinctions across different groups (Kruskal-Wallis H = 14.76, p < .05 for trauma experience by visa status). This study emphasizes the critical need for mental health interventions that account for the complex experiences of collective trauma among Afghan refugees, especially among identified subgroups. Tailoring mental health services to address the specific needs highlighted through disaggregated data can enhance support for Afghan refugees in the United States. This research contributes to a deeper understanding of the relationship between collective trauma and refugee mental health, advocating for nuanced care strategies in resettlement environments.

Study protocol of the GRoningen early-PD Ambroxol treatment (GREAT) trial: a randomized, double-blind, placebo-controlled, single center trial with ambroxol in Parkinson patients with a GBA mutation.

To date, no disease modifying therapies are available for Parkinson's disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson's Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson's Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. NCT05830396. Registration date: March 20, 2023.

Efficacy of acupuncture-related therapy in the treatment of primary dysmenorrhea: A network meta-analysis of randomized controlled trials

ObjectivesIn order to compare and rank the most effective acupuncture therapy for primary dysmenorrhea and provide evidence-based medical support for clinical treatment of this disease. MethodsA comprehensive search was conducted on China National Knowledge Infrastructure (CNKI), Wanfang Database, Information Chinese Journal Service Platform (VIP), China Biomedical Literature Service System (SinoMed), PubMed, Web of Science, Embase, and Cochrane Library databases from their inception to May 1, 2023. The Cochrane Collaboration Risk of Bias Tool was used to evaluate bias risk, and the GeMTC package of Stata 15.1 software and R 4.3.1 software was used to perform network Meta-analysis. Results70 studies were included, including 5772 patients with primary dysmenorrhea, involving 25 kinds of acupuncture techniques commonly used in clinic. The quality of the included literature was low, most of them did not mention the registration information of clinical trial centers, and the specific sample size estimation method was unclear. Some literature did not explain the specific random method, distribution concealment and blindness, so there was a certain publication bias and small sample effect. Results showed that for improving the clinical effective rate, the top three treatments were salt-separated moxibustion, massotherapy + acupoint patching, acupuncture + heat-sensitive moxibustion. In terms of reducing the visual analogue scale(VAS), the top three treatments were massotherapy + acupoint patching, acupuncture + acupoint patching and warm acupuncture. In terms of alleviating cox menstrual symptom scale (CMSS), the top three treatments were acupuncture + acupoint patching, acupoint patching and point embedding. In relieving TCM symptom score, the top three treatments were acupoint patching + heat-sensitive moxibustion, acupoint patching and moxibustion. ConclusionDifferent acupuncture therapies have more advantages than oral analgesics in improving the clinical effective rate, reducing VAS score, reducing CMSS score, and alleviating TCM symptom score. Among them, massage therapy + acupoint patching, acupuncture + acupoint patching and acupoint patching may be the best solutions for the treatment of primary dysmenorrhea. However, more large-sample, multi-center and high-quality randomized controlled trials are needed to demonstrate.

Real-world safety and effectiveness of anamorelin for cancer cachexia: Interim analysis of post-marketing surveillance in Japan.

Anamorelin was approved in Japan in 2021 to treat cancer cachexia associated with non-small cell lung, gastric, pancreatic, or colorectal cancers. Post-marketing surveillance is being conducted to evaluate the real-world safety and effectiveness of anamorelin. This prospective, observational surveillance registered all patients who started treatment with anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were defined as main safety specifications. Body weight (BW) and appetite were assessed as effectiveness specifications. This analysis was based on data as of January 21, 2023. The safety and effectiveness analysis sets included 6016 and 4511 patients, respectively. Treatment-related adverse events in ≥1% of patients were hyperglycemia (3.9%) and nausea (2.6%). The incidences of hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were 4.8%, 1.2%, and 1.1%, respectively. The mean changes (standard error [SE]) in BW from baseline to weeks 3, 12, 24, and 52 were 0.64 (0.05) kg, 1.19 (0.12) kg, 1.40 (0.21) kg, and 1.42 (0.39) kg, respectively. The mean changes (SE) in Functional Assessment of Anorexia/Cachexia Treatment 5-item Anorexia Symptom Scale total scores from baseline to weeks 3, 12, 24, and 52 were 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), and 5.3 (0.47), respectively, exceeding the clinically meaningful improvement score (2.0 points). The overall safety of anamorelin raised no new safety concerns, although continued caution may be required for hyperglycemia and nausea. Improvements in BW and appetite were also observed in real-world clinical settings.

Self-Perceived Vocal Symptoms and Discomfort in Amateur Church Singers

PurposeTo analyze self-perceived vocal symptoms and discomfort in amateur church singers and compare them between genders and church types. MethodsIt was a quantitative cross-sectional study involving 99 amateur church singers aged between 18 and 59 years. Data collection was carried out through the completion of a socio-demographic questionnaire, the Voice Symptom Scale (VoiSS), and the Vocal Tract Discomfort Scale (VTDS). The Mann-Whitney test was used for comparisons, and Spearman's correlation test was used for analyzing correlations between scale scores. The adopted significance level was 5% (p <0.05). ResultsThere was a prevalence of females (71.7%), amateur singers from Protestant churches (73.7%), with a mean age of 27.5 years. The average VoiSS total score was 22.6 points, the "limitation" domain was 12.3, the "emotional" domain was 2.55, and the "physical" domain was 7.7. The most self-perceived sensations in the VTDS were "dryness," "sore throat," and "itchiness" with mild to moderate intensity. There was a statistically significant difference between genders (p<0.05) and a positive correlation from weak (r=0.212) to strong magnitude (r=0.660) between vocal symptoms and vocal tract discomfort. There was no statistically significant difference between types of churches. ConclusionAmateur singers self-report high levels of vocal symptoms, which impact limitation, emotional, and physical domains. Furthermore, they experience vocal tract discomfort sensations, with dryness being the most frequently reported, followed by sore throat and itching. No significant differences were found between the scale scores and church types. However, females reported a greater frequency and intensity of vocal tract discomfort sensations. The greater the self-reported vocal symptoms in this population, the higher their self-reported frequency and intensity of vocal tract discomfort sensations. These findings underscore the importance of addressing vocal health issues in amateur singers to enhance their overall well-being.

Implementation and evaluation of the WHO maternity care model: a convergent parallel mixed-methods study protocol

BackgroundAccording to the World Health Organization (WHO), intrapartum care is considered a platform for providing respectful, personalized, and women-centered services to women. This study aims to investigate the intrapartum care model proposed by WHO.MethodsThis convergent parallel mixed-methods study will be carried out in qualitative and quantitative phases. In the quantitative phase (a quasi-experimental study), 108 pregnant women admitted to the maternity ward will be randomized to intervention (receiving intrapartum care based on the WHO model) and control group (receiving routine hospital care) before the beginning of the active stage of labor (cervix dilatation equal to 5 cm) and Wijma's delivery fear scale (DFS) will be completed for them and again at 7–8 cm dilatation. The participants of both groups will be followed up for 6 weeks after labor and then they will be invited to a relatively quiet place to complete the Childbirth Experience Questionnaire (CEQ 2.0), the Edinburgh Postpartum Depression Scale (EPDS), the Post-Traumatic Stress Disorder (PTSD) Symptom Scale (PSS-I), the Pregnancy and Childbirth Questionnaire (PCQ), exclusive breastfeeding and a checklist on willingness to give birth to another child. The qualitative phase will employ content analysis to explain mothers' views about the effects of this model especially subjective components of this model on their labor process after 4–6 weeks. The two phase's results will be discussed in combination.DiscussionThe implementation of such care models is expected to prevent mental disorders caused by negative experiences of childbirth, and also, prevent uncontrolled increases in cesarean sections. Clinical Trial Registrationhttps://fa.irct.ir/user/trial/68313/view, identifier (IRCT20120718010324N69).

The WHO Adult ADHD self-report Scale used in a clinical sample of patients with overlapping symptoms - psychometric properties of and scoring methods for the Swedish translation

Background The WHO Adult ADHD Self-report Scale (ASRSv1.1 and ASRS-S) is used for screening for attention-deficit/hyperactivity disorder (ADHD). The capacity of the Swedish version of the scale to discriminate ADHD from borderline personality disorder (BPD) and bipolar disorder (BP) has not been tested. Aim Evaluate scoring methods, psychometric properties, and diagnostic accuracy of the Swedish versions of ASRSv1.1/ASRS-S in a group of patients with ADHD and/or BPD and/or BP. Method A total of 151 young adult psychiatric patients diagnosed with ADHD, BPD and/or BD completed ASRSv1.1 and the Wender Utah Rating Scale (WURS) for ADHD symptoms, and the Sheehan Disability Scale (SDS) for functional impairment. ADHD diagnoses were assessed with the Schedule for Affective Disorders and Schizophrenia (K-SADS) interview. Both versions of the scale were analysed through dichotomised and non-dichotomised scoring for diagnostic accuracy analysis. Results The internal consistency for ASRSv1.1/ASRS-S was satisfactory with α 0.913 and 0.743, respectively. The two-factor structure of the ASRSv1.1 and the one factor structure of ASRS-S were supported by the confirmatory factor analyses. A strong positive correlation was found between ASRSv1.1 and WURS and a moderate level of correlation was found between ASRSv1.1 and SDS. The area under the curve for both scoring methods were excellent with an area under the curve (AUC) of 0.808 and 0.817, respectively. Optimal cut-off scores were in line with the original recommendations. Conclusion The Swedish translation of ASRSv1.1/ASRS-S has psychometric properties comparable to other populations and the capacity to screen for ADHD in patients with overlapping symptoms.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia

ObjectiveAlthough extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia.MethodsTo address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV.ResultsOur findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P&amp;lt; 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure.ConclusionOur research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.