Total Symptom Score Research Articles

Patient (pt) experience with and perceptions of transfusion-dependent (TD) and transfusion-independent (TI) myelofibrosis (MF): A qualitative interview study.

e23110 Background: MF is a rare myeloproliferative neoplasm for which Janus kinase inhibitors are the standard of care. Some Janus kinase inhibitors can exacerbate anemia, a hallmark feature of MF that increases in severity with disease progression. Red blood cell transfusions are an important component of anemia management, but transfusion dependence is an independent predictor of poor survival outcomes and is inversely correlated with quality of life (QOL). The current study aimed to elicit the perceived direct and indirect burden of transfusion dependence and its impact on pts with MF. Methods: Concept elicitation interviews were conducted remotely with Janus kinase inhibitor–experienced and symptomatic (MF Symptom Assessment Form v4.0 Total Symptom Score [TSS] ≥10) pts with MF across the US, UK, Germany, Italy, Spain, and Poland (N = 20). Five TD pts (≥2 blood transfusions in any 1 mo over the last 3 mo) and 15 TI pts (≤1 blood transfusion in any 1 mo over the last 3 mo) participated in 60-minute interviews, which followed a semistructured guide including open-ended questions and completion of ranking exercises and sociodemographic and clinical forms. Results: Of 20 pts, mean age was 59 years, 50% were male, and85% received a diagnosis of anemia after their MF diagnosis. Pts with anemia experienced a range of related symptoms, including fatigue (94%), weakness (53%), and night sweats (29%). These symptoms impacted several QOL domains, including emotional (88%) and physical (71%) health and social life (71%). Most pts (18 of 20) had received a transfusion in the past, of whom 5 were TD. In addition to higher transfusion burden, TD pts had higher symptom burden than TI pts (mean TSS, 30.8 vs 27.9).TD pts endorsed challenges with frequent transfusions relating to clinical concerns/safety (100%), convenience (100%), and travel (80%), all of which remained concerns when thinking about being TD in the future (40% each). These challenges resulted in emotional (80%) and physical (60%) impacts and impacts to activities of daily living (60%). Four of 5 (80%) reported that going ≥12 weeks without a transfusion would be helpful and positively impact their QOL. Similarly, TI pts felt it was important to remain TI, with 73% expressing concerns about becoming TD in the future. Regarding the most important MF treatment outcomes, MF symptom reduction and overall survival were the most common (40% each) among TD pts, and reduction/avoidance of transfusion was the most common (40%) among TI pts. Conclusions: These interviews characterize the substantial negative experiences with and perceptions of anemia and transfusions in pts with MF who are TD and those who are TI but concerned about becoming TD in the future. These findings highlight the value of treatment options that reduce/eliminate transfusion burden and prevent future transfusions in improving the experiences of pts with MF.

The mediating effect of positive expectations in the relationship between social support and post-traumatic stress disorder symptoms among parents of children with acute lymphoblastic leukemia

PurposeParents of children with cancer are exposed to risks of developing post-traumatic stress disorder (PTSD) symptoms, but few studies have explored PTSD symptoms of Chinese parents of children with acute lymphoblastic leukemia (ALL). Our study aimed to examine the association between social support and PTSD symptoms and to examine the mediating effect of positive expectations in this relationship among parents of children with ALL. MethodsA cross-sectional study was conducted of consecutive parents of children with ALL in the Shengjing Hospital of China Medical University. A total of 177 parents eligible for this study completed questionnaires on PTSD symptoms, perceived social support, optimism and general self-efficacy anonymously. Asymptotic and resampling strategies were used to examine how positive expectations mediated the association between perceived social support and PTSD symptoms. ResultsMean score of PTSD symptoms was 37.64 ± 14.44; 29.4% of the sample scored 44 and above, 19.8% scored 50 and above. After adjusting for covariates, perceived social support was negatively associated with the total score of PTSD symptoms (β = −0.209, p < 0.01). Positive expectations were found to mediate the relationship between perceived social support and PTSD symptoms, especially for the symptoms of avoidance and hyperarousal. ConclusionsOptimism and general self-efficacy fully mediated the association between perceived social support and PTSD symptoms. Therefore, social support and positive expectations should be included in PTSD preventions and treatments targeting Chinese parents of children with ALL.

Phase 3 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in patients with essential thrombocythemia (ET).

TPS6596 Background: ET is a myeloproliferative neoplasm (MPN) driven by mutations in JAK2, CALR, and MPL that is characterized by thrombocytosis and megakaryocyte hyperplasia. Currently available treatments can prevent thrombotic complications but do not substantially alter the natural history of ET. LSD1 is an enzyme that regulates hematopoietic stem and progenitor cell proliferation and is overexpressed in MPNs. In a phase 2 study, the LSD1 inhibitor bomedemstat was generally well tolerated and improved symptoms, durably reduced platelet and white blood cell counts, and reduced mutation burden in patients with ET. Here, we describe the methods for a randomized, open-label, phase 3 study (NCT06079879) that has been designed to evaluate bomedemstat versus best available therapy in patients with ET who had an inadequate response to or were intolerant of hydroxyurea. Methods: Key eligibility criteria include age ≥18 years, a diagnosis of ET per World Health Organization 2016 diagnostic criteria, a bone marrow fibrosis score of grade 0 or 1, a platelet count of &gt;450 x 109/L, and an absolute neutrophil count of ≥0.75 x 109/L. All patients must have a history of inadequate response to or intolerance of hydroxyurea per modified European LeukemiaNet (ELN) criteria. Patients will be randomly assigned 1:1 to bomedemstat 50 mg/day by mouth (starting dose) or investigator’s choice of best available therapy (anagrelide, busulfan, interferon alfa/pegylated interferon alpha, or ruxolitinib). Bomedemstat dose will be titrated to a target platelet count of ≥150 to ≤350 x 109/L. After 52 weeks, patients receiving best available therapy can cross over to bomedemstat at the investigator’s discretion and patients in the bomedemstat arm can continue on treatment (maximum of 156 weeks on study). Randomization will be stratified by hydroxyurea history (inadequate response vs intolerance) and MFSAF v4.0 baseline score (≥4 vs &lt;4). Clinic visits will occur every 2 weeks until week 12 and monthly thereafter. Adverse events will be graded per NCI CTCAE v5.0 criteria and monitored for up to 30 days after last dose of study drug. The primary end point is durable clinicohematologic response rate per modified ELN criteria. Secondary end points are duration of clinicohematologic response, duration of hematologic remission, change from baseline in total symptom and fatigue score per MFSAF v4.0 criteria, change from baseline in total fatigue score per the PROMIS Fatigue SF-7a scale, incidence of thrombotic or major hemorrhagic events, transformation to post-ET myelofibrosis or myelodysplastic syndrome/acute myeloid leukemia, event-free survival, and safety. Exploratory end points include pharmacokinetics, the proportion of patients reporting stability or improvement versus decline on the MSAF v4.0 and PROMIS Fatigue SF-7a domains, and molecular biomarkers. Approximately 300 patients will be enrolled. Clinical trial information: NCT06079879 .

Long-term outcomes following impedance-controlled radiofrequency ablation for the treatment of chronic rhinitis.

To assess long-term safety and effectiveness of a multipoint, impedance-controlled, RF ablation device for treatment of chronic rhinitis through 12-month follow-up. A prospective, multicenter study. Bilateral posterior nasal nerve (PNN) ablation was performed on all participants. Assessments at 6-, 9-, and 12-month visits included Visual Analog Scale Nasal Symptom Score (VAS NSS), reflective Total Nasal Symptom Score (rTNSS), mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini RQLQ), and adverse events. Thirty-six participants were enrolled and 35 completed the 12-month follow-up. All 5 VAS NSS items demonstrated statistically significant improvement (p < .0001) over baseline at all 3 time points. The total rTNSS improved from 7.9 ± 1.8 at baseline to 4.3 ± 2.1 at 6-months, 3.8 ± 2.4 at 9-months, and 4.0 ± 2.1 at 12-months (all p < .0001). At 12-months, 91% (31/35) of participants had achieved the minimum clinically important difference (MCID) of a reduction from baseline of ≥1 point and 80% (28/35) of the participants met the responder criteria of ≥30% reduction from baseline. The total mean mini RQLQ was reduced from 3.0 ± 1.0 at baseline to 1.4 ± 0.8 at 6-months, 1.4 ± 1.0 at 9-months, and 1.3 ± 0.8 at 12-months (all p < .0001). At 12-months, 86% (30/35) of participants achieved the MCID of a reduction from baseline of ≥0.4 points for the mini RQLQ. No related serious adverse events occurred during the study. Impedance-controlled RF ablation of the PNN is safe and resulted in durable, significant improvement in rhinitis symptoms and quality of life through 12-month follow-up. The study is registered at www.clinicaltrials.gov with the unique identifier of NCT05324397. 4.

VERIFY: A randomized controlled phase 3 study of the hepcidin mimetic rusfertide (PTG-300) in patients with polycythemia vera (PV).

TPS6592 Background: PV is a myeloproliferative neoplasm characterized by overproduction of red blood cells and increased risk of thrombosis. Patients may require frequent therapeutic phlebotomies (TP) alone or in combination with cytoreductive therapy to maintain hematocrit (HCT) &lt;45%. Hepcidin regulates iron homeostasis but is downregulated in PV, increasing iron availability for erythropoiesis, which complicates TP optimization. In a phase 2 study (REVIVE, NCT04057040), rusfertide led to rapid, sustained, and durable HCT control with over 90% of patients achieving TP independence in part 2.1 It was well tolerated; majority (77.1%) of treatment-emergent adverse events (TEAEs) had a maximum grade of 2. There were no Grade 4 or 5 TEAEs. The phase 3 study VERIFY (NCT05210790) aims to confirm efficacy and safety of rusfertide in patients with PV. Methods: VERIFY is a multicenter, global, randomized trial comparing efficacy and safety of rusfertide (starting dose: 20 mg subcutaneously once weekly) vs. placebo when added to ongoing therapy for PV. Patients with PV who require frequent TP with or without concurrent cytoreductive therapy to control HCT are included in this 3-part study: Part 1a: 1:1 randomized, double-blind, placebo-controlled, add-on parallel-group period lasting 32 weeks (Week 0-32); Part 1b: open-label treatment phase with cross-over for previous placebo-treated patients. During this phase, all patients who completed Part 1a successfully will receive rusfertide for 20 weeks (Week 32-52); and Part 2: long term extension phase where all patients who complete Part 1b will continue to receive rusfertide for 104 weeks (Week 52-156). Results: Major inclusion criteria prior to randomization include PV diagnosis by 2016 WHO criteria; ≥3 TP in the previous 28 weeks or ≥5 in the previous 12 months due to inadequate HCT control; HCT &lt;45%, white blood cells 4-20 × 109/L and platelets 100-1000 × 109/L at Week 0; stable PV therapy regimen in patients receiving cytoreduction at randomization; and cessation of cytoreductive therapy 2-6 months before screening in patients treated with TP alone. Major exclusion criteria are thrombosis or bleeding (active and/or chronic) within 2 months before randomization and a history of invasive malignancy within the previous 5 years. Primary endpoint is the proportion of patients achieving a response in Part 1a from Week 20-32. A response is defined as absence of TP eligibility. TP eligibility: HCT ≥45% and ≥3% higher than baseline HCT or HCT ≥48%. Secondary endpoints are mean number of TPs from Week 0-32; proportion of patients with HCT &lt;45% from Week 0-32; mean change from baseline to Week 32 in total fatigue score measured by PROMIS Short Form and in total symptom score measured by MFSAF v4.0. Conclusions: VERIFY opened in January 2022 and aims to enroll approximately 250 patients globally. Reference: 1. Ritchie EK, et al. Blood.2023;142(Suppl 1):745. Clinical trial information: NCT05210790 .

Patient (pt) interview–based content validation of the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0).

e23106 Background: Pts with myelofibrosis (MF) often experience debilitating symptoms that negatively impact health-related quality of life and functioning. The MFSAF v4.0 is a 7-item questionnaire assessing the burden of MF symptoms, including fatigue, night sweats, pruritus, abdominal discomfort, pain under left ribs, early satiety, and bone pain. Each item is evaluated on an 11-point numeric rating scale (NRS) from 0 (absent) to 10 (worst imaginable). We sought to evaluate the content validity of the MFSAF v4.0 in Janus kinase inhibitor–experienced pts with MF. Methods: Qualitative interviews were conducted remotely by trained interviewers with 20 Janus kinase inhibitor–experienced and symptomatic (MFSAF Total Symptom Score [TSS] ≥10) pts with MF from the US (n = 5) and UK, Germany, Italy, Poland, and Spain (n = 3 each). The interview began with a concept elicitation section to allow spontaneous reporting of important concepts prior to content validation of the MFSAF v4.0 items and NRS as relevant, important, and understandable to pts. Results: Mean pt age was 59.4 years; 50% were male, 55% were diagnosed within the past year, 95% were on any treatment for MF, and 75% were anemic. On average, pts had 2.1 transfusions within the past 3 mo. Mean MFSAF v4.0 TSS was 28.6.The top spontaneously endorsed symptoms were tired (70%), bone/muscle pain (70%), fatigue (55%), night sweats (45%), and pruritis (45%), many of which are also items in the MFSAF v4.0. An additional 18 symptoms were spontaneously mentioned by pts prior to completion of the MFSAF v4.0. Many of these other symptoms were endorsed by ≤10% of pts (1 or 2 pts each), and 90% of pts felt that the measure represented their experience and did not recommend inclusion of additional symptoms after reviewing the measure. Overall, pts showed a clear understanding of the MFSAF v4.0 (Table). No more than 3 pts (15%) mentioned that a given item was not relevant to their individual experience. Pts consistently felt that it was easy to select an answer on the response scale and were able to differentiate response options. When describing meaningful change in terms of NRS, pts most often suggested that an improvement of 2 to 4 points would be meaningful. Conclusions: Based on the findings from this study, the MFSAF v4.0 is a content-valid measure for pts with MF and captures the most important concepts. All items are comprehensible and relevant, with the NRS endorsed as an appropriate response scale. [Table: see text]

False-Positive Rates, Risk Factors, and Interpretations of the Vestibular/Ocular Motor Screening in Collegiate Athletes.

Biological sex and history of motion sickness are known modifiers associated with a false-positive baseline Vestibular/Ocular Motor Screening (VOMS). However, other factors may be associated with a false-positive VOMS in collegiate athletes. To identify contributing factors to false-positive VOMS assessments using population-specific criteria. We also critically appraised previously reported interpretation criteria. Descriptive laboratory study. Single-site collegiate athletic training clinic. National Collegiate Athletic Association Division I athletes (n = 462 [41% female]) aged 18.8 ± 1.4 years. Participants completed the Athlete Sleep Behavior Questionnaire, the 7-Item Generalized Anxiety Index, the Immediate Postconcussion Assessment and Cognitive Testing battery, the Patient Health Questionnaire-9, the Revised Head Injury Scale, the Sensory Organization Test, and the VOMS as part of a multidimensional baseline concussion assessment. Participants were classified into 2 groups based on whether they had a total symptom score of greater than or equal to 8 after VOMS administration, excluding the baseline checklist. We used χ2 and independent t tests to compare group demographics. A binary logistic regression with adjusted odds ratios (ORs) was used to evaluate the influence of sex, corrected vision, attention-deficit/hyperactivity disorder, Immediate Postconcussion Assessment and Cognitive Testing composite scores, concussion history, history of treatment for headache and/or migraine, Generalized Anxiety Index scores, Patient Health Questionnaire-9 scores, Athlete Sleep Behavior Questionnaire scores, and Sensory Organization Test equilibrium scores and somatosensory, visual, and vestibular sensory ratios on false-positive rates. Approximately 9.1% (42 of 462 [30 females]) met criteria for a false-positive VOMS. A significantly greater proportion of females had false positives (χ21 = 18.37, P < .001). Female sex (OR = 2.79; 95% CI = 1.17, 6.65; P = .02) and history of treatment for headache (OR = 4.99; 95% CI = 1.21, 20.59; P = .026) were the only significant predictors of false-positive VOMS. Depending on cutoff interpretation, false-positive rates using our data ranged from 9.1% to 22.5%. Our results support the most recent interpretation guidelines for the VOMS in collegiate athletes due to a low false-positive rate and ease of interpretation. Biological sex and history of headaches should be considered when administering the VOMS in the absence of a baseline.

Patient reported outcomes among U.S. Veterans living with myeloproliferative neoplasms.

e18528 Background: Myeloproliferative Neoplasms (MPNs) profoundly affect patients' well-being, necessitating effective symptom relief. Patient-reported outcomes are pivotal for care improvement, aligning with Centers for Medicare and Medicaid Services priorities. This study aims to assess MPN symptom burden among U.S. Veterans, examining risk levels, thrombo-hemorrhagic complications, medication use, information access, care, and service-connected benefits. Methods: Conducted as a cross-sectional survey from December 1, 2023, - January 22, 2024, all Veterans in the MPN Advocacy Education &amp; International database were recruited. Symptom burden was assessed using the validated MPN Symptom Assessment Form Total Symptom Score (MPN SAF TSS), with descriptive statistics and T-tests employed for analysis. Results: Of 61 respondents, 88% were male, 92% Caucasian, 88% served during the Vietnam war. The mean age was 73±7, with MPN diagnosis at 64±9 and a mean duration of 44±10 years from service-connected exposure. Key findings included 56% Polycythemia Vera, 26% Essential Thrombocythemia, 16% Primary Myelofibrosis, 70% JAK2, 10% CALR, 3% MPL, 14% unaware of their mutation status, and 34% unaware of MPN risk status. Seventeen (28%) underwent phlebotomy, 64% used Hydroxyurea, 29% Ruxolitinib, and 3% Interferon. Fatigue and itching were the predominant and severe symptoms (Table), with 43% reporting no symptom improvement. Mean MPN SAF TSS of all respondents was higher than prior study by Emanuel et.al. which adjusted for MPN subtype (36.4 vs. 21.6, p&lt;0.0001). Twelve (20%) reported bleeding and 10% reported venous thrombosis after MPN diagnosis, while 13% reported arterial thrombosis before MPN diagnosis. Twenty-two (36%) are not seeing an MPN specialist and 61% are not seeing a hematologist at their local Veterans Affairs Medical Centers. Twenty-three (38%) did not seek a second opinion while 43% do not have a caregiver. Respondents turn to MPN organizations (75%), physician offices (74%), Google Search (49%), Webinars (41%), and Facebook (23%) for information. Five (8%) received service-connected disability benefits. Conclusions: Veterans with MPNs endure a substantial symptom burden, surpassing previous studies, signifying suboptimal management. Limited access to care persists, necessitating enhanced support. However, self-reporting bias and potential limitations in activity assessment must be acknowledged. Efforts to enhance MPN awareness, specialized care, and support mechanisms are imperative for comprehensive management. [Table: see text]

Clinical significance of T helper-1/T helper-2 cytokines in peripheral blood of children with otitis media with effusion and allergic rhinitis

ObjectiveOtitis media with effusion (OME) is a prevalent and costly disease, especially in children. This article analyzed the expression patterns and clinical significance of T helper-1 (Th1)/Th2 cytokines in the peripheral blood of children with OME and allergic rhinitis (AR). MethodsSubjects were assigned to the OME + AR group and the Control group (children with OME), with their clinical baseline data documented. The correlations between Th1/Th2 cytokines and between the total nasal symptom score (TNSS) and Th1/Th2 cytokines were analyzed. The risk factors and the predictive value of Th1/Th2 cytokines for OME + AR were analyzed using logistics multivariate regression analysis and receiver operating characteristic curve. ResultsSignificant differences were observed in tympanic pressure/speech frequency/air conduction valve/TNSS score/immunoglobulin E (IgE) level between both groups. The OME + AR children exhibited evidently elevated interleukin-2 (IL-2)/tumor necrosis factor-α (TNF-α)/IL-4/IL-10/IL-6 levels and no significant difference in interferon-γ (IFN-γ) level. Th1/Th2 cytokines were remarkably positively-correlated with the TNSS score. IL-2/TNF-α/IL-4/IL-6 were risk factors for OME with AR. The area under the curves (AUCs) of IL-6/IL-2/IL-4/TNF-α levels in predicting the occurrence of OME + AR were 0.805/0.806/0.775/0.781, with sensitivities of 75.76 %/89.39 %/72.21 %/72.73 % and specificities of 74.29 %/61.34 %/72.86 %/70.00 %, and the cut-off values were 239.600/20.300/29.880/34.800 (pg/mL). The AUC of their combination in predicting OME + AR was 0.955 (93.94 % sensitivity, 85.71 % specificity). ConclusionTh1/Th2 cytokine levels were imbalanced and obviously positively-correlated with the TNSS score in OME + AR children. IL-2, TNF-α, IL-4, and IL-6 levels had auxiliary predictive value in the occurrence of OME + AR.

Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) in Chronic Myeloproliferative Neoplasms with Relation to Genetic Burden and Thrombosis

The Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in chronic myeloproliferative neoplasms (MPNs). However, insufficient data are available regarding the relationship among the MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationships with MPN-SAF TSS in MPN patients. One hundred thirty JAK2V617F-positive patients with MPNs were included in our study. We calculated the MPN-SAF TSS for all patients and compared it with their clinical characteristics. Patients with higher JAK2V617F mutation allele burden had higher MPN-SAF TSS values (p=0.008). Patients with thrombosis had higher MPN-SAF TSS than patients without thrombosis (p=0.003). The mean MPN-SAF TSS was higher in patients with primary myelofibrosis compared to those with polycythemia vera and essential thrombocythemia. Thrombosis was associated with increased symptom severity in several domains, including fatigue, abdominal discomfort, inactivity, night sweats, pruritus, weight loss, and early satiety. Additionally, an increase in JAK2 allele burden was observed with higher symptom scores. The MPN-SAF TSS proved to be a reliable tool for assessing symptom burden in Turkish MPN patients. Furthermore, the significant association between thrombosis occurrence and symptom severity suggests that thrombotic events may contribute to symptom development. Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of the MPN-SAF TSS in routine clinical practice to enhance patient care and management.

Topical steroids for chronic rhinosinusitis without nasal polyps: A systematic review and meta-analysis.

Evidence supporting topical steroids for the treatment of chronic rhinosinusitis without nasal polyposis (CRSsNP) is unclear. Recent trials describe alternative topical steroid delivery modalities, including rinses and exhalation delivery system (EDS), necessitating a re-examination of the current literature. Cochrane Library, CINAHL, PubMed, and Scopus databases were searched from inception to February 13, 2024 for placebo-controlled randomized control trials on topical steroids used to treat CRSsNP, including topical spray, nasal irrigation, sinonasal catheter, and EDS modalities. Primary outcome measures included total symptom scores (TSS) (Δ) and response rates (odds ratio). Ten trials (N=751) were included for meta-analysis, with a mean age of 47.5 years (range: 18-80 years; 95% confidence interval [CI]: 43.9-51.2 years). Topical steroids delivered by any method significantly improved TSS in CRSsNP patients (Δ0.4; 95% CI: 0.3-0.6; p<0.0001). When stratified by allergy status, CRSsNP patients without allergy had significantly improved TSS when treated with EDS (Δ0.4; 95% CI: 0.1-0.7; p=0.01), but not with topical spray (Δ0.04; 95% CI: -0.9 to 1.0; p=0.94). Patients treated with EDS or sinonasal catheter responded significantly better compared to placebo (odds ratio [OR]: 3.4; 95% CI: 1.9-6.0; p<0.0001; OR: 12.4; 95% CI: 1.8-83.8; p<0.01), whereas patients treated with topical spray had no significant difference (OR: 1.8; 95% CI: 0.9-4.0; p=0.12). Topical steroids are effective in treating CRSsNP, especially when delivered via EDS or sinonasal catheter. Future trials comparing steroid delivery mechanisms using validated outcome measures in CRSsNP populations are needed.

Examining Acute Symptoms After Sport-Related Concussion in Collegiate Athletes With Preinjury Migraines.

To examine whether a personal history of migraines is associated with worse acute symptom burden after sport-related concussion (SRC). Retrospective cohort study. National Collegiate Athletic Association Division III collegiate programs. Collegiate athletes from a prospective concussion surveillance system between 09, 2014, and 01, 2023. Preinjury migraines (yes/no) were self-reported by athletes. Post-Concussion Symptom Scale (PCSS) were collected within 3 days postinjury. Mann-Whitney U tests compared total PCSS scores and individual symptom scores between athletes with and without preinjury migraines. Chi-squared tests were used to compare proportions of athletes endorsing individual symptoms (ie, item score ≥1) between 2 groups. Multivariable regression analyzed potential predictors of PCSS scores. Of 1190 athletes with SRC, 93 (7.8%) reported a preinjury history of migraines. No significant difference in total PCSS scores was found between athletes with and without preinjury migraines (22.0 ± 16.4 vs 20.5 ± 15.8, U = 48 719.0, P = 0.471). Athletes with preinjury migraines reported greater severity of "sensitivity to light" (1.59 ± 1.59 vs 1.23 ± 1.41, P = 0.040) and "feeling more emotional" (0.91 ± 1.27 vs 0.70 ± 1.30; P = 0.008) and were more likely to endorse "feeling more emotional" (45.2% vs 29.5%, P = 0.002). No differences were found across all other symptoms, including headaches (migraine = 87.1% vs no migraine = 86.3%, P = 0.835). In a multivariable model, a history of migraine was not a significant predictor of acute PCSS scores, but those with a history of psychological disorders (β = 0.12, P <0 .001) and greater number of days to symptom evaluation (β = 0.08, P = 0.005) had higher PCSS scores. Collegiate athletes with a pre-existing history of migraines did not have higher acute symptom burden after SRC.

Interdigital-type antifungal socks for prevention and treatment of tinea pedis

BackgroundInterdigital tinea pedis is the most common type of foot infection, which is often treated by topical or systemic antifungals. Due to the increase in antifungal resistance, antifungal socks are becoming potential alternatives for the daily management of tinea pedis. MethodsIn this study, antifungal fibres were adopted to produce interdigital hygiene socks to split the third and fourth toe seams of the feet. In vitro antifungal activity was first examined to verify the effectiveness of the socks. Preventive efficacy against tinea pedis was then evaluated among healthy participants, followed by therapeutic effect detection in patients diagnosed with tinea pedis by analysing the improvement in total symptom scores (TTS). ResultsThe interdigital-type hygiene socks exhibited apparent antifungal activities in vitro. An in vivo study demonstrated significant preventive effects against tinea pedis for interdigital socks compared to plain socks (P = 0.011) and a lower TTS than noninterdigital (P = 0.04) or plain socks (P < 0.0001). Moreover, interdigital socks showed a total effectiveness rate of 72.9% in patients with tinea pedis, with most of the symptoms alleviated. ConclusionInterdigital-type hygiene socks not only exhibited in vitro antifungal activities but also showed significant prophylactic and therapeutic effects against interdigital tinea pedis in vivo.

Whole-brain intrinsic functional connectivity predicts symptoms and functioning in early psychosis

Theories of psychotic illness suggest that abnormal intrinsic functional connectivity may explain its characteristic positive and disorganization symptoms as well as lead to impaired general functioning. Here we used resting state functional magnetic resonance imaging (fMRI) to evaluate associations between these symptoms and the degree to which global connectivity is abnormal in early psychosis (EP). Eighty-six healthy controls (HCs) and 108 individuals with EP with resting state fMRI data were included in primary analyses. The EP group included 83 participants with schizophrenia-spectrum disorders and 25 with bipolar disorder type I with psychotic features. A global intrinsic connectivity “similarity index” for each EP individual was determined by calculating its correlation with the average HC connectivity matrix extracted using Schaefer atlases of multiple parcellations (100, 200, 300, and 400 region parcellations). As hypothesized, connectivity similarity with the average HC matrix was negatively associated with Brief Psychiatric Rating Scale total score, Scale for the Assessment of Positive Symptoms total score, and disorganization symptoms. Similarity was also positively associated with Global Assessment of Functioning score. Results were not driven by sex or diagnosis effects and were consistent across parcellation schemes. These results support the hypothesis that changes in whole-brain connectivity patterns are associated with psychosis symptoms and support the use of functional connectivity as a biomarker for these symptoms in EP.

Safety and efficacy of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: primary analysis of FREEDOM trial

The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 109/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (n = 35), nine (25.7%; 95% confidence interval 12.5–43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (n = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.

Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Randomized, Double-Blinded, Placebo-Controlled, Phase II Trial.

Conventional treatments for allergic rhinitis (AR) exhibit insufficiency and long-term use-related side effects. Considering the reported anti-inflammatory and immunoregulatory effects of Bojungikgi-tang (BJIGT), we aimed to assess its efficacy on persistent AR (PAR). Patients with PAR were randomly assigned in a 1:1:1 ratio into high-dose BJIGT, standard-dose BJIGT, and placebo groups, followed by 1-week run-in and 4-week treatment periods. The primary outcome included the mean change in Total Nasal Symptom Score (TNSS), with secondary outcomes encompassing the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, biomarkers, overall assessment, TNSS by AR pattern identification, and the Sasang constitution. The mean TNSS change was more improved in the BJIGT group than in the placebo group; however, no statistically significant differences were observed. Additional interaction effect analysis revealed a statistically significant improvement in the high-dose BJIGT group compared with the placebo group from weeks 1-2 to weeks 3-4. Regarding secondary outcomes, the BJIGT group exhibited similar or improved results compared with the placebo group, showing no statistically significant differences. No serious adverse effects or clinically significant changes in safety assessments were observed. Given that this study validated clinical improvement and safety, it serves as potential groundwork for pertinent future studies.

A Combined Kundalini Yoga and Cognitive Behavioral Therapy Program for Posttraumatic Stress Disorder: A Pilot Study.

Cognitive behavioral therapy (CBT) is one of the standard conventional treatments for posttraumatic stress disorder (PTSD). However, recent studies have reported the benefits of yoga for reducing PTSD symptoms including a Kundalini Yoga (KY) intervention. The purpose of this study was to test the efficacy of a novel combined 8-week CBT and KY program for treating PTSD symptoms and improving sleep quality in a single group trial of 26 adults with PTSD. PTSD symptoms (PTSD checklist-5) and sleep quality (Pittsburgh Sleep Quality Index) were assessed at baseline, post intervention, and at 2-month follow-up. Both CBT and yoga homework compliance were also measured. Total PTSD symptom scores as well as the cluster symptoms (intrusion, avoidance, arousal/reactivity, and negative alterations in cognitions and mood) were significantly improved following the program, all p < .01. The improvements in total PTSD scores, intrusion, avoidance, arousal/reactivity were maintained at follow-up, with all values still less (p < .01) than baseline. The negative alterations in cognitions and mood symptom cluster continued to improve further at follow-up compared to post-intervention values (p < .05). Total sleep score (p < .05) and the subscales of sleep disturbance (p < .01), daytime dysfunction (p < .05), and sleep quality (p < .01) were significantly improved after the program and these improvements were maintained at follow-up compared to baseline. Sleep medication use was decreased (p < .05) and sleep latency was improved (p < .01) at follow-up only compared to baseline. There was a significant positive correlation (p < .05) between the completion of the yoga home practice and post change in total sleep scores. These results show that a combined KY and CBT intervention resulted in decreased PTSD symptoms and improved sleep quality and suggest this program may constitute an additional treatment option for PTSD.

The effectiveness of subcutaneous immunotherapy in allergic diseases of children and adults

ObjectivesImmunotherapy is the gradual administration of increasing doses of allergens to reduce or eliminate the patient's adverse clinical response following exposure to these allergens. The goal of the current study was to evaluate the effectiveness of subcutaneous immunotherapy in patients with allergic diseases referred to the Bushehr Asthma and Allergy Clinic, Iran. Materials and methodsPatients with respiratory allergic diseases, who had positive skin prick test, randomly enrolled in this observational study and underwent immunotherapy for one year. To evaluate the efficacy of immunotherapy, two questionnaires were completed for all the patients before and one year after the start of immunotherapy, including the Total Nasal Symptom Score (TNSS) and Asthma Control Test (ACT). ResultsA total of 878 patients with asthma or allergic rhinitis disorder [53.6% (n=471) male and 46.4% (n=407) female] with a median (IQR) age of 28.0 (12.0–35.0) years were randomly enrolled in this observational study. Five hundred forty-nine patients (64.8%) were over 18 years old and 298 patients (33.9%) were under 18 years old, the age of the other patients was not known. The median (IQR) duration of disease was 84.0 (36.0–138.0) months. Rinithis allergy had most frequent than asthma [39.9% (n=350) vs. 22.2% (n=195), respectively] and 218 patients (24.8%) have both of them. After the treatment, 234 patients (54.5%) completely stop and 26.3% patient (n=113) used less than half of the drugs. The mean TNSS (n=259) and ACT (n=186) scores for patients had significant difference before and after immunotherapy [13.64 vs. 5.68, P<0.001; 7.91 vs. 17.43, P<0.001, respectively]. ConclusionThe mean TNSS and ACT score before and after the treatment significantly improved the patients’ symptoms. To conclude, standard immunotherapy can be effective in patients with moderate to severe allergic rhinitis and mild to moderate persistent allergic asthma to reduce clinical symptoms.

Oral immunotherapy with enteric-coated capsules for allergic rhinitis caused by house dust mites.

Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites. A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated. After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group. OIT is an effective and safe treatment for mite-induced AR.

A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy

Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. Changes in mean NAC TNSS did not differ between SCIT-assigned (n= 28) versus placebo-assigned (n= 29) participants (P= .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P= .04). A200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P< .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P= .002), while no effect was observed for IL-10 or IFN-γ. A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.