A Quantile Regression Analysis of Factors Associated with First-Time Maternal Fatigue in Korea

The aim of this cross-sectional study was to identify the factors associated with different percentiles of first-time maternal fatigue. A total of 123 first-time healthy mothers aged 18 years or older participated through an online survey. The fatigue was measured by the Korean version of the fatigue severity scale. Main variables were constructed based on the integrated fatigue model, which included mothers’ sleep quality, parenting stress, the amount of free time mothers have, the number of the child’s night wakings, general characteristics including socioeconomic status, and working status. Quantile regression was used to analyze the associated factors according to the fatigue level of first-time mothers with a young child. The mean age of the mothers and children were 32.11 years and 20.81 months, respectively. Mean fatigue score was 6.16 among the 75% quantile with high fatigue score. Lack of adequate free time in mothers, advanced maternal age, being a housewife, having a moderate income, and frequent night wakings of their child significantly increased fatigue among mothers in the third quantile of fatigue. To reduce fatigue, healthcare providers should focus on exploring ways to reduce maternal sleep disturbance and improve maternal sleep quality.

Prevalence of sleep disturbance and the association between poor disease control in people with ankylosing spondylitis within the Australian clinical setting (ASLEEP study): a real-world observational study using the OPAL dataset

Introduction Sleep disturbance and fatigue are commonly reported in ankylosing spondylitis (AS) but specific prevalence and the relationship to disease control are unknown. Method This retrospective non-interventional observational study of data from the OPAL dataset included patients with AS (ICD code M45, M45.0 or M08.1), aged 18 to 95 years and had completed ≥ 1 sleep questionnaire between 1 January 2019 and 30 September 2020. The prevalence of insomnia and obstructive sleep apnoea were assessed using the Insomnia Severity Index (ISI) and Multivariate Apnoea Prediction Index (MAPI), respectively. Propensity score (PS) matching based on sex, age and symptom duration increased comparability between patients administered tumour necrosis factor inhibitors (TNFi) and interleukin 17A inhibitors (IL-17Ai). Results Four hundred ninety-five patients were included. The mean ISI total score in the overall population was 8.6 ± 6.2. Self-reported moderate or severe clinical insomnia was present in 16% and 3.2% of patients, respectively. The mean MAPI score was 0.4 ± 0.3, self-reported apnoea was identified in 31.5% of patients and the mean FACIT-Fatigue score was 36.1 ± 10.7. In the PS matched population, the only treatment-related difference was the mean MAPI score (IL-17Ai 0.4 ± 0.3 and TNFi 0.3 ± 0.2, p = 0.046). Those with poor disease control (BASDAI ≥ 4) were more likely (odds ratio [OR] 7.29, 95% CI 2.37 to 22.46, p = 0.001) to have a greater severity of insomnia symptoms than those with good disease control. Conclusion In this real-world AS cohort, poor disease control was associated with sleep disturbance. Little difference in sleep disturbance was observed between biologic TNFi and IL-17Ai treatment. Key Points • Sleep disturbance and fatigue are common in patients with ankylosing spondylitis.• In our real-world cohort, self-reported apnoea was reported in one-third of patients; and one in five patients reported moderate to severe insomnia.• Those with poor disease control were more likely to experience greater sleep disturbance than those with good disease control.

Relationship between Carnitine Deficiency and Tyrosine Kinase Inhibitor Use in Patients with Chronic Myeloid Leukemia

Background: Some chemotherapeutic agents cause carnitine deficiency, which confers general fatigue; however, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. Objective: This study investigated carnitine concentrations in patients with CML treated with TKIs. Method: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The Brief Fatigue Inventory (BFI) and Cancer Fatigue Scale (CFS) were used to assess general fatigue developed during TKI therapy. Results: Fifty-five patients on TKIs were included; 12 (21.8%) had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. Conclusion: Carnitine deficiency is probably not a major cause of general fatigue, but may occur in patients with CML receiving TKIs.

Efficacy and safety of ferric carboxymaltose in Indian pregnant women with iron deficiency anemia

Background: Iron deficiency anemia (IDA) is a significant problem worldwide particularly in women. The aim of the study was to evaluate the effectiveness of intravenous ferric carboxymaltose (FCM) in in Indian pregnant women with anemia.Method: This was a single centre, prospective, observational, open label, clinical study at real life scenario with 4 weeks follow up. Fifty pregnant women with IDA and visiting to the Radhakrishna multispecialty hospital, Bangalore, for antenatal care were enrolled for the study. IV FCM was given as per the standard protocol. Change in the laboratory parameters such as hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), packed cell volume (PCV) level at baseline and after 4 weeks of completion of parenteral iron therapy was recorded and fatigue score was assessed. The pregnant women were monitored for the adverse events. Results: All pregnant women received a single IV infusion of FCM 1000 mg. A significant increase in the hemoglobin of 2.37±0.51 g/dl (p<0.001) was noted at 4 weeks, MCV rise of 19.89±21.94 (p<0.001) was noted at 4 weeks, MCHC rise was of 2.56±5.65 and PCV rise was of 4.45±2.67 (p<0.011) at over 4 weeks. Significant improvement in fatigue score was observed at 4 weeks after single FCM infusion. No adverse effects were observed in any pregnant woman throughout the duration of the study.Conclusions: This real-life observational study highlights IV FCM is effective in management of IDA in pregnant women and well tolerated. Trial registration number: CTRI/2021/02/030874

Effects of Breathing Meditation Training on Sustained Attention Level, Mindfulness Attention Awareness Level, and Mental State of Operating Room Nurses

Objectives: In this paper, we explore the effects of breathing meditation training on the sustained attention level, mindfulness attention awareness level, and mental state of nurses in the operating room. Methods: We enrolled 40 nurses from September 2019 to December 2019, and divided them into a control group (N=20) and an observation group (N=20) using a random number table. The control group received routine training, based on which the observation group received breathing meditation training. We compared their sustained attention index, fatigue score, mindfulness attention awareness score, mental state score, work stress score, career satisfaction score, and career happiness index. Results: After training, the sustained attention response time was shorter at 8:00 and 18:00 in the observation group than in the control group (p < .05). The physical fatigue score, mental fatigue score, reduced activity score, reduced motivation score, and overall fatigue score of the observation group were lower than those of the control group (p < .05). The observation group had a higher mindfulness attention awareness score than did the control group (p < .05). The SAS and SDS scores of the observation group were lower than those of the control group (p < .05). The work stress score of the observation group was lower than that of the control group, whereas the career satisfaction score and career happiness index were higher (p < .05). Conclusion: Breathing meditation training can improve the sustained attention level and mindfulness attention awareness level, reduce the feeling of fatigue and work stress, help adjust the mental state, and enhance the career satisfaction and career happiness of nurses in the operating room.

Clinically Important Difference for the FACIT-Fatigue Scale in Paroxysmal Nocturnal Hemoglobinuria: A Derivation from International PNH Registry Patient Data

Background: Fatigue is a common symptom associated with paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab, a C5 inhibitor approved for treatment of PNH, has been shown to significantly alleviate fatigue, as indicated by reduced scores on the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue). FACIT-Fatigue scores range from 0-52 (higher scores indicate less fatigue); this assessment is validated for use in patients with PNH and has been used extensively both in clinical trials and in the International PNH Registry. In patients with cancer, the FACIT-Fatigue clinically important difference (CID) is estimated to be improvement of 3-5 points. This CID is commonly applied in PNH studies; however, no disease-specific CID for FACIT-Fatigue has been estimated in patients with PNH. A PNH-specific CID would be informative in evaluating changes in fatigue impact and could serve as a more robust criterion for evaluating treatment efficacy. The objective of this analysis was to determine the FACIT-Fatigue CID for patients with PNH using distribution- and anchor-based approaches and real-world data from the International PNH Registry. Methods: Adults with PNH who initiated eculizumab within 28 days of enrollment in the PNH Registry as of January 2021 with non-missing baseline FACIT-Fatigue scores were included in the analysis. FACIT-Fatigue scores were assessed at baseline and 6, 12, 24, and 36 months. Two distribution-based CID estimates were calculated using: 1) 0.5 × SD and 2) standard error of measurement (SEM). The SEM was calculated as SD−sqrt(1-α), where α represents the internal consistency measurement Cronbach's alpha. Cronbach's alpha was calculated from the 13 FACIT-Fatigue subscales. Anchor-based estimates considered 2 continuous patient-reported outcome variables: 1) European Organization for Research and Treatment of Cancer (EORTC) Global Health Status Quality of Life (QoL) summary score (quartiles; higher scores indicate better quality of life), and 2) EORTC Global Health Status Fatigue Subscale score (quartiles; lower scores indicate less fatigue). The baseline FACIT-Fatigue score was calculated for each predefined categorization of the anchors; the mean of differences in FACIT-Fatigue between adjacent categories was calculated and referenced as the anchor-based CID. Changes in anchors and high disease activity (HDA) shift from baseline to each follow-up visit were then assessed by FACIT-Fatigue score change (≤1 CID, no change, or ≥1 CID). HDA was defined as lactate dehydrogenase ratio ≥1.5 × upper limit of normal and ≥1 of the following: history of a major adverse vascular event (including a thrombotic event); anemia; or physician-reported abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, or erectile dysfunction. Results: 423 patients were included in the analysis (Table). The majority of patients were white or of Caucasian descent (84%); 3% were of Hispanic or Latino ethnicity. At baseline, 93% of patients had physician documentation of fatigue in their medical history (mean FACIT-Fatigue score, 29.4). The 2 distribution-based CIDs were 7 using 0.5 × SD and 5 using SEM; internal consistency was high (α=0.87). For anchor-based measurements, the CID was 8 using the EORTC QoL score and 10 using the EORTC fatigue subscale score. The percentage of patients who changed from having HDA at baseline to no HDA at eculizumab-treated follow-up visits increased over time. Using the SEM as the referent CID (owing to the high α value), the majority of these patients experienced &gt;1 CID in FACIT-Fatigue that was sustained through 36 months (Figure). Results were similar when 0.5 × SD was used. Conclusion: Collectively, these results support the use of 5 points as the CID for FACIT-Fatigue in individual patients with PNH, which, although not necessarily the minimal value, is close to the range of CIDs reported in other diseases (3-5 points). This finding, obtained from a real-world dataset with a large number of patients, helps establish an important metric for assessment of the meaningful treatment response of patients with PNH. Of note, this CID is markedly smaller than the group average FACIT-Fatigue improvement of 10 points achieved with long-term eculizumab treatment in the pivotal blinded Phase 3 TRIUMPH study. Figure 1 Figure 1. Disclosures Cella: FACIT: Membership on an entity's Board of Directors or advisory committees. Ueda: Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Chugai Pharmaceutical: Consultancy, Honoraria, Research Funding; Alexion Pharma: Consultancy, Honoraria. Tomazos: Alexion, AstraZeneca Rare Disease: Current Employment. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Wang: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease: Current Employment. Schrezenmeier: Novartis: Honoraria; Alexion, AstraZeneca Rare Disease: Honoraria, Other: Travel support, Research Funding; Roche: Honoraria; Apellis: Honoraria; Sanofi: Honoraria.

12-Month Analysis of a Phase 2 Study of Iptacopan (LNP023) Monotherapy for Paroxysmal Nocturnal Hemoglobinuria

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematological disorder caused by somatic mutations in the phosphatidylinositol glycan A (PIGA) gene in hematopoietic stem cells, resulting in complement alternative pathway (AP)-mediated severe hemolysis, life-threatening thrombosis, and impaired bone marrow function. The current standard-of-care for PNH consists of anti-C5 blockade with either eculizumab or ravulizumab. While both monoclonal antibodies effectively control intravascular hemolysis (IVH), reduce thrombosis and improve long-term survival, a significant proportion of patients remains anemic and continues to require transfusions, largely due to persistent extravascular hemolysis (EVH). Conversely, pegcetacoplan, a recently FDA-approved anti-C3 inhibitor, prevents both IVH and EVH and showed superiority to eculizumab in improving hemoglobin (Hb) levels in PNH. Nevertheless, the need for effective oral treatment options in PNH remains unmet. Iptacopan (LNP023) is a new, oral, selective and potent first-in-class inhibitor of factor B, a key component of the AP. Recent phase 2 data showed that iptacopan effectively controls both IVH and EVH and leads to rapid, transfusion-free improvements in Hb levels in the majority of PNH patients. Methods: CLNP023X2204 (NCT03896152) is a multicenter, randomized, open-label phase 2 study in adult PNH patients with active hemolysis and no complement inhibitor treatment within 3 months prior to study entry. Patients are randomized to receive twice daily (BID) iptacopan in one of two dose-sequences, either 25 mg for 4 weeks followed by 100 mg for up to 2 years (Cohort 1) or 50 mg followed by 200 mg (Cohort 2). The key objectives are to assess the effect of iptacopan on markers of IVH/EVH (incl. lactate dehydrogenase (LDH)) and on Hb levels, as well as safety. 12-month interim results are summarized below. Results: The study has completed enrolment. A total of 13 patients (mean age 38.2 years, 7 female) were randomized to either Cohort 1 (n=7) or 2 (n=6). Mean (SD) lab values at baseline were LDH 2097.8 (911.2) U/L, reticulocytes 203.3 (82.9) x10E9/L, bilirubin 32.4 (10.1) µmol/L, and Hb 85.8 (13.2) g/L, and most patients required red blood cell transfusions in the prior 12 months (median 3.0, range 0-19). At the time of the interim analysis, 11 patients had been treated with iptacopan for at least 52 weeks, with a maximum treatment duration of 81 weeks; 2 patients discontinued treatment early, one after 2 days due to a non-serious adverse event of headache (hence not evaluable for the primary endpoint), the other after 13 weeks due to physician decision. Amongst the 12 evaluable patients, all of whom were anti-C5 naive, all reached the primary endpoint of lowering LDH by at least 60% within the first 12 weeks. The LDH response was rapid and durable, with all patients treated with ≥50 mg BID reaching this threshold after only one week of treatment and all ongoing patients except one maintaining the threshold up until the data cutoff, i.e., for at least 52 weeks. Equivalent improvements were also observed for other markers of IVH and EVH. Similarly, Hb levels improved significantly and durably in most patients, and all except one of the ongoing patients have remained transfusion-free since the start of iptacopan treatment. Moreover, no thromboembolic events occurred during the study, and the FACIT fatigue score improved significantly in most patients. Iptacopan monotherapy was safe, with no severe or serious adverse reported up to the data cutoff. Conclusion: Iptacopan is a new, well tolerated oral complement AP inhibitor that blocks both IVH and EVH in adult PNH patients with hemolytic PNH. 12-month results from this non-pivotal study demonstrate that iptacopan monotherapy leads to rapid and durable improvements in various hemolytic markers and meaningful and sustained clinical benefit as seen in improvements in Hb levels, transfusion requirement and FACIT fatigue score. These results suggest that proximal inhibition of the complement cascade parallels and further improves the hematological benefit seen with anti-C5 therapies, paving the way for the phase 3 evaluation of iptacopan as potentially new oral first-line therapy for patients with PNH. Figure 1 Figure 1. Disclosures Wong: Astellas Pharma, INc.: Research Funding. Li: Novartis: Current Employment, Current equity holder in publicly-traded company. Rozenberg: Novartis: Current Employment, Current equity holder in publicly-traded company. Nidamarthy: Novartis: Current Employment, Current equity holder in publicly-traded company. Chawla: Novartis: Current Employment, Current equity holder in publicly-traded company. Junge: Novartis: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure: Iptacopan (LNP023) is a new, oral, selective and potent first-in-class inhibitor of factor B, a key component of the complement alternative pathway. It is currently being investigated in paroxysmal nocturnal hemoglobinuria (PNH) as well as in several renal indications.

Fatigue and Its Related Factors Among Iranian Cancer Survivors

Introduction: Cancer-related fatigue (CRF) is one of the major problems experienced by cancer patients. Identifying the prevalence and factors associated with CRF may be effective in designing appropriate interventions to reduce this problem. This study aimed to examine the prevalence of CRF and its related factors among Iranian cancer survivors. Methods: The samples of this descriptive cross-sectional study included 131 cancer survivors referred to outpatient clinic of Shahid Gazi Hospital affiliated to Tabriz University of Medical Sciences. Brief fatigue inventory (BFI) questionnaire was used for data collection. The data were analyzed using SPSS software version 13, descriptive statistics, and regression analysis. Results: The mean (SD) fatigue score was 6.41 (1.68) and 89% of survivors reported that they had suffered from CRF. The factors affecting CRF included blood pressure, diabetes mellitus, anemia, serum levels of blood urea nitrogen (BUN), marital status, type of cancer, and physical activity. Conclusion: High level of CRF in cancer survivors requires special attention and designing effective interventions through considering the identified factors associated with CRF.

P061 The effect of anxiety on symptom burden in patients with obstructive sleep apnoea

Background There is a high prevalence of anxiety in patients with obstructive sleep apnoea and such patients often describe fatigue in addition to sleepiness. We currently use the Epworth Sleepiness Scale (ESS) to quantify sleepiness in our patients, but we do not have useful tools for assessing fatigue. Fatigue is a common symptom in patients with many medical conditions but has not been well studied in patients presenting to sleep services. Our hypothesis is that patients with obstructive sleep apnoea who have a comorbid anxiety disorder, as measured by the Hospital Anxiety and Depression Scale (HADS) are likely to have increased symptom burden such as fatigue or poorer functional outcomes of sleep. Methods Analysis of prospectively collected data from 128 adult patients referred for suspected obstructive sleep apnea to Monash University Health Sleep Clinic. All patients have completed a comprehensive questionnaire prior to their first clinical review assessing their symptom burden at baseline. Questionnaires completed include extensive symptom and medical history assessment, the Fatigue Severity Scale (FSS), ESS, HADS, Functional Outcomes of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI) and Global Fatigue Score. All patients were subsequently reviewed by a clinician and have overnight polysomnography data available. Progress to date; Data collected for all 128 participants. Preliminary analysis currently underway. Intended outcome & impact; We intend to examine whether the comorbidity of anxiety results in an increased or different symptom burden in patients referred for suspected obstructive sleep apnoea when compared to patients without a history of anxiety.

Severe Fatigue in Long COVID: Web-Based Quantitative Follow-up Study in Members of Online Long COVID Support Groups

Background Fatigue is the most commonly reported symptom in patients with persistent complaints following COVID-19 (ie, long COVID). Longitudinal studies examining the intensity of fatigue and differentiating between physical and mental fatigue are lacking. Objective The objectives of this study were to (1) assess the severity of fatigue over time in members of online long COVID peer support groups, and (2) assess whether members of these groups experienced mental fatigue, physical fatigue, or both. Methods A 2-wave web-based follow-up study was conducted in members of online long COVID peer support groups with a confirmed diagnosis approximately 3 and 6 months after the onset of infectious symptoms. Demographics, COVID-19 diagnosis, received health care (from medical professionals or allied health care professionals), fatigue (Checklist Individual Strength–subscale subjective fatigue [CIS-Fatigue]; 8-56 points), and physical and mental fatigue (self-constructed questions; 3-21 points) were assessed. Higher scores indicated more severe fatigue. A CIS-Fatigue score ≥36 points was used to qualify patients as having severe fatigue. Results A total of 239 patients with polymerase chain reaction/computed tomography–confirmed COVID-19 completed the survey 10 weeks (SD 2) and 23 weeks (SD 2) after onset of infectious symptoms, respectively (T1 and T2). Of these 239 patients, 198 (82.8%) were women; 142 (59.4%) had no self-reported pre-existing comorbidities; 208 (87%) self-reported being in good health before contracting COVID-19; and 62 (25.9%) were hospitalized during acute infection. The median age was 50 years (IQR 39-56). The vast majority of patients had severe fatigue at T1 and T2 (n=204, 85.4%, and n=188, 78.7%, respectively). No significant differences were found in the prevalence of normal, mild, and severe fatigue between T1 and T2 (P=.12). The median CIS-Fatigue score was 48 points (IQR 42-53) at T1, and it decreased from T1 to T2 (median change: –2 points, IQR –7 to 3; P<.001). At T1, a median physical fatigue score of 19 points (IQR 16-20) and a median mental fatigue score of 15 points (IQR 10-17) were reported; these scores were lower at T2 for physical but not for mental fatigue (median change for physical fatigue –1 point, IQR –3 to 0, P<.001; median change for mental fatigue 0 points, IQR –3 to 3, P=.52). At the time of completing the follow-up survey, 194/239 (81.2%) and 164/239 (68.6%) of all patients had received care from at least one medical professional and one allied health care professional, respectively. Conclusions Fatigue in members of online long COVID support groups with a confirmed COVID-19 diagnosis decreases from 10 to 23 weeks after onset of symptoms. Despite this, severe fatigue remains highly prevalent. Both physical and mental fatigue are present. It remains unclear whether and to what extent fatigue will resolve spontaneously in the longer term. Trial Registration Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.