Impact Scores Research Articles

Development and impact of a tailored eHealth resource on fibromyalgia patient's self-management and self-efficacy: A mixed methods approach.

To develop an eHealth resource to support fibromyalgia patients and explore it for usability and impact on their self-management and self-efficacy. Fibromyalgia is a complex, non-progressive chronic condition characterised by a bewildering array of symptoms for patients to self-manage. International guidelines recommend patients receive illness-specific information once diagnosed to promote self-management and improve health-related quality of life. A 3-phase mixed methods exploratory sequential design. Qualitative interviews explored the information and self-management needs of fibromyalgia patients attending a large tertiary hospital in Dublin. Identified themes together with an extensive review of the literature of interventions proven to be impactful by patients with fibromyalgia were utilised in the design and development of the eHealth resource. The resource was tested for usability and impact using pre and post-intervention outcomes measures. Patient interviews highlighted a lack of easy accessible evidenced information to support self-management implicating the urgent need for a practical solution through development of a tailored eHealth resource. Six themes emerged for inclusion; illness knowledge, primary symptoms, treatment options, self-management strategies, practical support and reliable resources. Forty-five patients who tested the site for usability and impact demonstrated a statistically significant improvement in self-efficacy after 4 weeks access with a medium positive effect size. Patients with the most severe fibromyalgia impact scores pre-intervention demonstrated the most improvement after 4 weeks. Patients gave the resource a System Usability Score A rating, highly recommending it for fellow patients diagnosed with fibromyalgia. The study demonstrated how the development of a novel eHealth resource positively impacted fibromyalgia patients' self-efficacy to cope with this debilitating condition. This study suggests that access to eHealth can positively impact patients self-efficacy, has the potential to be a template for eHealth development in other chronic conditions, supporting advanced nurse practitioners working in chronic disease management.

Analyzing Differentiated Climate Change Impacts on Women in the Wetland Area: A Case Study on Sunamganj District

Disadvantageous geo-location, dense population, and poverty make Bangladesh climate-sensitive, particularly in livelihoods. The impacts are detrimental to the economy, environment, and social development of the people of Dowarabazar and Jamalganj Upazila, Sunamganj District. This research aimed to scale the differentiated impacts of climate change on wetland women. To conduct the research, a survey approach following the Community Disaster Resilience Index (CDRI) was applied. The data were collected through questionnaire survey and observation. The sample size was 300 (150 males and 150 females). Simple random samplings were applied. The study included women of middle-aged, young, elderly, disabled, ethnic, religious minorities, widowed, destitute, and all income classes of poor and rich. It is found that the women's community is extremely vulnerable to different climatic impacts affecting women's capital of human, social, economic, physical, and natural. Women's social capital is highly impacted and the impact score is 3.54. Secondly, human capital (score is 3.07). The impact scores of natural and physical are 2.92 and 2.49. The lives and livelihoods of women have been severely curbed by climatic complications, vulnerable sanitation, poor house structure, and illiteracy. Proper management and access to income generation, empowerment, and social services are required for women's adaptation and resiliency.

Using the Impact-WEB_GIS Platform to Assess the Impacts of Environmental Sustainability Public Policies in the Lisbon Metropolitan Area

Urban environmental sustainability is a growing concern within the United Nations and the European Union’s ongoing policy agendas to fight climate change. This paper contributes to this debate by presenting the main impacts of the Operational Programme for Sustainability and Use of Resources (POSEUR 2014–2020) in the Lisbon Metropolitan Area (NUTS II). The analysis was completed using the Impact-WEB_GIS platform, specially developed for this study, supported by a territorial impact assessment methodology. In addition to the production of general impact scores, five analytic dimensions were further analysed, supported by state-of-the-art (i) low-emissions economy, (ii) adaptation to climate change, (iii) risk prevention and management, (iv) environmental protection and (v) resource efficiency. At a strategic level, the research created awareness of the need to adjust regional policy to the region’s characteristics on environmental sustainability matters.

Understanding anxiety experienced by young males with Duchenne muscular dystrophy: a qualitative focus group study

In this multi-methods study we explored the characteristics, causes and impact of anxiety in Duchenne muscular dystrophy (DMD) from the perspective of young males with DMD and their parents. Eight young males with DMD (7–18 years) and 14 parents participated in separate focus groups. Perspectives on anxiety were explored using semi-structured interview schedules. Themes were identified using Framework Analysis. Neurodevelopmental, emotional and behavioural symptom scores were obtained using standard instruments including the Strengths and Difficulties Questionnaire and Revised Children's Anxiety and Depression Scale. We identified six common anxiety characteristics: Catastrophic conclusions; Rigidly-held anxieties; Extreme distress; Social anxieties; Physical changes/needs; Unexpected/unfamiliar. Four further themes described influential systemic factors: Individual, Family, and Social responses and Physical environment and service contexts. All DMD participants had significantly higher total difficulties, emotional problems and impact scores than population norms. The Revised Children's Anxiety and Depression Scale showed low sensitivity in identifying anxiety symptoms. Fifty-seven percent (8/14) of parents who had wanted help for their son's anxiety were dissatisfied with the available support. In conclusion, anxiety can severely impact wellbeing and functioning of individuals with DMD. There are important nuances to consider when managing DMD-associated anxiety. We highlight the importance of multimodal assessment considering the multiple contexts within which anxiety arises.

Anthropogenic impacts on urban blue space and its reciprocal effect on human and socio-ecological health

Quantifying anthropogenic impacts on blue space (BS) and its effect on human and socio-ecological health was least explored. The present study aimed to do this in reference to the urban BS transformation scenario of Eastern India. To measure BS transformation, Landsat image-based water indices were run from 1990 to 2021. Anthropogenic impact score (AIS) and 7 components scores of 78 selected BS on 70 parameters related data driven from the field. Total 345 respondents were taken for human and socio-ecological health assessment. For this, depression (DEP), anxiety (ANX), stress (STR), physical activities (PA), social capital (SC), therapeutic landscape (TL) and environment building (EB) parameters were taken. The result exhibited that BS was reduced. About 50% of urban core BS was reported highly impacted. Human and socio-ecological health was identified as good in proximity to BS, but it was observed better in the cases of larger peripheral BS. AIS on BS was found to be positively associated with mental health (0.47–0.63) and negatively associated with PA, SC, TL and EB (−0.50 to −0.90). Standard residual in ordinary least square was reported low (−1.5 to 1.5) in 95% BS. Therefore, BS health restoration and management is crucial for sustaining the living environment.

Effect of Hypnosis on Pain, Anxiety, and Quality of Life in Female Patients with Fibromyalgia: Prospective, Randomized, Controlled Study

ABSTRACT This prospective, randomized, controlled study aimed to investigate the effects of standardized adjuvant hypnosis on pain, depression, anxiety, aerobic exercise practices, quality of life, and disease impact score in female patients with fibromyalgia syndrome (FMS). This study included 47 female patients with FMS who had been under treatment for at least six months. The hypnosis group (n = 24) received a total of three hypnosis sessions and was taught to patients’ self-hypnosis. The patients in this group practiced self-hypnosis for six months. During this period, all patients also continued their medical treatment. The Visual Analogue Scale (VAS) was used to determine the intensity of pain. At the end of the six-month follow-up period, it was determined that the patients of FMS with hypnosis therapy had lower pain intensity, FMS symptoms, depression, and anxiety symptoms, and better well-being than those in the control group (p < .05). Standardized hypnosis is an effective method in reducing pain, depression and anxiety symptoms and improving quality of life in patients with FMS.

Health-Related Quality of Life in Type 2 Diabetes Mellitus Patients at Moi County Referral Hospital in Taita-Taveta County, Kenya

Non-transmittable diseases are becoming a burden in Sub-Saharan Africa due to changing lifestyle habits like smoking, inactivity, and poor diet. Although diabetes was once thought to the affluents-only disease, it is now more commonly seen in low- and middle-income nations like Kenya. The cross-sectional study's goal was to determine socio-demographic and health-related characteristics affiliated to QOL (quality of life) as well as how this condition affected patients with T2DM (type 2 diabetes mellitus) at Moi County Referral Hospital (MCRH) in Taita-Taveta County. were. The study adopted ADDQOL (audit of diabetes dependent quality of life) tool with 19 items version 2006, no alterations were done, and license number HPR4458 was issued to utilize the tool in this study. The 165 patients were picked using a systematic random sampling method. 127(77percent) of the study's participants had a mean quality of life score concerning diabetes of -1.88, roughly corresponding to "quality of life would be much better in the absence of diabetes" at a score of –2. An average weighted impact score of -4.48, indicated an unfavourable impact on the patients' QOL by diabetes mellitus. Foot ulcers/sores (p=0.005; a OR=7.348) and numbness/pain in hands, legs, or feet (p=0.001; a OR=0.155) were associated to low quality of life. The socio-demographic characteristics were not related to the quality of life. The domain-specific element of "sex life" was considered the most essential and negatively impacted at a weighted impact score of -5.14. Overall, quality of life of T2DM patients in MCRH was low. It is important to focus on the often-overlooked health-related characteristics coupled with the disability adjusted life years of diabetic patients and how they both influence their quality of life

A follow-up study on the pain changes trend and effects in patients diagnosed with herpes zoster in Beijing City

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q1, Q3) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

Self-Reported Stuttering Severity Is Accurate: Informing Methods for Large-Scale Data Collection in Stuttering.

To our knowledge, there are no data examining the agreement between self-reported and clinician-rated stuttering severity. In the era of big data, self-reported ratings have great potential utility for large-scale data collection, where cost and time preclude in-depth assessment by a clinician. Equally, there is increasing emphasis on the need to recognize an individual's experience of their own condition. Here, we examined the agreement between self-reported stuttering severity compared to clinician ratings during a speech assessment. As a secondary objective, we determined whether self-reported stuttering severity correlated with an individual's subjective impact of stuttering. Speech-language pathologists conducted face-to-face speech assessments with 195 participants (137 males) aged 5-84 years, recruited from a cohort of people with self-reported stuttering. Stuttering severity was rated on a 10-point scale by the participant and by two speech-language pathologists. Participants also completed the Overall Assessment of the Subjective Experience of Stuttering (OASES). Clinician and participant ratings were compared. The association between stuttering severity and the OASES scores was examined. There was a strong positive correlation between speech-language pathologist and participant-reported ratings of stuttering severity. Participant-reported stuttering severity correlated weakly with the four OASES domains and with the OASES overall impact score. Participants were able to accurately rate their stuttering severity during a speech assessment using a simple one-item question. This finding indicates that self-report stuttering severity is a suitable method for large-scale data collection. Findings also support the collection of self-report subjective experience data using questionnaires, such as the OASES, which add vital information about the participants' experience of stuttering that is not captured by overt speech severity ratings alone.

Psychometric Properties of the Persian Version of the Dizziness Handicap Inventory for Patient Caregivers in Children

Background and Aim: Questionnaires are useful tools for clinicians. This study aimed to translate the Dizziness Handicap Inventory for Patient Caregivers (DHI-PC) into Persian (DHI-PC-P) and assess its psychometric properties for children aged 5–12 years. Methods: This is a descriptive-analytical psychometrics study. After obtaining permission from the developers of the DHI-PC, translation into Persian and cross-cultural adaptation were done according to the international guidelines for self-assessment tools recommended by the American Association of Orthopedic Surgeons. Participants were 21 parents (mean age: 38.05 years, SD=6.1 years, 18 female) and their children with dizziness (mean age 8.69 years, SD=2.41 years, 9 female) between the ages of 5–12 years old. Face validity, content validity, and test-retest reliability at an interval of 14–21 days were evaluated for the DHI-PC-P. Results: The face validity was confirmed qualitatively by the experts’ opinions and quantitatively by calculating the item impact score. Content validity was confirmed by calculating the content validity index and the content validity ratio (0.97 and 0.86, respectively). The internal consistency was good (Cronbach’s alpha=0.90). For the test- retest reliability, the intraclass correlation coefficient was obtained 0.94, indicating an excellent reliability. Conclusion: The DHI-PC-P can be used clinically as a valid and reliable tool for children with dizziness aged 5–12 years. Keywords: Questionnaire; dizziness handicap inventory; validity; reliability; vertigo; children

Design of a central tool for sustainability evaluation and weighting to decision-making support of contaminated soils remediation

Sustainable remediation remains unstandardized and ambiguously regulated, thereby limiting its adoption in the management of contaminated areas. Although a considerable number of tools are available for this purpose, numerous shortcomings continue to be detected, especially with regard to the integration of a complete assessment of impact and sustainability into a single framework. In view of these problems, the objective in this study was to develop and validate an integrated tool for assessing the sustainability of remediation techniques for contaminated soils. To support the sustainability analysis, were prepared impact assessment matrices, which list components and criteria for obtaining integrated impact scores for each sustainability dimension/pillar (i.e., social, economic, and environmental), factor, and component. These impact scores were incorporated and fitted into a mathematical model used to ascertain the sustainability of the techniques. The tool was subsequently validated by comparing and analyzing the sustainability with which five techniques: phytoremediation, electrokinetics and excavation/disposal (Case Study I), nanoremediation and soil washing (Case Study II). The techniques’ probabilities of sustainability followed the order presented in the preceding statement. The determination of sustainability was supported by the direct interaction between the effects derived under each dimension and technique. These findings led to the conclusion that the proposed tool prioritizes the basic principles of sustainability, which call for harmony among the three pillars, and that it is a favorable instrument for the evaluation and selection of a sustainable remediation technique.

The psychosocial burden of androgenetic alopecia in Saudi Arabia: A cross-sectional study.

The most prevalent cause of hair loss is androgenetic alopecia. Improved therapeutic modalities may result from knowing how stress affects hair growth, incorporating stress-coping methods into the treatment of hair loss disorders, and developing new pharmacotherapeutic approaches. This study aimed to examine the psychosocial burden of androgenetic alopecia in Saudi Arabia. A cross-sectional online survey study was conducted among patients with androgenetic alopecia in Saudi Arabia in February 2023. A previously developed questionnaire was adapted from a previously published tool and used in this study. This association between patients' characteristics and the level of psychosocial disease was identified using binary logistic regression analysis. This study included 1230 patients. The majority of the patients (78.0%) reported that they felt embarrassed by their androgenetic alopecia. The median score of the psychosocial impact of androgenetic alopecia on the patients was 1.00 (0.00-2.00), which is equal to 10.0%, reflecting a low level of psychosocial burden on the patients by their condition. Binary logistic regression analysis identified that patients without a family history of androgenetic alopecia were 36.0% less likely to be affected psychosocially by their condition (P < 0.01). A low-level psychosocial effect was seen in our study among individuals with androgenetic alopecia. Further research should be done to determine how the type of alopecia affects patients' psychological results, as well as the influence of the disease's duration on those outcomes. Dermatologists are recommended to raise patients' knowledge of their disease and lessen stigmatization in the meantime.

Same product, different score: how methodological differences affect EPD results

Abstract Purpose Demand for Environmental Product Declarations (EPDs) is already high and increasing in the construction and building sectors. The overall purpose of EPDs is comparability of product environmental performance, and they are thus developed in accordance with product category rules (PCRs): requirements and guidelines for how to make EPDs for one or more product groups. Since several organisations publish PCRs, there is a risk of creating conflicting rules leading to inconsistencies and jeopardising the objective of comparability. Methods This study analyses the causes for inconsistency and the consequences in terms of difference in the results across the life cycle assessment (LCA) models underlying the EPDs. Taking four EPD programmes and their actors as cases, first a document analysis was conducted to identify qualitative and quantitative differences in their guidelines. Further focusing on selected quantitative differences, a series of LCA models were designed for the same triple-glazed window product by adhering to the PCRs of each operator, to highlight the differences in results that occur when performing the same assessment via different but all formally selectable operators and compliant EPDs. Results and discussion Results show that the EPD of a specific product can return very different impact scores if one or the other guideline is followed. Results can vary more than 10% from the base scenarios, what we consider a significant variation. This is observed across all impact categories. Focusing specifically on the climate change impact, the results show that differences are due to the choice of energy mix, reference service life and other parameters. It is thus the combination of several modelling differences that leads to a overall divergence in results, rather than one single methodological choice. Conclusions Numerous different but at the same time compliant EPDs can be obtained for the same product, highlighting a serious harmonisation issue within the EPD system. EPDs are thus not necessarily accurate, and it remains doubtful whether EPD comparability can be achieved. This weakness of the EPD system can in the worst case be exploited by producers to obtain lower results and undermines the system. Recommendations Besides recommending using LCA for learning and process improvement rather than just for external communication and compliance, to increase harmonisation in the EPD system, we recommend limiting the number of product-specific PCRs (e.g. complementary PCRs), align default values, learn from verification, use just one background database, increase transparency and move towards one centralized operator.

The relationship between low back pain, pelvic tilt, and lumbar lordosis with urinary incontinence using the DIERS formetric 4D motion imaging system.

Urinary incontinence (UI) is a common public health problem and postural changes may be crucial in women presenting with UI. This study was aimed at evaluating the relationship between low back pain (LBP), pelvic tilt (PT), and lumbar lordosis (LL) in women with and without UI using the DIERS formetric 4D motion imaging system. To date no study has to our knowledge compared postural changes and LBP in women with UI using the DIERS 4D formetric system. This was a case-control study. We included 33 women with UI and 33 without incontinence. The severity of urogenital symptoms was assessed by the IIQ-7 (Incontinence Impact Score) and UDI-6 (Urogenital Distress Inventory), and disability owing to LBP was evaluated using the Oswestry Disability Index (ODI). Posture and movement assessment, LL angle, thoracic kyphosis, and PT assessment were performed with the DIERS Formetric 4D motion imaging system. The LL angle and pelvic torsion degree were higher in the incontinence group than in the control group (53.9 ± 9.5° vs 48.18 ± 8.3°; p= 0.012, 3.9 ± 4.1 vs 2.03 ± 1.8 mm; p= 0.018 respectively). The LBP visual analog scale value was also significantly higher in the incontinence group (5.09 ± 2.3 vs 1.7 ± 1.8 respectively, p< 0.0001). The LL angle showed a positive correlation with pelvic obliquity, (r = 0.321, p< 0.01) and fleche lombaire (r = 0.472, p< 0.01) and a negative correlation with lumbar range of motion measurements. Pelvic obliquity correlated positively with pelvic torsion (r = 0.649, p< 0.01), LBP (r = 0.369, p< 0.01), and fleche lombaire (r = 0.269, p< 0.01). Women with UI were more likely to have lumbopelvic sagittal alignment changes and a higher visual analog scale for LBP. These findings show the need for assessment of lumbopelvic posture in women with UI.

Associations between Epigenetic Age Acceleration and Psychoneurological Symptoms in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) affects approximately 100,000 predominantly Black or African American individuals in the United States. The disease has several acute and chronic complications that lead to a reduced median lifespan of 42 years, which is significantly shorter than the general US population. In this shortened lifespan, people experience deleterious psychoneurological symptoms including pain, sleep disturbances, depressive symptoms, and cognitive impairment. The high occurrence of these symptoms has negative effects on quality of life and function, and contributes to health disparities in this population. Evidence suggests a person's epigenetic age may be associated with inter-individual variability in psychoneurological symptoms in SCD. Epigenetic age is a promising biomarker because it reflects the cumulative effects of exposures to stressors at the psychosocial, physical and environmental level, by capturing the molecular processes occurring with declining tissue function through globally assessing DNA methylation patterns that account for the pace of cellular aging. Epigenetic age and age acceleration in relation to disease characteristics and symptom burden has been assessed in several chronic conditions such as cancer, obesity and Alzheimer's. None have assessed this association in SCD. To address this gap, our study aims to determine whether epigenetic age acceleration is associated with psychoneurological symptom burden (pain impact, emotional impact, sleep impact, and cognition) in SCD. Methods: Psychoneurological symptoms and DNA methylation were assessed in a subset of participants aged between 18 - 45 years enrolled in one of the Sickle Cell Disease Implementation Consortium sites. DNA methylation data were generated on the Infinium MethylationEPIC beadchip (Illumina) from the extracted DNA of blood specimens and used to calculate epigenetic age using five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, &amp; DunedinPACE). Psychoneurological symptoms were evaluated using validated instruments: the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and Quality of Life in Neurological Disorders (NeuroQoL). Data were converted to T-scores and were used to determine associations with epigenetic age acceleration for each of the epigenetic clocks. Higher T-scores in ASCQ-Me and NeuroQoL indicate more desirable (better) outcomes. Results: Among participants (n=89) included in the analysis, the mean (SD) chronologic age was 30.6 (8.0) years. A majority identified as female (60.7%), non-Hispanic Black or African American (92%), never married (76.4%), had Hb SS genotype (68.5%), were taking hydroxyurea (60.5%), and had at least 4 pain events in past year (53.5%). Two epigenetic clocks showed mean age acceleration (Horvath: 0.2 ±4.6 years; GrimAge: 12.6 ±4.0 years, whereas two clocks showed mean age deceleration (Hannum: -4.27 ±3.91 years; PhenoAge: -8.43 ±6.0 years). The DunedinPACE clock is on a different scale than other clocks, but also demonstrated evidence for accelerated aging whereby the epigenetic age increased 1.14 years for every chronologic year. Increased age acceleration was associated with worse pain impact scores (GrimAge β=-0.25, p= 0.02), worse emotional impact scores (GrimAge β=-0.24, p=0.03; Dunedin β= -0.30, p=0.01) greater sleep disturbance (Dunedin β=-0.22, p=0.04) and more depressive symptoms (Dunedin β=0.29, p=0.01) (Table 1). Conclusion: This was the first study, to our knowledge, that explored the relationship between epigenetic age and psychoneurological symptoms in SCD. Epigenetic age acceleration was associated with worse symptom scores. Our preliminary findings identified several variations in the associations between symptom outcomes and epigenetic age across the five clocks. These variations may be due to the differences in the models used to develop the clocks, as well as inherent differences in epigenetic loci used to calculate epigenetic age for each clock. Future assessment of those discrepancies is warranted to effectively characterize individuals at higher risk of age acceleration and higher symptom burden in SCD. Our findings also highlight the potential use of epigenetic age acceleration as a biological target for interventions aimed towards preventing age acceleration and symptom development, improving the quality of life of individuals with SCD.

Predicting Clonal Evolution to Secondary Myeloid Neoplasms in Aplastic Anemia through Machine Learning

Background: One of the major long-term complications in aplastic anemia (AA) is the clonal evolution to secondary myeloid neoplasms (sMNs) such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) 1. Hematopoietic stem cell transplantation (HSCT) is largely considered a curative treatment option for AA and is effective at preventing the clonal evolution of sMNs 2. However, patients over 40 years old or those with poor donor options are contraindicated for HSCT due to elevated post-transplant mortality rates 3. When treated with non-transplant strategies, patients with AA have indeed a high risk for acquisition/expansion of somatic myeloid mutations, with some harbingers of future clonal progression to full-blown MDS or AML. Older age, presence of myeloid mutations other than BCOR/L and PIGA at onset, and lack of response to standard immunosuppressive treatment (IST) have been identified as factors predictive for subsequent sMN evolution 4,5,6. If an individual patient's risk of developing a sMN could be assessed through a predictive model that uses information collected at initial AA diagnosis, providers may consider HSCT for traditionally contraindicated patients. However, no such predictive model that could aid in risk assessment currently exists. Methods: In our study, we utilized a large, multi-institutional cohort of patients diagnosed with AA to generate a comprehensive dataset. This dataset contained 76 variables, encompassing relevant clinical and molecular annotations. On this dataset, we trained a machine learning (ML) model to predict patients who would evolve sMNs. Variables with the highest feature impact score (FIS) in predicting clonal evolution to sMN were then chosen to be included in the final ML model, and the algorithm's fitness was calculated using the Leave-One-Out cross-validation method. Variables missing in more than 30% of subjects were imputed using K-Nearest Neighbors (N=20). Of our initial cohort of 455 patients, 213 patients were excluded from the study. 35 patients were excluded because they were treated with HSCT. 39 pediatric cases (defined as &amp;lt;18 years old at the time of diagnosis) were excluded from the study. 91 patients were removed for not receiving specific treatment (IST or HSCT). The remaining 77 patients were excluded due to having a sMN detected at the time of or prior to AA diagnosis, insufficient data, or detection of a germline mutation indicative of an inherited pathophysiology. Our final cohort included a total of 242 acquired AA patients from UT Southwestern Medical Center and Cleveland Clinic. Results: Among our final cohort of 242 patients, 119 (49.2%) were male. The cohort's mean and median ages at AA diagnosis were 53.1 years (SD = 18.9 years) and 58.1 years, respectively. The median follow-up time was 4.04 years. 80 (33.1%) of our patients had a clinically significant PNH clone (defined as &amp;gt;0.001%). 29 patients developed sMNs, with 24 developing MDS and 5 developing AML. Of patients who underwent clonal evolution to sMNs, the median age at the time of AA diagnosis and sMN diagnosis was 63.1 years and 67.2 years, respectively. The median time elapsed from initial AA diagnosis to sMN evolution was 3.78 years. The median time elapsed between initial AA diagnosis and earliest IST administration was 51 days. Chi-squared analysis showed that patients who received ATG treatment were more likely to develop sMNs, with 78.0% of all patients receiving ATG, while 96.6% of patients who developed sMNs had received ATG (p=0.00927). Our ML model achieved a sensitivity of 0.759, a specificity of 0.728, and an AUC of 0.78 using the ten variables with the highest feature impact score (FIS) to predict clonal evolution [Table 1]. All of the variables except for the presence of a PNH clone are positively correlated with sMN evolution. Nine of these variables are supported by existing literature 7,8. The feature with the third highest feature impact score, the time elapsed (days) between diagnosis and IST treatment, has not been established by previous studies and may be an important consideration in establishing optimal AA treatment guidelines. Conclusion: The strategic combination of this ML algorithm with clinical expertise has tremendous potential in improving health outcomes. Identification of patients at high risk for sMN and offering HSCT as a curative option upfront may lead to improved overall survival in AA patients.

Rare Germline Loss-of-Function Variants in HSP47 ( SERPINH1) Are Associated with an Intermediate Osteogenesis Imperfecta Phenotype Characterized By Atopic Inflammation and Increased Risk of Thrombosis

Background: There has been considerable interest in the collagen-specific chaperone HSP47 ( SERPINH1) as a potential drug target for the treatment of cirrhosis, fibrotic disease, and more recently, thrombosis (Thienel et al., Science 380, 178-187, 2023). While homozygous or compound heterozygous loss of function in SERPINH1 is known to cause a rare form of osteogenesis imperfecta (OI) in humans, little is known about the clinical effects of moderately decreased HSP47 activity. In order to assess the potential safety and efficacy of an antithrombotic strategy based on HSP47 blockade, we evaluated the clinical impacts of heterozygous loss-of-function variants in SERPINH1 in a dataset of over 400,000 individuals. Aims: Determine the clinical effects of SERPINH1 loss of function in a large-scale whole exome sequencing dataset. Methods: The UK Biobank (UKBB) contains paired whole exome sequencing and clinical data on 415,921 subjects in addition to plasma proteomics data for a subset of participants (N= 48,892). We identified all rare (MAF&amp;lt;0.1%)variants in SERPINH1 that were predicted in silico to alter protein activity (functional impact score ≥0.7). Using Firth's logistic regression, we controlled for age, sex, ancestry, and other risk factors and assessed the association between the presence of qualifying SERPINH1 variants and four thrombotic disorders: venous thromboembolism (VTE), non-cardioembolic ischemic stroke (NCEIS), myocardial infarction (MI), and peripheral arterial disease (PAD). Replication was performed in a composite dataset from the NIH All of Us program and the Mass General Brigham (MGB) Biobank (N=150,017). We also evaluated differences in the plasma levels of 1,472 proteins (Olink Explore 1536 proteomics panel) between carriers and non-carriers of qualifying SERPINH1 variants. Results: Rare qualifying variants in SERPINH1 were identified in 382 UKBB participants (100% heterozygous). On average, SERPINH1 variant carriers were of significantly shorter stature (P=3.97 x 10-5) and lower weight (P=0.006) than individuals without such variants, and this effect was more pronounced in subjects with higher functional impact scores ( Figure 1). By contrast, bone mineral density did not differ significantly as measured by calcaneal quantitative ultrasound and femur shaft dual x-ray absorptiometry. The presence of SERPINH1 variants was associated with significantly increased risk of VTE (OR=1.87, 95% CI: 1.21-2.76, P=0.006), MI (OR=1.98, 95% CI: 1.27-2.96, P=0.003), PAD (OR=2.37, 95% CI: 1.29-3.98, P=0.007), and NCEIS (OR=2.67, 95% CI: 1.24-4.98, P=0.015). Restricting the analysis to high-confidence loss-of-function variants (i.e., nonsense, frameshift, and essential splice site mutations) markedly boosted effect size estimates for MI, PAD, and NCEIS. The VTE and MI disease associations replicated in the composite dataset (VTE OR=3.29, 95% CI: 1.46-7.39, P=0.004; MI OR=2.31, 95% CI: 1.05-5.08, P=0.038). Additionally, the association with NCEIS demonstrated a strong trend towards significance in the replication dataset (OR=2.08, 95% CI: 0.90-4.83, P=0.088). Plasma proteome analysis showed a significant increase in several proteins related to asthma, atopic inflammation, and/or eosinophil activation among individuals with qualifying SERPINH1 variants, including RNASE3, DPP10, TSPAN1, CCL20, and IL10RA ( Figure 2). In order to further investigate these differences in circulating protein profile, we assessed the risk of obstructive asthma in a meta-analysis of the UKBB, All of Us, and MGB datasets (total N=565,455) and found that SERPINH1 variant carriers were significantly more likely to have disease (OR=1.32, 95% CI: 1.03-1.69, P=0.026). Conclusions: Loss of function in SERPINH1 is associated with a significantly increased risk of both venous and arterial thrombosis, raising concerns that long-term therapeutic inhibition of HSP47 may not be a safe or effective antithrombotic strategy. Our data indicate that SERPINH1 variant carriers experience higher levels of eosinophil-driven inflammation, which has consistently been linked to cardiovascular disease. Further, heterozygous SERPINH1 variant carriers appear to have an intermediate OI phenotype characterized by shorter stature but without significant differences in bone mineral density compared to non-carriers.

Differences in Knowledge of Female Athlete Triad and Relative Energy Deficiency in Sport in Female Cross-Country Athletes.

The female athlete triad (Triad) and relative energy deficiency in sport (REDs) describe potential health and performance consequences of low energy availability. We surveyed female cross-country athletes to assess differences in educational impact scores (EIS; knowledge score × confidence score factor) of Triad and REDs. Associations between EIS and participant characteristics (eg, mileage [current and peak], years of running experience, age, bone stress injury history, division level participation, academic area of study, Triad or REDs diagnoses, and Triad or REDs education) were explored. An evidence-based online survey was developed and administered via Qualtrics to female collegiate cross-country athletes (n = 275; age = 20 ± 1 years). A weak correlation existed between peak career mileage and EIS (r = 0.195; P = .010). Educational impact scores significantly differed in athletes with a related academic area of study versus those without (21.91 ± 5.16 and 16.11 ± 5.54, respectively). Educational impact scores significantly differed in athletes with Triad and REDs diagnoses (21.69 ± 5.85 and 22.58 ± 6.82, respectively) versus those without (16.80 ± 6.54 and 17.20 ± 6.34, respectively). Educational impact scores were higher in those who had received Triad education versus those who had not (21.03 ± 6.86 and 18.12 ± 6.82, respectively). A significant interaction between peak career mileage and Triad diagnosis was found (P = .005). Significant education-based and diagnosis differences suggest that Triad diagnoses correlate with peak career mileage. These findings support the facilitation of education to improve not only the treatment but also the prevention of Triad and REDs.

The IMPACT Score: A New Score to Predict the Risk of Early Mortality in Cardiogenic Shock Patients Treated With Venoarterial Extracorporeal Membrane Oxygenation

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) requires considerable human and financial resources. Few studies have focused on early mortality (ie, occurring within 72 hours after VA-ECMO implantation). The objective of this study was to establish a prognosis score-the IMPACT score (prediction of early mortality associated with VA-ECMO using preimplantation characteristics)-by determining the risk factors associated with early mortality. This was a retrospective and observational study. The study was conducted at a University hospital. This single-center retrospective study included 147 patients treated with VA-ECMO for cardiogenic shock between 2014 and 2021. The primary outcome was early mortality (ie, occurring within 72 hours after VA-ECMO implantation). Multivariate logistic regression was performed using a bootstrapping methodology to identify factors independently associated with early mortality. To construct the score, identified variables had points (pts) assigned corresponding to their odds ratio. A total of 147 patients were included in the study. Early mortality (<72 hours) was 26% (38 patients). Four variables were established: cardiac arrest (2 pts), lactate levels (3 pts), platelet count <100 g/L (4 pts), and renal-replacement therapy (5 pts). The IMPACT score had an area under the receiver operating characteristic curve of 0.78 (95% CI 0.86-0.70) to predict early mortality. In the authors' experience, 26% of patients treated with VA-ECMO presented early mortality. The IMPACT score is a reliable predictor of early mortality and may assist with VA-ECMO initiation decision-making.

Fine Particulate Matter Exposure and Health Impacts from Indoor Activities

Exposure to fine particulate matter (PM2.5) is an important contributor to global human disease burden, particularly indoors where people spend the majority of their time and exposure is highest. We propose a framework linking indoor PM2.5 emissions from human activities to exposure and health impacts, expressed in Disability-Adjusted Life Years (DALY). Derived dynamic indoor PM2.5 concentrations—capturing temporal variations through different window-opening scenarios and air renewal rates—are used to estimate uncertainty for a parametric model (up to a factor of 114). Intake fractions (fraction of emitted substance taken in (μgintake/μgemitted)), effect factors (μDALY/μgintake), related impact characterisation factors (health impact per unit mass emitted (μDALY/μgemitted)), and impact scores (health impact per hour activity (μDALY/hactivity)) are provided for 19 one-hour indoor activities and can be flexibly scaled to real activity durations. Indoor concentrations exceeded recommended World Health Organization (WHO) limits for all activities at low ventilation rates. Per person, 98 to 119 μDALY/hactivity (52 to 63 minuteslost/hactivity) was associated with traditional fuel cook stoves, with high air renewal rates (3 and 14 h-1). The burning of candles, at low air renewal rates of 0.2 to 0.6 h-1, results in 7 to 11 μDALY/hactivity (4 to 11 minuteslost/hactivity). Derived impact scores and characterisation factors serve as a starting point for integrating indoor PM2.5 emissions and exposure into life cycle impact and public health assessments.