Search

Introduction: Epidemiologic studies suggest that joint bleeding occurs in patients with mild‐to‐moderate haemophilia, including women and girls. However, most previous studies on the impacts of haemophilia focus on men with severe disease. Aim: To identify unmet needs in men and women with mild‐to‐moderate haemophilia. Methods: The Pain, Functional Impairment, and Quality of Life (P‐FiQ) study assessed the impact of pain on functional impairment and health‐related quality of life in men with haemophilia A or B of any severity. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B‐HERO‐S) study evaluated the psychosocial needs of adults and children with haemophilia B of any severity, including women and girls. Both studies employed patient‐reported outcome measures. Results: In the P‐FiQ study, 16% (62/381) of participants had mild and 13% (50/381) had moderate haemophilia. In the B‐HERO‐S study, 29% (86/299) of adult participants were female, 25% (74/299) had mild haemophilia, and 63% (189/299) had moderate haemophilia. In addition, 63% (46/74) of patients with mild and 86% (162/189) of patients with moderate haemophilia routinely infused factor products to prevent bleeding. Patients reported difficulty gaining access to factor products (54%; 142/263) and a haemophilia treatment centre (17%; 44/263). During the P‐FiQ study, 78% (48/62) of patients with mild and 87% (44/50) with moderate haemophilia described problems with pain on the Brief Pain Inventory. Patients also reported issues with anxiety, depression and relationships. Conclusions: Mild‐to‐moderate haemophilia has physical and psychosocial impacts on patients. We offer some solutions to help alleviate these impacts and resolve unmet needs. [ABSTRACT FROM AUTHOR]

Getting a hold on MDSCs: How myeloid-derived suppressor cells (MDSCs) arise and whether they can be therapeutically targeted akin to exhausted T cells are both areas of active investigation. A persistent challenge in studying MDSCs has been the identification of MDSC-specific cell surface markers that can facilitate their isolation and characterization. Here, by carrying out scRNAseq in a mouse model of breast cancer, Alshetaiwi et al. have defined gene signatures that distinguish MDSCs from other myeloid and granulocytic cells. By mining these datasets, they have identified CD84 to be a robust cell surface marker for identification of MDSCs in both human and murine breast cancer. Whether their findings can be extended to MDSCs in other cancer settings remains to be seen. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer–associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter–driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor–bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers. [ABSTRACT FROM AUTHOR]

Background: The ACTION study identified barriers to initiating and maintaining weight loss in patients with obesity; however, joint‐related issues (pain, mobility and bleeding) may affect perceptions of patients with haemophilia and obesity (PwHO). Aim: To identify patient and caregiver insights on the unique challenges of PwHO. Methods: Following IRB approval, adults who self‐identified as PwHO, spouses/partners of adult PwHO, and caregivers of adolescent PwHO (aged 12‐17 years) completed an online survey between December 2017 and April 2018. Results: Respondents included 124 adult PwHO, 45 spouses/partners and 42 caregivers. By calculated BMI, most adults were overweight (43%) or had obesity (51%); this differed from self‐reported weight category. PwHO goals were improving health conditions (60%), having more energy (54%), reducing risks of weight (46%), and losing any weight (44%). Issues related to joint health were secondary for PwHO but frequently reported by spouses/parents. Most perceived weight loss to be a high priority (66%) and their responsibility (64%) but required a complete lifestyle change (63%). Most anticipated that weight loss would reduce joint pain (62%), bleeding (58%) and factor use (52%) and increase mobility (62%). Weight discussions with healthcare providers (HCPs) were commonly reported (51%). HCP discussions targeted improving health conditions (46%), achieving any weight loss (44%), being more active (73%) and improving eating habits (72%). Most PwHO (65%) perceived obesity as a disease and believe that 10% weight loss would be extremely beneficial (78%). In the past 5 years, 80% discussed being overweight and 68% losing weight; a minority reported being successful (9%) or somewhat successful (38%) with weight loss. More realistic or specific (51%/47%) goals, resources (46%), referrals to weight‐loss programmes (41%) or dietitians (38%), meals or recipes (54%/50%), local or national (42%/41%) programmes for PwHO and success stories of PwHO (40%) are needed or would be helpful. Conclusions: PwHO, spouse/partners and caregivers exhibited awareness of general and haemophilia‐specific consequences of excess body weight. Most have tried general approaches to improve eating and increase activity with little success and desire more education on weight management and more details on specific actionable recommendations distributed through existing haemophilia channels. These insights will better inform the creation of weight‐loss programmes for this community. [ABSTRACT FROM AUTHOR]

Introduction: Limited evidence describes physical activity‐associated bleeding risks for people with haemophilia, and risks are usually described only generically. Aim: To assess activity‐specific ranges of risk for joint, soft tissue and head bleeds by identifying inherent and modifiable risk factors associated with each activity, based on opinions of expert physical therapists (PTs). Methods: Physical therapists from US haemophilia treatment centres (HTCs) participated in a survey of 101 physical activities. For each activity, PTs provided minimum/maximum risk scores (low = 1; high = 5), and indicated specific bleeding risks in six joints and three injury types (bruising, muscle bleeding, head injury). Risk drivers were identified from free‐text comments and explored at a consensus meeting, where they were categorized as inherent or modifiable and activity‐driven or patient‐driven. Results: Of 32 invited PTs, 17 participated; median experience was 24 years as a PT and 16 years at an HTC. Only a few activities had a wide range of risk assessments encompassing both lower and upper ends of the response range. Joint injury risks were consistent with position and physical requirements, and head and muscle bleed risks were associated with physical contact. Eight PTs participated in the consensus meeting; key risk drivers identified included progression from seasonal to year‐round participation, overtraining and improper body mechanics. Inherent risks included impact with surface/ball/equipment and field/surface condition; modifiable risks included safety equipment and tricks/stunts. Conclusions: These data provide a framework for discussion with patients/families, recognizing how certain activities may be modified to decrease risk, and identifying activities with nonmodifiable inherent risks. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Pain, functional impairment, anxiety, and depression associated with joint disease may affect health‐related quality of life (HRQoL) in people with hemophilia. Objective: To report detailed patient‐reported outcomes (PRO) assessments related to HRQoL in participants in the Pain, Functional Impairment, and Quality of Life (P‐FiQ) study. Methods: Pain and HRQoL were assessed via PRO instruments in US adult males with hemophilia A or B and a history of joint pain or bleeding. PRO instruments included EQ‐5D‐5L with visual analog scale, Brief Pain Inventory v2 Short Form, SF‐36v2, and Hemophilia Activities List. Instrument domain and item responses were described. Results: Responses were collected from 381 adult males with a median age of 34 years. Pain was observed across instruments and affected daily activities and quality of life. Respondents reported functional impairment that limited the kind of work and activities they participated in, with activities involving the lower extremities being most affected. A high prevalence of mental health disorders was identified across instruments. Conclusions: Pain and HRQoL were evaluated using multiple PRO instruments, which vary in timescales of assessment and levels of detail. More consistent clinical assessments and patient dialog regarding pain and aspects of HRQoL may help drive improved outcomes. [ABSTRACT FROM AUTHOR]

The psychosocial impact of hemophilia on activities was recently investigated in the Hemophilia Experiences, Results and Opportunities ( HERO) study (675 people with hemophilia and 561 caregivers of children with hemophilia in 10 countries). The impact of hemophilia B may not be accurately reflected in the HERO results, as ~75% of respondents described issues affecting males with hemophilia A. To address the needs of this population, the Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B- HERO-S) was developed as a pilot study in the United States in collaboration with the hemophilia community. The analysis reported here assessed engagement in recreational activities and changes to treatment regimens around activities as reported by 299 adults with hemophilia B and 150 caregivers of children with hemophilia B. Nearly all adults with hemophilia B (98%) experienced a negative impact on their participation in recreational activities due to hemophilia-related issues, and most caregivers (90%) reported that hemophilia B had a negative impact on their child's engagement in recreational activities. One of the main reasons identified for discontinuing past activities was the risk of bruising or bleeding (adults/children with hemophilia B, 49%/41%). In particular, adults with hemophilia B reported a history of activity-related bleeding, and most adults decreased their participation in high-risk activities as they aged. Substantial percentages of adults and children with hemophilia B (including mild/moderate severity) altered their treatment regimens to accommodate planned activities. These findings may help inform guidelines for individualizing treatment regimens around participation in recreational activities based on hemophilia severity, baseline factor level, and activity risk and intensity. [ABSTRACT FROM AUTHOR]