Sternal fixation for traumatic sternal fractures demonstrates better long-term quality of life outcomes than nonoperative management: A survey analysis.

INTRODUCTION: Sternal fractures are rare, causing significant pain, respiratory compromise, and decreased upper extremity range of motion. Sternal fixation (SF) is a viable treatment option; however, there remains a paucity of literature demonstrating long-term benefits. This study examined long-term outcomes of SF, hypothesizing they have better long-term quality of life (QoL) than patients managed nonoperatively (NOM). METHODS: This was a survey study at our level 1 academic hospital. All patients diagnosed with a sternal fracture were included from January 2016 to July 2021. Patients were grouped whether they received SF or NOM. Basic demographics were obtained. Three survey phone call attempts were conducted. The time from injury to survey was recorded. Outcomes included responses to the QoL survey, which included mobility, self-care, usual activities, chest pain/discomfort, and anxiety/depression. The survey scale is 1-5 (1 = worst condition possible; 5 = best possible condition). Patients were asked to rate their current health on a scale of 0-100 (100 being the best possible health imaginable). Chi square and t-tests were used. Significance was set at p < 0.05. RESULTS: Three hundred eighty four patients were surveyed. Sixty nine underwent SF and 315 were NOM. Thirty-eight (55.1%) SF patients and 126 (40%) NOM patients participated in the survey. Basic demographics were similar. Average days from sternal fracture to survey was 1198 (±492) for the SF group and 1454 (±567) for the NOM group. The SF cohort demonstrated statistically significant better QoL than the NOM cohort for all categories except anxiety/depression. CONCLUSION: SF provides better long-term QoL and better overall health scores compared to NOM.

Individual and area-level socioeconomic status, Life's Simple 7, and comorbid cardiovascular disease and cancer: a prospective analysis of the UK Biobank cohort.

OBJECTIVES: We aimed to investigate the associations of individual and area-level socioeconomic status (SES) with incident cardiovascular diseases (CVD) alone, cancer alone, and comorbid CVD and cancer, and the mediation role of cardiovascular health score in these associations. STUDY DESIGN: This was a population-based prospective cohort study. METHODS: We used data from the UK Biobank, a population-based prospective cohort study. Latent class analysis was used to create an individual-level SES index based on three indicators (household income, education level, and employment status), and the Townsend Index was defined as the area-level socioeconomic status. We used the American Heart Association's (AHA) Life's Simple 7 (smoking, body weight, physical activity, diet, blood pressure, blood glucose, and total cholesterol) to calculate the cardiovascular health score. We used Cox proportional hazard regression models to estimate the hazard ratio (HR) and 95% confidence interval (CI) adjusted for demographic, environmental, and genetic factors. RESULTS: Compared with high SES, the HRs in participants with low individual and area-level SES were 1.33 (95% confidence interval [CI] 1.29 to 1.38) and 1.24 (95% CI 1.20 to 1.29) for incident CVD, 0.96 (95% CI 0.93 to 0.99) and 0.95 (95%CI 0.92 to 0.98) for incident cancer, 1.32 (95%CI 1.24 to 1.40) and 1.15 (95%CI 1.08 to 1.22) for incident comorbid CVD and cancer, respectively. Additionally, the mediation proportion of CVD score for individual and area-level SES was 47.93% and 48.87% for incident CVD, 44.83% and 59.93% for incident comorbid CVD and cancer. The interactions between individual-level SES and CVD scores were significant on incident CVD, and comorbid CVD and cancer, and the protective associations were stronger in participants with high individual-level SES. CONCLUSIONS: Life's Simple 7 significantly mediated the associations between SES and comorbid CVD and cancer, while almost half of the associations remained unclear.

Persistent capillary rarefication in long COVID syndrome.

BACKGROUND: Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after the initial infection. METHODS: This prospective, observational study included 58 participants, 27 of whom were long COVID patients with persistent symptoms > 12 weeks after recovery from PCR-confirmed SARS-CoV-2 infection. Fifteen healthy volunteers and a historical cohort of critically ill COVID-19 patients (n = 16) served as controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version of Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell velocity (VRBC) and the microvascular health score (MVHS™) in sublingual microvessels with diameters 4-25 µm. MEASUREMENTS AND MAIN RESULTS: Although dimensions of the glycocalyx were comparable to those of healthy controls, a µm-precise analysis showed a significant decrease of vascular density, that exclusively affected very small capillaries (D5: - 45.16%; D6: - 35.60%; D7: - 22.79%). Plotting VRBC of capillaries and feed vessels showed that the number of capillaries perfused in long COVID patients was comparable to that of critically ill COVID-19 patients and did not respond adequately to local variations of tissue metabolic demand. MVHS was markedly reduced in the long COVID cohort (healthy 3.87 vs. long COVID 2.72 points; p = 0.002). CONCLUSIONS: Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.

18 F-FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients.

INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.

Diminished cortical bone density of long bones among children with haemophilic arthropathy.

INTRODUCTION: Children with haemophilia (CwH) have lower bone mineral density in the spine (trabecular bone) than healthy children. There are few studies focusing on bone mineral density in long bones (cortical bone). AIM: To evaluate bi-laterally the distal third of radius and midshaft tibias using quantitative ultrasound (QUS) and assess the speed of sound (SoS). METHODS: A cross-sectional study where 91 CwH and 91 age-matched healthy boys were included. Joint evaluation was determined with the Haemophilia Joint Health Score 2.1 and SoS values. The Z scores were measured with the Sunlight Omnisense 8000 S equipment. RESULTS: Ninety-one CwH (haemophilia A) were evaluated (26 mild form, 26 moderate, and 39 severe). Most patients were treated with on-demand factor replacement and had higher total HJHS scores according to severity (4.8, 14.8 and 14.1, respectively). Patients with moderate and severe disease showed a statistical difference in SoS values for both radius and tibias compared to controls. QUS Z-scores ≥-2 were more frequent in radius and tibias in CwH, but were statistically significant only in tibias when compared to controls (in 30% mild, 46% moderate, 28% severe, respectively). CONCLUSIONS: There was diminished cortical bone density in radius and tibias of CwH compared to healthy controls. Changes predominated in tibias, more frequently affected according to the severity of haemophilia. Early intervention with factor replacement combined with physical activity are key aspects to promote bone health.

Polygenic embryo screening: are there potential maternal and fetal harms?

Polygenic embryo screening (PES) and its derivate the Embryo Health Score (EHS) have generated interest in both infertile and fertile populations due to their potential ability to select embryos with a reduced risk of disease and improved long-term health outcomes. Concerns have been raised regarding the potential harms of IVF itself, including possible epigenetic changes that may affect the health of the offspring in late adulthood, which are not fully captured in the EHS calculation. Knowledge of the potential impacts of the trophectoderm biopsy, which is a key component of the PES procedure, on the offsprings' health is limited by the heterogeneity of the population characteristics used in the published studies. Nonetheless, the literature suggests a possible increased risk of preterm delivery, birth defects and pre-eclampsia after trophectoderm biopsy. Overall, the risks of PES for prenatal and postnatal health remain uncertain, and further research is needed. Counselling patients regarding these risks before considering PES is important, to provide an understanding of the risks and benefits. This review aims to highlight some of these issues, the need for continued investigation in this area, and the importance of informed decision-making in the context of PES.

Use of clinical scores in young Australian adults for prediction of atherosclerosis in middle age.

We sought to apply a simple cardiovascular health tool not requiring laboratory tests (the Fuster-BEWAT score, FBS) to predict subclinical atherosclerosis. This study included 2657 young adults (< 40 years of age). In the prognostic group (n = 894, followed for 13 years until aged 40-50 years at follow-up), the primary outcome was presence of carotid plaque measured by carotid ultrasound at follow-up. Of these 894 participants, 86 (9.6%) had unilateral, and 23 participants (2.6%) had bilateral, carotid plaques at follow-up. The baseline FBS was predictive of carotid plaque at follow-up [odds ratio OR = 0.86 (95% CI 0.77-0.96) per 1-SD increase in FBS], similar to prediction from Pooled Cohort Equation [PCE, OR = 0.72 (0.61-0.85) per 1-SD decrease in PCE]. Risk scores at baseline predicted outcomes more strongly than those at follow-up, and did so independently of any changes over 13 years of follow-up. Similar discrimination for predicting carotid plaque after 13 years was found for both baseline FBS [C-statistic = 0.68 (95% CI 0.62-0.74)] and PCE [C-statistic = 0.69 (95% CI 0.63-0.75)]. Application of this FBS prognostic information to a contemporary cohort of 1763 young adults anticipates the future development of plaque in 305 (17.3%), especially in the 1494 participants (85%) with ≤ 2 metrics of ideal health. In conclusions, FBS measured in young adulthood predicted atherosclerosis 13 years later in middle age, independent of score changes over the follow-up period, emphasizing the importance of early damage to vascular health. FBS may be a simple and feasible risk score for engaging low-risk young people with reduction of future cardiovascular risk.

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce. METHODS: We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels. RESULTS: The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores. CONCLUSION: In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

The Correlation Between the HEAD-US-C Score and HJHS in Hemophilic Arthropathy of the Knee.

OBJECTIVES: We aimed to discuss the correlation between the Hemophilia Early Detection Ultrasound in China (HEAD-US-C) score and the Hemophilia Joint Health Score version 2.1 (HJHS 2.1) of the knee joint in patients with hemophilia. METHODS: We included 70 male patients with hemophilia admitted to The Second Hospital of Shanxi Medical University; the patients' bilateral knee joints were evaluated using the HEAD-US-C score and HJHS. We analyzed factors influencing hemophilia arthropathy of the knee and examined the correlation between the HEAD-US-C score and HJHS. RESULTS: The joint injury severity was positively correlated with age and the number of bleeds (P < .001). Further, the HEAD-US-C score and HJHS differed according to the severity (both P < .001), but not type (P = .163 and P = .283, respectively), of hemophilia. There was a significant correlation between the HEAD-US-C score and HJHS (P < .001). CONCLUSIONS: Overall, all joint lesions observed on ultrasound corresponded to clinical joint functional abnormalities. Therefore, the HEAD-US-C is important for hemophilic arthropathy evaluation and is useful in explaining abnormal joint function.

Analysis and evaluation of developed and used health scores.

This systematic review provides an overview of existing multidimensional health scores, including an assessment of their holistic value (coverage of all determinants and dimensions of health), and a systematic comparison of their properties. The review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Literature searches were conducted in English (PubMed, Scopus, Web of Sciences) and German databases (BISp-Surf, BIBNET). All scores that considered health multidimensional on an individual level were included. Two independent reviewers screened and identified articles. The Quality assessment tool for studies with diverse design was used to assess study quality. Scores were recorded in a criteria grid to make their properties comparable, and the multidimensionality of the individual scores was evaluated using radar chart visualizations. Twenty-six studies met the inclusion criteria. Study quality was strong in eight, fair in twelve, and weak in six studies. Among the 26 studies, 21 different questionnaire-based scores were included, which all covered at least three of the five health dimensions (Five dimensions have been identified in a former literature research). Three scores covered all dimensions, but none covered all of the previously defined determinants. Thus, according to this works created definition (holistic = cover all dimensions with all determinants), no holistic health score exists, only multidimensional scores covering different dimensions and determinants. This review offers good comparability, as all the instruments were questionnaires, and could be used as a basis for future research. A universal (holistic) health construct should be defined and developed to improve the quantification of health.

What is health? The concept of health is very complex. Therefore, although several models and scientific studies exist, the entire theme has not yet been fully explored. With the goal to understand health holistically, this work investigated the multidimensional health scores developed to date. Health scores need to be valid, easy to grasp and use, efficient, and scalable. They should provide a reliable statement regarding an individual's health status as well as their future health chances. The basic architecture of the health score should contain more than one dimension of health. A total of 26 studies comprising 21 different health scores were identified with the above criteria. However, according to the definition, none of the health scores were holistic (matching all health dimensions and determinants); rather, they were multidimensional scores covering different dimensions and determinants.

Multidimensional sleep health is associated with mental well-being in Australian adults.

The few studies assessing the relationship between mental health and a multidimensional measure of sleep have been conducted in samples of almost exclusively women. In the present study, we therefore assessed associations of multidimensional sleep health with mental well-being in Australian adults. A cross-sectional, national online survey of sleep health was conducted in 2019 in 2,044 community dwelling adults aged 18-90 years. Composite scores of self-reported healthy sleep were based on Ru-SATED (R-SATED) dimensions of satisfaction, alertness, timing, efficiency and duration scored 0 (never/rarely), 1 (sometimes) or 2 (usually/always), and regularity (social jet lag) was scored 0 (≥1 hr) or 1 (<1 hr). Mental well-being was identified by a report of no problem on the EuroQol (European quality of life) five dimension five level scale (EQ-5D-5L) anxiety/depression scale, as well as absence of six chronic depressive symptoms. Ordinal logistic regression analyses determined associations of mental well-being with sleep dimensions, and total R-SATED (range 0-11) and SATED scores (0-10), adjusted for sociodemographic and health factors. In males and females, healthy categories of SATED dimensions (but not regularity) were associated with mental well-being. A 1 unit increase in the total SATED score (mean [SD] 6.6 [2.1]) was associated with less problems on the EQ-5D-5L (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.08-1.14) and fewer chronic depressive symptoms (OR 1.20, 95% CI 1.17-1.23). These estimates did not differ when the total R-SATED score was considered. Sleep health promotion focussing solely on traditional messaging around healthy sleep duration may limit mental health gains. Rather, a more holistic approach to public health messaging to improve sleep health literacy may be beneficial for mental well-being.

Long-term joint outcomes of regular low-dose prophylaxis in Chinese children with severe haemophilia A.

OBJECTIVES: To explore the long-term joint outcomes of low-dose prophylaxis in Chinese children with severe haemophilia A and to analyse their related factors. METHODS: We retrospectively analysed follow-up data from 21 severe haemophilia A children on regular low-dose prophylaxis for 6-10 years. We used International Prophylaxis Study Group magnetic resonance imaging score (IPSG MRI score), Hemophilia Joint Health Score (HJHS), number of target joints, and Hemophilia-Specific Quality of Life Index (Haemo-QoL) to evaluate joint outcomes. Factors associated with these outcomes were evaluated by statistical analysis. RESULTS: (1) The children were 1.75 to 17 years age at prophylaxis initiation. Median prophylactic factor VIII dose was 22.9 IU/kg per week. (2) At the end of follow-up: (a) The total IPSG MRI scores were 2-24 with 90.5% children exhibiting moderate to severe joint involvement (score 7-24); (b) The HJHS ranged 2-27, with 0-10 for 46.7% children and >10 for 53.3% children. There was a positive correlation between the MRI score and HJHS (p < .05); (c) Compared to their on-demand treatment period before prophylaxis, target joints numbers decreased, and no child needed auxiliary devices to walk; (d) Joint outcomes were positively correlated with the age at initiation of low-dose prophylaxis (p < .05) and negatively correlated with the treatment dose. CONCLUSION: Long-term low-dose prophylaxis had positive effect on joint outcomes compared with on-demand treatment. However, a certain degree of joint damage remained in all children indicating the need for improving the current strategy of low-dose prophylaxis.

Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study.

BACKGROUND: The availability of handheld, noninvasive sublingual video-microscopes allows for visualization of the microcirculation in critically ill patients. Recent studies demonstrate that reduced numbers of blood-perfused microvessels and increased penetration of erythrocytes into the endothelial glycocalyx are essential components of microvascular dysfunction. The aim of this study was to identify novel microvascular variables to determine the level of microvascular dysfunction in sepsis and its relationship with clinical variables. METHODS: This observational, prospective, cross-sectional study included 51 participants, of which 34 critically ill sepsis patients were recruited from intensive care units of a university hospital. Seventeen healthy volunteers served as controls. All participants underwent sublingual videomicroscopy by sidestream darkfield imaging. A new developed version of the Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell (RBC) velocity, RBC content, and blood flow in sublingual microvessels with diameters between 4 and 25 µm. RESULTS: A detailed analysis of adjacent diameter classes (1 µm each) of vessels between 4 and 25 µm revealed a severe reduction of vascular density in very small capillaries (5-7 µm), which correlated with markers of sepsis severity. Analysis of RBC velocity (VRBC) revealed a strong dependency between capillary and feed vessel VRBC in sepsis patients (R2 = 0.63, p < 0.0001) but not in healthy controls (R2 = 0.04, p = 0.43), indicating impaired capillary (de-)recruitment in sepsis. This finding enabled the calculation of capillary recruitment and dynamic capillary blood volume (CBVdynamic). Moreover, adjustment of PBR to feed vessel VRBC further improved discrimination between sepsis patients and controls by about 50%. By combining these dynamic microvascular and glycocalyx variables, we developed the microvascular health score (MVHSdynamic™), which decreased from 7.4 [4.6-8.7] in controls to 1.8 [1.4-2.7] in sepsis patients (p < 0.0001) and correlated with sepsis severity. CONCLUSION: We introduce new important diameter-specific quantification and differentiated analysis of RBC kinetics, a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect microvascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.

Quantifying Signal Quality for Joint Acoustic Emissions Using Graph-Based Spectral Embedding.

We present a new method for quantifying signal quality of joint acoustic emissions (JAEs) from the knee during unloaded flexion/extension (F/E) exercises. For ten F/E cycles, JAEs were recorded, in a clinical setting, from 34 healthy knees and 13 with a meniscus tear (n=24 subjects). The recordings were first segmented by F/E cycle and described using time and frequency domain features. Using these features, a symmetric k-nearest neighbor graph was created and described using a spectral embedding. We show how the underlying community structure of JAEs was comparable across joint health levels and was highly affected by artifacts. Each F/E cycle was scored by its distance from a diverse set of manually annotated, clean templates and removed if above the artifact threshold. We validate this methodology by showing an improvement in the distinction between the JAEs of healthy and injured knees. Graph community factor (GCF) was used to detect the number of communities in each recording and describe the heterogeneity of JAEs from each knee. Before artifact removal, there was no significant difference between the healthy and injured groups due to the impact of artifacts on the community construction. Following implementation of artifact removal, we observed improvement in knee health classification. The GCF value for the meniscus tear group was significantly higher than the healthy group (p<0.01). With more JAE recordings being taken in the clinic and at home, this paper addresses the need for a robust artifact removal method which is necessary for an accurate description of joint health.

Show me the evidence: Effectiveness of low-dose prophylaxis.

Prophylaxis is the gold standard treatment for haemophilia but requires more amount of clotting factor concentrates, than on demand therapy. Low dose prophylaxis is an alternative for countries with limited resources. There are data of evidence showing the superiority of low-dose prophylaxis than episodic treatment. Studies from China, India, Tunisia, Thailand and Indonesia reported experiences with low dose prophylaxis using outcome assessment. These studies have shown the effectiveness of various protocols regimen with once, twice or thrice injection of 10-15 UI Kg-1 per injection. These protocols allow reduction of joint bleeds and at least delay of joint damages. There is not enough long-term data nowadays, but low dose prophylaxis is certainly better than on demand therapy and should be considered as a first step of prophylaxis in some countries but not the final goal.

3D gait analysis, haemophilia joint health score, leg muscle laterality and biomarkers of joint damage: A cross-sectional comparative assessment of haemophilic arthropathy.

INTRODUCTION: 3D gait analysis has been proposed as a reproducible and valid method to assess abnormal gait patterns and to monitor disease progression in patients with haemophilia (PWH). AIM: This study aimed at comparing Gait Deviation Index (GDI) between adult PWH and healthy controls, and at assessing the agreement between outcome measures of haemophilic arthropathy. METHODS: Male PWH aged 18-49 years (prespecified subgroups: 18-25 vs 26-49 years) on prophylactic replacement therapy, and male healthy age-matched controls passed through a cross-sectional assessment panel. Besides the 3D gait analysis derived GDI, secondary outcomes included kinematic, kinetic and spatio-temporal gait parameters, the Haemophilia Joint Health Score (HJHS), electric impedance derived leg muscle laterality and inflammatory biomarkers. RESULTS: Patients with haemophilia (n = 18) walked slower, in shorter steps and accordingly with less functional range of motion in the hips and ankles, as compared to healthy controls (n = 24). Overall, PWH did not differ significantly in GDI and specific gait parameters. PWH had a higher mean HJHS (18.8 vs 2.6, P = .000) and leg muscle laterality (4.3% vs 1.5%, P = .004). A subgroup analysis revealed progressed gait pathology in PWH aged 26-49 years (not statistically significant). Leg muscle laterality was strongly correlated with HJHS (r = .76, P = .000), whereas GDI just moderately (r = -.39, P = .110). PWH had higher levels of the inflammatory markers CRP and IL-6. CONCLUSION: Progressed gait pathology was found in PWH, mainly those aged 26-49 years. Leg muscle laterality correlated strongly with HJHS and was identified as a promising tool for detecting progression and physiological consequences of haemophilic joint arthropathy.

Severe haemophilia A children on low-dose tertiary prophylaxis showed less joint deterioration and better maintenance of functional independence than children on on-demand treatment: A 6-year follow-up study.

BACKGROUND: In countries with limited resource, haemophilia patients have to choose low-dose prophylaxis or on-demand treatment (ODT) because of economic constraints. Whether low-dose prophylaxis can achieve better joint function outcome than ODT over long-term remains unclear. AIM: To investigate the long-term effect of low-dose tertiary prophylaxis versus ODT on joint health in severe haemophilia A children. METHODS: This was a retrospective study. We enrolled and followed 34 severe haemophilia boys in China receiving on-demand treatment (n = 18) or low-dose prophylaxis (10-15 IU/kg, 2-3 times per week) for a medium-term (6-18 months, n = 9) or longer-term (19-30 months, n = 7). We evaluated their haemophilia joint health score (HJHS) 2.1 and functional independence score in haemophilia (FISH) at baseline and at their 6-year follow-up visits. Their annual bleeding rate (ABR) and annual joint bleeding rate (AJBR) were also recorded. RESULTS: During the 6-year follow-up period, ABR and AJBR were similar between the 2 prophylaxis groups, with each of the 2 prophylaxis group rates being significantly better (lower) than the ODT group (P < .05). Compared to baseline values, evaluation at 6-year follow-up showed HJHS improvement in both prophylaxis groups, although significantly (P < .05) only in the longer-term prophylaxis group. The FISH score showed insignificant change in patients in each prophylaxis cohort, compared to significant worsening (P < .05) in the ODT group. CONCLUSION: Low-dose tertiary prophylaxis reduced ABR and AJBR of children with severe haemophilia and better maintained their functional independence by the FISH over the long term. Longer-term prophylaxis also improved their joint health status by the HJHS.

The paradox of aging and health-related quality of life in Asian Chinese: results from the Healthy Aging Longitudinal Study in Taiwan.

BACKGROUND: Declines in health, physical, cognitive, and mental function with age suggest a lower level of health-related quality of life (HRQoL) in late life; however, previous studies found that the associations were weak and varied, depending on the study designs and cohort characteristics. METHODS: The present study examined the paradox of aging in an East Asian context by regressing the age patterns of objective health indicators (physical, cognitive, and mental function), and subjective HRQoL (12-item Short Form, SF-12), on the independent and interactive effects of age and physical function in a cohort study of 5022 community-dwelling adults aged 55 and older in Taiwan. RESULTS: Age patterns differed across measures. The SF-12 mental health score (MCS) showed a slight positive association with age and this effect remained stable after controlling for various age-related covariates. The SF-12 physical health score (PCS), in turn, was negatively associated with age. Age differences in PCS were fully explained by age decrements in objective physical health. However, consistent with the so-called paradox of aging, the association between objective and subjective physical health weakened with age. CONCLUSION: These findings add to prior evidence indicating that - in spite of objective health decrements - subjective HRQoL is maintained in later life among Asian Chinese. Also, these paradoxical patterns appear to vary for mental and physical components of HRQoL, and future research is needed to explore the underlying mechanism. TRIAL REGISTRATION: Healthy Aging Longitudinal Study in Taiwan (HALST) is retrospectively registered at ClinicalTrials.gov on January 24, 2016 with trial registration number NCT02677831.

Advanced magnetic resonance imaging of cartilage components in haemophilic joints reveals that cartilage hemosiderin correlates with joint deterioration.

INTRODUCTION: Evidence suggests that toxic iron is involved in haemophilic joint destruction. AIM: To determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease. METHODS: Adults with haemophilia A or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results. RESULTS: MRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs  = -0.81, P < 0.001) and MRI scores (rs  = -0.52, P = 0.037). This was unexpected since UTE-T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects. Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE-T2* values. CONCLUSIONS: Iron accumulation can occur in cartilage (not only in synovium) and shows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint-specific MRI T2* sequences, may guide treatment optimization.

Treatment regimens and outcomes in severe and moderate haemophilia A in the UK: The THUNDER study.

INTRODUCTION: The THUNDER study provides an analysis of treatment patterns and outcomes in UK patients with severe or moderate haemophilia A (SHA/MHA) in 2015. METHODS: Patients with SHA or MHA registered with the UK National Haemophilia Database (NHD) were segregated by severity, inhibitor status and age. Haemophilia joint health score (HJHS) was derived from NHD records and treatment regimen and annualized bleed/joint-bleed rate (ABR/AJBR) from Haemtrack (HT) in HT-compliant patients. RESULTS: We report 1810 patients with SHA and 864 with MHA. Prophylaxis was used in 94.9% (n = 130/137) of HT-compliant children <12 years with SHA, falling to 74.1% (n = 123/166) aged ≥40 years. Median ABR increased with age (1.0, IQR 0.0-5.0, <12 years; 3.0 IQR, 1.0-8.0, ≥40 years). Inhibitors were present in 159 (8.8%) SHA and 34 (3.9%) MHA. Median ABR increased from 2.0 (<12 years) to 21.0 (≥40 years) in SHA inhibitor patients using prophylaxis. Prophylaxis was used by 68.8% of HT-compliant MHA patients (n = 106) (median FVIII baseline 0.01 IU/mL) associated with a median (IQR) ABR of 3.0 (1.0-7.0). Median HJHS (n = 453) increased with age in SHA and MHA. Median (IQR) HJHS was higher in SHA inhibitor (17.0, 0.0-64.5) than non- or past inhibitor patients (7.0, 0.0-23.0). CONCLUSIONS: Increasing ABR with age persists despite current prophylaxis regimens. SHA and MHA had similar ABR/AJBR and HJHS, leading to a suspicion that a subgroup of MHA may be relatively undertreated. More intensive prophylaxis may improve outcomes, but this requires further study.