Bleeding phenotype of patients with moderate haemophilia A and B assessed by thromboelastometry and thrombin generation

Introduction Predicting the bleeding phenotype is crucial for the management of patients with moderate haemophilia. Global coagulation assays evaluate haemostasis more comprehensively than conventional methods. Aim To explore global coagulation assays and the bleeding phenotype of patients with moderate haemophilia A (MHA) and B (MHB). Methods The MoHem study is a cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Thromboelastometry in whole blood and thrombin generation (TG) in platelet-poor plasma (1, 2.5 and 5 pM tissue factor (TF)) were compared with joint health (Haemophilia Joint Health Score (HJHS)) and treatment modality. Results We report on 61 patients from Oslo and Helsinki: 24 MHA and 37 MHB. By TG (2.5 pM TF), patients who had been without replacement therapy during the previous 12 months depicted higher endogenous thrombin potential (P = .03). In contrast, those who had low ETP (< median) captured higher HJHS (P = .02). Patients who had undergone orthopaedic surgery generated least thrombin (P = .02). By thromboelastometry, those without the need of factor consumption had short clotting times, and quick times to maximum velocity (< median values) (P = .03). Factor VIII/factor IX activity (FVIII/FIX:C) did not align with the bleeding phenotype, but FIX:C Conclusion TG differentiated patients with moderate haemophilia according to HJHS, annual factor consumption, and whether orthopaedic surgery had been performed. Thromboelastometry differentiated according to factor consumption only. Global coagulation assays may assist predicting the bleeding phenotype in moderate haemophilia.Peer reviewe

A social-technological epistemology of clinical decision-making as mediated by imaging.

In recent years there has been growing attention to the epistemology of clinical decision-making, but most studies have taken the individual physicians as the central object of analysis. In this paper we argue that knowing in current medical practice has an inherently social character and that imaging plays a mediating role in these practices. We have analyzed clinical decision-making within a medical expert team involved in diagnosis and treatment of patients with pulmonary hypertension (PH), a rare disease requiring multidisciplinary team involvement in diagnosis and management. Within our field study, we conducted observations, interviews, video tasks, and a panel discussion. Decision-making in the PH clinic involves combining evidence from heterogeneous sources into a cohesive framing of a patient, in which interpretations of the different sources can be made consistent with each other. Because pieces of evidence are generated by people with different expertise and interpretation and adjustments take place in interaction between different experts, we argue that this process is socially distributed. Multidisciplinary team meetings are an important place where information is shared, discussed, interpreted, and adjusted, allowing for a collective way of seeing and a shared language to be developed. We demonstrate this with an example of image processing in the PH service, an instance in which knowledge is distributed over multiple people who play a crucial role in generating an evaluation of right heart function. Finally, we argue that images fulfill a mediating role in distributed knowing in 3 ways: first, as enablers or tools in acquiring information; second, as communication facilitators; and third, as pervasively framing the epistemic domain. With this study of clinical decision-making in diagnosis and treatment of PH, we have shown that clinical decision-making is highly social and mediated by technologies. The epistemology of clinical decision-making needs to take social and technological mediation into account

Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model

The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study

Introduction Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB). Aim To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia. Methods A cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD-US and HJHS 2.1. Results We assessed 693 joints in 118 patients. HEAD-US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0-0), knees 0 (0-0) and ankles 0 (0-1). Respectively, by HJHS: elbows 0 (0-1), knees 0 (0-1) and ankles 0 (0-1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD-US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD-US correlated strongly with HJHS (elbows r = .70, knees r = .60 and ankles r = .65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD-US >= 1 point. Moreover, 26% had HJHS findings without HEAD-US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD-US. Conclusion Overall, the joints attained low scores implying good joint health. HEAD-US correlated strongly with HJHS. In 5%, HEAD-US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD-US, thus not necessarily reflecting arthropathy. HEAD-US therefore improves the joint assessment in moderate haemophilia.Peer reviewe

Patients recording clinical encounters: a path to empowerment? Assessment by mixed methods

OBJECTIVE: To examine the motivations of patients recording clinical encounters, covertly or otherwise, and why some do not wish to record encounters. DESIGN: Mixed-methods analysis of survey data and nested semistructured interviews. SETTING: Survey to UK audience, using social media and radio broadcast. PARTICIPANTS: 168 survey respondents, of whom 161 were 18 years of age or older (130 completions). Of the 56 participants who agreed to be contacted, we included data from 17 interviews. RESULTS: 19 (15%) respondents indicated having secretly recorded a clinical encounter and 14 (11%) were aware of someone who had secretly recorded a clinical encounter. 45 (35%) said they would consider recording secretly and 44 (34%) said they would record after asking permission. Totally, 69% of respondents indicated their desire to record clinical encounters, split equally between wanting to do so covertly or with permission. Thematic analysis of the interviews showed that most patients are motivated by the wish to replay, relisten and share the recording with others. Some are also motivated by the idea of owning a personal record, and its potential use as verification of a poor healthcare experience. The rationale for permission seeking was based on the wish to prioritise a trusting relationship with a health professional. Those who preferred to record covertly described a pre-existing lack of trust, a fear that recording would be denied, and a concern that an affronted clinician would deny them access to future care. There was a general wish that recording should be facilitated. CONCLUSIONS: Patients' prime motivation for recording is to enhance their experience of care, and to share it with others. Patients know that recording challenges the 'ceremonial order of the clinic', and so some decide to act covertly. Patients wanted clearer, more permissive policies to be developed

A digital advocate? Reactions of rural people who experience homelessness to the idea of recording clinical encounters

Are the benefits of recording clinical encounters shared across different groups, or do they vary based on social position? Studies show that educated patients record their clinical visits to enhance their experience, but very little is known about recording benefits among hard-to-reach populations. ObjectiveTo examine the reactions of homeless people to the idea of using a smartphone to record their own clinical encounter, either covertly or with permission from their physician. MethodWe conducted semi-structured interviews with individuals at a temporary housing shelter in Northern New England. A thematic analysis identified themes that were iteratively refined into representative groups. ResultsEighteen (18) interviews were conducted, 12 with women and six with men. Initial reactions to clinical recordings were positive (11 of 18). A majority (17 of 18) were willing to use recordings in future visits. A thematic analysis characterized data in two ways: (i) by providing reliable evidence for review, they functioned as an advocacy measure for patients; (ii) by promoting transparency and levelling social distance, this technology modified clinical relationships. DiscussionRecordings permitted the sharing of data with others, providing tangible proof of behaviour and refuting misconceptions. Asking permission to record appeared to modify relationships and level perceived social distance with clinicians. ConclusionsWe found that while many rural, disadvantaged individuals felt marginalized by the wide social distance between themselves and their clinicians, recording technology may serve as an advocate by holding both patients and doctors accountable and by permitting the burden of clinical proof to be shared

Do too many cooks spoil the broth? The effect of observers on doctor-patient interaction

Context The presence of additional medical personnel in consultations alters the focus of the doctor-patient interaction. Patients feel excluded from the interaction and relegated to the role of a non-person or prop, which leads to a loss of autonomy. Previous research has considered the psychological effects of the presence of additional persons on the interaction, but few studies have considered how these additional persons affect the performances of the consulting doctor and patient in the interaction. Methods A linguistic study drawing on the methods of discourse analysis was conducted to consider how the presence of additional medical personnel in the consultation alters doctors' responses to patients' questions, their management of patient-initiated topics, and their use of invitations to ask questions. Results When additional professionals were present in the consultation, the consultations were significantly longer than control group consultations (p=0.04) and significantly more patient-initiated topics remained unresolved at the close of the consultation (p=0.04). In consultations in which students were present, markedly fewer patient questions were answered than in control group consultations, and there was a notable reduction in the number of overt invitations to ask questions (both differences approached significance). There was, however, a significant reduction (p≤0.01) in the proportion of patient-initiated topics that were deferred when students were present in the consultation. Conclusions Previous research has identified a loss of patient focus when a patient sees doctors en masse. The results from the present study suggest that the presence of additional medical personnel can distract the focus of a consultation away from the patient, particularly when the additional participants are professionals rather than students. Further research is required to develop a greater understanding of multiple-doctor-patient interactions. A training programme should be developed to train consulting doctors at teaching hospitals to manage these multiple-doctor-patient consultations more effectively. Discuss ideas arising from this article at '' © Blackwell Publishing Ltd 2012