Healthcare professionals\u27 perspectives on working with patient-generated data for supporting person-centred HIV care

BACKGROUND We report on a UK study with Healthcare Professionals (HCPs) providing routine adult HIV care, to understand their experiences of working with Patient-generated Data (PGData) including Patient Reported Outcome Measures (PROMs), with the aim to inform the design of tools (e.g. electronic patient questionnaires) for supporting Person-centred Care. METHOD Semi-structured (individual and group) interviews were conducted (March 2020 to October 2022) with 15 HCPs (5 men, 10 women) from multi-disciplinary teams at: a large London HIV outpatient clinic (A); an Infectious Diseases service in Northern England (B). Due to COVID-19, all but one interview took place online. 90-minute interviews were supported by persona-based scenarios and infographics, prompting participants\u27 engagement with individual lived experiences. Transcribed audio-recordings were coded using Reflexive Thematic Analysis. Participants included: seven physicians; three psychologists; two nurses; health advisor; pharmacist; peer support worker. Two physicians, one nurse, and one psychologist at Clinic B participated in follow-up interviews focussing on PROMs. RESULTS Physicians needed to balance patient agendas with clinician agendas, highlighting the practical reality of time constraints for achieving this balance. Nurses and psychologists highlighted wider patient circumstances impacting personal information sharing, plus health inequities shaping access to internet-mediated tools. Post-pandemic, preference for in-person consultation was emphasised for good communication. The value of PROMs in HIV care was perceived in: facilitating face-to-face conversation with patients who struggle to articulate problems or discuss difficult topics; co-defining an agenda; helping both parties ask the right questions and acquire contextual information; tracking progress; helping meet BHIVA standards; capturing and evaluating experience of attending services; tailoring services. Differing use of PROMs at each clinic reflected geographical diversity and type of specialist providing the service. Perceived challenges of using PROMs for HIV care include: patients’ confidentiality concerns; questioning validity of PGData - honesty in self-reports, context of capture; time constraints for interpreting data; system interoperability for data processing and access by HCPs and patients. Design considerations include: visual presentation, for readability, discretion, accessibility; language formats; value of capturing information between consultations. CONCLUSION Interview findings evidence UK HIV Healthcare Professionals\u27 perspectives on how PGData including PROMs may support Person-centred Care, plus considerations for designing supportive data collection tools

Trust, Identity, Privacy, and Security Considerations for Designing a Peer Data Sharing Platform Between People Living With HIV

Resulting from treatment advances, the Human Immunodeficiency Virus (HIV) is now a long-term condition, and digital solutions are being developed to support people living with HIV in self-management. Sharing their health data with their peers may support self-management, but the trust, identity, privacy and security (TIPS) considerations of people living with HIV remain underexplored. Working with a peer researcher who is expert in the lived experience of HIV, we interviewed 26 people living with HIV in the United Kingdom (UK) to investigate how to design a peer data sharing platform. We also conducted rating activities with participants to capture their attitudes towards sharing personal data. Our mixed methods study showed that participants were highly sophisticated in their understanding of trust and in their requirements for robust privacy and security. They indicated willingness to share digital identity attributes, including gender, age, medical history, health and well-being data, but not details that could reveal their personal identity. Participants called for TIPS measures to foster and to sustain responsible data sharing within their community. These findings can inform the development of trustworthy and secure digital platforms that enable people living with HIV to share data with their peers and provide insights for researchers who wish to facilitate data sharing in other communities with stigmatised health conditions

Polonium-210 poisoning: a first-hand account

Background: Polonium-210 (210Po) gained widespread notoriety after the poisoning and subsequent death of Mr Alexander Litvinenko in London, UK, in 2006. Exposure to 210Po resulted initially in a clinical course that was indistinguishable from infection or exposure to chemical toxins, such as thallium. Methods: A 43-year-old man presented to his local hospital with acute abdominal pain, diarrhoea, and vomiting, and was admitted to the hospital because of dehydration and persistent gastrointestinal symptoms. He was initially diagnosed with gastroenteritis and treated with antibiotics. Clostridium difficile toxin was subsequently detected in his stools, which is when he first raised the possibility of being poisoned and revealed his background and former identity, having been admitted under a new identity with which he had been provided on being granted asylum in the UK. Within 6 days, the patient had developed thrombocytopenia and neutropenia, which was initially thought to be drug induced. By 2 weeks, in addition to bone marrow failure, he had evidence of alopecia and mucositis. Thallium poisoning was suspected and investigated but ultimately dismissed because blood levels of thallium, although raised, were lower than toxic concentrations. The patient continued to deteriorate and within 3 weeks had developed multiple organ failure requiring ventilation, haemofiltration, and cardiac support, associated with a drop in consciousness. On the 23rd day after he first became ill, he suffered a pulseless electrical activity cardiorespiratory arrest from which he could not be resuscitated and was pronounced dead. Findings: Urine analysis using gamma-ray spectroscopy on day 22 showed a characteristic 803 keV photon emission, raising the possibility of 210Po poisoning. Results of confirmatory analysis that became available after the patient's death established the presence of 210Po at concentrations about 109-times higher than normal background levels. Post-mortem tissue analyses showed autolysis and retention of 210Po at lethal doses in several organs. On the basis of the measured amounts and tissue distribution of 210Po, it was estimated that the patient had ingested several 1000 million becquerels (a few GBq), probably as a soluble salt (eg, chloride), which delivered very high and fatal radiation doses over a period of a few days. Interpretation: Early symptoms of 210Po poisoning are indistinguishable from those of a wide range of chemical toxins. Hence, the diagnosis can be delayed and even missed without a high degree of suspicion. Although body surface scanning with a standard Geiger counter was unable to detect the radiation emitted by 210Po, an atypical clinical course prompted active consideration of poisoning with radioactive material, with the diagnosis ultimately being made with gamma-ray spectroscopy of a urine sample

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

Gut immune components are severely compromised among persons with AIDS, which allows increased translocation of bacterial lipopolysaccharides (LPS) into the systemic circulation. These microbial LPS are reportedly increased in chronically HIV-infected individuals and findings have correlated convincingly with measures of immune activation. Immune reconstitution inflammatory syndrome (IRIS) is an adverse consequence of the restoration of pathogen-specific immune responses in a subset of HIV-infected subjects with underlying latent infections during the initial months of highly active antiretroviral treatment (HAART). Whether IRIS is the result of a response to a high antigen burden, an excessive response by the recovering immune system, exacerbated production of pro-inflammatory cytokines or a lack of immune regulation due to inability to produce regulatory cytokines remains to be determined. We theorize that those who develop IRIS have a high burden of proinflammatory cytokines produced also in response to systemic bacterial LPS that nonspecifically act on latent mycobacterial antigens. We also hypothesize that subjects that do not develop IRIS could have developed either tolerance (anergy) to persistent LPS/tubercle antigens or could have normal FOXP3+ gene and that those with defective FOXP3+ gene or those with enormous plasma LPS could be vulnerable to IRIS. The measure of microbial LPS, anti-LPS antibodies and nonspecific plasma cytokines in subjects on HAART shall predict the role of these components in IRIS

Does CD4+CD25+foxp3+ cell (Treg) and IL-10 profile determine susceptibility to immune reconstitution inflammatory syndrome (IRIS) in HIV disease?

HIV-specific T-lymphocyte responses that underlie IRIS are incomplete and largely remain hypothetical. Of the several mechanisms presented by the host to control host immunological damage, Treg cells are believed to play a critical role. Using the available experimental evidence, it is proposed that enormous synthesis of conventional FoxP3- Th cells (responsive) often renders subjects inherently vulnerable to IRIS, whereas that of natural FoxP3+ Treg cell synthesis predominate among subjects that may not progress to IRIS. We also propose that IRIS non-developers generate precursor T-cells with a high avidity to generate CD4+CD25+FoxP3+ Tregs whereas IRIS developers generate T-cells of intermediate avidity yielding Th0 cells and effector T-cells to mediate the generation of proinflammatory cytokines in response to cell-signaling factors (IL-2, IL-6 etc.). Researchers have shown that IL-10 Tregs (along with TGF-β, a known anti-inflammatory cytokine) limit immune responses against microbial antigens in addition to effectively controlling HIV replication, the prime objective of HAART. Although certain technical limitations are described herein, we advocate measures to test the role of Tregs in IRIS

Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure

Insulators and imprinting from flies to mammals

The nuclear factor CTCF has been shown to be necessary for the maintenance of genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now report in BMC Biology that the mechanisms responsible for maintaining the imprinted state in Drosophila may be evolutionarily conserved and that CTCF may also play a critical role in this process