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BMJ Paediatrics Open May 2024In paediatric oncology, 'breaking bad news'-BBN-like cancer diagnosis is perceived as particularly challenging. Enabling a trialogue between children with their...
INTRODUCTION
In paediatric oncology, 'breaking bad news'-BBN-like cancer diagnosis is perceived as particularly challenging. Enabling a trialogue between children with their relatives and health professionals requires profound communication skills. Lacking the skills, experience or adequate support tools might result in negative consequences for both paediatric oncologists as BBN transmitters and BBN receivers as children with cancer and their relatives.In contrast to oncology for adults, multiperspective studies that explore BBN experience and specific support needs are rare, especially in Germany. Systematically developed and practically piloted support instruments, which address the specific needs of paediatric oncology, are missing.
OBJECTIVE
To systematically design and mature in practice an orientation compass for preparing, delivering and following up on BBN conversations in paediatric oncology-so-called Orientierungskompass zur Übermittlung schwerwiegender Nachrichten in der Kinderonkologie (OKRA).
METHODS AND ANALYSIS
OKRA is based on a QUAL-quant mixed study design, comprising two phases. Four groups will contribute (1) experts through personal experience (representatives for children receiving BBN and their parents), (2) medical care providers and representatives of national medical societies, (3) ambulant psychosocial/psychological support providers and (4) researchers. In phase 1, multiperspective knowledge is generated through a participatory group Delphi that involves in-depth interviews, focus group discussions and questionnaires. This process culminates in formulating theses for a high-quality BBN process (output phase 1). In phase 2, based on the theses, a pilot orientation compass is designed. Through iterative cycles with the participatory action research method, this instrument will be piloted in three paediatric oncological settings and consequently optimised.
ETHICS AND DISSEMINATION
OKRA was approved on 19 September 2023 by the ethics committee of the Medical Faculty of the University of Cologne (No. 23-1187). After project completion, the OKRA compass will be distributed to multidisciplinary paediatric oncology teams throughout Germany.
TRIAL REGISTRATION NUMBER
DRKS00031691.
Topics: Humans; Child; Truth Disclosure; Germany; Neoplasms; Medical Oncology; Pediatrics; Communication; Physician-Patient Relations; Parents; Professional-Family Relations
PubMed: 38823801
DOI: 10.1136/bmjpo-2023-002473 -
Journal For Immunotherapy of Cancer May 2024To accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is...
BACKGROUND
To accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is necessary. Using a droplet-based microfluidic platform, we have established a method for multiparameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) natural killer (NK) cells are of increased interest in the current immunotherapy landscape and thus provide an optimal model for evaluating our novel methodology.
METHODS
For this approach, NK cells transduced with a CD19 CAR were compared with non-transduced NK cells in their ability to kill a lymphoma cell line. Using our microfluidic platform, we were able to quantify the increase in cytotoxicity and synaptic contact formation of CAR NK cells over non-transduced NK cells. We then optimized our droplet sorter and successfully used it to separate NK cells based on target cell killing to perform transcriptomic analyses.
RESULTS
Our data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for accelerating the pre-clinical screening of future immunotherapy treatments.
CONCLUSIONS
This study provides a new potential approach for enhanced early screening of immunotherapies to improve their development, with a highly relevant cell model to demonstrate. Additionally, our validation studies provided some potential insights into transcriptomic determinants influencing CAR NK cytotoxicity.
Topics: Killer Cells, Natural; Humans; Single-Cell Analysis; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Phenotype; Cytotoxicity, Immunologic; Genotype; Cell Line, Tumor
PubMed: 38821719
DOI: 10.1136/jitc-2024-008912 -
Journal For Immunotherapy of Cancer May 2024Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite...
Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study.
BACKGROUND
Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.
METHODS
In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC received nivolumab 240 mg plus relatlimab 160 mg intravenously every 2 weeks. The primary end point was investigator-assessed objective response rate (ORR).
RESULTS
A total of 50 previously treated patients received nivolumab plus relatlimab. With median follow-up of 47.4 (range 43.9-49.2) months, investigator-assessed ORR was 50% (95% CI 36% to 65%) and disease control rate was 70% (95% CI 55% to 82%). The median time to response per investigator was 2.8 (range 1.3-33.1) months, and median duration of response was 42.7 (range 2.8-47.0+) months. The median progression-free survival per investigator was 27.5 (95% CI 5.3 to 43.7) months with a progression-free survival rate at 3 years of 38%, and median overall survival was not reached (95% CI 17.2 months to not estimable), with a 56% overall survival rate at 3 years. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (24%), asthenia (16%), and hypothyroidism (12%). Grade 3 or 4 TRAEs were reported in 14% of patients, and TRAEs of any grade leading to discontinuation were observed in 8% of patients. No treatment-related deaths were reported.
CONCLUSIONS
Nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR metastatic CRC.
TRIAL REGISTRATION NUMBER
NCT02060188.
Topics: Humans; Nivolumab; Colorectal Neoplasms; Microsatellite Instability; Female; Male; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; DNA Mismatch Repair; Aged, 80 and over; Neoplasm Metastasis
PubMed: 38821718
DOI: 10.1136/jitc-2023-008689 -
BMJ Open May 2024The liberal use of blood cultures in emergency departments (EDs) leads to low yields and high numbers of false-positive results. False-positive, contaminated cultures...
INTRODUCTION
The liberal use of blood cultures in emergency departments (EDs) leads to low yields and high numbers of false-positive results. False-positive, contaminated cultures are associated with prolonged hospital stays, increased antibiotic usage and even higher hospital mortality rates. This trial aims to investigate whether a recently developed and validated machine learning model for predicting blood culture outcomes can safely and effectively guide clinicians in withholding unnecessary blood culture analysis.
METHODS AND ANALYSIS
A randomised controlled, non-inferiority trial comparing current practice with a machine learning-guided approach. The primary objective is to determine whether the machine learning based approach is non-inferior to standard practice based on 30-day mortality. Secondary outcomes include hospital length-of stay and hospital admission rates. Other outcomes include model performance and antibiotic usage. Participants will be recruited in the EDs of multiple hospitals in the Netherlands. A total of 7584 participants will be included.
ETHICS AND DISSEMINATION
Possible participants will receive verbal information and a paper information brochure regarding the trial. They will be given at least 1 hour consideration time before providing informed consent. Research results will be published in peer-reviewed journals. This study has been approved by the Amsterdam University Medical Centers' local medical ethics review committee (No 22.0567). The study will be conducted in concordance with the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act, General Data Privacy Regulation and Medical Device Regulation.
TRIAL REGISTRATION NUMBER
NCT06163781.
Topics: Humans; Emergency Service, Hospital; Machine Learning; Blood Culture; Netherlands; Hospital Mortality; Equivalence Trials as Topic; Length of Stay; Randomized Controlled Trials as Topic; Unnecessary Procedures; Anti-Bacterial Agents
PubMed: 38821574
DOI: 10.1136/bmjopen-2024-084053 -
Stroke and Vascular Neurology May 2024Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery...
BACKGROUND
Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals.
METHODS
We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups.
RESULTS
Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform.
CONCLUSIONS
Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.
PubMed: 38821555
DOI: 10.1136/svn-2023-002831 -
Stroke and Vascular Neurology May 2024Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH),...
BACKGROUND AND OBJECTIVES
Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed the detailed neurological indications for LAAC and outcomes after LAAC in high ICH risk patients.
METHODS
Study population included consecutive patients with NVAF who underwent LAAC in a single hospital network between January 2015 and October 2021 because of prior ICH or the presence of high ICH risk imaging markers on brain MRI (cerebral microbleeds (CMBs)). Primary safety and efficacy outcome measures were the occurrence of ICH and thromboembolic events, respectively, after LAAC.
RESULTS
Among 146 patients with NVAF who underwent LAAC for high ICH risk, 122 had a history of ICH, while 24 presented with high ICH risk imaging markers only. Mean age was 75.7±7.61, 42 (28.8%) were women. Mean CHADS-VASc score was 5.23±1.52. Of 122 patients with ICH history, 58 (47.5%) had intraparenchymal haemorrhage (IPH), 40 (32.8%) had traumatic ICH (T-ICH) and 18 (14.7%) had non-traumatic subdural haemorrhage. Of 85 patients with brain MRIs including necessary sequences, 43 (50.6%) were related to cerebral amyloid angiopathy and 37 (43.5%) to hypertensive microangiopathy. While 70% of patients were discharged on oral anticoagulants (OAC), 92% were not taking OAC at 1 year. Over 2.12 years mean follow-up, one patient had recurrent non-traumatic IPH (incidence rate (IR) 0.32 per 100 patient-years), five had T-ICH (IR 1.61 per 100 patient-years) and six had an ischaemic stroke (IR 1.94 per 100 patient-years).
CONCLUSIONS
Among patients with NVAF at high ICH risk, LAAC demonstrated a low risk of recurrent ICH or ischaemic stroke compared with previously published data. LAAC in high ICH risk populations should be considered in clinical practice per FDA approval and recent guidelines.
PubMed: 38821554
DOI: 10.1136/svn-2024-003142 -
JMIR Research Protocols May 2024The results of telemedicine intervention studies in patients with heart failure (HF) to reduce rehospitalization rate and mortality by early detection of HF...
Evaluation of Ambient Sensor Systems for the Early Detection of Heart Failure Decompensation in Older Patients Living at Home Alone: Protocol for a Prospective Cohort Study.
BACKGROUND
The results of telemedicine intervention studies in patients with heart failure (HF) to reduce rehospitalization rate and mortality by early detection of HF decompensation are encouraging. However, the benefits are lower than expected. A possible reason for this could be the fact that vital signs, including blood pressure, heart rate, heart rhythm, and weight changes, may not be ideal indicators of the early stages of HF decompensation but are more sensitive for acute events triggered by ischemic episodes or rhythm disturbances. Preliminary results indicate a potential role of ambient sensor-derived digital biomarkers in this setting.
OBJECTIVE
The aim of this study is to identify changes in ambient sensor system-derived digital biomarkers with a high potential for early detection of HF decompensation.
METHODS
This is a prospective interventional cohort study. A total of 24 consecutive patients with HF aged 70 years and older, living alone, and hospitalized for HF decompensation will be included. Physical activity in the apartment and toilet visits are quantified using a commercially available, passive, infrared motion sensing system (DomoHealth SA). Heart rate, respiration rate, and toss-and-turns in bed are recorded by using a commercially available Emfit QS device (Emfit Ltd), which is a contact-free piezoelectric sensor placed under the participant's mattress. Sensor data are visualized on a dedicated dashboard for easy monitoring by health professionals. Digital biomarkers are evaluated for predefined signs of HF decompensation, including particularly decreased physical activity; time spent in bed; increasing numbers of toilet visits at night; and increasing heart rate, respiration rate, and motion in bed at night. When predefined changes in digital biomarkers occur, patients will be called in for clinical evaluation, and N-terminal pro b-type natriuretic peptide measurement (an increase of >30% considered as significant) will be performed. The sensitivity and specificity of the different biomarkers and their combinations for the detection of HF decompensation will be calculated.
RESULTS
The study is in the data collection phase. Study recruitment started in February 2024. Data analysis is scheduled to start after all data are collected. As of manuscript submission, 5 patients have been recruited. Results are expected to be published by the end of 2025.
CONCLUSIONS
The results of this study will add to the current knowledge about opportunities for telemedicine to monitor older patients with HF living at home alone by evaluating the potential of ambient sensor systems for this purpose. Timely recognition of HF decompensation could enable proactive management, potentially reducing health care costs associated with preventable emergency presentations or hospitalizations.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06126848; https://clinicaltrials.gov/study/NCT06126848.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/55953.
Topics: Humans; Heart Failure; Prospective Studies; Aged; Early Diagnosis; Female; Male; Aged, 80 and over; Cohort Studies; Biomarkers; Telemedicine; Heart Rate; Independent Living
PubMed: 38820577
DOI: 10.2196/55953 -
JMIR Human Factors May 2024Type 2 diabetes (T2D) tremendously affects patient health and health care globally. Changing lifestyle behaviors can help curb the burden of T2D. However, health...
BACKGROUND
Type 2 diabetes (T2D) tremendously affects patient health and health care globally. Changing lifestyle behaviors can help curb the burden of T2D. However, health behavior change is a complex interplay of medical, behavioral, and psychological factors. Personalized lifestyle advice and promotion of self-management can help patients change their health behavior and improve glucose regulation. Digital tools are effective in areas of self-management and have great potential to support patient self-management due to low costs, 24/7 availability, and the option of dynamic automated feedback. To develop successful eHealth solutions, it is important to include stakeholders throughout the development and use a structured approach to guide the development team in planning, coordinating, and executing the development process.
OBJECTIVE
The aim of this study is to develop an integrated, eHealth-supported, educational care pathway for patients with T2D.
METHODS
The educational care pathway was developed using the first 3 phases of the Center for eHealth and Wellbeing Research roadmap: the contextual inquiry, the value specification, and the design phase. Following this roadmap, we used a scoping review about diabetes self-management education and eHealth, past experiences of eHealth practices in our hospital, focus groups with health care professionals (HCPs), and a patient panel to develop a prototype of an educational care pathway. This care pathway is called the Diabetes Box (Leiden University Medical Center) and consists of personalized education, digital educational material, self-measurements of glucose, blood pressure, activity, and sleep, and a smartphone app to bring it all together.
RESULTS
The scoping review highlights the importance of self-management education and the potential of telemonitoring and mobile apps for blood glucose regulation in patients with T2D. Focus groups with HCPs revealed the importance of including all relevant lifestyle factors, using a tailored approach, and using digital consultations. The contextual inquiry led to a set of values that stakeholders found important to include in the educational care pathway. All values were specified in biweekly meetings with key stakeholders, and a prototype was designed. This prototype was evaluated in a patient panel that revealed an overall positive impression of the care pathway but stressed that the number of apps should be restricted to one, that there should be no delay in glucose value visualization, and that insulin use should be incorporated into the app. Both patients and HCPs stressed the importance of direct automated feedback in the Diabetes Box.
CONCLUSIONS
After developing the Diabetes Box prototype using the Center for eHealth and Wellbeing Research roadmap, all stakeholders believe that the concept of the Diabetes Box is useful and feasible and that direct automated feedback and education on stress and sleep are essential. A pilot study is planned to assess feasibility, acceptability, and usefulness in more detail.
Topics: Humans; Diabetes Mellitus, Type 2; Telemedicine; Male; Female; Patient Education as Topic; Middle Aged; Self-Management; Self Care
PubMed: 38819880
DOI: 10.2196/45055 -
Annals of Indian Academy of Neurology May 2024Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke.
BACKGROUND
Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke.
OBJECTIVES
To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke.
MATERIALS AND METHODS
In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents.
RESULTS
A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628).
CONCLUSION
The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.
PubMed: 38819417
DOI: 10.4103/aian.aian_59_24 -
Annals of Indian Academy of Neurology May 2024Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer...
BACKGROUND
Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer functional outcomes. However, recent randomized controlled trials (RCTs) indicate that EVT for large vessel occlusion (LVO) strokes improves functional outcomes compared to medical management alone, despite higher hemorrhagic transformation rates, with no corresponding increase in symptomatic intracerebral hemorrhage (sICH) rates. The real-world outcomes of this intervention in Indian patients remain underexplored.
OBJECTIVES
To evaluate the real-world outcomes of EVT for large core acute ischemic strokes with LVO in an Indian population.
METHODS
We conducted a single-center, retrospective observational study using a 7 years prospective database of EVT in anterior circulation stroke patients. Patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3-5 were included. Clinical and radiologic data were analyzed, with the primary endpoint being 90-day modified Rankin scale (mRS) scores. Safety outcomes included rates of sICH and mortality. Descriptive statistical analysis was done using Microsoft Excel.
RESULTS
The study included 25 patients who met the inclusion criteria. Mean age of patients was 52.9 ± 14.3 years, and there were 13 (52%) males. Median ASPECTS was 5 (interquartile range 4-5). Successful recanalization, classified by modified Thrombolysis in Cerebral Infarction score, was 92%. Good functional recovery, that is, 90-day mRS 0-3, was achieved in nine (36%) patients. Safety outcomes: sICH was seen in four (16%) and mortality was reported in nine (36%) patients.
CONCLUSIONS
Our results reaffirm findings from RCTs, provide updated real-world evidence, and suggest that EVT is a viable option to be considered in selected patients with large core ischemic infarcts.
PubMed: 38819415
DOI: 10.4103/aian.aian_53_24