Commentary on: Vanzella LM, Cotie LM, Flores-Hukom M, Marzolini S, Konidis R, Ghisi GLM. Patients' Perceptions of Hybrid and Virtual-Only Care Models During the Cardiac Rehabilitation Patient Journey: A Qualitative Study. J Cardiovasc Nurs. Published online January 5, 2024.
Implications for practice and research The use of theoretical models integrating well-recognised techniques (eg, goal setting, action planning, telemonitoring, individual assessment/tailoring) to guide virtual cardiac rehabilitation (CR) is essential. Apart from teleconferencing, using advanced wearable devices, analytics and artificial intelligence techniques may improve personalised exercise and educational content capacity of future virtual CR studies.
Cardiac rehabilitation (CR) is a recommended treatment for patients with cardiovascular disease (CVDs), given the rising number of cardiac incidents due to ageing population and modern lifestyles.
by Ying Li, Jing Jia, Runze Lu, Liyan Dong, Lizhu Fang, Litao Sun, Zongyi Zhang, Qing Duan, Lijie Zhang, Kunzheng Lv, Huilai Ma
BackgroundQingdao, a historically high-risk area for hemorrhagic fever with renal syndrome (HFRS) in China, is undergoing agricultural mechanization and urbanization. However, the specific risk factors for HFRS in this context remain unclear. This study sought to determine the risk factors for HFRS in Qingdao.
MethodsCommunity-based, 1:2 case-control study. Each case was matched with two healthy neighborhood controls based on biological sex, age, and the same neighborhood or village. Univariate and multivariate conditional logistic regression analyses were performed. Furthermore, stratified analyses were performed to explore risk factor heterogeneity between the peak season for Hantaan virus (HTNV) type HFRS (October-January) and other months.
Results93 cases (73.2%, 93/127) reported from January 2022 to September 2023 and 186 controls completed this questionnaire. Farmers accounted for the highest proportion (68.8%, 64/93). In multivariate logistic regression analysis, there were three significant risk factors for HFRS: piles of firewood and/or grain in residential yards (odds ratio [OR]=3.75, 95% CI: 2.14–6.55), mite and/or flea bites (OR=1.83, 95% CI: 1.06–3.18) and contacting with rats and/or their excreta (OR=1.73, 95% CI: 1.09–2.74); three variables represented significant protective factors for HFRS: frequency of sun exposure for quilts and bedding (OR=0.41, 95% CI: 0.19–0.90), rodent control measures at home (OR=0.50, 95% CI: 0.30–0.81) and knowing the main sources of HFRS transmission (OR=0.58, 95% CI: 0.36–0.90). Stratified analysis revealed that the influence of these factors varied by season, with rodent contact and control measures being particularly salient during the HTNV peak season.
ConclusionThis study provides the first comprehensive evidence of risk and protective factors for HFRS in Qingdao, highlighting the role of rodent control, promoting comprehensive health education, environmental management, and personal protection. However, the results should be interpreted considering the study’s limitations, including a 73.2% response rate and the potential for recall bias.
Patients undergoing anterior cruciate ligament reconstruction (ACLR) and patellar fracture frequently present with substantial pain, swelling and inflammation. These pathophysiological changes not only intensify postoperative pain but also compromise the intra-articular environment via mechanical compression and localised microcirculatory deficits, thereby impeding recovery. Conventional interventions for postoperative swelling, such as cryotherapy and physical agent modalities, are commonly applied yet exhibit limited efficacy. Multilayer low-stretch bandage (MLB), with its gradient compression properties, has recently demonstrated superior swelling control and functional restoration; however, existing research primarily assesses short-term outcomes and lacks a systematic analysis across the postoperative continuum—acute, subacute and chronic phases—as well as long-term follow-up. This study therefore employs a multi-temporal intervention design and extended follow-up to evaluate the effectiveness of MLB in managing swelling, modulating pain and enhancing long-term knee function and activities of daily living across different recovery stages. The findings aim to furnish high-level evidence for knee rehabilitation protocols, refine clinical practice and ultimately improve patient quality of life.
This prospective, single-blind, randomised controlled trial will enrol 36 patients following ACLR and patellar fracture. Participants will be allocated at a 1:1 ratio through computerised randomisation to either an experimental group receiving MLB plus conventional rehabilitation, or a control group receiving conventional rehabilitation alone. The study spans 12 weeks, with follow-up assessments scheduled at baseline (T0), 4 weeks (T1), 8 weeks (T2) and 12 weeks (T3). Outcome measures comprise the Hospital for Special Surgery (HSS) Knee Rating Score, affected limb oedema regression rate, Visual Analogue Scale (VAS) pain score, knee range of motion, quadriceps and hamstring muscle strength, centre of pressure (COP) displacement parameters, proprioceptive testing, the 36-Item Short Form Health Survey (SF-36) and the Holden Walking Function Classification. A subsequent 1-year follow-up will assess long-term efficacy and patient satisfaction, while adverse events are strictly monitored throughout the entire study period. Adherence to Consolidated Standards of Reporting Trials guidelines is maintained, and a single-blind design ensures that both participants and assessors remain unaware of group assignments. This trial aims to establish an evidence-based foundation for optimising postoperative rehabilitation in this patient population.
Ethical approval for the study was obtained from the Medical Ethics Committee of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School (2025-0141-01). The results of the study will be published in a peer-reviewed medical journal.
ClinicalTrials.gov chiCTR2500100566. Registration date is 10 April 2025.
Evaluation of the impact of atherosclerotic cardiovascular disease (ASCVD), particularly polyvascular disease, on 30-day and 365-day mortality among intensive care unit (ICU) patients diagnosed with sepsis.
Retrospective cohort study.
This study was conducted using data from the Medical Information Mart for Intensive Care IV, a publicly available critical care database from a tertiary care hospital in the US.
A total of 7895 adult ICU patients with sepsis were included between 2008 and 2022. Among them, 3314 (41.97%) had ASCVD, defined by International Classification of Diseases (ICD) codes for coronary artery disease, peripheral artery disease or stroke.
The primary outcomes were all-cause mortality at 30 and 365 days following ICU admission.
ASCVD patients with a greater number of disease beds tend to be male, older, have lower body mass index, heart rates, mean blood pressure, respiratory rate and temperature, compared with non-ASCVD patients. Before propensity-score matching, patients with ASCVD (3314) had significantly higher 30-day (29.21% vs 24.14%, p
Integrated management of sepsis and ASCVD—using targeted interventions such as tailored pharmacotherapy and risk factor modification—may reduce mortality and morbidity in this high-risk population.
To pilot and evaluate the implementation of a structured Evidence-Based Rounds (EBR) education model in critical care.
A mixed data type design was used to evaluate Evidence-Based Rounds in a critical care setting. Structured observational data were captured and open-ended survey responses were submitted by attendees. Content analysis and descriptive statistics were used to analyse survey findings.
Seventeen rounds were completed between March 2023 and January 2024 with a total of n = 83 clinical staff members. From these, n = 55 staff completed and submitted evaluation surveys. Rounds were most frequently attended by nurses of all bandings including senior clinical nurses, support workers and student nurses. Evidence-Based Rounds were globally perceived as a positive and useful education strategy and staff were very willing to attend future sessions. Patient outcomes were not directly assessed and rounds specifically facilitated three outcomes: (1) helping staff apply evidence to practice, (2) building staff confidence in presenting clinical information and (3) supporting staff in identifying local improvements to patient care.
Evidence-Based Rounds are an adaptable effective model of bedside education within critical care. In our setting, staff perceived that this model facilitated the application of evidence in clinical practice and positively influenced feelings of confidence. Importantly, this education strategy empowered nurses to explore and identify improvements locally to patient care. Whilst this model offers a practical education approach to address some of the key critical care workforce issues, such as an expanding curriculum and loss of senior staff, it could also be widely adopted to other clinical areas.
Evidence-Based Rounds are perceived by staff as a successful bedside education model that facilitates nurses to apply evidence in practice. It is feasible that this strategy is a potentially sustainable, low-cost model for continuing professional development centred around routine clinical work.
No patient or public contribution.
To explore stakeholder perceptions on sugar-sweetened beverage (SSB) policies for Chinese children and adolescents and facilitators and challenges for policy implementation.
This study followed the sector governance analysis framework, which included three steps: context analysis, mapping stakeholders and stakeholder analysis. Context analysis comprised policy and literature reviews of existing domestic and international measures, complemented by expert consultation to clarify the policy context and identify relevant stakeholders. Guided by these insights, we mapped stakeholders for key informant interviews, in-depth interviews and focus group discussions to explore stakeholders’ perceptions of SSB policies. Qualitative data were collected and analysed through a thematic analysis approach.
Shanghai and Chongqing, China, July to August 2022.
37 stakeholders including policymakers, nutrition experts, industry and consumers (primary caregivers of children and adolescents aged 6–17 years).
Context and stakeholder analyses indicated rising SSB consumption among Chinese youth since 2000. Qualitative interviews reflected the absence of national policies due to inadequate policymaker awareness. Although policymakers and nutrition experts supported SSB policies, consumers were worried about their personal choices being affected and the industry feared innovation challenges and profit loss. Multiple stakeholders mentioned that a comprehensive national standard is lacking, which is needed to facilitate national policy roll-out. An initial focus on health education is suggested to raise awareness among policymakers and consumers to foster a supportive environment for SSB policy development.
Although SSB intake is rising among Chinese children, policymakers’ insufficient awareness and the lack of national standards hinder SSB policy development and implementation. Strategies that raise health knowledge and awareness among policymakers and consumers should be prioritised for now to assist future introduction of SSB standards and related policies.
Chronic subdural haematoma (CSDH) is a common neurosurgical condition in older adults, with a recurrence rate of approximately 7.1–13% after burr-hole drainage. Although surgical adjuncts such as subdural drains and middle meningeal artery embolisation may reduce recurrence, these are not suitable for all patients. Pharmacological strategies, including tranexamic acid, Goreisan and carbazochrome sodium sulfonate hydrate, have shown potential, but high-level evidence remains lacking. A prior retrospective study suggested that a triple oral regimen combining these agents may reduce recurrence. This randomised controlled trial aims to evaluate its efficacy and safety.
This is a prospective, multicentre, open-label, randomised controlled trial conducted across six hospitals in Ibaraki, Japan. A total of 180 patients undergoing first-time burr-hole surgery for CSDH will be randomised 1:1 to receive either triple therapy (Goreisan 7.5 g/day, carbazochrome sodium sulfonate hydrate 90 mg/day and tranexamic acid 750 mg/day for up to 90 days) or standard postoperative care. The primary outcome is recurrence requiring reoperation within 90 days. Secondary outcomes include time to recurrence and haematoma volume reduction on serial CT imaging. All analyses will follow the intention-to-treat principle, using logistic regression, Cox proportional hazards models and mixed-effects models.
Written, informed consent will be obtained from all participants at each participating hospital by trained staff from that hospital. The trial protocol has been approved by the ethics committee of the University of Tsukuba Hospital (approval no. TCRB23-025) and the Institutional Review Boards of all participating centres. Study findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. A summary of the results will also be provided to participating institutions and made publicly available in accordance with the BMJ Open data sharing policy.
jRCTs031240007.
The Communication and Symbolic Behaviour Scales Developmental Profile Infant–Toddler Checklist (CSBS DP ITC) is a screening tool designed to identify early deficits in social communication, expressive speech/language and symbolic functioning in children aged 6–24 months. This study aimed to translate and content validate the CSBS DP ITC into Modern Standard Arabic.
Methodological study involving translation and content validation.
The study was conducted in the United Arab Emirates.
The translation process involved five bilingual translators and one monolingual Arabic language expert. Ten experts participated in the content validation phase, and 10 parents of young children participated in the face validity assessment.
Content Validity Indices (CVIs), including the Item-level CVI (I-CVI), the Scale-level CVI by Average (S-CVI/Ave) and the S-CVI by Universal Agreement (S-CVI/UA), along with modified kappa statistics, were calculated to assess item-level and scale-level clarity, relevance and comprehensiveness.
Expert panel ratings showed high clarity (I-CVI: 0.8–1, S-CVI/Ave: 0.98, S-CVI/UA: 0.88) and similar relevance scores. Face validity assessments yielded clarity I-CVI scores of 0.9–1, with S-CVI/Ave at 0.98 and S-CVI/UA at 0.8. The modified kappa statistic ranged from 0.89 to 1, indicating strong agreement among parents.
The CSBS DP ITC was effectively translated and content validated into Modern Standard Arabic. The calculated CVI values ranged from excellent to acceptable. This step establishes a foundation before proceeding to full psychometric testing of the instrument, paving the way for a reliable and culturally appropriate tool to identify early communication delays for use across the Arab-speaking population.
by Natthakul Akarapredee, Chalirmporn Atasilp, Chonlaphat Sukasem, Pimonpan Jinda, Rattanaporn Sukprasong, Jiraporn Jensuriyarkun, Soravit Wongjitjanyong, Patompong Satapornpong, Natchaya Vanwong
IntroductionIrinotecan is a chemotherapy agent commonly prescribed for metastatic colorectal cancer but often leads to neutropenia. Variations in genes encoding drug-metabolizing enzymes and transporters may affect the toxicity and effectiveness of irinotecan. This study aimed to examine the impact of these genetic polymorphisms on irinotecan outcomes in Thai colorectal cancer patients.
MethodsThe study retrospectively analyzed 41 metastatic colorectal cancer patients treated with irinotecan-based chemotherapy. Genotyping was conducted for 23 single nucleotide polymorphisms in genes including UGT1A1, CYP3A4, CYP3A5, CES1, ABCB1, ABCC2, ABCC5, ABCG1, ABCG2, and SLCO1B1.Toxicity and efficacy were assessed, with statistical significance set at a Bonferroni-corrected P value Results
In terms of toxicity, UGT1A1*6 was significantly associated with both all-grade and severe neutropenia in the first cycle (p p p ABCC2 -24C > T variant was linked to all-grade neutropenia in the second cycle (p = 0.001). For efficacy, patients with the wild-type UGT1A1*6 had longer progression-free survival (PFS) (p SLCO1B1 521T > C variant was associated with improved PFS (p Conclusion
UGT1A1*6 and ABCC2 -24C > T variants emerge as potential predictors of irinotecan-induced neutropenia, while UGT1A1*6 and SLCO1B1 521T > C may serve as markers of prolonged PFS in Thai patients. Validation through larger prospective studies is essential to confirm and refine these genetic associations.
Palliative care reduces caregiver burden, alleviates patient symptoms, and supports treatment decision-making. However, despite these benefits, there is limited evidence on the effectiveness of palliative care interventions for caregivers of individuals with advanced dementia.
To integrate and analyze data on the effectiveness of palliative care interventions in improving caregiver outcomes in order to ensure that both patients and caregivers receive the support necessary for optimal care experiences, quality of life management, and advanced care planning.
A systematic search was conducted of six databases to identify relevant studies published from database inception to 12 December 2024. Randomized controlled trials (RCTs) investigating palliative care interventions for caregivers of people with advanced dementia were included. Version 2 of the Cochrane Risk of Bias tool was used to assess the risk of bias in the methodology of each study. Standardized mean differences (SMDs) between each intervention and control group were calculated. A random-effects DerSimonian and Laird model was applied to generate pooled SMD estimates for each outcome and assess its heterogeneity. A leave-one-out sensitivity analysis was performed to ensure the stability of the pooled effect sizes.
Eight RCTs were included in the final analysis. Palliative care interventions appeared to reduce conflict in decision-making among caregivers of people with advanced dementia.
Palliative care interventions were successful in reducing conflict in decision-making of caregivers of people with advanced dementia. However, the modality's effects on caregiver satisfaction and caregiver distress need further investigation.
Future palliative care interventions for caregivers of advanced dementia patients should focus on developing the contents of palliative care materials based on evidence-based evaluations and explore strategies to improve engagement between patients, caregivers, and healthcare professionals.
To examine clinical nurses' attitudes towards and self-reported experiences of family nursing in Japan following the relaxation of COVID-19 visitation restrictions. Particular attention is paid to early career nurses whose formative training occurred during visitation bans. The study focused on nurses' negative perceptions and emotional burdens associated with family involvement.
A quantitative-dominant mixed-methods cross-sectional study reported in accordance with the STROBE guideline.
Using a convenience sampling approach, a self-administered, paper-based questionnaire was distributed to clinical nurses in four general hospitals in Japan between January and May 2024. The questionnaire consisted of four parts: demographic and professional background, learning methods related to family nursing, 17 items including negatively valenced statements adapted from the Families' Importance in Nursing Care–Nurses' Attitudes (FINC-NA) scale, and one open-ended question. Quantitative data were analysed using descriptive statistics and t-tests, and qualitative responses were thematically analysed.
Of 1921 nurses invited, 957 responded (response rate: 49.8%), and data from 892 valid responses were analysed. Overall, the nurses demonstrated positive recognition of family nursing as a professional value but also reported lingering emotional burdens and practical challenges when interacting with families. Early-career nurses who began practice during the pandemic showed greater uncertainty and lower affective engagement. Thematic analysis revealed five key themes: relational disruption, emotional stress, moral conflict, reappraisal of family engagement and ongoing barriers.
The findings underscore the need to structurally and educationally reintegrate families into nursing care. Simulation-based training, clear institutional policies and hybrid communication models are essential to rebuild relational continuity and support nurses' emotional and ethical capacity for family nursing.
The findings highlight the need to structurally and educationally reintegrate families into clinical care to address the emotional burden and ambivalence reported by nurses. Organisational support—such as clear visitation policies, simulation-based education and reflective opportunities—can help rebuild nurses' relational competence and confidence in engaging with families. Creating supportive learning environments, including on-the-job mentoring and team-based reflection, may further facilitate the restoration of family nursing.
This study addressed how prolonged COVID-19 visitation restrictions disrupted family nursing practice in Japan, created generational differences in nurses' competencies, and shaped nurses' perceptions of family involvement. Nurses reported emotional strain, feelings of being monitored and lack of time when families were present. Early career nurses showed lower relational engagement, while experienced nurses expressed moral distress. ‘Latent indifference’ was also noted. The findings provide valuable insights for healthcare organisations, nurse educators and policymakers by informing strategies to reintegrate families into patient care, improve discharge planning and strengthen training models.
The STROBE checklist.
No patient or public contribution.
To examine the relationship between nurse managers' empowering leadership, nurses' resilience and organisational learning from incidents.
Cross-sectional observational study.
Secondary data from a study conducted in June–July 2022 was used. The sample included 1049 nurses working in three special-functioning hospitals. The self-administered questionnaires assessed nurse managers' empowering behaviours, nurses' resilience and attitudes and behaviours fostering organisational learning from incidents. The analysis employed multilevel analysis with hierarchical linear modelling.
Nurse managers' empowering behaviours and nurses' resilience were significantly positively associated with attitudes and behaviours fostering organisational learning from the following incident subscales: make efforts to identify the problem, discuss safety in the workplace, identify and give feedback to address the at-risk behaviour. The interaction of empowering behaviours and resilience was not significant.
Nurse managers' empowering behaviours and nurses' resilience can contribute to attitudes and behaviours that foster organisational learning, even when nurses face stressful incidents.
Fostering empowering leadership in nurse managers and resilience in nurses enhances organisational learning and improves safety and care quality.
The reporting is based on the STROBE guidelines.
This study did not include patient or public involvement in its design, conduct or reporting.
This study compared the reliability of two metabolic cart systems, Vyntus CPX and Vmax Encore 29N, to measure whole-body energy metabolism by indirect calorimetry (IC) in individuals with type 2 diabetes (T2D).
Randomised, prospective, crossover study.
Single-centre study conducted in the clinical research centre of the German Diabetes Study (GDS).
Five participants (3 men, 2 women, mean age 49±6 years, body mass index (BMI) 32.62±4.2 kg/m²) with T2D completed the study protocol. Eligibility requires existing participation in GDS and availability for four consecutive study days.
Participants underwent four IC measurements per day on four consecutive days, totalling 16 measurements per device. On each study day, two measurements with both devices, Vyntus CPX and Vmax Encore 29N, were performed in randomised order. Postcalorimetric gas calibration with normalisation was applied after each measurement.
Reliability of respiratory quotient (RQ) and resting energy expenditure (REE), as assessed from the coefficient of variation (CV) and 95% CIs.
Device comparison showed minor differences in CV (95% CI) for carbon dioxide production (VCO2) (3.5% vs 5.3%; 95% CI –8.2% to 8.0%), oxygen consumption (VO2) (3.4% vs 5.7%; 95% CI –9.3% to 8.2%), RQ (3.6% vs 2.3%; 95% CI –3.5% to 3.7%) and REE (3.1% vs 5.6%; 95% CI –8.4% to 7.8%). Postcalorimetric calibration did not consistently affect RQ or REE.
Vyntus CPX provides reliable IC measurements comparable to Vmax Encore 29N and may serve as a suitable replacement in clinical settings.
ClinicalTrials.gov identifier: NCT01055093.
Perioperative psychological symptoms are prevalent among patients undergoing lung surgery and can contribute to adverse clinical outcomes. Pharmacological interventions for these symptoms have inherent limitations. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-invasive therapeutic approach. This study aims to evaluate the efficacy of taVNS in managing perioperative psychological symptoms in patients undergoing elective thoracoscopic pneumonectomy under general anaesthesia.
This single-centre, prospective, randomised, double-blind, controlled trial will enrol 176 patients scheduled for elective thoracoscopic lung resection. Participants will be randomly allocated to either the active taVNS or the sham taVNS groups in a 1:1 ratio. Both groups will receive 30 min active or sham stimulation sessions at four time points: (1) the afternoon prior to surgery, (2) the morning of the surgery, (3) following extubation and (4) the first afternoon postsurgery. The primary outcome is the incidence of perioperative anxiety, assessed using the Hospital Anxiety and Depression Scale-Anxiety subscale. Secondary outcomes include depression scores, stress index, sleep quality, pain scores, incidence of postoperative delirium, fatigue, cough symptoms and postoperative recovery quality, all evaluated through validated assessment tools. Analyses will be conducted using intention-to-treat and per-protocol populations.
The Ethics Committee of Affiliated Hospital of Xuzhou Medical University granted approval for the study with approval number: XYFY2024-KL444-01. Dissemination will be via national anaesthesia conferences and publication in the peer-reviewed literature.
ChiCTR2400090542.
To identify enablers and barriers for scaling up non-communicable disease (NCD) interventions across diverse global contexts and to map these factors to the WHO’s health system building blocks.
A multi-method qualitative study applying the Consolidated Framework for Implementation Research to analyse data from multiple projects nearing or completing scale-up.
Global Alliance for Chronic Diseases-funded implementation research projects conducted across 18 low- and middle-income countries and high-income settings.
Data was derived from documents (n=77) including peer-reviewed publications, policy briefs, and reports and interviews with stakeholders (n=18) (eg, principal investigators, medical professionals, public health workers).
Various context-specific interventions targeting sustainable scale-up of NCD (eg, diabetes, hypertension, cardiovascular disease) interventions at the community, primary care or policy levels.
The primary outcome was identifying contextual enablers and barriers to intervention scale-up. Secondary outcomes included exploring how these factors aligned with health system building blocks (eg, leadership/governance, healthcare workforce).
Twenty enablers (eg, intervention adaptability, strong stakeholder engagement, local empowerment) and 25 barriers (eg, resource limitations, intervention complexity, stakeholder burnout) were identified. Contextual alignment, supportive governance and capacity building were critical for sustainability, while cultural misalignment and socio-political instability frequently hampered scaling efforts.
Tailoring interventions to local health systems, ensuring stakeholder co-ownership and incorporating strategies to mitigate stakeholder burn-out are essential to achieving sustainable, scalable NCD solutions. Future research should focus on integrating systematic cultural adaptation, sustainable financing and workforce capacity building into scale-up planning.
This study aimed to identify intraoperative and perioperative factors influencing 30-day mortality after cardiac surgery and to develop a risk score (POP-score) for its prediction.
Retrospective cohort study with multivariable regression analysis.
A tertiary care cardiac surgery centre in Austria; data from consecutive patients undergoing cardiac surgery between 2010 and 2020 were analysed.
A total of 8072 patients were included. The cohort was randomly divided into a derivation cohort (75%) and a validation cohort (25%).
The primary outcome measure was 30-day mortality. We analysed associations between intraoperative and perioperative variables and 30-day mortality, assessed via multivariable regression analysis.
Several factors were significantly associated with 30-day mortality, including intraoperative RBC transfusion (OR 3.407 (95% CI 2.124–5.464)), postoperative high-sensitive cardiac troponin T cut-off levels (OR 2.856 (95% CI 1.958 to 4.165)), need for dialysis/haemofiltration (OR 2.958 (95% CI 2.013 to 4.348)) and temporary extracorporeal membrane oxygenation support (OR 5.218 (95% CI 3.329 to 8.179)) (p
The validated POP-score provides an improved tool for predicting 30-day mortality after cardiac surgery by incorporating intraoperative and perioperative factors alongside the EuroSCORE II. Although model performance was evaluated using 7-day peak troponin data, the score can be calculated within the first 72 hours postoperatively in most patients, supporting its clinical applicability for early decision-making, resource allocation and patient counselling. Further research is warranted to assess its clinical utility in diverse populations.
Osteogenesis imperfecta (OI) is the most common inherited cause of bone fragility (approximately 1 in 16 000). People with OI suffer bone fragility causing fractures, pain and deformity; sarcopenia causing fatigue and poor endurance; aortic root dilatation and hearing loss. No drug currently has market authorisation to treat OI in Europe. Current standard-of-care is multidisciplinary, with pharmacological interventions—primarily bisphosphonates—directed at increasing bone mass; however, such interventions are of equivocal efficacy. The structural damage that can accumulate as a result of repeated fractures over time may not be reversible. The lack of a treatment with clearly defined efficacy in terms of reducing fracture frequency or the sarcopenia, that is increasingly recognised in this condition, leads to the consideration of alternatives based on what is known about the molecular pathophysiology of the condition. For reasons that are currently unclear, transforming growth factor beta (TGFβ) pathway signalling is increased in OI, and both studies in mouse models and more recently also in humans suggest that reducing TGFβ pathway signalling could be of benefit in OI. This demonstrator project tests the hypothesis that losartan, an antihypertensive agent known to reduce circulating TGFβ, will reduce bone turnover and bone loss and have a positive effect on muscle function and quality of life in adults and older adolescents with OI.
This is a phase 2/pilot, open-label, dose-escalating study. This study aims to identify the effective dose for losartan in this population to inform the design of a pivotal phase III study. The study aims to recruit 30 adolescents and adults aged 16 years and above with OI across secondary care study sites in the UK and Italy. Participants will be recruited from the patient populations attending for treatment of OI at the participating hospital sites or referred by clinicians at the Participant Identification Centres (PIC sites). Participants will be randomised to one of three ‘final doses’—25, 50 or 75 mg losartan once daily. All participants will start on 25 mg once daily. Those assigned to higher ‘final doses’ will increase in 25 mg once daily increments on day 8 and day 15 following safety assessments. The primary outcome measures are to establish the effective dose of losartan in OI patients, based on maximal reduction in the bone resorption marker carboxy-terminal crosslink of type I collagen telopeptide (CTX) over the 24-week period of the study.
Secondary outcome measures are to determine the changes in proxy efficacy outcomes for bone (turnover, mass, architecture and strength) using blood tests, high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA) and muscle (strength) using the ‘Timed Up and Go’ test. In addition, the changes in quality of life, including pain and fatigue, will be evaluated by using a disease-specific tool (OI-QOL) and a validated generic tool (EQ-5D-5L-VAS).
In the UK, the study protocol and amendments have been approved by the London Bridge Research Ethics Committee (REC reference: 23/LO/015) and by the Medicines and Healthcare products Regulatory Agency (MHRA). In Italy, the study protocol and amendments have been approved by the Italian and European ethics and regulatory authorities (Clinical Trials Information System European Union (CTIS EU) portal according to EU Regulation 536/2014). Final version of study protocol: Version 3.2, 05.03.2025. Final results will be disseminated in peer-reviewed journals through local OI, orthopaedic and other relevant clinical networks and at national and international meetings. Sheffield Children’s National Health Service Foundation Trust (UK) and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (Italy) are the joint study sponsors.
ISRCTN (ISRCTN13317811).
To develop prediction models for short-term outcomes following a first acute myocardial infarction (AMI) event (index) or for past AMI events (prevalent) in a national primary care cohort.
Retrospective cohort study using logistic regression models to estimate 1-year and 5-year risks of all-cause mortality and composite cardiovascular outcomes.
Primary care practices in England contributing data to the Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD databases between 2006 and 2019.
Patients with an incident (index) or prevalent AMI event. Models were trained on a random 80% sample of CPRD Aurum (n=1018 practices), internally validated on the remaining 20% (n=255) and externally validated using CPRD GOLD (n=248).
Discrimination assessed using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Calibration assessed using calibration plots.
In the index (prevalent) cohorts, 94 241 (64 789) patients were included in the training and internal validation sets, and 16 832 (7479) in the external validation set. For the index cohort, AUCs for 1-year [5-year] all-cause mortality were 0.802 (95% CI 0.793 to 0.812) [0.847 (0.841 to 0.853)] internally and 0.800 (0.790 to 0.810) [0.841 (0.835 to 0.847)] externally. For the primary composite outcome (stroke, heart failure and all-cause death), AUCs were 0.763 (0.756 to 0.771) [0.824 (0.818 to 0.830)] internally and 0.748 (0.739 to 0.756) [0.808 (0.801 to 0.815)] externally. Discrimination was higher in the prevalent cohort, particularly for 1-year mortality (AUC: 0.896, 95% CI 0.887 to 0.904). Models excluding treatment variables showed slightly lower but comparable performance. Calibration was acceptable across models.
These models can support clinicians in identifying patients at increased risk of short-term adverse outcomes following AMI, whether newly diagnosed or with a prior history. This can inform monitoring strategies and secondary prevention and guide patient counselling on modifiable risk factors.
by Darren Curnoe, Mohammed S. Sauffi, Hsiao Mei Goh, Xue-feng Sun, Roshan Peiris
The rarity of Late Pleistocene hominin remains from Insular Southeast Asia (ISEA) has hampered our ability to understand a crucial episode of human evolutionary history, namely, the global dispersal of Homo sapiens from Africa. Moreover, recent discoveries indicate a surprising level of taxic diversity during this time with at least two species—H. floresiensis and H. luzonensis—endemic to the region when H. sapiens first arrived. A third hominin dubbed the ‘Denisovans’ is shown from DNA evidence to have interbred with the ancestors of contemporary Indigenous populations across ISEA, New Guinea and Australia. Yet, the Denisovans have not been identified from the fossil record of the area despite recent breakthroughs in this regard on mainland East Asia. New excavations by our team at the Trader’s Cave in the Niah National Park (‘Niah Caves’), northern Borneo, have yielded an isolated hominin upper central permanent incisor dated with Optically Stimulated Luminescence dating of sediments to about 52 − 55 thousand years ago. Specimen SMD-TC-AA210 has a massive crown absolutely and relative to its root size, the crown is wide (mesiodistally) and relatively short (labiolingually). Morphologically, it exhibits a very strong degree of labial convexity, pronounced shovelling, and the bulging basal eminence exhibits several upward finger-like projections. Labial enamel wrinking on the enamel-dentine junction is expressed as two large ridges exhibiting numerous spine-like projections, and the lingual extensions on the enamel surface of the basal eminence are expressed as six extensions. This combination of crown size and morphological traits is not normally found in H. sapiens and instead characterises archaic members of Homo such as H. erectus, H. neanderthalensis and Middle Pleistocene hominins sharing a clade with H. heidelbergensis. The Trader’s Cave tooth suggests that an archaic hominin population inhabited northern Borneo just prior to or coincident with the arrival of H. sapiens as documented at the nearby West Mouth of the Niah Great Cave.by Michael C. Reed, Ayako Suzuki, Allison Cruikshank, Mizuki Suzuki, H. Frederik Nijhout
Homocysteine (Hcy), a sulfur-containing amino acid, is produced in prodigious quantities by the methionine cycle in the liver. Hcy is the major biomarker for cardio-vascular disorders and is associated with many other diseases. In previous work, we have explained why menstruating women have lower serum homocysteine than men due to higher concentrations of estradiol. In this study, we first present epidemiological evidence from NHANES data that synthetic estradiol supplementation lowers serum Hcy in post-menopausal women, but raises Hcy in pre-menopausal women. Secondly, we give an explanation of this puzzling phenomenon using previously developed mathematical models of one-carbon and glutathione metabolism. The simulation analysis demonstrated that the non-monotonic response of glutathione to rising estradiol levels may account for the differing Hcy responses to estradiol supplementation in postmenopausal versus premenopausal women, through activation of cystathionine β-synthase, a key enzyme regulating tissue homocysteine levels. Our findings further highlight the importance of considering menopausal status and synthetic hormone use when evaluating the health effects of homocysteine.