Evaluating individualized treatment effect predictions: A model-based perspective on discrimination and calibration assessment.

In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their performance. In this paper, we aim to facilitate the validation of prediction models for individualized treatment effects. The estimands of interest are defined based on the potential outcomes framework, which facilitates a comparison of existing and novel measures. In particular, we examine existing measures of discrimination for benefit (variations of the c-for-benefit), and propose model-based extensions to the treatment effect setting for discrimination and calibration metrics that have a strong basis in outcome risk prediction. The main focus is on randomized trial data with binary endpoints and on models that provide individualized treatment effect predictions and potential outcome predictions. We use simulated data to provide insight into the characteristics of the examined discrimination and calibration statistics under consideration, and further illustrate all methods in a trial of acute ischemic stroke treatment. The results show that the proposed model-based statistics had the best characteristics in terms of bias and accuracy. While resampling methods adjusted for the optimism of performance estimates in the development data, they had a high variance across replications that limited their accuracy. Therefore, individualized treatment effect models are best validated in independent data. To aid implementation, a software implementation of the proposed methods was made available in R.

Establishment and identification of bladder cancer cell sheet.

Cell sheet technology (CST) has primarily been applied in tissue engineering for repair purposes. Our preliminary research indicates that an in vivo prostate cancer model established using CST outperforms traditional cell suspension methods. However, the potential for CST to be used with bladder cancer cells has not yet been explored. In this study, we investigated the ability of two bladder cancer cell lines, T24 and 5637, to form cell sheets. We found that T24 cells successfully formed cell sheets. We then performed staining to evaluate the integrity, specific markers, and proliferation characteristics of the T24 cell sheets. Our findings demonstrate that bladder cancer cell sheets can be established, providing a valuable tool for both in vivo and in vitro bladder cancer studies and for personalized drug selection for patients.

Sex Differences in Pain Sensitivity in a Dutch Cohort: Cross-Sectional and Web-Based Multidimensional Study.

BACKGROUND: Sex is an important factor influencing the development and treatment of chronic pain, but the extent of its influence is still unclear. Other demographic factors as well as nonpharmacological interventions might influence pain sensitivity differently in men and women. OBJECTIVE: In this study, we aimed to investigate the influence of sex and other demographic, lifestyle, behavioral, clinical, and environmental factors on pain sensitivity in the Dutch population. Different films were used to investigate how they would impact pain sensitivity and what influence sex and other variables have on the effect of this simple intervention. METHODS: We performed a study consisting of 2 parts: (1) a cross-sectional research to investigate pain sensitivity differences between men and women and the influence of other demographic variables on the pain sensitivity in a Dutch cohort and (2) an internet intervention study to determine whether a short film could skew pain sensitivity. RESULTS: All respondents filled in a web-based demographic questionnaire and were randomized into 4 groups. The control group filled in the Pain Sensitivity Questionnaire without watching a preliminary film. A cross-sectional analysis was performed in the control group (n=1746). The other 3 groups watched short films: one group watched a film with scenes of nature (n=2650), another group watched a film on laughing people (n=2735), and the last group watched a film on physically painful events (n=2708). Immediately after the film viewing, participants were directed to the Pain Sensitivity Questionnaire to measure their pain sensitivity. The Pain Sensitivity Questionnaire score was stated as a mean per question on the numeric rating scale from 0-1. The cross-sectional study revealed no significant differences between men and women but showed male-female differences in the Pain Sensitivity Questionnaire when specific background factors were present. Watching a short film had a positive impact on the pain sensitivity of the respondents who had chronic pain, with a higher effect observed in female respondents. CONCLUSIONS: Scientists performing pain research need to account for factors that can influence the outcome of their study and be aware that these factors can be sex-dependent, and pain sensitivity should be analyzed accordingly. Even relatively small interventions such as watching a film can impact pain sensitivity, especially in respondents with current chronic pain. This effect can vary as well when different background factors are present. Our findings warrant further explorations of the possibilities that simple interventions bring for patients in personalized medicine. TRIAL REGISTRATION: Landelijk Trial Register NTR-new NL8182; https://onderzoekmetmensen.nl/en/trial/29537.

Assessment of the application of a novel three-dimension printing individualized titanium mesh in alveolar bone augmentation: A retrospective study.

OBJECTIVE: To assess the clinical and radiographic outcomes of alveolar ridge augmentation using a novel three-dimensional printed individualized titanium mesh (3D-PITM) for guided bone regeneration (GBR). MATERIALS AND METHODS: Preoperative cone-beam computed tomography (CBCT) was used to evaluate alveolar ridge defects, followed by augmentation with high-porosity 3D-PITM featuring circular and spindle-shaped pores. Postoperative CBCT scans were taken immediately and after 6 months of healing. These scans were compared with preoperative scans to calculate changes in bone volume, height, and width, along with the corresponding resorption rates. A statistical analysis of the results was then conducted. RESULTS: A total of 21 patients participated in the study, involving alveolar ridge augmentation at 38 implant sites. After 6 months of healing, the average bone augmentation volume of 21 patients remained at 489.71 ± 252.53 mm3, with a resorption rate of 16.05% ± 8.07%. For 38 implant sites, the average vertical bone increment was 3.63 ± 2.29 mm, with a resorption rate of 17.55% ± 15.10%. The horizontal bone increment at the designed implant platform was 4.43 ± 1.85 mm, with a resorption rate of 25.26% ± 15.73%. The horizontal bone increment 2 mm below the platform was 5.50 ± 2.48 mm, with a resorption rate of 16.03% ± 9.57%. The main complication was exposure to 3D-PITM, which occurred at a rate of 15.79%. CONCLUSION: The novel 3D-PITM used in GBR resulted in predictable bone augmentation. Moderate over-augmentation in the design, proper soft tissue management, and rigorous follow-ups are beneficial for reducing the graft resorption and the incidence of exposure.

Prolactinoma: Navigating the Dual Challenge of Side Effects and Treatment Strategies - A Comprehensive Review.

This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma's clinical complexities and therapeutic nuances to guide optimal patient care strategies.

A long term outcomes analysis of severe haemophilia A boys receiving 4 years prophylaxis on the Chinese Haemophilia Individualized escalating low dose Prophylaxis (CHIPS).

BACKGROUND: The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up. METHODS: Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system. RESULTS: A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3-6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20-25 lU/kg, every other day), 10 at step 3 (15-20 IU/kg, 3×/week), 2 at step 2 (10-15 lU/kg, 3×/week) and 1 at step 1 (10-15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score. CONCLUSION: Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings.

Values of circulating tumor DNA for non-small cell lung cancer patients receiving neoadjuvant therapy, progress and challenges: a narrative review.

Background and Objective: The value of circulating tumor DNA (ctDNA) in neoadjuvant therapy (NAT) for lung cancer remains controversial. Therefore, we conducted a review to further investigate the role of ctDNA in non-small cell lung cancer (NSCLC) patients undergoing NAT for individualized management. Methods: A search of online databases (PubMed, Embase, Web of Science, Science Direct, and Cochrane Library) was conducted to evaluate the value of ctDNA in predicting relapse, risk stratification, and efficacy of NAT in NSCLC. Only articles published in English within the last 25 years, between January 1st, 1998 and November 30th, 2023, were included. Additionally, the application of ctDNA in NSCLC is briefly reviewed. Key Content and Findings: ctDNA is a non-invasive and dynamic method that plays an important role in future treatment guidance. Additionally, ctDNA successfully predicted the effect of neoadjuvant immunotherapy before surgery, and positive testing was strongly correlated with a lower major pathological response or complete pathological response rate. Sequential testing of ctDNA may serve as a secondary indicator to guide the adjustment of treatment programs. However, the application of this method has been limited by false negative results, a lack of objective indicators, and high costs. These issues must be addressed by researchers. Conclusions: ctDNA has strong potential in NAT, based on positive preliminary studies. However, its widespread use is limited by the high cost of testing. Further research is needed to explore its value in risk stratification and treatment guidance in the future.

Development of radioiodine-labeled mequitazine for evaluation of hepatic CYP2D activity.

Background: As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity. Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine (123/125I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice. Results: In vitro metabolite analysis using mouse liver microsomes showed that 125I-BMQ is specifically metabolized by CYP2D. Biological distribution and SPECT imaging of 123/125I-BMQ in normal mice showed that injection 123/125I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D. Conclusion: 123/125I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.

Experiences of patients, parents, and healthcare professionals in the process of transitioning from hospital to community after inpatient pediatric rehabilitation among children with special health care needs.

PURPOSE: Children with Special Health Care Needs (CSHCN) may experience disruptions in education due to extended hospitalizations. The purpose of this study was to describe how CSHCN experience educational supports during inpatient rehabilitation and identify the ongoing challenges when planning to return to school. MATERIALS AND METHODS: Semi-structured focus groups were conducted with parents (n = 12), former patients (n = 20), and rehabilitation professionals (n = 8). RESULTS: Through qualitative thematic analysis based on descriptive phenomenology, we developed three themes: 1) Inpatient educational support such as instruction and schoolwork helped reduce the learning loss during hospitalization. However, these supports were sometimes complicated by lags in school approvals and challenges in coordination between systems. 2) Transition planning involved establishing necessary services to support CSHCN's educational and healthcare needs at school re-entry. However, families reported limited information and guidance as key barriers. 3) Dynamic courses of school re-entry required continued support after discharge. The participants recommended that reassessment and adjustment of transition plans were often necessary to account for evolving developmental and educational needs but were not always received. CONCLUSIONS: There is an ongoing need to improve communication between clinicians and educators, information for families, and long-term follow-up on the changing educational needs for CSHCN after rehabilitation.

School re-entry after extended hospitalization is challenging for children with special health care needs (CSHCN) due to school disruption, social disconnection, and change in functional abilities.The hospital-to-school transition processes include inpatient educational programs during hospitalization, pre-discharge transition planning, and the subsequent implementation and adjustment of transition plans to facilitate individualized school re-entry.Key areas in need of improving school re-entry include coordination between the hospital and school about rehabilitation and educational goals and information provided to families about transition processes, particularly for newly acquired health conditions.A common need expressed by parents and CSHCN is to simplify and accelerate the process to establish services that support children's educational and healthcare needs.

Individualized treatment effects of a digital alcohol intervention and their associations with participant characteristics and engagement.

AIMS: Conditional average treatment effects are often reported in intervention studies, in which assumptions are made regarding how effects are similar across a heterogeneous sample. Nonetheless, differing factors, such as genetics, age, and sex, can impact an intervention's effect on outcomes. The study aimed to estimate the individualized effects of a digital alcohol intervention among individuals looking online to reduce their drinking. METHODS: We used data from a randomized controlled trial (RCT), including 2129 adults from the Swedish general population. The RCT concerned a text message-based alcohol intervention that sought to engender change through increasing knowledge on how to change and instilling confidence in changing behaviour. Outcomes were total weekly alcohol consumption and monthly heavy episodic drinking. Individualized treatment effects were modelled using baseline characteristics (age, gender, alcohol consumption, and psychosocial variables) and engagement with the intervention content. RESULTS: We found evidence that the effects of the digital alcohol intervention were heterogeneous concerning participants' age, baseline alcohol consumption, confidence, and importance. For heavy episodic drinking, there was evidence that effects were heterogeneous concerning age, sex, and baseline alcohol consumption. Overall, women, older individuals, and heavier drinkers benefitted more from the intervention in terms of effect size. In addition, participants who engaged more with the goal-setting and screening content reported better outcomes. CONCLUSIONS: The results highlight how different individuals respond differently to a digital alcohol intervention. This allows insight into who benefits the most and least from the intervention and highlights the potential merit of designing interventions adapted to different individuals' needs.

High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial.

OBJECTIVES: To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. METHODS: Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3-5, and days 7-10) and related to severe outcomes (respiratory failure/intensive care unit admission). RESULTS: Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1ß, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3-5, accompanied by IL-8 and IL-6 at days 7-10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. CONCLUSIONS: An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

Effects of starting one lung ventilation and applying individualized PEEP right after patients are placed in lateral decubitus position on intraoperative oxygenation for patients undergoing thoracoscopic pulmonary lobectomy: study protocol for a randomized controlled trial.

BACKGROUND: For patients receiving one lung ventilation in thoracic surgery, numerous studies have proved the superiority of lung protective ventilation of low tidal volume combined with recruitment maneuvers (RM) and individualized PEEP. However, RM may lead to overinflation which aggravates lung injury and intrapulmonary shunt. According to CT results, atelectasis usually forms in gravity dependent lung regions, regardless of body position. So, during anesthesia induction in supine position, atelectasis usually forms in the dorsal parts of lungs, however, when patients are turned into lateral decubitus position, collapsed lung tissue in the dorsal parts would reexpand, while atelectasis would slowly reappear in the lower flank of the lung. We hypothesize that applying sufficient PEEP without RM before the formation of atelectasis in the lower flank of the lung may beas effective to prevent atelectasis and thus improve oxygenation as applying PEEP with RM. METHODS: A total of 84 patients scheduled for elective pulmonary lobe resection necessitating one lung ventilation will be recruited and randomized totwo parallel groups. For all patients, one lung ventilation is initiated the right after patients are turned into lateral decubitus position. For patients in the study group, individualized PEEP titration is started the moment one lung ventilation is started, while patients in the control group will receive a recruitment maneuver followed by individualized PEEP titration after initiation of one lung ventilation. The primary endpoint will be oxygenation index measured at T4. Secondary endpoints will include intrapulmonary shunt, respiratory mechanics, PPCs, and hemodynamic indicators. DISCUSSION: Numerous previous studies compared the effects of individualized PEEP applied alone with that applied in combination with RM on oxygenation index, PPCs, intrapulmonary shunt and respiratory mechanics after atelectasis was formed in patients receiving one lung ventilation during thoracoscopic surgery. In this study, we will apply individualized PEEP before the formation of atelectasis while not performing RM in patients allocated to the study group, and then we're going to observe its effects on the aspects mentioned above. The results of this trial will provide a ventilation strategy that may be conductive to improving intraoperative oxygenation and avoiding the detrimental effects of RM for patients receiving one lung ventilation. TRIAL REGISTRATION: www.Chictr.org.cn ChiCTR2400080682. Registered on February 5, 2024.

Investigating the relationship between individualized care, patient satisfaction and trust in nurses through structural equation modelling.

INTRODUCTIONS: The aim of this study was to demonstrate the impact of individualized nursing care on patient satisfaction and trust in nurses through structural equation modelling in patients receiving treatment in internal clinics. METHODS: The study is a descriptive, exploratory and cross-sectional research conducted with patients receiving treatment in the internal admission services of an educational research hospital between January and April 2023. According to sample calculations, it was determined that a minimum of 238 patients needed to be included in the study, and 286 patients who met the inclusion criteria and agreed to participate in the research formed the study sample. Data were collected using the 'Patient Identification Form', 'Individualized Care Scale-Patient Version', 'Newcastle Nursing Care Satisfaction Scale' and the 'Trust in Nurses Scale'. RESULTS: The level of awareness of nursing actions supporting individuality was found to be 2.71 ± 0.99, the level of perceiving individuality was 2.88 ± 0.99, the average level of nursing care satisfaction measured 77.17 ± 12.67 and the average level of trust in nurses was 21.92 ± 3.04. It was determined that as patients' awareness of nursing actions supporting individuality and their perception of individuality in care increased, they remained more satisfied with their care and had greater trust in nurses. CONCLUSIONS: Patients who perceived receiving individualized care were found to have higher levels of patient satisfaction and trust in nurses. Additionally, it was observed that as participants' satisfaction with their care increased, their trust in nurses also increased.

Derivation and validation of the first web-based nomogram to predict the spontaneous pregnancy after reproductive surgery using machine learning models.

Objective: Infertility remains a significant global burden over the years. Reproductive surgery is an effective strategy for infertile women. Early prediction of spontaneous pregnancy after reproductive surgery is of high interest for the patients seeking the infertility treatment. However, there are no high-quality models and clinical applicable tools to predict the probability of natural conception after reproductive surgery. Methods: The eligible data involving 1013 patients who operated for infertility between June 2016 and June 2021 in Yantai Yuhuangding Hospital in China, were randomly divided into training and internal testing cohorts. 195 subjects from the Linyi People's Hospital in China were considered for external validation. Both univariate combining with multivariate logistic regression and the least absolute shrinkage and selection operator (LASSO) algorithm were performed to identify independent predictors. Multiple common machine learning algorithms, namely logistic regression, decision tree, random forest, support vector machine, k-nearest neighbor, and extreme gradient boosting, were employed to construct the predictive models. The optimal model was verified by evaluating the model performance in both the internal and external validation datasets. Results: Six clinical indicators, including female age, infertility type, duration of infertility, intraoperative diagnosis, ovulation monitoring, and anti-Müllerian hormone (AMH) level, were screened out. Based on the logistic regression model's superior clinical predictive value, as indicated by the area under the receiver operating characteristic curve (AUC) in both the internal (0.870) and external (0.880) validation sets, we ultimately selected it as the optimal model. Consequently, we utilized it to generate a web-based nomogram for predicting the probability of spontaneous pregnancy after reproductive surgery. Furthermore, the calibration curve, Hosmer-Lemeshow (H-L) test, the decision curve analysis (DCA) and clinical impact curve analysis (CIC) demonstrated that the model has superior calibration degree, clinical net benefit and generalization ability, which were confirmed by both internal and external validations. Conclusion: Overall, our developed first nomogram with online operation provides an early and accurate prediction for the probability of natural conception after reproductive surgery, which helps clinicians and infertile couples make sensible decision of choosing the mode of subsequent conception, natural or IVF, to further improve the clinical practices of infertility treatment.

Diagnosis and management of arrhythmogenic cardiomyopathy: a case report.

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial atrophy which progressively extends from the epicardium towards the endocardium, resulting in wall thinning. It is one of the leading causes of sudden death in young people. Postmortem studies demonstrate that up to 70-80% of the cases have biventricular involvement. Variable penetrance and expressivity results in a wide phenotypic spectrum, challenging diagnostic accuracy of advanced multimodality imaging tools. Prompt recognition, non-invasive imaging, risk stratification for sudden cardiac death (SCD), and preventive measures are paramount to improve prognosis. Case summary: Here, we present a 22-year-old Black male who was referred to our electrophysiology clinic with palpitations, remote syncope, and a family history of SCD. Over 3 years, he developed gradually worsening symptomatic palpitations. While physical exam and transthoracic echocardiography were unremarkable, his cardiac magnetic resonance imaging was consistent with biventricular ACM. Genetic testing confirmed ACM, revealing double heterozygosity in DSG2 and PKP2. Given the elevated estimated risk of life-threatening dysrhythmias, a subcutaneous cardiac defibrillator was successfully implanted. Discussion: Frequently, patients with ACM have more than one mutation in the same gene (compound heterozygosity) or in a second gene (double heterozygosity). Genetic counselling is strongly recommended for family members of the proband. The diagnosis of ACM may be mimicked by other diseases (cardiac sarcoidosis, dilated cardiomyopathy, amyloidosis), thus genetic testing can be useful to determine the presence of the disease. The present report provides an overview of the clinical course, diagnostic criteria, risk stratification, and prognostication for patients with ACM.

Machine learning-derived prognostic signature for progression-free survival in non-metastatic nasopharyngeal carcinoma.

BACKGROUND: Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. METHODS: A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. RESULTS: The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). CONCLUSION: MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Exploring the impact of rehabilitation on post-surgical recovery in elbow fracture patients: a cohort study.

INTRODUCTION: Elbow fractures, characterized by their complexity, present significant challenges in post-surgical recovery, with rehabilitation playing a critical role in functional outcomes. This study explores the efficacy of rehabilitative interventions in enhancing joint range of motion (ROM) and reducing complications following surgery for both stable and unstable elbow fractures. METHODS: A cohort of 15 patients, divided based on the stability of their elbow fractures and whether they received post-operative rehabilitation, was analyzed retrospectively. Measurements of ROM-including flexion, extension, pronation, and supination-were taken at three follow-ups: 15-, 30-, and 45-day post surgery. The study assessed the impact of rehabilitation on ROM recovery and the resolution of post-surgical complications. RESULTS: The findings indicated no statistically significant differences in ROM improvements between patients who underwent rehabilitation and those who did not, across all types of movements measured. However, early rehabilitative care was observed to potentially aid in the mitigation of complications such as joint stiffness, especially in patients with stable fractures. CONCLUSION: While rehabilitation did not universally improve ROM recovery in elbow fracture patients, it showed potential in addressing post-operative complications. The study underscores the importance of individualized rehabilitation plans and highlights the need for further research to establish evidence-based guidelines for post-surgical care in elbow fractures.

Personalized goals of people living with dementia and family carers: A content analysis of goals set within an individually tailored psychosocial intervention trial.

Introduction: Person-centered goals capture individual priorities in personal contexts. Goal Attainment Scaling (GAS) has been used in drug trials involving people living with dementia (PLWD) but GAS has been characterized as difficult to incorporate into trials and clinical practice. We used GAS in a trial of New Interventions for Independence in Dementia Study (NIDUS)-family, a manualized care and support intervention, as the primary outcome and to tailor the interventions to goals set. We aimed to assess the feasibility and content of baseline goal-setting. Methods: We developed training for nonclinical facilitators to set individualized GAS goals remotely with PLWD and family carer dyads, or carers alone, in the intervention trial, during the COVID-19 pandemic. A qualitative content analysis of the goals set explored participants' priorities and unmet needs, to consider how existing GAS goal domains might be extended in a psychosocial intervention trial context. Results: Eleven facilitators were successfully trained to set and score GAS goals. A total of 313/328 (95%) participants were able to collaboratively set three to five goals with the facilitators. Of these, 302 randomized participating dyads set 1043 (mean 3.5, range 3 to 5) goals. We deductively coded 719 (69%) goals into five existing GAS domains (mood, behavior, self-care, cognition, and instrumental activities of daily living); 324 (31%) goals were inductively coded into four new domains: carer break, carer mood, carer behavior, and carer sleep. The most frequently set goals pertained to social support. There was little variation in types of goals set based on the context of who set them or level of pandemic restrictions in place. Discussion: It is feasible for people without clinical training to set GAS holistic goals for PLWD and family carers in the community. GAS has potential to facilitate personalization of care and support interventions, such as NIDUS-family, and facilitate the roll out of more personalized care. Highlights: Goal Attainment Scaling (GAS) can capture meaningful priorities of people with dementia and their family carers.A psychosocial intervention RCT used GAS as the primary outcome measure and goals were set collaboratively by non-clinically trained facilitators.The findings underscore the feasibility of using GAS as an outcome measure with this population.The content analysis findings unveiled the diversity in experiences and priorities of the study participants.GAS has the potential to support the implementation of more person-centred approaches to dementia care.