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Circulating Tumor HPV DNA, Antibodies to HPV16 Early Proteins, and Oral HPV16 DNA As Biomarkers for HPV-Related Oropharyngeal Cancer Screening
No full textBackground: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.
Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.
Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E antibodies and ctHPVDNA using a droplet digital PCR (ddPCR)-based assay that measures circulating tumor tissue modified viral (TTMV)-HPV DNA (NavDx, Naveris, Inc.). We calculated frequency distributions of variables of interest and agreement between the biomarkers.
Results We enrolled 1045 subjects between April 2017 and April 2024. The 954 subjects with results for all three biomarkers were included in the analysis. The prevalence was 4.9% for oral HPV16 DNA, 0.7% for HPV16 E antibodies, and 0.5% for TTMV-HPV DNA.Conclusions: The low prevalence of all three biomarkers shows their potential to identify high-risk individuals eligible for further clinical HPV-related cancer screening
Communicating Blood Test Results in Primary Care: A Mixed-Methods Systematic Review
No full textBackground: Online records access, including test results, was rolled out as part of changes to the GP contract in England in 2023. Blood test result communication is important for patient-centred care, patient safety, and primary care workload. Evidence is needed to ensure that test results are communicated safely and efficiently to patients in primary care.
Aim: To summarise existing evidence for blood test result communication between primary care providers and their patients and carers.
Design and setting: A mixed-methods systematic review was undertaken.
Method: MEDLINE, Embase, PsycInfo (Ovid), CINAHL (EBSCOhost), and the Cochrane Library were searched from January 2013-September 2023. Qualitative or quantitative studies that provided information on the communication of blood test results by primary care staff to adult patients and carers were eligible for inclusion.
Results: There were 71 included studies, including 10 experimental studies and no randomised controlled trials. Study quality was mostly poor and risk of bias was high, partly owing to a lack of reported information. The studies found that patients want more information about their blood test results, particularly in terms of \u27what next\u27, and prefer results to be provided quickly. Electronic methods, such as online access or text messages, were generally well accepted but not by everyone, and not for all results. Clinicians\u27 opinions were mixed as to whether online direct release of test results to patients was beneficial or could cause problems, such as increased patient anxiety and increased workload.
Conclusion: A range of evidence has been identified on patient and clinician preferences, and barriers and facilitators to test communication, which is particularly important in the current NHS context of a move towards patient online access
Dietary Interventions to Support and Improve Sleep Disturbances and Insomnia Disorder in Menopause: From Bench to Bedside
No full textSleep is essential for maintaining physical and psychological health, and also cognitive health (referred to as \u27brain health\u27). However, the transition to menopause has a direct impact upon sleep. Sleep disturbances are reported by approximately 40%-60% of menopausal women, and insomnia disorder is also prevalent. Diet-based interventions could potentially be used to improve subjective sleep quality in this population, and although there are several promising interventions which have been used in other groups that could be trialled, the evidence base is currently lacking. One particularly promising area for future research is that these interventions might be used alongside, or instead of, established treatments for insomnia disorder. This may also help to prevent the development of longer-term insomnia disorder. Future studies should use well-controlled, adequately powered, clinical trial designs to assess the effectiveness of dietary interventions in improving subjective sleep quality, treating insomnia disorder, and preventing acute sleep disturbances from progressing to chronic insomnia. Given the strong association between sleep and neurodegeneration, optimizing sleep in menopausal women, using targeted diet-based strategies, may have significant implications for brain health
Using Video Ethnography and Stimulated Recall Interviews to Describe the Diagnostic Process in the Emergency Department
No full textObjectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.
Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED physician practice for 11 participants from February 2022 to July 2023. Participants wore a head-mounted video camera while providing care to ED patients, and in subsequent stimulated recall interviews, revealed their thinking throughout the diagnostic process.
Results: We recorded 24.42 h of video overall (average 2.22 h per participant). We identified four major themes in the ED diagnostic process: (1) quality communication facilitates information flow, (2) cognition is complex and distributed across patients and the ED team, (3) artifacts can enhance the diagnostic process, and (4) there is a need to balance efficiency with safety and accuracy.
Conclusions: Illustrating physicians\u27 cognitive processes through video ethnography coupled with stimulated recall interviews helped advance our understanding of the diagnostic process and is a foundational step for identifying improvement opportunities
Early Prediction of Mortality and Morbidities in Vlbw Preterm Neonates Using Machine Learning
No full textBackground: Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories.
Hypothesis: Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants.
Methods: ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation strategy. These models were then tested on a separate cohort (n = 447) to evaluate the final model performance.
Results: Among the seven ML algorithms employed, tree-based ensemble models, specifically Random Forest (RF) and XGBoost, had the best performance metrics. The area under the receiver operating characteristic curve (AUROC) of sepsis with or without meningitis (0.73), NEC (0.73), BPD (0.71), and mortality (0.74) exceeded 0.7, while the area under Precision-Recall curve (AUPRC) for all outcomes was greater than the prevalence, demonstrating effective risk stratification in VLBW preterm infants.
Conclusions: Our study demonstrates the potential of predictive analytics leveraging ML techniques in advancing precision medicine.
Impact: Reliable prediction of adverse outcomes before they occur has the potential to institute interventions and possibly improve health trajectories in VLBW preterm infants. We used machine learning to develop and test predictive models for mortality and five major morbidities in VLBW preterm infants. Individualized prediction of outcomes and individualized interventions will advance Precision Medicine in Neonatology
A Novel Approach to Calculating Expected Total Fetal Lung Volume in Fetuses With Isolated Congenital Diaphragmatic Hernia and Fetal Growth Restriction: A Theoretical Computational Simulation
No full textObjectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.
Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to calculate corrected O/E TFLV. Estimated mortality probabilities and CDH severity were compared pre- and post-adjustment.
Results: Standard vs. corrected O/E TFLV means differed significantly (36.2% vs. 43.5 %) (p\u3c 0.001), as did corrected mortality probabilities (60.2% vs. 58.6 %) (p\u3c 0.001). CDH severity shifted: severe to moderate (17.1 %) and moderate to mild (8.6 %) with corrected O/E TFLV. Two-week corrections had greater impact than 1-week. Positive correlation existed between O/E TFLV and percent difference in values, while GA showed a negative correlation with the percent differences.
Conclusions: This simulation shows how using weight-adjusted GA norms affects O/E TFLV calculations. For fetuses with isolated CDH and FGR, adjusted GA increases O/E TFLV, reduces mortality estimates, and changes CDH severity classification, possibly affecting fetal intervention eligibility. Real patient studies are needed to confirm these findings
Project Evolve: An International Analysis of Postimmunotherapy Lineage Switch, an Emergent Form of Relapse in Leukemia
No full textLineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as lineage drift were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of \u3c 40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS
Ethical Considerations of Deep Brain Stimulation for Treatment Refractory Schizophrenia: Surveying Stakeholders
No full textIntroduction: Ethical concerns have been raised by both current and historically controversial neurosurgical interventions for treatment-refractory schizophrenia and schizoaffective disorder (TR-SZ). Considering advances in next-generation deep brain stimulation (DBS), initial success in treating a few cases of TR-SZ, and how challenging trial enrollment is, transparency and disseminating knowledge about DBS is important, as is input from involved groups. Here information was presented about DBS as an experimental treatment option for TR-SZ to stakeholders to gauge enthusiasm after consideration of potential risks and benefits.
Methods: Stakeholders were presented with information about DBS (total n = 629). Opinions about whether DBS should be an option for people with TR-SZ and acceptable response rates considering DBS risks were collected from research participants with SZ, treatment-refractory Parkinson’s disease (TR-PD) approved for DBS, caregivers for either SZ or TR-PD participants, and attendees at medical school presentations. In addition, the attendees were asked to decide whether DBS is appropriate for 4 cases who want DBS, one with PD, 2 with OCD and 1 with SZ. Chi-square, pairwise comparisons, and Duncan Multiple Range Test were performed with significance at p \u3c 0.05.
Results: Most (83%) research participants and presentation audience members agreed that DBS should be an option for TR-SZ and 40% thought the potential benefits outweigh the risks of DBS with at least a 41–60% response rate. Audience approval of DBS was similar for the PD (30%), SZ (52%) and the OCD case with psychosis (56%), but there was a higher rate of approval (77%) for the OCD case whose compulsions involved self-harm. The majority (73–86%) of the audience thought that they would want to try DBS if they had TR-PD, TR-OCD, or TR-SZ.
Conclusions: Despite difficulty in recruiting patients for DBS clinical trials for TR-SZ, the consensus among 83% of stakeholders was that DBS should be an option for people with severe TR-SZ. Our approach to disseminate general knowledge then gather opinions among diverse stakeholders was to ensure the development of DBS clinical trials for the new indication TR-SZ is a relevant option despite the known difficulties in enrollment. These findings may help prevent disparities in access to advanced DBS therapeutics
Anxious Traits Intensify the Impact of Depressive Symptoms on Stigma in People Living with HIV.
No full textBackground/Objectives: Despite medical advances, stigma remains a major challenge for people living with HIV (PLWH). This study examined clinical, sociodemographic, and psychological predictors of HIV-related stigma, and explored whether affective temperament moderates the impact of depression on stigma.
Methods: This cross-sectional observational study included 97 PLWH attending a tertiary infectious disease unit in Rome, Italy. Participants completed a battery of validated psychometric instruments assessing depressive symptoms, anxiety, manic symptoms, mixed affective states, general psychopathology, impulsivity, and affective temperament. HIV-related stigma was evaluated using the Berger HIV Stigma Scale, which measures personalized stigma, disclosure concerns, negative self-image, and concerns with public attitudes. Descriptive statistics were used to characterize the sample. Univariate linear regressions were conducted to explore associations between clinical, psychometric, and sociodemographic variables and each stigma subdimension, as well as the total stigma score. Variables significant at p \u3c 0.05 were included in five multivariate linear regression models. Moderation analyses were subsequently performed to assess whether affective temperaments moderated the relationship between significant psychopathological predictors and stigma. Bonferroni correction was applied where appropriate.
Results: Higher depressive symptom scores are significantly associated with greater internalized stigma (B = 0.902, p = 0.006) and total stigma (B = 2.603, p = 0.008). Furthermore, moderation analyses showed that anxious temperament significantly intensified the relationship between depressive symptoms and both negative self-image (interaction term B = 0.125, p = 0.001) and total stigma (B = 0.336, p = 0.002).
Conclusions: Depressive symptoms and anxious temperament are associated with HIV-related stigma. Integrating psychological screening and targeted interventions for mood and temperament vulnerabilities may help reduce stigma burden in PLWH and improve psychosocial outcomes
Fast and Accurate Measurement of Small Field Dosimetry Using a Novel Scintillation Detector
No full textBackground: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.
Purpose: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD in small fields, with a scanning time that is 5 to 10 times faster than traditional methods.
Method: PDDs, profiles, and output factors were measured on a Varian TrueBeam 6XFFF photon beam for the field sizes of 0.5 × 0.5 cm2, 1 × 1 cm2, 2 × 2 cm2, 3 × 3 cm2, and 4 × 4 cm2 using a new PSD from blue physics (BP-PSD). These measurements were compared with those obtained using a well-established PSD (Standard Imaging W2), micro-diamond (TN60019, PTW-Freiburg, Germany), and micro-silicon detectors (TN60023, PTW-Freiburg, Germany). Owing to its fast response, the BP-PSD enabled the collection of beam profiles at 31 depths, which were used to derive the PDD while avoiding detector misalignment along the beam path. Data was collected in a water tank controlled by the PTW BeamScan software. The pulse-by-pulse raw data from BP-PSD were converted to respective dosimetry data using in-house software.
Result: The BP-PSD demonstrated excellent agreement with other detectors for small-field output factors (FOFs), with a maximum variation of 1.6%. The BP-PSD also showed strong agreement in PDD measurements with an ion chamber (TN31013) for both 3 × 3 cm2 and 10 × 10 cm2 field sizes, achieving a 98% gamma passing rate (gamma criteria: 1 mm, 3%). For the profile measurements, the BP-PSD showed consistency with both the micro-diamond and micro-silicon diode detectors, with less than 1% variation in measured penumbra length. At a 3 × 3 cm2 field size, the measured penumbra length (4 mm) agreed with previously published data (3.86-4.2 mm). Additionally, for an extremely small field size (0.5 × 0.5 cm2), the indirect PDD measurements derived from profiles showed significant improvement compared to the direct measurement without beam inclination correction.
Conclusion: The BP-PSD has proven to be a robust and reliable detector for small-field dosimetry. It shows excellent agreement with other detectors in measuring small FOFs, profiles, and PDDs, while achieving significantly faster scanning speeds in a water tank