Archives of Clinical and Biomedical Research

Study question. Are endometrial gene expression profiles reproducible across hormone replacement therapy (HRT) cycles and across different regions of the same endometrial biopsy? Summary answer. Endometrial transcriptomic profiles were highly reproducible across HRT cycles and across non-adjacent and adjacent regions of the same biopsy. What is known already. Endometrial transcriptomic analyses are increasingly used to understand endometrial physiology and to evaluate endometrial reproductive potential. However, this approach requires an endometrial biopsy in a prior endometrial cycle to the embryo transfer cycle in the IVF treatment. Therefore, endometrial transcriptomic analyses rely on the assumption that the gene expression profile is representative of subsequent endometrial cycles and of the whole biopsy specimen. However, inter-cycle and intra-biopsy reproducibility remain insufficiently characterized. Study design, size, duration. This was a prospective, single-center, observational clinical study including 20 participants recruited between June 2024 and March 2025. Participants/materials, setting, methods. Participants underwent two different endometrial preparation cycles under the same HRT conditions at a private fertility clinic, and an endometrial biopsy was collected during both cycles, with the same duration of progesterone exposure, in the mid-secretory phase by the same clinician. RNA was processed for whole endometrial transcriptome analysis using RNA sequencing. Three paired comparisons were performed: biopsies from the same participant collected in different cycles, non-adjacent regions of the same biopsy, and adjacent regions of the same biopsy. Gene expression reproducibility was assessed using Pearson correlation, hierarchical clustering, principal component analysis, and paired differential gene expression analysis. The reproducibility of estimated cell-type proportions was also assessed by deconvolution to observe potential differences in cellular composition. Main results and the role of chance. In the inter-cycle endometrial gene expression comparison, the mean {+/-} standard deviation (SD) gene expression correlation coefficient within participant pairs was 0.974 {+/-} 0.012, significantly higher than that observed between participant pairs (p = 1.56 x 10-6), the mean {+/-} SD Euclidean distance was significantly lower within than between participant pairs (p = 2.24 x 10-6), and no differentially expressed genes were identified within participant pairs. Principal component analysis and hierarchical clustering further supported the similarity of most paired samples. Intra-biopsy comparisons showed even higher reproducibility, with both non-adjacent and adjacent biopsy regions showing mean {+/-} SD correlation coefficients of 0.986 {+/-} 0.003 and 0.986 {+/-} 0.002, respectively. The correlation coefficients were significantly higher than those observed between biopsy pairs (p = 9.91 x 10-12 and p = 2.14 x 10-12, respectively). No differentially expressed genes were detected within intra-biopsy pairs, all paired regions clustered together by hierarchical clustering and principal component analysis, and intra-biopsy pairs showed lower Euclidean distances than inter-biopsy pairs (p = 9.91 x 10-12 and p = 2.14 x 10-12 in non-adjacent and adjacent regions, respectively). Estimated cell-type proportions did not differ significantly between paired samples in any of the three comparisons. Limitations, reasons for caution. The findings are specific to samples analyzed using the AmpliSeq Transcriptome Human Gene Expression Panel protocol. Although other transcriptomic platforms should be tested, we are expecting the same reproducibility due to the consistency of RNA seq platforms. All biopsies were collected by the same clinician, so operator-related variability could not be directly assessed. These findings can be extrapolated only to HRT cycles. Wider implications of the findings. These findings support the reproducibility of endometrial gene expression profiles under controlled HRT conditions from biopsies collected by the same clinician and suggest that a single biopsy region can provide a representative molecular profile of the whole biopsy specimen. These findings strengthen the methodological basis for bulk endometrial RNA sequencing studies and support the reliability of transcriptomic-based tools for endometrial evaluation in an endometrial cycle prior to an embryo transfer cycle for reproductive medicine.

Background: Clinical decision support (CDS) systems may improve chronic pain management by providing guideline-based recommendations within clinical workflows. However, low clinician use can limit their effectiveness. Understanding the association between CDS use and guideline-recommended care may help distinguish implementation challenges from limitations in CDS functionality. Objective: To estimate the association of OneSheet, a CDS system for chronic pain management, and guideline-recommended care when the system was used during patient encounters. Methods: We conducted a per-protocol secondary data analysis of data from a pragmatic randomized clinical trial conducted from October 2020 to May 2022 across 25 primary care clinics at 2 academic health systems in Indiana and North Carolina. The parent trial enrolled 137 primary care clinicians. This analysis included 145511 eligible chronic pain encounters and 15480 long term opioid therapy (LTOT) encounters that occurred after OneSheet implementation. OneSheet use at a patient encounter was the exposure of interest. Propensity score matching was used to create comparable groups of encounters with and without OneSheet use. Outcomes included documentation of pain-related goals, documentation of pain and function using the Pain, Enjoyment of Life and General Activity (PEG) scale, prescription drug monitoring (PDMP) review, urine drug screening (UDS) orders, and naloxone orders. Results: OneSheet was used in 959 of 145511 chronic pain encounters (0.7%) and 582 of 15480 LTOT encounters (4.0%). In matched analyses, OneSheet use was associated with increased documentation of pain-related goals (relative risk (RR)=11.70 (95% CI 4.25-32.50) and PEG score documentation (RR=9.70 (95% CI 4.14-22.31). Among LTOT encounters, OneSheet use was associated with increased UDS ordering (RR=1.52 (95% CI 1.40-1.65) and PDMP review (RR=1.06 (95% CI 1.03-1.09), but decreased naloxone ordering (RR=0.13 (95% CI, 0.02-0.90). Conclusions: OneSheet use was associated with several guideline-recommended chronic pain management actions, suggesting that they system may support care quality when clinicians use it. However, use was rare, indicating that increasing routine use through better workflow integration may be necessary to achieve population-level improvements in chronic pain care.

Background: European Association of Urology (EAU) Guidelines identify urogenital infections as a possible treatable cause of infertility, yet the current recommendation for antibiotic treatment remains weak due to a lack of high-quality evidence. We evaluated the effect of antibiotic treatment of asymptomatic urogenital infections on both conventional and apoptosis-related (flow cytometry sperm apoptosis test, FACS-APO) sperm parameters, as well as on pregnancy outcomes, in infertile couples. Methods: In this retrospective, single-centre study, we analysed 265 couples with an asymptomatic urogenital infection (Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, and Chlamydia trachomatis) confirmed in at least one partner by first-void urine testing, who received simultaneous antibiotic treatment. Paired conventional semen analysis and FACS-APO were performed before and 0-9 months after treatment completion. Partner infection concordance, the effect of follow-up timing on treatment response, and pregnancy outcomes within 12 months were also assessed. Results: Sperm concentration, total sperm count, total and progressive motility, and the proportion of viable sperm increased significantly after treatment, while the proportion of late apoptotic / necrotic sperm and calculated sperm DNA fragmentation decreased significantly (all p<0.05); the proportion of early apoptotic sperm remained unchanged, and semen volume did not change. Among 244 couples with complete bilateral microbiological testing, Ureaplasma urealyticum was by far the most prevalent pathogen (57.8% of men, 87.7% of women), and female partner positivity given male positivity was 83.0%. The improvement in sperm concentration and total sperm count was most pronounced within 3 months after treatment and diminished, or reversed, beyond 6 months. Pregnancy was achieved in 127 of 265 couples (47.9%; per-protocol rate 53.4%) within 12 months, most commonly following in vitro fertilization (72/127) or spontaneously (21/127). Conclusions: Antibiotic treatment of asymptomatic urogenital infections in infertile couples was associated with significant improvement in conventional semen parameters and a reduction in sperm apoptosis and calculated DNA fragmentation. Given the retrospective, uncontrolled design, these findings should be regarded as hypothesis-generating rather than definitive proof of a causal, fertility-enhancing effect, and warrant confirmation in prospective controlled studies.

Background. Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events in almost any organ. While myocarditis has received the most attention, data on pericardial disease with ICI use are limited. We examined pericardial adverse event reporting with nine ICIs using the FDA Adverse Event Reporting System (FAERS). Methods. We combined legacy AERS and current FAERS quarterly files from January 2011 to June 2026 into 18,629,240 unique cases, deduplicated by case number, and removed cases the FDA had listed as deleted. ICI exposure was identified from generic names, brand names, development code names and the active-ingredient field. Pericardial events were defined by seven MedDRA preferred terms. We estimated reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian information components (IC) and empirical Bayes geometric means (EBGM). We also examined myocarditis co-reporting, time trends, a comparison with other antineoplastic agents, a MedDRA query-based outcome, and 14 alternative definitions. Results. The analysis included 18,514,045 cases: 277,434 involved an ICI, 34,792 carried a pericardial term, and 1,680 had both. Pericardial events were reported disproportionately with ICIs (ROR 3.35 (95% CI 3.19 to 3.52); PRR 3.34; IC025 1.62). Eight of nine agents had a ROR above 1 (3.32 to 5.63). Among the most frequently reported terms, estimates were highest for cardiac tamponade (5.59 (95% CI 4.98 to 6.28)), followed by pericardial effusion (3.83 (95% CI 3.60 to 4.07)) and pericarditis (2.09 (95% CI 1.89 to 2.31)). After removing cases that also reported myocarditis, the ROR was 3.13 (95% CI 2.98 to 3.30). Most sensitivity analyses gave similar estimates (ROR 3.13 to 3.47); defining exposure by generic drug names alone, which identified only 44% of exposed cases, gave 3.99. Compared with cases naming other L01 antineoplastic agents, the ROR was 1.13 (95% CI 1.08 to 1.19): 1.28 (95% CI 1.20 to 1.36) for ICI-only cases and 0.96 (95% CI 0.89 to 1.04) when another antineoplastic was also named. The ICI-specific reporting odds ratio fell each quarter (odds ratio 0.977 per quarter, 95% CI 0.973 to 0.980). Conclusions. In FAERS, pericardial events were reported more often with ICIs than with other drugs across most agents and terms; however, incidence and causation cannot be determined. The excess over other antineoplastic agents was small, and reporting disproportionality declined over time. These findings support clinical awareness of pericardial disease in patients receiving ICIs and warrant study in data that can measure incidence.

In resource-limited settings plasma is usually transported to centralized laboratories for HIV RNA quantification; often by motor vehicles using dry ice. Any decay in plasma HIV RNA when near the threshold used to define virologic failure could impact clinical management. However, maintaining a cold chain during transport can be costly and limit the frequency of shipments, which can delay clinical assessments and also negatively impact patient care. Transporting plasma at ambient temperatures could facilitate timely measurements of plasma HIV RNA viral loads (VL). We conducted a stability study of HIV RNA in plasma held for 1, 3, 5, and 7 days at a range of temperatures (4{degrees}C, 30{degrees}C, and 37{degrees}C) to simulate the durations and temperatures specimens could experience during transport. Thirteen large volume plasma specimens with VL ranging from 2.7-5.53 log10 copies/mL were evaluated. Mean changes in VL between Day-0 to Day-1, Day-3, Day-5 or Day-7 were calculated, with decays >0.5 log10 c/mL considered clinically relevant. Compared to Day 0, the VL of plasma stored at 4{degrees}C and 30{degrees}C remained stable across the Days tested. The VL in plasma stored at 37{degrees}C had a progressive decline at Day-1, Day-3, Day-5 and Day-7 (means of -0.04, -0.19, -0.33. -0.34 log10 c/mL, respectively), with a decay of >0.5 log10 observed in 3/13 (23%) specimens at Day-7. A linear regression analysis showed that plasma specimens stored at 37{degrees}C significantly decayed over time (slope -0.054, 95% CI -0.079, -0.029; p=0.01). Any decay observed among specimens stored at 4{degrees}C and 30{degrees}C was not clinically relevant nor statistically significant. Our observations suggest that HIV RNA levels in plasma should remain stable if transported to centralized laboratories at ambient temperatures of [&le;]30{degrees}C or chilled by cold packs over a period [&le;]7 days. Transporting specimens with cold packs instead of dry ice could reduce costs and facilitate the timely monitoring of VL used to assess and guide antiretroviral therapy.

Importance: Nirsevimab, a monoclonal antibody against RSV, was implemented in France in September 2023. Recently, rare resistance-associated substitutions were described in RSV but the effectiveness according to lineages remains unclear. Objective: We aimed to estimate the effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages. Design: We conducted a multicenter test-negative case-control study from October 15, 2023 to March 15, 2025. Setting: This study was based on data from three national multicentric prospective studies. The 12 participating centers were secondary or tertiary hospital with a pediatric department located in France. Participants: We included all children younger than 12 months who were hospitalized for RSV bronchiolitis in one of the participating centers in France during the two first RSV epidemic seasons following the implementation of nirsevimab (from October 15, 2023 to February 29, 2024, and from October 10, 2024 to March 15, 2025). Main outcomes and measures: The main outcome of the study was the RSV test result of bronchiolitis cases. RSV whole-genome sequencing was performed using a tiled amplicon approach covering the complete viral genome, as previously described in the POLYRES studies. We estimated the effectiveness of nirsevimab by a multivariable logistic regression model adjusted for potential confounders. We estimated the adjusted risk of immunization failure for each lineage by calculating relative odds ratio to a reference lineage. A range of sensitivity analyses were conducted. Results: We included 3019 infants with bronchiolitis among which 2273 had a positive RSV test (case patients) and 746 had a negative RSV test (control patients). Overall, 373/2273 (16.4%) case patients were immunized by nirsevimab versus 423/746 (56.7%) control patients. The adjusted effectiveness of nirsevimab against hospitalization for bronchiolitis was 88.4% (95% CI, 84.5-91.4) with RSV-B and 79.4% (95% CI, 73.7-83.8) with RSV-A. The risk of immunization failure was 3.2-fold (95% CI 1.8-5.7) higher for lineages derived from A.D.3 than for lineages derived from B.D.4.1. Conclusion and relevance: In this multicentric case-control study, we observed that nirsevimab effectiveness was variable across RSV lineages, with a lower effectiveness against A.D.3 lineages compare to others. Further surveillance is needed to confirm these findings and assess their implication on RSV lineages epidemiology as nirsevimab use expands.

Abstract Objective: Examine whether prenatal adversity is associated with Neonatal Opioid Withdrawal Syndrome (NOWS) severity and the need for pharmacological treatment in infants with prenatal opioid exposure. Study Design: Prospective cohort study of 235 infants from a multi-center study of infants with prenatal opioid exposure. Maternal factors were assessed using the electronic medical record and maternal questionnaires. Latent Class Analysis (LCA) was used to derive mutually exclusive prenatal adversity groups. Results: A 3-class LCA solution provided the best fit to the data and showed 3 distinct groups: one low adversity group (Class 3, 38.7%) and 2 high adversity groups. Infants born to mothers with elevated demographic, medical, polysubstance, and mental health risk factors (Class 1, 31.9%) were more likely to require pharmacological treatment for NOWS (OR=7.70, 95% CI: 3.65-17.14) and had higher NOWS severity, as indexed by longer length of stay ({beta} = 6.08, 95% CI: 4.09-8.07), and higher maximum Finnegan scores ({beta} = 2.62, 95% CI: 1.49-3.76). Infants born to mothers with elevated medical and polysubstance risk factors (Class 2, 29.4%) were also more likely to receive pharmacological treatment for NOWS (OR=3.22, 95% CI: 1.56-6.78) and had higher NOWS severity, as indexed by higher likelihood of receiving adjunctive medication (OR=3.62, 95% CI: 1.11-12.99). Conclusion: Maternal sociodemographic, mental health, substance use, and medical adversity may serve as an early marker of NOWS severity and may aid in the prediction of which neonates will require pharmacological treatment for NOWS. Early identification of infants at high risk for NOWS could lead to earlier treatment and the potential to reduce NOWS severity, length of stay, and associated healthcare costs.

Introduction: Fighting the ventilator (FV) is characterized by a patients active counteraction of respiratory gas flow across multiple breaths during mechanical ventilation. An effective ventilation is prevented during such episodes. The objective of this exploratory study was to evaluate clinicians knowledge, perception and agreement regarding this condition. Methods: In a cross-sectional online survey, medical professionals with experience in intensive care medicine (mostly neonatal and pediatric patients) responded to 11 questions covering various clinical aspects of FV. Results: All respondents were familiar with the phenomenon and assessed it to be clinically relevant. Neonates were perceived to be predominantly affected. Promoting factors of FV included inadequate sedation and ventilation-associated factors. In clinical practice, the participants identified FV by clinical evaluation, analysis of ventilator waveforms and capnography and used both pharmacological and non-pharmacological intervention strategies. There was no consensus concerning the English terminology of the condition. Only few respondents were familiar with local guidelines to manage FV. Conclusion: Although there was consensus on the relevance of FV, diagnostics and management strategies were highly heterogeneous. Many participants agreed that poor patient-ventilator synchrony was an important cause of FV. Future work should focus on characterizing and generating evidence on FV.

Background: Localized or segmental overgrowth is a rare condition that may co-occur with vascular malformations. These diseases generally are caused by somatic mutations in the PI3K/AKT/mTOR pathway. Most lesions are progressive and may cause symptoms including pain, functional impairment, and disfigurement. Treatment options are limited, especially for the overgrowth component. Objective: To evaluate the efficacy and safety of the mTOR inhibitor sirolimus in patients with overgrowth with or without a vascular malformation over a 6-months treatment period. Methods: We conducted a single-arm, open-label, phase II study including 18 patients (12 pediatric, six adult) with overgrowth, all of whom initiated oral sirolimus. 16/18 (88.9%) participants received oral sirolimus for 6 months, with dosing adjusted to achieve target blood trough levels of 3-8 ng/mL. Primary outcome was radiological response at six months assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary outcome parameters were evaluated at three, six and nine months and included size and visual appearance of the overgrowth, quality of life (QoL), pain intensity, performance status, and safety. Results: No patient achieved complete or partial radiological response. 17 of 18 patients (94.4%) maintained stable disease at month six; one was not evaluable. QoL measured with WHOQOL-BREF improved modestly in patients aged >= 18 years (n=5, mean difference to baseline +9.3 (95%-CI: -0.9 to 19.5) in physical and +9.2 (95%-CI: 0.7 to 17.7) in psychological domains at month 6). In pediatric participants, no relevant improvement in KINDL total scores was observed over the study period. No significant changes occurred in pain scores. Performance status measured by the Lansky/Karnofsky scales showed minor improvement (mean +3.5 points (95%-CI: 1.0 to 6.1)). All patients experienced at least one adverse event, but no serious adverse events or CTCAE v5.0 grade [&ge;]3 toxicities occurred. Sirolimus was well tolerated. Six patients decided to resume sirolimus after study completion. Conclusions: Sirolimus induced minor lesion shrinkage in a subset of patients, although this did not meet the predefined radiological RECIST endpoint. However, sirolimus can lead to functional improvement in some adults, which may indicate that the primary radiological outcome did not capture patient-perceived benefit.

Abstract Many women experience menopausal symptoms after stopping hormone replacement therapy (HRT). An evidence gap remains regarding how women and healthcare professionals (HCPs) make decisions about discontinuing and restarting HRT. Aim To explore experiences of HCPs that support women when they discontinue and restart HRT. Design and setting Qualitative study with HCPs working in NHS primary care. Method Semi-structured interviews with HCPs (n = 15) conducted between October 2025 and March 2026. A preliminary coding template was created using the discussion guide as a framework. Each interview was then coded inductively against the template which developed iteratively. Team based discussion helped refine codes into themes and sub-themes, and a subsequent conceptual model was created. Results The model describes HCPs experiences of supporting women to discontinue HRT as an iterative process characterised by uncertainty. Discussions about discontinuation were commonly prompted by changes in clinical risk or annual HRT review, but decisions about whether and when to stop also depended on womens symptoms, side effects, life stage and readiness. HCPs described agreeing an individualised discontinuation strategy, providing support during the process, and reviewing women after discontinuation to consider alternative treatments or, where appropriate, restarting HRT. Conclusion HCPs recognise the importance of readiness to discontinue and that decision making should be woman led, with HCP support, clear practice guidance and opportunities to revisit treatment. Further research is needed to support women weigh up their personalised risk and benefit of continuing/discontinuing and identify discontinuation strategies that limit resurgent symptoms.

Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.

Computed tomography (CT) interpretation requires recognition of the anatomical level of each slice. Classification may facilitate preprocessing and AI-assisted fracture diagnosis. We developed deep learning models to classify craniofacial CT slices into six anatomical categories. A total of 11,769 images were collected from a multicenter database involving 10 Japanese university hospitals and the public Head-Neck-Radiomics-HN1 dataset. Patients were divided into training (70%) and evaluation (30%) sets. Five CNN architectures were trained from scratch, and hard- and soft-voting ensembles were evaluated. Individual-model accuracy ranged from 94.72% to 96.09%; the hard-voting ensemble achieved 96.46% accuracy (Cohen's k = 0.954). Although performance differed among individual models (Cochran's Q = 99.29, p < 0.001), the ensemble did not significantly outperform EfficientNetV2B1 (McNemar's p = 0.163). Errors occurred mainly between adjacent anatomical regions. Deep learning can classify craniofacial CT slices accurately and may support automated dataset organization and AI-assisted fracture diagnosis. External validation is needed.

Background: Pressure pain threshold (PPT) is commonly assessed using pressure algometry. Self-administered algometry could reduce examiner involvement and may facilitate repeated assessment outside specialist settings. Objective: To examine the concurrent agreement of a previously described syringe-based pneumatic algometer with a commercially available comparator during self-administered PPT measurement in healthy adults. Methods: Thirty healthy volunteers completed researcher-administered and self-administered pain threshold measurements utilizing an AMF-500 device and the syringe-based pneumatic algometer. Results: During self-administration, measurements from the two devices were strongly correlated (r = 0.82, p < 0.05); the mean paired difference was 6.01 N (95% CI, -0.58 to 12.59 N). Self-administered test values were lower than researcher-administered test values in the fixed-order comparison (p = 0.0029). Conclusion: According to our findings the proposed device is a valid tool for autoalgometry and may potentially be introduced as an element of routine self-assessment of PPT.

Objectives To evaluate discrepancies between radiologists and referring physicians in the interpretation of diagnostic probabilities conveyed by common Japanese expressions used in radiology reports. Materials and Methods Fifteen expressions commonly used to convey diagnostic probabilities in radiology reports were selected by five attending radiologists. An anonymous online survey was distributed to 26 radiologists and 33 referring physicians at a single institution. Participants assigned a diagnostic probability (from 0% to 100% in 10% increments) to each expression. Differences in median probabilities between radiologists and referring physicians were analyzed using the Mann-Whitney U test. Variability in interpretation was assessed using interquartile range (IQR), with IQR [&ge;] 30% defined as substantial variability. Results All radiologists (26/26) and 97% of referring physicians (32/33) completed the survey. Seven of the 15 expressions showed statistically significant differences in interpretation between radiologists and referring physicians: "c/w" (80% vs. 60%; p = 0.031), the Japanese equivalents of "present" (100% vs. 100%; p = 0.024), "suspect of" (80% vs. 70%; p = 0.007), "possibly" (50% vs. 70%; p < 0.001), "unlikely" (10% vs. 10%; p = 0.022), "cannot be ruled out" (25% vs. 40%; p < 0.001), and "not inconsistent with" (80% vs. 90%; p = 0.008). Substantial variability in interpretation (IQR [&ge;] 30%) was observed for four expressions: "cannot be ruled out" (IQR, 10%-40%), "s/o" (IQR, 60%-90%), "c/w" (IQR, 50%-90%), and "not inconsistent with" (IQR, 70%-100%). Conclusion This study revealed that nearly half of the Japanese expressions commonly used to convey diagnostic probabilities were interpreted differently by radiologists and referring physicians. These discrepancies highlight the need for a standardized lexicon to improve clarity and consistency in radiology reporting.

Children living with HIV face significant challenges with adherence to daily oral antiretroviral (ARV) treatment due to poor palatability, complicated dosing, and caregiver burden. Long-acting delivery systems designed specifically for children may help overcome these barriers. Microarray patches, also known as microneedle patches, are a needle-free drug delivery technology that could simplify treatment administration and improve adherence. This study explored the acceptability and usability of a pediatric ARV microarray patch prototype among stakeholders in South Africa and Uganda, two countries with a high burden of pediatric HIV. A formative study was conducted in 2024 with 48 participants, including caregivers, community health workers, health care providers, and decision-makers. Data were collected through qualitative methods: interviews, simulated use sessions, and observations. Participants demonstrated high usability of the prototype, with 97% completing all application steps and nearly all reporting the prototype as easy to use and expressing confidence in successful administration. Most participants found the prototypes size, wear time, and temporary skin changes acceptable, and all preferred a weekly patch over daily oral treatment. Applying multiple patches at once to achieve a therapeutic dose was considered feasible. Decision-makers foresaw strong programmatic fit of a pediatric ARV microarray patch if caregivers apply the patch at home following initial facility-based guidance. Overall, the pediatric ARV microarray patch prototype was perceived as highly acceptable and usable across diverse end users, findings that generally align with studies of microarray patches for other use cases (e.g., contraception, HIV pre-exposure prophylaxis, vaccine delivery). The simplicity, comfort, and convenience of a pediatric ARV microarray patch could substantially improve treatment adherence and quality of life for children living with HIV. Further development and clinical evaluation are warranted to advance this promising technology toward real-world use.

This paper examines the impact of Cancer Care Ontario's regionalization of lung cancer surgery on blood transfusion use for thoracic surgery at The Ottawa Hospital. Using aggregate data scraped from the paper ''Changing trends in blood transfusion: an analysis of 244,013 hospitalizations'' by Shehata et al. (2014) we estimated the effect regionalization on the log mean number of blood transfusions among thoracic surgeons (who treat lung cancer), utilizing other surgical specialties as controls. We found that the average number of blood transfusions increased significantly among thoracic surgeons following the opening of a new cancer care centre at the hospital in December 2009, while control specialties showed no parallel change. Contextualizing these results in a modified ''population level'' treatment threshold model, it is argued that the main driver of this increase in blood transfusions among thoracic surgeons was due to the influx of less skilled thoracic surgeons to The Ottawa Hospital, and the closing of thoracic surgery units at smaller hospitals which was part of the broader regionalization process.

Faster ultrahigh-resolution (UHR) photon-counting CT acquisitions facilitate breath-hold imaging, but identical reconstruction settings may conceal differences in spatial resolution. To assess spatial resolution and depiction of small airways and venous stents across helical UHR acquisition configurations. Stationary wire, airway, and venous-stent phantoms underwent one acquisition per configuration using five configurations on a dual-source scanner at 120 kVp. Reconstructions used 0.2- and 0.4-mm thicknesses, the same sharp kernel, and iterative reconstruction strength 1. We measured the full-width at half-maximum of the slice sensitivity profile (SSP) and spatial frequency at 20% of the modulation transfer function (MTF20). Rank-based F tests with Holm adjustment assessed configuration differences in resolution and variability across slices. Airway detection used a profile contrast-to-noise criterion; stent assessment was qualitative. Calculated acquisition time for 400-mm coverage decreased from 9.80 to 1.30 seconds between the slowest and fastest configurations. At 0.2-mm reconstruction thickness, median SSP increased from 0.316 to 0.496 mm, and median MTF20 decreased from 2.870 to 2.059 lp/mm (both P<.001). Interquartile ranges increased from 0.047 to 0.197 mm for SSP and from 0.256 to 0.654 lp/mm for MTF20 (both variability P<.001). Increasing reconstruction thickness to 0.4 mm increased SSP by a median 0.221 mm across 2459 matched slice-wire measurements (P<.001). At 0.2-mm reconstruction thickness, 0.4- and 0.6-mm lumens with 0.2-mm walls were detected only in the slowest configuration. Faster configurations showed less distinct stent struts and greater adjacent-wall distortion. Faster helical UHR photon-counting CT configurations had poorer spatial resolution despite identical nominal slice thickness. Consistent acquisition and reconstruction settings are important for longitudinal comparisons.

Background: Comprehensive evaluations of lung nodule detection methods remain limited, particularly regarding data from clinical routine, novel photon-counting CT (PCCT) technology, and the comparison of academic and commercial models. Materials and Methods: This retrospective study collected 1860 routine PCCT scans acquired at Hannover Medical School from 2021 to 2024. We compared four deep-learning-based lung nodule detection models, which were developed for conventional CT, namely the publicly available TotalSegmentator, nnDetection, and RadYOLO methods, as well as a commercial lung computer-aided detection (CAD) system. We evaluated the inter-model agreement in an unannotated cohort (n=1699), sensitivity in a smaller cohort of 25 manually annotated scans, and false positives as detections in 136 report-negative scans. Results: In the unannotated cohort, the commercial CAD system detected 7071, TotalSegmentator 4264, nnDetection 5254, and RadYOLO 3122 nodules. Overall, the inter-model agreement was low, and the models produced substantially different candidate nodules. Approximately 1300 nodules were detected by all models, representing 18.7% - 42.8% of each model's detections. 15.4% - 37.4% of a model's detections did not match any other model. The models showed moderate sensitivity (between 0.71, 95%-CI [0.64, 0.77], and 0.83, 95%-CI [0.77, 0.88]), and TotalSegmentator and RadYOLO produced few false positives per scan (both 0.85, 95%-CI [0.70, 1.02]). Conclusion: The lung nodules detected by four deep learning models showed high variation and a lack of consensus on clinical PCCT data. These findings highlight the importance of model benchmarking and local validation when deploying models in real-world clinical workflows.

Population Services International (PSI) set out to demonstrate the engagement of the private sector in increasing access to modern contraceptives through innovative financing strategies, with a focus on marginalised populations, by implementing the SARAL or Universal Access to Quality Contraception (UAQ) project in the city of Agra, Uttar Pradesh. The objective of the UAQ program was to provide a full basket of choices of family planning methods to newly-married women, incentivising them to delay pregnancy for a specified period. A cross-sectional baseline survey was conducted in Agra during the month of June 2022, covering 1240 currently married women. Using baseline survey data, this paper examined the determinants of women's preference for an additional child, and whether supply-side family planning interventions alone are sufficient to drive adoption of family planning methods. Regression analysis was done to find the determinants of wanting more children and the determinants of the willingness to join the program. The results show that the two most significant variables in determining a womans preference for another child are the total number of children she already has, and not having any male children resulting in a strong son preference. The most significant variable in determining a womans preference for enrolling herself in the SARAL program is whether she has faced financial constraints in accessing family planning methods, with other determinants being inconvenience of using contraceptive methods, exposure to the governments outreach about family planning, and preference for a male child. The findings indicate that womens preferences for an additional child are mostly based on their own desires, and are generally determined by the number and gender of their existing children. However, when it comes to the use of family planning methods, the husbands views are a critical factor in making family planning decisions - this would imply that family planning programs need to reach out not just to women, but to their husbands as well. Raising awareness of, and increasing exposure to family planning services is much needed, and programs should incorporate a strong Information, Education and Communication (IEC) component.

Modern clinical medicine depends on reducing complex human realities into forms that support knowledge, judgment, and action. Such reduction is indispensable to scientific medicine, but necessarily selective. A medical framing may therefore remain well warranted within medicine while becoming insufficient in relation to the reality of a particular patient. What happens clinically when the adequacy of such a framing itself becomes uncertain remains insufficiently understood. We conducted an abductive, theory-generating qualitative study of 44 patients who attended a supplementary Dialogue-Based Outpatient Clinic within a breast oncology service in Japan between 2021 and 2023, comprising 111 consultations. The clinic had no predefined clinical agenda, allowing patients to raise concerns that mattered to them. Through iterative comparison within and across cases, we examined how patients' concerns were understood and responded to clinically. Across cases, a recurrent clinical process became apparent when patient reality called the adequacy of existing medical framing into question. Exploration of patients' concerns could expose a consequential mismatch between their reality and the framing through which medicine understands and represents clinical reality. Such mismatches prompted inquiry into medical framing to identify what required reopening. Reopening occurred when the identified framing, previously treated as provisionally settled, became reconsiderable in relation to the patient's reality. Reconsideration involved examining what had been reopened and exploring clinical responses through dialogue between clinician and patient, followed by a clinical response and provisional closure. We describe this recurrent process as Clinical Epistemic Reopening (CER). CER identifies a clinical process through which the framing produced by medicine's necessary selectivity in making complex reality clinically knowable and actionable can itself become reconsiderable when patient reality reveals its limits. CER can thereby reverse the usual direction of clinical scrutiny: aspects of medicine that ordinarily function as means of understanding and acting upon the patient can themselves become objects of clinical inquiry. CER thus allows medicine to remain open to patient reality beyond the limits of its existing framings.