Both prior pre-eclamptic pregnancy and menopausal hormone therapy (MHT) are determinants for breast cancer (BC). To study the effects of prior pre-eclampsia and MHT use on BC risk. Register-based cohort study with follow-up for BC (Finnish Cancer Register 1987-2023) and MHT use (National Reimbursement Register 1994-2019). Nationwide population-based study in Finland. Women with prior pre-eclampsia (n = 31 688) and age-matched control women without pre-eclampsia (n = 91 726) who had given birth in 1969-1993. The BC risks were compared between prior pre-eclamptic and control women and between prior pre-eclamptic MHT users and non-users. Breast cancer occurred less frequently (p = 0.02) in prior pre-eclamptic women (6.6%, n = 2095) than in the controls (7.0%, n = 6410). The age-adjusted BC risk in prior pre-eclamptic women (aHR=0.89, 95% CI 0.83-0.94) was reduced. No clinical characteristics from pre-eclamptic pregnancy (e.g. severity) predicted the magnitude of the BC risk reduction.MHT use was accompanied with comparable BC risk rise in prior pre-eclamptic and control women (1.25, 1.12-1.40 vs. 1.30, 1.18-1.42). The increased risk with any MHT use was seen in both cohorts already after 5 years. This was primarily associated to estrogen-progestogen use, whereas estrogen only was not associated with BC risk in prior pre-eclamptic women. BC risk is reduced in women with a history of pre-eclampsia. The MHT-associated increase in BC risk is similar among women with or without a history of pre-eclampsia. Thus, pre-eclampsia is no contraindication for the use of MHT.
Machine perfusion technology has redefined donor and recipient criteria for liver transplantation. Despite increasing adoption, data regarding graft and recipient factors associated with unsuccessful normothermic machine perfusion (NMP) outcomes remain limited. The Organ Procurement and Transplantation Network database was used to retrospectively identify adult patients undergoing deceased donor liver transplantation with NMP preservation between January 10, 2021, and December 31, 2024. Populations were stratified by 1-year graft status, with donor and recipient factors compared. Logistic regression identified factors independently associated with NMP graft failure, and center analyses assessed program-level impacts. Among 4928 NMP cases, 398 (8.1%) experienced 1-year graft failure. They were more frequently admitted to the intensive care unit (ICU) at transplant (21.1% vs. 10.6%, p < 0.001) and had more complex abdominal histories, including higher rates of TIPS(17.0% vs. 12.0%), prior abdominal surgery (64.1% vs. 54.7%), and prior liver transplant (10.3% vs. 3.4%) (all p < 0.01). Regression analysis identified increased odds of graft failure with MELD score 35 (aOR 2.10 [1.21-3.63]), low recipient functional status (aOR 2.05 [1.31-3.21]), and prior abdominal surgery (aOR 1.33 [1.01-1.76]). Alcohol-associated liver disease (aOR 0.36 [0.23-0.56]) was the only factor conferring a protective effect. Centers with higher-than-expected standardized NMP graft failure rates were higher-volume programs with low-risk case mixes; no centers had persistently high standardized failure rates throughout the study period. Recipient factors, particularly those conferring surgical complexity, are more significantly associated with NMP graft failure than donor factors. Despite increased adoption of perfusion technologies to mitigate donor and operative risk, transplant provider clinical judgment remains critical for optimizing recipient-donor matching and outcomes.
A subset of patients with septic shock remains hypoperfused or requires escalating vasopressor support despite initial resuscitation. Although this pattern may suggest progression toward refractory septic shock, early high vasopressor requirements or persistent hypoperfusion may still reflect potentially modifiable contributors, including unresolved infection, inadequate fluid administration, metabolic derangements, iatrogenic factors, or cardiac dysfunction. The recent SCCM/ESICM consensus provides expert-derived criteria for refractory septic shock, but the preceding bedside process of reassessing potentially reversible contributors remains less explicitly operationalized. This Perspective proposes a pragmatic framework for structured reassessment in apparent refractory septic shock. Refractoriness is approached as a multidimensional construct shaped by severity, time in shock, and prior optimization, in line with current consensus criteria. To operationalize the optimization dimension, we present the "usual suspects": a parallel, hypothesis-driven bedside reassessment of potentially reversible contributors during an apparent-refractory trajectory. Antimicrobial adequacy and source-control status provide the foundational substrate. In parallel, clinicians may reassess fluid responsiveness, tolerance, and efficiency; endocrine, metabolic, and iatrogenic contributors to vasoplegia, such as acidemia and sedation burden; and cardiac mechanisms, including ventricular performance, ventriculo-arterial coupling, and dynamic left ventricular outflow tract obstruction. The relative contribution of each domain is expected to vary across patients and over time, requiring reassessment guided by the dominant physiology rather than by a fixed sequence. This framework is intended as an operational companion to current consensus definitions of refractory septic shock. By organizing the bedside evaluation of potentially reversible contributors, it may help clinicians interpret persistent hypoperfusion and vasopressor escalation during the transition from apparent to established refractoriness.
Burnout among healthcare workers, especially in maternity units, is prevalent globally and exacerbated in resource-constrained contexts, contributing to decreased quality of care. Doctors in a maternity care unit (MCU) in a large Namibian public hospital complex were found to be at high risk of burnout, indicating need for intervention. Existing burnout interventions are predominantly individually-focused, created in a top-down manner and devised in high-resource settings. A dearth of research exists on burnout interventions that are contextually-fitted to low- and middle-resource settings in sub-Saharan Africa. This research aimed to explore how a burnout intervention could be co-created with local stakeholders in a Namibian public hospital MCU through an Interactive Learning and Action (ILA) approach. A research team comprising doctors of varying clinical levels was recruited and senior management figures were consulted throughout the ILA process. The iterative action-research process consisted of workshops with specific objectives, a training session, dialogue sessions and evaluative interviews. Based on a needs assessment, the research team devised ideas for six interventions. Priority setting of these interventions selected a mentorship programme to be fully developed and implemented. Outputs of each co-creation session created inputs for the next. After initial implementation of the intervention, adaptations were made based on input from end-users. End-evaluation showed the intervention's potential to prevent and mitigate burnout by stimulating increased feelings of support, strengthening social relationships, and building trust. Barriers to uptake included distant mentorship style, lack of accountability, and perception of the intervention as an increased workload. Facilitators encompassed enthusiastic and personal mentorship style and positive perceptions of the intervention as helpful with matters like case management. Co-creating and implementing a context-specific intervention to address healthcare worker burnout appeared feasible in a sub-Saharan African context without funding. By leveraging local knowledge and skills, co-researchers collaboratively devised solutions addressing the needs of various levels of staff, created ownership of the intervention, and proactively integrated accommodations to contextual constraints into its design and implementation. Embracing local- and user-led co-creation in intervention development offers a promising avenue for addressing complex challenges.
The built environment, comprising homes, buildings, roads, public spaces, infrastructure, land use, civic design, and amenities, has a considerable influence on occupational health. In India's tea plantations, where women comprise majority of the workforce, the built environment plays a crucial role in determining occupational health. The aforementioned point can be explained by the co-occurrence of living and working conditions, which often coexist in tea plantations, further resulting in vulnerabilities to the health of women workers. Therefore, to understand the influence of built environment on the occupational health of women workers in tea plantations of India, the present paper employs a systematic review using the PRISMA 2020 framework. In the first search, 421 studies were identified, of which 21 studies met all the inclusion criteria. A quality appraisal and risk of bias of the included studies have been undertaken. The results identified that musculoskeletal disorders (MSDs) are the most prevalent occupational health consequence, affecting over 80 % of the women workers in Indian tea plantations, substantiated by a range of estimates in the studies reviewed. Gendered disparities in wage earning, self-autonomy, and dual responsibilities often lead to emotional distress, as delineated in minimal of the reviewed studies, grounded on self-disclosed or qualitative analysis. Further, deprived housing conditions and other facilities across the reviewed studies reflect institutional negligence. Therefore, by conducting a systematic synthesis of occupational health of women workers in the Indian tea plantation sector through the lens of the built environment, prior accounts have been extended. Addressing these issues is essential for safeguarding women workers, which will ensure the longevity of the Indian tea industry.
Finely tuned Gamma (FTG) activity-spontaneous narrowband Gamma oscillations (sFTG) or entrained to half the stimulation frequency (eFTG)-is typically linked to on-medication states and dyskinesia in Parkinson's disease (PD), making it a potential physiomarker for adaptive deep brain stimulation (aDBS). However, its characteristics and determinants remain unclear. This exploratory study examined FTG prevalence, clinical correlates, and associations with DBS parameters, to guide future prospective work. Local field potentials recorded in the subthalamic nucleus (STN) of PD patients with Percept neurostimulator were retrospectively analyzed, based on a predefined set of clinically relevant questions. Among 67 patients (134 STNs), sFTG occurred in 19% of STNs, and 1:2 eFTG in 28%. FTG was always associated with a medication, stimulation, or a stun-effect induced ON-state or a combination thereof, but could occur independent of dyskinesia. sFTG was most often observed during the transition from β to eFTG (54%), and rarely co-occurred shortly with eFTG (19%). β activity often co-occurred with FTG (50%), showing an inverse power relation with 1:2 eFTG. The occurrence of 1:2 eFTG depended on stimulation amplitudes. In 12 STN (9%), subharmonic artifacts occurred. FTG seems to be associated with an overall ON-state, independent of dyskinesia. The ratio 1:2 eFTG likely reflects entrainment of the neural populations underlying sFTG, but can occur without prior occurrence of sFTG, depending on stimulation amplitude consistent with "Arnold's tongue" framework. Future research should further specify β and FTG subtype interactions, while accounting for artifacts. Combining these physiomarkers may improve aDBS algorithms. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
The present study aimed to evaluate the impact of intracanal medicaments-calcium hydroxide (CH) and calcium hydroxide/nano-chitosan (CH/NC)-on the push-out bond strength (POBS) of AH Plus (AHP) and NeoSEALER Flo (NSF). Nano-chitosan (NC) characterization was done using transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential analysis. Sixty extracted maxillary central incisors were instrumented up to X5 (50/0.06). Based on intracanal medicament used, specimens were allocated into three groups (n = 20): Group I; no intracanal medicament (control), Group II; (CH), and Group III; (CH/NC). Intracanal medicaments were removed after one week of incubation. Each group was subdivided based on sealer used (n = 10): subgroup A (AHP) and subgroup B (NSF). Obturation was performed with cold lateral compaction. After one week of incubation, roots were sectioned and a universal testing machine was used to evaluate POBS. Three-way ANOVA and Chi-square tests were conducted at 0.05 significance level. TEM showed mostly spherical NC particles with diameters less than 50 nm. DLS analysis revealed a hydrodynamic Z-average diameter of 62.4 nm with a polydispersity index of 0.195. Zeta potential analysis demonstrated a positive surface charge of + 47.57 mV. The "medication" factor, "medication/sealer", "medication/root level" and "sealer/root level" interactions significantly affected POBS (P < 0.05). Neither "sealer" nor "root level" factors significantly affected POBS (P > 0.05). Pooled POBS data revealed that: IA and IB subgroups were significantly higher than IIA, IIB, IIIA and IIIB subgroups (P < 0.05). Regarding failure mode, tested subgroups showed no significant difference (P > 0.05). Under the conditions of this study, prior application of CH or CH/NC reduced POBS for both sealers compared with controls. The addition of NC to CH did not provide a statistically significant improvement in POBS compared to CH alone. Overall, AHP and NSF demonstrated comparable POBS to root canal dentin.
COVID-19 infection risk has not been evenly distributed across racial groups, with exposure being shaped by social and structural factors. The emergence of highly transmissible variants (i.e., Omicron) dramatically increased infection rates. However, it remains unclear whether racial disparities in infection risk disappeared or persisted over the course of the pandemic. To understand how SARS-CoV-2 infection risk differed between racial groups in Canada and whether those disparities changed with the Omicron variant. We analyzed cross-sectional SARS-CoV-2 seroprevalence data from the Canadian Blood Services serosurveillance program (June 2020 to April 2023) using a previously described dynamic susceptible-infection model, while accounting for seroreversion. Race-specific force of infection was estimated for the pre-Omicron and Omicron periods (with the emergence of Omicron defined as beginning December 26, 2021). Prior to Omicron, racialized individuals had a 121% higher force of infection (IRR = 2.205; 95% CI: 2.115-2.299). During the Omicron period, infection rates rose significantly within each racial group relative to the pre-Omicron period, with a 55.52-fold increase among White individuals and a 31.27-fold increase among racialized individuals. Despite this, racialized individuals remained disproportionately affected following the emergence of Omicron, with 24% higher infection rates than those of their White counterparts (IRR = 1.242; 95% CI: 1.231-1.253). Widespread infection during Omicron did not result in epidemiologic equity, as racialized populations continued to experience higher infection risk despite crude seroprevalence depicting convergence.
Understanding the pathways through which diet affects human metabolism is a central task in nutritional epidemiology. This article proposes novel methodology to identify food items associated with blood metabolites in 2 cohorts of healthcare professionals. We analyze 244 metabolites characterized by statistical complexities that include skewness, left-censoring, and structural missingness. Though existing methods can address such factors in low-dimensional settings, they cannot exploit the nutritional or statistical relationships among the 30 considered food intake variables, and they are unsuitable for performing high-dimensional inference. To address these challenges, we develop a novel Bayesian variable selection framework for metabolite response variables based on a skew-normal censored mixture model, while exploiting substantive information on the considered food items via a Markov random field prior. Applying this methodology to the cohort data identifies multiple metabolite-diet associations that are consistent with previous research as well as several potentially novel associations that were not detected using standard methods. The proposed approach is implemented in the R package multimetab, facilitating its use in high-dimensional metabolomic analyses.
Brg1 is a core ATPase subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex that regulates DNA accessibility for RNA polymerase II (Pol II), transcription factors, and DNA repair enzymes. Phosphoproteomic profiling of highly malignant ovarian clear cell carcinoma (OCCC) cell lines revealed reduced levels of several SWI/SNF components and decreased Brg1 phosphorylation within its histone-binding region. Prior work showed that phosphorylation-mimic and phosphorylation-deficient mutants alter chromatin-silencing factors, producing chromatin condensation and decondensation, respectively. Here, we performed RNA-seq in Brg1-deficient JHOC-5 cells and in isogenic cells expressing Brg1-WT, phosphorylation-mimic brg1-S1452D, or phosphorylation-deficient brg1-S1452A. PCA and hierarchical clustering separated brg1-S1452A from the other lines, indicating a strong transcriptional impact of Ser1452 dephosphorylation. JHOC-5 and brg1-S1452A shared altered expression of Pol II-promoter-regulated genes. Apoptosis genes (BCL2, FGFR2, ZC3H12A, and NFKBIA) showed reciprocal expression between brg1-S1452D and brg1-S1452A, consistent with increased and decreased apoptosis, respectively. Genes linked to cell adhesion/migration and neuronal development also differed, accompanied by reduced cell circularity in brg1-S1452A. Overall, Brg1 phosphorylation at Ser1452 shapes SWI/SNF-mediated chromatin remodeling to regulate transcriptional programs controlling apoptosis and cell morphology.
Aortic pseudoaneurysm secondary to Mycobacterium tuberculosis infection is exceedingly rare. Extrinsic compression of the left main coronary artery by an aortic pseudoaneurysm is also uncommon, and cases attributable to tuberculosis are particularly rare. This report describes a mid-ascending aortic pseudoaneurysm causing left main coronary artery compression resulting in cardiac arrest in a patient with a history of tuberculosis, which was successfully managed with emergent surgical intervention. A 76-year-old man with a history of tuberculosis and radiologic findings suggestive of previous tuberculous disease experienced cardiac arrest prior to transfer and was referred to the authors' institution. Coronary angiography, performed because of chest pain and elevated cardiac biomarkers, demonstrated extrinsic compression of the left main coronary artery by an ascending aortic pseudoaneurysm. Return of spontaneous circulation was achieved after approximately 48 min of cardiopulmonary resuscitation. Upon arrival at our emergency department, computed tomography revealed a 6-cm pseudoaneurysm of the proximal-to-mid ascending aorta. Emergent surgical resection of necrotic ascending aortic tissue and graft replacement of the ascending aorta were performed, and the postoperative course was favorable. Ascending aortic pseudoaneurysm may cause sudden cardiac arrest through extrinsic compression of the left main coronary artery. In patients with a history or radiologic evidence of tuberculosis, tuberculosis-related involvement may be considered, but definitive surgical treatment should not be delayed in life-threatening presentations.
Accurate delineation of cerebrovascular structures from Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) and Computed Tomography Angiography (CTA) is essential for the clinical diagnosis and treatment of cerebrovascular diseases. However, the intricate topology and fine-scale nature of cerebral vessels pose significant challenges for deep learning methods, which often struggle to capture long-range dependencies and precise morphological details. In this work, we propose VesMamba, a deep learning framework that integrates explicit vascular morphological priors into a state-space model. Unlike generic SSM-based methods that rely on fixed scanning patterns, we introduce a Tri-oriented Vessel-aware Mamba (ToVM) module, which dynamically reorders input 1D sequences using cerebrovascular edge features to better model complex vascular structures. Complementarily, we present the 3D Large-Small Gated Convolution (LSGC) module after the ToVM module to preserve critical spatial information. We conducted extensive experiments on two TOF-MRA and one CTA dataset, comparing our method with eight state-of-the-art approaches. Our results show that VesMamba achieves superior performance on the majority of evaluation metrics relative to all competing methods.
This study aimed to describe characteristics of people with elevated BMI by presence versus absence of obesity diagnosis and trends over time. Data from adults with recorded BMI ≥ 30 kg/m2 (United States [US]; Optum's deidentified Clinformatics Data Mart database) or ≥ 25 kg/m2 (Japan; Medical Data Vision) between 2016 and 2024 were included. Characteristics were described at index (most recent BMI or obesity diagnosis), stratified by presence versus absence of prior recorded obesity diagnosis. In the United States (N = 3,584,120; 70.1% with obesity diagnosis), prevalence of interrelated diseases was high overall and higher in those with versus without obesity diagnosis, e.g., type 2 diabetes (49.3% vs. 29.9%), chronic kidney disease (32.9% vs. 18.8%), and heart failure (23.3% vs. 9.8%). In Japan (N = 3,140,900; 2.3% with obesity diagnosis), interrelated disease burden was also higher in those with versus without obesity diagnosis, e.g., type 2 diabetes (42.2% vs. 25.9%) and chronic kidney disease (14.3% vs. 8.6%). In the United States, interrelated disease burden was generally higher for those first diagnosed in 2024 versus those diagnosed in 2016-2020. In people with elevated BMI in the United States and Japan, there was underdiagnosis of obesity and a high prevalence of interrelated diseases.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, characterized by favorable prognosis and low incidence of distant metastasis. However, brain metastasis from PTC is rare, and its development years after the initial diagnosis is even more uncommon. Given the potential clinical implications of late metastasis, there is a need to reconsider follow-up strategies for high-risk PTC patients. A 54-year-old woman with a history of PTC diagnosed 8 years earlier presented with progressive headaches and mild left-sided hemiparesis. She had previously undergone multiple surgeries and radioiodine therapy after the initial diagnosis and had a history of childhood neck irradiation. Imaging revealed a brain mass, which was confirmed as isolated brain metastasis from PTC following biopsy after surgical resection. Despite persistently undetectable serum thyroglobulin (Tg) levels and no lymph node metastasis at the time of primary surgery, this patient developed isolated brain metastasis 8 years after initial treatment. The patient underwent craniotomy to remove the metastatic brain lesion. No adjuvant radiotherapy was given postoperatively. The patient recovered well after surgery, with mild left-sided hemiparesis (4/5 muscle strength). At the most recent follow-up, no additional distant metastases were detected. This case highlights the importance of extending the follow-up period for high-risk PTC patients, including those with prior neck irradiation or aggressive tumor features. Late metastasis can occur even in patients with initially favorable prognoses and normal biochemical markers. Imaging-based surveillance is necessary to detect late metastasis early. The findings support extended follow-up strategies to enable timely intervention and improve outcomes in high-risk patients with PTC.
Communication skills are central to clinical practice and are typically assessed through Objective Structured Clinical Examinations (OSCEs). Prior research indicates that self-reported questionnaires, simulated-patient evaluations, and expert assessments each offer valuable yet non-interchangeable perspectives on medical students' communication skills. However, it remains unclear whether these assessment modalities, when collected during the academic year, can predict subsequent OSCE performances and thereby help identify students struggling to meet communication competency standards. This study examined whether self-reported empathy, the ability to recognize others' emotions, and simulated-patient evaluations of communication skills predict later OSCE performances in medical students. Data were drawn from the ETMED‑L longitudinal open-cohort project at the University of Lausanne. The third- and fifth-year medical students who completed the yearly ETMED‑L online questionnaire and consented to the use of their communication skills evaluations were eligible for the present study. Self-reported empathy was assessed using validated multidimensional instruments and the ability to recognize others' emotions was measured with a performance-based task. Simulated patients used a standardized form to evaluate communication skills during mandatory formative interviews. OSCE performances were rated by experts using structured communication grids and total exam points. Structural equation modelling was used to examine how self-reported empathy, the ability to recognize others' emotions, and simulated-patient evaluations independently and jointly predict OSCE performances. A sample of 468 third‑year and 399 fifth‑year students were analyzed. In both cohorts, self‑reported empathy, the ability to recognize others' emotions, and simulated-patient evaluations independently predicted OSCE performances. In combined models, only simulated-patient evaluations remained significant predictors of OSCE performances, with a moderate effect size for the third-year cohort and a small effect size for the fifth-year cohort. Simulated-patient evaluations of student communication skills during formative training are more strongly associated with later expert-rated OSCE performances than both self-reported empathy and a performance-based measure of the ability to recognize others' emotions. These findings underscore the practical value of structured simulated‑patient programs within competency‑based medical curricula, as they may help identify students who have difficulty attaining required communication competencies.
Our understanding of trypsin, its zymogenicity and its inhibition is intimately intertwined with the history of biochemistry. Early structural studies revealed its close relationship to chymotrypsin, with its active site triad, oxyanion hole and N-terminus involved in a buried salt bridge near the active site. Its complex with basic pancreatic trypsin inhibitor provided a model for how peptide substrates bind to and are cleaved by the proteinase. Analysis of crystals of trypsinogen by Wolfram Bode and Robert Huber revealed that a large region of the zymogen is disordered prior to proteolytic activation, with an associated disruption of the oxyanion hole and substrate binding pockets, highlighting the importance of disorder in protein function. As archetype of numerous therapeutically important serine proteinases, trypsin can also serve as a surrogate for structure-based drug design. Trypsin variants designed for ligand binding studies resulted however in an unexpected plasticity of the mutant proteins that underlines the complexity of protein stability. A trypsin variant selected for peptide ligation (reverse proteolysis) was shown to possess zymogen-like characteristics that proved central to its application in modification of therapeutic proteins. The review pays homage to the seminal works of Bode and Huber and their influence on modern structural biology.
Myxomas are the most prevalent primary cardiac tumors, primarily found in the left atrium. Symptoms include mitral valve obstruction and systemic embolization, leading to complications like ischemic stroke. Accurate diagnosis through cardiac evaluation is crucial to prevent delays in treatment and recurrence of symptoms. A 53-year-old male patient with a history of an acute stroke three months prior and an incomplete workup presented with right-sided hemiplegia and dysarthria. A diagnosis of acute stroke was made, and the patient was managed with mechanical thrombectomy, retrieving a large clot in the Middle Cerebral Artery (MCA) territory. Cardiac workup revealed a large mobile mass in the left atrium, and a diagnosis of myxoma was made. The tumor was removed successfully via thoracotomy. The patient remained asymptomatic without any residual mass. While cardiac myxomas are primarily benign tumors, they can occasionally lead to catastrophic complications. A comprehensive cardiac evaluation, including Transthoracic Echocardiography (TTE), is essential in stroke cases where a cardioembolic source is suspected to identify the underlying pathology. Our case highlights how omission of TTE during the index admission resulted in recurrent stroke despite anticoagulation and underscores the preventable nature of such complications through routine cardiac imaging in suspected cardioembolic events.
Feeding difficulties are common in early infancy and may persist beyond the neonatal period, affecting growth, development, and the parent-infant relationship. While existing research has largely focused on short-term breastfeeding outcomes, there is limited understanding of how early feeding challenges evolve across infancy and early childhood. To examine associations between maternal-reported feeding challenges experienced during the birth hospitalisation and the presence of ongoing feeding difficulties in infancy and early childhood, and to describe the frequency, nature, and progression of early and current feeding concerns. A cross-sectional online survey was completed by 147 mothers of children born between 2020 and 2023, predominantly from Australia, who experienced feeding difficulties from birth. The questionnaire included structured and open-ended questions regarding hospital feeding experiences, post-discharge outcomes, and current feeding status. Descriptive statistics and Fisher's Exact Tests were used to examine associations between early feeding challenges and current feeding difficulties. Feeding difficulties during the initial hospital stay were reported by 68% of participants, and 32.7% of the children were reported to have current feeding problems. Early sucking difficulties and tongue-tie were significantly associated with ongoing feeding concerns (p = 0.039 and p = 0.036, respectively). Tube feeding and the absence of breastfeeding during hospitalisation were more commonly reported among infants with early feeding difficulties. Nearly one-third of infants required hospital readmission post-discharge, most commonly for feeding-related complications. Maternal reports suggest that early feeding challenges identified during hospitalisation are commonly reported and may be associated with ongoing feeding difficulties in infancy and early childhood. These findings highlight the importance of early identification, multidisciplinary assessment, and consistent feeding support prior to discharge. Further prospective research is needed to determine which screening and support approaches most effectively improve long-term feeding outcomes.
Persistent hiccups lasting more than 48 hours are rare but can markedly impair quality of life. Conventional therapies are often limited by transient efficacy, side effects, invasiveness, highlighting the need for safer and more effective options. A 62-year-old male with chronic hepatitis B, hypertension, type 2 diabetes, prior pulmonary tuberculosis, and gastrointestinal disorders presented with fever for 7 days and persistent hiccups for 4 days, occurring at a frequency of 40 to 50 times per minute. Symptoms significantly interfered with eating, sleeping, and daily activities. After excluding central nervous system and metabolic causes, the patient was diagnosed with persistent hiccups associated with pulmonary infection and gastrointestinal dysfunction. An initial ultrasound-guided phrenic nerve block provided transient relief for about 4 hours. Subsequently, combined therapy with daily phrenic nerve block and twice-daily percutaneous auricular vagus nerve stimulation (aVNS) was administered for 3 consecutive days. By day 7, the hiccups had resolved completely, with the hiccups assessment instrument score decreasing from 9 to 0 and the Pittsburgh sleep quality index score improving from 16 to 2. After initiation of aVNS, the patient was followed up for 1 month after discharge. No recurrence of persistent hiccups, delayed complications, or treatment-related adverse events were observed during follow-up. This case suggests that ultrasound-guided phrenic nerve block combined with aVNS may offer a minimally invasive, safe, and effective treatment option for persistent hiccups unresponsive to conventional therapy. Larger studies are warranted to validate efficacy and long-term outcomes.
Functional decline in middle-aged and older adults involves transitions among functional independence, mild limitation, and severe limitation. Prior studies have often used binary disability endpoints, leaving it unclear how multidimensional adversity burden relates to staged deterioration. Using the China Health and Retirement Longitudinal Study (CHARLS) as the discovery cohort and the English Longitudinal Study of Ageing (ELSA), Survey of Health, Ageing and Retirement in Europe (SHARE), and Mexican Health and Aging Study (MHAS) as validation cohorts, we examined whether baseline adversity burden was associated with subsequent functional-state deterioration and reduced maintenance of independence. Participants were aged ≥50 years. Records with missing age or age coding above 100 years were excluded. CHARLS used a 7-domain adversity score, whereas ELSA, SHARE, and MHAS used a harmonized 4-domain score. Functional status was classified using cohort-specific daily-function difficulty counts as independence, mild limitation, or severe limitation. Adjacent-wave person-interval data were analyzed with generalized estimating equations to estimate deterioration between consecutive waves. Robustness analyses included inverse probability weighting, multiple imputation, deterioration or death, baseline-independence restriction, exclusion of the first follow-up interval, leave-one-domain-out analyses, and a 4-cohort 1-stage pooled model. CHARLS baseline sample included 13,717 participants; 11,518 entered the complete-covariate transition model. Each additional adversity domain was associated with higher odds of functional-state deterioration (odds ratio [OR], 1.323; 95% confidence interval [CI], 1.293-1.352). The association was stronger among participants starting from independence (OR, 1.377) and remained present among those with mild limitation who experienced further deterioration (OR, 1.193). External validation showed consistent associations in ELSA (OR, 1.513), SHARE (OR, 1.373), and MHAS (OR, 1.349). The fixed-effect pooled OR was 1.402 (95% CI, 1.374-1.430), and the random-effects estimate was similar (OR, 1.409; 95% CI, 1.317-1.507). Maintenance of independence was lowest in the high-adversity group. Multidimensional adversity burden served as a longitudinal risk marker for functional deterioration and reduced maintenance of independence. These findings support risk stratification and identification of high-adversity groups for future integrated intervention studies, although further harmonized validation and prospective intervention evidence are needed before the score can be used as an intervention-guiding tool.