Accurately distinguishing between healthy and diseased states is fundamental to clinical diagnostics. This paper introduces the Harmonic Fowlkes-Mallows (HFM) index, a novel and robust metric for assessing diagnostic accuracy and identifying optimal cut-off points. The proposed HFM index integrates performance across both positive and negative classes by combining the traditional Fowlkes-Mallows Index (FM) with the proposed Negative Fowlkes-Mallows Index (NFM), using a weighted harmonic mean. Unlike conventional measures such as the F1-score or Youden Index, HFM provides a more comprehensive evaluation of classification performance by simultaneously addressing sensitivity and specificity. Additionally, it incorporates a tunable β parameter to adjust for asymmetries in class importance. Through simulation studies, the HFM index demonstrates strong performance in binary classification tasks and proves effective in selecting optimal decision thresholds. To further demonstrate its practical utility, we apply the HFM index to real-world breast cancer data and compare its performance with other diagnostic accuracy measures.
To evaluate the effects of predictable and unpredictable chronic stress on the development and severity of periapical lesions in rats. Thirty-two male Wistar rats were randomly allocated into four groups (n = 8 each): control, apical periodontitis without stress, apical periodontitis with predictable stress, and apical periodontitis with unpredictable stress. Emotional stress protocols were applied for 42 days, and apical periodontitis was induced on day 21 by pulp exposure. Stress induction was confirmed through behavioural evaluation using the open field and Y-maze tests. The severity of periapical lesions was assessed by microcomputed tomography and histological analysis. Data were analysed using Student's t-test, Mann-Whitney, one-way ANOVA, or Kruskal-Wallis tests (p < 0.05). Behavioural tests confirmed successful stress induction, with both stressed groups demonstrating reduced exploratory activity compared to non-stressed animals. Animals exposed to unpredictable stress developed significantly larger periapical lesions and exhibited higher inflammatory infiltrate scores than those subjected to predictable stress or no stress (p < 0.05). Microcomputed tomography findings corroborated the histological results, confirming the greater severity of apical periodontitis in the unpredictable stress group (p < 0.05). Unpredictable chronic stress significantly exacerbated the development and severity of periapical lesions, suggesting that stress predictability may act as a modulatory factor in apical periodontitis progression.
Lipedema is a prevalent chronic condition in women, characterized by a painful and symmetrical accumulation of adipose tissue primarily in the lower limbs. Its diagnosis is based on specific clinical characteristics; however, these characteristics lack robust scientific validation. Furthermore, lipedema is frequently misdiagnosed as obesity. This study aims to compare quality of life and physical and psychological characteristics between patients with obesity with and without lipedema. This cross-sectional study included 30 patients with obesity and lipedema (Lip-Obes group) and 29 patients with only obesity (nonLip-Obes group). Quality of life, body composition (BMI, fat free mass, fat mass, waist-to-hip ratio, waist-to-height ratio, leg volume), pain (pain pattern, pressure pain thresholds, pain interference, pain distribution, symptoms of neuropathic pain), physical functioning (hand grip strength, quadriceps strength, functional exercise capacity, functional mobility and physical activity level), and psychosocial functioning (pain catastrophizing, depression, anxiety, and stress, body image dissatisfaction, self-efficacy, and eating difficulties) were assessed using clinical measurements and self-reported outcomes. Statistical analyses were performed using independent t-tests or Mann-Whitney U tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables. A two-sided p-value of < 0.05 was considered statistically significant. Compared to the nonLip-Obes group, the Lip-Obes group showed greater impairments in quality of life (p < 0.05). Despite similar body composition variables, the Lip-Obes group had lower waist-to-hip, waist-to-height, upper leg-to-waist, and lower leg-to-waist ratios, as well as higher total limb volume than the nonLip-Obes group. Additionally, the Lip-Obes group reported higher pain intensity, lower pressure pain thresholds in the arms and legs, and greater pain interference than the nonLip-Obes group (p < 0.05). Although hand-grip strength and physical activity levels were comparable, the Lip-Obes group exhibited lower quadriceps strength, functional exercise capacity, and functional mobility (p < 0.05). Additionally, the Lip-Obes group reported higher pain catastrophizing, greater body image dissatisfaction, and more severe eating difficulties than the nonLip-Obes group (p < 0.05). No significant differences were found in depression, anxiety, stress, or self-efficacy between groups (p > 0.05). This cross-sectional study highlights the complex nature of lipedema, providing preliminary evidence of differences in quality of life and distinct body composition and physical and physiological characteristics between patients with obesity with and without lipedema. These results emphasize the need for further research to identify diagnostic biomarkers for lipedema through in-depth investigations. Future studies should also focus on developing and optimizing a multidisciplinary treatment approach tailored to the unique characteristics of patients with lipedema.
Several ultrasound risk stratification systems have been developed mainly with the aim of identifying benign lesions and thereby avoiding unnecessary fine needle aspiration (FNA) cytology. This randomized controlled trial assessed if the use of an ultrasound risk stratification system improved identification of lesions requiring surgical treatment. This was a multi-centre, unblinded and interventional randomized trial comparing selective and non-selective FNA in Western Sweden. Patients were randomized to either selective cytology according to EU-TIRADS criteria or non-selective cytology. A total of 195 patients were included, 93 in the non-selective group and 102 in the selective group, between February 2022 and December 2023. The frequency of nodules with Bethesda category IV-VI (primary outcome) was higher in the selective group (26% versus 13%, p=0.039). The rate of malignancy (secondary outcome) was similar in both groups; 8% in the selective group versus 5% in the non-selective group. The frequency of patients undergoing cytology was reduced from 83% in the non-selective group, to 71% in the selective group. Considering only patients with at least one nodule yielding EU-TIRADS 3 or higher, cytology was omitted in 7% of patients in the selective group, whereas no cytology was omitted in the non-selective group. This randomized controlled trial supports the use of EU-TIRADS to correctly select neoplastic nodules for FNA without missing thyroid cancer. The proportion of patients where FNA can be safely omitted using EU-TIRADS may however be exaggerated, indicating a need for further refinement of risk stratification systems for thyroid cancer diagnostics. Ultrasound is usually the first imaging test used to examine thyroid nodules (lumps in the thyroid gland). Over the past 15 years, several ultrasound-based systems have been developed to estimate the risk that a nodule is cancerous. These systems mainly aim to identify harmless (benign) nodules so that unnecessary needle tests—called fine needle aspiration (FNA)—can be avoided.This study presents results from the first randomized trial investigating whether using such an ultrasound risk system improves the identification of nodules that do not need FNA. The main goal of this study was to see how well the EU-TIRADS system can identify thyroid nodules that should be tested with FNA. The main outcome we looked at was how often these biopsies showed results that could indicate cancer (Bethesda categories IV–VI), since these findings usually lead to more tests or treatment. We expected that using EU-TIRADS to carefully select which nodules to biopsy would result in a higher proportion of these concerning findings compared to biopsying nodules without using this system.A second goal was to understand the risk of missing thyroid cancer when using EU-TIRADS. To measure this, we calculated the rate of malignancy (ROM), which is the number of patients diagnosed with thyroid cancer after surgery divided by the total number of patients examined in each group. We expected that this rate would be similar between the two groups, meaning that using EU-TIRADS would not increase the risk of missing cancer. This was a regional, multi-centre study carried out at four hospitals in Western Sweden. It was a forward-looking (prospective), randomized, and unblinded trial.Patients were randomly assigned to one of two groups: Selective testing: FNA was only performed based on recommendations from an ultrasound risk system called EU-TIRADS.Non-selective testing: FNA was performed more routinely, without strict use of the risk system. Between February 2022 and December 2023, 195 patients took part in the study: 93 in the non-selective group and 102 in the selective group. Nodules classified as higher risk (Bethesda categories IV–VI) were more common in the selective group (26%) than in the non-selective group (13%).The actual cancer rate was similar in both groups: 8% in the selective group and 5% in the non-selective group.The number of patients who underwent FNA was lower in the selective group (71%) compared to the non-selective group (83%).When looking only at patients with nodules considered at least mildly suspicious (i.e. EU-TIRADS 3 or higher): FNA was omitted in 7% of patients in the selective group.No patients omitted FNA in the non-selective group.This randomized study supports using the EU-TIRADS system to help decide which thyroid nodules should be tested with FNA, without missing cancers. However, the results suggest that the number of patients who can safely avoid FNA using this system may have been overestimated. This means that further improvements to these risk assessment systems are still needed.
Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype-phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria. A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher's exact tests. Ciprofloxacin non-susceptibility was high at 86.0%. Resistance was primarily driven by a conserved chromosomal mutation profile; the combination of gyrA S83L, gyrA D87N, and parC S80I was present in 85 isolates and was associated with ciprofloxacin non-susceptibility in all affected isolates in this cohort. Isolates with only gyrA mutations were resistant to nalidixic acid but susceptible to ciprofloxacin, consistent with a stepwise resistance pathway. In this cohort, the triple QRDR signature (gyrA S83L + gyrA D87N/Y + parC S80I) was a perfect positive predictor of ciprofloxacin non-susceptibility (85/85; 100%). The ST131 lineage dominated, accounting for 21.5% of isolates and universally carrying the complete triple QRDR profile; notably, no ST131 isolate carried a PMQR determinant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 15.0% of isolates but were not independently associated with ciprofloxacin non-susceptibility in this cohort in the absence of concomitant QRDR mutations. Efflux pump genes were ubiquitous and non-predictive. Notably, six isolates, all from urine, were non-susceptible (R/I) despite lacking all known QRDR and PMQR determinants, pointing to uncharacterized mechanisms. In a multivariable logistic regression model that included ST131 status, PMQR carriage, and parE mutation status, ST131 was associated with ciprofloxacin non-susceptibility (adjusted OR 5.96, 95% CI 1.21-29.4, p = 0.028), whereas PMQR carriage was not (adjusted OR 0.94, 95% CI 0.18-4.85, p = 0.94). The triple QRDR signature was not included in this model because it perfectly predicted ciprofloxacin non-susceptibility in this cohort. Resistance patterns varied by clinical source, with the highest burden in bloodstream and wound infections. This stepwise hierarchy from first-step gyrA mutations to the classic triple QRDR profile is summarised in the graphical abstract, Fig. 1. Fluoroquinolone resistance in Nigerian clinical E. coli is predominantly driven by chromosomal QRDR mutations within successful clones like ST131. PMQR genes and efflux pumps appeared to play a supplementary role rather than being independent drivers of ciprofloxacin resistance in this cohort. These data support prioritising key QRDR mutations in genomic reporting and local stewardship decisions, while the QRDR-negative resistant urine isolates require further investigation.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may affect cognition, but its association with incident dementia remains inconsistent. We explored the association of SARS-CoV-2 infection and its vaccination with dementia risk in a nationwide sample of middle-aged and older adults. This nested case-control study used electronic healthcare data from Israel's largest health provider. Participants were dementia-free individuals aged ≥ 50 years at baseline (March 2020), followed up until May 2022. Incident dementia cases were matched to dementia-free controls using density sampling by age, sex, and date of entry to the study, with a ratio of 1:10. SARS-CoV-2 was defined by positive polymerase chain reaction (PCR) or institutional antigen tests. Multivariable conditional logistic regression models evaluated the association of SARS-CoV-2, its severity and vaccination, and pneumonia as a comparator, with dementia risk. Among the 1,145,322 eligible participants, 27,280 dementia cases were matched to 272,800 controls. SARS-CoV-2 infection was associated with increased dementia risk (OR = 1.18; 95% CI 1.12-1.24; p < 0.001). This association was confined to hospitalized individuals with mild (OR = 2.39; 95% CI 2.07-2.76) and moderate-to-severe disease (OR = 1.93; 95% CI 1.70-2.20), was comparable to pneumonia (OR = 1.89; 95% CI 1.80-1.99), and was no longer evident after 6 months (OR = 1.04; 95% CI 0.96-1.12). COVID-19 vaccination was associated with 7%, 15%, and 31% lower dementia risk after two, three, and four doses, respectively. Unvaccinated individuals with prior COVID-19 had the highest dementia risk. Dementia diagnoses are increased after COVID-19, especially in hospitalized patients. Risk is comparable to other respiratory infections.
Programa Criança Feliz (PCF) is Brazil's home visitation program aimed at enhancing early childhood development. Evaluations of the program have found significant program challenges and implementation barriers, including the lack of a structured curriculum, insufficient training, and little supervisory support. This study tests the revised content of the home visits and new implementation strategies aimed at addressing these barriers and enhancing the quality of PCF home visits. The implementation strategies were piloted across 8 diverse municipalities in an implementation feasibility trial. The strategy bundle included a 40-hour initial training for home visitors using demonstration and simulation-based methods (based on the Reach Up methodology), an 8-hour supervision-focused training module for supervisors, and standardized home visit guidelines and an activities compendium. The new strategies were assessed using a one group pre-post analysis along with mixed methods to assess the extent to which they were acceptable, feasible, and associated with a change in home visit quality. A paired t-test and an independent t-test analysis were used to assess the change in home visit quality. The implementation outcomes were assessed with qualitative analysis and the Framework Method approach. The proposed home visitation guidelines, material, training, and supervision process were determined to be highly acceptable, feasible, and associated with improved quality of home visits. The home visit quality scores significantly increased by 14.68 points (SD = 14.89, CI 95%: 7.27-22.08, p = 0.0006), according to the paired t-test. The study participants provide insightful suggestions for adaptations that can occur before testing the strategies more broadly. Key suggested adaptations included adjusting activity difficulty to individual developmental levels rather than age alone, shortening training duration to improve staff access, and incorporating guidance for culturally diverse and traditional communities. The findings suggest three transferable design principles for home visitation and paraprofessional-delivered public health programs: reducing excessive discretion through structured, age-appropriate visit guidance; externalizing quality through experiential training methods such as demonstration and role-play; and embedding feedback loops through structured supervision and monitoring. These principles may generalize to programs facing heterogeneous staff preparation, high turnover, and limited supervisory capacity.
To evaluate cognitive and executive function (EF) in children with obstetric brachial plexus injury (OBPI), and the potential effects of injury severity and surgical intervention. Fifty-two children aged 6-12 years were assessed: 30 with OBPI (Type IIa: n = 10, Type IIb: n = 11, Type III-IV: n = 9) and 22 children with typical development. Cognitive function was measured using the Dynamic Occupational Therapy Cognitive Assessment for Children (DOTCA-Ch), and EF was assessed via parent-reported Childhood Executive Functioning Inventory (CHEXI). Non-parametric tests and subgroup analyses were conducted, with false discovery rate (FDR) correction applied for multiple comparisons. Children with OBPI scored significantly lower on total and domain-specific DOTCA-Ch measures (median [IQR]: 85 [72-95] vs. 125 [115-135]; q = 0.002), with large effect sizes (Cliff's δ = -0.82 to -0.90). No significant differences were found in CHEXI EF composites. Subgroup analyses showed no statistically significant effects of surgery or Narakas classification, although trends indicated potentially poorer cognitive outcomes in children with Narakas type III-IV. Children with OBPI had lower cognitive function than children with typical development but there was no difference in EF. Findings support integrating cognitive assessments into management of children with OBPI.
Asthma is a clinically heterogeneous airway disorder characterized by complex interactions between environmental exposures, immune activation, and molecular regulatory programs, whose underlying mechanisms are not fully elucidated by known genetic loci. DNA methylation serves as a mechanistic interface bridging genetic predisposition and environmental influences; however, most epigenetic studies remain confined to isolated CpG sites, lacking robust biological interpretability. We developed a cross-tissue, multi-cohort, and mechanistically interpretable epigenetic framework to delineate pathway-level methylation mechanisms underlying asthma. Leveraging data from 908 participants across one combined training cohort and three independent validation cohorts, we constructed a linear support vector classifier based on pathway-derived methylation scores. Additionally, SHapley Additive exPlanations (SHAP) were applied to quantify the contributions of individual pathways. To assess the statistical significance of pathway contributions, one-sample t-tests were performed for each pathway's SHAP values against zero, followed by Benjamini-Hochberg false discovery rate (FDR) correction to obtain adjusted p values. The model exhibited reproducible and cross-tissue performance, achieving area under the curve (AUC) values of 0.792 (95% CI: 0.782-0.799; GSE65163) and 0.980 (95% CI: 0.974-0.990; GSE201872) in two airway epithelial cohorts, and 0.736 (95% CI: 0.690-0.771; GSE104471) in peripheral blood samples. Pathway interpretability analyses identified dominant roles of amino acid metabolism, epithelial and mesodermal developmental programs, metabolic-immune transport pathways, and neuroimmune signalling in shaping asthma-associated methylation patterns. Mediation analyses further revealed that these pathways influence asthma both directly and indirectly via eosinophil activity, epithelial proliferative dynamics, and nitric oxide-linked airway inflammation. Notably, pathways annotated by GO:0061205 and GO:0098727 exerted significant direct effects independent of immune intermediates. This study describes a pathway-level methylation model designed for biological interpretability that shows associations with both clinical severity and latent molecular heterogeneity. It provides statistical evidence contributing to the understanding of epigenetic, immune, and metabolic signatures in asthma, offering a potential framework warranting further validation for precision respiratory medicine.
Prompt diagnosis and treatment of malaria remain central to malaria control strategies. The World Health Organization recommends testing suspected malaria cases before treatment using rapid diagnostic tests (RDTs) or microscopy. However, evidence on the readiness of health facilities to implement this policy in high-burden Nigerian states remains limited. This study assessed facility readiness, testing-before-treatment (TBT) coverage, and facility-level determinants of malaria diagnostic readiness among public health facilities in Kaduna and Kano States, Nigeria. A cross-sectional health facility assessment was conducted across 418 public health facilities in Kaduna and Kano States between August 5 and 28, 2025. A stratified two-stage sampling approach was used, with primary health facilities randomly selected proportionally across all 67 Local Government Areas and all secondary facilities purposively included. Data were collected using a structured Health Facility Assessment questionnaire. Facility readiness was assessed using five indicators: availability of RDTs, availability of microscopy services, trained staff on malaria case management, availability of standard operating procedures, and absence of stock-outs of RDTs or artemisinin-based combination therapy within the previous three months. A composite readiness index (0-5) was constructed and facilities were classified as having full or partial readiness. Associations between facility characteristics and readiness were examined using multivariable logistic regression. All facilities had RDTs and trained staff on malaria case management, and none reported commodity stock-outs during the three-month reference period. Overall, 381 facilities (91.1%) demonstrated full readiness, with a mean readiness score of 4.91 ± 0.29. Microscopy services were available in 23.0% of facilities. Most facilities reported high TBT coverage, with 90.4% reporting ≥ 85% testing coverage. Secondary facilities (aOR = 2.15, 95% CI:1.06-4.36), urban location (aOR = 1.78, 95% CI:1.01-3.12), supportive supervision (aOR = 2.54, 95% CI:1.28-5.02), malaria focal persons (aOR = 2.92, 95% CI:1.63-5.23), and availability of free malaria commodities (aOR = 1.98, 95% CI:1.07-3.68) were significantly associated with full readiness. Public health facilities assessed in Kaduna and Kano States demonstrated high structural readiness for malaria diagnosis. Study limitations include the cross-sectional design, reliance on facility records which may be subject to reporting bias, and the exclusion of private health facilities, limiting generalizability. These findings highlight the need for sustained commodity security, regular supportive supervision, and targeted investments in rural facilities to maintain and strengthen diagnostic readiness.
The lack of healthcare trust is strongly associated with low rates of access and utilization of care, adherence to medical advice, and adverse health outcomes, especially among vulnerable populations. We used a descriptive qualitative design and employed thematic analysis to examine the contributing factors to the lack of trust in healthcare among African immigrants in Florida, US. We conducted in-depth interviews with 19 participants selected through purposive and snowball sampling. The interviews were audio-recorded, transcribed verbatim, and thematically analysed using Nvivo14 software. The findings revealed two overarching themes: (a) personal and (b) institutional factors of lack of healthcare trust. Personal factors included language and communication challenges, lack of knowledge, past negative healthcare experiences, fear of losing legal status, and the use of traditional medicine and prayer as a substitute for modern medicine. Institutional factors included providers' lack of knowledge, wrong assumptions and ignorance, lack of diversity in healthcare, repeated tests and burdensome documentation, malpractice, lack of financial transparency and unfair cost, over-medicalisation, racial divide and discrimination, and unfavourable policy conditions. The findings suggest a holistic approach that involves improving healthcare navigation skills among African immigrants; adopting a patient-centred approach; enhancing health literacy; strengthening cultural competency training and education on tropical medicine for healthcare providers; promoting diversity within the healthcare workforce; and engaging in anti-racism practices that ensure provider accountability. It is also critical to promote policies that ensure financial transparency and coordinated care, reduce unnecessary testing and documentation, and promote safe and equitable access to healthcare for African immigrants.
Diabetes mellitus is a chronic metabolic disorder characterised by impaired glucose homeostasis, resulting in persistent hyperglycaemia. Accurate and prompt diagnosis is essential for early intervention and prevention of long-term complications. Fasting blood glucose levels have traditionally been central to the diagnosis and monitoring of diabetes mellitus. However, growing evidence highlights the clinical relevance of non-fasting glucose measures, including postprandial glucose, random plasma glucose, and glycated haemoglobin (HbA1c) levels. Practical challenges, safety concerns, and evolving insights into glucose physiology have prompted renewed interest in flexible and context-driven approaches to glucose testing. This narrative review examines the physiological basis of fasting and non-fasting glucose regulation and critically evaluates their roles in diabetes screening, diagnosis, and monitoring. It also discusses the strengths and limitations of measuring fasting blood glucose, oral glucose tolerance, HbA1c, random plasma glucose, postprandial glucose, and continuous glucose monitoring. Special attention is given to pre-analytical and practical considerations, patient safety, and the ability of non-fasting measures to capture early metabolic dysfunction and real-world glycaemic exposure. This article reviews evidence supporting the prognostic value of postprandial hyperglycaemia and the expanding role of non-fasting monitoring tools. Non-fasting glucose testing offers substantial advantages in terms of accessibility, safety, and clinical relevance, and is well-suited for population screening and routine diabetes monitoring. Fasting glucose testing remains essential for specific diagnostic and research applications, particularly when strict metabolic standardisation is required. A context-driven framework that prioritises non-fasting approaches while reserving fasting tests for targeted indications provides a balanced and patient-centred strategy for contemporary diabetes care.
Food insecurity (FI) is associated with poorer physical and mental health outcomes, exacerbation of chronic diseases, and decreased access to healthcare. Children experiencing FI face additional risks, including lower psychosocial functioning and reduced academic achievement. Although national initiatives call for integrating nutrition support services into healthcare, clinical workflows for FI screening and referral remain inconsistently implemented and difficult to sustain. The goal of this study is to refine, adapt, and optimize a comprehensive FI screening and referral program, and identify effective implementation strategies for pediatric healthcare systems. We will use a RollOut Implementation and Optimization (ROIO) trial design to iteratively implement and refine the implementation strategies for our FI screening and referral program (I-FRESH: Implementing Food Referrals for Equity and Sustained Health) across 4 pediatric clinics. I-FRESH includes: (1) FI screening; (2) assessment of family needs and readiness to access services; (3) referral and navigation support to community nutrition programs; and (4) follow-up to assess fit, utilization, and ongoing needs. The Pragmatic, Robust Implementation and Sustainability Model (PRISM) will guide adaptation and evaluation of contextual determinants, while RE-AIM will guide assessment of outcomes (implementation feasibility and acceptability, fidelity, adoption, reach, effectiveness, and maintenance). We will identify several implementation strategies to increase the likelihood that I-FRESH can be successfully implemented and sustained in a pediatric healthcare system. We will enroll 240 participants and assess preliminary effectiveness on family‑level food security and pediatric nutrition‑related health outcomes (e.g. weight status, blood pressure, lipids, HbA1c, liver function tests). The information gathered in this trial will be utilized in the development of a fully powered Type 2 Hybrid Effectiveness-Implementation Trial that will test the effectiveness of the identified implementation strategies and impact of the FI program on clinical outcomes. By integrating PRISM and RE-AIM within an iterative ROIO design, this study will generate a scalable, contextresponsive implementation model for addressing FI in pediatric healthcare settings. Findings will inform sustainable strategies that link families to highquality nutrition support programs and improve nutritionrelated health outcomes for lowincome children. NCT06661538.
Fungal keratitis is an uncommon condition that can occur after refractive surgery. Herein, we report a case of early postoperative Aspergillus keratitis in an immunocompetent patient following photorefractive keratectomy (PRK). We report a case of a 21-year-old white man with no past ocular or systemic diseases who underwent bilateral PRK for myopia. Seven days after surgery, he presented to his surgeon, complaining of eye redness and blurred vision that had started 3 days prior. First, empirical antibiotic therapy was initiated, and antifungal agents were subsequently added based on the direct microscopic smear examination of corneal scrapings. The polymerase chain reaction test revealed an Aspergillus corneal infection, and after 7 days of antifungal treatment, significant clinical improvement was observed. This case revealed the necessity of considering atypical microorganisms, such as fungi, in the differential diagnosis of early post-PRK keratitis and highlights the role of direct smear and polymerase chain reaction tests in diagnosis, timely treatment initiation, and subsequently favorable clinical outcomes.
This study aimed to evaluate the in vitro effects of commercially available teething gels with different formulations on epithelial barrier integrity and cellular viability. Six commercially available teething gels were tested at concentrations of 0.1%, 20%, 50%, and 80%. Cellular viability was assessed using the MTT assay in human gingival mesenchymal stem cells after 72 h of exposure. Epithelial barrier integrity was evaluated by measuring transepithelial electrical resistance (TEER) in HaCaT keratinocyte cells cultured on transwell inserts at 24, 48, and 72 h. Statistical analyses were performed using IBM SPSS Statistics 27, applying mixed-design and two-way ANOVA with appropriate post hoc tests, with significance set at p < 0.05. TEER values differed significantly according to gel type, concentration, and exposure time (p < 0.05). At 0.1%, significant intergroup differences were observed at 24 h (p = 0.001) and 72 h (p = 0.017), with Dentinox showing significantly lower TEER values than Gengigel, Aftamed, Buccotherm, and Jack N'Jill. At 20%, 50%, and 80% concentrations, Dentinox consistently exhibited reduced TEER levels at 24-72 h (p = 0.001), whereas Gengigel showed higher TEER values mainly at 24 h (20%) and 72 h (50%), and Buccotherm at 48 h across higher concentrations. MTT analysis revealed significant gel- and concentration-dependent differences at 20%, 50%, and 80% (p = 0.001). Jack N'Jill exhibited higher cell viability at 20%, while both Jack N'Jill and Buccotherm showed higher viability at 50% and 80%. Teething gels exert formulation, concentration, and time-dependent effects on epithelial barrier integrity and cellular viability, emphasizing the need for careful evaluation of products intended for infant use. This study demonstrates that teething gels with different formulations and concentrations can differentially affect epithelial barrier integrity and cellular viability. These findings highlight the clinical importance of carefully evaluating teething gel composition and concentration, particularly for products intended for use in infants and young children.
Social determinants of health influence maternal and perinatal outcomes, yet tools to operationalize these risks in clinical care remain scarce. We aimed to study social determinants in Brazilian pregnant women and develop a social vulnerability index (SVI) that could correlate with pregnancy and perinatal outcomes. The present study was a secondary analysis of 1565 low-risk nulliparous women enrolled in two Brazilian cohort studies. We selected vulnerability indicators from sociodemographic data and tested the performance and risk association of multiple SVI models with any adverse outcome (preterm birth, gestational diabetes mellitus, pre-eclampsia, small or large for gestational age, low 5-min Apgar score, neonatal intubation, neonatal intensive care unit admission, fetal or neonatal death) using chi-square tests, logistic regression, and receiver operating characteristic analysis. Advanced maternal age, non-white ethnicity, and exclusive publicly funded antenatal care were the most consistent vulnerability predictors of adverse outcomes. The final three-variable SVI demonstrated a significant dose-response gradient, with maternal adverse outcomes increasing from 16.4% (no vulnerabilities) to 43.8% (3 vulnerabilities) and perinatal adverse outcomes rising from 22.1% to 35.6%. The model presented a sensitivity of 64.71%, a specificity of 42.56%, a positive predictive value of 47.46% and a negative predictive value of 60.07% for any adverse outcome. The three-variable SVI offers a simple, reproducible, and context-adapted screening tool for primary care. Either for individual or population screening, it can be easily combined with clinical risk assessment, targeting those who may benefit from equity-oriented maternal health strategies.
Home delivery continues to be a significant factor contributing to maternal mortality in Africa, particularly among rural women with limited access to skilled birth attendants and healthcare facilities. Factors influencing home delivery operate at individual, household, and community levels. Therefore, this study aimed to examine the prevalence and risk factors of home delivery among rural women in 28 African countries. This retrospective cross-sectional study analyzed the most recent Demographic and Health Surveys (2011-2024) from 28 African countries. The weighted sample included 103,011 rural women of reproductive age. We performed descriptive analysis, chi-square tests, and binary logistic regression. Results are presented as frequencies, percentages, and odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05. The overall prevalence of home delivery among rural women in Africa was 34.01% [95% CI: 23.33%-35.26%], ranging from 5.91% in Rwanda to 85.19% in Chad. Women with mistimed pregnancy [aOR = 0.79, 95% CI = 0.76-0.82] and those with unwanted pregnancy [aOR = 0.86, 95% CI = 0.81-0.92] had lower odds of home delivery. Risk factors included having four or more births [aOR = 2.04, 95% CI = 1.91-2.17], no/other religion [aOR = 2.41, 95% CI = 2.24-2.56] and those in Central Africa [aOR = 2.09, 95% CI = 1.98-2.19]. This research reveals that home delivery remains prevalent among rural women in Africa, with significant between-country disparities. Key risk factors include high parity, no/other religion, and Central African residence. Programs should prioritize multiparous women and expand maternal health services across all religious groups. Additionally, context-specific policies and targeted investments are needed in Central Africa to address regional disparities.
Patient satisfaction with complete dentures is multifactorial, with aesthetics being a key determinant. The color match between the denture base and the patient's natural gingiva is a critical aspect of denture aesthetics; however, its specific impact on satisfaction remained unclear. This study aimed to investigate the relationship between the color difference of the denture base from the natural gingiva and patient satisfaction with complete dentures. In this descriptive-analytical study, 88 edentulous patients (62 men, 26 women) scheduled for complete denture treatment were enrolled. The closest match to the patient's gingival color was selected by a dentist using the Ivoclar Ivobase Shade Guide. Patients also independently selected their preferred base color. All dentures were fabricated using a single shade of acrylic resin (Pref) as standard color. Patient satisfaction was assessed using a Visual Analog Scale (VAS, 0-10) at two time points: at delivery and at a one-week follow-up. Data on age, gender, education level, and color choices were collected. Statistical analysis was performed using SPSS 27 with Mann-Whitney, Kruskal-Wallis, and Spearman's rank correlation tests. Patient satisfaction showed no significant correlation with age, gender, education level, or the patient's own color choice (P > 0.05). However, a significant positive correlation was found between satisfaction and the dentist's initial color selection (P = 0.006). This relationship was stronger at the follow-up session compared to the delivery session. The findings indicate that the dentist's assessment of gingival color, leading to a closer match between the denture base and natural tissues, could be associated with patient satisfaction. Patient self-selection of color did not significantly influence satisfaction levels.
Post-treatment weight gain and gut dysbiosis are important concerns in breast cancer patients. However, evidence on the gut microbiota in this population, particularly in relation to physical activity, is limited. Therefore, we compared gut microbiota in breast cancer patients with obesity with healthy controls and non-cancer controls with obesity and subsequently examined the effects of a combined dance and dietary intervention on gut microbiota, metabolic health, physical fitness, and quality of life. The observational part compared gut microbiota in breast cancer patients with obesity (BCO, BMI 32.43 ± 4.90 kg/m2) with non-cancer controls with obesity (OC, BMI 37.78 ± 6.68 kg/m2) and healthy controls (HC, BMI 21.26 ± 1.26 kg/m2). A controlled trial was conducted in breast cancer patients with obesity, with an intervention group (INT, n = 13) receiving a 12-week combined dance and dietary intervention and non-intervention controls (CTRL, n = 10). Gut microbiota was assessed using 16S rRNA sequencing, physical fitness was evaluated by an incremental bicycle ergometer test and motor tests, and quality of life was measured using the EORTC QLQ-C30 and BR23 questionnaires. In the observational study, breast cancer patients showed significant differences in beta diversity and a lower relative abundance of health-associated bacteria (e.g., Faecalibacterium prausnitzii) compared with both controls. In the controlled trial, the intervention led to a significant improvement in body composition, physical fitness (e.g., Vo2max, handgrip strength), and several validated quality-of-life domains (e.g., fatigue, body image). A statistically significant difference in beta diversity at the post-intervention phylum level was observed (p = 0.046, R2 = 0.11). Microbiota composition within INT shifted toward, increased health-associated taxa (Bifidobacterium spp.) and reduced opportunistic pathogens (Klebsiella oxytoca). However, a decrease in butyrate-producing taxa (Ruminococcus bromii, Ruminiclostridium hungatei) was also observed. Breast cancer patients showed more negative shifts in gut microbiota compared with both controls. In addition, a 12-week combined dance and dietary intervention improved body composition, physical fitness, quality of life, and was associated with mixed but potentially beneficial changes in select gut microbiota taxa among breast cancer patients with obesity. Clinical trial registration number: NCT07213271.
Complex algorithms and prediction models are increasingly being developed, investigated and applied for clinical use in medical laboratories and beyond. Proper algorithmic functioning in a clinical setting is of the utmost importance to ensure patient safety. Recently, a tumor marker-based, longitudinal, machine learning model (mSTOP) was developed to predict which non-small cell lung cancer patients would not respond to (chemo-)immunotherapy early in the treatment process. This model was then clinically implemented in a hospital setting for which ICT infrastructure was developed to allow for the model's automated and real-time application. To ensure the appropriate functioning of the ICT infrastructure and the algorithm, a quality control (QC) strategy was developed and executed similarly to normal internal QC for clinical tests performed routinely in the laboratory. This quality control strategy entitled; scenario-based multiparametric quality control (MPQC) is based on the input and output values of different pre-specified scenarios obtained from the original clinical validation study. This perspective aims to justify and elucidate the concept of this QC strategy for quality control of complex algorithms operated in a clinical setting.