Category: Nevin Manimala

Przegl Epidemiol. 2025 Oct 3;79(2):300-310. doi: 10.32394/pe/205497. Epub 2025 Jul 2.

ABSTRACT

BACKGROUND: Antimicrobial resistance is a major public health threat, with extended-spectrum β-lactamase (ESBL)-producing bacteria from the Enterobacteriaceae family classified by the WHO as critical priority pathogens. The COVID-19 pandemic affected global antibiotic consumption patterns, potentially influencing the resistance of ESBL(+) strains and the frequency of bacterial infections in hospitals.

OBJECTIVE: This study aimed to analyze the trends in the prevalence of infections caused by ESBL-producing bacteria (Enterobacteriaceae family) in a district hospital in the Lower Silesian Voivodeship during the peri-pandemic period (2017-2023) and assess the relationship between antibiotic consumption and changes in resistance.

MATERIAL AND METHODS: A retrospective cohort study was conducted using microbiological and pharmacological data from the Healthcare Complex in Oława. 34,629 clinical specimen cultures from 77,829 hospitalized patients were analyzed. The study focused on Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. with an ESBL resistance mechanism. The consumption of β-lactam antibiotics from Anatomical Therapeutic Chemical (ATC) Classification System groups J01C and J01D was assessed. Statistical trend and correlation analysis was applied.

RESULTS: The incidence of ESBL(+) bacterial infections showed no significant trends. The pre-pandemic prevalence of ESBL(+) strains was low (6.42%-24.49%), rising to 56.25% in 2020 and peaking at 100% in 2021-2022. In 2023, resistant isolates declined to 77.50%. A 50.2% increase in β-lactam antibiotic consumption (J01D, mainly cephalosporins) was recorded in 2020. The highest proportion of ESBL(+) infections occurred in non-surgical wards (40.97%) and long-term care facilities (25.88%).

CONCLUSIONS: Data analysis from 2017-2023 revealed no significant trends in incidence of ESBL(+) infections but an increase in β-lactam resistance. In 2020, the prevalence of ESBL(+) strains and antibiotic consumption, especially cephalosporins, increased. However, the lack of a significant correlation between antibiotic consumption and resistance suggests that other factors, such as resistant strain transmission or persistent colonization, play a crucial role. These findings highlight the need for enhanced resistance monitoring and rational antibiotic stewardship strategies.

PMID:41042965 | DOI:10.32394/pe/205497

Indian J Dent Res. 2025 Apr 1;36(2):228-235. doi: 10.4103/ijdr.ijdr_682_24. Epub 2025 Oct 1.

ABSTRACT

OBJECTIVES: C-shaped root canal morphology presents significant challenges in endodontic treatment due to its complex anatomy. This systematic review and meta-analysis evaluated the prevalence of C-shaped canal anatomy in mandibular second premolars and examined the influence of geographic variation on prevalence rates.

MATERIALS AND METHODS: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, systematically searching five electronic databases: PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar. Eligible studies included cross-sectional, prospective, and observational studies on C-shaped canal prevalence in adult mandibular second premolars.

STATISTICAL ANALYSIS: A random-effects model in RStudio software was used to calculate the pooled prevalence and 95% confidence intervals (CI) of C-shaped canals.

RESULTS: The pooled prevalence based on participants was 1.31% (CI: 0.68-2.53; I² = 90%; P < 0.01). Based on the number of teeth, the prevalence was 0.96% (CI: 0.46-2.00; I² = 93%; P < 0.01), also with high heterogeneity. Geographic analysis showed the highest prevalence in South America 5.83% (CI: 0.57-40.04; I² = 95%; P < 0.01) and the lowest in Australia 0.42% (CI: 0.31-0.93).

CONCLUSIONS: The study demonstrated variability in the prevalence of C-shaped canals, with a pooled estimate of 1.31% based on participant-level data and 0.96% based on tooth-level assessment. The substantial heterogeneity observed across studies highlights the morphological diversity of root canal systems. Geographic differences were observed, with the highest prevalence in South America and the lowest in Australia. These findings underscore the importance of region-specific diagnostic vigilance.

PMID:41042605 | DOI:10.4103/ijdr.ijdr_682_24

Indian J Dent Res. 2025 Apr 1;36(2):213-218. doi: 10.4103/ijdr.ijdr_354_23. Epub 2025 Oct 1.

ABSTRACT

CONTEXT: Desensitizing agents are commonly used to minimize dentin hypersensitivity caused by tooth whitening procedures. The objective was to evaluate the evolution of enamel colour and porosity after home-use tooth whitening with and without a desensitizing agent.

METHODS: Individual trays with different concentrations of hydrogen peroxide (HP) or carbamide peroxide (CP) bleaching agents were tested with and without prior use of a desensitizing agent. Whitening efficacy was evaluated by spectrophotometer, and the enamel surface alteration was examined by scanning electron microscope. The one-way ANOVA followed by Tukey’s post hoc test was used to assess differences in the colour variations among the groups, independently for the middle third, cervical third, and grouped thirds. The paired t-test was used to assess the differences in colour variation between the middle third and the cervical third, independently for each of the groups.

RESULTS: The analysis of colour variation (ΔE) showed that there was no statistical difference among the groups with or without application of a desensitizer (P > 0.05). The change in enamel morphology was proportional to the concentration of the bleaching agent. The microscopy images obtained from the groups using a desensitizer prior to the bleaching agent were similar to those of the groups in which the bleaching agent was used alone.

CONCLUSIONS: The association of home bleaching agents with a desensitizing agent did not influence the final result of the bleaching procedure.

PMID:41042604 | DOI:10.4103/ijdr.ijdr_354_23

JMIR Res Protoc. 2025 Oct 3;14:e66202. doi: 10.2196/66202.

ABSTRACT

BACKGROUND: Preeclampsia is 1 of the 3 leading causes of maternal mortality worldwide. Unfortunately, its exact pathogenesis is still unclear. Published metabolomic and gene expression analyses point to coenzyme A (CoA) restriction in the placenta as a factor underpinning the observed complications of preeclampsia, but this hypothesis has never been tested.

OBJECTIVE: This pilot study aims to discover evidence supporting the CoA-restriction hypothesis through 2 avenues. The first of these involves developing a procedure for the quantitative determination of metabolites to discover if harmful metabolites are elevated in patients with preeclampsia, while the second seeks to emulate the onset of CoA restriction in cultured cells.

METHODS: This manuscript provides a rationale and a protocol for a clinical study and laboratory experiments to test the hypothesis. The methods have 3 key aspects. Phase 1 comprises optimization of assays of 5 key metabolites arising from CoA restriction, namely L-leucine, ketoisovalerate, ketodeoxycholate, oleic acid, and sphingosine-1-phosphate. Phase 2 comprises recruitment of patients to obtain serum samples to measure the metabolites, and phase 3 comprises culturing and treating trophoblast cells to induce CoA restriction and test the effects of the metabolites on the cells. Patients with preeclampsia and healthy controls will be recruited based on World Health Organization criteria for preeclampsia. Exclusion criteria include multiple pregnancies, premature rupture of membranes, and various medical complications. Blood samples will be collected and analyzed using high-performance liquid chromatography/mass spectrometry (HPLC/MS) to quantify key metabolites associated with CoA restriction. For trophoblast cell studies, BeWo cells will be cultured under conditions likely to induce CoA restriction, including hypoxia and human chorionic gonadotropin supplementation, and will also be treated with the key metabolites to determine what effect they might have. Cell viability, apoptosis, energy metabolism, and gene expression (focusing on genes involved in CoA synthesis and metabolism) will be assessed. Statistical analysis will involve 2-tailed t tests or Mann-Whitney U tests to compare metabolite concentrations between patients with preeclampsia and controls. A correlation matrix will be used to explore associations between metabolite levels and patient characteristics.

RESULTS: Institutional review board ethics approval has been obtained for this study. Patient recruitment started April 1, 2025. The 5 metabolites have been purchased in synthetic form and used to optimize the HPLC/MS assays in preparation for receiving blood samples. The trophoblast cell-line culture is being optimized.

CONCLUSIONS: The findings of this study will demonstrate that key metabolite concentrations can be quantified using HPLC/MS and indicate if CoA restriction is associated with preeclampsia. If so, this provides a significant, novel avenue for research into the treatment and prevention of the disease.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/66202.

PMID:41042598 | DOI:10.2196/66202

Epileptic Disord. 2025 Oct 3. doi: 10.1002/epd2.70112. Online ahead of print.

ABSTRACT

OBJECTIVE: Progressive myoclonic epilepsy type 1 (EPM1) is a neurodegenerative disease caused by biallelic variants in the cystatin B (CSTB) gene. Despite a progressive course, phenotype severity varies among patients, even within families. We studied the potential role of APOE ε4 in modifying phenotypic diversity in EPM1, given its established association with neurodegeneration, particularly in Alzheimer’s disease.

METHODS: APOE genotypes were determined for 65 genetically verified EPM1 patients homozygous for the CSTB expansion mutation. The Unified Myoclonus Rating Scale (UMRS), Quality of Life in Epilepsy Inventory-31 questionnaire (QOLIE-31), intellectual ability (WAIS-R), clinical data, and quantitative neuroimaging data were compared between APOE ε4 carriers and noncarriers to assess potential correlations with EPM1 severity. Volumetric analysis was performed on MRI data, while diffusion tensor imaging (DTI) was analyzed using Tract-Based Spatial Statistics (TBSS) and atlas-based white matter (WM) tract region of interest (ROI) analysis.

RESULTS: The cohort included 20 ε4 carriers (16 ε3/ε4 and 4 ε4/ε4) and 45 ε4 noncarriers (36 ε3/ε3, 8 ε2/ε3, and 1 ε2/ε2). No significant differences were found in UMRS or disease duration. Carriers had better QOLIE-31 scores in emotional well-being (p = .047), energy/fatigue (p = .048), and medical effects (p = .024). In volumetric analysis, carriers exhibited greater preservation of bilateral hippocampal and amygdalar volumes but demonstrated more pronounced cortical thinning in the left lingual gyrus, right lateral occipital gyrus, and right posterior cingulate (p < .05). Carriers exhibited more widespread WM degeneration in DTI, characterized by reduced fractional anisotropy (FA) and increased mean diffusivity (MD).

SIGNIFICANCE: Despite greater white matter degeneration and reduced cortical thickness, APOE ε4 carriers exhibited preserved deep brain volumes and better self-reported well-being. This study highlights the complex interplay between genetic factors and neurodegenerative processes. Our future research aims to provide more natural history data of EPM1 and correlate long-term phenotypic data with additional geno-phenotypic analyses.

PMID:41042579 | DOI:10.1002/epd2.70112

Endocr Connect. 2025 Oct 3:EC-25-0290. doi: 10.1530/EC-25-0290. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the clinical spectrum, ARMC5 mutation distribution, and metabolic/cardiovascular risks in patients with radiologically suspected primary bilateral macronodular adrenal hyperplasia (PBMAH).

DESIGN: Cross-sectional study.

METHODS: We analyzed clinical characteristics and germline ARMC5 mutations in patients meeting radiologic criteria for PBMAH (bilateral adrenal nodules ≥1 cm), excluding non-adrenocortical lesions or bilateral adenomas with adrenal atrophy.

RESULTS: The subgroup distribution among 485 patients with radiologically suspected PBMAH was as follows: nonfunctional adrenal tumors (NFAT, 30.1%), mild autonomous cortisol secretion (MACS, 41%), overt Cushing’s syndrome (CS, 14.4%), primary aldosteronism (PA, 8.9%), and coexisting PA and MACS (PA+MACS, 5.6%). Imaging revealed a higher proportion of multiple confluent adrenal nodules in the MACS and CS groups compared to others (P<0.05). Cortisol-related comorbidities (hypertension, diabetes, etc.) showed no statistically significant differences between MACS and NFAT. Germline ARMC5 testing in 62 unrelated patients identified 7 novel pathogenic variants. Pathogenic mutations were detected only in MACS and CS groups, with no significant difference observed between them (P>0.05). Multiple confluent nodules were present in all ARMC5-mutated patients (16/16) but in fewer ARMC5 wild-type patients (20/44), with high sensitivity and negative predictive value for the prediction of germline pathogenic mutations.

CONCLUSION: No significant cortisol-related comorbidity differences were observed between radiologically suspected PBMAH patients with NFAT and MACS. Germline ARMC5 screening should prioritize patients with radiological findings of multiple confluent macronodules.

SIGNIFICANCE STATEMENT: Our work provides new insights into the management of primary bilateral macronodular adrenal hyperplasia (PBMAH): 1) MACS and NFAT patients with radiologically suspected PBMAH (i.e., bilateral benign adrenal macronodules) may require equal clinical attention; 2) We identified 7 novel ARMC5 pathogenic variants; 3) Multiple confluent adrenal nodules on imaging demonstrate predictive value for ARMC5 pathogenic mutations, refining genetic screening criteria.

PMID:41042544 | DOI:10.1530/EC-25-0290

JAMA Health Forum. 2025 Oct 3;6(10):e253479. doi: 10.1001/jamahealthforum.2025.3479.

ABSTRACT

IMPORTANCE: Persistent disparities in mortality across countries suggest uneven improvements in living standards and access to life-extending health technologies, as well as context-specific obstacles. Studies have analyzed cross-country inequality in mortality but have not widely contextualized those disparities in terms of developmental progress relative to a frontier representing a level of mortality achievable with broad access to the best health-enhancing technology and living standards available.

OBJECTIVE: To examine probability of premature death (PPD)-defined as probability of dying before 70 years of age-across countries and regions, benchmarking progress as years behind the lowest country-level PPD (the frontier).

DESIGN AND SETTING: This cross-sectional study used aggregate-level data from the 2024 United Nations World Population Prospects and Human Mortality Database to calculate PPD across 7 global regions and the 30 most populous countries. Data were analyzed from May to September 2025.

MAIN OUTCOME AND MEASURES: The primary outcomes were PPD and the number of years behind the lowest country-level PPD.

RESULTS: The frontier PPD fell from 57% to 12% from 1900 to 2019. Sub-Saharan Africa’s PPD in 2019 was 52%, corresponding to the 1916 frontier PPD. However, sub-Saharan Africa had converged toward the frontier by over 40 years since 2000, when it had a 65% PPD. China has been converging toward the frontier since 1970, having been 93 years behind the frontier PPD in 1970 (with a 60% PPD) and 35 years behind in 2019 (21% PPD). The US has diverged away from the frontier, having been 29 years behind in 1970 (38% PPD) and 38 years in 2019 (22% PPD). Of the regions included, the North Atlantic (Western Europe and Canada) was the closest to the frontier, being 13 years behind in 2019 (15% PPD). The US, Central and Eastern Europe, and sub-Saharan Africa were the furthest above the 2019 PPD Preston curve (ie, they had a greater PPD than predicted by their per capita gross domestic product).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, disparities in PPD were likely to reflect major inequality in access to health-enhancing technologies and living standards, as well as context-specific obstacles. Technological and medical advancements leading to universal health benefits need to be rapidly and fairly disseminated.

PMID:41042526 | DOI:10.1001/jamahealthforum.2025.3479

JAMA Health Forum. 2025 Oct 3;6(10):e253871. doi: 10.1001/jamahealthforum.2025.3871.

ABSTRACT

IMPORTANCE: The US has faced persistent antibiotic shortages over the past decade, compromising patient care, public health, and national security. Understanding the global sources of US antibiotic imports is critical to inform policies to improve supply chain resilience.

OBJECTIVE: To identify the global sources of US antibiotic imports, focusing on finished dosage forms (FDFs) and active pharmaceutical ingredients (APIs) between 1992 and 2024.

DESIGN AND SETTING: This cross-sectional study of US antibiotic importation records used data from USA Trade Online from January 1992 to July 2024. Data included import volumes, costs, and the originating country.

MAIN OUTCOMES AND MEASURES: Trends in annual import volumes for antibiotic FDFs and APIs (metric tons), spending and price per kilogram (inflation-adjusted dollars), and market concentration measured by the Herfindahl-Hirschman Index (HHI). An HHI less than 1500 indicates an unconcentrated (ie, competitive) market, 1500 to 2500 indicates a moderate concentration, and greater than 2500 indicates high concentration.

RESULTS: The final sample included 50 FDF-originating countries and 52 API-originating countries. Compared with the annual volume of US antibiotic FDF imports in 1992, the annual volume in 2024 increased 2595.0%, while the annual volume of API imports remained relatively stable. Mean inflation-adjusted importation prices for FDFs decreased from $1836.03 per kg in 1992 to $177.44 per kg in 2024. For APIs, mean prices decreased from $351.74 per kg in 2003 to $65.69 per kilogram in 2024. From 2020 to 2024, India was the leading originating country for FDFs (31.9% of the total imported volume and 18.2% of the total imported cost), followed by Italy (13.4% of the total volume and 22.4% of the total cost). China was the leading originating country for APIs (62.6% of the total imported volume and 28.7% of the total cost), followed by Bulgaria (16.1% of the total volume and 3.8% of the total cost). Italy was the originating country for 2.6% of API imported volume but accounted for 27.9% of the importation costs. HHI revealed that FDF importation has become unconcentrated since 2020 (HHI, 1500-2500), while API importation markets are highly concentrated (2024 HHI, >5000).

CONCLUSIONS AND RELEVANCE: This study found that US antibiotic importation relies on diversified global sources for FDFs but primarily on China for APIs. Policies to strengthen domestic production and diversify sourcing are critical to mitigate supply chain vulnerabilities. Improved traceability and targeted strategies for specific antibiotics are recommended to safeguard public health and national security.

PMID:41042525 | DOI:10.1001/jamahealthforum.2025.3871

JAMA Netw Open. 2025 Oct 1;8(10):e2535137. doi: 10.1001/jamanetworkopen.2025.35137.

ABSTRACT

IMPORTANCE: Hospital-acquired venous thromboembolism (HA-VTE) remains a leading cause of preventable death among hospitalized adults in the US. Despite numerous attempts to prognosticate HA-VTE with risk models, no single model has outperformed the rest, and the effectiveness of such models to drive prophylaxis decisions is unknown. Testing such systems in urban and rural settings may inform their generalizability.

OBJECTIVE: To conduct a randomized clinical trial to assess the effectiveness of artificial intelligence (AI)-driven clinical decision support (CDS) in reducing HA-VTE incidence in adults across urban and rural hospital settings.

DESIGN, SETTING, AND PARTICIPANTS: This parallel-group, single-blind, pragmatic randomized clinical trial is planned to be conducted from October 1, 2025, through September 30, 2027, by the Vanderbilt University Medical Center, a major academic health system in Tennessee. The study population will include adult (aged ≥18 years) patients admitted to medical, surgical, and intensive care units who may be at high risk for VTE and with no active or contraindication to deep vein thrombosis prophylaxis at Vanderbilt Adult Hospital in urban Nashville and 3 affiliated hospitals serving rural communities in Middle Tennessee.

INTERVENTION: Patients will be randomized 1:1 within the electronic health record to receive either VTE-AI-driven CDS (nudge practice alert [intervention arm]) or standard care using traditional risk assessment (control arm).

MAIN OUTCOME AND MEASURES: The primary outcome will be incidence of HA-VTE. Secondary trial outcomes will be process metrics, including length of stay, readmission rates, safety, and bleeding events. Outcomes will be analyzed using descriptive statistics and compared using Poisson regression.

DISCUSSION: Using a validated prognostic model, this study is one of the first to provide insights into whether AI-driven CDS can effectively reduce HA-VTE incidence without increasing adverse events. This study also is intended to provide insights into the usefulness of the same AI model implemented across urban and rural settings. The study’s findings and statistical code will be shared with the public through peer-reviewed publication and ClinicalTrials.gov.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06939803.

PMID:41042513 | DOI:10.1001/jamanetworkopen.2025.35137

JAMA Netw Open. 2025 Oct 1;8(10):e2535200. doi: 10.1001/jamanetworkopen.2025.35200.

ABSTRACT

IMPORTANCE: It is unclear whether performing surgery for most patients with an acute subdural hematoma (ASDH) and traumatic brain injury (TBI) is superior to conservative treatment.

OBJECTIVE: To compare the effectiveness of a strategy preferring acute surgical ASDH evacuation with one preferring initial conservative treatment.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study used data from February 1, 2014, to July 31, 2018, from the prospective observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study, conducted at 18 Level 1 trauma centers in the US. The study included patients with nonpenetrating TBI presenting to the emergency department and admitted within 24 hours after injury with ASDH detected on acute head computed tomography scan. Statistical analysis was performed from December 1, 2022, to December 20, 2024.

EXPOSURES: Acute surgical hematoma evacuation vs initial conservative treatment, comparing outcomes between centers according to treatment preferences, measured by the case mix-adjusted probability of undergoing acute surgery (vs conservative treatment) per center.

MAIN OUTCOMES AND MEASURES: Functional disability at 6 months was assessed with the Glasgow Outcome Scale-Extended at 6 months, analyzed with ordinal logistic regression adjusted for prespecified confounders, quantified with a common odds ratio (OR). Variation in center preference was quantified with a median OR (MOR).

RESULTS: Of 2697 included patients, 711 (mean [SD] age, 46.5 [19.4] years; 539 men [76%]) had an ASDH, of whom 148 (21%) underwent acute cranial surgery and 563 (79%) underwent initial conservative treatment. The acute surgery cohort had lower mean (SD) Glasgow Coma Scale scores (6.8 [4.4] vs 11.4 [4.6]), more pupil abnormalities (both pupils unreacting: 43 of 133 [32%] vs 41 of 477 [9%]), and fewer isolated ASDHs (eg, more with concurrent intracranial lesions; 92 of 133 [69%] vs 297 of 563 [53%%]) compared with the conservative treatment cohort. In the surgical cohort, 129 of 148 patients (87%) underwent decompressive craniectomy (DC), and 17 of 148 (11%) underwent craniotomy. In the conservative treatment cohort, 67 of 563 patients (12%) underwent delayed cranial surgery (DC or craniotomy). The proportion of patients undergoing acute surgery ranged from 0% to 86% (median, 17% [IQR, 5%-27%]) between centers, with up to a 3-fold higher probability of prognostically similar patients receiving acute surgery in one center compared with another random center (MOR, 2.95 [95% CI, 1.79-7.47]; P = .06). Center preference for acute surgery over initial conservative treatment was not associated with a better outcome (OR, 1.05 [95% CI, 0.88-1.26] per 22% [IQR, 5%-27%] increase in acute surgery at a given trauma center).

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study, similar patients with traumatic ASDH were treated differently due to center-specific treatment preferences. Outcomes were similar in centers preferring surgical evacuation and those preferring initial conservative treatment. This study suggests that, for a patient with ASDH for whom a neurosurgeon experiences clinical equipoise between acute surgery vs (initial) conservative treatment, conservative treatment may be considered.

PMID:41042512 | DOI:10.1001/jamanetworkopen.2025.35200