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Association of potentially inappropriate medications with rehospitalisation and death within three months in older patients: a systematic review and meta-analysis

Int J Clin Pharm. 2025 Sep 25. doi: 10.1007/s11096-025-02013-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Potentially inappropriate medications (PIMs) are medications with an unfavourable risk-benefit profile for patients aged ≥ 65 years. Currently, several screening tools are available and are used in clinical practice to identify PIMs.

AIM: Our objective was to systematically synthesize the available evidence on the association between potentially inappropriate medications (PIMs), as identified by various screening tools including STOPP/START and the Beers Criteria, and the outcomes of rehospitalization and mortality within three months in older patients.

METHOD: Adhering to Cochrane standards, we conducted a systematic review and meta-analysis to investigate the outcomes of patients aged 65 years and older, comparing those with at least one PIM identified by any explicit screening tool to those without PIMs. Primary outcomes were readmission and/or death within three months. The databases of Embase, MEDLINE, and CENTRAL were searched for retrospective as well as prospective observational studies published between 1991 and May 17 2024. The risk of bias was assessed for all included studies.

RESULTS: In total, 1,642 studies were identified through the systematic search. Nine observational studies were included in this review. Our analysis revealed a statistically significant association between the overall presence of PIMs and rehospitalisation; odds ratio (OR) 1.47 [95% confidence interval (CI) 1.02 to 2.13, p = 0.045]. While stratification according to STOPP/START criteria yielded a statistically significant OR of 1.84 [CI 1.08 to 3.12, p = 0.024; n = 5], no statistically significant difference was seen according to Beers list [OR 1.25, CI 0.86 to 1.81, p = 0.235; n = 5]. Furthermore, no significant association was found between PIMs and mortality in either the overall analysis or the stratification according to the Beers and STOPP/START criteria. The risk of bias in the included studies was moderate to serious, and the certainty of evidence was very low.

CONCLUSION: The use of PIM screening tools during medication evaluations may reduce the risk of rehospitalisation and potentially lower mortality in older patients. However, further studies are warranted to confirm the association with adverse outcomes.

PMID:40996586 | DOI:10.1007/s11096-025-02013-y

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Beyond the bladder: Escherichia coli UTIs drive systemic inflammation and RANKL-mediated bone resorption

Ir J Med Sci. 2025 Sep 25. doi: 10.1007/s11845-025-04093-1. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic inflammation associated with recurrent urinary tract infections (rUTIs) can adversely affect bone metabolism. This study aimed to explore the interactions between vitamin D status, inflammatory markers, and bone turnover in patients with rUTIs, with a focus on the differences between infections caused by Escherichia coli and those caused by non-E. coli pathogens.

METHODS: In this cross-sectional study, 50 patients with rUTIs (25 with E. coli-induced infections and 25 with infections caused by non-E. coli pathogens) were evaluated. The serum levels of 25-hydroxyvitamin D (vitamin D), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), receptor activator of nuclear factor kappa-Β ligand (RANKL), and the bone resorption marker C-terminal telopeptide of type I collagen (CTX-I) were measured. Statistical analyses included group comparisons, correlation assessments, receiver operating characteristic (ROC) curve analysis, and multiple linear regression.

RESULTS: Patients in the E. coli group had significantly lower serum vitamin D levels and elevated levels of IL-6, RANKL, and CTX-I than those in the non-E. coli group (all p < 0.001). Vitamin D levels showed a strong inverse correlation with RANKL levels (r = – 0.593). In the multiple regression analysis, IL-6 and RANKL emerged as the only independent predictors of CTX-I, collectively accounting for 60% of the variance (R2 = 0.60).

CONCLUSION: Recurrent urinary tract infections caused by E. coli are associated with a clinical profile characterized by vitamin D deficiency and inflammation-mediated bone resorption driven by the IL-6/RANKL signaling pathway. These findings highlight the previously underappreciated osteoimmunological impact of common bacterial infections and suggest that skeletal health should be an important consideration in the management of patients with rUTIs.

PMID:40996582 | DOI:10.1007/s11845-025-04093-1

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Retinal ischemic perivascular lesion “a subclinical ischemic sign” in the fellow eye of patients with retinal vein occlusion

Int Ophthalmol. 2025 Sep 25;45(1):383. doi: 10.1007/s10792-025-03756-3.

ABSTRACT

BACKGROUND: To examine the prevalence of retinal ischemic perivascular lesions (RIPLs) in the fellow eye of patients with retinal vein occlusion (RVO) and investigate their relationship with systemic vascular diseases.

METHODS: In this retrospective case-control observational study, 91 fellow eyes of RVO patients (91 eyes) and the eyes of 63 age-matched healthy (63 eyes) volunteers were evaluated. RIPLs were assessed by examining cross-sectional scans from 6 × 6 mm optical coherence tomography angiography (OCTA). Quadrantal superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively analyzed in the RIPL areas. The relationship between vascular diseases (hypertension, diabetes, coronary artery disease, carotid stenosis, atrial fibrillation, stroke, myocardial infarction) in participants and RIPL was also investigated.

RESULTS: RIPLs were found in 25 eyes (27.4%) of RVO patients and five eyes (7.9%) in the control group (p = 0.018). There were statistically significant differences in DCP VD (%) in the superior (p = 0.024) and inferior (p = 0.044) temporal quadrants, where RIPLs were more common. RVO in the fellow eye was associated with a 5-fold increase in the possibility of the presence of RIPL compared with controls (OR = 5.00, 95% CI = 1.01- 15.11). Presence of RIPLs was associated with 5.13-fold higher odds of carotid artery stenosis (OR = 5.13, 95% CI = 1.02- 28.25) and 4.94-fold higher odds of a history of myocardial infarction (OR = 4.94, 95% CI = 1.24- 58.25).

CONCLUSION: RIPL, a subclinical retinal ischemic lesion, was found at rates almost 3.5 times higher in the fellow eye of RVO patients. These lesions are significantly associated with carotid artery stenosis and a history of myocardial infarction. RIPL may be an ophthalmological indicator that can be used for systemic macrovascular disease.

PMID:40996561 | DOI:10.1007/s10792-025-03756-3

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Neuroimaging of Ictal MEG: An Evaluation of Magnetic Source Imaging Techniques

Brain Topogr. 2025 Sep 25;38(6):66. doi: 10.1007/s10548-025-01132-z.

ABSTRACT

Magnetoencephalography (MEG) is a valuable tool in the presurgical workup of refractory epilepsy patients. Ictal Magnetic Source Imaging (MSI) can more accurately localize the ictal onset zone, aiding presurgical planning. Nevertheless, the optimal approach for ictal MSI remains undetermined. To evaluate the effectiveness of distinct ictal MSI techniques, assessing their performance based on the ictal onset pattern (IOP). Design: Retrospective study. 16 ictal MEG events from 12 epilepsy patients were retrospectively analyzed. Techniques employed include the traditional sECD, and alternative approaches comprising the linearly constrained minimum variance (LCMV) beamforming, kurtosis beamforming, and dynamic statistical parametric mapping (dSPM). Seizures were classified into IOP groups: ictal discharge, rhythmic activity (RA), slow RA, and fast activity. Sublobar and lobar concordance and the minimum Euclidean distance (Dmin) were evaluated using SEEG data as ground truth. sECD fitting failed for three seizures, whereas alternative techniques demonstrated superiority. LCMV showed the highest sublobar concordance. No significant differences in Dmin across techniques were found. All techniques performed better in the ictal discharge group. Performance declined in the rhythmic activity IOP group, especially in lower frequencies, although LCMV performed better. ECD, beamforming, and dSPM are effective techniques for ictal MEG analysis. Beamforming techniques are particularly important when ECD is unsuitable. The IOP should be considered when selecting the appropriate ictal MSI technique. Optimizing MSI techniques and customizing them based on seizure characteristics can aid in invasive study planning and potentially improve post-surgical outcomes.

PMID:40996556 | DOI:10.1007/s10548-025-01132-z

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Enhancing lipase activity in Aspergillus niger through CRISPR/Cas9-mediated protease gene knockout and fermentation optimization

Biotechnol Lett. 2025 Sep 25;47(5):114. doi: 10.1007/s10529-025-03657-6.

ABSTRACT

The engineered Aspergillus niger strain AnCALB005 was selected as the research strain, which is a high-yield strain of Candida antarctica B lipase constructed in our laboratory. CRISPR/Cas9-mediated gene knockout was employed to construct the multiple protease-deficient strains targeting five genes (pepA, pepB, pepC, pepE and pepF) in the A. niger AnCALB005. Among the engineered variants, a triple-knockout strain lacking pepA, pepB, and pepF demonstrated 56% enhanced hydrolytic lipase activity relative to the parental strain. Fermentation culture conditions were initially screened through single-factor experiments. Building on these results, critical parameters were statistically determined via Plackett-Burman (PB) design. This was followed by a steepest ascent method combined with Box-Behnken (BB) response surface methodology. Key factors influencing lipase production (identified as maltose concentration, corn steep concentration, and shaking speed) were optimized. The final optimized fermentation conditions comprised: maltose (52 g/L), corn steep (52 g/L), K2HPO4 (5 g/L), soybean cake flour (30 g/L), initial pH 6.5, inoculation amount 10% (v/v), and shaking speed 220 rpm. Under the optimized fermentation conditions, Shake-flask validation of the engineered A. niger yielded a lipase activity of 46.66 U/mL, representing an increase of 92.01%. Scale-up fermentation in a 5 L bioreactor applying these optimized conditions over 120 h of cultivation achieved a lipase activity of 79.31 U/mL.

PMID:40996539 | DOI:10.1007/s10529-025-03657-6

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Multi-Compartmental Staged Progression Endemic Models with Fast Transitions

J Math Biol. 2025 Sep 25;91(5):49. doi: 10.1007/s00285-025-02291-0.

ABSTRACT

We present a model of infectious disease dynamics where individuals can transition between different compartments, which may have distinct epidemiological characteristics. Within each compartment, epidemic dynamics are represented by a staged progression epidemic model. Individual transitions between compartments occur on a faster time scale, allowing the initial model to be reduced for analysis. In the reduced model, disease eradication and endemicity are characterized by the basic reproduction number. The relationship between this basic reproduction number and those associated with each compartment is analyzed by considering each compartment in isolation. This allows the study of the role of transitions in epidemic dynamics. Endemicity is represented by uniform persistence relative to the total number of infected individuals. It is verified that, for a sufficiently large ratio between time scales, the initial model shares the uniform persistence of the reduced model. The influence of transitions on disease eradication/endemicity is illustrated by different results. In particular, the conditions for transition rates are determined so that endemicity (eradication) in each isolated compartment results in global eradication (endemicity). These results can provide some tools for managing epidemics in the context of individuals transiting between compartments with different epidemiological properties.

PMID:40996532 | DOI:10.1007/s00285-025-02291-0

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Dementia(associated) deaths in Bavaria-analysis of comorbidities based on multiple cause of death statistics from 2020 to 2022

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 Sep 25. doi: 10.1007/s00103-025-04130-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Dementia is already one of the leading causes of death in Germany. Due to the demographic change, the number of dementia-related deaths will continue to rise in the future. The diversity of “dementia” and the increasing importance of multimorbidity require all diseases listed on the death certificate to be included in the analyses. The aim of this article is to analyse all persons deceased “from” and “with” dementia in Bavaria (= dementia-associated deaths) with regard to their socio-demographic characteristics and to group them based on their comorbidities.

METHOD: Since 2020, multiple causes of death statistics have been available in Bavaria. This allows for the inclusion of all other diseases contributing to death to be used in the analyses. The Bavarian dementia-related deaths from 2020 to 2022 were grouped into clusters based on their comorbidities using latent class analysis.

RESULTS: Approximately 19% of all deaths were dementia related. Among these, seven clusters were found: one multimorbidity cluster, one cardiovascular cluster, two infection clusters, two clusters with neurodegenerative diseases and one vascular cluster. The deceased of the clusters differed significantly in terms of age, gender, underlying cause and comorbidities.

DISCUSSION: The results of the multiple cause of death analysis indicated a possible underestimation of more specific types of dementia such as vascular dementia. In addition, identifying different combinations of diseases in dementia-related deaths can provide information on suitable treatment methods, preventive measures and possibilities to adapt care structures.

PMID:40996526 | DOI:10.1007/s00103-025-04130-5

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Effect of the Chelating Agent Alendronic Acid versus EDTA on the Physicochemical Properties of Dentine

Eur Endod J. 2025 Sep;10(5):397-405. doi: 10.14744/eej.2025.28482.

ABSTRACT

OBJECTIVE: The present study aimed to evaluate the changes in the physicochemical properties of dentine after irrigation with a solution of 0.22% alendronic acid (AA) as a chelating agent compared to 17% ethylene-diaminetetraacetic acid (EDTA).

METHODS: A total of 48 extracted premolars and molars that were intact, free of caries or cracks, without root canal treatment and restorations were collected. The roots were randomised into three groups (n=16): Group A: Distilled Water (dH2O); Group B: 17% EDTA, and Group C: 0.22% AA. Longitudinal sections of the dentine with a root of 1x1x10 mm were made with a diamond disc and a low-speed handpiece for bending tests (n=9). For morphological analysis, images were taken with a scanning electron microscope, crystallographic analysis with X-ray diffraction, and chemical analysis with Fourier Transform Infrared Spectroscopy (FTIR) and Vickers Hardness. For this purpose, cross-sections were made through the root using the Isomet to obtain 3 mm thick dentine discs (n=14). The samples were stored in dH2O for up to 24 h before use and dried at room temperature before exposure to chelating solutions for 1 h in a Stuart STR6D mixer at 50 rpm. For data comparison, the Kruskal-Wallis statistical test was used (α=0.05).

RESULTS: The chelating solutions of EDTA and AA cause alterations in the physicochemical structure of dentine, attacking mainly the inorganic part (Hydroxyapatite), which was observed in the decrease in intensity of the peaks in the X-ray diffraction pattern of hydroxyapatite. This generated a greater exposure of the collagen fibres that were observed in SEM and the increase in the bands characteristic to Collagen Type I in the infrared spectrum at 1645, 1550, and 1240 cm-1 belonging to amide I (C=O), amide II (N-H) and amide III (C-N), significantly affecting its dentine hardness (p=0.001).

CONCLUSION: AA can be used as a chelating agent in the area of dentistry. It does not generate a significant demineralising effect that modifies the physicochemical properties of dentine, as observed with EDTA.

PMID:40995721 | DOI:10.14744/eej.2025.28482

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Healing Outcome of Different Aqueous-based Calcium Hydroxide Intracanal Medicament in Patients with Pulpal Necrosis and Symptomatic Apical Periodontitis: A Randomised Controlled Trial

Eur Endod J. 2025 Sep;10(5):365-373. doi: 10.14744/eej.2025.04909.

ABSTRACT

OBJECTIVE: This study aimed to assess and compare the healing outcome associated with different aqueous-based calcium hydroxide intracanal medicaments in patients with pulpal necrosis and symptomatic apical periodontitis.

METHODS: Seventy five patients with pulpal necrosis and symptomatic apical periodontitis in permanent mandibular molar teeth were selected as the part of this study. The participants were randomly allocated to three groups, each comprising 25 patients, based on the type of intracanal medicament used during the treatment procedure. Group 1 consisted of calcium hydroxide (CH) mixed with 0.9% saline (NS), Group 2 contained CH combined with 2% lidocaine, and Group 3 included CH with 2% chlorhexidine (CHX). The Periapical Index Score was utilized to assess the healing of periapical lesions in preoperative and post-operative periapical radiographs at 3 month intervals for 12 months. The Kruskal-Wallis test was used to determine the significance, with Post Hoc Dunn tests for multiple comparisons.

RESULTS: At the 12-month follow-up, the CH+CHX group demonstrated significantly improved periapical healing, with a mean PAI score of 1.57 +- 0.66, compared to CH+LA (2.27+-0.63) and CH+NS (2.48+-0.79), with Kruskal-Wallis p<0.05. The mean time to achieve a healthy periapical status (PAI ≤2) was shortest in the CH+CHX group (8.10+-3.28 months), followed by CH+NS (8.23+-3.28 months) and CH+LA (8.25+-3.31 months), with the multivariate Log-Rank test indicating a statistically significant difference among the groups (p<0.05).

CONCLUSION: The findings of this study indicate that CH when combined with 2% CHX as an aqueous vehicle demonstrated superior healing of periapical lesions in patients with pulpal necrosis and symptomatic apical periodontitis compared to saline or lidocaine.

PMID:40995720 | DOI:10.14744/eej.2025.04909

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Impact of Different Nickel-titanium Instruments on Apical Micro-cracks Formation and Residual Amount of Root Canal Filling Materials Following Retreatment Procedure

Eur Endod J. 2025 Sep;10(5):420-431. doi: 10.14744/eej.2025.09226.

ABSTRACT

OBJECTIVE: This study aimed to evaluate and compare the dentinal defects caused by three different retreat-ment systems [Endostar RE Endo, XP-endo Retreatment, and MANI Gutta-Percha Removal (GPR)] and to assess the percentage of residual root canal filling material following the retreatment procedure.

METHODS: Sixty extracted mandibular second premolars with straight oval canals were used. The roots were standardized to a length of 14 mm. All samples were instrumented with NiTi instruments up to size 30.04, then filled using single cone technique with AH plus sealer and gutta-percha. Four groups were created from the samples. Group 1 served as the negative control (n=15), while the remaining three groups (n=15 each) were categorized based on the retreatment system used. Stereomicroscope at magnification 45 x was used to evaluate the incidence of crack formation and propagation at apex of the roots and the residual volume percentage of root filling materials in groups of Endostar RE, MANI GPR, Xp retreatment systems assessed using CBCT. Fisher’s exact test was used to analyze the incidence and propagation of cracks, while one-way ANOVA and Tukey’s post hoc test were applied to assess differences in residual filling material volume among the groups P values at 0.05.

RESULTS: There is significance difference (p=0.028) between the Endostar and Xp retreatment system. The highest of dentinal defect (1015) with Endostar retreatment system followed by (415) with GPR system and (215) with XP endo retreatment system.Highest residual filling material mean at Endostar RE retreatment system (51.97) and lowest mean (39.07) at Xp retreatment system A statistically significant difference was observed between the groups (p<0.001), particularly between the Endostar and XP retreatment systems.

CONCLUSION: No system was capable of completely eliminating obturated materials. The XP-endo Retreat-ment system showed the lowest incidence of crack formation and propagation and proved to be the most effective in removing gutta-percha and sealer.

PMID:40995718 | DOI:10.14744/eej.2025.09226