Nevin Manimala

Paediatr Drugs. 2025 Jan 28. doi: 10.1007/s40272-025-00682-w. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established.

OBJECTIVES: This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children.

PATIENTS AND METHODS: In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment.

RESULTS: Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ² = 2.237, P = 0.135).

CONCLUSIONS: Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety.

CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2100054340 (Date of Trial Registration: 14 December 2021).

PMID:39873962 | DOI:10.1007/s40272-025-00682-w

Acta Ophthalmol. 2025 Jan 28. doi: 10.1111/aos.17440. Online ahead of print.

ABSTRACT

PURPOSE: To explore the potential correlation between subjective and measured visual function, as well as to analyse the influence of eye disease, socioeconomic factors and emotional dimensions.

METHODS: Semi-structured interviews, physical examinations and functional tests (n = 1203). Demographics covered sex, marital status, education, household economy, smoking and alcohol. Participants (born in 1944) rated their visual function (n = 533); those misjudging (n = 48) were studied. Group A (n = 18) had low presenting visual acuity (PVA) but reported good vision; Group B (n = 30) had normal PVA but reported low vision. Control group (n = 485) matched subjective and measured visual function. Ophthalmic examination tested visual acuity (VA), visual field and contrast sensitivity (CS). Psychometric tests: NEO-FFI, sense of coherence (SOC) and Montgomery-Åsberg Depression Rating Scale (MADRS).

STATISTICAL TESTS: chi-square, t-tests, Mann-Whitney U test and logistic regression.

RESULTS: Of the population, 91% made correct assumptions about their vision. The 9% who made incorrect assumptions about their vision ability (combining groups A + B) were more likely to live alone (p = 0.02) and had lower household incomes compared to the control group (p = 0.04). Additionally, the exhibited significantly lower PVA and BCVA, a higher prevalence of visual field defects (p = 0.02) and lower CS, mean 1.63 (p = 0.005). Group A (3.4%) were women (p = 0.002) with the personality of extraversion, mean 40.0 (p = 0.01). Group B (5.6%) had more self-reported eye diseases (p = 0.01), lower CS (p = 0.01), lower educational level (p = 0.03) and border significantly lower SOC (p = 0.06).

CONCLUSIONS: The perception of visual function is shaped by awareness of an eye disease but is additionally influenced by sex, socioeconomic factors and emotional parameters.

PMID:39873951 | DOI:10.1111/aos.17440

Ophthalmol Ther. 2025 Jan 28. doi: 10.1007/s40123-024-01089-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen. This study aimed to report the safety and efficacy profile of lotilaner ophthalmic solution (0.25%) from a pooled analysis of two pivotal trials in patients with Demodex blepharitis.

METHODS: Pooled data were analyzed from two randomized, double-masked, vehicle-controlled clinical trials [phase 2b/3 Saturn-1 (NCT04475432) and phase 3 Saturn-2 (NCT04784091)] in which patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution (0.25%) (study group) or the vehicle formulation without lotilaner (control group), twice daily for 6 weeks. The outcome measures were the proportion of patients with 0-2 collarettes (grade 0 collarettes), mite eradication, erythema cure, and the proportion of patients with ≤ 10 collarettes (grade 0 or 1 collarettes) at day 43.

RESULTS: Overall, 833 participants were randomized to receive either the study drug (N = 415) or vehicle (N = 418). On day 43, 49.8% of patients in the study group vs. 9.9% in the control group (p < 0.0001) had collarette grade 0 (0-2 collarettes). A reduction to ≤ 10 collarettes (grade 0 or 1 collarettes) was achieved in 85.1% of patients in study group vs. 28.0% in control group (p < 0.0001). The proportion of patients achieving mite eradication (60.2% vs. 16.1%, p < 0.0001) and erythema cure (24.9% vs. 7.9%, p < 0.0001) were also statistically significantly higher in the study group compared to the control group. The rates of adverse events were low in both studies, with no serious drug-related ocular adverse events reported. As many as 92% of patients rated the study drop as neutral to very comfortable.

CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution (0.25%) for 6 weeks demonstrated statistical significance for all outcome measures compared to the vehicle control, with low rates of adverse events and a high rate of drop comfort.

PMID:39873946 | DOI:10.1007/s40123-024-01089-5

AMB Express. 2025 Jan 28;15(1):15. doi: 10.1186/s13568-024-01797-y.

ABSTRACT

The urgent need to address the growing problem of antimicrobial resistance in multidrug-resistant bacteria requires the development of pioneering approaches to treatment. The present study aims to evaluate the antimicrobial potential of the essential oils (EOs) of Moringa oleifera (moringa), Cinnamomum verum (cinnamon), and Nigella sativa (black seed) and the synergistic effect of the mixture of these oils against Staphylococcus aureus MCC 1351. Statistical modeling revealed cinnamon oil had the highest individual antimicrobial potency, followed by black seed oil. The combination of the three EOs exhibited significant synergistic effects compared to the individual oils, with a Fractional Inhibitory Concentration (∑FIC) index of 0.27. L-Optimal mixture design of response surface methodology (RSM) identified the optimal mixture as moringa: cinnamon: black seed oils by the ratio of (1:1:1) in run 15 (0.338:0.307:0.355 mL) (v/v). This mixture exhibited significant antibacterial efficacy, outperforming individual oils and conventional antibiotics like tetracycline. Specifically, the combination reduced the MIC values from 3.12, 0.78, and 6.25 to 0.25, 0.06, and 0.78 μg/mL for moringa, cinnamon, and black seed oil, respectively. Synergistic interactions between oils further boosted efficacy, with moringa-cinnamon and cinnamon-black seed pairings exhibiting the strongest synergies. The developed predictive models for IZD and MIC showed excellent fit, with R² values of 0.9843 and 0.9958, respectively. Pareto chart analysis highlighted the predominant individual and synergistic effects, with the Moringa-Cinnamon interaction exhibiting the highest positive synergy. Notably, the oil mixture of run 15 demonstrated excellent biocompatibility, maintaining 97.6% viability of normal human skin fibroblasts (HSF) after 24 h exposure to 200 μL EOs of the mixture per mL. Gas chromatography mass spectrometry (GC/MS) identified abundant bioactive phytochemicals like cinnamaldehyde, linoleic acid, and palmitic acid methyl esters underlying the observed antimicrobial effects. This rationally designed, synergistic phytochemical combination presents a promising natural therapeutic against antibiotic-resistant S. aureus while exhibiting minimal cytotoxicity. The results underscore how combining essential oils could help address the issue of antibiotic resistance in S. aureus.

PMID:39873942 | DOI:10.1186/s13568-024-01797-y

Eur J Dent Educ. 2025 Jan 27. doi: 10.1111/eje.13076. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the impact of community-based dental education (CBDE) on the learning experiences of undergraduate dental students and recent dental graduates from two diverse geographical regions.

METHODS: The study followed a cross-sectional design, conducted online using Google Forms, with ethical approval from Qatar University. A non-probability purposive sampling method was used to recruit dental students and recent graduates from three institutions in India and one in Qatar. A questionnaire based on 20 closed-ended items and two open-ended questions, developed by a team of dental academics, was used for data collection. Data analysis involved descriptive statistics, analysis of variance (ANOVA) and thematic analysis for open-ended responses.

RESULTS: The study included 148 participants, with 116 female (78.37%) and 32 male (21.62%) students, mostly from India (75%) and the rest from Qatar (25%). ANOVA revealed significant differences based on age, country and stage of education (p < 0.001). Dental interns had the highest mean score (1.12 ± 0.8), while Year 2 students had the lowest (0.75 ± 1.08). Female participants had a slightly higher mean score (1.05 ± 0.77) than male participants (0.92 ± 0.98), although this difference was not statistically significant (p = 0.127). Key challenges included inadequate support and cultural barriers in India, and conflicts with religious obligations and didactic workload in Qatar. Recommendations focused on enhancing field activities, logistical support and mentorship programmes.

CONCLUSIONS: The study shows that dental students value CBDE for developing essential skills for community engagement. However, challenges differ across socio-cultural contexts, highlighting the need for more localised and supportive frameworks to improve CBDE experiences. The variation in student perceptions by age, education stage and country suggests that CBDE strategies should be flexible and adaptable to address the diverse learning needs of students.

PMID:39871109 | DOI:10.1111/eje.13076

Spine Deform. 2025 Jan 27. doi: 10.1007/s43390-025-01048-5. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the sites where the tether breaks in vertebral body tethering (VBT) cases.

METHODS: Intraoperative evaluation of broken tethers in patients who had anterior revision.

INCLUSION CRITERIA: anterior revision of VBT cases with explantation of the full implant and photo documentation. Eight patients met the inclusion criteria. The primary variable of interest was the location of tether breakage in relation to the vertebral curve and the tether-screw interface. Another variable of interest was to evaluate the difference in breakage rates between anterior and posterior tethers in double tether cases.

RESULTS: Sixty tethers bridging the intervertebral disc within this cohort of eight patients were found. Seven implants were removed from thoracolumbar curves and one implant from a thoracic curve. We identified 32 tether breakages. Double tethers were used in six patients. In these six cases, 15 breakages were found in the posterior tether and 13 in the anterior tether. Four cases (50%) exhibited breakages at the apex, eight cases (100%) at the lowest instrumented vertebra (LIV), and five cases (63%) at the uppermost-instrumented vertebra (UIV). Five tether breakages (in three cases with double tether) were observed at the screw sites, while the remaining 27 exhibited cord breakages near the intervertebral discs. In double tether systems, statistical analysis did not reveal any significant difference in breakage rates between anterior and posterior tethers.

CONCLUSIONS: In VBT cases, the tether breaks mostly at the level of the intervertebral disc, adjacent to the lowest instrumented vertebra.

LEVEL OF EVIDENCE: Level IV (Case series with no comparison group).

PMID:39871083 | DOI:10.1007/s43390-025-01048-5

Oral Radiol. 2025 Jan 27. doi: 10.1007/s11282-025-00802-9. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluates the potential of pulp volume/total tooth-volume measurements of canine teeth in relation to chronologic age in patients with cleft lip and palate (CLP). The significance of this study lies in its exploration of the usability of these measurements for age determination in CLP patients, providing a novel perspective to the existing literature.

METHODS: Cone beam computed tomography images of 33 patients (16 females, 17 males) with unilateral CLP aged 14-45 years and 33 age- and sex-matched healthy individuals (16 females, 17 males) were retrospectively evaluated. Using ITK-SNAP software, pulp and whole tooth volumes of canine teeth on the non-defect side of CLP patients and the corresponding side of healthy individuals were measured. Their relationship with chronologic age was evaluated, and comparisons were made between the CLP and control groups.

RESULTS: No statistically significant difference was observed between the whole tooth volume, pulp volume, and pulp volume/total tooth-volume ratios of the control and CLP groups. A paired t test comparing chronologic age and calculated mean age of both groups found no significant difference.

CONCLUSIONS: The results show that the pulp and total tooth-volume ratios of canine teeth in the non-defect areas of individuals with unilateral CLP correlate with chronologic age and can be used reliably for age determination. This indicates that individuals with CLP can be evaluated similarly to healthy individuals, allowing accurate age estimation based on dental measurements.

PMID:39871068 | DOI:10.1007/s11282-025-00802-9

Ann Biomed Eng. 2025 Jan 27. doi: 10.1007/s10439-025-03684-4. Online ahead of print.

ABSTRACT

Titanium (Ti)-based materials are favored for hard tissue applications, yet their bioinertness limits their success. This study hypothesizes that functionalizing Ti materials with chitosan nano/microspheres and calcitriol (VD) will enhance their bioactivity by improving cellular activities and mineralization. To test this, chitosan particles were applied uniformly onto Ti surfaces using electrophoretic deposition (EPD) at 20 V for 3 minutes. VD was then loaded onto the coated surfaces, and the release profile of VD was monitored. Human fetal osteoblastic cells (hFOB) were cultured on the VD-loaded Ti surfaces. Cellular activities such as proliferation, Alkaline phosphatase (ALP) activity, osteogenic gene expression (runt-related transcription factor 2 (Runx2), collagen type 1 (Col I), osteocalcin ( OCn), osteopontin (OP)), and mineralization were assessed. Von Kossa staining was performed to analyze mineralization, and the expression of cell adhesion proteins (N-cadherin (NC), integrin alpha V (IaV), integrin beta 3, (Ib3)) was measured. The results showed that approximately 50% of the VD released over 50 hours. The chitosan coating increased surface roughness three-fold, and this, combined with VD release, resulted in reduced cell proliferation but increased ALP activity, suggesting enhanced differentiation. VD-functionalized Ti surfaces showed statistically significant differences in osteogenic gene expressions, particularly on rougher surfaces. Additionally, the expression of cell adhesion proteins (NC, IaV, Ib3) was upregulated on VD-containing coated surfaces. Von Kossa analysis revealed that surface roughness significantly enhanced mineralization, particularly on VD-free surfaces by day 7, while mineralization on VD-containing bare surfaces started on day 14. These findings demonstrate that VD-loaded chitosan coatings significantly enhance the biocompatibility and bioactivity of Ti-based materials, highlighting their potential for applications in bone regeneration.

PMID:39871063 | DOI:10.1007/s10439-025-03684-4

J Vet Intern Med. 2025 Mar-Apr;39(2):e70002. doi: 10.1111/jvim.70002.

ABSTRACT

BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker for the early diagnosis of AKI.

OBJECTIVES: To evaluate uNGAL in dogs with non-associative immune mediated hemolytic anemia (IMHA) and to evaluate whether uNGAL correlates with disease severity markers, negative prognostic indicators and outcome.

ANIMALS: Twenty-two dogs with non-associative IMHA and 14 healthy dogs.

METHODS: Prospective case-control study. uNGAL was measured by a commercially available ELISA-kit and corrected to urine creatinine (uNGAL to creatinine ratio [UNCR]). uNGAL and UNCR of IMHA cases were compared to that of healthy dogs and the correlation with other clinicopathological markers was evaluated. uNGAL and UNCR were also compared between dogs with a CHAOS or ASA score < 3 and ≥ 3.

RESULTS: uNGAL and UNCR were significantly higher in dogs with IMHA when compared to healthy controls (uNGAL median 114.58 and 0.43 ng/mL, respectively, p < 0.001; UNCR median 174.87 and 0.13 ng/mg, respectively, p < 0.001). uNGAL and UNCR were moderately positively correlated with urea (p = 0.005, r = 0.58, 0.20-0.81 95% CI and p = 0.001, r = 0.64, 0.29-0.84 95% CI, respectively) and total bilirubin (p = 0.003, r = 0.60, 0.22-0.82 95% CI and p = 0.002, r = 0.62, 0.25-0.83 95% CI, respectively). These were also significantly higher in dogs with hemoglobinuria compared to those without (uNGAL: median 269 and 30.99 ng/mL, respectively, p < 0.001; UNCR: median 585.3 and 352 37.47 ng/mg, respectively, p < 0.001). There was no statistically significant difference in uNGAL or UNCR when assessing survival to discharge (p = 0.24 and p = 0.16, respectively, 95% CI).

CONCLUSIONS: This study suggests that renal injury might be underappreciated in dogs with IMHA.

PMID:39871050 | DOI:10.1111/jvim.70002

Int Urol Nephrol. 2025 Jan 27. doi: 10.1007/s11255-025-04389-2. Online ahead of print.

ABSTRACT

PURPOSE: To identify prognostic factors for overall survival (OS) and develop a prognostic score in patients receiving docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

METHODS: Retrospective analysis was conducted on mCRPC patients treated with docetaxel at a German tertiary center between March 2010 and November 2023. Prognostic clinical and laboratory factors were analyzed using uni- and multivariable logistic regression. Next, the result of the modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) (cut-off ≥3), the presence of high-volume bone metastases (as defined by CHAARTED criteria), hemoglobin (Hb) (cut off < 13.2 g/dl), Gleason score ≥8, and presence of visceral metastases were combined into the Metastasized Prostate Cancer Survival Score (MeProCSS). Patients were then stratified into three prognostic groups. Their OS was assessed by Kaplan-Meier analysis.

RESULTS: Median OS for the overall cohort (n = 153) and the first-line cohort (n = 83) was 18 and 21.5 months, respectively. In multivariable analysis, high-volume bone metastases and Hb levels below the norm were significant predictors of shorter OS in the total cohort. The MeProCSS demonstrated an area under curve (AUC) of 0.837 in the overall cohort and 0.946 in first-line cohort. Kaplan-Meier analysis revealed a significant association between lower MeProCSS and longer OS in both the overall (p<0.001) and first-line (p = 0.035) cohort.

CONCLUSION: MeProCSS, consisting of routinely collected parameters prior to the start of chemotherapy, seems to effectively stratify patients with mCRPC into risk groups based on their metastatic burden, nutritional and inflammatory status. This model may guide treatment decisions and reveal a potentially often underestimated or overlooked urgency for additional measures as supportive palliative care in mCRPC patients. Further large and prospective studies are necessary for validation of MeProCSS-also in other systemic PC therapy regimens.

PMID:39871032 | DOI:10.1007/s11255-025-04389-2