Nevin Manimala

Ther Innov Regul Sci. 2025 Aug 21. doi: 10.1007/s43441-025-00863-2. Online ahead of print.

ABSTRACT

Medical devices used in health care should fulfill the requirements of the technical regulations to protect patient health. Difficulties in enforcing stricter rules in the new medical device regulations may negatively affect the continuity of care. This study examines the status of manufacturers’ compliance with medical device regulations, based on predefined criteria, and proposes a collaborative action plan and an approach to verify regulatory compliance. We conducted a nationwide survey comprising questions grouped by criteria to understand the status of the manufacturers in terms of compliance with the Medical Device Regulation. Four hundred sixty-seven manufacturers participated in the survey. We achieved a Cronbach’s alpha of 0.77, which indicates that the survey is statistically reliable. We applied the independent samples t-test to the responses to determine significant features per question and employed factor analysis to investigate the relationships of the questions. The results of independent samples t-tests showed statistically significant differences across groups in replies to several survey items (p < 0.05), indicating that participants’ opinions varied based on their demographic characteristics. We applied Exploratory Factor Analysis to introduce the relationships between the questions. The analysis revealed that manufacturers continue to face substantial challenges in acquiring sufficient knowledge and operational capability to meet MDR requirements. In light of these findings, we focused on the person responsible for regulatory compliance, who plays a central role in maintaining regulatory compliance within manufacturing organizations. We proposed an action plan at the macro level to introduce more effective action plans in cooperation with other stakeholders, including healthcare providers, and a verification approach for regulatory compliance to enhance the Person Responsible for Regulatory Compliance’s competence. Manufacturers should implement effective postmarketing clinical follow-up plans involving device-oriented parameters for monitoring in the healthcare system, especially in collaboration with health professionals.

PMID:40839208 | DOI:10.1007/s43441-025-00863-2

Environ Monit Assess. 2025 Aug 21;197(9):1033. doi: 10.1007/s10661-025-14446-z.

ABSTRACT

This study focuses on the rarely ventured assessment of the flood-induced heavy metal contamination in the water sources in a flood-prone region in India, emphasizing human health risks using average daily dose (ADD), hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR). Results showed children were more vulnerable to exposure than adults, and ingestion was the main route of exposure, followed by dermal and inhalation. The contribution of Cd to the cumulative HI for children was the highest, exceeding the maximum acceptable risk level of 1.0 × 10^-4. The values of single HI were elevated after flooding, but did not exceed the critical value of 1. The highest CR contributor was Cr, followed by Cd, Ni, and Pb, with lifetime CR within the acceptable limit of 10^-6-10^-4. Heavy metal pollution index (HPI) was found to be > 100 for both river and groundwater, indicating “severe” contamination status with Cd, Mn, and Fe being the prime contributors. The paired t-static revealed significant differences in the metal concentrations before and after floods. Factors extracted by principal components analysis (PCA) indicated the influence of floods as a source of metal contamination integrated with anthropogenic and geogenic sources. The findings form an important database for monitoring, mitigating, and remediating flood-induced contaminations and human health effects in riverine systems.

PMID:40839204 | DOI:10.1007/s10661-025-14446-z

Clin Rheumatol. 2025 Aug 21. doi: 10.1007/s10067-025-07630-6. Online ahead of print.

ABSTRACT

OBJECTIVE: Understand the willingness and preference of patients with knee osteoarthritis for biological treatment, and the current status of knee osteoarthritis treatment.

METHODS: KOA patients with grades 1-4 Kellgren-Ray (K-L) in the knee of our imaging department from November 1, 2022, solstice May 1, 2023, were included in this single-center cross-sectional survey. The questionnaire was designed through the online questionnaire platform, and 502 questionnaires were completed, of which 393 were eligible for this study.

RESULTS: (1) Basic information: 66.67% (262/393), female, male 33.33% (131/393), male: 1:2; patients aged 45-69 years 89.06% (350/393); 28.50% (112/393); first degree relatives’ osteoarthritis 6.87% (27/393); hyperlipidemia 10.94% (43/393); hypertension 30.79% (121/393); diabetes 9.16% (36/393). (2) Disease assessment: the patients had a significant negative relationship between Lysholm score and WOMAC score, with a correlation coefficient of – 0.632, p < 0.01. Using the Kruskal-Wallis test statistic, the Lysholm score showed different K-L grade samples for the WOMAC score (p < 0.01). (3) Classical treatment: 84.99% of the subjects had no attempted basic treatment for osteoarthritis. 94.40% had not tried 4 exercise therapies for osteoarthritis. 96.95% had not attempted physical therapy for osteoarthritis. 98.73% did not try exercise aids for osteoarthritis. 67.94% had not tried TCM treatment for osteoarthritis, accounting for 18.58%, two accounted for 10.69%, three accounted for 2.04%, and four accounted for 0.76%. 77.35% did not try nonsteroidal anti-inflammatory drugs for osteoarthritis, 16.03%, 6.36%, and six 0.25%. 87.02% had not tried non-class NSAIDs analgesic drugs for osteoarthritis, using weak opioid analgesics 10.69% and strong opioid analgesics 2.29%. 95.93% denied previous use of glucocorticoids for osteoarthritis, 16 but not consistently. 85.75% had not tried using slow-acting drugs (SYSADOAs) to relieve OA symptoms, 11.45% and 2.80%, respectively. 99.24% denied taking antidepressant anxiety medication for osteoarthritis. 92.37% denied attempted knee cavity injection (sodium hyaluronate, glucocorticoids), 25 had sodium hyaluronate injection in the joint cavity, 6.36%, and 5 had glucocorticoid injection, 1.27%. (4) Biological therapy situation: 96.44% did not know the biological therapy of the knee cavity for osteoarthritis. 96.69% were not recommended for knee cavity biological treatment, 13 people were recommended, accounting for 3.31%, of which 11 were recommended by doctors, accounting for 84.62% (11/13), and relatives recommended for 15.38% (11/13). In the Likert5 scoring method of joint cavity biological treatment, 10 people in this study were very reluctant, accounting for 2.54%; 37 preferred unwilling, accounting for 9.41%; 264, average, accounting for 67.18%; 40 preferred, accounting for 10.18%; 42, very willing, accounting for 10.69%. The stepwise regression analysis of the factors affecting the willingness to treat joint cavity biotherapy, the previous treatment with sodium hyaluronate or corticosteroid knee cavity injection, WOMAC score will have a significant positive effect on the willingness score of joint cavity biotherapy. In addition, age had a significant negative effect on the willingness to treat the joint cavity. (5) The analysis was performed by MaxDiff: efficacy, course of treatment, side effects, medical expenses, and administration pathways (oral, external use, and intra-articular injection), subject preference for choosing a joint cavity biotherapy. The preferred shares are, respectively. Efficacy > side effect > medical expenses > course of treatment > administration pathways, 69.42% > 15.85% > 6.39% > 4.93% > 3.41%.

CONCLUSION: In this study, KOA subjects, most had not received osteoarthritis-related standard treatment, and the proportion of TCM treatment was relatively high. The low awareness rate of knee biological therapy, the joint cavity injection treatment, high WOMAC score, and age have an impact on the treatment intention of biologics. Efficacy is the most important factor in patient preference for KOA treatment. Key Points • The low awareness rate of knee biological therapy, the joint cavity injection treatment, high WOMAC score, and age have an impact on the treatment intention of biologics. • Efficacy is the most important factor in patient preference for KOA treatment.

PMID:40839199 | DOI:10.1007/s10067-025-07630-6

Int J Dermatol. 2025 Aug 21. doi: 10.1111/ijd.70025. Online ahead of print.

ABSTRACT

BACKGROUND: Secukinumab, a fully human, monoclonal antibody targeting interleukin-17A, is approved for moderate-to-severe HS in adults. This study evaluated pharmacokinetics (PK), high-sensitivity C-reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials.

METHODS: An exploratory analysis of pooled Phase-3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure-response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed.

RESULTS: Mean serum trough concentration at Weeks 16, 24, and 52 was ~2-fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals.

CONCLUSION: Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose-response relationship observed.

TRIAL REGISTRATION: NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302).

PMID:40839197 | DOI:10.1111/ijd.70025

J Robot Surg. 2025 Aug 21;19(1):503. doi: 10.1007/s11701-025-02666-x.

ABSTRACT

While robotic surgery has been dominated by a single platform in the United States for over 25 years, the introduction of new robotic systems may have an impact on subjective workload. Therefore, we aimed to establish baseline workload measurements for operating room team members using the DaVinci surgical robot during robotic hernia procedures, providing reference points for evaluating team adaptation as new robotic platforms are introduced. Within the operating room, subjective workload refers to the physical, cognitive, and temporal demands experienced during surgical procedures. We prospectively collected NASA-TLX surveys from surgeons, circulators, and scrub staff performing robotic hernia repairs between February-December 2024. Baseline demographics and prior robotic experience were collected for each participant. Surveys assessed subjective workload across six NASA-TLX domains and surgeon assessment of case complexity relative to other procedures (Easiest 1/3, Average, Hardest 1/3). Case-specific information was extracted from the electronic medical record. We used linear mixed-effects models (LMMs) to analyze role-based and complexity-related workload, which accounts for within-subject correlation from repeated measurements collected from the same individuals across different surgical cases. A total of 131 post-operative surveys were analyzed from 14 participants across 72 robotic hernia cases. Robotic OR team members reported similar baseline workload with the highest overall workload reported by circulators (mean 30.6, 95% CI 22.1-39.2), followed by scrub staff (mean 25.1, 95% CI 16.5-33.7). Surgeons experienced the lowest overall workload (mean 24.4, 95% CI 10.2-38.6), however, demonstrated a significant stepwise increase in workload with increasing case complexity (mean 11.4 to 41.5, Cohen’s d = 3.41, 95% CI [2.31, 4.51], p < 0.0001), while circulators and scrub staff were unaffected. Comparisons across NASA-TLX domains showed that circulators reported significantly worse self-assessed performance (mean difference vs. surgeons: 14.97, 95% CI [8.84, 21.10], p = 0.001; vs. scrub staff: 9.60, 95% CI [4.21, 14.99], p = 0.002) and higher effort compared to other team members (mean difference vs scrub staff: 11.07, 95% CI [3.20, 18.94], p = 0.017). These findings provide one of the first role-specific benchmarks for intraoperative workload in robotic hernia surgery, representing essential reference metrics against which new robotic platforms can be evaluated. Further exploration of these role-specific challenges is needed to determine if there are opportunities to optimize workload to improve patient safety, team efficiency, and staff well-being as new platforms are adopted.

PMID:40839192 | DOI:10.1007/s11701-025-02666-x

Curr Opin Oncol. 2025 Aug 12. doi: 10.1097/CCO.0000000000001184. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Immunotherapy has transformed the management of several malignancies, yet its role in rare breast cancer histologies remains poorly defined due to limited research and few dedicated clinical trials. This review critically assesses current knowledge and emerging opportunities for immunotherapy in these uncommon breast cancer subtypes.

RECENT FINDINGS: Rare breast cancer histologies exhibit heterogeneous immunogenicity, including variable expression of programmed death-ligand 1 (PD-L1), differing levels of tumor-infiltrating lymphocytes (TILs), and distinct mutational burdens. Recent studies highlight potential immunotherapy responsiveness in metaplastic, invasive lobular, apocrine, and other rare breast cancer types, though predictive biomarkers like PD-L1 and tumor mutational burden (TMB) alone appear insufficient. Currently, only two clinical trials specifically target rare breast cancer histologies, emphasizing significant knowledge gaps.

SUMMARY: The effectiveness of immunotherapy in rare breast cancer histologies remains limited, likely due to inadequate patient selection using current biomarkers such as PD-L1 and TMB. Further research must focus on refining predictive biomarkers to better identify patients likely to from immunotherapy and enhance outcomes in these challenging clinical settings.

PMID:40838334 | DOI:10.1097/CCO.0000000000001184

J Periodontol. 2025 Aug 21. doi: 10.1002/JPER.24-0735. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory cytokines play a significant role in the pathogenesis of both autoimmune hypothyroidism and periodontal disease. The cumulative effect of these inflammatory markers may lead to extensive periodontal breakdown. This study was undertaken to assess the prevalence and severity of periodontitis, to correlate clinical attachment loss (CAL), and periodontal inflamed surface area (PISA) with anti-thyroid peroxidase (anti-TPO) antibody, triiodothyronine (T3), thyroxine (T4), thyroid- stimulating hormone (TSH), and C-reactive protein (CRP) in autoimmune hypothyroid patients and systemically healthy subjects.

METHODS: This cross-sectional study comprised of 65 autoimmune hypothyroid patients under treatment and 75 systemically healthy subjects. All participants were evaluated for periodontal parameters (bleeding on probing (BoP), probing pocket depth (PPD), CAL, oral hygiene index-simplified (OHI-S Index), Plaque Index (PI) and PISA) and systemic parameters (T3, T4, TSH, anti-TPO antibody, and CRP). Analysis of quantitative and qualitative data was done by unpaired t-test and Chi-Square test, respectively.

RESULTS: Prevalence and severity of periodontitis in the autoimmune hypothyroid group were significantly higher compared with the systemically healthy group (p < 0.001). CAL, PISA, T3, TSH, and anti-TPO antibody were significantly higher in the autoimmune hypothyroid group as compared with the systemically healthy group. Mean CAL and PISA were positively correlated with anti-TPO antibody, T3, T4, TSH, and CRP. The multivariate linear regression model with dependent variable mean CAL showed that anti-TPO antibody was significantly associated with mean CAL (β = 0.001, p = 0.02).

CONCLUSIONS: Autoimmune hypothyroid subjects exhibited a higher prevalence and severity of periodontitis compared with the systemically healthy group. BoP, PPD, CAL and PISA were also higher in autoimmune hypothyroid group as compared with the systemically healthy group. A statistically significant positive correlation of CAL, and PISA with anti-TPO antibody, T3, TSH, and CRP was observed.

PLAIN LANGUAGE SUMMARY: This study assessed the link between autoimmune hypothyroidism (a condition characterized by decreased thyroid function) and periodontitis by comparing 65 individuals with autoimmune hypothyroidism undergoing treatment to 75 healthy subjects. This research measured periodontal health indicators, thyroid hormone levels, and inflammatory markers. Results indicated that those with autoimmune hypothyroidism experienced more severe periodontal disease and increased periodontal tissue loss. They also showed elevated levels of specific thyroid antibodies and thyroid hormonal imbalances. Importantly, a significant positive association was found between the extent of periodontal tissue loss and these thyroid-related markers, especially the anti-TPO antibody. In conclusion, individuals with autoimmune hypothyroidism are at a higher risk for severe periodontal disease, suggesting a relationship between thyroid dysfunction and periodontal health. Therefore, it is crucial for both periodontists and endocrinologists to recognize this association when planning appropriate treatments.

PMID:40838332 | DOI:10.1002/JPER.24-0735

Phys Chem Chem Phys. 2025 Aug 21. doi: 10.1039/d5cp01466b. Online ahead of print.

ABSTRACT

The bimolecular reactions between CH₃F and H₂⁺, HD⁺ and D₂⁺ have been studied in the range of collision energies between ∼0 and k_B × 30 K using a merged-beam approach. The ion-molecule reactions were investigated following photoexciting of H₂ (HD, D₂) to high Rydberg states in a supersonic beam, merging the Rydberg-molecule beam with a cold supersonic beam of CH₃F using a surface-electrode Rydberg-Stark deflector and monitoring the CH₃⁺, CH₂F⁺ and CH₃F⁺ ions generated by the reactions of H₂⁺ (HD⁺, D₂⁺) with CH₃F within the distant orbit of the Rydberg electron. In all three reaction systems, a strong increase of the rate coefficients was observed at collision energies below k_B × 4 K. Branching ratios for the formation of CH₃⁺, CH₂F⁺ and CH₃F⁺ were measured for all three reactions as a function of the collision energy. The branching ratio for the formation of CH₃⁺ was found to decrease with increasing deuteration of the hydrogen molecular ion and to increase at collision energies below k_B × 4 K. The experimental results were interpreted using model calculations based on a rotationally adiabatic capture model as well as using classical trajectory simulations. The reaction products are shown to be generated in two distinct mechanisms: electron transfer leading to a dominant CH₂F⁺ and a weaker CH₃F⁺ product channel, and short-range complex formation leading predominantly to CH₃⁺ by F^– transfer, with a weaker contribution of CH₂F⁺ by H^– transfer. The model calculations highlight the role played by quantum-statistical and stereodynamical effects associated with the J = 1, |K| = 1 ground state of para-CH₃F and by the reduced mass of the colliding partners: the orientation of CH₃F molecules induced by the electric field of the ion favours the production of CH₃⁺ by F^– transfer at low collision energies and the slower approach of the reaction partners with increasing reduced mass favours electron transfer at intermediate distances.

PMID:40838331 | DOI:10.1039/d5cp01466b

Vasa. 2025 Aug 21. doi: 10.1024/0301-1526/a001225. Online ahead of print.

ABSTRACT

Background: We investigated the safety and efficacy of antiplatelet therapy in preventing native arteriovenous fistula (AVF) dysfunction. Patients and methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) evaluating the effects of antiplatelet therapy following native AVF creation were eligible for inclusion. The primary endpoint was AVF primary patency. Secondary endpoints included AVF maturation, abandonment, and overall bleeding. Results: Twelve RCTs, comprising 2,491 patients, were incorporated in the analysis. The included studies assessed aspirin, clopidogrel, ticlopidine, and dypiridamole across various dosing regimens. The postoperative administration of antiplatelets, regardless of the specific drug or dose, was associated with improved AVF primary patency compared to controls or placebo, odds ratio (OR) 2.28 (95% CI: 1.42-3.65). Subgroup analysis showed no significant differences for aspirin 100mg daily or clopidogrel 75mg daily compared to controls/placebo, with ORs of 1.08 (95% CI: 0.76-1.54) and 2.16 (95% CI: 0.95-4.91), respectively. In contrast, ticlopidine 250mg twice daily significantly improved patency, OR 3.48 (95% CI: 1.46-8.26). Additionally non-statistically significant differences were identified between the antiplatelet and control/placebo groups in terms of maturation, OR 1.58 (95% CI: 0.81-3.09), AVF abandonment, risk ratio (RR) 0.93 (95% CI: 0.58-1.50), or overall bleeding RR 1.18 (95% CI: 0.77-1.81). Finally, meta-regression analysis of the antiplatelet groups pooled estimates revealed a negative association between maturation and follow-up duration (β =-0.1235, p<.01), and treatment duration and abandonment outcomes (β =-0.065, p<.01). Conclusions: This review demonstrated the safety and efficacy of antiplatelet therapy in preserving AVF patency, with ticlopidine and clopidogrel emerging as the primary contributors to this outcome. These findings suggest the potentially beneficial role of adenosine diphosphate (ADP) receptor antagonists in maintaining AVF patency.

PMID:40838310 | DOI:10.1024/0301-1526/a001225

ANZ J Surg. 2025 Aug 21. doi: 10.1111/ans.70279. Online ahead of print.

ABSTRACT

BACKGROUND: Pelvic exenteration (PE) including en-block resection of two or more adjacent pelvic organs, regional lymph nodes, and pelvic side wall is a major surgical undertaking with associated morbidity. This study aims to assess the rate of urological intervention and complications of PE at an Australian quaternary centre.

METHODS: Patients undergoing PE with a genitourinary component between January 2003 and July 2021 were included. Data were collected prospectively and analyzed retrospectively. Complications were defined as early (< 30 days) or late (≥ 30 days) using the Clavien-Dindo classification.

RESULTS: A total of 424 patients underwent PE, of whom 213 (50.2%) had a genitourinary component. Early post-operative (30-day) mortality was 0.5% and overall survival was 59.6%. Early urological complications occurred in 106 (49.8%) patients, with 11 (5.2%) experiencing an early urine leak and five (2.3%) sustaining ureteric injury. A late urological complication eventuated in 56 (26.3%) patients, with 19 (8.9%) patients developing non-malignant ureteric stricture requiring upper tract intervention. Chronic kidney disease developed post-operatively in 39 (18.3%) patients at the completion of patient follow-up. Female sex and primary (versus recurrent) malignancy were the only statistically significant predictors of new chronic renal impairment (OR [95% CI] 2.86 (1.33-6.16) and 2.18 (1.09-4.34), respectively). No pre-operative clinicopathological factors predicted urine leak.

CONCLUSIONS: Our experience with PE over a long follow-up period demonstrates urological complication rates consistent with the literature associated with urinary diversion and anastomosis, with expected rates of urine leak and ureteric stricture. Further research is required to better delineate and mitigate risk factors for genitourinary complications.

PMID:40838304 | DOI:10.1111/ans.70279