Category: Nevin Manimala

J Antimicrob Chemother. 2025 Dec 4:dkaf435. doi: 10.1093/jac/dkaf435. Online ahead of print.

ABSTRACT

BACKGROUND: Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity.

OBJECTIVE: To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010-2020).

METHODS: A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin).

RESULTS: Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance.

CONCLUSIONS: Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections.

PMID:41342135 | DOI:10.1093/jac/dkaf435

Eur J Neurol. 2025 Dec;32(12):e70440. doi: 10.1111/ene.70440.

ABSTRACT

BACKGROUND: Insurance data allow insights into dispensations of medications. This retrospective study over 49 months examined dispensations of monoclonal antibodies against calcitonin gene-related peptide (CGRP-mAbs).

METHODS: Using nationwide insurance data, we examined dispensations of erenumab, fremanezumab, or galcanezumab from September 1, 2018 to September 30, 2022. We examined the duration of treatment and breaks (Kaplan-Meier curves, medians, quartiles), persistence (proportion of days covered), and switches, acute medications, and other preventatives.

RESULTS: Of 8.8 million persons, 8934 were at least once dispensed a CGRP-mAb (83.5% women, median age 45 years). Median individual follow-up time was 710 days, median duration of treatment with any CGRP-mAb was 297 days, 42.9% had CGRP-mAbs for at least 1 year. Median duration of treatment with the first-ever CGRP-mAb was 327 days; 63.4% experienced a therapy break. Within 1 year after stopping, 53.5% resumed the same CGRP-mAb, 16.9% another CGRP-mAb, 29.6% did not resume any CGRP-mAb; 13.7% started a second CGRP-mAb and 1.7% a third. 22% definitively stopped therapy within their follow-up. Dispensation of triptans decreased during and after therapy with CGRP-mAbs; dispensation of other acute prescription medications was low without change. 11.4% had other preventatives before and 2.4% during CGRP-mAb therapy. The proportion of days covered was 96%.

CONCLUSIONS: In this nationwide study persistence with CGRP-mAbs was excellent; dispensations of triptans and other preventatives decreased during CGRP-mAb therapy. Therapy breaks were common, but the majority resumed CGRP-mAbs, which indicates the need for long-term prophylaxis.

PMID:41342133 | DOI:10.1111/ene.70440

Lung Cancer. 2025 Nov 21;211:108851. doi: 10.1016/j.lungcan.2025.108851. Online ahead of print.

ABSTRACT

BACKGROUND: In an integrated analysis of phase I/II trials (STARTRK-2, STARTRK-1, ALKA-372-001), entrectinib induced responses in global populations with advanced ROS1-fusion positive (ROS1-fp) non-small cell lung cancer (NSCLC). This study reports updated efficacy and safety data in Asian patients from the integrated analysis (cutoff: 16 July 2023).

METHODS: Asian patients with ROS1 tyrosine kinase inhibitor-naïve locally advanced/metastatic ROS1-fp NSCLC, with/without central nervous system (CNS) metastasis were included. The primary endpoints were overall response rate (ORR) and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, IC-DoR, and safety. An exploratory subgroup analysis of patients naïve to systemic therapy in the metastatic setting (1L) was also investigated.

RESULTS: The efficacy-evaluable population included 99 patients. Median (range) age was 53 (20, 86) years; 32.3 % of patients had baseline CNS metastases. Confirmed ORR was 68.7 % (95 % confidence interval [CI] 58.6 %-77.6 %); median DoR was 18.6 months (95 % CI 11.1-38.5). Confirmed IC-ORR was 34.8 % (95 % CI 16.4 %-57.3 %); median IC-DoR was 9.4 months (95 % CI 6.8-not evaluable). Median time to CNS progression was 28.9 months (95 % CI 15.7-41.4). In the 1L population (n = 40), confirmed ORR was 67.5 % (95 % CI 50.9 %-81.4 %); median DoR was 38.5 months (95 % CI 11.1-not evaluable). The most frequent treatment-related adverse events were weight increased (45.9 %), constipation (40.4 %), and dysgeusia (39.4 %).

CONCLUSION: This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

PMID:41337800 | DOI:10.1016/j.lungcan.2025.108851

Hum Immunol. 2025 Dec 2;87(1):111618. doi: 10.1016/j.humimm.2025.111618. Online ahead of print.

ABSTRACT

Autoimmune thyroid disease (AITD) is among the most common autoimmune diseases, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), but their pathophysiological mechanism isn’t fully understood with multiple involved genetic factors. Programmed cell death-1 (PD-1) boosts the suppression of regulatory T cells. The promoter region polymorphism rs36084323 affected PD-1 gene transcription and activation in many cancer and autoimmune diseases. Genetic correlation between this polymorphism and AITD pathogenesis was evaluated in Egyptian patients & included: Group 1; fifty-five GD patients & forty five HT patients, Group 2; one hundred fifty controls by PCR-RFLP technique. GD patients showed significantly higher AG, AA, and A allele frequencies of the PD-1 rs36084323 gene than the control group with no significant disparities between HT patients and controls for any genotype or allele. When analyzing all AITD patients compared to control group, only the A allele showed higher frequency approaching statistical significance (p = 0.057). AA genotype and elevated free T4 were significant risk factors for GD, while elevated TSH was a significant protective factor for GD and a significant risk factor for HT. PD-1 rs36084323 polymorphism differs between GD and HT and is associated with higher risk of GD in Egyptian patients.

PMID:41337788 | DOI:10.1016/j.humimm.2025.111618

Am J Hosp Palliat Care. 2025 Dec 3:10499091251405385. doi: 10.1177/10499091251405385. Online ahead of print.

ABSTRACT

BackgroundPalliative care (PC) has the potential to alleviate symptom burden and enhance quality of life, yet use of PC among American Indians lags significantly behind whites.MethodsThis randomized clinical trial employed a randomized, complete block, posttest-only control group design to evaluate the efficacy of a culture-centric narrative video message to increase knowledge of and communication about PC among AI adults residing in three Great Plains Reservations compared to a general PC message or no message. Measures included participants’ knowledge of and intentions to discuss PC using a posttest survey.ResultsN = 320 individuals completed the survey. Both the culture-centric and general messages demonstrated statistically significant results for increasing participants’ PC knowledge compared to the no message group. The culture-centric message participants had greater odds of feeling the emotions and agreeing with the characters compared to the general message; however, there were no differences noted in intentions to discuss PC.ConclusionsThis study demonstrates the importance of messaging to improve PC knowledge and reduce misperceptions among populations with a history of mistrust of healthcare institutions. Embedding the culture’s values and ways of understanding serious illness care can serve to break down barriers in PC acceptance and provide opportunities for improving quality of life for AIs with serious illness.

PMID:41337781 | DOI:10.1177/10499091251405385

Pain Physician. 2025 Nov;28(6):E657-E665.

ABSTRACT

BACKGROUND: Low dose ketamine infusions (LDKI) may provide adequate adjuvant analgesia while reducing postoperative opioid consumption in specific populations, such as patients with opioid tolerance or high intensity postoperative pain. However, there is currently limited data on the incidence of central nervous system adverse effects such as delirium, hallucinations, agitation, sedation, or nightmares using LDKI in treating postoperative pain.

OBJECTIVES: We aimed to compare the incidence of central nervous system adverse effects in patients receiving an LDKI compared with patients not receiving an LDKI for the first postoperative 48 hours.

STUDY DESIGN: Unicentric prospective cohort comparative study.

SETTING: An academic university hospital.

METHODS: Patients older than 18 who underwent major orthopedic, abdominal, or thoracic surgery were grouped into those who received an LDKI (LDKI group, n = 101), and patients who did not receive ketamine (non-K group, n = 138) based on the responsible anesthesiologist decision. The LDKI group received a 0.1 mg/kg/h ketamine infusion as part of a multimodal analgesic plan. The primary outcome was a composite of postoperative LDKI-related central nervous system adverse effects (delirium, hallucinations, or nightmares) within the first 48 hours after exposure compared with the non-K group. The secondary outcomes were pain intensity and cardiovascular variables (blood pressure and heart rate).

RESULTS: There were no differences in cognitive dysfunction (delirium), agitation or sedation between groups (P > 0.05). The primary composite objective of central nervous system symptoms occurred in 12.9% of the LDKI group compared with 2.2% in the non-K group. The adjusted risk of psychomimetic symptoms using propensity score matching was an odds ratio of 4.84 (95% CI, 1.33 – 17.76) with a P value < 0.016. The cumulative incidence of nightmares (8.9% vs 0.72%, P = 0.001) and hallucinations (6.8% vs 2.2%, P = 0.071) were both higher in the LDKI group.Hemodynamic variables were not statistically different between groups. Pain level was significantly lower in the LDKI group (P = 0.03), however, both groups presented a mean Visual Analog Scale score below 4 mm.

LIMITATIONS: Our study is limited by its observational method, since no intervention was assigned by the investigator.

CONCLUSIONS: An LDKI (0.1 mg/kg/h) for postoperative pain is associated with a low incidence of minor central nervous system effects, i.e., nightmares and hallucinations. There is no significant association with major central nervous system adverse effects, such as delirium, sedation, or agitation, supporting its safety as an adjuvant in multimodal analgesia.

PMID:41337769

Pain Physician. 2025 Nov;28(6):519-526.

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is characterized by the destruction of the articular cartilage and narrowing of the joint space and bone formations around the joint due to mechanical, genetic, and inflammatory causes. The hip joints are some of the most commonly affected in OA. Hip OA is also known as coxarthrosis.

OBJECTIVES: This study aimed to compare the effects of conventional radiofrequency (RF) to those of intraarticular steroid treatment methods on pain, limitations, and quality of life in patients who had advanced OA of the hip and could not undergo surgery for any reason.

STUDY DESIGN: The study was designed as a randomized, prospective single-center study.

SETTING: A total of 40 patients with advanced primary hip OA who met the inclusion criteria were included in the study.

METHODS: Patients were randomized into 2 groups, each of which included 20 individuals. One group received conventional (thermal) radiofrequency ablation (RFA) to the femoral and obturator sensory branches of the hip, while the other group received intraarticular steroid injections in their hips. Scores on the Visual Analog Scale (VAS) and the physical-function component of the Medical Outcomes Study Short Form Health Survey (SF-36) were completed before, one month after, and 3 months after the procedure. The VAS was recorded both at rest and during activity. Each patient’s gender, body mass index (BMI), affected hip side, duration of pain, and previous treatments for the hip were recorded, as were the procedure-related complications each patient experienced.

RESULTS: Forty patients were followed up on for 3 months. The analysis revealed that at both one month and 3 months after treatment, the 2 groups of patients showed a significant improvement in their scores on the resting VAS, activity VAS, and physical-function component of the SF-36 from the pre-procedure values (P < 0.05). As for resting VAS scores in the hip intraarticular steroid injection (HIASI) group and activity VAS scores in the thermal radiofrequency ablation (TRFA) group, there was a statistically significant difference between the groups at one month and 3 months after the procedure, respectively (P < 0.05). This study found a statistically significant correlation between hip stage and age, but no significant correlation was found for gender and weight. No difference between the groups appeared in the complications related to the procedure at the 3-month follow-up.

LIMITATIONS: The follow-up period was relatively short. The sample size was small, and to avoid neuritis, a half dose of triamcinolone acetonide was given to the patients in the TRFA group.

CONCLUSIONS: Conventional RF is more effective at treating the symptoms of advanced coxarthrosis than are intraarticular steroids, based on observations of the activity in the 3-month follow-up of patients with the condition.

PMID:41337764

Pain Physician. 2025 Nov;28(6):511-518.

ABSTRACT

BACKGROUND: Post cardiac surgery pain remains a problem for a significant number of patients. While opioids have long been used for cardiac surgery pain control and hemodynamic stability, methods to improve pain control while also reducing reliance on opioids are desired. Intravenous lidocaine has shown promise for pain and opioid reduction in multiple operative settings, yet its role in cardiac surgery lacks conclusive data.

OBJECTIVE: To determine the effect of intravenous lidocaine on pain scores and opioid consumption in the first 48 hours post cardiac surgery.

STUDY DESIGN: Preplanned substudy of a single-center, double-blind, placebo-controlled, randomized controlled trial.

SETTING: This study was conducted in a tertiary/quaternary care academic hospital in the United States.

METHODS: Following institutional review board approval and informed consent, a total of 449 patients who met the inclusion criteria were enrolled and randomized to receive either a bolus of one mg/kg of lidocaine administered after anesthesia induction followed immediately by a continuous infusion at 48 mu-g/kg/min for the first hour, 24 mu-g/kg/min for the second hour, and 10 mu-g/kg/min for the next 46 hours (lidocaine group) or normal saline (placebo group). Primary outcomes were Visual Analog Scale (VAS) scores and opioid consumption in of morphine milligram equivalents at 24 and 48 hours post surgery. Secondary endpoints included the administration of other nonopiod analgesic medications, postoperative antiemetic medication use, intensive care unit length of stay, hospital length of stay, and time to return of bowel function. Univariable and multivariable regression analyses were performed.

RESULTS: A total of 215 patients who received a placebo and 218 patients who received lidocaine were evaluated. We observed a statistically significant difference in VAS pain score at postoperative 24 hours (adjusted mean difference -0.68; 95%CI, -1.23 to 0.13; P = 0.016) between patients treated with lidocaine vs placebo; however, no difference was observed at postoperative 48 hours. The cumulative opioid use in morphine milligram equivalents was not significant, both in univariable and multivariable analysis, at all timepoints between patients receiving lidocaine vs placebo. Among secondary outcomes, the only significant effect was a decrease in odds of acetaminophen use in the first postoperative 48 hours (adj. odds ratio 0.54; 95% CI 0.32 to 0.90, P = 0.018).

LIMITATIONS: Although pain scores were a preplanned outcome of the parent study, opioid consumption was not. Furthermore, postoperative pain management was not specifically standardized for this study.

CONCLUSIONS: We found that intravenous lidocaine resulted in a statistically significant decrease in VAS pain scores at 24 hours post cardiac surgery, with no difference in opioid consumption. While this pain benefit has been noted in other surgical patient populations, our findings are important since patients undergoing cardiac surgery are unique given the physiologic changes associated with cardiopulmonary bypass graft.

PMID:41337763

Pain Physician. 2025 Nov;28(6):495-510.

ABSTRACT

BACKGROUND: Observational studies have reported relationships among physical activity (PA), leisure sedentary behaviors (LSBs), lifestyle habits, and chronic pain (CP). However, these findings may be unreliable due to confounding biases.

OBJECTIVES: To evaluate the causal effects of PA, LSB, and lifestyle habits on CP.

STUDY DESIGN: This study performed a 2-sample Mendelian randomization to assess the causal effects of the 3 exposures of interest on MCP and evaluated the robustness of the results through a series of sensitivity analyses.

SETTING: The genetic instruments were obtained from UK Biobank, which provides publicly accessible genome-wide association studies (GWAS) summary statistics based on individuals of European ancestry.

METHODS: We used GWAS summary statistics of multisite chronic pain (MCP) in 387,649 individuals from the UK Biobank to identify genetically predicted MCP. Data on PA, LSBs, and lifestyle habits were derived from large GWAS datasets (n > 300,000). Causal effects were assessed by inverse variance weighted (IVW), MR-Egger, weighted median, maximum likelihood, and penalized weighted median. Sensitivity analyses, including MR-PRESSO, Cochran’s Q test, MR-Egger intercept, and leave-one-out analysis, were performed to evaluate the robustness of the MR results.

RESULTS: The results of univariable MR analyses indicated that genetically predicted computer use (OR = 0.905 [0.832, 0.984]) and strenuous sports or other exercises (SSOEs) (OR = 0.490 [0.361, 0.664]) reduced the risk of MCP. Watching television (OR = 1.320 [1.262, 1.380]) and smoking initiation (OR =1.164 [1.122, 1.207]) increased the risk of MCP. Reverse inference results showed that watching television (beta = 0.256 [0.170, 0.341]) and smoking initiation (OR = 1.475 [1.257, 1.732) were risk factors for MCP, while SSOEs (OR = 0.900 [0.871, 0.931) and VPA (OR = 0.945 [0.900, 0.993]) reduced the likelihood of MCP.

LIMITATIONS: This study was unable to use non-overlapping samples to assess the causal association in every 2-sample MR analysis due to the restriction of GWAS datasets, resulting in inevitable bias.

CONCLUSION: This study revealed that television-watching and smoking initiation increased the risk of CP, while computer use and vigorous PA served as protective factors.

PMID:41337762

JMIR Form Res. 2025 Dec 3;9:e80082. doi: 10.2196/80082.

ABSTRACT

BACKGROUND: Video games are becoming increasingly accessible and occupy a prominent position among students’ leisure activities. Recent studies have demonstrated that engagement with video games can facilitate the development of specific abilities, such as visuospatial skills and hand-eye coordination. Thus, it seemed relevant to investigate whether the practice of playing video games could enhance the technical capabilities of novice dental students.

OBJECTIVE: The objective of this study was to ascertain whether dental students who identified themselves as video game players exhibited differences in fundamental technical skills in comparison to students who identified as nonplayers. This preliminary study aimed to validate the methodology and measurement tools for a subsequent prospective study.

METHODS: Second-year dental students who were novices in the field of preclinical dental practice were divided into 2 groups: one designated nonplayers and the other players. The visual, motor, and cognitive coordination of the students was assessed using 3 different tests. The initial assessment focused on evaluating spatial ability, while the subsequent assessments addressed arm-hand coordination and the velocity of execution. The study data were collected in September 2021.

RESULTS: This study included 92 second-year dental students (mean age 19.49, SD 0.8 years). Thirty-seven students were placed in the player group (40%), while 55 were placed in the nonplayer group (60%). The findings showed no statistically significant differences between the two groups when the 3 distinct tests were administered. The nonplayer group made fewer mistakes on the test evaluating spatial ability (P=.051) and achieved a higher score on the modified Precision Manual Dexterity Test, which evaluates arm-hand coordination, compared to the player group (P=.17), but without statistical significance. The nonplayer group took more time to perform the pulpotomy during the third test, which evaluated execution speed, compared to the player group, again without significance (P=.87).

CONCLUSIONS: This study did not demonstrate significant differences between player and nonplayer dental students who participated in the study with regard to their fundamental technical abilities in a preclinical training environment. Nevertheless, it validated the feasibility of a methodology for a future longitudinal study to concentrate on the evolution of acquiring technical skills during preclinical training in these two populations. Consequently, further investigation is warranted to determine the potential impact of video games on the acquisition of surgical skills, including in dentistry.

PMID:41337749 | DOI:10.2196/80082