Nevin Manimala

Pharmaceut Med. 2025 Sep 22. doi: 10.1007/s40290-025-00586-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Regulatory agencies and policy makers increasingly recognize real-world evidence (RWE) as a valuable complement to randomized controlled trials (RCTs) in oncology, yet data on how US physicians who treat cancer use and perceive RWE remain limited. The study aimed to assess attitudes toward RWE among US physicians who treat cancer, including their confidence in interpreting it and reliance across clinical decision contexts.

METHODS: A cross-sectional national survey was administered in November 2024 to licensed US physicians who treat cancer, recruited from the American Society of Clinical Oncology (ASCO) member directory, using a random sample stratified by state population. Inclusion criteria were active US medical licensure and current involvement in oncology patient care. The survey instrument included sections on demographics and practice characteristics; RWE familiarity and usage frequency; comparative reliance on RWE versus RCTs in treatment selection, dosing, and outcome prediction (scales ranging from 0 to 10: 0 = complete reliance on RCT data, 10 = complete reliance on RWE); perceived barriers to adoption (4-point scale); and potential facilitators (4-point scale). Categorical data were summarized as counts and percentages, and continuous variables were summarized as means and standard deviations (SD). Chi-squared tests were used to compare categorical variables across groups, paired t tests were used to assess differences in mean reliance scores, and Spearman’s rho was used to evaluate correlations. Statistical significance was set at p < 0.05.

RESULTS: In total, 128 completed surveys were received. Overall, 94% of respondents (n = 120) were at least “somewhat familiar” with RWE, 14% (n = 18) used it “often,” and 3% (n = 4) reported daily use. 49% (n = 63) felt confident interpreting RWE studies, with late-career physicians (> 20 years of experience) less confident than their early and mid-career peers. Reliance on RWE was lower for treatment selection (mean 3.0, SD 1.7) than for dosing (mean 3.7, SD 2.0) or outcome prediction (mean 3.8, SD 2.0) (p < 0.001). Top barriers included reconciling conflicting RWE versus RCT data, data completeness, and bias. Key facilitators included improved analytical standards, guideline integration, and additional training.

CONCLUSIONS: While awareness of RWE is high among US physicians who treat cancer, they apply it selectively on the basis of clinical context, showing notably lower reliance for treatment selection. Addressing concerns about methodological rigor, data quality, and interpretive skills may strengthen RWE’s integration into oncology care.

PMID:40982185 | DOI:10.1007/s40290-025-00586-7

Acta Anaesthesiol Scand. 2025 Oct;69(9):e70124. doi: 10.1111/aas.70124.

ABSTRACT

BACKGROUND: Antibiotics are widely used in intensive care units (ICUs), yet detailed nationwide data on ICU-specific consumption are limited. In 2012, the Danish Health Authority introduced a policy framework to promote prudent antibiotic use. We evaluated national trends in antibiotic consumption across Danish ICUs from 2013 to 2023 considering this initiative.

METHODS: We conducted a nationwide observational study including all adult ICUs across 29 public hospitals in Denmark. All ICU admissions from January 1, 2013, to December 31, 2023, were included, covering 1,121,639 ICU patient days. Antibiotic consumption was assessed using defined daily doses (DDD) derived from national sales data. No interventions were implemented.

RESULTS: During the study period, a total of 1,624,281 DDD of intravenous antibiotics were administered. Overall antibiotic consumption declined from 1705 to 1348 DDD per 1000 patient days, representing a 21% relative reduction. Marked decreases were observed for fluoroquinolones (-80%), first- and second-generation cephalosporins (-61%), and carbapenems (-34%). Conversely, consumption of penicillins with beta-lactamase inhibitors increased by 139%. Run chart analyses indicated these trends were non-random. Importantly, no deterioration in clinical outcomes was observed. Antibiotic consumption varied widely across ICUs and regions. According to both WHO’s AWaRe framework and a modified national classification, ‘Watch’ antibiotics accounted for the largest share of consumption.

CONCLUSION: In this nationwide study of Danish ICUs, antibiotic consumption decreased substantially over an 11-year period-driven by reductions in broad-spectrum classes-without evidence of worsening clinical outcomes. These data document a sustained decline in broad-spectrum antibiotic use in Danish intensive-care practice and may provide a benchmark for other high-income healthcare systems.

EDITORIAL COMMENT: This inventory of antibiotics consumption in Danish intensive care units demonstrates a recent reduction in broad-spectrum antibiotic ordering which differs from the well-known increase of antibiotics used in health care in general.

PMID:40982183 | DOI:10.1111/aas.70124

Acta Neurol Belg. 2025 Sep 22. doi: 10.1007/s13760-025-02892-y. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic Intracranial Hypertension (IIH) has been associated with comorbid sleep disorders. Although emerging evidence suggests a link between IIH and sleep disorders, yet this association remains underexplored. This case -control study aims to evaluate the prevalence of sleep-related abnormalities in patients with IIH using validated screening and severity assessment tools.

METHODS: 120 newly diagnosed, drug naive IIH patients and 40 age and gender matched controls were enrolled. Baseline characteristics and clinical parameters were evaluated. Headache severity was assessed using MIDAS and HIT6 questionnaires. Sleep disturbances were assessed using the Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), restless leg syndrome (RLS) scale, Berlin Questionnaire, and STOP-BANG questionnaire. Statistical analysis was conducted using SPSS v27.

RESULTS: The mean age of patients was 34.92 (9.42) years. IIH cases were predominately female (85%). Cases had significantly higher BMI (85% were overweight and obese). Poor sleep quality (PSQI ≥ 5) was significantly more common in IIH patients (46.67%) than controls (15%) (p < 0.001). High OSA risk was also more prevalent in IIH patients based on Berlin and STOP-BANG scores (p = 0.013 and p = 0.044 respectively). Although rates of Daytime sleepiness, RLS and Insomnia were higher in the IIH group, these differences were not statistically significant.

CONCLUSION: Patients with IIH exhibit significantly higher rates of sleep disturbances, particularly poor sleep quality, and increased risk of OSA based on screening tools, which were also associated with higher BMI and psychiatric comorbidities. These findings underscore the importance of routine sleep screening in IIH patients.

PMID:40982163 | DOI:10.1007/s13760-025-02892-y

Mol Biol Rep. 2025 Sep 22;52(1):941. doi: 10.1007/s11033-025-11059-0.

ABSTRACT

BACKGROUND: Mutations in NKG2D gene increase the risk of cancer, including chronic myeloid leukemia (CML). The Mutational landscape of exon 8 of NKG2D gene remains poorly characterized, especially in CML.

PURPOSE: Exploring the mutations in exon 8 of NKG2D gene of CML patients, examine its interactions with other genes, and evaluate associated biochemical, hematological and clinical-pathological parameters.

METHODOLOGY: Blood samples from CML patients and healthy controls were collected for molecular, biochemical and hematological assessments. Mutations in exon 8 of NKG2D gene were detected using Sanger sequencing. NKG2D gene interactions were predicted via GeneMANIA database.

RESULTS: in exon 8 of the NKG2D gene, mutations (substitution and deletion) were detected in 88% of CML patients, with 50% carrying multiple variants. Nine single nucleotide polymorphisms (SNPs) were identified, including eight substitutions and one deletion. The most frequent substitution was G > GC and six variants were novel. Homozygous 414G > C had the highest mutation score. GeneMANIA analysis revealed strong interactions between NKG2D and 20 other genes, notably HCST gene, with co-expression and pathway interactions involving thirteen and eleven genes, respectively. LDH levels were significantly higher in patients, while uric acid levels showed no significant difference. CML patients also had higher MID% and lower RBC count, hemoglobin and hematocrit levels. In addition, there were no statistically significant correlations between mutation burden and biochemical/hematological parameters.

CONCLUSION: NKG2D exon 8 mutations are highly prevalent among CML patients, with multiple or novel variants identified. A strong interaction profile of NKG2D with immune-related genes, indicating possible roles in leukemogenesis.

PMID:40982140 | DOI:10.1007/s11033-025-11059-0

Rheumatol Int. 2025 Sep 22;45(10):231. doi: 10.1007/s00296-025-05983-4.

ABSTRACT

Takayasu arteritis is a rare inflammatory disease that primarily affects medium- and large-sized arteries, particularly the aorta and its branches. The Hata classification defines six angiographic types based on the involved aortic segments. Clinical symptoms May vary depending on the distribution of arterial involvement. This systematic review and meta-analysis aimed to estimate the pooled prevalence of each angiographic type and evaluate their associations with clinical Manifestations.A systematic search of electronic databases was conducted to identify studies reporting angiographic classifications and clinical symptoms in patients with Takayasu arteritis. Pooled prevalence estimates were calculated using R software, including subgroup analyses by geographic area and imaging modality. Meta-regression was used to assess associations between angiographic types and specific clinical features.Type V was the most common angiographic subtype, with a pooled prevalence of 43.49%, while type III was the least common, 5.32%. Subgroup analyses showed statistically significant differences only for type IIb, based on modality types. Meta-regression revealed significant correlations between angiographic types and clinical symptoms, with Type V exhibiting the greatest severity, and types IIb and III the lowest.This meta-analysis highlights the varying distribution of angiographic types of Takayasu arteritis and their significant associations with clinical symptoms, which may guide prognostic and management strategies.

PMID:40982119 | DOI:10.1007/s00296-025-05983-4

Eur J Trauma Emerg Surg. 2025 Sep 22;51(1):294. doi: 10.1007/s00068-025-02967-8.

ABSTRACT

PURPOSE: The aim of the study is to introduce our experiences and surgical tips of free vascularized fibular grafting (FVFG) for the treatment of osteonecrosis of the femoral head (ONFH), and explore the clinical effect of the procedure.

METHODS: Between March 2016 and September 2022, the clinical data of 23 patients (26 hips) with ONFH were respectively analyzed. The involved hips were classified as stages III (23.1%), IIIA (57.7%), and IIIB (19.2%) according to the Association Research Circulation Osseous (ARCO) classification. The mean preoperative Harris Hip Score (HHS) was 60.9 ± 9.0. All patients were implemented the FVFG. The fibular bone flap was harvested 10 cm distal to the tip of the fibular head. Regular postoperative follow-up was performed to assess the union of the fibula flap and development of ONFH, and to examine the hip function. Statistically differences were analyzed between the preoperative and postoperative HSS (P < 0.05).

RESULTS: All patients were followed up for 13 to 93 months, and the HHS was 90. 9 ± 4. 5 at the last follow-up, indicating a statistically significant improvement compared to that preoperatively (P < 0.001). Postoperative X-rays, CT and MRI revealed no displacement of the fibular bone flap, and all the bone flap healed well without evidence of ONFH progression.

CONCLUSIONS: The treatment of ONFH with FVFG can significantly improve the hip joint function of patients. Incorporating these surgical tips and our experiences may contribute to improved procedural accuracy, enhanced effectiveness, potential cost-efficiency, and broader applicability for dissemination.

PMID:40982114 | DOI:10.1007/s00068-025-02967-8

Pediatr Surg Int. 2025 Sep 22;41(1):302. doi: 10.1007/s00383-025-06195-4.

ABSTRACT

PURPOSE: Pectus excavatum (PE) is the most common congenital chest wall deformity. While often perceived as a cosmetic issue, PE can impair cardiopulmonary function. Surgical correction has evolved from the Ravitch procedure to the minimally invasive Nuss technique, which offers reduced surgical risks and improved postoperative outcomes. However, diagnostic and therapeutic variability persists, highlighting the need for expert consensus.

METHODS: A 31-question web-based survey was distributed to CWIG members and PE specialists between November 2024 and January 2025. The survey explored five key domains: demographics, preoperative evaluation, surgical indications and timing, operative technique, and postoperative management. Responses from 100 international surgeons were analyzed.

RESULTS: The most common indications for surgery were severe deformity (88.9%), Haller index > 3.25 (78.8%), psychosocial distress (77.8%), and symptoms (77.8%). Technique selection was influenced by prior surgery (48%) and surgeon experience (45.9%). For complex cases, 90.8% preferred the double-bar technique. Most surgeons removed the bar within 2-3 years (86.6%). Postoperative pain was primarily managed with oral analgesics (64.6%) and IV pumps (47.5%). Early complications included pneumothorax (68.1%) and infections (62.8%); bar displacement (78%) was the most frequent late complication.

CONCLUSION: Despite widespread adoption of the Nuss procedure, significant variation remains in PE management. These findings emphasize the need for standardized, evidence-based guidelines to optimize patient outcomes.

PMID:40982104 | DOI:10.1007/s00383-025-06195-4

Ir J Med Sci. 2025 Sep 22. doi: 10.1007/s11845-025-04090-4. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to determine the prevalence of sarcopenia in postmenopausal women under the age of 60 and to evaluate the relationship between sarcopenia, bone mineral density (BMD), and clinical parameters.

MATERIALS AND METHODS: This cross-sectional study included 52 postmenopausal women under the age of 60, classified as osteoporotic or non-osteoporotic based on DXA results. Sarcopenia was assessed using the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Muscle strength was measured using handgrip strength and the five-time sit-to-stand test (5STS), and muscle mass was assessed with the Tanita BC-418MA device. Skeletal muscle mass indices (SMMI) were calculated based on height², weight, and BMI.

RESULTS: Fat-free mass (FFM), skeletal muscle mass (SMM), and SMM/height² values were significantly lower in the osteoporotic group compared to the non-osteoporotic group (p < 0.05). No significant differences were found between the groups in handgrip strength or 5STS results. Sarcopenia prevalence varied depending on the muscle index used: 17.3% based on SMM/BMI (23.1% in the osteoporotic group, 11.5% in the non-osteoporotic group), 11.5% based on SMM/weight (3.8% vs. 19.2%), and 3.8% based on SMM/height² (equal in both groups). These differences were not statistically significant (p > 0.05). Femoral neck and lumbar BMD and T-scores showed positive correlations with FFM and SMM, but not with muscle strength tests.

CONCLUSION: In our study, sarcopenia prevalence did not significantly differ between osteoporotic and non-osteoporotic postmenopausal women under 60. However, the lower muscle mass observed in the osteoporotic group may indicate early structural changes associated with sarcopenia. The lack of difference in functional capacity suggests that these changes may not yet be clinically apparent.

PMID:40982103 | DOI:10.1007/s11845-025-04090-4

Spine Deform. 2025 Sep 22. doi: 10.1007/s43390-025-01188-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether using stable vertebra on push-prone traction radiographs for selecting the lowest instrumented vertebra (LIV) in adolescent idiopathic scoliosis (AIS) patients with Lenke types 3C and 6C undergoing posterior spinal surgery can preserve more lumbar motion segments while still achieving satisfactory surgical outcomes.

BACKGROUND: AIS patients requiring surgical treatment typically present with progressive curves exceeding 40° and are skeletally immature. This study specifically focuses on AIS patients exhibiting Lenke curve types 3C and 6C, which include structural thoracic as well as thoracolumbar and lumbar curves. The selection of the LIV remains a contentious issue due to concerns about distal adding-on and the potential for spinal imbalance postoperatively. Existing literature suggests that longer fusion constructs and positioning the LIV below L3 can lead to significant functional limitations and accelerated disc degeneration. While Lenke advocated for identifying the stable vertebra (SV) as the LIV, our recent study indicates that push-prone traction radiographs provide superior predictability for correcting postoperative spinal alignment. This study aims to evaluate the effectiveness of using the stable vertebra identified through push-prone traction radiographs as the LIV in preserving segmental motion during posterior spinal surgery for managing Lenke type 3C and 6C curves.

METHODS: AIS patients with Lenke type 3C and 6C who underwent posterior spinal surgery between 2021 and 2024 were enrolled in the study. Preoperative 36-inch whole spine radiographs, including push-prone traction view, were obtained for curve flexibility assessment. The lowest instrumented vertebra (LIV) was determined by identifying the stable vertebra (SV) on push-prone traction radiographs. Demographic data, including sex, age, BMI, Lenke’s curve type, and pre- and postoperative major coronal Cobb angle, thoracic kyphosis, lumbar lordosis, and C7 to central sacral vertical line (C7-CSVL), were collected. Statistical analysis was conducted to assess the differences in curve magnitudes between pre- and postoperative measurements.

RESULTS: Thirty-six AIS patients (33 female and 3 male) with a mean age of 13.9 ± 2.2 years were included in this study, with a mean follow-up period of 28.4 months. Preoperatively, the cohort presented with Lenke type 3C (24 out of 36) and Lenke type 6C (12 out of 36). The preoperative thoracic curve was corrected to an average of 5.7°, demonstrating an average correction rate of 89%. Similarly, the preoperative lumbar curve was corrected to an average of 5° with a correction rate of 90%.

CONCLUSION: Push-prone traction radiographs may serve as an alternative method for determining the optimal LIV level in patients with Lenke type 3C and 6C. Identifying stable vertebra on push-prone traction radiographs as LIV can potentially preserve more lumbar motion segments while achieving favorable surgical outcomes.

PMID:40982098 | DOI:10.1007/s43390-025-01188-8

Ann Bot. 2025 Sep 22:mcaf231. doi: 10.1093/aob/mcaf231. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Antibiotics are natural compounds produced by microorganisms that have long existed in ecosystems. However, the widespread clinical and agricultural use of antibiotics has intensified selective pressures on bacteria, leading to the proliferation of antibiotic resistance genes (ARGs). The increasing prevalence of these genetic elements in clinical and environmental settings now poses a major global health threat. While ARGs are well documented in anthropogenically influenced environments, their distribution and origins in remote ecosystems, such as the boreal forests, remain poorly understood. Here, we investigate the occurrence, diversity, and potential origins of ARGs in the boreal lichen Cladonia stellaris.

METHODS: We conducted the first targeted assessment of ARGs in lichens by analyzing 42 C. stellaris samples from northern and southern lichen woodlands (LWs) in eastern Canada. Using high-throughput quantitative PCR, we screened for 33 ARGs and three mobile genetic elements (MGEs), quantifying their relative abundance. Bacterial community composition was characterized via 16S rRNA gene sequencing. Statistical analyses evaluated geographical patterns, co-occurrence between ARGs and bacterial taxa, and the influence of latitude on ARG distribution.

KEY RESULTS: Ten ARGs conferring resistance to four antibiotic classes (aminoglycosides, beta-lactams, quinolones and sulfonamides), along with one MGE, were detected. The ARGs blaCTX-M-1, qnrB, and qepA were highly prevalent, with qepA often surpassing 16S rRNA gene abundance. Only qnrB showed significantly higher abundance in southern samples. Latitude significantly influenced ARG profiles, whereas bacterial community composition did not.

CONCLUSIONS: Our findings demonstrate that C. stellaris harbors diverse ARGs in remote boreal ecosystems with limited anthropogenic influence. Proposed explanations for ARG presence include long-distance dispersal via bioaerosols and endogenous development within lichen microbiomes, yet these remain speculative. Future work incorporating bacterial isolation, whole-genome sequencing, metatranscriptomics, air sampling, and metabolomic profiling is necessary to unravel the ecology and evolution of ARGs in natural habitats.

PMID:40977499 | DOI:10.1093/aob/mcaf231