Nevin Manimala

RMD Open. 2025 Aug 14;11(3):e005785. doi: 10.1136/rmdopen-2025-005785.

ABSTRACT

OBJECTIVE: To investigate the prevalence of difficult-to-treat psoriatic arthritis (D2T-PsA) and classify patients with persistent inflammatory PsA (PIPsA) and non-inflammatory PsA (NIPsA) based on a combination of clinical and musculoskeletal ultrasound (MSUS) evidence of inflammation.

METHODS: A multicentre cross-sectional study was conducted on PsA patients treated with biological disease-modifying anti-rheumatic drugs/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). D2T-PsA status was characterised by an inadequate response to ≥2 classes of b/tsDMARDs and the persistence of active disease, defined as a DAPSA >14.

RESULTS: Out of 517 PsA patients on b/tsDMARDs, 53 (10.3%) met the criteria for D2T-PsA with 30 (57%) classified as PIPsA and 23 (43%) classified as NIPsA. The PIPsA phenotype had higher swollen joint count (2.5 (IQR 1.0-7.0) vs 0.0 (IQR 0.0-1.0), p<0.001), dactylitis (20% vs 0%, p=0.030) and nail psoriasis (40% vs 13%, p=0.027). Conversely, NIPsA patients had significantly greater ΔPtGA-PhGA (4.0 (IQR 2.5-5.0) vs 0.0 (IQR 0.0-1.5), p<0.001), higher tender points (16.0 (IQR 0.0-18.0) vs 0.0 (IQR 0.0-8.0), p=0.009), a higher SPARCC enthesitis index (5.0 (IQR 2.0-8.0) vs 2.0 (IQR 0.0-5.0), p=0.023). The MSUS showed higher ultrasound activity (3.81±2.0 vs 0.91±0.5, p<0.001) and greater structural damage (4.12±1.0 vs 2.38±2.1, p<0.001), with both activity and damage scores being higher in PIPsA patients.

CONCLUSION: The classification into PIPsA and NIPsA based on easily detectable clinical features can support a tailored therapeutic management of patients with D2T-PsA.

PMID:40813109 | DOI:10.1136/rmdopen-2025-005785

RMD Open. 2025 Aug 14;11(3):e005557. doi: 10.1136/rmdopen-2025-005557.

ABSTRACT

BACKGROUND: Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).

METHODS: This was a phase II, randomised, double-blind, placebo-controlled, multicentre study including patients with a diagnosis of systemic lupus erythematosus with active LN. Patients were randomly assigned (2:1) to receive either intravenous iscalimab (10 mg/kg) or placebo for 24 weeks on top of SoC for LN. The primary efficacy endpoint was the ratio from baseline in urinary protein-to-creatinine ratio (UPCR) at week 24. Safety assessments included adverse events (AEs) and serious AEs (SAEs) during treatment and follow-up up to 49 weeks.

FINDINGS: Of the 57 patients (iscalimab, n=39; placebo, n=18) randomised, 31 (54.4%) completed the study. The primary efficacy endpoint was met: at week 24, the relative improvement from baseline in proteinuria (UPCR) was 63.1% and 36.3% in the iscalimab and placebo arms, respectively. UPCR to baseline at week 24 showed a statistically significant reduction of 42.1% in the iscalimab versus placebo arm. Most AEs were of mild to moderate severity in both treatment arms. Overall, seven SAEs were reported in six patients (15.4%) in the iscalimab arm versus four in three patients (16.7%) in the placebo arm.

INTERPRETATION: Iscalimab showed a significant improvement in proteinuria (UPCR) in patients with active LN. Iscalimab was generally well tolerated with the exception of a few severe infections and one case of macrophage-activation syndrome in immunosuppressed and comorbid patients.

TRIAL REGISTRATION NUMBER: NCT03610516.

PMID:40813108 | DOI:10.1136/rmdopen-2025-005557

Stat Med. 2025 Aug;44(18-19):e70222. doi: 10.1002/sim.70222.

ABSTRACT

Advancements in wearable device technology have enabled accelerometers to continuously record minute-by-minute physical activity over consecutive days, yielding curves serially correlated in dense and regular longitudinal design. Motivated by a large-scale cohort of physical activity data throughout a week, the collected repeatedly measured functional data exhibits longitudinal (interday) and functional (intraday) interactions on fine grids. To accommodate this complex data structure and investigate the relationship between health assessment results and weekly physical activity patterns, we propose an innovative and efficient two-dimensional functional mixed-effect model (2dFMM), characterizing the longitudinal and functional cross-variability while incorporating two-dimensional fixed effects and four-dimensional correlation structure in marginal representation. We develop a fast three-stage estimation procedure to provide accurate fixed-effect inference for model interpretability and improve computational efficiency when encountering large datasets. We find strong evidence of intraday and interday varying significant associations between physical activity and mental health assessments among our cohort population, which sheds light on possible intervention strategies targeting daily physical activity patterns to improve school adolescent mental health. Our method is also used in environmental data to illustrate the wide applicability.

PMID:40813095 | DOI:10.1002/sim.70222

Huan Jing Ke Xue. 2025 Aug 8;46(8):5059-5069. doi: 10.13227/j.hjkx.202407169.

ABSTRACT

The heavy metal pollution in the sediments of tributaries directly affects the water quality of the Yangtze River. To investigate the distribution characteristics and pollution sources of heavy metals in the sediments of the incoming rivers in typical cities of the lower Yangtze River, the Nanjing section of the Yangtze River was selected as the study area. Sediment samples were collected from 16 monitoring points, and the monitoring data for As, Hg, Cr, Pb, Cd, Cu, and Zn were statistically analyzed. The potential ecological risk index method and the geo-accumulation index method were used to comprehensively evaluate the heavy metals in the sediments of the incoming rivers. Pearson correlation analysis and positive matrix factorization （PMF） were employed to analyze the sources of heavy metals in the sediments. The results indicated that the average values of seven heavy metals in the sediments of the incoming rivers were generally higher than those in the Yangtze River sediments, with all heavy metal coefficients of variation in the incoming river sediments exceeding 40%, indicating strong spatial heterogeneity. The primary heavy metal in the incoming river sediments in the Nanjing section of the Yangtze River was Cd, and the accumulation level and potential ecological risk of heavy metals in the Shitou River sediments were significantly higher than those in other incoming rivers. From upstream to downstream in the Nanjing section of the Yangtze River, the potential ecological risk index gradually increased, showing a spatial distribution characteristic of “lower upstream, higher downstream.” When P &lt; 0.01, Pearson correlation analysis indicated significant positive correlations among multiple heavy metals, suggesting that they may share common pollution sources. The results of the positive matrix factorization method （PMF） indicated that the main pollution sources of the incoming rivers included industrial pollution （26%）, agricultural pollution （29.7%）, and transportation （29.5%）, with the remaining 14.8% attributed to natural sources.

PMID:40813024 | DOI:10.13227/j.hjkx.202407169

Lancet Psychiatry. 2025 Sep;12(9):660-672. doi: 10.1016/S2215-0366(25)00217-2.

ABSTRACT

BACKGROUND: Family dynamics are implicated in self-harm and suicidality among children and adolescents. However, whether negative family dynamics confer a prospective risk and positive family dynamics confer a protective effect is not understood. To address this research gap, we aimed to summarise the prospective, longitudinal evidence examining the relationship between family dynamics, self-harm, and suicidality (ie, suicidal thoughts and behaviours) during childhood and adolescence.

METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO, and ERIC, as well as CINAHL, without language restrictions, from the date of database inception to May 20, 2025. Observational studies were eligible if they prospectively followed up a cohort of children and adolescents (age <20 years) from a general population, community, or school showing either no elevated risk or typical development of self-harm and suicidality for a minimum of 12 months. Eligible studies had to have included prospectively measured family dynamics, including positive (eg, emotionally supportive) and negative (eg, harsh, aversive, or punitive) parenting behaviours and family functioning (eg, family cohesion) or dysfunction (eg, discord or conflict) in childhood or adolescence. Extracted data consisted of study-level information and characteristics, participant characteristics, descriptions of study measures, and study results. Extracted data were entered into Covidence for consensus. The primary outcomes were self-harm (ie, thoughts of non-suicidal self-harm or self-injury, and non-suicidal self-harm or self-injury) and suicidality (ie, suicidal ideation and suicide attempt) over any reporting period. We examined individual and combined outcomes using a random-effects model. We assessed study quality using a modified Newcastle-Ottawa scale. This study is registered with PROSPERO (CRD42023434804).

FINDINGS: We screened 3860 articles and retained 38 studies, of which all 38 contributed to the narrative synthesis and 24 to the quantitative analyses. Altogether, the studies comprised 101 879 children and adolescents. Most study samples were from the USA (12 [32%]) or China (11 [29%]), with exposure and outcome ascertainment 12 months apart (25 [66%] studies) from age 10 years to 19 years (36 [95%]). Data stratified by sex, gender, race, or ethnicity were not consistently available. Female participants constituted a larger proportion of the samples than did male participants (ranges 42-100% vs 28-58%). Exposure to negative parenting was associated with an increased likelihood of combined self-harm and suicidal ideation (OR 1·29 [95% CI 1·15-1·46]) and non-suicidal self-harm or self-injury (1·46 [1·25-1·71]), but not suicidal ideation (1·07 [0·92-1·24]). Negative parenting practices and continuously measured self-harm and suicidality were not significantly associated. Positive parenting practices were not associated with suicidal ideation or with combined self-harm and suicidal ideation. Family dysfunction was longitudinally associated with an increased combined likelihood of self-harm and suicidality (OR 1·29 [95% CI 1·13-1·48]) and non-specific self-harm (1·70 [1·10-2·63]), but not suicide attempt (1·24 [0·93-1·66]). The overall rating of study quality was moderate (mean 6·5 of 10·0 stars [SD 1·29]).

INTERPRETATION: Negative parenting practices and family dysfunction seem to precede self-harm and suicidality among children and adolescents. Reducing negative family dynamics could alleviate these severe mental health concerns in the short term and assisting families to minimise early-life exposure to these dynamics could prevent the onset of self-harm and suicidality.

FUNDING: Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award Program and Canada Research Chairs Program.

PMID:40812960 | DOI:10.1016/S2215-0366(25)00217-2

J Tradit Chin Med. 2025 Aug;45(4):909-921. doi: 10.19852/j.cnki.jtcm.2025.04.021.

ABSTRACT

OBJECTIVE: To utilize the Traditional Chinese Medicine constitution (TCMC) as a complementary and alternative approach for early disease detection and treatment, with a focus on Yin and Yang deficiency constitutions, which serve as key references for disease prevention and management.

METHODS: The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database. This database was used for differential expression genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA), and the characteristic genes were then obtained in the dataset using a machine learning method. The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods, and the hub genes were enriched and analyzed. Subsequently, the hub genes of Yin and Yang deficiency constitution were validated using external datasets. Receiver operating characteristic (ROC) analysis was used on each hub genes of the two groups to further understand their diagnostic performance. The miRNA-lncRNA-gene network was used to further analyze the hub genes. Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.

RESULTS: The GSE87474 dataset was used for DEGs analysis and WGCNA. Using machine learning analyses, we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions, respectively. The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway, whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis-keratan sulfate. The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1 (SAMTOR, also named C7orf60), cofilin 2 (CFL2), cytohesin 1 interacting protein (CYTIP), G protein-coupled receptor 183 (GPR183), hippocampus abundant transcript 1 (HIAT1), kelch like family member 15 (KLHL15), mitogen-activated protein kinase 6 (MAPK6), and prostaglandin-endoperoxide synthase 2 (PTGS2) in Yin deficiency and fucosy-ltransferase 8 (FUT8), TATA-box binding protein associated factor, RNA polymerase I subunit D (TAF1D), zinc finger protein 24 (ZNF24), MAPK6, and leptin receptor overlapping transcript like 1 (LEPROTL1) in Yang deficiency. The ROC results indicated that these genes have diagnostic value. MAPK6 is a shared hub gene for Yin and Yang deficiencies.

CONCLUSIONS: This study identified C7orf60, CFL2, CYTIP, GPR183, HIAT1, KLHL15, MAPK6, and PTGS2 in Yin deficiency and FUT8, TAF1D, ZNF24, MAPK6, and LEPROTL1 in Yang deficiency as potential biomarkers, providing insights into their pathogenesis. This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.

PMID:40810238 | DOI:10.19852/j.cnki.jtcm.2025.04.021

J Tradit Chin Med. 2025 Aug;45(4):836-844. doi: 10.19852/j.cnki.jtcm.2025.04.012.

ABSTRACT

OBJECTIVE: To evaluate the effect of Yiqi Liangxue Shengji prescription (, YQLXSJ) on cardiac function and outcomes in acute myocardial infarction (AMI) patients with myocardial ischemia-reperfusion injury (MIRI) and to determine its clinical efficacy.

METHODS: This prospective, randomized, double-blind, placebo-controlled trial enrolled hospitalized patients with AMI who underwent percutaneous coronary intervention and experienced MIRI either intraoperatively or postoperatively. Participants were randomly allocated to the treatment group, which received YQLXSJ, or the control group, which received a placebo, concurrent with standard Western Medicine therapy. The intervention period lasted 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF), determined by echocardiography. Secondary outcomes included N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) levels, left ventricular internal diameter, major adverse cardiovascular events (MACE), angina pectoris scores, and Chinese medicine evidence scores.

RESULTS: Following 8 weeks of intervention, the treatment group demonstrated a significant increase in LVEF and a marked reduction in NT-proBNP when compared to the control group. There was also a significant decrease in peak cTnI levels, Chinese medicine evidence scores, and angina pectoris scores. The control group’s left ventricular end-systolic diameter (LVESD) significantly increased compared to baseline after 8 weeks (P < 0.05), whereas the treatment group’s LVESD showed no significant change from baseline (P > 0.05). Although the treatment group showed a downward trend in MACE incidence compared to the control group, this difference was not statistically significant (P > 0.05).

CONCLUSIONS: This study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

PMID:40810229 | DOI:10.19852/j.cnki.jtcm.2025.04.012

Head Neck. 2025 Aug 14. doi: 10.1002/hed.70016. Online ahead of print.

ABSTRACT

BACKGROUND: Disparities in access to otolaryngology and cancer care exist across the United States. However, little is known about the geographic distribution of fellowship-trained head and neck cancer (HNC) surgeons.

METHODS: A cross-sectional study of American Head and Neck Society (AHNS) fellowship graduates from July 1, 1997 to June 30, 2022 was conducted. Geospatial and statistical analysis was conducted to assess current practice location and correlations with training regions.

RESULTS: Among 688 graduates, 622 practice in the US or Canada. Most graduates remained in the region of their training. Geospatial analysis showed concentration of graduates in urban areas, with 152 of 3142 US counties having higher-than-expected density. Underserved regions were identified in the southeastern US, southern border, and western states.

CONCLUSIONS: Head and neck surgical fellowship graduates predominantly practice in large urban areas, leaving rural and underserved regions with limited access to complex HNC care. Strategic interventions are needed to address these gaps.

PMID:40810214 | DOI:10.1002/hed.70016

J Patient Saf. 2025 Aug 14. doi: 10.1097/PTS.0000000000001406. Online ahead of print.

ABSTRACT

BACKGROUND: Medication-related inappropriateness (MRI) poses a significant risk to elderly patients, particularly in aged care settings, where complex medication regimens and health care challenges increase the likelihood of errors. Addressing MRI is critical to enhancing patient safety and improving health outcomes for older adults. This study aims to evaluate the effectiveness of interventions designed to reduce MRI and improve prescribing practices in elderly populations through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis were conducted following the Cochrane Handbook for Systematic Reviews of Interventions. Databases including MEDLINE, EMBASE, CINAHL, PubMed, and EBSCOhost were searched from April 2020 to November 2023. Randomized controlled trials (RCTs) and nonrandomized controlled studies evaluating interventions for reducing MRI in elderly patients receiving care in various healthcare settings were included. Eight studies involving a total of 33,170 participants across 7 countries qualified for analysis. The pooled odds ratio (OR) with a 95% CI was calculated to measure intervention effectiveness. Statistical heterogeneity was assessed using the Higgins I² statistic, and a random-effects model was applied to account for variability.

RESULTS: Interventions ranged from educational programs and peer reviews to computerised decision-support systems. The meta-analysis demonstrated a significant reduction in MRI, with a pooled OR of 0.43 (95% CI: 0.31-0.60), indicating a 57% reduction in inappropriate prescribing. Educational interventions were particularly effective, fostering improved prescriber behavior and medication safety. However, high heterogeneity (I²=92%) underscored variations in patient demographics, care settings, and intervention designs.

CONCLUSIONS: Educational interventions and decision-support systems are found to significantly reduce the inappropriate prescribing of medication in older patients. More research is required to address variability, determine long-term outcomes, and facilitate broader implementation to improve medication safety.

PMID:40810201 | DOI:10.1097/PTS.0000000000001406

Infect Drug Resist. 2025 Aug 9;18:3977-3991. doi: 10.2147/IDR.S542467. eCollection 2025.

ABSTRACT

PURPOSE: The emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB) has led to a critical challenge in antimicrobial therapy. This study aimed to assess the efficacy of colistin (COL) combined with ceftazidime/avibactam (CAZ/AVI) in the treatment of CR-GNB infections.

PATIENTS AND METHODS: A retrospective, single-center observational study was conducted on patients diagnosed with CR-GNB infections who were treated with COL combined with CAZ/AVI (C/C), COL combined with Tigecycline (C/T), and COL combined with meropenem (C/M). The primary outcome measure was the rate of microbiological clearance within seven days, while secondary outcomes included changes in inflammatory markers, severe illness-related scores, length of stay, and survival rates.

RESULTS: Among the 95 patients analyzed, the C/C treatment regimen resulted in a higher rate of microbiological clearance (64.7%) compared to C/T (24.1%) and C/M (25.0%) (P=0.002 and P=0.001). In the subgroup analysis for treating infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), the 7-day microbial clearance rates in the C/C, C/T, and C/M groups were 57.9%, 25.0%, and 29.4%, respectively (P = 0.122). Inflammatory markers, including white blood cell count, c-reactive protein, and procalcitonin, showed improvements in three groups. The decrease of some indicators was statistically significant. However, no significant differences in mortality rates were observed across the treatment groups. Furthermore, the survival curve analysis indicates that the survival time of the C/M treatment regimen is significantly longer than that of the C/C treatment regimen.

CONCLUSION: The C/C treatment regimen appears to be more effective in achieving microbiological clearance and improving inflammatory parameters in patients with CR-GNB infections. While the impact on survival rates and survival duration requires further investigation, the C/C regimen warrants consideration as a potent therapeutic option for CR-GNB infections.

PMID:40810173 | PMC:PMC12348888 | DOI:10.2147/IDR.S542467