Tag: pubmed

Drugs. 2026 Jan 19. doi: 10.1007/s40265-025-02274-x. Online ahead of print.

ABSTRACT

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease, but effective therapies remain limited. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are primarily used to lower low-density lipoprotein cholesterol (LDL-C), yet their effects on Lp(a) have been inconsistently reported. This umbrella review synthesizes meta-analytic evidence on PCSK9 inhibitors and Lp(a).

METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library through April 2025 for meta-analyses of randomized controlled trials (RCTs) comparing PCSK9 inhibitors (alirocumab, evolocumab, inclisiran) with placebo or standard therapy. The primary outcome was mean percentage change in Lp(a). Methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), and evidence certainty was graded with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Overlap of primary trials was quantified using the Corrected Covered Area (CCA), and sensitivity analyses were performed to account for overlapping evidence.

RESULTS: Twenty-one meta-analyses (116 RCTs; 231,796 participants) were included. The PCSK9 inhibitors consistently reduced Lp(a): evolocumab (29.68-46.68%; high certainty), alirocumab (18.55-26.46%; high certainty), and inclisiran (18.00%; high certainty). Higher biweekly doses yielded larger decreases (e.g., alirocumab 150 mg: 24.6%; evolocumab 140 mg: 26.8%, high certainty). Reductions were dose-dependent and broadly consistent across populations, comparators, follow-up durations, and baseline Lp(a). The Lp(a) reductions correlated modestly with LDL-C (β = 0.28; 95% CI 0.07-0.49) and apolipoprotein B (apoB) (β = 0.33; 95% CI 0.03-0.63). Concomitant reductions in LDL-C, apoB, and major adverse cardiovascular events were supported by high and moderate certainty evidence. Safety was favorable, with injection-site reactions being the most common adverse event. Sensitivity analyses confirmed robustness of findings after accounting for overlapping trials.

CONCLUSIONS: The PCSK9 inhibitors, particularly evolocumab 140 mg every 2 weeks, significantly lower Lp(a) alongside LDL-C and apoB. These findings highlight the consistent Lp(a)-lowering effect of PCSK9 inhibitors. However, the observed cardiovascular benefits are largely attributable to concomitant LDL-C reduction, and the incremental contribution of Lp(a) lowering remains uncertain. Confirmation from outcome trials specifically designed to target Lp(a) is required.

REGISTRATION: PROSPERO CRD420251048597.

PMID:41549171 | DOI:10.1007/s40265-025-02274-x

Int J Legal Med. 2026 Jan 19. doi: 10.1007/s00414-025-03713-w. Online ahead of print.

ABSTRACT

Postmortem interval (PMI) estimation is mandatory in any forensic investigation. Although it remains a very challenging task, particularly in skeletonized human remains. Luminol chemiluminescence has been explored as a tool for PMI estimation, however, its application requires further experimental validation to ensure accuracy and reproducibility. The present research aims to increase the objectivity of PMI estimation by quantifying the light emission from the luminol chemiluminescence reaction. For this purpose, a sample of clavicles collected from 24 adult individuals of both sexes, with known PMI ranging from 7 to approximately 500 years, was selected. After being reduced to powder, the samples were analyzed on a CCD camera with an image intensifier, and the reaction Ipeak was measured. The results obtained revealed a clear inverse relationship between PMI and Ipeak values. A segmented regression analysis identified a statistically supported threshold at approximately 30 years postmortem, distinguishing a variable early postmortem phase from a long-term phase characterized by consistently low and minimally variable chemiluminescence intensities. This pilot study supports the validity of quantifying the luminol chemiluminescence reaction as a feasible and informative presumptive screening tool for PMI estimation, with potential applicability in distinguishing remains of forensic interest from those of archaeological relevance.

PMID:41549170 | DOI:10.1007/s00414-025-03713-w

J Man Manip Ther. 2026 Jan 18:1-13. doi: 10.1080/10669817.2026.2614009. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the efficacy of cervical physical therapy (e.g. cervical mobilization, exercise, and myofascial treatments) on pressure pain thresholds (PPTs) in patients with migraine, compared to no treatment, sham treatment, or usual medical care.

METHOD: A systematic search was performed in PubMed, Embase.com, Web of Science, SPORTDiscus, Cinahl Plus and PEDro. Two independent reviewers assessed the selected randomized controlled trials (RCTs). The risk of bias was assessed using the Cochrane risk of bias tool 2, and the certainty of evidence was evaluated according to the GRADE approach. The meta-analysis included PPTs from cervical muscles and cephalic muscles.

RESULTS: Five papers out of 965 screened papers met our inclusion criteria, of which two originated from the same randomized controlled trial. Four RCTs had some risk of bias due to the absence of a pre-specified analysis plan and missing outcome data. One RCT had a high risk of bias due to a lack of information on concealment and blinding. All studies reported increased PPTs after cervical treatment. However, statistically significant differences were only found for the sternocleidomastoid muscle (mean difference (MD) 1.13 kg/cm²; 95% confidence interval (CI): 0.48 to 1.78) and the frontal muscle (MD 0.53 kg/cm²; 95% CI: 0.07 to 1.00). The certainty of evidence was low to very low.

CONCLUSION: The efficacy of cervical physical therapy on PPTs is uncertain. More studies of high methodological quality are needed to elucidate the pain-modulatory effects of cervical physical therapy in migraine.

PMID:41548105 | DOI:10.1080/10669817.2026.2614009

Drug Dev Ind Pharm. 2026 Jan 18:1-21. doi: 10.1080/03639045.2026.2618506. Online ahead of print.

ABSTRACT

SignificanceThe liposomal formulation reveals a safe, sustained, and efficient ocular drug delivery to improve the therapeutic potential of dorozolamide hydrochloride in glaucoma treatment.ObjectiveA liposomal formulation of Dorzolamide hydrochloride was developed and evaluated for sustained ocular delivery with improved permeation and safety.MethodsLiposomes were prepared using the thin-film hydration method and optimized through a 3² full factorial design, analysing the effects of phosphatidylcholine and cholesterol on entrapment efficiency and drug release via response surface methodology.ResultsThe optimized formulation, containing 200 mg phosphatidylcholine and 40 mg cholesterol, exhibited a vesicle size of 98.22 ± 10.03 nm, zeta potential of -21.53 ± 1.02 mV, and high entrapment efficiency (97.5%). In vitro studies confirmed sustained drug release over 8 hours, while ex vivo transcorneal permeation was 1.8 times greater than that of marketed eye drops. Safety assessments using Hen’s Egg Test-Chorioallantoic Membrane(HET-CAM) and Draize tests established the formulation as non-irritant and isotonic.ConclusionOverall, the liposomal system significantly enhanced ocular bioavailability and demonstrated potential as a safe and effective option for long-term glaucoma therapy.

PMID:41548087 | DOI:10.1080/03639045.2026.2618506

Ann Med. 2026 Dec;58(1):2616970. doi: 10.1080/07853890.2026.2616970. Epub 2026 Jan 18.

ABSTRACT

BACKGROUND: Hearing loss (HL) is the leading cause of disability worldwide, with a particularly severe impact on low- and middle-income countries and causing a huge economic burden. While child HL prevention exists, working-age adults (WAP) struggle to avoid occupational and environmental risks.

METHOD: Using Global Burden of Disease 2021 data, this study analyzed global HL prevalence trends in the WAP (1992-2021). Analyses included age-standardized prevalence rates (ASPR), estimated annual percentage change, and age-period-cohort (APC) modeling, stratified by gender, age, cause, severity, and Social Demographic Index (SDI).

RESULT: Global WAP HL prevalence significantly increased to 524 million in 2021 (a 56.9% increase since 1992), primarily due to population growth and aging. Age period cohort (APC) analysis revealed different patterns: as age increases, risk increases and cyclical effects generally increased (except in low SDI regions). The upward trend of birth cohorts in high to middle SDI countries was worrying. In addition, this study also observed that there was a gender difference in the prevalence trend of HL in WAP (male incidence rate was higher, but female growth was faster), and the patient population was gradually younger. Improved trends from 2017-2021 globally and regionally suggest a potential, albeit unexpected, positive influence of the COVID-19 pandemic on HL prevalence.

CONCLUSION: The global HL burden in the WAP is large and uneven, necessitating targeted interventions focusing on modifiable risks and SDI disparities. Further research is essential to understand the trends observed during the COVID-19 pandemic and to improve prevention strategies.

PMID:41548082 | DOI:10.1080/07853890.2026.2616970

Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70325. doi: 10.1002/pds.70325.

ABSTRACT

PURPOSE: This study investigates the impact of Balance solutions on the risks of technique failure, death, and the first episode of peritonitis in incident peritoneal dialysis (PD) patients.

METHODS: From the database of Taiwan’s National Health Insurance, patients with newly diagnosed end-stage kidney disease receiving PD for at least 90 days and treated with Balance solutions at the initiation of PD from 2009 to 2020 were identified. For each Balance solution user, 10 patients using conventional PD solutions, matched by the index year, were randomly selected as the control cohort. Risks of technique failure, death and the first episode of peritonitis were compared between the two cohorts by the end of 2021.

RESULTS: Compared to the controls, the Balance solution users had an insignificant lower technique failure [156.3 vs. 172.0 per 1000 person-years; adjusted hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.79-1.08] and mortality (203.5 vs. 223.7 per 1000 person-years; adjusted HR = 0.96, 95% CI = 0.83-1.09). The incident first episode of peritonitis was insignificant higher for the Balance solution cohort (139.9 vs. 117.1 per 1000 person-years), with an adjusted HR = 1.14 (95% CI = 0.94-1.37). However, the adjusted HR of the first peritonitis episode was 1.24 (95% CI = 1.02-1.49) using the time-dependent model.

CONCLUSIONS: The use of Balance solution is associated with similar risks of technique failure and mortality, but probably an increased risk of the first episode of peritonitis, compared with the use of conventional solutions among incident PD patients.

PMID:41548054 | DOI:10.1002/pds.70325

Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70328. doi: 10.1002/pds.70328.

ABSTRACT

PURPOSE: Claims data are a valuable source to study neonatal outcomes across a wide range of clinical questions. Infants’ delayed enrollment in infant insurance poses challenges in capture of neonatal outcomes, which may be charged to the maternal health plan, posing misclassification risks. We evaluated outcome ascertainment across three infant enrollment scenarios.

METHODS: We used Merative MarketScan databases (2012-2018) in the United States to construct a mother-infant linked cohort and assess the outcome ascertaiment precision with varying infant enrollment requirement.

RESULT: We found that allowing delayed infant enrollment in their own insurance within the first 4 weeks of life retained sample size, nearly doubled case numbers and yielded outcome prevalences similar to those of cohorts with full enrollment since birth. Use of maternal claims in addition to infant claims in this cohort made minor contributions to case capture for neonatal-specific outcomes, while significantly decreasing specificity of more general outcomes. Longer delays in enrollment yielded lower outcome prevalences with higher contributions of maternal claims even for neonatal-specific outcomes. For small for gestational age (SGA), both maternal and infant claims contributed similar proportions of cases.

CONCLUSION: These findings inform strategies for outcome ascertainment in claims-based perinatal research and emphasize outcome-specific case ascertainment strategies to balance sensitivity and specificity.

PMID:41548053 | DOI:10.1002/pds.70328

J Orthop Res. 2026 Jan;44(1):e70145. doi: 10.1002/jor.70145.

ABSTRACT

Raman spectroscopy is a molecular fingerprinting technique that uses inelastic light scattering to characterize material composition and has been widely applied to bone quality assessment. In this ex vivo feasibility study, we tested whether Raman spectroscopy could predict femoral neck T-scores (n = 58) from specimens obtained during elective total hip arthroplasty and classify them as normal, osteopenic, or osteoporotic. Bone samples were excited using a near-infrared, multiple spatial mode, semiconductor laser (830 nm, 150 mW), and scattered light was collected for spectral analysis. Custom MATLAB code calculated Raman outcomes. T-scores were determined from bone mineral density acquired from dual-energy X-ray absorptiometry. Raman components were correlated with T-score using simple linear or partial least squares regressions (PLSR). Bone health classifications were assessed through receiver operating characteristic curves (ROC), area under the ROC curves (AUC), and descriptive statistics. Simple linear regression models identified mineral maturity/crystallinity (MMC) as the strongest single-variable predictor of T-score in males (R² = 0.20, 95% CI 0.00-0.43) and females (R² = 0.22, 95% CI 0.00-0.46). MMC showed fair discrimination between normal and osteopenic or osteoporotic groups in males (AUC = 0.76, 95% CI 0.56-0.97; 0.77, 95% CI 0.55-0.99) and females (AUC = 0.73, 95% CI 0.52-0.95; 0.70, 95% CI 0.47-0.92). PLSR (including mineral-to-matrix ratio, carbonate-to-phosphate ratio, MMC, and pyridinoline) slightly improved combined sex T-score correlation (R² = 0.28, 95% CI 0.05-0.55) and male normal versus osteoporotic classification (AUC = 0.89, 95% CI 0.75-1.00). This ex vivo feasibility study demonstrates the potential of Raman spectroscopy to differentiate bone quality.

PMID:41548052 | DOI:10.1002/jor.70145

HGG Adv. 2026 Jan 16:100573. doi: 10.1016/j.xhgg.2026.100573. Online ahead of print.

ABSTRACT

Optimal selection of instrumental variables (IVs) from a single gene region in cis-Mendelian randomization is challenging as variants are highly correlated due to linkage disequilibrium (LD). Using only the lead variant is convenient but may not achieve full statistical power if multiple signals exist. We compared four selection methods that incorporate correlated non-lead variants, including LD-pruning, conditional and joint analysis (COJO), Sum of Single Effects (SuSiE) regression, and principal component analysis (PCA), and evaluated their ability to increase instrument strength, measured by variance explained in the exposure (R²), relative to the lead-variant-only approach. We applied these methods to circulating haptoglobin (HP), to simulated traits with known variance explained, and to 15 additional gene regions where non-lead cis-pQTLs contributed varying proportions of cis-genetic variance. R² was estimated from variant-protein association estimates (Fenland study, N=10,708) using LD from the UK Biobank (N=356,557). In the HP region, the four methods produced a median proportional gain in R² of 145.1% compared with the lead variant alone (range: 69.6% – 169.4%), with a median reduction in the MR standard error of 36.3% (range: -37.9% to -19.3%). In simulations, all methods were able to recover the expected genetic variance. Across the 15 gene regions, methods incorporating non-lead variants consistently outperformed the lead-variant-only approach. Variant selection methods incorporating correlated non-lead variants can reliably improve instrument strength in cis-MR analyses. We recommend using such methods but advise comparing their estimates with the lead-variant-only estimate to safeguard against numerical instability.

PMID:41548043 | DOI:10.1016/j.xhgg.2026.100573

Sci Rep. 2026 Jan 17. doi: 10.1038/s41598-026-36444-y. Online ahead of print.

ABSTRACT

Stress urinary incontinence (SUI) is usually associated with aging and parity, but repetitive intra-abdominal pressure during physical activity can also trigger its onset in young women. Horseback riding, despite potential benefits for pelvic floor strengthening, may also contribute to pelvic floor strain and urinary symptoms. The study included 100 Polish women aged 21-54 engaged in horse riding, both recreational (85%) and professional (15%). Participants were divided into three age groups and screened for urinary incontinence symptoms. Quality of life was assessed with validated questionnaires (IIQ-7, UDI-6SF) and a custom 25-item survey covering equestrian practice, reproductive history, urinary symptoms, and general health. Statistical analyses were performed in R using non-parametric tests, correlation, and logistic regression. Stress urinary incontinence was reported by 36% of participants, significantly impairing quality of life. Women with higher BMI, older age, and childbirth history demonstrated increased symptom prevalence and higher IIQ-7 and UDI-6 scores (p < 0.05). Training type, frequency, and duration were not significantly associated with outcomes, except for shorter riding experience, which correlated with higher UDI-6 scores. Logistic regression identified age (OR = 1.07) and BMI (OR = 1.16) as risk factors, while greater height reduced SUI odds (OR = 0.92). Urinary incontinence is a relevant issue among female horse riders, negatively affecting physical, social, and emotional well-being. Age, BMI and childbirth history play crucial roles in the incidence of SUI symptoms. The longer the training experience, the lower is reported urinary incontinence distress. Preventive measures such as pelvic floor training, individualized physiotherapy, and interdisciplinary care may reduce symptom burden and support longer professional activity. Raising awareness and encouraging early intervention are essential to improving athletes’ quality of life.

PMID:41548020 | DOI:10.1038/s41598-026-36444-y