Tag: nevin manimala

Adv Ther. 2025 Sep 23. doi: 10.1007/s12325-025-03368-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Valoctocogene roxaparvovec is a single administration gene therapy treatment that enables endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. Valoctocogene roxaparvovec is associated with a higher probability of being bleed-free, improvements in annualized bleed rates, and improvements in health-related quality of life compared with FVIII prophylaxis. The economic value of valoctocogene roxaparvovec will be determined, in part, by the duration of time over which the treatment effect is maintained, and the consequences associated with loss of response. Therefore, this analysis aimed to estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating pivotal and longer-term trial data (Phase 3 GENEr8-1 4- to 5-year and a Phase 1/2 study 7-year data) to inform decision-making.

METHODS: Using data from the pivotal Phase 3 study GENEr8-1 and longer-term data from the 6E13 vg/kg cohort of Phase 1/2 Study 270-201, time to loss of response was analyzed within a time-to-event analysis framework. Loss of response was defined as a combination of: FVIII level decline < 5% and return to continuous prophylactic treatment and experiencing ≥ 2 treated bleed events in the previous 6 months at the time of return to prophylactic treatment.

RESULTS: Data were available for 134 participants from GENEr8-1, and 7 participants from Study 270-201. The main analysis results for predicted median durability ranged from 11.0 to 17.0 years considering the three statistically best-fitting parametric distributions; considering five plausible distributions, results ranged from 8.1 to 25.6 years. In scenario analyses using different definitions of loss of response, the results were broadly similar, with median durability ranging from 7.2 to 31.8 years.

CONCLUSION: This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years).

TRIAL REGISTRATION NUMBER: GENEr8-1: ClinicalTrials.gov identifier, NCT03370913. Study 270-201: ClinicalTrials.gov identifier NCT02576795.

PMID:40986187 | DOI:10.1007/s12325-025-03368-4

Adv Ther. 2025 Sep 23. doi: 10.1007/s12325-025-03348-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Four monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are approved for migraine prevention and commonly prescribed/reimbursed after the failure of repurposed anti-migraine medications. Participants achieving clinical response [e.g., ≥ 50% monthly migraine days (MMDs) reduction] during an anti-CGRP mAb trial are likely to continue treatment. We calculated number needed to treat (NNT) and quarterly cost per responder (CPR) across four anti-CGRP mAbs.

METHODS: Data were from randomized, double-blind, placebo-controlled phase 3b clinical trials that evaluated anti-CGRP mAbs (eptinezumab, fremanezumab, galcanezumab, erenumab) for migraine prevention in adults with episodic or chronic migraine for whom 2-4 prior preventive treatments have failed. NNT was calculated as 1 divided by absolute risk reduction (difference between active treatment and placebo in the proportion of participants with ≥ 50% or ≥ 75% MMD reduction over Weeks 1-12). CPR was calculated by multiplying NNT by the quarterly (3-month) drug acquisition CPR (£), based on the reimbursed list price in the United Kingdom (CPR could not be calculated for eptinezumab 300 mg). Statistical comparisons were not made.

RESULTS: All anti-CGRP mAbs demonstrated higher rates of ≥ 50% and ≥ 75% MMD reduction than their respective placebo (p < 0.05). The NNT to achieve ≥ 50% MMD reduction ranged from 2.7 (eptinezumab 300 mg) to 6.0 (erenumab 140 mg), and for ≥ 75%, 6.0 (eptinezumab 300 mg) to 16.2 (fremanezumab 675 mg/q). The cost per ≥ 50% responder ranged from £4647 (eptinezumab 100 mg) to £7009 (erenumab 140 mg), and for ≥ 75%, £9850 (eptinezumab 100 mg) to £21,862 (fremanezumab 675 mg/q).

CONCLUSIONS: These results show that, for most anti-CGRP mAbs, a low number of participants (< 10) with migraine need to be treated to achieve one person with a ≥ 50% or ≥ 75% reduction in MMDs over Weeks 1-12, with CPR ranging from £4647 (eptinezumab 100 mg) to £21,862 (fremanezumab 675 mg/q).

PMID:40986186 | DOI:10.1007/s12325-025-03348-8

Future Cardiol. 2025 Sep 23:1-9. doi: 10.1080/14796678.2025.2564029. Online ahead of print.

ABSTRACT

BACKGROUND: The triglyceride – glucose (TyG) index is a surrogate of insulin resistance and may predict vascular risk. We evaluated whether baseline TyG is associated with incident stroke and all-cause mortality in adults with diabetes.

METHODS: We analyzed 10,000 UK Biobank participants with diabetes and no baseline cardiovascular disease. TyG was calculated from fasting triglycerides and glucose and categorized into quartiles. Outcomes (stroke; all-cause mortality) were ascertained via hospital and death registries. Cox models estimated hazard ratios (HRs) adjusting for demographic, lifestyle, and clinical covariates.

RESULTS: Over a median 12.8 years, 620 strokes and 688 deaths occurred. Compared with Q1, Q4 had higher risks of stroke (HR 1.45, 95% CI 1.18-1.80) and mortality (HR 1.42, 95% CI 1.17-1.73). Each 1-SD higher TyG was associated with ~ 19% higher stroke risk (HR 1.19, 95% CI 1.07-1.32) and ~ 16% higher mortality risk (HR 1.16, 95% CI 1.05-1.29). Associations were consistent across age, sex, and BMI subgroups and robust in sensitivity analyses, including extended adjustment.

CONCLUSIONS: Higher TyG is independently associated with increased risks of stroke and all-cause mortality among individuals with diabetes. As an inexpensive measure derived from routine tests, TyG may aid risk stratification and inform targeted prevention in this high-risk population.

PMID:40985184 | DOI:10.1080/14796678.2025.2564029

Orthop Surg. 2025 Sep 23. doi: 10.1111/os.70179. Online ahead of print.

ABSTRACT

OBJECTIVE: Since the 1960s, although open reduction and internal fixation for ankle fractures has been widely used, it is associated with complications such as wound dehiscence, infection, prominent hardware, and failure. Closed reduction and internal fixation, on the other hand, offers greater biomechanical strength, requires minimal incisions, and features low-profile hardware. Our study compares the efficacy of elastic locking intramedullary nails (ELIN) fixation featuring minimally invasive microenvironmental protection microstress shielding versus rigid internal fixation (RIF) for trimalleolar fractures.

METHODS: This retrospective study included a total of 39 patients (2020-2024), comprising 10 men and 29 women (mean age, 55.9 years), who were assigned to the ELIN group or the RIF group. Comparing the different variables between the two groups, including surgical incision length, intraoperative blood loss, operative time, time until union, time to device removal, AOFAS scores, ankle dorsiflexion, and plantar flexion, postoperative complications, and patient satisfaction. The surgical incision length, intraoperative blood loss, and operative time conformed to a normal distribution, so the independent t-tests were used for statistical analysis. Time until union, time to device removal, AOFAS scores, ankle dorsiflexion, and plantar flexion, and patient satisfaction did not conform to a normal distribution; thus, the Mann-Whitney U test was adopted.

RESULTS: All 39 patients were completed the surgery successfully. ELIN fixation is superior to RIF in surgical incision length (p < 0.001), intraoperative blood loss (p = 0.047), operative time (p < 0.001), time until union (p = 0.003), and time to device removal (p < 0.001), with significant differences in the above parameters between the two groups. The AOFAS scores (p = 0.553), ankle dorsiflexion (p = 0.904), and plantar flexion (p = 0.799) were not significantly different between the two groups. One case of ankle pain was reported in each group at the sixth month postoperatively. By the end of the follow-up, the pain in these two cases had lessened or even disappeared after the patients reduced weight bearing on the injured ankle joint and took non-steroidal anti-inflammatory drugs under medical guidance. There was a surgical incision infection case in the RIF group, which healed after 3 weeks following daily wound dressing and use of sensitive antibiotics.

CONCLUSION: Compared with RIF, ELIN offers advantages including minimally invasive procedures, faster fracture union, shorter time to device removal, a more aesthetically pleasing appearance of the wound, and high patient satisfaction in treating trimalleolar fractures. These advantages well embody the concept of enhanced recovery after surgery. In contrast to traditional intramedullary fixation, ELIN realized locking fixation, reducing the risk of nail backing out and even nail fracture; however, it is more difficult to remove the nail.

PMID:40985157 | DOI:10.1111/os.70179

Clin Chem Lab Med. 2025 Sep 24. doi: 10.1515/cclm-2025-1011. Online ahead of print.

ABSTRACT

OBJECTIVES: The European Organization for External Quality Assurance Providers in Laboratory Medicine (EQALM) Haematology Working Group (WG) has previously provided two guidelines to support the standardization of haematology blood smear external quality assessment (EQA) (Vives CJL, Albarède S, Flandrin G, Heller S, Horvath K, Houwen B, et al. Guidelines for blood smear preparation and staining procedure for setting up an external quality assessment scheme for blood smear interpretation. Part I: control material. Clin Chem Lab Med 2004;42:922-6; Vives CJL, Van Blerk M, Albarède S, Gutierrez G, Heller S, Nordin G, et al. Guidelines for setting up an external quality assessment scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting. Clin Chem Lab Med 2006;44:1039-43) but these recommendations did not include analytical performance specifications. In this paper the WG provides advice on the performance specifications for the evaluation of blood cell identification, comments on morphological characteristics and diagnostic hypothesis.

METHODS: To develop these specifications, the WG made a survey of the practices in use by EQALM members and provided a standard set of EQA data, provided by one of the members, for performance evaluation.

RESULTS: The results of this exercise show a variation in the performance assessment outcomes from one EQA provider to another, suggesting that a degree of standardisation would be of benefit to participating laboratories.

CONCLUSIONS: The WG has provided advice on common performance specifications, based on model 1 of the Milan Consensus (Sandberg S, Fraser CG, Horvath AR, Jansen R, Jones G, Oosterhuis W, et al. Defining analytical performance specifications: consensus statement from the 1st strategic conference of the European federation of clinical chemistry and laboratory medicine. Clin Chem Lab Med 2015;53:833-5).

PMID:40985149 | DOI:10.1515/cclm-2025-1011

Kidney Res Clin Pract. 2025 Sep 9. doi: 10.23876/j.krcp.24.292. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a growing global health challenge, with smoking identified as a significant risk factor. This study investigates the long-term impact of adolescent smoking initiation on end-stage kidney disease (ESKD) development.

METHODS: A retrospective cohort study was conducted using data from the Korean National Health Insurance Service claims database. The cohort included 201,678 CKD patients aged ≥40 years with a documented smoking history. Patients were stratified by smoking initiation age (<20 years vs. ≥20 years) and cumulative smoking exposure (pack-year, PY). The primary outcome was ESKD incidence, defined as kidney replacement therapy initiation. Cox proportional hazards models assessed the relationship between smoking initiation age, smoking burden, and ESKD risk.

RESULTS: During a median 6.8-year follow-up period, 6,334 patients progressed to ESKD (incidence rate, 3.63 per 1,000 PYs). Those with higher PYs were older and had more comorbidities, such as hypertension and diabetes mellitus. Patients who began smoking before age 20 years and accumulated ≥20 PYs had a significantly higher risk of ESKD (hazard ratio, 1.26; 95% confidence interval, 1.16-1.38) compared to those with the same exposure but later smoking initiation. Increased cumulative smoking exposure further elevated the risk. When PYs were divided according to initiation age, a higher ratio was associated with an increased risk of ESKD.

CONCLUSION: Early smoking initiation during adolescence was associated with a significantly higher risk of progression to ESKD in patients with CKD, especially in those with higher cumulative smoking exposure. Public health interventions focusing on preventing adolescent smoking can mitigate the long-term burden of CKD progression.

PMID:40985140 | DOI:10.23876/j.krcp.24.292

Diabetes Technol Ther. 2025 Sep 23. doi: 10.1177/15209156251379505. Online ahead of print.

ABSTRACT

Objective: The CRISTAL trial indicated that advanced hybrid closed loop (AHCL) therapy with MiniMed™ 780G in type 1 diabetes pregnancy did not improve time in range (TIRp) compared with standard insulin therapy (SoC), but improved TIRp overnight and reduced time below range (TBRp). We aimed to evaluate the effect of AHCL therapy across different subgroups. Research Design and Methods: This secondary analysis of the CRISTAL randomized controlled trial compared glycemic outcomes (TIRp, TIRp overnight, TBRp, and TBRp overnight) averaged over the antenatal period (14-, 20-, 26-, and 33-weeks’ gestation) between the AHCL and SoC groups, within subgroups defined by baseline characteristics. Results: In women with baseline HbA1c <7.0%, the AHCL group (n = 35) had a significantly higher TIRp than SoC (n = 37), with a mean difference of 5.64% (95% confidence interval [95% CI]: 1.32-9.96), corresponding to 1 h 21 min more TIRp per day and 11.89% (95% CI: 7.01-16.76) higher TIRp overnight. In women without prior AHCL use, TIRp was 6.29% higher (95% CI: 0.90-11.68) and overnight TIRp 11.91% higher (95% CI: 5.65-18.16) in the AHCL group (n = 24) compared with SoC (n = 28). In women without higher education, AHCL users (n = 14) had a significantly higher TIRp compared with SoC (n = 14) with a difference of 7.33% (95% CI: 0.88-13.78). TBRp was significantly lower in AHCL users with baseline HbA1c <7.0% and in women without prior AHCL use. Conclusions: AHCL therapy improved glycemic management in pregnant women with baseline HbA1c <7.0%, in women without prior AHCL use, and in women without higher education, indicating that AHCL might particularly benefit these subgroups.

PMID:40985127 | DOI:10.1177/15209156251379505

Eur J Neurosci. 2025 Sep;62(6):e70245. doi: 10.1111/ejn.70245.

ABSTRACT

Studies evaluating cognitive functions in patients with obsessive-compulsive disorder (OCD) have yielded inconsistent results in various cognitive domains. One key reason for contradictory findings is the frequent occurrence of comorbid psychiatric disorders in OCD. Attention deficit hyperactivity disorder (ADHD), especially in childhood, is one of the most common comorbidities in OCD. The aim of the current study was to identify potential differences in cognitive functions caused by childhood ADHD in adult OCD patients while minimizing the effects of symptoms that frequently accompany OCD, such as anxiety, depression, and age. The study included 35 OCD patients with childhood ADHD (OCD + cADHD), 44 OCD patients without childhood ADHD (OCD-cADHD), and 40 healthy controls (HC). Hamilton Depression and Anxiety Scales were applied to all participants. Next, the Cambridge Neuropsychological Test Automated Battery (CANTAB) [Paired-Associate-Learning (PAL), Cambridge Gambling Task (CGT), Stop Signal Test (SST), and Intra-/Extra-Dimensional Set-Shifting Test (IED)] was administered. The OCD patients without childhood ADHD (OCD – cADHD) exhibited higher mean scores in CGT-Risk-Taking and Bet Ratio compared to the HC. However, OCD patients with childhood ADHD (OCD + cADHD) also showed higher mean scores in CGT-Bet Ratio compared to the HC. The mean number of IED-Total Errors and IED-Total Trials was higher in the OCD + cADHD group compared to the HC. The OCD + cADHD group had a higher mean number of SST-Direction Errors and Missed Trials than other groups. The results of the current study suggest that even when potential confounding factors such as depression and anxiety are neutralized, the presence of childhood ADHD in adult patients with OCD led to differences in cognitive domains related to decision-making, flexible thinking, and impulsivity.

PMID:40985125 | DOI:10.1111/ejn.70245

BJPsych Open. 2025 Sep 23;11(5):e220. doi: 10.1192/bjo.2025.10834.

ABSTRACT

BACKGROUND: First-episode psychosis (FEP) is a critical phase in psychotic disorders where early intervention significantly influences long-term outcomes. Catatonia, characterised by motor, behavioural, and psychological abnormalities, is an under-recognised aspect of FEP.

AIMS: This study examines catatonia prevalence in affective and non-affective FEP, its role as a severity indicator across psychopathological domains, its correlations with other symptoms and its association with clinical syndromes.

METHOD: A cross-sectional study was conducted with 58 FEP patients (38 females, 20 males) aged 15-55 years. Of those, 40 were antipsychotic-naive, and 18 had minimal prior antipsychotic exposure. Participants were recruited from acute psychiatric units. Catatonia was assessed using the Bush Francis Catatonia Rating Scale (BFCRS), while psychopathology was evaluated with the Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale (CDS) and Young Mania Rating Scale (YMRS). Data analysis included descriptive statistics, t-tests, X² tests, and multivariable regression using SPSS version 25 for Windows.

RESULTS: Catatonic signs were identified in 22.4% of cases based on the Bush Francis Catatonia Screening Instrument (BFCSI) criteria (BFCSI-positive group, defined as ≥2 signs present for over 24 h), indicating potential catatonia. Prevalence varied by criteria: 13.8% (DSM-IV), 10.3% (Fink and Taylor), 10.38% (ICD-11) and 8.6% (DSM-5). Catatonic patients had more years of education and significantly higher PANSS totals, Emsley negative, disorganised, excited, and anxiety scores. Catatonic signs moderately correlated with Emsley disorganised scores. Regression analysis identified PANSS total and Emsley domain scores as significant predictors of catatonia severity.

CONCLUSIONS: Catatonia is notably prevalent in FEP and associated with severe psychopathology, particularly in negative and disorganised domains. These findings underscore the importance of improving recognition of catatonia in early psychosis. Larger longitudinal studies are needed to confirm these findings and explore treatment implications.

PMID:40985102 | DOI:10.1192/bjo.2025.10834

Acta Otorhinolaryngol Ital. 2025 Aug;45(4):280-286. doi: 10.14639/0392-100X-A731.

ABSTRACT

OBJECTIVE: Chronic kidney disease (CKD) is a global health problem with a significant impact on patients’ quality of life. Haemodialysis, a common treatment for advanced CKD, can profoundly affect vestibular function, which plays a critical role in maintaining balance and spatial orientation.

METHODS: This prospective study was conducted over a 6-month period at the Magna Graecia University and included 18 adult patients with CKD stage 5, undergoing haemodialysis. Vestibular function was assessed using the Visual Analogue Scale (VAS) for the symptom of unsteadiness and the video Head Impulse Test (vHIT) for the vestibulo-ocular reflex (VOR) gain.

RESULTS: Our results showed a statistically significant decrease in VOR gain from 0.99 at T0 to 0.92 at T1 (T-test p = 0.034 and Welch Test p = 0.037), accompanied by an increase in VAS instability scores, after the dialysis session. These results suggest a worsening of vestibular function as a result of haemodialysis.

CONCLUSIONS: These results highlight the need for early diagnosis and timely intervention, such as vestibular rehabilitation, to reduce the risk of falls and improve the quality of life in CKD patients undergoing haemodialysis. Future research should investigate the long-term effects of haemodialysis on vestibular function.

PMID:40985095 | DOI:10.14639/0392-100X-A731