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Nevin Manimala Statistics

Reoperation risks between 1-level and 2-level cervical disc arthroplasty: analysis of a cohort of patients from a national spine registry

Neurosurg Focus. 2026 Jul 1;61(1):E3. doi: 10.3171/2026.3.FOCUS251150.

ABSTRACT

OBJECTIVE: The aim of this study was to determine if there is a difference in reoperations for adjacent segment disease (ASD) and all-cause reoperations between 1-level and contiguous 2-level cervical disc arthroplasty (CDA).

METHODS: A retrospective cohort study was conducted on patients (18-60 years of age) with cervical degenerative disc disease who underwent a primary 1-level or 2-level CDA using data from a national spine registry. Cox proportional hazards regression was used to evaluate reoperations for all-cause risks. Hazard ratios (HRs) and 95% confidence intervals are presented; a p value < 0.05 was the significance threshold.

RESULTS: The cohort consisted of 650 patients with 1-level CDA and 159 patients with 2-level CDA. The mean overall observational follow-up was 6.2 years (SD 4.3 years) for 1-level CDA and 4.2 years (SD 3.1 years) for 2-level CDA. The 5-year incidence of ASD reoperations was higher in 1-level CDA (4.7%, 95% CI 2.8%-6.6%) compared to 2-level CDA (1.1%, 95% CI 0.0%-3.15%). In Cox regression analysis, there was no statistical difference in all-cause reoperations between 1-level CDA and 2-level CDA (HR 0.93, 95% CI 0.44-1.94; p = 0.84). Few events in 2-level ASD reoperations allowed determination of hazard ratio.

CONCLUSIONS: This study is the first large real-world analysis outside of investigational device exemption trials to show no significant difference in all-cause reoperation rates between 1-level and 2-level CDA. Notably, the 5-year incidence of ASD-related reoperations was substantially higher following 1-level CDA compared with 2-level CDA. The reason for this discrepancy remains unclear. One possibility is surgeon selection bias-where an adjacent degenerative level may be left untreated during a 1-level CDA under the assumption that motion preservation would protect against adjacent segment deterioration. Alternatively, the higher ASD rate may simply reflect the natural history of cervical spondylosis rather than device effect. Further investigation is needed to determine the true drivers of this observation.

PMID:42385245 | DOI:10.3171/2026.3.FOCUS251150

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Nevin Manimala Statistics

Short-term radiographic outcomes and early safety of anterior cervical hybrid arthroplasty-fusion versus fusion constructs: a single-surgeon analysis

Neurosurg Focus. 2026 Jul 1;61(1):E9. doi: 10.3171/2026.3.FOCUS251207.

ABSTRACT

OBJECTIVE: Anterior cervical disc arthroplasty offers theoretical advantages over fusion such as quicker recovery and decreased biomechanical stress at adjacent levels. However, anterior cervical discectomy and fusion (ACDF) may be beneficial for patients with dynamic instability or advanced spondylosis. In patients with multilevel cervical degenerative disc disease, anterior cervical hybrid arthroplasty-fusion (ACHAF) constructs may allow for personalized approaches, addressing level-specific pathology while offering other theoretical advantages such as requiring a shorter anterior plate (if utilized), potentially reducing complications and risk of dysphagia. The authors aimed to evaluate radiographic outcomes and early safety of ACHAF compared with ACDF.

METHODS: This is a single-center retrospective study of patients who underwent 2- or 3-level ACHAF or ACDF between January 2021 and May 2025 by the senior author. In the ACHAF group, arthroplasty was performed at the most cephalad level. Radiographic parameters (C2-7 lordosis, C2-7 sagittal vertical axis [cSVA], and Cobb angle and height of the disc immediately proximal to the construct) were assessed preoperatively and at 6 months postoperatively. Clinical outcomes included length of stay and rates of return to the emergency department (ED) within 90 days, complications, dysphagia at 6 months postoperatively, and reoperation during the study period.

RESULTS: A total of 66 patients met the study criteria: 23 underwent ACHAF and 43 underwent ACDF (mean age 57.9 years). There was no difference in change of C2-7 lordosis or cSVA. The ACHAF group exhibited a decreased adjacent disc Cobb angle and increased disc height postoperatively, whereas the ACDF group exhibited an increased disc Cobb angle and decreased disc height (p < 0.001). Dysphagia at 6 months was more frequent in ACDF patients (32.6% vs 8.7%, p = 0.04). There was no significant difference in reoperation rates during the study period. Complications (p = 0.29) were more common in the ACDF group, and return to ED was more frequent in the ACHAF group (p = 0.71), although these did not meet statistical significance. There was no difference in rates of discharge on postoperative day 1 (p > 0.99).

CONCLUSIONS: ACHAF constructs possibly reduce stress on the proximal unoperated motion segment due to adjacent load sharing from the arthroplasty. Furthermore, dysphagia at 6 months postoperatively was less prevalent in the ACHAF group. Additional studies are needed to determine if ACHAF is associated with differences in patient-reported outcomes or long-term differences in rates of dysphagia or reoperation.

PMID:42385243 | DOI:10.3171/2026.3.FOCUS251207

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Nevin Manimala Statistics

Posterior lumbar facet arthroplasty versus fusion for the treatment of spondylolisthesis: 3-year results from the Total Posterior Spine System investigational device exemption study

Neurosurg Focus. 2026 Jul 1;61(1):E12. doi: 10.3171/2026.3.FOCUS2624.

ABSTRACT

OBJECTIVE: The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial.

METHODS: This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35-80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations.

RESULTS: One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329).

CONCLUSIONS: Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

PMID:42385242 | DOI:10.3171/2026.3.FOCUS2624

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Nevin Manimala Statistics

Identifiable Copula-Double-Cox Models: A Fully Parametric Framework for Dependent Right-Censored Survival Data

Stat Med. 2026 Jul;45(15-17):e70647. doi: 10.1002/sim.70647.

ABSTRACT

Dependent censoring, common in medical studies with informative dropout, invalidates standard Cox regression by violating the independent censoring assumption. While copula-based methods offer flexible dependence modeling, their parametric extensions face identifiability barriers. We address this problem through a novel fully identifiable parametric model that synergizes double-Cox marginal structures with copula dependence, which is called the copula-double-Cox model. Using Weibull or generalized exponential (GenExp) distributions, the double-Cox model links both scale and shape parameters to covariates via Cox-type regressions. This structure accommodates non-proportional hazards while containing the standard Cox model as a special case. We establish identifiability under dependent censoring and derive consistent estimators for baseline parameters, regression coefficients, and copula association. Simulations confirm robustness to association structure misspecification and over-parameterization. Estimation accuracy is supported by asymptotic theory and standard error evaluation via the observed information matrix. Finally, we illustrate the proposed approach through a real-world application to a dataset on monoclonal gammopathy of undetermined significance (MGUS), highlighting its practical relevance. The results show that our method provides an interpretable characterization of covariate effects on both failure time and censoring time through its double-Cox structure. An open-source R implementation of the copula-double-Cox model is provided on GitHub.

PMID:42385224 | DOI:10.1002/sim.70647

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Effectiveness of Digital Tools in Supporting Young Caregivers: A Systematic Review

Early Interv Psychiatry. 2026 Jul;20(7):e70215. doi: 10.1111/eip.70215.

ABSTRACT

AIM: To evaluate the effectiveness of digital interventions in supporting young caregivers’ mental health, well-being, and caregiving experiences, and to assess implementation factors including adherence and acceptability.

METHOD: We systematically searched six databases (MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central, and Scopus) and grey literature sources from inception to March 2025, identifying studies evaluating digital interventions for caregivers aged 25 years or younger. Study selection, data extraction, and risk of bias assessment were conducted independently by two reviewers. Due to substantial heterogeneity, narrative synthesis was performed following the Synthesis Without Meta-analysis (SWiM) reporting guidelines.

RESULTS: From 752 records, six studies met inclusion criteria, comprising three randomized controlled trials, one feasibility study, and two development/adaptation studies. Interventions included web-based platforms, mobile applications, audio-conferencing systems, and e-learning platforms. Digital tools showed limited effectiveness for mental health outcomes but demonstrated promise for quality-of-life improvements, with one trial showing statistically significant results (Wilks’ λ = 0.95, F(4, 418) = 2.74, p = 0.03). Adherence varied dramatically between self-guided platforms (26%) and structured programs (93%). All RCTs demonstrated a high risk of bias.

DISCUSSION: These findings reveal a ‘digital paradox’ whereby the theoretical advantages of accessibility failed to translate into engagement without human facilitation. Digital interventions for young caregivers require hybrid models combining technological convenience with relational support, structured flexibility, and continuous co-design with young caregivers to optimize engagement and effectiveness. The limited number of included studies and uniformly high risk of bias across RCTs underscore the need for pragmatic trials with robust implementation evaluations.

PROSPERO REGISTRATION: CRD42024604175.

PMID:42385212 | DOI:10.1111/eip.70215

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Nevin Manimala Statistics

Relationships Between Health Literacy and Quality of Life in Patients With Ischaemic Stroke: The Mediating Role of Fear of Disease Progression

Int J Nurs Pract. 2026;32(4):e70162. doi: 10.1111/ijn.70162.

ABSTRACT

BACKGROUND: Health literacy and fear of disease progression can predict quality of life, yet the underlying mechanisms among these three factors remain poorly understood.

AIM: This study aimed to investigate the hypothesis that health literacy among patients with ischemic stroke is associated with fear of disease progression and both directly and indirectly influence quality of life through the mediating role of fear of disease progression.

METHODS: Between December 2023 and June 2024, questionnaires were distributed to 300 in-patients with ischemic stroke selected by convenience sampling from the neurology departments of three tertiary general hospitals in the Xiangxi region of Hunan Province. Assessments were conducted using the General Information Questionnaire, the Medical Outcomes Study Short Form 36 (SF-36), Health Literacy Management Scale (HeLMS) and Fear of Progression Questionnaire-Short Form (FoP-Q-SF). Pearson correlation analysis was employed to examine the correlations between variables; AMOS 24.0 statistical analysis software was used to explore the pathways and effect sizes of fear of disease progression and health literacy on quality of life.

RESULTS: Health literacy was positively correlated with quality of life (r = 0.412, p < 0.01), while fear of disease progression was negatively correlated with quality of life (r = -0.445, p < 0.01). Fear of disease progression partially mediated the relationship between health literacy and quality of life, accounting for 41.3% of the total effect.

CONCLUSIONS: Findings support the development of targeted psychosocial intervention strategies aimed at enhancing patients’ health literacy to effectively alleviate disease-related fear, ultimately improving quality of life and optimizing care outcomes for stroke patients.

PMID:42385192 | DOI:10.1111/ijn.70162

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Nevin Manimala Statistics

Moving From Individualized Risk-Based Prevention to Benefit-Based Prevention: Estimating Individualized Life-Years Gained From Prevention Services as a Basis for Eligibility

Stat Med. 2026 Jul;45(15-17):e70659. doi: 10.1002/sim.70659.

ABSTRACT

The current bedrock of precision prevention is selecting high-risk individuals for screening or other prevention services under the assumption that those at highest risk would have the highest benefit from prevention services. However, this may not hold when disease risk and competing mortality are highly correlated. In such cases, risk-based prevention may preferentially select older individuals with multiple comorbidities who would have substantially reduced life-years gainable from the service and increased risks of harm from any resulting surgical procedures. For such prevention services, we propose a benefit-based selection strategy in which individuals are selected according to their expected gain in life-years (i.e., difference in mean survival time with and without the prevention service). We estimate the expected gain in life-years for individuals in a target screening population by combining data from a randomized trial, which may not be population-representative, and data from a population-representative survey that has larger sample size, more covariates, and longer follow-up time to evaluate mortality than the trial. We derive the Taylor-linearized variances for the estimated expected gain in life-years that take into account the randomness due to both trial and survey sample. We show that benefit-based selection of ever-smokers for lung-cancer screening can identify individuals with more favorable benefit-harm trade-offs compared to risk-based selection. Using simulation studies, we examine the conditions in which one strategy may be preferable over the other.

PMID:42385157 | DOI:10.1002/sim.70659

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Nevin Manimala Statistics

Syndemics, violence and injury: exploring historical relationships between infectious disease epidemics and violent crime in South Africa

Int J Inj Contr Saf Promot. 2026 Jul 1:1-16. doi: 10.1080/17457300.2026.2689077. Online ahead of print.

ABSTRACT

This paper explores historical and contemporary intersections between mass-mortality epidemics and violent crime in South Africa, focusing on four major epidemics – Spanish Flu, tuberculosis, HIV, and Covid-19. The study integrates epidemiological data and contextual historical information such as crime statistics, archival records, and secondary scholarship to explore whether epidemic-driven mortality crises are associated with subsequent changes in violence and injury profiles. With the possible exception of gendered violence, the study finds little evidence that earlier epidemics directly contributed to rapid or sustained increases in violent crime, despite causing substantial adult mortality and long-term social and economic disruption. A comparison between epidemic and socio-economic profiles strongly suggests that the significant increases in violent crime recorded after the Covid-19 pandemic are highly localised, and may be more strongly related to lockdown responses, including alcohol restrictions, rather than the effects of disease itself.

PMID:42385127 | DOI:10.1080/17457300.2026.2689077

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Nevin Manimala Statistics

Phase I/II Study of Sonrotoclax (BGB-11417) Monotherapy in Patients With Mantle Cell Lymphoma Previously Treated With Anti-CD20 Therapy and a Bruton Tyrosine Kinase Inhibitor

J Clin Oncol. 2026 Jul 1:JCO2600550. doi: 10.1200/JCO-26-00550. Online ahead of print.

ABSTRACT

PURPOSE: Mantle cell lymphoma (MCL) is a rare and typically aggressive B-cell non-Hodgkin lymphoma characterized by recurrent relapse after short remissions. Sonrotoclax (BGB-11417) is a next-generation B-cell lymphoma 2 inhibitor with greater selectivity and potency than venetoclax, a shorter half-life, and no drug accumulation. Sonrotoclax monotherapy was evaluated in Bruton tyrosine kinase inhibitor-pretreated patients with relapsed/refractory (R/R) MCL.

METHODS: BGB-11417-201 (ClinicalTrials.gov identifier: NCT05471843) is an ongoing global, open-label, phase I/II trial. Sonrotoclax was orally administered once daily with gradual, 4-week ramp-up to 160 mg or 320 mg to mitigate tumor lysis syndrome (TLS). The primary end point was overall response rate by the independent review committee (ORR-IRC) per Lugano classification; secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 125 patients were enrolled and assigned to receive sonrotoclax 160 mg (n = 10) or 320 mg (n = 115) target doses once daily. Most patients had advanced disease (stage IV, 78.3%) and were heavily pretreated (median prior therapies, 3). In efficacy-evaluable patients (n = 103), the ORR-IRC was 52.4% (95% CI, 42.4 to 62.4), a statistically significant increase versus the historic control ORR (30%; P < .0001); the complete response rate was 15.5%. Responses were seen across high-risk subgroups, including patients with TP53 mutation (59.1%). With a median study follow-up of 14.2 months, the median DOR-IRC was 15.8 months, and the median PFS-IRC was 6.5 months. Median OS was not reached. The most common all-grade/grade ≥3 treatment-emergent adverse events were neutropenia (35.7%/19.1%), thrombocytopenia (24.3%/9.6%), and anemia (24.3%/7.8%). TLS occurred in 7.0% of patients; all cases resolved without sequelae.

CONCLUSION: Sonrotoclax demonstrated rapid, durable responses and manageable safety in heavily pretreated patients with R/R MCL, including high-risk subgroups, supporting its further clinical evaluation as an oral therapy for R/R MCL.

PMID:42385124 | DOI:10.1200/JCO-26-00550

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Nevin Manimala Statistics

Genetic Risk for Alzheimer Disease, Midlife Hypertension, and Dementia: The ARIC Neurocognitive Study

Neurology. 2026 Jul 28;107(2):e218280. doi: 10.1212/WNL.0000000000218280. Epub 2026 Jul 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Genetics represent a nonmodifiable risk factor for Alzheimer disease (AD), with 60%-80% heritability. Midlife hypertension is a modifiable risk factor for both dementia and death. Our primary objective was to determine how genetic risk for AD modifies the association between hypertension and dementia.

METHODS: The Atherosclerosis Risk in Communities Study is an ongoing community-based prospective cohort study of 4 US centers. We analyzed White and Black participants free of dementia at age 55 years with genotypes and blood pressure measured at visit 1 (1987-1989). Three genetic risk groups (low, medium, high) were defined based on tertiles of a race-specific AD polygenic risk score. Dementia was ascertained through cognitive testing, informant interviews, hospitalization, codes and death records. Death was ascertained through the National Death Index. We examined the association of midlife hypertension with incident dementia within 3 genetic risk groups using Cox proportional-hazards and cumulative incidence function estimations. We used age 55 years as the time origin, with left truncation to allow entry at ages older than 55 years; age on December 31, 2022, was the administrative censoring date.

RESULTS: Among 8,931 White and 2,666 Black participants, the median follow up time was 26.6 and 23.8 years, the mean age was 54.0/53.5 years, and 53.0%/62.5% were female, respectively. After adjusting for demographics, midlife hypertension was significantly associated with dementia incidence across all genetic risk groups among White participants (low risk hazard ratio [HR] 1.29; 95% CI 1.07-1.55, medium risk HR 1.34; 95% CI 1.13-1.58, high risk HR 1.19; 95% CI 1.03-1.38) and among Black participants at high genetic risk (HR 1.31; 95% CI 1.04-1.66). Associations for low and medium genetic risk Black participants were consistent but not statistically significant. There were no significant differences in association of hypertension with dementia by AD genetic risk group. Individuals with hypertension had a 0%-2% higher probability of developing dementia by age 80 and a 6%-13% lower probability of dementia-free survival to age 80 years vs those without hypertension, across race and genetic risk groups.

DISCUSSION: Genetic risk for AD does not modify the association between hypertension and dementia. These data support the fact that all individuals with hypertension are likely to benefit from antihypertensive treatment.

PMID:42385118 | DOI:10.1212/WNL.0000000000218280