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Nevin Manimala Statistics

Large-scale survival analysis with a cure fraction

Biometrics. 2024 Oct 3;80(4):ujae138. doi: 10.1093/biomtc/ujae138.

ABSTRACT

With the advent of massive survival data with a cure fraction, large-scale regression for analyzing the effects of risk factors on a general population has become an emerging challenge. This article proposes a new probability-weighted method for estimation and inference for semiparametric cure regression models. We develop a flexible formulation of the mixture cure model consisting of the model-free incidence and the latency assumed by the semiparametric proportional hazards model. The susceptible probability assesses the concordance between the observations and the latency. With the susceptible probability as weight, we propose a weighted estimating equation method in a small-scale setting. Robust nonparametric estimation of the weight permits stable implementation of the estimation of regression parameters. A recursive probability-weighted estimation method based on data blocks with smaller sizes is further proposed, which achieves computational and memory efficiency in a large-scale or online setting. Asymptotic properties of the proposed estimators are established. We conduct simulation studies and a real data application to demonstrate the empirical performance of the proposed method.

PMID:39578979 | DOI:10.1093/biomtc/ujae138

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Nevin Manimala Statistics

An exploratory penalized regression to identify combined effects of temporal variables-application to agri-environmental issues

Biometrics. 2024 Oct 3;80(4):ujae134. doi: 10.1093/biomtc/ujae134.

ABSTRACT

The development of sensors is opening new avenues in several fields of activity. Concerning agricultural crops, complex combinations of agri-environmental dynamics, such as soil and climate variables, are now commonly recorded. These new kinds of measurements are an opportunity to improve knowledge of the drivers of crop yield and crop quality at harvest. This involves renewing statistical approaches to account for the combined variations of these dynamic variables, here considered as temporal variables. The objective of the paper is to estimate an interpretable model to study the influence of the two combined inputs on a scalar output. A Sparse and Structured Procedure is proposed to Identify Combined Effects of Formatted temporal Predictors, hereafter denoted S piceFP. The method is based on the transformation of both temporal variables into categorical variables by defining joint modalities, from which a collection of multiple regression models is then derived. The regressors are the frequencies associated with joint class intervals. The class intervals and related regression coefficients are determined using a generalized fused lasso. S piceFP is a generic and exploratory approach. The simulations we performed show that it is flexible enough to select the non-null or influential modalities of values. A motivating example for grape quality is presented.

PMID:39578978 | DOI:10.1093/biomtc/ujae134

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Nevin Manimala Statistics

Comparative Efficacy and Safety of Different Balloon Angioplasty Procedures for Infrapopliteal Artery Lesions in Chronic Limb-Threatening Ischemia Patients: A Systematic Review and Network Meta-Analysis

J Endovasc Ther. 2024 Nov 23:15266028241292954. doi: 10.1177/15266028241292954. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal endovascular method to treat infrapopliteal chronic limb-threatening ischemia (CLTI) remains to be determined, given the limitations of stent use in infrapopliteal artery disease. We performed a network meta-analysis (NWM) of randomized controlled trials (RCTs) to simultaneously compare the outcomes of different balloon angioplasty procedures for infrapopliteal artery lesions in CLTI patients.

METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, and PubMed. 8 eligible RCTs involving 3 endovascular modalities or combinations (plain old balloon angioplasty [POBA], drug-coated balloon [DCB], orbital atherectomy plus plain old balloon angioplasty [OA+POBA]) were included. Primary outcomes were efficacy (12-month clinically driven target lesion revascularization [CDTLR]) and safety (12-month major amputation and all-cause mortality). We used random-effects models based on the frequentist framework.

RESULTS: Plain old balloon angioplasty had a higher 12-month CDTLR rate than DCB (relative risk [RR]: 2.11, confidence interval [CI]: 1.33, 3.34) in the NWM and this result was still statistically significant (RR: 0.47, CI: 0.30, 0.75) in subgroup analyses. According to the SUCRA value, in terms of 12-month CDTLR, OA+POBA was considered the best treatment (SUCRA=72.2), while POBA was considered the worst treatment (SUCRA=8.9). In terms of 12-month all-cause mortality, OA+POBA was considered the best treatment (SUCRA=95.0), while DCB was considered the worst treatment (SUCRA=12.8). In terms of 12-month major amputation, POBA was considered the best treatment (SUCRA=72.0), while DCB was considered the worst treatment (SUCRA=23.0).

CONCLUSIONS: In infrapopliteal CLTI disease, DCB showed a significantly lower 12-month CDTLR in comparison to POBA. There is no statistically significant evidence to suggest that DCB raises safety concerns. The SUCRA values of OA+POBA indicate that it might offer a superior treatment option compared to DCB or POBA in terms of CDTLR and mortality. This advantage, however, was not sustained when major-amputation rates were analyzed. Consequently, further RCTs are required to examine the potential benefits of OA and other forms of atherectomy for managing infrapopliteal CLTI disease.

CLINICAL IMPACT: The findings of this study provide further evidence for the safety of DCB in the application of infrapopliteal CLTI disease and suggest preliminary benefits of atherectomy. These results are likely to encourage further research and application of these treatment modalities in managing infrapopliteal CLTI.POBA has been a traditional approach for treating infrapopliteal artery disease. The current evidence supports clinicians in exploring and utilizing DCB and atherectomy as better treatments.We focused on the performance of different balloon angioplasty procedures in infrapopliteal CLTI, considering the characteristics of infrapopliteal CLTI.

PMID:39578965 | DOI:10.1177/15266028241292954

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Nevin Manimala Statistics

From data collection to downstream data use: Malaysia’s experience with ICD-11

Health Inf Manag. 2024 Nov 23:18333583241295717. doi: 10.1177/18333583241295717. Online ahead of print.

ABSTRACT

BACKGROUND: The transition of systems to the International Statistical Classification of Diseases 11th Version (ICD-11) allows access to comprehensive data that accurately portray the complexity of morbidity and mortality data in Malaysia.

OBJECTIVE: To demonstrate Malaysia’s experience in implementing ICD-11, from data collection to downstream data use applications.

METHOD AND IMPLEMENTATION: We describe improvements to existing data source systems and downstream data applications. For non-HIS and HIS (ICD-10) systems, data were manually entered into the health management information system equipped with ICD-11 or automatically mapped from ICD-10 to ICD-11. Following these system improvements, we collected and reported ICD-11 data from all hospitals nationwide, regardless of the individual systems’ status in ICD-11 use.

DISCUSSION: Lessons learnt related to legacy systems; ICD-11 releases and system updates; mapping; reporting; human resources and related applications.

CONCLUSION: With careful planning, standardisation of the collection and use of ICD-11 data can be accomplished with limited resources and in a complex environment with heterogeneous systems.

IMPLICATIONS: Use of ICD-11 data in downstream data applications improves data quality to answer specific business or research questions.

PMID:39578964 | DOI:10.1177/18333583241295717

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Nevin Manimala Statistics

Skeletal Muscle Index Changes on Locoregional Treatment Application After FOLFIRINOX and Survival in Pancreatic Cancer

J Cachexia Sarcopenia Muscle. 2024 Nov 23. doi: 10.1002/jcsm.13643. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) require complex management strategies. This study evaluated the prognostic significance of the perichemotherapy skeletal muscle index (SMI) and carbohydrate antigen 19-9 (CA 19-9) in patients with BRPC or LAPC treated with FOLFIRINOX.

METHODS: We retrospectively evaluated 227 patients with BR or LAPC who received at least four cycles of chemotherapy between 2015 and 2020. We analysed chemotherapy response, changes in SMI (ΔSMI, %) on computed tomography (CT) and CA19-9 to determine their impact on progression-free survival (PFS) and overall survival (OS). After the early application of loco-regional treatments (LRT) within 3 months after completing four cycles of chemotherapy, the outcomes were compared between ΔSMI and CA19-9 subgroups.

RESULTS: Among 227 patients (median age, 60 years; 124 [54.6%] male) with 97 BR and 130 LAPC, 50.7% showed partial response (PR) to chemotherapy, 44.5% showed stable disease and 4.8% showed progressive disease (PD). Post-chemotherapy CA19-9 levels were normalized in 41.0% of patients. The high and low ΔSMI groups (based on the gender-specific cut-off of -8.6% for males and -2.9% for females) comprised 114 (50.2%) and 113 (49.8%) patients, respectively. The high ΔSMI group had poorer survival rates than the low ΔSMI group in both PFS (HR = 1.32, p = 0.05) and OS (HR = 1.74, p = 0.001). Multivariable analysis showed that ΔSMI (high vs. low; PFS, HR = 1.39, p = 0.03; OS, HR = 1.82, p < 0.001) and post-chemotherapy response (PD vs. PR/SD; PFS, HR = 18.69, p < 0.001; OS, HR = 6.19, p < 0.001) were independently associated with both PFS and OS. Additionally, the post-chemotherapy CA19-9 (≥ 37 vs. < 37; HR = 1.48, p = 0.01) was an independent predictor for PFS. Early application of LRT after chemotherapy significantly improved PFS and OS in both ΔSMI groups (all p < 0.05). However, it was not beneficial in the group with high ΔSMI and post-chemotherapy CA19-9 ≥ 37 (PFS, p = 0.39 and OS, p = 0.33).

CONCLUSIONS: Progressive sarcopenic deterioration after four cycles of chemotherapy was associated with poor survival outcomes in patients with BR or LAPC after FOLFIRINOX. We also investigated the optimal clinical setting for the early application LRTs using the ΔSMI and post-chemotherapy CA 19-9.

PMID:39578950 | DOI:10.1002/jcsm.13643

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Nevin Manimala Statistics

Gamma-delta T Cells in Bladder Cancer Draining Lymph Nodes

Iran J Immunol. 2024 Nov 23;21(4). doi: 10.22034/iji.2024.103549.2846. Online ahead of print.

ABSTRACT

BACKGROUND: Gamma-delta (γδ) T cells are a distinct subset of T cells with a receptor composed of γ and δ chains. Their ability to directly recognize stress-induced molecules and non-peptide antigens expressed by cancer cells, along with their capacity to produce cytokines and interact with other immune cells, makes them potentially significant contributors to immune-based treatments.

OBJECTIVE: To investigate the presence and frequency of Tγδ cells in tumor-draining lymph nodes of patients with bladder cancer (BC), and to assess their association with prognostic parameters.

METHODS: Forty-nine fresh tumor-draining lymph nodes from untreated patients with BC were minced to obtain single cells. The cells were surface-stained with anti-CD3, anti-TCRγδ, and anti-HLA-DR antibodies, then acquired on a four-color FACSCalibur flow cytometer, and analyzed by FlowJo software.

RESULTS: On average, 2.07% ± 1.99% of CD3+ lymphocytes in regional nodes of BC exhibited a γδ T phenotype. A considerable percentage of these cells (37.90% ± 24.42%) expressed HLA-DR. Statistical analysis revealed that while the frequency of γδ T cells showed no variation among patients with different prognoses, the HLA-DR+ subset was higher in T4 patients than in T2 patients (p=0.031). These cells also tended to be increased in stage III compared to stage II (p=0.077).

CONCLUSION: The data collectively indicated an association of HLA-DR expressing γδ T cells with prognostic factors related to tumor progression (higher T-group and stage), suggesting their potential involvement in disease progression. However, future research, including longitudinal studies with larger cohorts, needs to validate these findings and elucidate the functional roles of γδ T cells in the immune response against BC.

PMID:39578946 | DOI:10.22034/iji.2024.103549.2846

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Nevin Manimala Statistics

Prospective Clinical Study on the Accuracy of Static Computer-Assisted Implant Surgery in Patients With Distal Free-End Implants. Conventional Versus CAD-CAM Surgical Guides

Clin Oral Implants Res. 2024 Nov 23. doi: 10.1111/clr.14384. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the accuracy of CAD-CAM and conventional guides in the static computer-assisted implant surgery (sCAIS) placement of distal free-end implants.

MATERIAL AND METHODS: A prospective, controlled, and blinded quasi-experimental study was done involving 27 patients (76 implants) distributed into two groups according to the surgical guide manufacturing approach used: conventional (control group [CG]) or CAD-CAM (test group [TG]). The implants were planned in the software and the surgical guides were manufactured. Fully guided implant placement was carried out and the deviations were measured along with secondary variables as potential confounding factors. Descriptive analyses were performed on mean, standard deviation (SD), and interquartile range (IQR). In the comparative/inferential analysis hypothesis, contrasts were made of the quantitative and qualitative variables and multiple linear models were generated to adjust for the different confounding variables recorded.

RESULTS: Coronal horizontal deviation (CHD) was significantly greater in CG (1.52 mm) versus TG (1.04 mm) (p = 0.004). Apical horizontal deviation (AHD) in turn was 1.67 versus 1.46 mm, respectively; angular deviation was 2.87 versus 3.64; and vertical deviation was -0.1 versus -0.05 mm, with no significant differences between the groups (p > 0.05). A greater sleeve height, positioning in premolars versus molars, and the use of shorter implants, were associated with greater accuracy in relation to CHD and/or AHD (p < 0.05). The implant success rate at 1 year was 92.1%, 90.7% in TG, and 100% in CG, being statistically significant (p = 0.026) at the implant level, but not significant at the patient level.

CONCLUSIONS: The CAD-CAM surgical guides proved to be more accurate than the conventional guides in the sCAIS placement of distal free-end implants, with statistically significant differences being observed in terms of CHD. All implant failures occurred in TG (6 implants/3 patients).

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06404385.

PMID:39578942 | DOI:10.1111/clr.14384

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Nevin Manimala Statistics

Retinal and choroidal microvascular assessment of children receiving recombinant growth hormone therapy : Study design: a prospective observational comparative study

Int J Retina Vitreous. 2024 Nov 22;10(1):90. doi: 10.1186/s40942-024-00610-z.

ABSTRACT

BACKGROUND: The purpose of this study is to evaluate the retinal and choroidal microvascular state in children with congenital isolated growth hormone deficiency (IGHD) and determine the effect of recombinant human growth hormone treatment on these structures compared with healthy controls.

METHODS: The study included children with IGHD under recombinant human GH treatment as group one and another group of healthy controls. Both groups were examined using optical coherence tomography angiography (OCTA). Data concerning superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and retinal thickness were recorded.

RESULTS: The study included two equal groups of 30 individuals. Both groups had no statistically significant differences in age, gender, weight, or spherical equivalent. However, subjects of group II were taller than those of group I (p = 0.011). OCTA images of the SCP, DCP, and CC vessel density revealed statistically non-significant differences between the two groups.

CONCLUSION: Children receiving recombinant growth hormone therapy showed no changes in the retinal and choroidal microvasculature or macular thickness.

TRIAL REGISTRATION NUMBER: 1094/03/2024 by Minia University Faculty of Medicine Institutional Review Board. Another registration number is UMIN000055654.

PMID:39578934 | DOI:10.1186/s40942-024-00610-z

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Nevin Manimala Statistics

Fractures in Oxford unicompartmental knee arthroplasty are associated with a decreased medial keel-cortex distance of the tibial implant

Knee Surg Relat Res. 2024 Nov 22;36(1):36. doi: 10.1186/s43019-024-00237-2.

ABSTRACT

PURPOSE: This retrospective single-center study aimed to investigate incidence and risk factors influencing tibial periprosthetic fractures (TPF) in Oxford unicompartmental knee arthroplasty (UKA), with a specific focus on tibial component positioning and sizing.

METHODS: A total of 2063 patients with medial UKA using the Oxford® mobile partial knee implant were analyzed between July 2014 and September 2022. Various preoperative and postoperative radiographic parameters determining pre- and postoperative alignment and implant positioning, incidence and characteristics of periprosthetic fractures, and patient demographics were assessed. Statistical analyses, including Mann-Whitney U test and logistic regression, were conducted to identify significant associations and predictors of tibial fractures.

RESULTS: Of the 1853 cases that were finally included in the study, 19 (1%) patients experienced TPF. The fracture group presented with a significantly shorter relative mediolateral and posteroanterior distance between the keel and cortex [mediolateral: 23.3% (23.2-24.8%) versus 27.1% (25.7-28.3%), p < 0.001; posteroanterior: 8.4% (6.3-10.3%) versus 10.0% (9.8-10.1%), p = 0.004]. Additionally, an increased posterior tibial slope in pre- and postoperative radiographs [preoperative: 10.4° (8.6-11.1°) versus 7.7° (5.4-10.0°), p < 0.001; postoperative 9.1° ± 3.1° versus 7.5° (5.9-9.0°), p = 0.030] was observed in the fracture group. Furthermore, the use of smaller-sized implants (AA) was associated with higher fracture rates (p < 0.001). Anatomical variants, such as a medial overhanging tibial plateau, were not observed.

CONCLUSIONS: In UKA, type Oxford TPF are linked to shorter mediolateral and posteroanterior keel-cortex distances, increased pre- and postoperative PTS, and small implant sizes (AA). Fracture lines often extend from the distal keel to the medial tibial cortex. These findings emphasize the importance of precise implant positioning and sizing to minimize fracture risk. Level of evidence Retrospective single-center study, III.

PMID:39578924 | DOI:10.1186/s43019-024-00237-2

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Nevin Manimala Statistics

Cycling sensitivity across migraine phases: A longitudinal case-control study

Eur J Pain. 2024 Nov 23. doi: 10.1002/ejp.4761. Online ahead of print.

ABSTRACT

BACKGROUND: Functional neuroimaging studies indicate that central transmission of trigeminal pain may commence up to 48 h prior to the onset of headache. Whether these cyclic changes are associated with somatosensory alteration remains incompletely understood.

METHODS: The present study aimed to investigate the temporal progression of somatosensory alterations preceding the onset of a migraine attack. Patients with menstrually related migraine (n = 10) and matched healthy controls (n = 13) underwent consecutive daily quantitative sensory tests, commencing 6 days prior to the expected onset of the migraine attack and menstruation. Each subject was investigated for 7-11 consecutive days, resulting in 85 and 91 days of experimentation for the respective cohorts.

RESULTS: Electrical/heat/cold pain thresholds showed a phase-dependent decline towards the spontaneous migraine attack, which had commenced 48 h prior to the onset of the headache. The pain thresholds further declined towards the ictal phase, with only the electrical pain threshold reaching statistical significance (ictal vs. preictal). In healthy controls, the pain thresholds remained stable and unaltered during the consecutive daily measurements. In an exploratory analysis, the pain thresholds at baseline (interictal phase) were comparable between both cohorts.

CONCLUSIONS: The data suggest the existence of a trigeminal somatosensory alteration in the preictal phase of migraine, occurring up to 48 h prior to the onset of the headache. This change occurred in a chronologically synchronous manner with the brain activation in the preictal phase in functional neuroimaging studies. It will be important to combine pain threshold measurement and functional neuroimaging in future studies.

SIGNIFICANCE: Our data suggest the existence of a somatosensory behavioural correlate of the functional neuroimaging changes starting 48 h before the onset of headache. Despite the concurrence of the behavioural and functional neuroimaging changes in a chronological sequence, the next step in elucidating the cause of migraine is to combine the behavioural and functional neuroimaging changes in a temporal sequence, i.e. to identify the generator behind the cyclic sensory fluctuation.

PMID:39578922 | DOI:10.1002/ejp.4761