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Nevin Manimala Statistics

Connectivity patterns of the core resting-state networks associated with apathy in late-life depression

J Psychiatry Neurosci. 2023 Nov 1;48(6):E404-E413. doi: 10.1503/jpn.230008. Print 2023 Nov-Dec.

ABSTRACT

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD.

METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings.

RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network.

LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions.

CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

PMID:37914222 | DOI:10.1503/jpn.230008

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Nevin Manimala Statistics

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

Int J Radiat Oncol Biol Phys. 2023 Oct 30:S0360-3016(23)08025-2. doi: 10.1016/j.ijrobp.2023.10.025. Online ahead of print.

ABSTRACT

PURPOSE: The number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients.

METHODS: The XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine-Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs).

RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p<0.05) and a higher incidence of LRFs (SHR=1.54 [1.00-2.38], p=.05) compared with single-agent cisplatin, whereas OS (HR=1.15 [0.80-1.65], p=.46) was comparable. There were no oncological differences between single-agent and multi-agent cisplatin regimens (all p>.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009).

CONCLUSIONS: Single-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients.

TRIAL REGISTRATION: XXX.

PMID:37914144 | DOI:10.1016/j.ijrobp.2023.10.025

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Nevin Manimala Statistics

Searching a methods topic: practical challenges and implications for search design

J Clin Epidemiol. 2023 Oct 30:S0895-4356(23)00277-9. doi: 10.1016/j.jclinepi.2023.10.017. Online ahead of print.

ABSTRACT

Performing a systematic search of a methods topic (e.g., “risk of bias”, “subgroup analysis”) in biomedical databases such as MEDLINE or Embase can be challenging. In this commentary, we address common search-related challenges, including inconsistent terminology for methods and suboptimal indexing. We suggest that reviewers addressing methods topics, compared to clinical topics, may start with specific, methods-oriented journals; invest extra time to scrutinize index terms and identify alternative terms; try citation search and machine learning assisted screening; and anticipate lower sensitivity and precision.

PMID:37914105 | DOI:10.1016/j.jclinepi.2023.10.017

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Nevin Manimala Statistics

Examining the association between objective physical activity and momentary pain: a systematic review of studies using ambulatory assessment

J Pain. 2023 Oct 30:S1526-5900(23)00593-X. doi: 10.1016/j.jpain.2023.10.021. Online ahead of print.

ABSTRACT

Chronic pain (CP) is a debilitating and increasingly common health condition that adversely impacts function, including physical activity (PA). Research using ambulatory assessment (AA) methods (e.g., ecological momentary assessment, actigraphy) offers promise for elucidating the relationship between momentary pain and objective PA in CP populations. This study aimed to systematically review articles assessing the association between momentary pain and PA in adults with CP as measured using AA and to make recommendations for the measurement and study of this relationship. Five databases were systematically searched, and 13 unique records (N = 768) met inclusion criteria. CP conditions included mixed/nonspecific CP (k = 3), low back pain (k = 2), fibromyalgia (k = 1), unspecified arthritis (k =1), and hip/knee osteoarthritis (k = 6). Average age of participants across studies was 55.29 years and the majority identified as women (60.68%) and White (83.16%). All studies measured objective PA via actigraphy, and momentary pain with either a diary/log or ratings on an actigraph. Studies varied in quantification of PA (i.e., activity counts, step count, moderate-vigorous PA), statistical method (i.e., correlation, regression, multilevel modelling), and inclusion of moderators (e.g., pain acceptance). Studies reported mixed results for the pain-PA relationship. This heterogeneity suggests that no summarizing conclusions can be drawn about the pain-PA relationship without further investigation into its complex nuances. More within-person and exploratory examinations that maximize the richness of AA data are needed. Greater understanding of this relationship can inform psychotherapeutic and behavioral recommendations to improve CP outcomes. PROSPERO registration number: CRD42023389913. PERSPECTIVE: This article presents a systematic review of the literature on the association between momentary pain and physical activity in adults with chronic pain as measured using ambulatory assessment methods. Better understanding this nuanced relationship could help elucidate areas for timely intervention and may inform clinical recommendations to improve CP outcomes.

PMID:37914094 | DOI:10.1016/j.jpain.2023.10.021

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Nevin Manimala Statistics

The impact of sleep disturbances on endogenous pain modulation: a systematic review and meta-analysis

J Pain. 2023 Oct 30:S1526-5900(23)00596-5. doi: 10.1016/j.jpain.2023.10.023. Online ahead of print.

ABSTRACT

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep related outcomes (e.g., poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6151 references, and 37 studies met eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP:0.31 [95%CI:-0.30 to 0.92]; p=0.321; CPM:0.40 [95%CI:-0.06 to 0.85] p=0.088) nor in clinical populations when such association was assessed via correlation (TSP:-0.00 [95%CI:-0.22 to 0.21] p=0.970; CPM:0.12 [95%CI:-0.05 to 0.29]; p=0.181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI:0.98 to 1.88]; p<0.001) but not in males (-0.30 [95%CI:-2.69 to 1.60]; p=0.760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVES: This review shines light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

PMID:37914093 | DOI:10.1016/j.jpain.2023.10.023

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Nevin Manimala Statistics

Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy

Kidney Int. 2023 Oct 30:S0085-2538(23)00754-8. doi: 10.1016/j.kint.2023.09.027. Online ahead of print.

ABSTRACT

Targeting the alternative complement pathway is an attractive therapeutic strategy given its role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Iptacopan (LNP023) is an oral, proximal alternative complement inhibitor that specifically binds to Factor B. Our randomized, double-blind, parallel-group adaptive Phase 2 study (NCT03373461) enrolled patients with biopsy-confirmed IgAN (within previous three years) with estimated glomerular filtration rates of 30 mL/min/1.73 m2 and over and urine protein 0.75 g/24 hours and over on stable doses of renin angiotensin system inhibitors. Patients were randomized to four iptacopan doses (10, 50, 100, or 200 mg bid) or placebo for either a three-month (Part 1; 46 patients) or a six-month (Part 2; 66 patients) treatment period. The primary analysis evaluated the dose-response relationship of iptacopan versus placebo on 24-hour urine protein-to-creatinine ratio (UPCR) at three months. Other efficacy, safety and biomarker parameters were assessed. Baseline characteristics were generally well-balanced across treatment arms. There was a statistically significant dose-response effect, with 23% reduction in UPCR achieved with iptacopan 200 mg bid (80% confidence interval 8 -34%) at three months. UPCR decreased further through six months in iptacopan 100 and 200 mg arms (from a mean of 1.3 g/g at baseline to 0.8 g/g at six months in the 200 mg arm). A sustained reduction in complement biomarkers levels including plasma Bb, serum Wieslab, and urinary C5b-9 was observed. Iptacopan was well-tolerated, with no reports of deaths, treatment-related serious adverse events or bacterial infections, and led to strong inhibition of alternative complement pathway activity and persistent proteinuria reduction in patients with IgAN. Thus, our findings support further evaluation of iptacopan in the ongoing Phase 3 trial (APPLAUSE-IgAN; NCT04578834).

PMID:37914086 | DOI:10.1016/j.kint.2023.09.027

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Nevin Manimala Statistics

Multi-center multi-vendor evaluation of dose volume histogram creation consistencies for eight commercial radiotherapy dosimetric systems

Pract Radiat Oncol. 2023 Oct 30:S1879-8500(23)00290-4. doi: 10.1016/j.prro.2023.09.009. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate dose volume histogram (DVH) construction differences across eight major commercial treatment planning systems (TPSs) and dose reporting systems (DRSs) for clinically treated plans of various anatomical sites and target sizes.

MATERIALS AND METHODS: Dose files from ten selected clinically treated plans with a hypo-fractionation, stereotactic radiotherapy prescription or sharp dose gradients such as head and neck plans ranging from prescription doses of 18 Gy in 1 fraction to 70 Gy in 35 fractions, each calculated at 0.25 cm and 0.125 cm grid size, were created and anonymized in Eclipse TPS, and exported to seven other major TPS (Pinnacle, RayStation, Elements) and DRS (MIM, Mobius, ProKnow, and Velocity) systems for comparison. Dose-volume constraint points of clinical importance for each plan were collected from each evaluated system (D0.03cc[Gy], volume, and the mean dose were used for structures without specified constraints). Each reported constraint type and structure volume was normalized to the value from Eclipse for a pairwise comparison. A Wilcoxon Rank Sum test was used for statistical significance and a multivariable regression model was evaluated adjusting for plan, grid size, and distance to target center.

RESULTS: For all DVH points relative to Eclipse, all systems reported median values within 1.0% difference of each other, however they were all different from Eclipse. Considering mean values, Pinnacle, RayStation, and Elements averaged at 1.038, 1.046, 1.024 respectively, while MIM, Mobius, ProKnow, and Velocity reported 1.026, 1.050, 1.033 and 1.022 respectively relative to Eclipse. Smaller dose grid size improved agreement between the systems marginally without statistical significance. For structure volumes relative to Eclipse, larger differences are seen across all systems with a range in median values up to 3.0% difference and mean up to 10.1% difference.

CONCLUSION: Large variations were observed between all systems. Eclipse generally reported, at statistically significant levels, lower values than all other evaluated systems. The non-significant change resulting from lowering the dose grid resolution indicates that this resolution may be less important than other aspects of calculating DVH curves, such as the 3D modeling of the structure.

PMID:37914082 | DOI:10.1016/j.prro.2023.09.009

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Nevin Manimala Statistics

Bone flap resorption after cranioplasty: risk factors and proposal of the Flap Integrity Score

World Neurosurg. 2023 Oct 30:S1878-8750(23)01530-9. doi: 10.1016/j.wneu.2023.10.124. Online ahead of print.

ABSTRACT

BACKGROUND: Bone flap resorption is a known complication of post-decompressive autologous cranioplasty. Although several potential etiopathogenetic factors have been investigated, their role is still under discussion. To further complicate things, resorption is not an all-or-nothing event, patients frequently presenting with different degrees of flap remodeling. Focus of this paper was to describe the elaboration of a score quantifying bone resorption according to a set of clinical and radiological criteria, hopefully allowing prompt identification of patients needing re-surgery before the development of adverse events.

METHODS: In a 10-years-time, 281 autologous cranioplasties were performed at our Institution following decompressive craniectomy. Pertinent clinical and radiological information was registered. A set of 3 clinical and 3 radiological parameters was established to score the degree of resorption, identified under the acronym FIS (Flap Integrity Score). Three groups of patients emerged, respectively showing no (208), partial (32) and advanced (41) resorption.

RESULTS: An overall 14.6% incidence of advanced bone resorption was found in our series. Younger age, bone multifragmentation, higher post-cranioplasty GOS scores, < 2 cm distance of medial craniectomy border from the midline, and cause leading to decompressive craniectomy were associated to a statistically significant higher risk of developing a relevant bone flap resorption. The first three variables confirmed as risk factors at multivariate analysis. FIS well discriminated the 3 different groups.

CONCLUSIONS: Autologous bone repositioning is still a valuable, low-cost, cosmetically and functionally satisfactory procedure. Nonetheless, although resorption affects a minor percentage of patients, its early identification and treatment can improve long term results.

PMID:37914077 | DOI:10.1016/j.wneu.2023.10.124

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Nevin Manimala Statistics

Impact of Previous Open Abdominal Surgery on Open Abdominal Aortic Repair: A Study from the NSQIP Database

Ann Vasc Surg. 2023 Oct 30:S0890-5096(23)00723-9. doi: 10.1016/j.avsg.2023.09.066. Online ahead of print.

ABSTRACT

OBJECTIVE: While EVAR has become a first-line strategy in many centers, open repair (OSR) of abdominal aortic aneurysms (AAA) is still the best option for certain patients. A significant number of patients who are offered OSR for AAA have been previously submitted to other open abdominal surgeries (PAS). It is unclear, however, how this may impact their outcomes. The purpose of this study was to determine if there is an association between PAS and outcomes of OSR of AAA.

METHODS: This is a Retrospective cohort study, based on clinical data from the American College of Surgeons National Surgical Quality Improvement Program database (NSQIP), including all patients undergoing elective OSR for AAA between 2011-2017. Excluded were patients with missing data on prior abdominal surgery, supramesenteric clamping, or urgent repairs. Patients with prior abdominal surgery (PAS) and patients without prior abdominal surgeries (nonPAS) were compared. The primary outcome was 30-day postoperative mortality. Secondary outcomes were operating time, ischemic colitis, postoperative complications, and lengths of hospital stay.

RESULTS: Of the 2034 patients included, 27% had previous open abdominal surgery and 73% did not. Overall, the median age was 71[IQR 65-76], 72% of patients were male, 44% were smokers, and the average BMI was 27 kg/m2. Univariate analysis showed no difference in postoperative 30-day mortality (4.0% PAS vs 4.1% nonPAS, p=0.91) or overall postoperative complication rates (33% PAS vs 29% nonPAS, p=0.07). Previous open abdominal surgery was significantly associated with longer operating times (p=0.032) and an almost doubled rate of ischemic colitis (4.7% PAS vs 2.6% nonPAS, p=0.02). Postoperative ICU and hospitalization were also significantly longer in patients with prior abdominal surgery (p=.005 and p=.014, respectively). Finally, there were significantly less patients discharged home, as opposed to institutionalized care (75,7%PAS down from 82,4%nonPAS, p=0,001). Despite these initial univariate analysis results, on multivariate analysis PAS actually did not prove to be a statistically significant independent risk factor for 30-day mortality, ischemic colitis or longer operating times.

CONCLUSION: This study suggests that patients who have undergone PAS may have some disadvantages in OSR of AAA. However, these negative trends do not go so far as to statistically significantly identify PAS as an independent risk factor for 30day mortality, ischemic colitis, or longer operating times. As such, we suggest that a history of previous open abdominal surgery, in and of its own, should not exclude patients from consideration for open aortic abdominal aneurysm repair.

PMID:37914074 | DOI:10.1016/j.avsg.2023.09.066

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Accuracy of the PEARL-DGS Formula for Intraocular Lens Power Calculation in Post-Myopic Laser Refractive Corneal Surgery Eyes

Am J Ophthalmol. 2023 Oct 30:S0002-9394(23)00450-6. doi: 10.1016/j.ajo.2023.10.020. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the accuracy of the PEARL-DGS formula for intraocular lens (IOL) power calculation in post-myopic laser refractive corneal surgery eyes.

DESIGN: Retrospective case series METHODS: A total of 139 eyes of 139 patients (mean axial length: 27.4 ± 2.1 mm), who had prior myopic laser refractive corneal surgery and subsequent cataract surgery using Tecnis ZCB00 from March 2018 to February 2023 were included. Refractive outcomes of five formulas (Barrett True K, Haigis-L, Hoffer-QST, PEARL-DGS, and Shammas-PL) were evaluated. Prediction error was defined as the difference between the measured and predicted postoperative refractive spherical equivalent using the IOL power actually implanted. Mean prediction error (MPE), median absolute prediction error (MedAE), mean absolute prediction error were calculated.

RESULTS: Without constant optimization, the PEARL-DGS resulted in a MPE of +0.05 ± 0.65 D, while the other formulas resulted in myopic shifts. The MedAEs of the formulas were 0.39, 0.53, 0.65, 0.85, and 1.11 D for the PEARL-DGS, Hoffer-QST, Barrett True K, Shammas-PL, and Haigis-L, respectively, in order of magnitude (P < 0.05). With constant optimization, there were no statistically significant differences in the MedAEs among the five formulas (P = 0.388).

CONCLUSIONS: In comparison to other IOL formulas, the PEARL-DGS resulted in better refractive outcomes after cataract surgery in post-myopic laser refractive corneal surgery eyes without constant optimization. We suggest that PEARL-DGS be considered as the first choice for IOL power calculation in these eyes when the clinicians do not have their optimized constants.

PMID:37914063 | DOI:10.1016/j.ajo.2023.10.020