Tag: nevin manimala

BMJ Open Respir Res. 2023 Oct;10(1):e001643. doi: 10.1136/bmjresp-2023-001643.

ABSTRACT

INTRODUCTION: Several studies have reported that exposure to antibiotics can lead to asthma during early childhood. However, the association between antibiotic use and risk of asthma in the adult population remains unclear. This study aimed to investigate the association between antibiotic use and asthma in adults.

METHODS: We used data from the National Health Insurance Service (NHIS)-Health Screening Cohort, which included participants aged ≥40 years who had health screening examination data in 2005-2006. A total of 248 961 participants with a mean age of 55.43 years were enrolled in this retrospective cohort study. To evaluate antibiotic exposure from the NHIS database for 5 years (2002-2006), cumulative usage and multiclass prescriptions were identified, respectively. During the follow-up period (2007-2019), 42 452 patients were diagnosed with asthma. A multivariate Cox proportional hazard regression model was used to assess the association between antibiotic use and newly diagnosed asthma.

RESULTS: Participants with antibiotic use for ≥91 days showed a higher risk of asthma (adjusted HR (aHR) 1.84, 95% CI 1.72 to 1.96) compared with participants who did not use antibiotics (n=38 450), with a duration-dependent association (p_trend<0.001). Furthermore, ≥4 antibiotic class user group had an increased risk of asthma (aHR 1.44, 95% CI 1.39 to 1.49) compared with one class of antibiotic use (n=64 698). Also, one class of antibiotic use had a higher risk of asthma (aHR 1.21, 95% CI 1.17 to 1.26) compared with non-users, and it also showed a duration-dependent relationship in all classes, including 1, 2, 3 and ≥4 class group (p_trend<0.001). The duration-response relationship between antibiotic use and increased risk of asthma remained in our sensitivity analyses with the washout and shifting of the index date.

CONCLUSIONS: The duration-response pattern observed in antibiotic use and asthma may suggest the implication of proper antibiotic use and management in adults.

PMID:37914233 | DOI:10.1136/bmjresp-2023-001643

Dent Mater J. 2023 Oct 31. doi: 10.4012/dmj.2023-048. Online ahead of print.

ABSTRACT

This study aimed to assess the effect of different calcium silicate-based root canal sealers (CSRS) on osteogenic effect in human periodontal ligament cells (hPDLCs). hPDLCs were cultured in a medium containing extract of 5 types of CSRS. The specimens were assessed by the cell cytotoxicity test, alkaline phosphatase staining, alizarin red S staining, quantitative real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. The diluted concentrations of extracted solutions had no significant effect on the viability of hPDLCs. There was a statistically significant difference in the mRNA expression level of bone sialoprotein (BSP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) among some groups. The protein expressions of BSP, OCN, and RUNX2 were significantly higher in some groups compared to the control group. The CSRS did not interfere with the osteogenic differentiation of hPDLCs, compared to the control group. CSRS are shown to have biocompatibility and osteogenic differentiation effect on hPDLCs.

PMID:37914232 | DOI:10.4012/dmj.2023-048

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

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

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

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

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

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

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

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