Nevin Manimala

J Epidemiol Community Health. 2023 Nov 1:jech-2023-221147. doi: 10.1136/jech-2023-221147. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to investigate the association between childhood adversity and COVID-19-related hospitalisation and COVID-19-related mortality in the UK Biobank.

DESIGN: Cohort study.

SETTING: UK.

PARTICIPANTS: 151 200 participants in the UK Biobank cohort who had completed the Childhood Trauma Screen were alive at the start of the COVID-19 pandemic (January 2020) and were still active in the UK Biobank when hospitalisation and mortality data were most recently updated (November 2021).

MAIN OUTCOME MEASURES: COVID-19-related hospitalisation and COVID-19-related mortality.

RESULTS: Higher self-reports of childhood adversity were related to greater likelihood of COVID-19-related hospitalisation in all statistical models. In models adjusted for age, ethnicity and sex, childhood adversity was associated with an odds ratio (OR) of 1.227 of hospitalisation (95% CI 1.153 to 1.306, childhood adversity z=6.49, p<0.005) and an OR of 1.25 of a COVID-19-related death (95% CI 1.11 to 1.424, childhood adversity z=3.5, p<0.005). Adjustment for potential confounds attenuated these associations, although associations remained statistically significant.

CONCLUSIONS: Childhood adversity was significantly associated with COVID-19-related hospitalisation and COVID-19-related mortality after adjusting for sociodemographic and health confounders. Further research is needed to clarify the biological and psychosocial processes underlying these associations to inform public health intervention and prevention strategies to minimise COVID-19 disparities.

PMID:37914378 | DOI:10.1136/jech-2023-221147

Magn Reson Med Sci. 2023 Nov 2. doi: 10.2463/mrms.mp.2023-0074. Online ahead of print.

ABSTRACT

PURPOSE: Recently, the utility of non-contrast MR endolymphatic hydrops imaging was reported, but the pitfall was indicated based on T2 preparation pulse sensitiveness to local static magnetic field (B0) inhomogeneity. The purpose of this study is to clarify the effects of surrounding magnetic environment of temporal bone to lymphatic fluid signal intensity on the T2 preparation and fluid attenuated inversion recovery pulse combination (T2prep 3D-FLAIR) technique in human inner ear study.

METHODS: We prepared a custom-made phantom comprising a chicken leg bone submersed in saline. To evaluate signal characteristics of saline close to bone, multiple TE gradient echoes, T2 relaxation time measurement, and T2prep 3D-FLAIR image were acquired. In the vicinity of the vestibule of a healthy volunteer, similar examinations were executed. Additionally, to investigate the influence of the magnetic environment from B0, the evaluation was performed in five head position settings relative to B0.

RESULTS: In both the phantom case and volunteer case, together with T2 star signal intensity attenuation, T2 relaxation time shortening was observed on fluid around bone. Specifically, at the outer edge in the vestibule and cochlea of the volunteer, T2 relaxation time was shorter than that of center of vestibule and that of cochlea. In the T2prep 3D-FLAIR image, higher signal intensity was observed at the same location on the outer edge of them. These results showed that bone affects surrounding fluid magnetic environment. Also, for B0 influence, despite a large area variation ratio, there is no statistically significant difference correlated to orientation within B0.

CONCLUSION: The surrounding magnetic environment of the temporal bone affects lymphatic fluid signals of the peripheral part of the human inner ear on T2prep 3D-FLAIR technique.

PMID:37914371 | DOI:10.2463/mrms.mp.2023-0074

Biol Pharm Bull. 2023;46(11):1609-1618. doi: 10.1248/bpb.b23-00466.

ABSTRACT

The modified Cockcroft-Gault (CG) equation, previously developed for an aged-oriented cohort, was validated in a newly obtained dataset. Estimates of creatinine clearance (CCr) using this equation were found to be more accurate than those determined using the conventional CG equation, particularly for patients exceeding 65 years of age. We identified a subset of patients in this cohort whose estimates were inadequate. Using statistical analysis, we found that the deviation from estimates was attributed to a decreased albumin level. In addition, we determined a reduced albumin cutoff value for the modified CG equation to obtain a good estimate. Univariate linear regression analysis was applied to measure the CCr in this cohort and identify parameters related to body composition, and we found that extracellular water (ECW)/total body water (TBW) and body fat (%) were relevant. Using measured values of ECW/TBW and body fat (%), a multivariate linear regression (MLR) estimating equation was developed based on the modified CG equation. This equation was applied to a cohort over 65 years of age, and it was found that a good estimate was obtained for older patients with low albumin levels. Thus, we propose a flow diagram that illustrates conditions for selecting an appropriate estimating equation from among the CG, modified CG, and MLR equations.

PMID:37914363 | DOI:10.1248/bpb.b23-00466

BMJ Open. 2023 Nov 1;13(11):e073027. doi: 10.1136/bmjopen-2023-073027.

ABSTRACT

INTRODUCTION: In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data.

METHODS AND ANALYSIS: Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated.

ETHICS AND DISSEMINATION: Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.

PMID:37914306 | DOI:10.1136/bmjopen-2023-073027

Tohoku J Exp Med. 2023 Nov 2. doi: 10.1620/tjem.2023.J090. Online ahead of print.

NO ABSTRACT

PMID:37914284 | DOI:10.1620/tjem.2023.J090

Urol Pract. 2023 Nov 1:101097UPJ0000000000000489. doi: 10.1097/UPJ.0000000000000489. Online ahead of print.

ABSTRACT

PURPOSE: Current American Urological Association (AUA) guidelines mandate a risk-stratified approach for the evaluation of microhematuria. Urine genomic tests with high negative predictive value could further reduce unnecessary diagnostic testing and morbidity, but the economic impact is unknown. This study modeled the financial impact of Cxbladder Detect (Pacific Edge Diagnostics, Hummelstown, PA) on microhematuria evaluations.

MATERIALS AND METHODS: A decision tree analysis was constructed by Coreva Scientific (Königswinter, Germany) comparing one-year costs of the standard microhematuria evaluation using the AUA Guidelines versus an algorithm incorporating Cxbladder Detect. Cxbladder Detect positive patients had cystoscopy and imaging, whereas patients with negative tests were re-evaluated in 6 months. Patients with positive diagnostic testing underwent cystoscopy, and positive cystoscopies led to TURBT. Test performance was based on published literature and costs were based on Medicare allowable fees.

RESULTS: Using the decision tree model, the average savings of using Cxbladder Detect was $559 compared with the standard of care, with an average reduction of 0.38 procedures per patient. Probabilistic analysis showed statistical significance with a median reduction in the total cost of $498 per patient (95% CrI [-1,356, -2]) and a significant median reduction in diagnostic procedures per patient of 0.36 (95% CrI [-0.52, -0.16]) without impact on the number of cancers diagnosed.

CONCLUSIONS: This model-based study demonstrates the potential economic value of using a Cxbladder-driven protocol for microhematuria evaluations.

PMID:37914255 | DOI:10.1097/UPJ.0000000000000489

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