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Nevin Manimala Statistics

Design and statistics of pharmacokinetic drug-drug, herb-drug, and food-drug interaction studies in oncology patients

Biomed Pharmacother. 2023 May 10;163:114823. doi: 10.1016/j.biopha.2023.114823. Online ahead of print.

ABSTRACT

Polypharmacy is becoming increasingly prevalent in society. Patients with polypharmacy are at greater risk for drug-drug interactions, which can influence the efficacy of treatment. Especially, in oncology this is a concern since neoplasms are increasing prevalent with age, as well as polypharmacy is. Besides drug-drug interactions, also herb-drug and food-drug interactions could be present. Knowledge of these interactions is of great importance for safe and effective anti-cancer treatment, because the therapeutic window of most of these oncologic drugs are small. To study pharmacokinetic interaction effects, a cross-over pharmacokinetic study is a widely used, efficient and scientifically robust design. Yet, several aspects need to be considered when carrying out an interaction study. This includes the knowledge of the advantages and disadvantages of a cross-over design. Furthermore, determination of the end point and research question of interest, calculation of the required sample size, analysis of the generated data with a robust statistical plan and consideration of the logtransformation for some pharmacokinetic parameters are important aspects to consider. Even though some guidelines exist regarding these key issues, no clear overview exists. In this article an overview of these aspects is provided and their effect is discussed.

PMID:37172331 | DOI:10.1016/j.biopha.2023.114823

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Nevin Manimala Statistics

An Exploratory Study of the Effect of Tinnitus on Listening Effort Using EEG and Pupillometry

Otolaryngol Head Neck Surg. 2023 May 12. doi: 10.1002/ohn.367. Online ahead of print.

ABSTRACT

OBJECTIVE: Previous behavioral studies on listening effort in tinnitus patients did not consider extended high-frequency hearing thresholds and had conflicting results. This inconsistency may be related that listening effort is not evaluated by the central nervous system (CNS) and autonomic nervous system (ANS), which are directly related to tinnitus pathophysiology. This study matches hearing thresholds at all frequencies, including the extended high-frequency and reduces hearing loss to objectively evaluate listening effort over the CNS and ANS simultaneously in tinnitus patients.

STUDY DESIGN: Case-control study.

SETTING: University hospital.

METHODS: Sixteen chronic tinnitus patients and 23 matched healthy controls having normal pure-tone averages with symmetrical hearing thresholds were included. Subjects were evaluated with 0.125 to 20 kHz pure-tone audiometry, Montreal Cognitive Assessment Test (MoCA), Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), electroencephalography (EEG), and pupillometry.

RESULTS: Pupil dilation and EEG alpha band in the “coding” phase of the sentence presented in tinnitus patients was less than in the control group (p < .05). VAS score was higher in the tinnitus group (p < .01). Also, there was no statistically significant relationship between EEG and pupillometry components and THI or MoCA (p > .05).

CONCLUSION: This study suggests that tinnitus patients may need to make an extra effort to listen. Also, pupillometry may not be sufficiently reliable to assess listening effort in ANS-related pathologies. Considering the possible listening difficulties in tinnitus patients, reducing the listening difficulties, especially in noisy environments, can be added to the goals of tinnitus therapy protocols.

PMID:37172313 | DOI:10.1002/ohn.367

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Nevin Manimala Statistics

Effect of the Lacticaseibacillus paracasei JLM Strain Against Brucella abortus Strains in Ripened Cheese

Foodborne Pathog Dis. 2023 May;20(5):169-176. doi: 10.1089/fpd.2022.0063.

ABSTRACT

This study evaluated the antagonistic effect of the Lacticaseibacillus paracasei JLM strain isolated from aguamiel, against Brucella abortus RB51, S19, and 2308 strains, during the manufacture of soft-ripened cheese. First, the tolerance of Lc. paracasei JLM was tested with pH values and bile salt concentrations for 3 h to simulate digestive tract conditions. The antagonistic effect against B. abortus strains was evaluated through double-layer diffusion and agar well diffusion assays. In addition, the stability of the cell-free supernatant (CFS) was tested with the agar well diffusion method under different conditions of temperature, pH, and treatment with digestive enzymes. Finally, the antagonistic effect against B. abortus strains was observed during the manufacture of ripened cheese for 31 days at 4°C and 25°C using the Lc. paracasei JLM strain as starter culture. The results showed that the Lc. paracasei JLM strain remains viable after exposure to different pH values (from 3.00 to 7.00) and concentrations of bile salts (from 0.5% to 7%). Moreover, the results demonstrate that the growth of the three B. abortus strains was inhibited in both antagonism tests and that CFS maintained 86% activity after heat treatment at 100°C, 121°C, or enzymatic digestion (proteinase K, trypsin, chymotrypsin), but it was inactivated at pH levels above 6. Finally, Lc. paracasei JLM completely inhibited the growth of B. abortus in ripened cheese at 25°C from day 17 and showed greater inhibition on the B. abortus RB51 strain in the ripened cheese at 4°C, showing statistical differences for the B. abortus S19 and B. abortus 2308 strains. The current research concluded that the Lc. paracasei JLM strain has an antagonistic effect on B. abortus, enhancing the potential of its use in the future as a probiotic.

PMID:37172300 | DOI:10.1089/fpd.2022.0063

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Nevin Manimala Statistics

Direct Measurement of the Cosmic-Ray Helium Spectrum from 40 GeV to 250 TeV with the Calorimetric Electron Telescope on the International Space Station

Phys Rev Lett. 2023 Apr 28;130(17):171002. doi: 10.1103/PhysRevLett.130.171002.

ABSTRACT

We present the results of a direct measurement of the cosmic-ray helium spectrum with the CALET instrument in operation on the International Space Station since 2015. The observation period covered by this analysis spans from October 13, 2015, to April 30, 2022 (2392 days). The very wide dynamic range of CALET allowed for the collection of helium data over a large energy interval, from ∼40 GeV to ∼250 TeV, for the first time with a single instrument in low Earth orbit. The measured spectrum shows evidence of a deviation of the flux from a single power law by more than 8σ with a progressive spectral hardening from a few hundred GeV to a few tens of TeV. This result is consistent with the data reported by space instruments including PAMELA, AMS-02, and DAMPE and balloon instruments including CREAM. At higher energy we report the onset of a softening of the helium spectrum around 30 TeV (total kinetic energy). Though affected by large uncertainties in the highest energy bins, the observation of a flux reduction turns out to be consistent with the most recent results of DAMPE. A double broken power law is found to fit simultaneously both spectral features: the hardening (at lower energy) and the softening (at higher energy). A measurement of the proton to helium flux ratio in the energy range from 60 GeV/n to about 60 TeV/n is also presented, using the CALET proton flux recently updated with higher statistics.

PMID:37172251 | DOI:10.1103/PhysRevLett.130.171002

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Nevin Manimala Statistics

Neural Importance Sampling for Rapid and Reliable Gravitational-Wave Inference

Phys Rev Lett. 2023 Apr 28;130(17):171403. doi: 10.1103/PhysRevLett.130.171403.

ABSTRACT

We combine amortized neural posterior estimation with importance sampling for fast and accurate gravitational-wave inference. We first generate a rapid proposal for the Bayesian posterior using neural networks, and then attach importance weights based on the underlying likelihood and prior. This provides (1) a corrected posterior free from network inaccuracies, (2) a performance diagnostic (the sample efficiency) for assessing the proposal and identifying failure cases, and (3) an unbiased estimate of the Bayesian evidence. By establishing this independent verification and correction mechanism we address some of the most frequent criticisms against deep learning for scientific inference. We carry out a large study analyzing 42 binary black hole mergers observed by LIGO and Virgo with the SEOBNRv4PHM and IMRPhenomXPHM waveform models. This shows a median sample efficiency of ≈10% (2 orders of magnitude better than standard samplers) as well as a tenfold reduction in the statistical uncertainty in the log evidence. Given these advantages, we expect a significant impact on gravitational-wave inference, and for this approach to serve as a paradigm for harnessing deep learning methods in scientific applications.

PMID:37172245 | DOI:10.1103/PhysRevLett.130.171403

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Nevin Manimala Statistics

Diagnostic application of intraoral ultrasonography to assess furcation involvement in mandibular first molars

Dentomaxillofac Radiol. 2023 May 12:20230027. doi: 10.1259/dmfr.20230027. Online ahead of print.

ABSTRACT

OBJECTIVES: The objectives were to clarify if intraoral ultrasonography (USG) is: (1) more accurate than conventional periodontal examinations in detection of furcation involvement, and (2) comparable to conventional periodontal examinations in accurate horizontal classification of furcation involvement in comparison to cone beam computed tomography (CBCT).

METHODS: The buccal furcation in 61 lower first molars were evaluated with conventional periodontal examinations, intraoral USG and CBCT. The presence and classification of the horizontal depth of furcation involvement were defined clinically by assessment with a Nabers periodontal probe and a periapical radiograph with reference to the bone loss under the fornix. The horizontal depth of furcation involvement was measured in intraoral USG and CBCT images. Based on the measurements, presence diagnosis and horizontal classification were performed. Results from conventional periodontal examinationsand intraoral USG were compared with those from CBCT.

RESULTS: κ value (κ) for agreement of presence diagnosis of furcation involvement between intraoral USG and CBCT was 0.792, while agreement with conventional periodontal examinations was 0.225. Diagnostic accuracy of intraoral USG exhibited higher values (sensitivity: 98.3%, accuracy: 98.4 %) than conventional periodontal examinations (81.4% and 81.9 %). Weighted κ statistics showed substantial agreement in the classification between intraoral USG and CBCT (κ = 0.674). High agreement (ICC: 0.914) for the measurement of horizontal depth of furcation involvement was found between intraoral USG and CBCT.

CONCLUSIONS: Intraoral USG may be a reliable diagnostic tool for assessment of furcation involvement of mandibular molars with a similar performance to CBCT, but without ionizing radiation.

PMID:37172223 | DOI:10.1259/dmfr.20230027

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Nevin Manimala Statistics

Combining serum metabolomic profiles with traditional risk factors improves 10-year cardiovascular risk prediction in people with type 2 diabetes

Eur J Prev Cardiol. 2023 May 12:zwad160. doi: 10.1093/eurjpc/zwad160. Online ahead of print.

ABSTRACT

AIMS: To identify a group of metabolites associated with incident CVD in people with type 2 diabetes and assess its predictive performance over-and-above a current CVD risk score (QRISK3).

METHODS: A panel of 228 serum metabolites was measured at baseline in 1,066 individuals with type 2 diabetes (Edinburgh Type 2 Diabetes Study) who were then followed up for CVD over the subsequent 10 years. We applied 100 repeats of Cox LASSO (least absolute shrinkage and selection operator) to select metabolites with frequency >90% as components for a metabolites-based risk score (MRS). The predictive performance of the MRS was assessed in relation to a reference model which was based on QRISK3 plus prevalent CVD and statin use at baseline.

RESULTS: Of 1,021 available individuals, 255 (25.0%) developed CVD (median follow-up: 10.6 years). Twelve metabolites relating to fluid balance, ketone bodies, amino acids, fatty acids, glycolysis and lipoproteins were selected to construct the MRS which showed positive association with 10-year cardiovascular risk following adjustment for traditional risk factors [HR 2.67 (95%CI 1.96, 3.64)]. C-statistic was 0.709 (95%CI 0.679, 0.739) for the reference model alone, increasing slightly to 0.728 (95%CI 0.700, 0.757) following addition of the MRS. Compared with the reference model, the net reclassification index and integrated discrimination index for the reference model plus the MRS was 0.362 (95%CI 0.179, 0.506) and 0.041 (95%CI 0.020, 0.071), respectively.

CONCLUSIONS: Metabolomics data might improve predictive performance of current CVD risk scores based on traditional risk factors in people with type 2 diabetes. External validation is warranted to assess the generalizability of improved CVD risk prediction using the MRS.

PMID:37172216 | DOI:10.1093/eurjpc/zwad160

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Nevin Manimala Statistics

Mortality Risk of Hot Nights: A Nationwide Population-Based Retrospective Study in Japan

Environ Health Perspect. 2023 May;131(5):57005. doi: 10.1289/EHP11444. Epub 2023 May 12.

ABSTRACT

BACKGROUND: The health effects of heat are well documented; however, limited information is available regarding the health risks of hot nights. Hot nights have become more common, increasing at a faster rate than hot days, making it urgent to understand the characteristics of the hot night risk.

OBJECTIVES: We estimated the effects of hot nights on the cause- and location-specific mortality in a nationwide assessment over 43 y (1973-2015) using a unified analytical framework in the 47 prefectures of Japan.

METHODS: Hot nights were defined as days with a) minimum temperature 25°C (HN25) and b) minimum temperature 95th percentile (HN95th) for the prefecture. We conducted a time-series analysis using a two-stage approach during the hot night occurrence season (April-November). For each prefecture, we estimated associations between hot nights and mortality controlling for potential confounders including daily mean temperature. We then used a random-effects meta-analytic model to estimate the pooled cumulative association.

RESULTS: Overall, 24,721,226 deaths were included in this study. Nationally, all-cause mortality increased by 9%-10% [HN25 relative risk (RR)=1.09, 95% confidence interval (CI): 1.08, 1.10; HN95th RR=1.10, 95% CI: 1.09, 1.11] during hot nights in comparison with nonhot nights. All 11 cause-specific mortalities were strongly associated with hot nights, and the corresponding associations appeared to be acute and lasted a few weeks, depending on the cause of death. The strength of the association between hot nights and mortality varied among prefectures. We found a higher mortality risk from hot nights in early summer in comparison with the late summer in all regions.

CONCLUSIONS: Our findings support the evidence of mortality impacts from hot nights in excess of that explicable by daily mean temperature and have implications useful for establishing public health policy and research efforts estimating the health effects of climate change. https://doi.org/10.1289/EHP11444.

PMID:37172196 | DOI:10.1289/EHP11444

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Nevin Manimala Statistics

Impact of Professional Background on Inter-Annotator Variability and Accuracy During Annotation of Clinical Notes

Stud Health Technol Inform. 2023 May 2;301:248-253. doi: 10.3233/SHTI230048.

ABSTRACT

BACKGROUND: The aging population’s need for treatment of chronic diseases is exhibiting a marked increase in urgency, with heart failure being one of the most severe diseases in this regard. To improve outpatient care of these patients and reduce hospitalization rates, the telemedical disease management program HerzMobil was developed in the past.

OBJECTIVE: This work aims to analyze the inter-annotator variability among two professional groups (healthcare and engineering) involved in this program’s annotation process of free-text clinical notes using categories.

METHODS: A dataset of 1,300 text snippets was annotated by 13 annotators with different backgrounds. Inter-annotator variability and accuracy were evaluated using the F1-score and analyzed for differences between categories, annotators, and their professional backgrounds.

RESULTS: The results show a significant difference between note categories concerning inter-annotator variability (p<0.0001) and accuracy (p<0.0001). However, there was no statistically significant difference between the two annotator groups, neither concerning inter-annotator variability (p=0.15) nor accuracy (p=0.84).

CONCLUSION: Professional background had no significant impact on the annotation of free-text HerzMobil notes.

PMID:37172189 | DOI:10.3233/SHTI230048

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Nevin Manimala Statistics

ELGA Terminology Server for Clinical Decision Support: A Case-Study Using an Existing Knowledge Base, CDS Hooks and FHIR

Stud Health Technol Inform. 2023 May 2;301:125-130. doi: 10.3233/SHTI230025.

ABSTRACT

BACKGROUND: There are many medical knowledge bases with potential for supporting medical professionals in their decision-making during routine care, yet usage of these sources remains low. Standardized linking of Clinical Decision Support (CDS) applications and existing medical knowledge bases is not a common practice.

OBJECTIVES: Using existing eHealth standards to increase the utilization of knowledge bases and implement a prototype.

METHODS: Linking an existing online knowledge base via a FHIR CodeSystem supplement to the Austrian national EHR (ELGA) terminology server and accessing these data using CDS Hooks and FHIR.

RESULTS: We tested the approach by incorporating photosensitivity data of medications into a local copy of the Austrian terminology server. These data are directly used by a CDS Hooks compliant CDS service.

CONCLUSION: The Austrian Terminology Server could be an important interface to access existing knowledge bases from within EHR systems. FHIR and CDS Hooks could lead the way for a simple and open integration of CDS services into EHR systems.

PMID:37172166 | DOI:10.3233/SHTI230025