Tag: pubmed

Int J Pharm. 2023 Jun 24:123178. doi: 10.1016/j.ijpharm.2023.123178. Online ahead of print.

ABSTRACT

Implementation of the design space (DS) is a scientific concept for ensuring quality to be submitted as a part of the regulatory filing of a drug product for approval to market. An empirical approach is constructing the DS based on the regression model whose inputs are process parameters and material attributes over the different unit operations, i.e., a high-dimensional statistical model. While the high-dimensional model assures quality and process flexibility through a comprehensive process understanding, it has difficulty visualizing the feasible range of input parameters, i.e., DS. Therefore, this study proposes a greedy approach to constructing the extensive and flexible low-dimensional DS based on the high-dimensional statistical model and the observed internal representations that satisfies both comprehensive process understanding and the DS visualization capability. Introducing the observed correlation structure enabled the dimensionality reduction of the DS. The non-critical controllable parameters were fixed to the target values in visualizing the low-dimensional DS as a function of critical parameters. The expected variation of non-critical non-controllable parameters was considered the source of variation in prediction. The case study demonstrated the proposed approach’s usefulness for developing the pharmaceutical manufacturing process.

PMID:37364782 | DOI:10.1016/j.ijpharm.2023.123178

Int J Cardiol. 2023 Jun 24:131144. doi: 10.1016/j.ijcard.2023.131144. Online ahead of print.

ABSTRACT

BACKGROUND: Septic patients are predisposed to myocardial injury manifested as cardiac troponin release (TnR). Prognostic significance and management implications of TnR and its relationship to fluid resuscitation and outcomes in the intensive care unit (ICU) setting has not been fully elucidated.

METHODS: A total of 24,778 patients with sepsis from eICU-CRD, MIMIC-III and MIMIC-IV databases were included in this retrospective study. In-hospital mortality and one-year survival were examined using multivariable regression analysis and Kaplan-Meier survival analysis with overlap weighting adjustment, as well as generalized additive models for fluid resuscitation. Results TnR on admission was associated with higher in-hospital mortality [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.23-1.43; p < 0.001 in unweighted analysis and adjusted OR = 1.39; 95% CI = 1.29-1.50; P < 0.001 with overlap weighting]. One-year mortality was higher in patients with admission TnR (P = 0.002). A trend was noted for association between admission TnR and 1-year mortality [adjusted OR = 1.16; 95% CI = 0.99-1.37; P = 0.067 in unweighted analysis] while the association was statistically significant after overlap weighting (adjusted OR = 1.25; 95% CI = 1.06-1.47; P = 0.008). Patients with admission TnR were less likely to benefit from more liberal fluid resuscitation. Adequate fluid resuscitation (80 ml/kg in the first 24 h of ICU stay) was associated with lower in-hospital mortality in septic patients without TnR but not in those with admission TnR.

CONCLUSIONS: Admission TnR is significantly associated with higher in-hospital mortality and 1-year mortality among septic patients. Adequate fluid resuscitation improves in-hospital mortality in septic patients without but not with admission TnR.

PMID:37364714 | DOI:10.1016/j.ijcard.2023.131144

J Affect Disord. 2023 Jun 24:S0165-0327(23)00815-7. doi: 10.1016/j.jad.2023.06.049. Online ahead of print.

NO ABSTRACT

PMID:37364656 | DOI:10.1016/j.jad.2023.06.049

Int J Sports Med. 2023 Jun 26. doi: 10.1055/a-2117-9490. Online ahead of print.

ABSTRACT

The aim of the present study is to determine the associations between lower-extremity muscle strength qualities and change of direction (CoD) performance. Three databases were used to perform a systematic literature search, and up to September 30 2022. From the studies that met the inclusion criteria, the Pearson’s r correlation coefficient to examine relationships muscle strength qualities and COD performance was extracted. The quality of included studies was evaluated by the modified version of the Downs and Black Quality Index tool. Heterogeneity was testified via the Q statistic and I2, and Egger’s test was used to assess small study bias. The results revealed that lower-extremity maximal strength (pooled: r=-0.54, dynamic: r=-0.60, static: r=-0.41), joint strength (pooled: r=-0.59, EXT-ecc: r=-0.63, FLEX-ecc: r=-0.59), reactive strength (r=-0.42) and power (pooled: r=-0.45, jump height: r=-0.41, jump distance: r=-0.60, peak power: r=-0.41) were negatively and moderately related to CoD performance. To conclude, the results highlight that a number of muscle strength qualities are associated with CoD performance, that are pertinent to specific phases of a directional change. It should be noted that the conclusions of this study do not establish causality and further research is needed to better understand their training effects and underlying mechanisms.

PMID:37364608 | DOI:10.1055/a-2117-9490

Laryngorhinootologie. 2023 Jun 26. doi: 10.1055/a-2077-8619. Online ahead of print.

ABSTRACT

One aim of our large-scale catamnesis was to prove that neuro-otological diagnostics and knowledge are a fundamental prerequisite in counseling, but also that the counterpart, the patient, has to be reached in his or her distress. For this purpose, we had developed an own 6-part scaled questionnaire on the understanding of the counseled and on the feeling of being understood as a patient. Through its evaluation we had hoped to obtain reliable findings with regard to individual effect factors.Therefore we had mailed to 699 outpatients who had been counseled by us. In 295, the hearing findings, the Mini-Tinnitus Questionnaire (TF 12) and the Hospitality Anxiety and Depression Scores (HADS) could be compared at two measurement points at least 6 months apart.While counseling was found to be sustainable in symptom reduction and compliance to implement recommended interventions, no significant single interactional factor in counseling was detected by our examiation after proper statistics were obtained.In the article, the steps taken and corrections made are also pointed out with regard to the appropriate statistical approach, also to point out that primarily clinicians often need the support of trained statisticians.

PMID:37364602 | DOI:10.1055/a-2077-8619

Homeopathy. 2023 Jun 26. doi: 10.1055/s-0043-1769506. Online ahead of print.

ABSTRACT

BACKGROUND: Pre-diabetes (PD) contributes importantly to the disease burden worldwide and is a precursor to stroke, cardiovascular diseases, as well as type-2 diabetes mellitus.

OBJECTIVE: In this project, the efficacy of individualized homeopathic medicines (IHMs) was explored against placebos in the treatment of PD.

METHODS: A 6-month, double-blind, randomized, placebo-controlled trial was conducted at the outpatient departments of a homeopathic medical college and hospital in India. Sixty participants with PD were randomized to receive either IHMs (n = 30) or identical-looking placebos (n = 30). Concomitant care measures were advised to both groups of participants in terms of dietary advice, yoga, meditation and exercise. The primary outcome measures were fasting blood sugar (FBS) and the oral glucose tolerance test (OGTT); the secondary outcome was the Diabetes Symptom Checklist-Revised (DSC-R) score. All the outcomes were measured at baseline and after 3 and 6 months of treatment. Inter-group differences and effect sizes (Cohen’s d) were calculated using two-way repeated measures analysis of variance models after adjusting baseline differences using analysis of co-variance on the intention-to-treat data.

RESULTS: Between-group differences in FBS were statistically significant, favored IHMs against placebos (F _1,58 = 7.798, p = 0.007) but not for OGTT (F _1,58 = 1.691, p = 0.199). The secondary outcome, DSC-R total score, favoring IHMs significantly compared with placebos (F _1,58 = 15.752, p < 0.001). Calcarea Carbonicum, Thuja occidentalis and Sulphur were the most frequently prescribed medicines. No harm or serious adverse events were recorded from either of the participant groups.

CONCLUSION: IHMs produced significantly better results than placebos in FBS and in DSC-R scores but not in OGTT. Independent replications with larger sample sizes are warranted to substantiate the findings.

TRIAL REGISTRATION: CTRI/2019/10/021711.

PMID:37364594 | DOI:10.1055/s-0043-1769506

Int J Food Microbiol. 2023 Jun 22;402:110301. doi: 10.1016/j.ijfoodmicro.2023.110301. Online ahead of print.

ABSTRACT

The removal of C. difficile inoculated on fresh spinach leaves washed with antimicrobial solutions was investigated. In addition, the effect of washing solutions on the total aerobic mesophilic bacteria (TAMB) and Enterobacteriaceae in the fresh spinach was examined. The fresh spinach was washed through immersion in different concentrations (MIC, 2xMIC, and 4xMIC) of the natural disinfectant solution (NDS) consisting of EDTA, borax, and epigallocatechin gallate (EGCG) content developed in our laboratory and green tea extract-acetic acid (GTE-AA) for varying contact times (5 and 15 min). Different concentrations (50, 100, and 200 ppm) of sodium hypochlorite (NaOCl) and tap water as the control group were used to compare the effectiveness of the NDS. In addition, the effects of washing on the color, texture, and total phenol content of the spinach were determined. No statistical difference was observed in the washing of the spinach leaves with NDS prepared at 2xMIC and 4xMIC concentrations, while inhibition of C. difficile ranged between 2.11 and 2.32 logs. The highest inhibition was observed in the application of 50 ppm NaOCl for 15 min with a decrease of 2.88 logs in C. difficile spores. The GTE-AA and NDS decreased the number of TAMB by 2.27-3.08 log and, 3.21-3.66 log, respectively. Washing spinach leaves with natural disinfectant for 5 min caused a decrease of 2.58 logs in Enterobacteriaceae load, while washing with 50 ppm NaOCl for 15 min reduced Enterobacteriaceae load by 4 logs. Tap water was ineffective in reducing any microbial load. No difference was detected in the color parameters of the spinach through all washes. Although all antimicrobial washes made a difference in the texture of the spinach, the greatest loss in firmness was observed in the spinach washed with NaOCl. Washing spinach with epigallocatechin-based wash solutions can remove C. difficile in possible C. difficile contamination, thereby reducing the environmental load of C. difficile. Epigallocatechin-based disinfectants can be an alternative to chlorine-based disinfectants in improving the microbial quality of vegetables.

PMID:37364320 | DOI:10.1016/j.ijfoodmicro.2023.110301

Food Chem. 2023 Jun 20;427:136655. doi: 10.1016/j.foodchem.2023.136655. Online ahead of print.

ABSTRACT

Coffee is a relevant source of dietary exposure for neoformed furan, alkyl furans and acrylamide. In this study, different statistical methods (hierarchical cluster analysis, correlation analysis, partial least squares regression analysis) were used for characterizing the formation of these process contaminants in green coffee beans roasted under the same standardized conditions. The results displayed a strong correlation between sucrose levels and furans in relation to the other sugars analyzed, while acrylamide formation was strongly related to the free asparagine. The data suggest that a sufficiently large amino acid pool in green coffee favors Maillard-induced acrylamide formation from asparagine, while reactions amongst the carbonyl-containing sugar fragmentation products leading to furan formation are suppressed. If the pool of free amino acids is small, it is depleted faster during roasting, thus favoring the formation of furans by caramelization, basically a sugar degradation process in which reactive carbonyl substances are generated and react together.

PMID:37364312 | DOI:10.1016/j.foodchem.2023.136655

Environ Int. 2023 Jun 24;178:108064. doi: 10.1016/j.envint.2023.108064. Online ahead of print.

ABSTRACT

INTRODUCTION: Native American communities suffer disproportionately from elevated metal exposures and increased risk for cardiovascular diseases and diabetes. DNA methylation is a sensitive biomarker of aging-related processes and novel epigenetic-based “clocks” can be used to estimate accelerated biological aging that may underlie increased risk. Metals alter DNA methylation, yet little is known about their individual and combined impact on epigenetic age acceleration. Our objective was to investigate the associations of metals on several DNA methylation-based aging measures in the Strong Heart Study (SHS) cohort.

METHODS: Blood DNA methylation data from 2,301 SHS participants was used to calculate age acceleration of epigenetic clocks (PhenoAge, GrimAge, DunedinPACE, Hannum, Horvath). Urinary metals [arsenic (As), cadmium (Cd), tungsten (W), zinc (Zn), selenium (Se), molybdenum (Mo)] were creatinine-adjusted and categorized into quartiles. We examined associations of individual metals through linear regression models and used Bayesian Kernel Machine Regression (BKMR) for the impact of the total metal mixture on epigenetic age acceleration.

RESULTS: The mixture of nonessential metals (W, As, Cd) was associated with greater GrimAge acceleration and DunedinPACE, while the essential metal mixture (Se, Zn, Mo) was associated with lower epigenetic age acceleration. Cd was associated with increased epigenetic age acceleration across all clocks and BKMR analysis suggested nonlinear associations between Se and DunedinPACE, GrimAge, and PhenoAge acceleration. No interactions between individual metals were observed. The associations between Cd, Zn, and epigenetic age acceleration were greater in never smokers in comparison to current/former smokers.

CONCLUSION: Nonessential metals were positively associated with greater epigenetic age acceleration, with strongest associations observed between Cd and DunedinPACE and GrimAge acceleration. In contrast, essential metals were associated with lower epigenetic aging. Examining the influence of metal mixtures on epigenetic age acceleration can provide insight into metals and aging-related diseases.

PMID:37364305 | DOI:10.1016/j.envint.2023.108064

Anesthesiology. 2023 Jun 26. doi: 10.1097/ALN.0000000000004667. Online ahead of print.

ABSTRACT

BACKGROUND: The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty (TKA) is unclear. We conducted this network meta-analysis to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, following TKA.

METHODS: Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection iPACK to LIA for TKA were considered. The two primary outcomes were area under the curve (AUC) pain scores and postoperative function over 24-48 hours. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 hours, opioid consumption (0-24- and 25-48-hours), and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach.

RESULTS: Twenty-seven studies (2,317 patients) investigating the addition of i) single-injection ACB, ii) continuous ACB, iii) single-injection ACB and single-injection iPACK, and iv) continuous ACB and single-injection iPACK to LIA, compared to LIA alone, were included. For AUC 24-48-hour pain, the addition of continuous ACB with single-injection iPACK displayed the highest p-score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection iPACK displayed the highest p-score probability (87%) of being most effective for postoperative function.

CONCLUSIONS: Our results suggest that continuous ACB, but not single-injection ACB and/or single-injection iPACK, can provide statistically superior analgesia when added to LIA for TKA compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable.

PMID:37364292 | DOI:10.1097/ALN.0000000000004667