Novel p<i>K</i>_a/DFT-Based Theoretical Model for Predicting the Drug Loading and Release of a pH-Responsive Drug Delivery System

Herein, we present a theoretical model that combines classical p<i>K</i>_a theory with quantum mechanical calculations to predict the extent of interaction between acid-/base-dependent species over a full range of pH conditions. To demonstrate the theoretical model, we have predicted the drug loading and release of a pH-responsive drug delivery system consisting of sulfasalazine, an anionic anti-inflammatory drug molecule, loaded onto the positively charged trimethylammonium (TA)-functionalized mesoporous silica nanoparticle surface. The model relies on the possible combinations of pH-dependent states of the surface (S) and drug (D) molecules as neutral (0) and deprotonated (−1) states, whose relative probabilities depend on their p<i>K</i>_a value and the desired pH. The four possible combinations were identified as S⁰D⁰, S⁰D^–1, S^–1D⁰, and S^–1D^–1, and periodic density functional theory calculations were performed for systems comprising drug fragments adsorbed onto a model TA-functionalized quartz surface to calculate the pH-dependent interaction energy (<i>E</i>_int^pH). The <i>E</i>_int^pH value was attractive at the acidic environment of stomach (pH 2–5), where a drug is loaded and repulsive at neutral or slightly basic pH in the small intestine where it is released; the behavior is in accordance with the experimentally reported data. We also validated the experimental necessity of surface functionalization

Epidemiological and clinical characteristics of fall-related injuries: a retrospective study

Background Fall-related injuries are important public health problem worldwide. We aimed to describe the epidemiological and clinical characteristics of fall-related injuries in a level 1 trauma center. Method A retrospective analysis of Qatar Trauma Registry data was conducted on patients admitted for fall-related injuries between 2010 and 2017. Comparative analyses of data by gender, age-groups and height of falls were performed to describe the epidemiological and clinical characteristics of patients, and in-hospital outcomes. Results A total of 4040 patients with fall-related injuries were identified in the study duration which corresponds to the rate of 2.34 per 10,000 population. Although the rate of fall-related injuries decreased over the years, the average number of patients per year remained high accounting for 32% of the hospitalized patients with moderate to severe injuries. Most of the injuries affected the head (36%) followed by spines (29%) and chest (23%). Males were predominant (89%), more likely to fall at workplace, fall from a greater height and have polytrauma than females. The working age-group (20–59 years) constituted the majority of injured (73%) and were more likely to fall at workplace, and to fall from higher heights compared to the older adults who sustained more fall at home. Overall in-hospital mortality was 3%. Outcomes including longer hospital length of stay and mortality were generally correlated with the height of fall except for the fall at home. Conclusion Fall-related injuries remain as significant burden even in a level 1 trauma center. Variations in the pattern of injuries by age, gender and height of fall provide important information for targeted preventive measures.Other Information Published in: BMC Public Health License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1186/s12889-020-09268-2</p

Validation of ERICVA risk score as a predictor of one year amputation-free survival of patients with critical limb ischemia

Background: The ERICVA score was derived to predict amputation-free survival in patients with critical limb ischemia (CLI). It may be a useful tool to stratify patients in trials of novel interventions to treat CLI but, as yet, it has not been externally validated. Methods: A prospective database of CLI patients was developed during prescreening of patients for a phase 1 stem cell therapy clinical trial. The primary outcome was amputation free survival (AFS) at 1 year. Both the full ERICVA scale (11 parameters) and simplified ERICVA scale (5 parameters) were validated. Data analysis was performed by calculation of the area under the receiver operating characteristic (ROC) curve examining the predictive value of the scores. The Chi-square test was used to examine the association between risk group and one-year AFS and the cumulative survival of the three risk groups was compared using Kaplan Meier survival curves. Results: A series of 179 CLI patients were included in the analysis. The Chi-square test of independence showed a significant association between the risk group (high, medium and low) and one-year AFS outcome (P = 0.0007). Kaplan-Meier survival curve showed significant difference in one-year AFS between the three risk groups (log-rank P < 0.001). The area under the curve (AUC) was found to be 0.63 and 0.61 for the full and simplified score, respectively. The sensitivity of the full score was 0.44 with specificity of 0.84. The simplified score had a sensitivity of 0.28 and specificity of 0.92. Conclusion: The ERICVA risk score system was found to have a fair validity but cannot be considered reliable as a single predictor of one year AFS of CLI patients. The simplified score had an AUC almost identical to the full score and can accordingly replace the full score

Patterns and Effects of Admission Hyperglycemia and Inflammatory Response in Trauma Patients: A Prospective Clinical Study

Background The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients. Methods A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6, IL-18 and hs-CRP. Patients were categorized into four groups [non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)]. The inflammatory markers were measured on three time points (admission, 24 h and 48 h). Generalized estimating equations (GEE) were used to account for the correlation for the inflammatory markers. Pearson’s correlation test and logistic regression analysis were also performed. Results During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (50% had SIH and 50% had DH). Patients with SIH were younger, had significantly higher Injury Severity Score (ISS), higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p = 0.005), lower Trauma Injury Severity Score (p = 0.01) and lower GCS (p = 0.001). Patients with hyperglycemia had higher in-hospital mortality than the normoglycemia group (12.5% vs 3.7%; p = 0.02). A significant correlation was identified between the initial blood glucose level and serum lactate, IL-6, ISS and hospital length of stay. Overall rate of change in slope 88.54 (95% CI:-143.39–33.68) points was found more in hyperglycemia than normoglycemia group (p = 0.002) for IL-6 values, whereas there was no statistical significant change in slopes of age, gender and their interaction. The initial IL-6 levels correlated with ISS (r = 0.40, p = 0.001). On-admission hyperglycemia had an adjusted odds ratio 2.42 (95% CI: 1.076–5.447, p = 0.03) for severe injury (ISS > 12) after adjusting for age, shock index and blood transfusion. Conclusions In trauma patients, on-admission hyperglycemia correlates well with the initial serum IL-6 level and is associated with more severe injuries. Therefore, it could be a simple marker of injury severity and useful tool for patient triage and risk assessment. Trial registration This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016. https://clinicaltrials.gov/ct2/show/NCT02999386.Other Information Published in: World Journal of Surgery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00268-021-06190-5</p