Evaluation of the Revised Trauma Score, MGAP, and GAP scoring systems in predicting mortality of adult trauma patients in a low-resource setting.

BACKGROUND: Numerous trauma scoring systems have been developed in an attempt to accurately and efficiently predict the prognosis of emergent trauma cases. However, it has been questioned as to whether the accuracy and pragmatism of such systems still hold in lower-resource settings that exist in many hospitals in lower- and middle-income countries (LMICs). In this study, it was hypothesized that the physiologically-based Revised Trauma Score (RTS), Mechanism/Glasgow Coma Scale/Age/Pressure (MGAP) score, and Glasgow Coma Scale/Age/Pressure (GAP) score would be effective at predicting mortality outcomes using clinical data at presentation in a representative LMIC hospital in Upper Egypt. METHODS: This was a retrospective analysis of the medical records of trauma patients at Beni-Suef University Hospital. Medical records of all trauma patients admitted to the hospital over the 8-month period from January to August 2016 were reviewed. For each case, the RTS, MGAP, and GAP scores were calculated using clinical data at presentation, and mortality prediction was correlated to the actual in-hospital outcome. RESULTS: The Area Under the Receiver Operating Characteristic (AUROC) was calculated to be 0.879, 0.890, and 0.881 for the MGAP, GAP, and RTS respectively, with all three scores showing good discriminatory ability. With regards to prevalence-dependent statistics, all three scores demonstrated efficacy in ruling out mortality upon presentation with negative predictive values > 95%, while the MGAP score best captured the mortality subgroup with a sensitivity of 94%. Adjustment of cutoff scores showed a steep trade-off between optimizing the positive predictive values versus the sensitivities. CONCLUSION: The RTS, MGAP, and GAP all showed good discriminatory capabilities per AUROC. Given the relative simplicity and potentially added clinical benefit in capturing critically ill patients, the MGAP score should be further studied for stratifying risk of incoming trauma patients to the emergency department, allowing for more efficacious triage of patients in lower-resource healthcare settings.

APOE2 Heterozygosity Reduces Hippocampal Soluble Amyloid-ß42 Levels in Non-Hyperlipidemic Mice.

APOE2 lowers Alzheimer's disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-ß peptide (Aß) (EFAD) to evaluate the effect of APOE2 dosage on Aß pathology. We found that heterozygous mice do not exhibit hyperlipidemia. Hippocampal but not cortical levels of soluble Aß42 followed the order E2/2FAD > E2/3FAD≤E3/3FAD and E2/2FAD > E2/4FAD < E4/4FAD without an effect on insoluble Aß42. These findings offer initial insights on the impact of APOE2 on Aß pathology.

A novel apoE-mimetic increases brain apoE levels, reduces Aß pathology and improves memory when treated before onset of pathology in male mice that express APOE3.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive dysfunction and amyloid plaques composed of the amyloid-beta peptide (Aß). APOE is the greatest genetic risk for AD with APOE4 increasing risk up to ~ 15-fold compared to APOE3. Evidence suggests that levels and lipidation of the apoE protein could regulate AD progression. In glia, apoE is lipidated via cholesterol efflux from intracellular pools, primarily by the ATP-binding cassette transporter A1 (ABCA1). Therefore, increasing ABCA1 activity is suggested to be a therapeutic approach for AD. CS-6253 (CS) is a novel apoE mimetic peptide that was developed to bind and stabilize ABCA1 and maintain its localization into the plasma membrane therefore promoting cholesterol efflux. The goal of this study was to determine whether CS could modulate apoE levels and lipidation, Aß pathology, and behavior in a model that expresses human APOE and overproduce Aß. METHODS: In vitro, APOE3-glia or APOE4-glia were treated with CS. In vivo, male and female, E3FAD (5xFAD+/-/APOE3+/+) and E4FAD (5xFAD+/-/APOE4+/+) mice were treated with CS via intraperitoneal injection at early (from 4 to 8 months of age) and late ages (from 8 to 10 months of age). ApoE levels, ABCA1 levels and, apoE lipidation were measured by western blot and ELISA. Aß and amyloid levels were assessed by histochemistry and ELISA. Learning and memory were tested by Morris Water Maze and synaptic proteins were measured by Western blot. RESULTS: CS treatment increased apoE levels and cholesterol efflux in primary glial cultures. In young male E3FAD mice, CS treatment increased soluble apoE and lipid-associated apoE, reduced soluble oAß and insoluble Aß levels as well as Aß and amyloid deposition, and improved memory and synaptic protein levels. CS treatment did not induce any therapeutic benefits in young female E3FAD and E4FAD mice or in any groups when treatment was started at later ages. CONCLUSIONS: CS treatment reduced Aß pathology and improved memory only in young male E3FAD, the cohort with the least AD pathology. Therefore, the degree of Aß pathology or Aß overproduction may impact the ability of targeting ABCA1 to be an effective AD therapeutic. This suggests that ABCA1-stabilizing treatment by CS-6253 works best in conditions of modest Aß levels.

Saudi mothers' preferences about breaking bad news concerning newborns: a structured verbal questionnaire.

BACKGROUND: Breaking bad news (BBN) to parents whose newborn has a major disease is an ethical dilemma. In Saudi Arabia, BBN about newborns is performed according to the parental preferences that have been reported from non-Arabic/non-Islamic countries. Saudi mothers' preferences about BBN have not yet been studied. Therefore, we aimed to elicit the preferences of Saudi mothers about BBN concerning newborns. METHODS: We selected a convenience sample of 402 Saudi mothers, aged 18-50 years, who had no previous experience with BBN. We selected them via a simple number-randomization scheme from the premises of a level III Saudi hospital between October of 2009 and January of 2011. We used a hypothetical situation (BBN about trisomy 21) to elicit their preferences about BBN concerning newborns via a structured verbal questionnaire composed of 12 multiple-choice questions. We expressed their preferences as percentages (95% confidence interval), and we used the Kendall's W test (W) to assess the degree of agreement in preferences. RESULTS: The Saudi mothers preferred that BBN be conducted with both parents together (64% [60-69]), albeit with weak levels of agreement (W = 0.29). They showed moderate agreement in their preferences that BBN should be conducted early (79% [75-83], W = 0.48), in detail (81% [77-85], W = 0.52), in person (88% [85-91], W = 0.58), and in a quiet setting (86% [83-90], W = 0.53). With extremely weak agreement, they preferred to have a known person present for support during BBN (56% [51-61], W = 0.01), to have close bodily contact with their babies (66% [61-70], W = 0.10), and to have no another patients present (64% [59-68], W = 0.08). They showed moderate levels of agreement in their desires to detail, in advance, their preferences about process of BBN by giving a reversible, written informed consent that could be utilized for guidance, if needed (80% [76-84], W = 0.36). CONCLUSIONS: In our experience, Saudi mothers' preferences about BBN concerning newborns are varied, suggesting that a "one-size-fits-all" approach is inappropriate. A reversible, written informed consent detailing their preferences about BBN that would be kept in their medical records and utilized for guidance, if needed, may be the best solution, given this level of diversity. These findings merit further study.

Completeness of Medical Records of Trauma Patients Admitted to the Emergency Unit of a University Hospital, Upper Egypt.

Trauma records in Egyptian hospitals are widely suspected to be inadequate for developing a practical and useful trauma registry, which is critical for informing both primary and secondary prevention. We reviewed archived paper records of trauma patients admitted to the Beni-Suef University Hospital in Upper Egypt for completeness in four domains: demographic data including contact information, administrative data tracking patients from admission to discharge, clinical data including vital signs and Glasgow Coma Scale scores, and data describing the causal traumatic event (mechanism of injury, activity at the time of injury, and location/setting). The majority of the 539 medical records included in the study had significant deficiencies in the four reviewed domains. Overall, 74.3% of demographic fields, 66.5% of administrative fields, 55.0% of clinical fields, and just 19.9% of fields detailing the causal event were found to be completed. Critically, oxygen saturation, arrival time, and contact information were reported in only 7.6%, 25.8%, and 43.6% of the records, respectively. Less than a fourth of the records provided any details about the cause of trauma. Accordingly, the current, paper-based medical record system at Beni-Suef University Hospital is insufficient for the development of a practical trauma registry. More efforts are needed to develop efficient and comprehensive documentation of trauma data in order to inform and improve patient care.

Knowledge of and attitudes towards cardiopulmonary resuscitation among junior doctors and medical students in Upper Egypt: cross-sectional study.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is a fundamental skill that should be acquired by all medical community members. This study aims to evaluate the knowledge and attitudes of junior doctors and medical students towards CPR and CPR training at Beni-Suef University Hospital in Upper Egypt, a representative region with conditions common to LMIC settings. PARTICIPANTS AND METHODS: In this cross-sectional study, a total of 205 participants (60 junior doctors and 145 medical students) responded to a self-administered questionnaire assessing their knowledge regarding basic life support (BLS) and CPR techniques in neonates, children, and adults, in addition to attitudes towards the importance and necessity of CPR and CPR training. RESULTS: Of the 60 junior doctors that participated in the study, only 31.7% had adequate knowledge of CPR, but up to 95% reported positive attitudes towards CPR training. Among the 145 medical student participants, only 6.2% had adequate knowledge of CPR, while 91% reported positive attitudes towards training. Deficiencies in CPR knowledge were more apparent in questions related to CPR in children and neonates. Junior doctors and medical students with previous CPR training demonstrated significantly better CPR knowledge than their counterparts without prior training. A statistically significant positive correlation was detected between CPR knowledge and attitude towards CPR training among medical students (r = 0.41, p < 0.001). CONCLUSION: The results of this study demonstrate suboptimal and inadequate CPR knowledge among junior doctors and medical students in a representative hospital in Upper Egypt. However, participants reported overwhelmingly positive attitudes and eagerness towards the implementation of CPR training. Further research needs to be done to establish CPR skill proficiency as well as to investigate barriers to CPR training, effectiveness of available programs, and the potential implementation of such a program in Egypt and other LMICs.

Technical Note: Dosimetric impact of spherical applicator size in Intrabeam™ IORT for treating unicentric breast cancer lesions.

PURPOSE: To characterize the dosimetric impact of using different sizes of spherical applicators in Intrabeam™ Intraoperative Radiation Therapy (IB-IORT) to treat unicentric cancer lesions after breast-conserving lumpectomy. METHODS: Using the commissioned depth dose rates, the three-dimensional dosages of the 3.5, 4.0, 4.5, and 5.0 cm spherical applicators of the IB-IORT PRS400 machine were established. Five different cancer cell infiltration depths of unicentric breast lesions were formulated by a linearly declining cancer cell density distribution from the surgical surface. The equivalent uniform dose (EUD), which is the dosage of a homogeneous dose treatment for killing the same amount of cancer cells as IB-IORT in the same target volume, was then calculated using the modified linear quadratic model (MLQ). The radiobiological response of two types of cancer cell lines and three types of normal tissues in the TARGIT-A clinical trial of 20 Gy dose was estimated. The study was carried out for an acutely responding breast cancer cell line with an α/ß ratio of 10 and a slow responding breast cancer cell line with an α/ß ratio of 3.85, respectively. The cancer cell density at the surgical excision surface was assumed to be 0.01%, 0.1%, 1%, and 10%, respectively. The three types of normal tissue are radiosensitive, moderate radiosensitive, and radioresistant, respectively. The therapeutic ratio (TR), which was defined by a ratio between the survival fractions of normal tissue cells respectively in IB-IORT and in homogeneous dose treatments, was calculated. RESULTS: The EUDs are moderately dependent on the applicator size (increasing from 1 to 10% depending on the cancer infiltrating depth when increasing diameter by 0.5 cm), not on the cancer cell radiosensitivity (differing by less than 1.30% between two cancer cell lines), and not dependent on the cancer cell population density at the surgical excision surface (differing by 0% among the tested surface densities). The EUDs decrease with the cancer cell maximum infiltrating depth. EUD of a 10 mm spherical shell target volume is about 50% of EUD of a 1 mm spherical shell. TRs are dependent on the applicator size, cancer cell infiltrating depth, and the radiosensitivities of cancer cells and normal tissue. A smaller size of applicator was found to produce a greater TR for a shallowly seated lesion (<5 mm), while a large size of applicator is better to treating a deeply seated lesion (>5 mm). CONCLUSIONS: The applicator size has a moderate impact on the EUDs, a greater size of applicator will deliver a greater EUD at the same cancer cell infiltrating depth, but a smaller size of applicator is seen to produce a greater TR for the shallow lesions (depth <5 mm). In addition, a greater size of applicator is preferred for treating a deeply seated lesion (depth >5 mm) because it produces a greater TR and EUD than a smaller size of applicator. IB-IORT is a preferable alternative to uniform dose treatment when treating unicentric breast cancer at smaller infiltration depths.