Experiences with pre-graduate research among Danish medical students and doctors.

INTRODUCTION: Pre-graduate research is popular among medical students. Concerns about time constraints and lack of mentorship have been raised in international studies. The extent to which these issues affect Danish medical students remains unclear. We therefore aimed to assess the conditions and outcomes of pre-graduate research among medical students from the University of Copenhagen. METHODS: A descriptive, cross-sectional, questionnaire-based survey on experiences from pre-graduate research was distributed to medical students and recently graduated medical doctors from the University of Copenhagen who had engaged in full-time pre-graduate research. The survey covered 1) working hours and income, 2) publications and authorship and 3) work environment and well-being. RESULTS: A total of 437 pre-graduate researchers participated in the survey. Pre-graduate research often involved a period outside of medical school (88%) and typically lasted a year (56%), with clinical research being the most common focus (68%). Almost a third worked longer hours (29%) than agreed and additional hours were commonly provided after the research period. Scholarships of 10,000 DKK a month were the primary source of income (72%). Most participants achieved their publication goals (62%) and experiences on work environment and well-being were generally positive. CONCLUSION: Pre-graduate research provides a conducive environment for medical students to engage in scientific research. Hovewer, engaging in pre-graduate research entails long working hours, is inadequately remunerated and often requires students to take leave from medical school. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Traffic light optimization with low penetration rate vehicle trajectory data.

Traffic light optimization is known to be a cost-effective method for reducing congestion and energy consumption in urban areas without changing physical road infrastructure. However, due to the high installation and maintenance costs of vehicle detectors, most intersections are controlled by fixed-time traffic signals that are not regularly optimized. To alleviate traffic congestion at intersections, we present a large-scale traffic signal re-timing system that uses a small percentage of vehicle trajectories as the only input without reliance on any detectors. We develop the probabilistic time-space diagram, which establishes the connection between a stochastic point-queue model and vehicle trajectories under the proposed Newellian coordinates. This model enables us to reconstruct the recurrent spatial-temporal traffic state by aggregating sufficient historical data. Optimization algorithms are then developed to update traffic signal parameters for intersections with optimality gaps. A real-world citywide test of the system was conducted in Birmingham, Michigan, and demonstrated that it decreased the delay and number of stops at signalized intersections by up to 20% and 30%, respectively. This system provides a scalable, sustainable, and efficient solution to traffic light optimization and can potentially be applied to every fixed-time signalized intersection in the world.

Impact Resistance of 3D-Printed Continuous Hybrid Fiber-Reinforced Composites.

Improving the resilience of 3D-printed composites through material extrusion technology (MEX) is an ongoing challenge in order to meet the rigorous requirements of critical applications. The primary objective of this research was to enhance the impact resistance of 3D-printed composites by incorporating continuous hybrid fibers. Herein, continuous virgin carbon (1k) and Kevlar (130D and 200D) fibers were used with different weight and volume fractions as reinforcing fibers to produce hybrid and non-hybrid composites for impact resistance testing to obtain energy absorption with different impact energies: 20 J, 30 J, 40 J, and 50 J. Moreover, 0°/90° fiber orientations were used. Hybrid composites with combinations of PLA + CF + 130D KF and PLA + CF + 200D KF showed higher impact resistance, less damaged areas (71.45% to 90.486%), and higher energy absorption (5.52-11.64% more) behaviors compared to PLA + CF non-hybrids. CT scan images provided strong evidence to resist the fracture and breakage patterns, because the stiffness and elongation properties of the fibers acted together in the hybrids specimens. Furthermore, positive hybrid effects of the PLA + CF + KF hybrids also showed an ideal match of toughness and flexibility in order to resist the impacts. In the future, these hybrids will have the potential to replace the single type of composites in the fields of aerospace and automobiles.

Effect of melatonin in patients with low anterior resection syndrome (MELLARS): a study protocol for a randomised, placebo-controlled, crossover trial.

INTRODUCTION: After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of flatus and/or stool incontinence, evacuation frequency, re-evacuation and urgency. The circadian hormone, melatonin, has shown to possess anti-inflammatory properties, and in high doses, it reduces bowel movements. The aim of the study is to investigate if locally administered melatonin has an alleviating effect on LARS. Secondarily, the effect of melatonin on bowel movements, other patient-reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels and rectal mucosa histology will be examined. METHODS AND ANALYSIS: This is a randomised, placebo-controlled, double-blinded, two-period crossover trial. The participants are randomised to 28 days of 25 mg melatonin administered rectally via an enema daily (or placebo) followed by a 28-day washout and then 28 days of placebo (or melatonin). Three participants will be included in an internal feasibility test. They will receive 25 mg of melatonin daily for 28 days. Data from these participants will be used to assess the feasibility of the rectally administered melatonin and to analyse the course of recruitment and outcome measurements. Afterwards, 18 participants will be included in the crossover trial. The severity of the LARS symptoms will be evaluated using the LARS Score on the first and last day of each treatment period. ETHICS AND DISSEMINATION: The Regional Ethics Committee, the Danish Medicines Agency and the Data and Development Support in Region Zealand approved this study. The study will be performed according to the Helsinki II declaration. Written informed consent will be obtained from all participants. The results of the study will be submitted to peer-reviewed journals for publication and presented at congresses. TRIAL REGISTRATION NUMBERS: EudraCT Registry (2020-004442-11) and ClinicalTrial.gov Registry (NCT05042700).

Myocardial injury and long-term oncological outcomes in patients undergoing surgery for colorectal cancer.

PURPOSE: Myocardial injury after noncardiac surgery (MINS) is associated with increased mortality and postoperative complications. In patients with colorectal cancer (CRC), postoperative complications are a risk factor for cancer recurrence and disease-free survival. This study investigates the association between MINS and long-term oncological outcomes in patients with CRC in an ERAS setting. METHODS: This retrospective cohort study was conducted at Zealand University Hospital, Denmark, between June 2015 and July 2017. Patients undergoing CRC surgery were included if troponin was measured twice after surgery. Outcomes were all-cause mortality, recurrence, and disease-free survival within five years of surgery. RESULTS: Among 586 patients, 42 suffered MINS. After five years, 36% of patients with MINS and 26% without MINS had died, p = 0.15. When adjusted for sex, age and UICC, the hazard ratio (aHR) for 1-year all-cause mortality, recurrence, and disease-free survival were 2.40 [0.93-6.22], 1.47 [0.19-11.29], and 2.25 [0.95-5.32] for patients with MINS compared with those without, respectively. Further adjusting for ASA status, performance status, smoking, and laparotomies, the aHR for 3- and 5-year all-cause mortality were 1.05 [0.51-2.15] and 1.11 [0.62-1.99], respectively. Similarly, the aHR for 3- and 5-year recurrence were 1.38 [0.46-4.51], and 1.49 [0.56-3.98] and for 3- and 5-year disease-free survival the aHR were 1.19 [0.63-2.23], and 1.19 [0.70-2.03]. CONCLUSION: In absolute numbers, we found no difference in all-cause mortality and recurrence in patients with and without MINS. In adjusted Cox regression analyses, the hazard was increased for all-cause mortality, recurrence, and disease-free survival in patients with MINS without reaching statistical significance.

Mobile technology features and technostress in mandatory online teaching during the COVID-19 crisis.

Technostress is defined as any unhealthy condition caused by dealing with modern technology in various harmful ways; examples of technostress include addiction and stress. Even though technostress has been extensively studied in the literature, little attention has been paid to investigating technostress among academics who work in exceptional circumstances, such as crises, and who might be experiencing different psychological states due to those circumstances. To fill the gap, this study aims to explore the factors influencing technostress among school teachers. The study examined technostress's level and factor graphics structure among 692 academics from different Arab countries during COVID-19. The technostress factors and their stories were explored and measured using sequential mixed methods and confirmatory and exploratory factor analysis. The study discusses various factors' direct and indirect effects on mobile technology integration in education and the theoretical and practical implications of managing technostress in online classes. A model of techno-stressors among Arab academics was found to include: schedule overload, complexity, uncertainty, uselessness, invasion, and compulsion. The direct effect of various factors on mobile technology integration in education is mainly positive, while indirect effects are more varied. The theoretical and practical implications of managing technostress in online classes include: considering the psychological and physiological impact of technostress on students' learning performance, decreasing overall satisfaction with the learning experience, and improving the overall quality of online courses. As a result of this study's findings, a new perspective is provided on how academics in particular circumstances (in this study, the occupation of Palestine) may behave and feel toward technology in teaching.

Lung anomaly detection from respiratory sound database (sound signals).

Chest or upper body auscultation has long been considered a useful part of the physical examination going back to the time of Hippocrates. However, it did not become a prevalent practice until the invention of the stethoscope by Rene Laennec in 1816, which made the practice suitable and hygienic. Pulmonary disease is a kind of sickness that affects the lungs and various parts of the respiratory system. Lung diseases are the third largest cause of death in the world. According to the World Health Organization (WHO), the five major respiratory diseases, namely chronic obstructive pulmonary disease (COPD), tuberculosis, acute lower respiratory tract infection (LRTI), asthma, and lung cancer, cause the death of more than 3 million people each year worldwide. Respiratory sounds disclose significant information regarding the lungs of patients. Numerous methods are developed for analyzing the lung sounds. However, clinical approaches require qualified pulmonologists to diagnose such kind of signals appropriately and are also time consuming. Hence, an efficient Fractional Water Cycle Swarm Optimizer-based Deep Residual Network (Fr-WCSO-based DRN) is developed in this research for detecting the pulmonary abnormalities using respiratory sounds signals. The proposed Fr-WCSO is newly designed by the incorporation of Fractional Calculus (FC) and Water Cycle Swarm Optimizer WCSO. Meanwhile, WCSO is the combination of Water Cycle Algorithm (WCA) with Competitive Swarm Optimizer (CSO). The respiratory input sound signals are pre-processed and the important features needed for the further processing are effectively extracted. With the extracted features, data augmentation is carried out for minimizing the over fitting issues for improving the overall detection performance. Once data augmentation is done, feature selection is performed using proposed Fr-WCSO algorithm. Finally, pulmonary abnormality detection is performed using DRN where the training procedure of DRN is performed using the developed Fr-WCSO algorithm. The developed method achieved superior performance by considering the evaluation measures, namely True Positive Rate (TPR), True Negative Rate (TNR) and testing accuracy with the values of 0.963(96.3%), 0.932,(93.2%) and 0.948(94.8%), respectively.

Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial.

BACKGROUND: In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. METHODS: We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. RESULTS: A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). CONCLUSIONS: Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts. TRIAL REGISTRATION NUMBER: NCT04591379.

Emergence of multidrug-resistant ST11 blaKPC-2 producing Klebsiella pneumoniae coharboring blaCTX-M and blaSHV in Pakistan.

INTRODUCTION: Carbapenemases are primarily responsible for the intensified spread of multidrug-resistant (MDR) K. pneumoniae by virtue of antibiotics overuse. Therefore, frequent investigation of high-risk clones especially from developing world is crucial to curtail global spread. METHODOLOGY: In this observational study, 107 K. pneumoniae were retrieved and confirmed genotypically from April 2018 to March 2020 from tertiary care hospitals in Lahore, Pakistan. Carbapenemases and extended-spectrum ß-lactamases were verified by Polymerase Chain Reaction and Sanger sequencing. Multilocus sequence typing and plasmid replicon typing were used to assign clonal lineages and plasmid replicons. RESULTS: Among the K. pneumoniae, 72.9% (78/107) strains were carbapenem resistant (CR) with 65.4% (51/78) exhibiting carbapenemase producing phenotype. Among CR K. pneumoniae 38.5% (30/78) strains exhibited the following carbapenemase genotypes: blaNDM-1 (26.7%, 8/30), blaOXA-48 (26.7%, 8/30), blaKPC-2 (20.0%, 6/30), blaVIM (10.0%, 3/30), blaNDM-1/blaOXA-48 (10.0%, 3/30), blaOXA-48/blaVIM (3.3%, 1/30) and blaOXA-48/blaIMP (3.3%, 1/30). Tigecycline and polymyxin-B retained susceptible profile. ß-lactam drugs showed intermediate to high resistance. The occurrence of CR K. pneumoniae infections was significantly associated with wound (39.7%, p = 0.0007), pus (38.5%, p = 0.009), general surgery (34.6%, p = 0.002) and intensive-care unit (26.9%, p = 0.04). blaKPC-2 producing K. pneumoniae coharboring blaCTX-M/blaSHV (66.7%) and blaCTX-M (33.3%) exhibited sequence type (ST) 258 (n = 4) and ST11 (n = 2) sequence types with IncFII, IncN, IncFIIA, IncL/M and IncFIIK plasmids. CONCLUSIONS: This is the first report describing the emergence of MDR blaKPC-2 producing K. pneumoniae ST11 coharboring blaCTX-M and blaSHV in Pakistan.

The nexus of environment-related technologies and consumption-based carbon emissions in top five emitters: empirical analysis through dynamic common correlated effects estimator.

Climate action got attention from the United Nation's Sustainable Development Goals (SDGs). Although a large number of studies are investigating the said phenomenon, however, the literature on the top five responsible countries is unable to evaluate the role of environment-related technologies (ERTs) and institutional quality (IQ). The top five consumption-based carbon dioxide (CBCO2) emitting economies, i.e., China, India, Japan, Russia, and the USA, are considerable stakeholders in this challenge. To fill this void, with the latest data available from 1992 to 2017, short- and long-run relationships are estimated with dynamic common correlated effects estimator and augmented mean group in the framework of EKC hypothesis. Reported results indicate the negative effect of ERTs and IQ towards CBCO2, which means that adoption of ERTs and better IQ is supportive in controlling environmental degradation. Findings are also robust to the policy implications for the UN's SDGs.

Risk of Atopic Disorders in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic urticaria (CU) has been associated with several systemic and autoimmune disorders. The association with atopic disorders is however controversial. The objective of this study was to perform a systematic review and meta-analysis to assess the association between CU and the atopic disorders: atopic dermatitis (AD), asthma, and allergic rhinoconjunctivitis (ARC). METHODS: Search hits from PubMed, Embase, Cochrane Library, and Web of Science were systematically reviewed. English papers from 2000 to present, containing original data of the association (prevalence, incidence, or risk) between CU and any atopic disorder(s), were included. Pooled point prevalence and OR with 95% confidence intervals were calculated with a random effects model. RESULTS: A total of 8,108 search hits were screened and reviewed. Thirty-eight studies met all inclusion criteria. The estimated pooled point prevalence of AD, asthma, and ARC in CU was 7% (5-11%, I2 = 99%), 12% (9-15%, I2 = 100%), and 22% (16-29%, I2 = 100%), respectively. Pooled ORs were estimated to 2.75 (2.05-3.68, I2 = 94%) for AD, 1.87 (1.01-3.45, I2 = 100%) for asthma, and 2.94 (1.84-4.68, I2 = 100%) for ARC. CONCLUSION: Pooled point prevalences of atopic disorders in CU were comparable to the general population. However, studies that compared prevalences with controls from the same population all found a significantly increased risk of atopic disorders in CU. Results should however be interpreted with caution as high heterogeneity was found in all analyses.

Design and development of hybrid optimization enabled deep learning model for COVID-19 detection with comparative analysis with DCNN, BIAT-GRU, XGBoost.

The recent investigation has started for evaluating the human respiratory sounds, like voice recorded, cough, and breathing from hospital confirmed Covid-19 tools, which differs from healthy person's sound. The cough-based detection of Covid-19 also considered with non-respiratory and respiratory sounds data related with all declared situations. Covid-19 is respiratory disease, which is usually produced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, it is more indispensable to detect the positive cases for reducing further spread of virus, and former treatment of affected patients. With constant rise in the COVID-19 cases, there has been a constant rise in the need of efficient and safe ways to detect an infected individual. With the cases multiplying constantly, the current detecting devices like RT-PCR and fast testing kits have become short in supply. An effectual Covid-19 detection model using devised hybrid Honey Badger Optimization-based Deep Neuro Fuzzy Network (HBO-DNFN) is developed in this paper. Here, the audio signal is considered as input for detecting Covid-19. The gaussian filter is applied to input signal for removing the noises and then feature extraction is performed. The substantial features, like spectral roll-off, spectral bandwidth, Mel frequency cepstral coefficients (MFCC), spectral flatness, zero crossing rate, spectral centroid, mean square energy and spectral contract are extracted for further processing. Finally, DNFN is applied for detecting Covid-19 and the deep leaning model is trained by designed hybrid HBO algorithm. Accordingly, the developed Hybrid HBO method is newly designed by incorporating Honey Badger optimization Algorithm (HBA) and Jaya algorithm. The performance of developed Covid-19 detection model is evaluated using three metrics, like testing accuracy, sensitivity and specificity. The developed Hybrid HBO-based DNFN is outpaced than other existing approaches in terms of testing accuracy, sensitivity and specificity of "0.9176, 0.9218 and 0. 9219". All the test results are validated with the k-fold cross validation method in order to make an assessment of the generalizability of these results. When k-fold value is 9, sensitivity of existing techniques and developed JHBO-based DNFN is 0.8982, 0.8816, 0.8938, and 0.9207. The sensitivity of developed approach is improved by means of gaussian filtering model. The specificity of DCNN is 0.9125, BI-AT-GRU is 0.8926, and XGBoost is 0.9014, while developed JHBO-based DNFN is 0.9219 in k-fold value 9.

The Effect of Educational Program on Pain Management, Self-Efficacy Behavior, and Quality of Life among Adult Diabetic Patients with Peripheral Neuropathy Pain: A Randomized Controlled Trial.

OBJECTIVE: Jordan has a high prevalence of painful diabetic peripheral neuropathy (PDPN), leg complications, and amputations due to diabetes. This study evaluated the effect of educational programs on pain management, self-efficacy behaviors, and quality of life (QoL) among adult patients with PDPN. METHODS: The randomized controlled trial study was conducted at the Jordanian Ministry of Health hospitals between October 2019 - March 2020. Seventy-two adult patients with PDPN were randomized to an experimental group of 36 patients who attended an educational program and a control group who followed routine diabetic care in the study setting. The data were collected using a socio-demographic and diabetes clinical/laboratory data form, the numeric rating scale (NRS), diabetes self-efficacy scale (DSES), and the quality-of-life questionnaire (EQ-5D). The intervention program consisted of four educational sessions at weekly intervals. Pre-test and post-test evaluations were conducted. RESULTS: After the educational intervention, the mean scores of the NRS (p=0.020), DSES (p<0.001), and EQ-5D (p<0.001) in the experimental group improved significantly improved compared to those in the control group. Additionally, while there were no significant correlations between the three study outcomes in the pre-test stage, correlations were observed to be significant after the educational intervention. CONCLUSION: This study shows that the design and implementation of educational intervention combined with routine diabetic care facilitate effective pain management, self-efficacy behaviors, and QoL of patients with PDPN. The health care providers are recommended to use the educational programs for such patients at various levels of services in both health centers and diabetes clinics.

Gastrointestinal involvement attenuates COVID-19 severity and mortality

Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of coronavirus disease 2019 (COVID-19), we investigated the impact of GI infection on disease pathogenesis in three large cohorts of patients in the United States and Europe. Unexpectedly, we observed that GI involvement was associated with a significant reduction in disease severity and mortality, with an accompanying reduction in key inflammatory proteins including IL-6, CXCL8, IL-17A and CCL28 in circulation. In a fourth cohort of COVID-19 patients in which GI biopsies were obtained, we identified severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within small intestinal enterocytes for the first time in vivo but failed to obtain culturable virus. High dimensional analyses of GI tissues confirmed low levels of cellular inflammation in the GI lamina propria and an active downregulation of key inflammatory genes including IFNG, CXCL8, CXCL2 and IL1B among others. These data draw attention to organ-level heterogeneity in disease pathogenesis and highlight the role of the GI tract in attenuating SARS-CoV-2-associated inflammation with related mortality benefit.

Prevention of depression in patients with cancer: A systematic review and meta-analysis of randomized controlled trials.

Depression and depressive symptoms are prevalent in patients with cancer. Depression is underdiagnosed and therefore, patients often receive inadequate treatment for depression. We have assessed the evidence of primary prophylactic treatment for depression in patients with cancer. The systematic review was prospectively registered at PROSPERO and was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Five electronic databases were searched on the 31st of May 2018 and two independent reviewers screened the papers. Randomized controlled trials of adult patients with cancer treated prophylactically with an antidepressive intervention of any kind using validated assessment tools to measure depression or depressive symptoms were included. No language or publication year restrictions were applied. Seven out of eighteen studies reported a statistically significant prophylactic effect on depression. The studies were classified into three groups based on the type of intervention. The meta-analyses showed a significant difference in favour of pharmacotherapy (RR 0.34, 95% CI 0.18; 0.63), psychotherapy (SMD -0.23,95% CI -0.46; 0.00), and other interventions (SMD -0.17, 95% CI -0.31; -0.03). Only one study had overall low risk of bias and the rest had high risk of bias predominantly due to blinding, incomplete data, or allocation concealment. Preventive measures have been examined in patients with cancer, but no convincing evidence for any specific intervention is present. Depression in patients with cancer can be prevented and prophylactic treatment should be given during oncological treatment but further high quality studies testing safe interventions are still needed.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

BACKGROUND: Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. METHODS: The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants' bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. RESULTS: 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32-7.05) and 5.98 (CI 5.19-6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. CONCLUSIONS: Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.

The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial.

Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo-controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l-arginine, asymmetric dimethylarginine, and uric acid. Thirty-one patients were included in the study. The intention-to-treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29-0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.

Developing a low budget trauma registry.

Trauma registry plays an essential role in collecting epidemiological injury data which is used in quality care improvement and research. This paper was planned toshare our experience of having developed a low-budget user-friendly trauma registry with the help of Microsoft Access. This was used because of its ease of use, quickdevelopment style, and support for relational database d esign. Var iable i nc lud ed in our registr y were demographics, description of injury, International Classification of Disease 9 Clinical Modification (ICD9- CM) external injury classification codes, date and time of arrival, length of hospital stay, referral to and from hospital, physiological assessment along with scores for assessing the injury severity. Developing a local trauma registry helped us in scrutinising our practice, and we believe that a national or regional trauma registry is the need of the hour in Pakistan. This will highlight the concerns specific to our society in providing quality trauma care.

A QUALITY BY DESIGN APPROACH: FABRICATION, CHARACTERIZATION AND EVALUATION OF OPTIMIZED TRANSDERMAL THERAPEUTIC SYSTEM FOR ANTIRHEUMATIC LORNOXICAM.

Microemulsion was prepared using several concentrations of selected oil (pine oil), surfactant (cre- mophor RH40), co-surfactant (isopropanol) and water to improve bioavailability by increasing solubility and permeability of lomoxicam, which was then incorporated to carbomer 940 gel base to fabricate microemulsion based gel (MEBG) to sustained permeability for transdermal delivery. Initially, the formulations were investi- gated for physicochemical characteristics, i.e., pH, conductivity, viscosity, refractive index, zeta size, poly-dis- persity index and Atomic Force Microscopy. Also, the significance of the components on in vitro permeability was observed to find out optimum microemulsion (ME,) using Box-Behnken-Design (BBD). MEBG was com- pared for in vitro permeation, stability, skin irritation and anti-inflammatory studies using control gel and in vivo bioavailability study with oral tablet. Microemulsions exhibited the physiological pH (5.35-5.99), oil in water nature (139-185 tsiemens/cm), isotropic (1.3390-1.4166), narrow size (62 nm), homogeneity, Newtonian flow (52-160 centipoise) and spherical shape. Predicted values (Q2, flux, lag time) of optimized microemulsions derived from BBD were in reasonable agreement with experimental values. The formulations were stable and non-irritating to the skin. Significant difference was investigated when comparing percent inhibition of edema of MEBG (80%) and control gel (40%) with respect to standard. The MEBG behavior differed significantly from oral tablet formulation in vivo bioavailability. Such BBD based estimation will reduce time and cost in drug designing, delivery and targeting.

ASSESSMENT OF GUAR AND XANTHAN GUM BASED FLOATING DRUG DELIVERY SYSTEM CONTAINING MEFENAMIC ACID.

We aimed to assess guar and xantban gum based floating drug delivery system containing mefenamic acid. Floating tablets of nefenamic acid were formulated with different concentrations of guar and xanthan gum via wet granulation method. The flow properties of granules that is: bulk density, tapped density, flow rate, Carr index, Hausner's ratio, compressibility index and angle of repose as well as physical parameters of the compressed tablets including: hardness, friability, thickness and swelling indices were determined and found to be good. Xanthan gum was superior to guar gum in maintaining drug release, but a combination of polymers was found to be the best for achieving sustained release up to 12 h due to the synergistic effect of both gums. Drug release mechanism was best explained by Korsmeyer-Peppas model. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies showed absence of any visible interaction. Stability studies at 40°C (75% RH) showed that the formulation was stable at elevated temperature. It can be concluded that floating tablets can be used as a sustained release matrix due to their superior characteristics.