Search results for: retrospective cohort study

Authors: K. Hinde, R. Bookun, P. Tran

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Percutaneous CT guided biopsies provide a fast, minimally invasive, cost effective and safe method for obtaining tissue for histopathology and culture. Standards for diagnostic yield vary depending on whether the tissue is being obtained for histopathology or culture. We present a retrospective audit from Western Health in Melbourne Australia over a 12-month period which aimed to determine the diagnostic yield, technical success and complication rate for CT guided bone biopsies and identify factors affecting these results. The digital imaging storage program (Synapse Picture Archiving and Communication System – Fujifilm Australia) was analysed with key word searches from October 2015 to October 2016. Nineteen CT guided bone biopsies were performed during this time. The most common referring unit was oncology, work up imaging included CT, MRI, bone scan and PET scan. The complication rate was 0%, overall diagnostic yield was 74% with a technical success of 95%. When performing biopsies for histologic analysis diagnostic yield was 85% and when performing biopsies for bacterial culture diagnostic yield was 60%. There was no significant relationship identified between size of lesion, distance of lesion to skin, lesion appearance on CT, the number of samples taken or gauge of needle to diagnostic yield or technical success. CT guided bone biopsy at Western Health meets the standard reported at other major clinical centres for technical success and safety. It is a useful investigation in identification of primary malignancy in distal bone metastases.

Keywords: bone biopsy, computed tomography, core biopsy, histopathology

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Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

Procedia PDF Downloads 227

Authors: Ryan B. Simpson, Margaret A. Waskow, Aishwarya Venkat, Elena N. Naumova

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The Centers for Disease Control and Prevention (CDC) estimate that 31 known foodborne pathogens cause 9.4 million cases of these illnesses annually in US. Over 90% of these illnesses are associated with exposure to Campylobacter, Cryptosporidium, Cyclospora, Listeria, Salmonella, Shigella, Shiga-Toxin Producing E.Coli (STEC), Vibrio, and Yersinia. Contaminated products contain parasites typically causing an intestinal illness manifested by diarrhea, stomach cramping, nausea, weight loss, fatigue and may result in deaths in fragile populations. Since 1998, the National Outbreak Reporting System (NORS) has allowed for routine collection of suspected and laboratory-confirmed cases of food poisoning. While retrospective analyses have revealed common pathogen-specific seasonal patterns, little is known concerning the stability of those patterns over time and whether they can be used for preventative forecasting. The objective of this study is to construct a calendar of foodborne outbreaks of nine infections based on the peak timing of outbreak incidence in the US from 1996 to 2017. Reported cases were abstracted from FoodNet for Salmonella (135115), Campylobacter (121099), Shigella (48520), Cryptosporidium (21701), STEC (18022), Yersinia (3602), Vibrio (3000), Listeria (2543), and Cyclospora (758). Monthly counts were compiled for each agent, seasonal peak timing and peak intensity were estimated, and the stability of seasonal peaks and synchronization of infections was examined. Negative Binomial harmonic regression models with the delta-method were applied to derive confidence intervals for the peak timing for each year and overall study period estimates. Preliminary results indicate that five infections continue to lead as major causes of outbreaks, exhibiting steady upward trends with annual increases in cases ranging from 2.71% (95%CI: [2.38, 3.05]) in Campylobacter, 4.78% (95%CI: [4.14, 5.41]) in Salmonella, 7.09% (95%CI: [6.38, 7.82]) in E.Coli, 7.71% (95%CI: [6.94, 8.49]) in Cryptosporidium, and 8.67% (95%CI: [7.55, 9.80]) in Vibrio. Strong synchronization of summer outbreaks were observed, caused by Campylobacter, Vibrio, E.Coli and Salmonella, peaking at 7.57 ± 0.33, 7.84 ± 0.47, 7.85 ± 0.37, and 7.82 ± 0.14 calendar months, respectively, with the serial cross-correlation ranging 0.81-0.88 (p < 0.001). Over 21 years, Listeria and Cryptosporidium peaks (8.43 ± 0.77 and 8.52 ± 0.45 months, respectively) have a tendency to arrive 1-2 weeks earlier, while Vibrio peaks (7.8 ± 0.47) delay by 2-3 weeks. These findings will be incorporated in the forecast models to predict common paths of the spread, long-term trends, and the synchronization of outbreaks across etiological agents. The predictive modeling of foodborne outbreaks should consider long-term changes in seasonal timing, spatiotemporal trends, and sources of contamination.

Keywords: foodborne outbreak, national outbreak reporting system, predictive modeling, seasonality

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Authors: Rami Hashish, Manon Limousis-Gayda, Caitlin H. McCleery

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Introduction: A leading cause of emergency room visits among youth (in the United States), is sports-related traumatic brain injuries. Mild traumatic brain injuries (mTBIs), also called concussions, are caused by linear and/or angular acceleration experienced at the head and represent an increasing societal burden. Due to the developing nature of the brain in youth, there is a great risk for long-term neuropsychological deficiencies following a concussion. Accordingly, the purpose of this paper is to investigate incidence rates of concussion across gender for the five most common youth sports in the United States. These include basketball, track and field, soccer, baseball (boys), softball (girls), football (boys), and volleyball (girls). Methods: A PubMed search was performed for four search themes combined. The first theme identified the outcomes (concussion, brain injuries, mild traumatic brain injury, etc.). The second theme identified the sport (American football, soccer, basketball, softball, volleyball, track, and field, etc.). The third theme identified the population (adolescence, children, youth, boys, girls). The last theme identified the study design (prevalence, frequency, incidence, prospective). Ultimately, 473 studies were surveyed, with 15 fulfilling the criteria: prospective study presenting original data and incidence of concussion in the relevant youth sport. The following data were extracted from the selected studies: population age, total study population, total athletic exposures (AE) and incidence rate per 1000 athletic exposures (IR/1000). Two One-Way ANOVA and a Tukey’s post hoc test were conducted using SPSS. Results: From the 15 selected studies, statistical analysis revealed the incidence of concussion per 1000 AEs across the considered sports ranged from 0.014 (girl’s track and field) to 0.780 (boy’s football). Average IR/1000 across all sports was 0.483 and 0.268 for boys and girls, respectively; this difference in IR was found to be statistically significant (p=0.013). Tukey’s post hoc test showed that football had significantly higher IR/1000 than boys’ basketball (p=0.022), soccer (p=0.033) and track and field (p=0.026). No statistical difference was found for concussion incidence between girls’ sports. Removal of football was found to lower the IR/1000 for boys without a statistical difference (p=0.101) compared to girls. Discussion: Football was the only sport showing a statistically significant difference in concussion incidence rate relative to other sports (within gender). Males were overall more likely to be concussed than females when football was included (1.8x), whereas concussion was more likely for females when football was excluded. While the significantly higher rate of concussion in football is not surprising because of the nature and rules of the sport, it is concerning that research has shown higher incidence of concussion in practices than games. Interestingly, findings indicate that girls’ sports are more concussive overall when football is removed. This appears to counter the common notion that boys’ sports are more physically taxing and dangerous. Future research should focus on understanding the concussive mechanisms of injury in each sport to enable effective rule changes.

Keywords: gender, football, soccer, traumatic brain injury

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Authors: Michal Lysek, Mike Danilovic, Jasmine Lihua Liu

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HMS Industrial Networks AB has been recognized as one of the most innovative companies in the industrial communication industry worldwide. The creation of their Anybus innovation during the 1990s contributed considerably to the company’s success. From inception, HMS’ employees were innovating for the purpose of creating new business (the creation phase). After the Anybus innovation, they began the process of internationalization (the commercialization phase), which in turn led them to concentrate on cost reduction, product quality, delivery precision, operational efficiency, and increasing growth (the growth phase). As a result of this transformation, performing new radical innovations have become more complicated. The purpose of our research was to explore the dynamics of innovation at HMS from the aspect of key actors, activities, and events, over the three phases, in order to understand what led to the creation of their Anybus innovation, and why it has become increasingly challenging for HMS to create new radical innovations for the future. Our research methodology was based on a longitudinal, retrospective study from the inception of HMS in 1988 to 2014, a single case study inspired by the grounded theory approach. We conducted 47 interviews and collected 1 024 historical documents for our research. Our analysis has revealed that HMS’ success in creating the Anybus, and developing a successful business around the innovation, was based on three main capabilities – cultivating customer relations on different managerial and organizational levels, inspiring business relations, and balancing complementary human assets for the purpose of business creation. The success of HMS has turned the management’s attention away from past activities of key actors, of their behavior, and how they influenced and stimulated the creation of radical innovations. Nowadays, they are rhetorically focusing on creativity and innovation. All the while, their real actions put emphasis on growth, cost reduction, product quality, delivery precision, operational efficiency, and moneymaking. In the process of becoming an international company, HMS gradually refocused. In so doing they became profitable and successful, but they also forgot what made them innovative in the first place. Fortunately, HMS’ management has come to realize that this is the case and they are now in search of recapturing innovation once again. Our analysis indicates that HMS’ management is facing several barriers to innovation related path dependency and other lock-in phenomena. HMS’ management has been captured, trapped in their mindset and actions, by the success of the past. But now their future has to be secured, and they have come to realize that moneymaking is not everything. In recent years, HMS’ management have begun to search for innovation once more, in order to recapture their past capabilities for creating radical innovations. In order to unlock their managerial perceptions of customer needs and their counter-innovation driven activities and events, to utilize the full potential of their employees and capture the innovation opportunity for the future.

Keywords: barriers to innovation, dynamics of innovation, in search of excellence and innovation, radical innovation

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Authors: Mehrnaz Mostafavi

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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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Authors: Alejandra Sierra, Gloria Valadez, Adriana Dávalos, Mirliana Ramírez

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For years, the Pan American Health Organization/World Health Organization and other organizations have made efforts to the improve access and the quality of prenatal care as part of comprehensive programs for maternal and neonatal health, the standards of care have been renewed in order to migrate from a medical perspective to a holistic perspective. However, despite the efforts currently antenatal care models have not been verified by a scientific evaluation in order to determine their effectiveness. The teenage pregnancy is considered as a very important phenomenon since it has been strongly associated with inequalities, poverty and the lack of gender quality; therefore it is important to analyze the antenatal care that’s been given, including not only the clinical intervention but also the activities surrounding the advertising and the health education. In this study, the objective was to describe if the previously established activities (on the prenatal care models) are being performed in the care of pregnant teenagers attending prenatal care in health institutions in two cities in México and Chile during 2013. Methods: Observational and descriptive study, of a transversal cohort. 170 pregnant women (13-19 years) were included in prenatal care in two health institutions (100 women from León-Mexico and 70 from Chile-Coquimbo). Data collection: direct survey, perinatal clinical record card which was used as checklists: WHO antenatal care model WHO-2003, Official Mexican Standard NOM-007-SSA2-1993 and Personalized Service Manual on Reproductive Process- Chile Crece Contigo; for data analysis descriptive statistics were used. The project was approved by the relevant ethics committees. Results: Regarding the fulfillment of interventions focused on physical, gynecological exam, immunizations, monitoring signs and biochemical parameters in both groups was met by more than 84%; the activities of guidance and counseling pregnant teenagers in Leon compliance rates were below 50%, on the other hand, although pregnant women in Coquimbo had a higher percentage of compliance, no one reached 100%. The topics that less was oriented were: family planning, signs and symptoms of complications and labor. Conclusions: Although the coverage of the interventions indicated in the prenatal care models was high, there were still shortcomings in the fulfillment of activities to orientation, education and health promotion. Deficiencies in adherence to prenatal care guidelines could be due to different circumstances such as lack of registration or incomplete filling of medical records, lack of medical supplies or health personnel, absences of people at prenatal check-up appointments, among many others. Therefore, studies are required to evaluate the quality of prenatal care and the effectiveness of existing models, considering the role of the different actors (pregnant women, professionals and health institutions) involved in the functionality and quality of prenatal care models, in order to create strategies to design or improve the application of a complete process of promotion and prevention of maternal and child health as well as sexual and reproductive health in general.

Keywords: adolescent health, health systems, maternal health, primary health care

Procedia PDF Downloads 195

Authors: Amin Masoumiganjgah, Luke Salmon, Julianne Burnton, Fahimeh Bagheri, Gavin Lenton, S. L. Ezekial Tan

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Introduction: The incidence of proximal biceps tenodesis and acute distal biceps repair is increasing, and rehabilitation protocols following both are variable. Golf is a popular sport within Australia, and the Gold Coast has become a Mecca for golfers, with more courses per capita than anywhere else in the world. Currently, there are no clear guidelines regarding return to golf play following biceps procedures. The aim of this study was to determine biceps brachii activation during the golf swing through electromyographic analysis, and subsequently, aid in rehabilitation guidelines and return to golf following tenodesis and repair. Methods: Subjects were amateur golfers with no previous upper limb surgery. Surface electromyography (EMG) and high-speed video recording were used to analyse activation of the left and right biceps brachii and the anterior deltoid during the golf swing. Each participant’s maximum voluntary contraction (MVC) was recorded, and they were then required to hit a golf ball aiming for specific distances of 2, 50, 100 and 150 metres at a driving range. Noraxon myoResearch and Matlab were used for data analysis. Mean % MVC was calculated for leading and trailing arms during the full swing and its’ 4 phases: back-swing, acceleration, early follow-through and late follow-through. Results: 12 golfers (2 female and 10 male), participated in the study. Median age was 27 (25 – 38), with all being right handed. Over all distances, the mean activation of the short and long head of biceps brachii was < 10% through the full swing. When breaking down the 50, 100 and 150m swing into phases, mean MVC activation was lowest in backswing (5.1%), followed by acceleration (9.7%), early follow-through (9.2%), and late follow-through (21.4%). There was more variation and slightly higher activation in the right biceps (trailing arm) in backswing, acceleration, and early follow-through; with higher activation in the leading arm in late follow-through (25.4% leading, 17.3% trailing). 2m putts resulted in low MVC values (3.1% ) with little variation across swing phases. There was considerable individual variation in results – one tense subject averaged 11.0% biceps MVC through the 2m putting stroke and others recorded peak mean MVC biceps activations of 68.9% at 50m, 101.3% at 100m, and 111.3% at 150m. Discussion: Previous studies have investigated the role of rotator cuff, spine, and hip muscles during the golf swing however, to our knowledge, this is the first study that investigates the activation of biceps brachii. Many rehabilitation programs following a biceps tenodesis or repair allow active range against gravity and restrict strengthening exercises until 6 weeks, and this does not appear to be associated with any adverse outcome. Previous studies demonstrate a range of < 10% MVC is similar to the unloaded biceps brachii during walking(1), active elbow flexion with the hand positioned either in pronation or supination will produce MVC < 20% throughout range(2) and elbow flexion with a 4kg dumbbell can produce mean MVC’s of around 40%(3). Our study demonstrates that increasing activation is associated with the leading arm, increasing shot distance and the late follow-through phase. Although the cohort mean MVC of the biceps brachii is <10% through the full swing, variability is high and biceps activation reach peak mean MVC’s of over 100% in different swing phases for some individuals. Given these EMG values, caution is advised when advising patients post biceps procedures to return to long distance golf shots, particularly when the leading arm is involved. Even though it would appear that putting would be as safe as having an unloaded hand out of a sling following biceps procedures, the variability of activation patterns across different golfers would lead us to caution against accelerated golf rehabilitation in those who may be particularly tense golfers. The 50m short iron shot was too long to consider as a chip shot and more work can be done in this area to determine the safety of chipping.

Keywords: electromyographic analysis, biceps brachii rupture, golf swing, tendon surgery

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Authors: Francis Zerd, Brian E. Moore, Atuganile E. Malango, Patrick W. Hosokawa, Kevin O. Lillehei, Laurence Lemery Mchome, D. Ryan Ormond

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Introduction: Since neuropathologic diagnosis in the developing world is hampered by limitations in technical infrastructure, trained laboratory personnel, and subspecialty-trained pathologists, the use of telepathology for diagnostic support, second-opinion consultations, and ongoing training holds promise as a means of addressing these challenges. This research aims to assess the utility of static teleneuropathology in improving neuropathologic diagnoses in low- and middle-income countries. Methods: Consecutive neurosurgical biopsy and resection specimens obtained at Muhimbili National Hospital in Tanzania between July 1, 2018, and June 30, 2019, were selected for retrospective, blinded static-image neuropathologic review followed by on-site review by an expert neuropathologist. Results: A total of 75 neuropathologic cases were reviewed. The agreement of static images and on-site glass diagnosis was 71% with strict criteria and 88% with less stringent criteria. This represents an overall improvement in diagnostic accuracy from 36% by general pathologists to 71% by a neuropathologist using static telepathology (or 76% to 88% with less stringent criteria). Conclusions: Telepathology offers a suitable means of providing diagnostic support, second-opinion consultations, and ongoing training to pathologists practicing in resource-limited countries. Moreover, static digital teleneuropathology is an uncomplicated, cost-effective, and reliable way to achieve these goals.

Keywords: neuropathology, resource-limited settings, static image, Tanzania, teleneuropathology

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Authors: Sarah E. Nelson, Casey Weiner, Alexander Sigmon, Jun Hua, Haris I. Sair, Jose I. Suarez, Robert D. Stevens

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Graph-theoretical information from structural connectomes indicated significant connectivity changes and improved acute prognostication in a Random Forest (RF) model in aneurysmal subarachnoid hemorrhage (aSAH), which can lead to significant morbidity and mortality and has traditionally been fraught by poor methods to predict outcome. This study’s hypothesis was that structural connectivity changes occur in canonical brain networks of acute aSAH patients, and that these changes are associated with functional outcome at six months. In a prospective cohort of patients admitted to a single institution for management of acute aSAH, patients underwent diffusion tensor imaging (DTI) as part of a multimodal MRI scan. A weighted undirected structural connectome was created of each patient’s images using Constant Solid Angle (CSA) tractography, with 176 regions of interest (ROIs) defined by the Johns Hopkins Eve atlas. ROIs were sorted into four networks: Default Mode Network, Executive Control Network, Salience Network, and Whole Brain. The resulting nodes and edges were characterized using graph-theoretic features, including Node Strength (NS), Betweenness Centrality (BC), Network Degree (ND), and Connectedness (C). Clinical (including demographics and World Federation of Neurologic Surgeons scale) and graph features were used separately and in combination to train RF and Logistic Regression classifiers to predict two outcomes: dichotomized modified Rankin Score (mRS) at discharge and at six months after discharge (favorable outcome mRS 0-2, unfavorable outcome mRS 3-6). A total of 56 aSAH patients underwent DTI a median (IQR) of 7 (IQR=8.5) days after admission. The best performing model (RF) combining clinical and DTI graph features had a mean Area Under the Receiver Operator Characteristic Curve (AUROC) of 0.88 ± 0.00 and Area Under the Precision Recall Curve (AUPRC) of 0.95 ± 0.00 over 500 trials. The combined model performed better than the clinical model alone (AUROC 0.81 ± 0.01, AUPRC 0.91 ± 0.00). The highest-ranked graph features for prediction were NS, BC, and ND. These results indicate reorganization of the connectome early after aSAH. The performance of clinical prognostic models was increased significantly by the inclusion of DTI-derived graph connectivity metrics. This methodology could significantly improve prognostication of aSAH.

Keywords: connectomics, diffusion tensor imaging, graph theory, machine learning, subarachnoid hemorrhage

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Authors: Nelson Igaba, C. Onaga, S. Hlongwane

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Background: Medical Male Circumcision (MMC) is part of a comprehensive HIV prevention strategy. The quality of MMC done at Right To Care (RtC) sites is maintained by Continuous Quality Improvement (CQI) based on findings of assessments by internal and independent external assessors who evaluate such parameters as the quality of the surgical procedure, infection control, etc. There are 12 RtC MMC teams in Mpumalanga, two of which are headed by Medical Officers and 10 by Clinical Associates (Clin A). Objectives: To compare the quality (i) of care rendered at doctor headed sites (DHS) versus Clin A headed sites (CHS); (ii) of CQI assessments (external versus internal). Methodology: A retrospective review of data from RightMax™ (a novel RtC data management system) and CQI reports (external and internal) was done. CQI assessment scores of October 2015 and October 2016 were taken as the baseline and latest respectively. Four sites with 745-810 circumcisions per annum were purposively selected; the two DHS (group A) and two CHS (group B). Statistical analyses were conducted using R (2017 version). Results: There were no significant difference in latest CQI scores between the two groups (DHS and CHS) (Anova, F = 1.97, df = 1, P = 0.165); between internal and external CQI assessment scores (Anova, F = 2.251, df = 1, P = 0.139) or among the individual sites (Anova, F = 1.095, df = 2, P = 0.341). Of the total of 16 adverse events reported by the four sites in the 12 months reviewed (all were infections), there was no statistical evidence that the documented severity of the infection was different for DHS and CHS (Fisher’s exact test, p-value = 0.269). Conclusion: At RtC VMMC sites in Mpumalanga, internal and external/independent CQI assessments are comparable, and quality of care of VMMC is standardized with the performance of well-supervised clinical associates comparing well with those of medical officers.

Keywords: adverse events, Right to Care, male medical circumcision, continuous quality improvement

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: John Ahluwalia

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As an affluent first-world nation, Canada took swift and comprehensive action during the outbreak of the SARS-CoV-2 (COVID-19) pandemic compared to other countries in the same socio-economic cohort. The United States has stumbled to overcome obstacles most developed nations have faced, which has led to significantly more per capita cases and deaths. The initial outbreaks of COVID-19 occurred in the US and Canada within days of each other and posed similar potentially catastrophic threats to public health, the economy, and governmental stability. On a macro level, events that take place in the US have a direct impact on Canada. For example, both countries tend to enter and exit economic recessions at approximately the same time, they are each other’s largest trading partners, and their currencies are inexorably linked. Variables intrinsic to Canada’s national infrastructure have been instrumental in the country’s efforts to flatten the curve of COVID-19 cases and deaths. Canada’s coordinated multi-level governmental effort has allowed it to create and enforce policies related to COVID-19 at both the national and provincial levels. Canada’s policy of universal health care is another variable. Health care and public health measures are enforced on a provincial level, and it is within each province’s jurisdiction to dictate standards for public safety based on scientific evidence. Rather than introducing confusion and the possibility of competition for resources such as PPE and vaccines, Canada’s multi-level chain of government authority has provided consistent policies supporting national public health and local delivery of medical care. This paper will demonstrate that the coordinated efforts on provincial and federal levels have been the linchpin in Canada’s relative success in containing the deadly spread of the COVID-19 virus.

Keywords: COVID-19, canada, GIS, geospatial analysis

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Authors: Grace Fangmin Tan, Elaine Yiling Tay, Elizabeth Huiwen Tham, Andrea Wei Ching Yeo

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Background: While accidental poisonings in children may seem unavoidable, knowledge of circumstances surrounding such incidents and identification of risk factors is important in the development of secondary prevention strategies. Some risk factors include age of the child, lack of adequate supervision and improper storage of substances. The aim of this study is to assess risk factors and circumstances influencing outcomes in these children. Methodology: A retrospective medical record review of all accidental poisoning cases presenting to the Children’s Emergency at National University Hospital (NUH), Singapore between January 2014 and December 2015 was conducted. Information on demographics, poisoning circumstances and clinical outcomes were collected. Results: Ninety-nine of a total of 186 poisoning cases were accidental ingestions, with a mean age of 4.7 (range 0.4 to 18.3 years). The gender distribution is rather equal with 52(52.5%) females and 47(47.5%) males. Seventy-nine (79.8%) were self-administered by the child and in 20 cases (20.2%), the substance was administered erroneously by caregivers 12/20 (60.0%) of whom were given the wrong drug dose while 8/20 (40.0%) were given the wrong substance. Self-administration was associated with presentation to the ED within 12 hours (p=0.027, OR 6.65, 95% CI 1.24-35.72). Notably, 94.9% of the cases involved substances kept within reach of the child. Sixty-nine (82.1%) had the substance kept in the original container, 3(3.6%) in food containers, 8(9.5%) in other containers and 4(4.8%) without a container. Of the 50 cases with information on labelling, 40/50(80.0%) were accurately labelled, 2/50 (4.0%) wrongly labelled, and 8/50 (16.0%) were unlabelled. Implicated substances included personal care products (11.1%), household cleaning products (3.0%), and different classes of drugs such as paracetamol (22.2%), antihistamines (17.2%) and sympathomimetics (8.1%). Children < 3 years of age were 4.8 times more likely to be poisoned by household substances than children >3 years of age (p=0.009, 95% CI 1.48-15.77). Prehospital interventions were more likely to have been done in poisoning with household substances (p=0.005, OR 6.12 95% CI 1.73-21.68). Fifty-nine (59.6%) were asymptomatic, 34 (34.3%) had a Poisoning Severity Score (PSS) grade of 1 (minor) and 6 (6.1%) grade 2 (moderate). Older children were 9.3 times more likely to be symptomatic (p<0.001, 95% CI 3.15-27.25). Thirty (32%) required admission. Conclusion: A significant proportion of accidental poisoning cases were due to medication administration errors by caregivers, which should be preventable. Risk factors for accidental poisoning included lack of adequate caregiver supervision, improper labelling and young age of the child. There is an urgent need to improve caregiver counselling during medication dispensing as well as to educate caregivers on basic child safety measures in the home to prevent future accidental poisonings.

Keywords: accidental, caregiver, paediatrics, poisoning

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Authors: Daniela Magalhaes, Jorge Pedro, Pedro Souteiro, Joao S. Neves, Sofia Castro-Oliveira, Vanessa Guerreiro, Rita Bettencourt- Silva, Maria M. Costa, Ana Varela, Joana Queiros, Paula Freitas, Davide Carvalho

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Introduction: Obesity is an independent risk factor for renal dysfunction. Our aims were: (1) evaluate the impact of bariatric surgery (BS) on renal function; (2) clarify the factors determining the postoperative evolution of the glomerular filtration rate (GFR); (3) access the occurrence of oxalate-mediated renal complications. Methods: We investigated a cohort of 1448 obese patients who underwent bariatric surgery. Those with basal GFR (GFR0) < 30mL/min or without information about the GFR 2-year post-surgery (GFR2) were excluded. Results: We included 725 patients, of whom 647 (89.2%) women, with 41 (IQR 34-51) years, a median weight of 112.4 (IQR 103.0-125.0) kg and a median BMI of 43.4 (IQR 40.6-46.9) kg/m2. Of these, 459 (63.3%) performed gastric bypass (RYGB), 144 (19.9%) placed an adjustable gastric band (AGB) and 122 (16.8%) underwent vertical gastrectomy (VG). At 2-year post-surgery, excess weight loss (EWL) was 60.1 (IQR 43.7-72.4) %. There was a significant improve of metabolic and inflammatory status, as well as a significant decrease in the proportion of patients with diabetes, arterial hypertension and dyslipidemia (p < 0.0001). At baseline, 38 (5.2%) of subjects had hyperfiltration with a GFR0 ≥ 125mL/min/1.73m2, 492 (67.9%) had a GFR0 90-124 mL/min/1.73m2, 178 (24.6%) had a GFR0 60-89 mL/min/1.73m2, and 17 (2.3%) had a GFR0 < 60 mL/min/1.73m2. GFR decreased in 63.2% of patients with hyperfiltration (ΔGFR=-2.5±7.6), and increased in 96.6% (ΔGFR=22.2±12.0) and 82.4% (ΔGFR=24.3±30.0) of the subjects with GFR0 60-89 and < 60 mL/min/1.73m2, respectively ( p < 0.0001). This trend was maintained when adjustment was made for the type of surgery performed. Of 321 patients, 10 (3.3%) had a urinary albumin excretion (UAE) > 300 mg/dL (A3), 44 (14.6%) had a UAE 30-300 mg/dL (A2) and 247 (82.1%) has a UAE < 30 mg/dL (A1). Albuminuria decreased after surgery and at 2-year follow-up only 1 (0.3%) patient had A3, 17 (5.6%) had A2 and 283 (94%) had A1 (p < 0,0001). In multivariate analysis, the variables independently associated with ΔGFR were BMI (positively) and fasting plasma glucose (negatively). During the 2-year follow-up, only 57 of the 725 patients had transient urinary excretion of calcium oxalate crystals. None has records of oxalate-mediated renal complications at our center. Conclusions: The evolution of GFR after BS seems to depend on the initial renal function, as it decreases in subjects with hyperfiltration, but tends to increase in those with renal dysfunction. Our results suggest that BS is associated with improvement of renal outcomes, without significant increase of renal complications. So, apart the clear benefits in metabolic and inflammatory status, maybe obese adults with nondialysis-dependent CKD should be referred for bariatric surgery evaluation.

Keywords: albuminuria, bariatric surgery, glomerular filtration rate, renal function

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Authors: Shivakumar M, Leslie Edward S Lewis, Shashikala Devadiga, Sonia Khurana

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Introduction: Methylxanthines are used for the treatment of AOP, to facilitate extubation and as a prophylactic agent to prevent apnea. Though the popularity of Caffeine has risen, it is expensive in a resource constrained developing countries like India. Objective: To evaluate the cost-effectiveness of Caffeine compared with Aminophylline treatment for AOP with respect to additional ventilatory resource utilized in different birth weight categorization. Design, Settings and Participants – Single centered, retrospective economic evaluation was done. Participants included preterm newborns with < 34 completed weeks of gestation age that were recruited under an Indian Council of Medical Research funded randomized clinical trial. Per protocol data was included from Neonatal Intensive Care Unit, Kasturba Hospital, Manipal, India between April 2012 and December 2014. Exposure: Preterm neonates were randomly allocated to either Caffeine or Aminophylline as per the trial protocol. Outcomes and Measures – We assessed surfactant requirement, duration of Invasive and Non-Invasive Ventilation, Total Methylxanthine cost and additional cost for respiratory support bared by the payers per day during hospital stay. For the purpose of this study Newborns were stratified as Category A – < 1000g, Category B – 1001 to 1500g and Category C – 1501 to 2500g. Results: Total 146 (Caffeine -72 and Aminophylline – 74) babies with Mean ± SD gestation age of 29.63 ± 1.89 weeks were assessed. 32.19% constitute of Category A, 55.48% were B and 12.33% were C. The difference in median duration of additional NIV and IMV support was statistically insignificant. However 60% of neonates who received Caffeine required additional surfactant therapy (p=0.02). The total median (IQR) cost of Caffeine was significantly high with Rs.10535 (Q3-6317.50, Q1-15992.50) where against Aminophylline cost was Rs.352 (Q3-236, Q1-709) (p < 0.001). The additional costs spent on respiratory support per day in neonates on either Methylxanthines were found to be statistically insignificant in the entire weight based category of our study. Whereas in Category B, the median O2 charges per day were found to have more in Caffeine treated newborns (p=0.05) with border line significance. In category A, providing one day NIV or IMV support significantly increases the unit log cost of Caffeine by 13.6% (CI – 95% ranging from 4 to 24; p=0.005) over log cost of Aminophylline. Conclusion: Cost of Caffeine is expensive than Aminophylline. It was found to be equally efficacious in reducing the number duration of NIV or IMV support. However adjusted with the NIV and IMV days of support, neonates fall in category A and category B who were on Caffeine pays excess amount of respiratory charges per day over aminophylline. In perspective of resource poor settings Aminophylline is cost saving and economically approachable.

Keywords: methylxanthines include caffeine and aminophylline, AOP (apnea of prematurity), IMV (invasive mechanical ventilation), NIV (non invasive ventilation), category a – <1000g, category b – 1001 to 1500g and category c – 1501 to 2500g

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Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy

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Diabetes mellitus is the most common etiology of end-stage renal disease (ESRD). Also, diabetic nephropathy is the etiology of ESRD in approximately 23% of kidney transplant recipients. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. However, patients require close follow-up after transplantation due to medical complications. Diabetes mellitus can affect patient morbidity and mortality due to possible effects of immunosuppressive therapy on glucose metabolism. We compared the frequency of medical complications and the outcomes in diabetic and non-diabetic kidney transplant recipients. Materials and Methods: This retrospective study conducted in 498 patients who underwent kidney transplant surgery at our center in 10-year periods. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). The medical complications, graft functions, causes of graft loss and death were obtained from medical records. Results: There was no significant difference between recipient age, duration of dialysis, body mass index, gender, donor type, donor age, dialysis type, histories of HBV, HCV and coronary artery disease between two groups. The history of hypertension in diabetics was higher (69% vs. 36%, p < 0.001). The ratios of hypertension (50.1% vs. 57.1%), pneumonia (21.9% vs. 20%), urinary infection (16.9% vs. 20%), transaminase elevation (11.5% vs. 20%), hyperpotasemia (14.7% vs. 17.1%), hyponatremia (9.7% vs. 20%), hypotension (7.1% vs. 7.9%), hypocalcemia (1.4% vs. 0%), thrombocytopenia (8.6% vs. 8.6%), hypoglycemia (0.7% vs. 0%) and neutropenia (1.8% vs. 0%) were comparable in non-diabetic and diabetic groups, respectively. The frequency of hyperglycaemia in diabetics was higher (8.6% vs. 54.3%, p < 0.001). After transplantation, primary non-function (3.4% vs. 2.6%), delayed graft function (25.1% vs. 34.2%) and acute rejection (7.3% vs. 10.5%) ratios of in non-diabetic and diabetic groups were similar, respectively. Hospitalization durations in non-diabetics and diabetics were 22.5 ± 17.5 and 18.7 ± 13 day (p=0.094). Mean serum creatinine levels in non-diabetics and diabetics were 1.54 ± 0.74 and 1.52 ± 0.62 mg/dL at 6th month. Forty patients had graft loss. The ratios of graft loss and death in non-diabetic and diabetic groups were 8.2% vs. 7.1% and 7.1% vs. 2.6% (p > 0.05). There was no significant relationship between graft and patient survivals with the development of medical complication. Conclusion: As a result, medical complications are common in the early period. Hyperglycaemia was frequently seen following transplantation due to the effects of immunosuppressant regimens. However, the frequency of other medical complications in diabetic patients did not differ from non-diabetic one. The most important cause of death is still infections. The development of medical complications during the first 6 months did not significantly affect transplant outcomes.

Keywords: kidney transplantation, diabetes mellitus, complication, graft function

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Authors: Hussain-Abdulah Arjmand, Nikki S. Rickard

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The response to stress can be highly heterogenous, and may be influenced by methodological factors. The integrity of data will be optimized by measuring both positive and negative affective responses to an event, by measuring responses in real time as close to the stressful event as possible, and by utilizing data collection methods that do not interfere with naturalistic behaviours. The aim of the current study was to explore short term prototypical responses to major stressor events on outcome measures encompassing both positive and negative indicators of psychological functioning. A novel mobile experience sampling methodology (m-ESM) was utilized to monitor both effective responses to stressors in real time. A smartphone mental health app (‘Moodprism’) which prompts users daily to report both their positive and negative mood, as well as whether any significant event had occurred in the past 24 hours, was developed for this purpose. A sample of 142 participants was recruited as part of the promotion of this app. Participants’ daily reported experience of stressor events, levels of depressive symptoms and positive affect were collected across a 30 day period as they used the app. For each participant, major stressor events were identified on the subjective severity of the event rated by the user. Depression and positive affect ratings were extracted for the three days following the event. Responses to the event were scaled relative to their general reactivity across the remainder of the 30 day period. Participants were first clustered into groups based on initial reactivity and subsequent recovery following a stressor event. This revealed distinct patterns of responding along depressive symptomatology and positive affect. Participants were then grouped based on allocations to clusters in each outcome variable. A highly individualised nature in which participants respond to stressor events, in symptoms of depression and levels of positive affect, was observed. A complete description of the novel profiles identified will be presented at the conference. These findings suggest that real-time measurement of both positive and negative functioning to stressors yields a more complex set of responses than previously observed with retrospective reporting. The use of smartphone technology to measure individualized responding also proved to shed significant insight.

Keywords: depression, experience sampling methodology, positive functioning, resilience

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Mathieu Audet, Monica Soliman, Emilie Eve Gravel, Rebecca Friesdorf

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Access to higher education is critical for reducing social inequalities. The Canada Learning Bond (CLB) is a government savings incentive aimed at increasing higher education access for children of low income families by providing money toward a Registered Education Savings Plan. To better understand the educational and financial decision-making of low income families, Employment Social Development Canada conducted qualitative fieldwork with eligible parents and children, teachers, and community organizations promoting the Bond. Insights from this fieldwork were then used to develop letters to better target the needs and experiences of eligible families. In the present study, we conducted a randomized controlled trial with children ages 12 to 13, the oldest cohort of eligible children, to test the effectiveness of the new letters. Parents or caregivers of 150,088 eligible children were assigned to one of five letter conditions promoting the Bond or to a control condition that did not receive a letter. The letter conditions were: (a) the standard letter from past outreach, (b) a letter presenting the exact amount the child was eligible to receive, enhancing the salience of benefits, (c) a letter with a social norm, (d) a letter with an image emphasizing the feasibility of higher education by presenting the diversity of options (i.e., college, trade schools, apprenticeships) – many participants interviewed viewed that university was unfeasible, and (e) a letter minimizing references to 'saving' (i.e., not framing the Bond explicitly as a savings incentive) – a concept that did not resonate with low income families who felt they could not afford to save. The exact amount was also presented in letters (c) through (e). The letter minimizing references to 'saving' and presenting the exact amount had the highest net take-up rate at 6.6%, compared to 3.5% for the standard letter group. Furthermore, this trial’s BI-informed letters showed the largest impact on take-up so far, with a net take-up of 5.7% compared to 3.0% and 3.9% in the first two trials. This research highlights the value of mixed-method approaches combining qualitative and behavioural insights methods for developing context-sensitive interventions for social programs. By gaining a deeper understanding of the needs and experiences of program users through qualitative fieldwork, and then integrating these insights into behaviourally informed communications, we were able to increase take-up of an education savings program, which may ultimately improve access to higher education in children of low income families.

Keywords: access to higher education, behavioral insights, government, innovation, mixed-methods, social programs

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Authors: Antarip Bhattacharya, Dhritiman Maitra

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Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia due to autonomous production of parathormone (PTH) and the third most common endocrine disorder. Upto 2% of postmenopausal women could have this condition. Primary hyperparathyroidism is characterized by hypercalcemia with a high or insufficiently suppressed level of parathyroid hormone and is caused by a solitary parathyroid adenoma in 85-90% of patients. PHPT may also be caused by parathyroid hyperplasia (involving multiple glands) or parathyroid carcinoma. Associated morbidities and sequelae include decreased bone mineral density, fractures, kidney stones, hypertension, cardiac comorbidities and psychiatric disorder which entail huge costs for treatment. In the year 2021, by virtue of running a Breast and Endocrine Surgery clinic in a Tier 1 city at a tertiary care hospital, the opportunity to be associated with patients of hyperparathyroidism came our way. Here, we shall describe the spectrum of clinical presentations and customisation of treatment for parathyroid diseases with reference to the above patients. A retrospective analysis of the data of all patients presenting with symptoms of parathyroid diseases was made and classified according to the cause. 13 patients had presented with symptoms of hyperparathyroidism and each case presented with unique symptoms and necessitated detailed evaluation. The treatment or surgery offered to each patient was tailored to his/her individual disease and led to favourable outcomes. Diseases affecting parathyroid are not as rare as we believe. Each case merits detailed clinical evaluation, investigations and tailoring of suitable treatment with regard to medical management and extent of surgery. Intra-operative frozen section/iOPTH monitoring are really useful adjuncts for intra-operative decision making.

Keywords: hyperparathyroidism, parathyroid adenoma, parathyroid surgery, PTH

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Authors: Jonathan Sahu, Jill Aylott

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Individuals with Autism, Intellectual and Developmental disabilities (AIDD) are one of the most vulnerable groups in society, hampered not only by their own limitations to understand and interact with the wider society, but also societal limitations in perception and understanding. Communication to express their needs and wishes is fundamental to enable such individuals to live and prosper in society. This research project was designed as an organisational case study, in a large secondary health care hospital within the National Health Service (NHS), to assess the quality of care provided to people with AIDD and to review the role of advocacy to reduce health inequalities in these individuals. Methods: The research methodology adopted was as an “insider researcher”. Data collection included both quantitative and qualitative data i.e. a mixed method approach. A semi-structured interview schedule was designed and used to obtain qualitative and quantitative primary data from a wide range of interdisciplinary frontline health care workers to assess their understanding and awareness of systems, processes and evidence based practice to offer a quality service to people with AIDD. Secondary data were obtained from sources within the organisation, in keeping with “Case Study” as a primary method, and organisational performance data were then compared against national benchmarking standards. Further data sources were accessed to help evaluate the effectiveness of different types of advocacy that were present in the organisation. This was gauged by measures of user and carer experience in the form of retrospective survey analysis, incidents and complaints. Results: Secondary data demonstrate near compliance of the Organisation with the current national benchmarking standard (Monitor Compliance Framework). However, primary data demonstrate poor knowledge of the Mental Capacity Act 2005, poor knowledge of organisational systems, processes and evidence based practice applied for people with AIDD. In addition there was poor knowledge and awareness of frontline health care workers of advocacy and advocacy schemes for this group. Conclusions: A significant amount of work needs to be undertaken to improve the quality of care delivered to individuals with AIDD. An operational strategy promoting the widespread dissemination of information may not be the best approach to deliver quality care and optimal patient experience and patient advocacy. In addition, a more robust set of standards, with appropriate metrics, needs to be developed to assess organisational performance which will stand the test of professional and public scrutiny.

Keywords: advocacy, autism, health inequalities, intellectual developmental disabilities, quality of care

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Mark A. S. Laidlaw, Howard W. Mielke

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In California between the late 1920’s and 1986 the lead concentrations in urban soils and dust climbed rapidly following the deposition of greater than 387,000 tonnes of lead emitted from gasoline. Previous research indicates that when children are lead exposed around 90% of the lead is retained in their bones and teeth due to the substitution of lead for calcium. Lead in children’s bones has been shown to accumulate over time and is highest in inner-city urban areas, lower in suburban areas and lowest in rural areas. It is also known that women’s bones demineralize during pregnancy due to the foetus's high demand for calcium. Lead accumulates in women’s bones during childhood and the accumulated lead is subsequently released during pregnancy – a lagged response. This results in calcium plus lead to enter the blood stream and cross the placenta to expose the foetus with lead. In 1970 in the United States, the average age of a first‐time mother was about 21. In 2008, the average age was 25.1. In this study, it is demonstrated that in California there is a forward lagged relationship between the accumulated emissions of lead from vehicle fuel additives and later autism prevalence trends between the 1990’s and current time period. Regression analysis between a 24 year forward lag of accumulated lead emissions and autism prevalence trends in California are associated strongly (R2=0.95, p=0.00000000127). It is hypothesized that autism in genetically susceptible children may stem from vehicle fuel lead emission exposures of their mothers during childhood and that the release of stored lead during subsequent pregnancy resulted in lead exposure of foetuses during a critical developmental period. It is furthermore hypothesized that the 24 years forward lag between lead exposures has occurred because that is time period is the average length for women to enter childbearing age. To test the hypothesis that lead in mothers bones is associated with autism, it is hypothesized that retrospective case-control studies would show an association between the lead in mother’s bones and autism. Furthermore, it is hypothesized that the forward lagged relationship between accumulated historical vehicle fuel lead emissions (or air lead concentrations) and autism prevalence trends will be similar in cities at the national and international scale. If further epidemiological studies indicate a strong relationship between accumulated vehicle fuel lead emissions (or accumulated air lead concentrations) and lead in mother’s bones and autism rates, then urban areas may require extensive soil intervention to prevent the development of autism in children.

Keywords: autism, bones, lead, gasoline, petrol, prevalence

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Authors: Emil Iskandarov, Nazrin Agayeva

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Background: The effectiveness of hormone suppressive therapy (HST) in patients with nodular goiter (NG) is controversial. The aim of this study was to identify the impact of long-time HST on the Quality of Life (QoL) of patients with NG. Material and Methods: A retrospective analysis of 146 patients with NG showed treated with HST showed that in 38,4% of cases, HST was not effective. Nodules were increased in size and moreover, and new nodules were developed. Statistical procedure identified the predictors of resistant nodules: only one nodule in the left lobe; nodule size >17mm; calcinate within the nodule. 174 patients with NG, by whom predictors of resistant nodules were established, were informed about the results of previous research and surgery was suggested. Eighty-eight patients (the basic group) agreed with surgery and thyroidectomy was led. 86 patients (control group) ignored the suggestion and wished to receive HST. 3, 6 and 12 months after starting HST; control group patients were examined. HST was non-effective and patients, due to developing symptoms, were operated on. Patients in both groups were followed up 3, 6 and 12 months after thyroidectomy. Quality of Life was checked with the SF-36 survey form and compared between groups. The statistical analysis was performed with the non-parametric Mann–Whitney U test and with the Student t-test. P values ＜0.05 were considered statistically significant. Results and Discussions: QoL of patients in the basic and control groups 3 months after surgery was almost the same. However, Emotional problems severely interfered with patients in a control group with normal social activities with family, friends, and neighbors. The causes were related to the non-effective HST treatment before surgery: stress for forgetting to take drugs timely every day for a long time; blood tests for thyroid hormone level; needle biopsies of nodules for cancer screening and regular ultrasound investigations, which showed that nodules not diminished in size. Changing the treatment method after 1-year non-effective HST and delayed surgery negatively impacted patient's QoL. Social role functioning and mental health in the control group were also impaired and the difference between the results in the basic group was statistically significant (p <0.05). Conclusion: Predictors, such as only one nodule, the width of nodules more than 17mm, and the existence of calcinate within the nodule, are able to forecast the resistant nodules. HST in patients with resistant nodules is non-effective and surgery is suggested in patients with resistant nodules in the thyroid gland. Long time HST has a negative impact on the QoL patient after surgery.

Keywords: thyroid gland, nodule, hormone suppressive therapy, quality of life

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Authors: Victor Au, Khin Maung Than, Zaw Win Aung, Linawati Jumat

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Background & Objectives: Cardiac arrests can occur anywhere or anytime, and most of the cases will be brought to the emergency department except the cases that happened in at in-patient setting. Raja IsteriPangiran Anak Saleha (RIPAS) Hospital is the only tertiary government hospital which located in Brunei Muara district and received all referral from other Brunei districts. Data of cardiac arrests in Brunei Darussalam scattered between Emergency Medical Ambulance Services (EMAS), Emergency Department (ED), general inpatient wards, and Intensive Care Unit (ICU). In this audit, we only focused on cardiac arrest cases which had happened or presented to the emergency department RIPAS Hospital. Theobjectives of this audit were to look at demographic of cardiac arrest cases and the survival to discharge rate of In-Hospital Cardiac Arrest (IHCA) and Out-Hospital Cardiac Arrest (OHCA). Methodology: This audit retrospective study was conducted on all cardiac arrest cases that underwent Cardiopulmonary Resuscitation (CPR) in ED RIPAS Hospital, Brunei Muara, in the year 2019-2020. All cardiac arrest cases that happened or were brought in to emergency department were included. All the relevant data were retrieved from ED visit registry book and electronic medical record “Bru-HIMS” with keyword diagnosis of “cardiac arrest”. Data were analyzed and tabulated using Excel software. Result: 313 cardiac arrests were recorded in the emergency department in year 2019-2020. 92% cases were categorized as OHCA, and the remaining 8% as IHCA. Majority of the cases were male with age between 50-60 years old. In OHCA subgroup, only 12.4% received bystander CPR, and 0.4% received Automatic External Defibrillator (AED) before emergency medical personnel arrived. Initial shockable rhythm in IHCA group accounted for 12% compare to 4.9% in OHCA group. Outcome of ED resuscitation, 32% of IHCA group achieved return of spontaneous circulation (ROSC) with a survival to discharge rate was 16%. For OHCA group, 12.35% achieved ROSC, but unfortunately, none of them survive till discharge. Conclusion: Standardized registry for cardiac arrest in the emergency department is required to provide valid baseline data to measure the quality and outcome of cardiac arrest. Zero survival rate for out hospital cardiac arrest is very concerning, and it might represent the significant breach in cardiac arrest chains of survival. Systematic prospective data collection is needed to identify contributing factors and to improve resuscitation outcome.

Keywords: cardiac arrest, OHCA, IHCA, resuscitation, emergency department

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Authors: Mohammad H. Yarmohammadian, Fatemeh Rezaei

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Introduction: Improving patient safety in health systems is one of the main priorities in healthcare systems, so clinical risk management in organizations has become increasingly significant. Although several tools have been developed for clinical risk management, each has its own limitations. Aims: This study aims to develop a comprehensive tool that can complete the limitations of each risk assessment and management tools with the advantage of other tools. Methods: Procedure was determined in two main stages included development of an initial model during meetings with the professors and literature review, then implementation and verification of final model. Subjects and Methods: This study is a quantitative − qualitative research. In terms of qualitative dimension, method of focus groups with inductive approach is used. To evaluate the results of the qualitative study, quantitative assessment of the two parts of the fourth phase and seven phases of the research was conducted. Purposive and stratification sampling of various responsible teams for the selected process was conducted in the operating room. Final model verified in eight phases through application of activity breakdown structure, failure mode and effects analysis (FMEA), healthcare risk priority number (RPN), root cause analysis (RCA), FT, and Eindhoven Classification model (ECM) tools. This model has been conducted typically on patients admitted in a day-clinic ward of a public hospital for surgery in October 2012 to June. Statistical Analysis Used: Qualitative data analysis was done through content analysis and quantitative analysis done through checklist and edited RPN tables. Results: After verification the final model in eight-step, patient's admission process for surgery was developed by focus discussion group (FDG) members in five main phases. Then with adopted methodology of FMEA, 85 failure modes along with its causes, effects, and preventive capabilities was set in the tables. Developed tables to calculate RPN index contain three criteria for severity, two criteria for probability, and two criteria for preventability. Tree failure modes were above determined significant risk limitation (RPN > 250). After a 3-month period, patient's misidentification incidents were the most frequent reported events. Each RPN criterion of misidentification events compared and found that various RPN number for tree misidentification reported events could be determine against predicted score in previous phase. Identified root causes through fault tree categorized with ECM. Wrong side surgery event was selected by focus discussion group to purpose improvement action. The most important causes were lack of planning for number and priority of surgical procedures. After prioritization of the suggested interventions, computerized registration system in health information system (HIS) was adopted to prepare the action plan in the final phase. Conclusion: Complexity of health care industry requires risk managers to have a multifaceted vision. Therefore, applying only one of retrospective or prospective tools for risk management does not work and each organization must provide conditions for potential application of these methods in its organization. The results of this study showed that the integrated clinical risk management model can be used in hospitals as an efficient tool in order to improve clinical governance.

Keywords: failure modes and effective analysis, risk management, root cause analysis, model

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Authors: Matthew T. McCarthy, Sarah Janse, Natalie M. Pizzimenti, Anthony K. Savino, Brian Crosser, Sean C. Rose

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Concussion is diagnosed clinically using a comprehensive history and exam, supported by ancillary testing. Frequently, symptom checklists are used as part of the evaluation of concussion. Existing symptom scales are based on a subjective Likert scale, without relation of symptoms to clinical or functional impairment. This is a retrospective review of 133 patients under age 30 seen in an outpatient neurology practice within 30 days of a probable or definite concussion. Each patient completed 2 symptom checklists at the initial visit – the SCAT-3 symptom evaluation (22 symptoms, 0-6 scale) and a scale based on the degree of clinical impairment for each symptom (22 symptoms, 0-3 scale related to functional impact of the symptom). Final clearance date was determined by the treating physician. 60.9% of patients were male with mean age 15.7 years (SD 2.3). Mean time from concussion to first visit was 6.9 days (SD 6.2), and 101 patients had definite concussions (75.9%), while 32 were diagnosed as probable (24.1%). 94 patients had a known clearance date (70.7%) with mean clearance time of 20.6 days (SD 18.6) and median clearance time of 19 days (95% CI 16-21). Mean total symptom score was 27.2 (SD 22.9) on the SCAT-3 and 14.7 (SD 11.9) for the functional impairment scale. Pearson’s correlation between the two scales was 0.98 (p < 0.001). After adjusting for patient and injury characteristics, an equivalent increase in score on each scale was associated with longer time to clearance (SCAT-3 hazard ratio 0.885, 95%CI 0.835-0.938, p < 0.001; functional impairment scale hazard ratio 0.851, 95%CI 0.802-0.902, p < 0.001). A concussion symptom scale based on degree of functional impairment correlates strongly with the SCAT-3 scale and demonstrates a similar association with time to clearance. By assessing the degree of impact on clinical functioning, this symptom scale reflects a more intuitive approach to rating symptoms and can be used in the management of concussion.

Keywords: checklist, concussion, neurology, scale, sports, symptoms

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Authors: Brandy Yee, Dianne Yee

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Through the exploration of the lived experiences, beliefs and values of instructional leaders, teachers and students in Finland, Germany and Canada, we investigated the factors which contribute to developmentally responsive, intellectually engaging middle-level learning environments for early adolescents. Student-centred leadership dimensions, effective instructional practices and student agency were examined through the lens of current policy and research on middle-level learning environments emerging from the Canadian province of Manitoba. Consideration of these three research perspectives in the context of early adolescent learning, placed against an international backdrop, provided a previously undocumented perspective on leading, teaching and learning in the middle years. Aligning with a social constructivist, qualitative research paradigm, the study incorporated collective case study methodology, along with constructivist grounded theory methods of data analysis. Data were collected through semi-structured individual and focus group interviews and document review, as well as direct and participant observation. Three case study narratives were developed to share the rich stories of study participants, who had been selected using maximum variation and intensity sampling techniques. Interview transcript data were coded using processes from constructivist grounded theory. A cross-case analysis yielded a conceptual framework highlighting key factors that were found to be significant in the establishment of developmentally responsive, intellectually engaging middle-level learning environments. Seven core categories emerged from the cross-case analysis as common to all three countries. Within the visual conceptual framework (which depicts the interconnected nature of leading, teaching and learning in middle-level learning environments), these seven core categories were grouped into Essential Factors (student agency, voice and choice), Contextual Factors (instructional practices; school culture; engaging families and the community), Synergistic Factors (instructional leadership) and Cornerstone Factors (education as a fundamental cultural value; preservice, in-service and ongoing teacher development). In addition, sub-factors emerged from recurring codes in the data and identified specific characteristics and actions found in developmentally responsive, intellectually engaging middle-level learning environments. Although this study focused on 12 schools in Finland, Germany and Canada, it informs the practice of educators working with early adolescent learners in middle-level learning environments internationally. The authentic voices of early adolescent learners are the most important resource educators have to gauge if they are creating effective learning environments for their students. Ongoing professional dialogue and learning is essential to ensure teachers are supported in their work and develop the pedagogical practices needed to meet the needs of early adolescent learners. It is critical to balance consistency, coherence and dependability in the school environment with the necessary flexibility in order to support the unique learning needs of early adolescents. Educators must intentionally create a school culture that unites teachers, students and their families in support of a common purpose, as well as nurture positive relationships between the school and its community. A large, urban school district in Canada has implemented a school cohort-based model to begin to bring developmentally responsive, intellectually engaging middle-level learning environments to scale.

Keywords: developmentally responsive learning environments, early adolescents, middle level learning, middle years, instructional leadership, instructional practices, intellectually engaging learning environments, leadership dimensions, student agency

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Authors: Samy A. Khalil, U. Ali Rahoma

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The measurements of solar radiation, satellite data has been routinely utilize to estimate solar energy. However, the temporal coverage of satellite data has some limits. The reanalysis, also known as "retrospective analysis" of the atmosphere's parameters, is produce by fusing the output of NWP (Numerical Weather Prediction) models with observation data from a variety of sources, including ground, and satellite, ship, and aircraft observation. The result is a comprehensive record of the parameters affecting weather and climate. The effectiveness of reanalysis datasets (ERA-5) for North Africa was evaluate against high-quality surfaces measured using statistical analysis. Estimating the distribution of global solar radiation (GSR) over five chosen areas in North Africa through ten-years during the period time from 2011 to 2020. To investigate seasonal change in dataset performance, a seasonal statistical analysis was conduct, which showed a considerable difference in mistakes throughout the year. By altering the temporal resolution of the data used for comparison, the performance of the dataset is alter. Better performance is indicate by the data's monthly mean values, but data accuracy is degraded. Solar resource assessment and power estimation are discuses using the ERA-5 solar radiation data. The average values of mean bias error (MBE), root mean square error (RMSE) and mean absolute error (MAE) of the reanalysis data of solar radiation vary from 0.079 to 0.222, 0.055 to 0.178, and 0.0145 to 0.198 respectively during the period time in the present research. The correlation coefficient (R2) varies from 0.93 to 99% during the period time in the present research. This research's objective is to provide a reliable representation of the world's solar radiation to aid in the use of solar energy in all sectors.

Keywords: solar energy, ERA-5 analysis data, global solar radiation, North Africa

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