Qatar Foundation Annual Research Conference Proceedings Volume 2016 Issue 1
- تاريخ المؤتمر: 22-23 Mar 2016
- الموقع: Qatar National Convention Center (QNCC), Doha, Qatar
- رقم المجلد: 2016
- المنشور: ٢١ مارس ٢٠١٦
261 - 280 of 656 نتائج
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Effectiveness of a Cost Effective Competency Workshop in Disseminating Knowledge of ‘Clinical Practice Guideline’ among Physical Therapist in a Tertiary Level Hospital in Qatar
المؤلفون: MS AjimshaBackground
Clinical guidelines are systematically developed statements designed to help practitioners and patients to make decisions about appropriate health care (Field and Lohr 1992). Higher quality of care and improved cost effectiveness are important goals in guideline development, optimally resulting in improved health (Woolf et al., 1999). Moreover, the process of guideline development addresses the need to decrease variability in professional practice, and practitioners' desire to legitimize their profession in the eyes of external stakeholders (Grimshaw et al., 1995a, Grimshaw et al., 1995b, Grol and Grimshaw 2003, Grol et al., 2004). The concept of evidence-based practice, supported by clinical guidelines, is a common aspect of health care today. Currently there is no formal training or education sessions to unify the Physical therapy practice in the department, which in turn resulting in greater practice variations and results. Grater variability in professional practice directly influences the outcome of patient care. To counteract this, Physical therapy unit, Rumailah hospital, Qatar has developed Physical therapy specific clinical practice guideline called ‘PAAS Guideline’ (Physical Therapy After Acute Stroke) to enhance the effectiveness and efficiency of post acute stroke Physical therapy care. Evidence argues that guideline-adherent care results in better health outcomes, quality of care, shorter treatment period and reduced cost of care. The phase I of the PAAS G adherence trail focuses on the knowledge dissemination phase of the clinical practice guideline through a structured competency workshop and its effectiveness. ‘Physical Therapy After Acute Stroke’ (PAAS) guidelines is a professional Physical therapy guideline for patients with stroke; based on scientific evidence, intended to optimize patient care ‘exclusively’ developed by the Physical therapists of Rumailah hospital. The goal of the PAAS guideline is to improve the quality, transparency, and uniformity of the physical therapy provided to patients whose main diagnosis is a stroke (cerebrovascular accident), throughout the chain of integrated care, by explicitly describing the Physical therapist's management of these patients on the basis of scientific research, adjusted where necessary on the basis of consensus among Physical therapy experts in primary, secondary and tertiary care, as well as associated professions in the field.
Objective
To find out the effectiveness of a cost effective competency workshop in disseminating knowledge of ‘Physical Therapy After Acute Stroke (PAAS) guideline’ among physical therapist of Rumailah Hospital, Qatar Method Participants and procedure: Through the intranet system of the Hamad Medical Corporation the competency workshop was announced well in advance of the date. The workshop and the competency training were made mandatory for all the Physical therapists practicing the neurological Physical therapy of Rumailah hospital. The supervisors of other Physical therapy department were informed to select physical therapists practicing stroke physical therapy in their unit in order to coalesce the practice across the corporation.
Workshop Structure
The program offered Physical therapists free one day eight hour PAAS guideline training. Upon successful completion of the workshop (60% marks in the post competency examination), participants will receive a ‘PAAS guideline competency certificate’ of one year validity. One full day was prepared as a competency training day by cancelling all the clinical related works of that day. The essential clinical duties of the day were rescheduled to one public holiday with 2 physical therapists on overtime coverage. The cost of the program was strictly controlled with an intention to create a cost effective workshop model which can be employed even in other units. We used our gym hall as the lecture room with all the furniture and audio-visual medias of the department. A two time simple snack was provided by using unit and hospital petty cash facility. All the printing and the publication works were done using the unit internal resources. Medical corporation media was informed to cover the event. The pre and post workshop competency exam were conducted at the beginning and very end of the program with 30 minutes given to answer 20 guideline related questions. A feedback recording was taken concerning the workshop and the arrangement in a structured course feedback form.
The training
Program agenda of the workshop was announced well in advance of the date (Table 1). All the topics were the direct reflections of the PAAS guideline converted to power point presentations. The 1-day, 8 hour training was organized in a ‘constructivist didactics’ way followed by clinically relevant examples as a way to maximize active participation by the attendees. A course and session objectives and lesson plan were given before every presentation. For every five slides of the powerpoint presentation, one review question was given inorder to refresh and refocus the attendees back to the session. The conclusion was made interactive by highlighting all the key points discussed on the session and by randomly asking the attendees to expand the key words into ideas that has learned. A five minute break was given for every presentation which was used as a question and answer session. The specialists of the department of the physical therapy, conducted the training. All the training presentations were unified in there structure and content and verified for errors well in advance of the course. The PAAS guideline was made available to all the participants before the workshop. Participating Physical therapists received author-developed handouts adapted from the workshop. The guideline was presented as seven sessions covering the seven topics of the PAAS guideline. The trainers did not target training with special conclusion nor were attendees told what would be learned and evaluated at the end of the training. However, participants were encouraged to increase the number and diversity of reflections used, diminish the frequency of questions and increase the use of open questions. PAAS guideline knowledge building was the clear goal of the training, but the emphasis was on the participants understanding and amalgamation of the given evidences with the current practices and experiences they have.
Competency examination
The participants of the PAAS guideline training were required to complete a guideline competency exam at the beginning and at the end of the training. The objectives of the competency exam was to evaluate and document the percentage of knowledge acquisition by the attendees. We believed that a respectable launch of the PASS guideline implementation should begin from an effective and equally distributed knowledge dissemination process. Twenty questions were created from the eight sessions of the guideline based on the Bloom's taxonomy. PAAS competency examination was designed with 10% questions to test the knowledge domain, 20% with comprehension, 25% with application, 20% analysis, 15% with synthesis and 10% to test the evaluation skills (Fig. 1). A total 30 minutes were provided to complete the examination. Test validation As a part of test validation 3 Physical therapy specialists with stroke rehabilitation experience from different hospital background were given the designed questionnaire and were asked to mark any questions that were unclear to them when they were taking the test. After the test, a discussion session was organized to ensure their understanding of the test questions was the same as what was intended. Two questions were adjusted based on this ‘internal pre-testing’ measure.
Results
The candidates were given the pre and post examination with the same question set. No information or clues were given to the participants regarding the posttest examination during the pretest or workshop. The same question set was used inorder to quantify the transfer of knowledge from the workshop. The maximum possible mark in the question set was 20. The average mark scored by the candidates in the pretest was six (6) out of 20 with standard deviation of (SD) 1.9. The average mark scored by the candidates in the post test was 14.5 out of 20 with standard deviation of (SD) 3.0 indicating difference of 8.5 marks with standard deviation of (SD) 1.6 between the two examinations. This has proven that the cost effective competency workshop succeeded in improving PAAS guideline knowledge to 141.7% compared to the pre workshop. Figure 2 represents the PAAS G examination mark analysis. A paired t test was executed to analyze the pre and post workshop test results. The t statistics was observed as, t = 21.496, and p = 0.001; ie, 0.001 probability of this result occurring by chance, under the null hypothesis of no difference. The null hypothesis was rejected, since p < 0.05 (Table 2).
Conclusion
There is strong evidence (p < 0.05) that the cost effective competency workshop improved PAAS G knowledge. In this data set, it improved marks, on average, by approximately 8.5 points or 141.7% with a 95% Confidence Interval (7.7–9.3). The feedback evaluation revealed an overall very good to excellent rating for the competency workshop (Fig. 3).
Implication
PAAS guidelines is a professional Physical therapy guideline for patients with stroke; based on scientific evidence, intended to optimize patient care, developed by the guideline task force of Physical therapy unit, Rumailah Hospital. PAAS Guideline offers recommendations for appropriate care. An evaluation of the guideline adherence and practice variations helps to fine tune the Physical therapy care to a highest possible standard of practice. A proper assessment of the relationship between the process of Physical therapy care and outcomes with a comprehensive set of process indicators will be implemented during the year 2016. We strongly believe that by means of systematic approach and implementation we can change the culture of practice so that it can suit and align with the international quality care in evidence based manner there by uplifting the corporation and its vision of becoming an internationally recognized center of excellence in health care. We believe that this ‘small changes will make a big difference in our health care system in the coming years’.
Physical Therapy, Practice behavior, Clinical practice guideline, Adherence
References
Field, Marilyn J., and Kathleen N. Lohr. “A provisional instrument for assessing clinical practice guidelines.” (1992). Grimshaw, Jeremy, et al. “Developing and implementing clinical practice guidelines.” Quality in Health care 4.1 (1995): 55.
Grimshaw, Jeremy, Martin Eccles, and Ian Russell. “Developing clinically valid practice guidelines.” Journal of evaluation in clinical practice 1.1 (1995): 37–48.
Grol, Richard. “Successes and failures in the implementation of evidence-based guidelines for clinical practice.” Medical care 39.8 (2001): II–46.
Grol, Richard, and Jeremy Grimshaw. “From best evidence to best practice: effective implementation of change in patients' care.” The lancet 362.9391 (2003): 1225–1230.
Woolf, Steven H., et al. “Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines.” BMJ: British Medical Journal 318.7182 (1999): 527.
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A Knitted/Non-Woven Composite Polycaprolactone Scaffold for Tissue Engineering of the Aortic Valve
The use of mechanical or animal derived valves were replaced by tissue engineered (TE) heart valves (HV) due to their disadvantages such as thrombogenicity and poor durability. A tissue engineered valve, ideally mimics the function of a native valve by responding to growth and physiological forces. It is also believed to have a longer life span, close to that of a native valve. Knitting is a versatile technology, which offers a large spectrum of products and solutions that are of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex geometries and structures by precisely assembling the yarn by forming interlocked loops to desired positions. Furthermore, the yarns can be knitted precisely to reproduce the anisotropic structure of native heart valve. The advantages of this industry has convinced scientists to employ knitting to construct a HV scaffold. Inherently the knitting yields strong but open structures that individually, cannot be used due to their permeability to the fluids. Several studies to seal the pores with hydrogels have shown poor results. Therefore, a new composite material, which is a combination of knitted structure with non-woven structure of the same polymer, namely bioresorbable polycaprolactone (PCL) has been developed and described in this study. The knitted layer provides the desired mechanical stability while nano-fibers of non–woven PCL seals the construct, and makes it functional. Moreover, both types of employed fibers (micro and nano) facilitate the oriented growth of cells in a longitudinal direction, and, consequently, enable the deposition of extra-cellular matrixes (ECM) proteins in an oriented manner. This technique, therefore, has a potential to provide a functional composite PCL-based scaffold. An additional task of this report is to describe example of interaction between tissue and textile engineers. To enable that interaction the textile engineers had to gain a basic understanding of structural and mechanical aspects of the heart valve and, tissue engineers needed to acquire the knowledge of tools and capacities that are essential in knitting technology.
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Neurological Disorders: A Network Perspective from Dense Electroencephalography
المؤلفون: Mahmoud Hassan and Fabrice WendlingIntroduction
Most of neurological disorders are network-based diseases. The networks associated with these diseases usually involve spatially disturbed brain regions. Thus efforts were recently evolving from identifying pathological “zones” toward identifying “networks”. In a very recent review, Fornito and colleagues revealed that the identification of alterations in brain networks is one of the most promising paradigms in brain disorders research (Fornito and Bullmore, 2014; Fornito et al., 2015). So far, approaches based on graph theory have characterized the brain networks as sets of nodes connected by edges (Bullmore and Sporns, 2009). Once the nodes (brain regions) and edges (functional/structural connections between regions) are defined from neuroimaging technique, methods based on graph theory may be used to describe the topological properties of the identified networks. This network-based analysis has been largely used to investigate normal (Bressler and Menon, 2010) and pathological (Fornito et al., 2015) brain activities from numerous modalities. It has been used in many clinical applications such as Alzheimer's disease (He et al., 2008; Lo et al., 2010; Mallio et al., 2015; Stam et al., 2007), schizophrenia (Fornito et al., 2011; Liu et al., 2008; van den Heuvel et al., 2013) and autism (Guye et al., 2010; Li et al., 2014). However, a precise tracking of the spatiotemporal dynamics of large-scale pathological networks is still an unsolved issue (Hutchison et al., 2013). The only noninvasive technique that provides the sufficient temporal resolution to track dynamics of brain activity at millisecond scale is the Electro/Magneto encephalogram (EEG/MEG).
Methods
Therefore, the focus of our work is to develop advanced methods to, noninvasively, identify dynamics of functional brain networks using dense EEG signals (256 electrodes). The key advantage of our method, called ‘EEG source connectivity’ (Fig. 1), is the possibility of identifying functional brain networks with excellent temporal (∼ 1 ms) and spatial resolutions (Hassan et al., 2015a; Hassan et al., 2014; Hassan et al., 2015b). The EEG source connectivity involves two main steps: i) the reconstruction of regional time series by solving the EEG inverse problem and ii) the estimation of the functional connectivity using phase synchronization among oscillations present in the time-courses of reconstructed regional time series. The method was originally developed to track dynamics of functional brain networks during short time cognitive activity such as picture naming task ( < 1 second) (Hassan et al., 2015a). In this abstract, we show the first results of applying EEG source connectivity method to two neurological disorders: Epilepsy and Parkinson's disease. Figure 1: Illustrative structure of the proposed method. Dense EEG were used to record data from patients (and healthy control). Structural MRI images will be also recorded, segmented and then anatomically parcellated into a desired number of brain regions (regions of interest). The functional connectivity was then computed giving rise to high-resolution functional brain networks. These networks (graphs) will be finally characterized (quantified) using approach from graph theory to characterize the brain networks (regions and sub regions) involved in the analyzed pathology.
Results
First, in the context of epilepsy, data were recorded from epileptic patients who underwent a full pre-surgical evaluation for drug-resistant partial epilepsy. The patients had a comprehensive evaluation including detailed history and neurological examination, neuropsychological testing, structural MRI, standard 32-channels (Micromed) as well as High-Resolution 256-channels (EGI, Electrical Geodesic Inc.) scalp EEG with video recordings and intracerebral EEG recordings (SEEG). We applied our method to identify epileptogenic networks from the scalp dense-EEG. We also estimated the functional network from depth-EEG. The results revealed a very good matching between networks identified from noninvasive EEG and those obtained using the intra-cerebral electrodes (ground truth). We were able, for the first time from scalp recordings, to identify the network of brain regions (nodes) involved in the generation of the seizure as selected by the epileptologist. Second, we recently applied the EEG source connectivity method to detect alterations in functional networks involved in cognitive impairments. Dense-EEG (128 electrodes) were recorded during task-free paradigm (resting state, eye closed) to produce whole-brain functional connectivity networks in patients with different cognitive phenotypes (Dujardin et al., 2013): 1) cognitively intact patients, 2) patients with mild cognitive impairment and 3) patients with very severe cognitive impairment. Functional connectivity was assessed between each pair of 68 brain regions in 124 patients at different EEG frequency bands. Network measures were realized at global level topology, region-wise connectivity and edge-wise connectivity. Using Network Based Statistics (NBS) (Zalesky et al., 2010), results showed significant differences at alpha band (7–13 Hz) between all groups. The quantification of the networks showed that most of significant alterations (decreased connections) were frontotemporal (functional connections between frontal and temporal lobes) which perfectly match with previous findings of cognitive impairments in patient with neurodegenerative disorders (Pievani et al., 2011).
Discussion
We consider that the identification of pathological brain networks from noninvasive EEG recordings is a topic of great interest. The results of the EEG source connectivity methods on cognitive task (Hassan et al., 2015a) as well on neurological disorders such as epilepsy and Parkinson's disease as presented here, may open new perspectives in the clinical use of such approach. These network dysfunctions may be specific to the clinical syndromes and, in Parkinson's disease and frontotemporal dementia for instance, network disruption may track the pattern of pathological alterations. We speculate that our findings might have practical repercussions for diagnostic purpose, allowing earlier detection of neurodegenerative diseases and tracking of disease development.
Acknowledgment
This work has received a French government support granted to the CominLabs excellence laboratory and managed by the National Research Agency in the “Investing for the Future” program under reference ANR-10-LABX-07-01.
References
Bressler, S.L., Menon, V., 2010. Large-scale brain networks in cognition: emerging methods and principles. Trends in cognitive sciences 14, 277–290.
Bullmore, E., Sporns, O., 2009. Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews Neuroscience 10, 186–198.
Dujardin, K., Leentjens, A.F., Langlois, C., Moonen, A.J., Duits, A.A., Carette, A.S., Duhamel, A., 2013. The spectrum of cognitive disorders in Parkinson's disease: A data-driven approach. Movement Disorders 28, 183–189.
Fornito, A., Bullmore, E.T., 2014. Connectomics: a new paradigm for understanding brain disease. European Neuropsychopharmacology.
Fornito, A., Yoon, J., Zalesky, A., Bullmore, E.T., Carter, C.S., 2011. General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance. Biological psychiatry 70, 64–72.
Fornito, A., Zalesky, A., Breakspear, M., 2015. The connectomics of brain disorders. Nature Reviews Neuroscience 16, 159–172.
Guye, M., Bettus, G., Bartolomei, F., Cozzone, P.J., 2010. Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks. Magnetic Resonance Materials in Physics, Biology and Medicine 23, 409–421.
Hassan, M., Benquet, P., Biraben, A., Berrou, C., Dufor, O., Wendling, F., 2015a. Dynamic reorganization of functional brain networks during picture naming. Cortex 73, 276–288.
Hassan, M., Dufor, O., Merlet, I., Berrou, C., Wendling, F., 2014. EEG Source Connectivity Analysis: From Dense Array Recordings to Brain Networks. PloS one 9, e105041.
Hassan, M., Shamas, M., Khalil, M., El Falou, W., Wendling, F., 2015b. EEGNET: An Open Source Tool for Analyzing and Visualizing M/EEG Connectome. PloS one 10, e0138297.
He, Y., Chen, Z., Evans, A., 2008. Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease. The Journal of neuroscience 28, 4756–4766.
Hutchison, R.M., Womelsdorf, T., Allen, E.A., Bandettini, P.A., Calhoun, V.D., Corbetta, M., Della Penna, S., Duyn, J.H., Glover, G.H., Gonzalez-Castillo, J., 2013. Dynamic functional connectivity: promise, issues, and interpretations. NeuroImage 80, 360–378.
Li, H., Xue, Z., Ellmore, T.M., Frye, R.E., Wong, S.T., 2014. Network-based analysis reveals stronger local diffusion-based connectivity and different correlations with oral language skills in brains of children with high functioning autism spectrum disorders. Human brain mapping 35, 396–413.
Liu, Y., Liang, M., Zhou, Y., He, Y., Hao, Y., Song, M., Yu, C., Liu, H., Liu, Z., Jiang, T., 2008. Disrupted small-world networks in schizophrenia. Brain 131, 945–961.
Lo, C.-Y., Wang, P.-N., Chou, K.-H., Wang, J., He, Y., Lin, C.-P., 2010. Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer's disease. The Journal of neuroscience 30, 16876–16885.
Mallio, C.A., Schmidt, R., Reus, M.A., Vernieri, F., Quintiliani, L., Curcio, G., Beomonte Zobel, B., Quattrocchi, C.C., den Heuvel, M.P., 2015. Epicentral Disruption of Structural Connectivity in Alzheimer's Disease. CNS Neuroscience & Therapeutics.
Pievani, M., de Haan, W., Wu, T., Seeley, W.W., Frisoni, G.B., 2011. Functional network disruption in the degenerative dementias. The Lancet Neurology 10, 829–843.
Stam, C., Jones, B., Nolte, G., Breakspear, M., Scheltens, P., 2007. Small-world networks and functional connectivity in Alzheimer's disease. Cerebral Cortex 17, 92–99.
van den Heuvel, M.P., Sporns, O., Collin, G., Scheewe, T., Mandl, R.C., Cahn, W., Goñi, J., Pol, H.E.H., Kahn, R.S., 2013. Abnormal rich club organization and functional brain dynamics in schizophrenia. JAMA psychiatry 70, 783–792.
Zalesky, A., Fornito, A., Bullmore, E.T., 2010. Network-based statistic: identifying differences in brain networks. NeuroImage 53, 1197–1207.
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Antibiotic Prophylaxis in Surgical Procedures and the Threats of Fecal Carriage of the ESBL Producer Organisms
المؤلفون: Humberto Guanche GarcellHealthcare associated infections (HAI) are unnecessary adverse events as they are preventable with proper implementation of the best evidence about the topic. The surgical site infections (SSI) account the 17% of HAI in the U.S. In South Asian countries the pooled estimate of SSI incidence according to a recently published meta-analysis was 8.6%, meanwhile a report of Rosenthal and colleagues describes higher incidence in low-income countries compared with U.S. data. In addition to the patient safety issues, the economic impact of these infections should be considered. In U.S. the total annual costs for the 5 major infections were $9.8 billion, with SSI contributing the most to overall costs (33.7% of the total), followed by the devices associated infections and Clostridium difficile infections.
In European university hospital, the mean additional postoperative length of hospital stay was 16.8 days; and the mean additional in-hospital duration of antibiotic therapy was 7.4 days. The perioperative antibiotic prophylaxis constitutes a key prevention practice, with a high quality of evidence for its implementation. Antibiotic prophylaxis is aimed to reduce the incidence of SSI by preventing the development of infection caused by organisms that colonize or contaminate the surgical site. The adequate use of perioperative antibiotic prophylaxis can reduce the rate of SSI in up to 50%. Multidrug-resistant organisms Antimicrobial resistance is a worldwide problem with a significant impact in morbidity and mortality at the community level, and also in health care facilities. Nearly 20% of pathogens reported from all healthcare associated infections to NHSN (CDC) were multidrug-resistant organisms (MDRO).
The CDC estimates that the annual impact of antibiotic-resistant infections on the U.S. economy is $20–35 billion in excess direct health care costs, with additional costs to society for lost productivity as high as $35 billion per year and 8 million additional days in hospitals. Extended-spectrum β-lactamase producing Enterobacteriaceae is frequent in healthcare associated infections and in the community.
Worldwide dissemination of plasmid-borne extended-spectrum b-lactamases (ESBL) is a public health concern since community-acquired infections caused by ESBL-producing Escherichia coli (among other Enterobacteriaceae) are becoming increasingly frequent. The problem of ESBL production is no longer limited to community-onset or hospital-acquired infections. Faecal carriage of ESBL-producing Enterobacteriaceae, by asymptomatic individuals, has been noted in many parts of the world. There is observed a variable frequency of ESBL carriage in diverse studied population from Korea (9.3%), UK (11.3%), Sweden (6.8%) and Paris (6%). Studies conducted in Eastern Mediterranean countries has shown fecal carriage of 12.7% in Saudi Arabia, 13.4% in Lybia and 21% in Egypt. No reports about studies conducted in Qatar have been published. MDRO prevention approaches can be broadly categorized and should include measures to prevent infection among patients who are uninfected carriers of an MDRO. The problem Appendicitis is the most common reason for acute abdominal pain in with a lifetime risk of 8.6% for males and 6.7% for females. Appendectomy constitutes the principal emergency surgical procedure in The Cuban Hospital (Dukhan, Qatar). During the period January, 2013-October, 2015 have been performed 561 appendectomies, been reported 22 (4.1%) cases with surgical site infections. As a consequence, an excess of the length of stay of 3.8 days and antimicrobial consumption of 77.84 daily defined doses was identified in patients with SSI compared with those without SSI. In culture samples collected during surgical procedure, due to the evidence of fluid in the surgical site, was identified Escherichia coli ESBL producer in 23.3% of the positive cultures, meanwhile in positive cultures of surgical site infections the 65% of the microbial agents identified were extended spectrum beta-lactamase producers (E.coli, 12 patients; Klebsiella pneumonia, 1 patient). The standard perioperative prophylaxis performed in our patients is a combination of cefuroxime (beta-lactam antimicrobial) and metronidazole. Compliance with antibiotic prophylaxis in patients with surgical site infection was 86.4%, 100% and 91% for timely administration, proper doses and selection of the antimicrobials and discontinuation before 24 hr after the surgical procedure, respectively. – Research questionso Is the fecal carrier of ESBL producer organisms at increased risk of surgical site infections after appendectomy or others surgical procedures that involve intestinal incision? o Could be prevented these surgical site infections with a targeted antimicrobial prophylaxis? – Hypothesiso Fecal carriage of ESBL producer organisms increases the risk of surgical site infections in patients with appendicitis or colon surgeries, which could be prevented by a targeted antimicrobial prophylaxis. – Research o A cohort study of patients who underwent to appendectomies and colon surgery. – Expected resultso Identify the prevalence of fecal carriages of ESBL producer organismso Describe the risk of acquired surgical site infection in fecal carriage of ESBL producer organisms. o Analyze the potential use of targeted antimicrobial prophylaxis in surgical procedures that involve the colon. – Conclusiono The prevention of surgical site infections constitutes a challenge in the daily medical practice. o The changing environment of the MDROs in the community imposes of a challenge for healthcare professionals, which should review its practices according to the new trends of antimicrobial resistance and the frequency of microbial colonization in the population. Healthcare associated infections (HAI) are unnecessary adverse events as they are preventable with proper implementation of the best evidence about the topic.
The surgical site infections (SSI) account the 17% of HAI in the U.S. (Yokoe DS, 2014). In South Asian countries the pooled estimate of SSI incidence according to a recently published meta-analysis was 8.6% (95% CI, 5.8%–11.4%), meanwhile a report of Rosenthal and colleagues describes higher incidence in low-income countries compared with U.S. data (Rosenthal, 2013; Lin Ling M, 2015).
In addition to the patient safety issues, the economic impact of these infections should be considered. In U.S. the total annual costs for the 5 major infections were $9.8 billion (95% CI, $8.3–$11.5 billion), with surgical site infections contributing the most to overall costs (33.7% of the total), followed by the devices associated infections and Clostridium difficile infections (Zimlichman E, 2013).
In European university hospital, the mean additional postoperative length of hospital stay was 16.8 days (95% CI, 13–20.6 days); and the mean additional in-hospital duration of antibiotic therapy was 7.4 days (95% CI, 5.1–9.6 days) (Weber 2008). As is widely shown in the literature from high-income countries, including the United States, the incidence of HAI can be reduced by as much as 30%, and by 55% in the case of SSI, through the implementation of an effective surveillance approach (Umscheid CA, 2011).
The perioperative antibiotic prophylaxis constitutes a key prevention practice, which according to the 2014 SHEA recommendation achieve a high quality of evidence for its implementation (Anderson, 2008) (Yokoe, 2014). Antibiotic prophylaxis is aimed to reduce the incidence of SSI by preventing the development of infection caused by organisms that colonize or contaminate the surgical site.
The antimicrobial agents for prophylaxis should be: 1) active against the pathogens most likely to contaminate the surgical site, 2) given in an appropriate dosage and at a time that ensures adequate serum and tissue concentrations during the period of potential contamination, 3) Safe, and 4) administered for the shortest effective period to minimize adverse effects, the development of resistance, and costs. The predominant organisms causing SSIs after clean procedures are skin flora. In clean-contaminated procedures, including abdominal procedures and heart, kidney, and liver transplantations, the predominant organisms include gram-negative rods and enterococci in addition to skin flora. (Bratzler DW, 2013). The main target of antibiotic prophylaxis is the wound and should be considered, in addition of choose the proper antimicrobial (according to the surgical site or procedure), the timing of administration and it duration after the surgical procedure. The adequate use of perioperative antibiotic prophylaxis can reduce the rate of SSI in up to 50%. Multidrug-resistant organisms Antimicrobial resistance is a worldwide problem with a significant impact in morbidity and mortality at the community level, and also in health care facilities. Nearly 20% of pathogens reported from all healthcare associated infections to NHSN (CDC) were multidrug-resistant organisms (Sievert DM, 2013).
The Centers for Disease Control and Prevention (CDC) estimates that the annual impact of antibiotic-resistant infections on the U.S. economy is $20–35 billion in excess direct health care costs, with additional costs to society for lost productivity as high as $35 billion per year and 8 million additional days in hospitals. (Report of the US President, 2014). Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL) is frequent in healthcare associated infections and in the community.
Worldwide dissemination of plasmid-borne extended-spectrum b-lactamases (ESBLs) is a public health concern since community-acquired infections caused by ESBL-producing Escherichia coli (among other Enterobacteriaceae) are becoming increasingly frequent (Pitout JDD, 2005).
The problem of ESBL production is no longer limited to community-onset or hospital-acquired infections. Faecal carriage of ESBL-producing Enterobacteriaceae, particularly the CTX-M producers, by asymptomatic individuals has been noted in many parts of the world. There is observed a variable frequency of ESBL carriage in diverse studied population from Korea (9.3%), UK (11.3%), Sweden (6.8%) and Paris (6%) (Beom King J, 2014; Wickramasinghe NH, 2012, Stromdahl H, 2011, Nicolas-Chanoine MH, 2013). Studies conducted in Eastern Mediterranean countries has shown fecal carriage of 12.7% in Saudi Arabia (Kader AA, 2009), 13.4% in Lybia (Ahmed SF, 2014) and 21% in Egypt (Bassyouni RH, 2015). No reports about studies conducted in Qatar have been published. In the face of rising resistance rates and limited treatment options, prevention of MDRO infections is paramount. MDRO prevention approaches can be broadly categorized and should include measures to prevent infection among patients who are uninfected carriers of an MDRO. The Goals of the National action plan to combat antibiotic resistant bacteria (White House, Washington, 2015) define the need of the use of a rapid test for early diagnosis of multidrug-resistant organisms. The problem Appendicitis is the most common reason for acute abdominal pain in with a lifetime risk of 8.6% for males and 6.7% for females (Flum DR, 2015). Appendectomy, mainly using the laparoscopic technique, constitutes the principal emergency surgical procedure in The Cuban Hospital (Dukhan, Qatar). During the period January, 2013-October, 2015 have been performed 561 appendectomies, been reported 22 (4.1%) cases with surgical site infections. As a consequence, an excess of the length of stay of 3.8 days and antimicrobial consumption of 77.84 daily defined doses was identified in patients with SSI compared with those without SSI. In culture samples collected during surgical procedure, due to the evidence of fluid in the surgical site, was identified Escherichia coli ESBL producer in 23.3% of the positive cultures, meanwhile in positive cultures of surgical site infections the 65% of the microbial agents identified were extended spectrum beta-lactamase producers (E.coli, 12 patients; Klebsiella pneumonia, 1 patient). The standard perioperative prophylaxis performed in our patients is a combination of cefuroxime (beta-lactam antimicrobial) and metronidazole. Compliance with antibiotic prophylaxis in patients with surgical site infection was 86.4%, 100% and 91% for timely administration, proper doses and selection of the antimicrobials and discontinuation before 24 hr after the surgical procedure, respectively. – Research questions o Is the fecal carrier of ESBL producer organisms at increased risk of surgical site infections after appendectomy or others surgical procedures that involve intestinal incision? o Could be prevented these surgical site infections with a targeted antimicrobial prophylaxis? – Hypothesis o Fecal carriage of ESBL producer organisms increases the risk of surgical site infections in patients with appendicitis or colon surgeries, which could be prevented by a targeted antimicrobial prophylaxis. – Research o A cohort study of patients who underwent to appendectomies and colon surgery. – Expected results o Identify the prevalence of fecal carriages of ESBL producer organisms o Describe the risk of acquired surgical site infection in fecal carriage of ESBL producer organisms. o Analyze the potential use of targeted antimicrobial prophylaxis in surgical procedures that involve the colon. – Conclusion o The prevention of surgical site infections constitutes a challenge in the daily medical practice. o The changing environment of the multidrug-resistant organism in the community imposes of a challenge for healthcare professionals, which should review its practices according to the new trends of antimicrobial resistance and the frequency of microbial colonization in the population.
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Chlamydia Pneumoniae and Carotid Plaque Morphology: The Link with Ischemic Stroke
المؤلفون: Ahmed D Khattab, Ann Walkley, Ibtisam S Ali, David Wertheim and Leopold J StreletzBackground
There has been some anecdotal evidence linking certain infectious pathogens (such as Chlamydia pneumoniae) with stroke. C. pneumoniae infection may be one of several contributing factors for the development of inflammation of blood vessels and atherosclerosis. Furthermore, a number of inflammatory markers (such as plasma CRP, fibrinogen, IL-6, IL-1ra, ESR, WCC) have recently been linked with acute ischemic stroke. However, their value in predicting short and long-term prognosis has been questioned and deemed to be not useful in defining outcomes due to the lack of evidence and cost implications.
Aims
The aims of this study are to (i) investigate the presence of C. pneumoniae in both echogenic and echolucent carotid plaques; and (ii) explore their role in the destabilization of the plaque, leading to embolization and cerebrovascular events.
Methods
(i) Study design: A prospective study involving carotid plaque specimens collected from routine endarterectomy surgical operations. Carotid plaques were removed en bloc during surgery to preserve the entire plaque structure. (ii) Carotid plaque samples: Twenty specimens of carotid atherosclerotic plaques (ten predominantly echolucent, Types I & II and ten predominantly echogenic Types III & IV) were used. The non-invasive ultrasonic appearance (i.e. echogenicity or echolucency) and the quantitative grading of these plaques were determined pre-operatively using duplex scanning aided by computerized measurements according to the criteria adopted by Gray-Weale et al. (1988). (iii) Immunohistochemistry: Levels of C. pneumoniae, Matrix Metalloproteinase-3 (MMP3), Nitric Oxide Synthase (NOS), Superoxide Dismutase (SOD) enzymes in echogenic (fibrous) and echolucent (lipid-laden) atherosclerotic carotid plaques were determined using immuno-histochemical and Western blotting techniques. (iv) Histological methods: Haematoxylin-Eosin stain was performed to stain the slides that will be used for morphological studies by light microscopy. For Laser Scanning Confocal Microscopy (LSCM), slides were stained with saturated aqueous fluorescein for a few minutes and then dehydrated, cleared and mounted in DPX. Carotid plaque specimens were first examined by light microscopy (at magnification 10, 40 times) to characterize the following histological features: necrosis, calcification, fibrous cap, erosion or ulceration, hemorrhage, fibrous tissue and lipid content. Sections from the same specimens were then analyzed using LSCM; slides were viewed with 488 excitation and 515 LP emission. The presence or absence as well as the pattern of distribution of these markers (proteins) were correlated with the histological and preoperative ultrasonic appearances of the plaques.
Results
Ultrasound imaging of carotid plaques revealed 10 with echolucent (lipid-laden/unstable) properties and 10 with echogenic (fibrous/stable) features. Intense immune-reactivity for C pneumoniae was observed in two thirds of echolucent plaques, clustering near endothelial cells of the intimal region, and in the neo-endothelial regions of the specimens. By contrast, low level and scattered C pneumoniae immune-reactivity was observed in echogenic plaques. MMP-3 (stromelysin) level was higher in echolucent than in echogenic plaques. High levels of this enzyme were observed near regions of ulceration, necrosis and in areas where the fibrous cap was thin or torn. Isoforms of NOS enzymes were seen in all carotid plaques irrespective of intra-plaque features however, levels of inducible NOS (NOS-II) were higher in echolucent than in echogenic plaques. Higher levels of immune-reactive SOD were also observed in plaques with higher degree of stenosis (more than 75%–80% measured by ultrasound scan). No direct relationship was evident between the neurological features experienced by the study group and the immuno-histochemical findings. There was however a relationship between the morphology of the plaque and the immuno-histochemical results. Both bright-field microscopy and Laser Scanning Confocal Microscopy (LSCM) were used to generate 3D images of surgically removed carotid plaques. 3D imaging of carotid plaques, using LSCM showed that most specimens were predominately composed of lipid material, comprising necrotic core of amorphous debris and cholesterol clefts, with varying degrees of fibrous tissue present in all plaques. Regions of actual fibrous cap disruption and some ulceration were also seen. Fraying of the fibrous cap was notable with fibrous cap erosion and exposure of underlying necrotic core to lumen. The extent of breaks in the fibrous cap varied with each plaque. Evidence of carotid plaque vulnerability (to rupture) was demonstrated by reduced fibrous cap thickness, a large lipid-necrotic core, and increased inflammatory cells infiltrate with evidence of cracking.
Discussion
Although the findings of this study are suggestive that C. pneumoniae may be involved in the worsening and destabilization of the carotid atherosclerotic plaque, more evidence is needed to ascertain whether C. pneumoniae infection may be an independent, modifiable risk factor for ischemic stroke. Results of this study also showed that MMP3 or its pro-enzyme may play an important role in digesting fibrous tissue of the plaque, leading to thinning or tearing of the fibrous cap. This might result in subsequent destabilization of the plaque, leading to embolization and cerebrovascular events. Furthermore, increased level of SOD expression in carotid plaques might be linked to the degree of stenosis of the affected carotid artery. Enzymes identified in this study may have been influenced by (i) inflammatory conditions prevailing in these plaques (e.g., C. pneumoniae might be responsible for triggering cascades of inflammatory events leading to activation of these enzymes), or (ii) shear stress which might be responsible for stimulation of these enzymes. The 3D geometry of carotid plaque also showed evidence of shearing stresses, resulting from fluid flow which might contribute to the degree of instability of the plaque. This is a complex process which might also include the mechanical activation of enzymes such as matrix metalloproteinases, nitric oxide synthases and Superoxide Dismutase. The behavior of these enzymes in response to fluctuations in the velocity field in both echogenic and echolucent plaques is yet to be investigated. Possible activation of these enzymes by fluid dynamical instabilities and the implications of such activation on the destabilization and progression of atherosclerotic plaques require further investigation. Once the role of 3D geometry and microrheology on plaque stability has been investigated and quantified, more opportunities will be available for translating the results into clinical applications.
Conclusion
There is a need for stronger evidence to assist in the diagnosis, treatment, and secondary prevention of stroke in patients in whom an infectious cause for stroke is probable. It has been suggested that mechanically induced or flow-sensitive enzymes contain positive and negative shear stress response elements in their encoding genes and can be stimulated or suppressed according to the nature of blood flow. However, it is still not possible to show any definite link between specific enzyme(s) and cerebrovascular events. Such an association is probably multifactorial and mediated by a combination of the degree of stenosis, plaque morphology, dynamic and biological factors. We are currently investigating the link between certain inflammatory markers and cerebral blood flow and cerebral auto-regulation in patients presenting with Transient Ischemic Attack (TIA or mini stroke) for the first time to explore further the role of inflammation in stroke. This study has just started; it involves 200 patients recruited from Qatar and UK. One of its outcomes will be to correlate impaired cerebral auto-regulation with a range of pro-inflammatory and anti-inflammatory markers in first time TIA patients. In doing so, we will study the profile, rather than just the level, of these inflammatory markers in each patient, taking into account the time lapse between onset of symptoms and the collection of blood specimen (for cytokines analysis) from each patient. “Part of this study was made possible by grant NPRP 6 – 565 – 3 – 141 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the author[s].”
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Analysis of the Relationship between Physical Self-Concept and Body Composition
المؤلفون: Zsuzsanna Kneffel, Suhair Saleh, Wajiha Ghazi, Deema Qawassmi and Lina MajedBody image is a psychological construct which refers to self-concept including self-image and feelings an individual perceives regarding his or her body. Several studies have examined how women subjectively perceive their bodies in Western cultures compared to objective measures. However, limited studies have examined this relationship among women in the Gulf region (e.g., Qatar) in which Islamic traditional clothing (i.e., Abaya) is typically adopted and possible differences in the judgment of a healthy body shape might be found. The purpose of this study was to see whether there is a connection between the objective body composition measures [i.e., body weight (BW), body height (BH), body mass index (BMI)] and the subjective measures of physical self-description. We expect to find a tendency among females in this study to estimate a thinner body image compared to their current/measured one.
Methods
female volunteers (18–26 years) were recruited from Qatar University. We measured their body composition (i.e., BW, BH and BMI). We used the short version of the Physical Self-Description Questionnaire (PSDQ), a multidimensional physical self-concept instrument with 11 original subscales including: body fat, health, appearance, global physical self-concept. The collected data for all variables were analyzed using Statistical software (v.12, DELL) for correlations using Pearson's coefficients.
Results
Based on the BMI results, 25.7% of the participants were classified as overweight or obese (12.3% and 13.4%, respectively). Results indicated a significant negative moderate correlation between the global physical self-concept on one side and BMI (r = − 0.27) and BW (r = − 2.0) on the other. Furthermore, the perceived body fat showed significant negative correlation with BMI (r = − 0.57) and with BW (r = − 0.52). The inter-correlation within the subscales showed that the perceived body fat was significantly correlated with appearance (r = 0.25), health (r = 0.16) and global physical score (r = 0.34).
Conclusion
Our results indicated a clear and logic relationship between perceived global physical self-concept scores and participants' body composition (i.e., negative correlation). However, an interesting result in line with our hypothesis and concerning the way participants perceived their own body fat indicates a negatively correlation with BMI and BW. In the studied population, a possible interpretation could be done based on the positive link revealed between perceived body fat, perceived appearance, perceived health and global physical score. Indeed, this could indicate that the ideal perceived body might be different and higher than norms presented in the World Health Organization classification. To get further insights on the nature of these relationships, we have started new investigations on the relationship between the other subscales of physical self-description and a comprehensive physical fitness test (ALPHA-FIT Test, UK).
Keywords
physical self-concept, body image, body composition, Qatar
This publication was made possible by UREP grant ν17-044-3-011 from the Qatar national research fund (a member of Qatar foundation). The statements made herein are solely the responsibility of the authors.
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Corneal Confocal Microscopy Identifies Neuronal Pathology in Patients with Stroke Independent of Glycemic Status and Cerebral Pathology on MRI
Background
Worldwide, cerebrovascular disease (CVD) is the leading disease-related cause of chronic disability; the second most common cause of death and dementia; and a significant burden to patients, caregivers, and healthcare systems. Major risk factors for stroke include diabetes, hypertension, smoking and dyslipidemia which are highly prevalent in the gulf region. Indeed in Qatar, the incidence of cerebrovascular disease is increasing and most patients have major vascular risk factors. In data from the HMC Stroke Registry ∼71% of patients presenting with stroke had diabetes and indeed diabetes was undiagnosed at the time of presentation in 35% of patients. Current imaging techniques to detect early sub-clinical cerebral damage and hence those at risk of stroke includes computerized tomography (CT) and magnetic resonance imaging (MRI). MRI in particular can detect features of small vessel disease such as accumulating silent infarcts, cerebral microbleeds [CMB], periventricular white matter hyperintensity and perivascular spaces which all predict a higher risk of stroke. However, these abnormalities provide a measure of vascular and not neuronal integrity and it is not feasible or practical to undertake MRI simply to identify those at risk of stroke. There is therefore an unmet need for a rapid, non-invasive, sensitive, cost-effective, reproducible and easily imaging biomarker for neuronal damage in subjects at risk of stroke. We have pioneered the technique of corneal confocal microscopy (CCM). Our studies (NIH (5RO1-NS46259-03, R01DK077903-01A1 NINDS), JDRF (17-2008-1031, 8-2008-362)) have shown that corneal confocal microscopy (CCM) can quantify early axonal damage in diabetic neuropathy (1), reliably (2), with high sensitivity and specificity (3). Furthermore, we have shown that subjects with impaired glucose tolerance (IGT) and other vascular risk factors also show corneal nerve loss using CCM (4). Furthermore, these abnormalities improve with an improvement in blood pressure, lipids and HbA1c, all risk factors for stroke (5) and with change in glucose tolerance (6). We have recently published a large normative reference database (7) and developed an automated image analysis algorithm to enable rapid and objective quantification of corneal nerve morphology (8). We therefore hypothesized that CCM may identify corneal nerve loss driven by the common vascular risk factors which may lead to stroke and thereby provide a surrogate for cerebral neuronal loss. Hence, CCM may allow us to identify subjects who may be at high risk of developing stroke and enable risk stratification and targeted risk factor intervention in these individuals.
Aim
We undertook CCM in a cohort of patients admitted to HMC with a clinical and radiological diagnosis of stroke.
Methods
17 stroke patients (age: 53.13 ± 9.09, years) and 15 age-matched healthy control participants (age: 55.30 ± 8.98, years) underwent corneal nerve assessment using CCM (Heidelberg HRT III) to quantify corneal nerve fiber density (CNFD)(no./mm2), corneal nerve fiber branch density (CNFBD)(no./mm2), corneal nerve fiber nerve length (CNFL)(mm/mm2) and corneal nerve fiber tortuosity (TC) and metabolic testing. Stroke patients underwent detailed neurological assessment to define the severity of the stroke using a National Institute of Health Stroke Scale (NIHSS), 3D Carotid Doppler and 3 Tesla MRI. Stroke patients were stratified into different groups for analysis: Normoglycemia (HbA1c < 5.7) (age: 57 ± 8.12, years, n = 5) v dysglycemia (HbA1c ≥ 5.7), n = 12); neurological disability: NIHSS < 4 (n = 9) v NIHSS ≥ 4 (n = 8), Pathology on MRI: < 10 silent infarcts n = 5 v > 10 silent infarcts (n = 4), patients with periventricular white matter hyperintensity (n = 11) v no periventricular white matter hyperintensity (n = 4).
Results
There was significant difference in HbA1c (8.51 ± 2.35; 5.72 ± 0.36, %, p < 0.001) between stroke patients with dysglycemia and healthy control participants and patients with dysglycemia compared to normoglycemia (8.51 ± 2.35; 5.18 ± 0.35, %, p < 0.009). There was no difference in the total cholesterol (4.96 ± 1.62, 5.34 ± 0.80, mmol/L, p < 0.457), triglycerides (1.32 ± 0.35, 1.64 ± 0.48, mmol/L, p < 0.118), HDL (1.73 ± 1.57, 1.44 ± 0.47, mmol/L, p < 0.527), LDL (2.92 ± 1.42, 3.16 ± 0.69, mmol/L, p < 0.593), hypertension (hypertensive/normal tension, 1/11, 0/15, p < 0.255), height (172.00 ± 4.24, 169.24 ± 9.85, cm, p < 0.708) weight (88.50 ± 13.44, 81.51 ± 13.37, kg, p < 0.500) or BMI (30.00 ± 2.83, 28.47 ± 4.44, Kg/m2, p < 0.649) between stroke patients and control subjects. There was a significant reduction in CNFD (30.47 ± 5.76; 39.50 ± 8.49; p < 0.043) but no change in CNBD (117.50 ± 25.99; 100.54 ± 37.30; p < 0.365), CNFL (29.49 ± 2.65; 27.45 ± 5.56; p < 0.447) or CNFT (19.27 ± 5.07; 15.32 ± 3.94; p < 0.091) in the stroke patients with NGT as compared to the healthy control participants. There was a significant reduction in CNFD (30.17 ± 5.68; 39.06 ± 8.36; p < 0.004) and increase in CNBD (127.71 ± 34.09; 97.80 ± 37.49; p < 0.042) and CNFT (18.57 ± 4.36; 14.93 ± 4.08; p < 0.035) but no change in CNFL (27.06 ± 4.76; 26.97 ± 5.67; p < 0.965) in stroke patients with dysglycemia as compared to the healthy control participants. There was no difference in CNFD (30.17 ± 5.68; 30.47 ± 5.76; p < 0.921), CNBD (127.71 ± 34.09; 117.50 ± 25.99; p < 0.559), CNFT (18.57 ± 4.36; 19.27 ± 5.07; p < 0.777) or CNFL (27.06 ± 4.76; 29.49 ± 2.65; p < 0.306) between stroke patients with and without dysglycemia. There was no significant difference in CNFD (30.36 ± 5.26; 30.14 ± 6.17; p < 0.941), CNBD (123.46 ± 32.58; 126.12 ± 32.37; p < 0.869), CNFT (19.26 ± 5.30; 18.22 ± 3.48; p < 0.645) or CNFL (27.05 ± 4.38; 28.60 ± 4.38; p < 0.479) in stroke patients with NIHSS < 4 compared to NIHSS ≥ 4. There was no significant difference in CNFD (30.52 ± 5.27; 32.16 ± 7.73; p < 0.715), CNBD (120.00 ± 39.76; 134.96 ± 43.98; p < 0.609), CNFT (15.71 ± 2.55; 17.61 ± 4.59; p < 0.453) or CNFL (26.54 ± 5.43; 28.43 ± 4.90; p < 0.606) in stroke patients with silent infarcts < 10 vs ≥ 10. There was no significant difference in CNFD (30.18 ± 5.15; 30.08 ± 6.00; p < 0.973), CNBD (127.20 ± 28.08; 121.35 ± 45.78; p < 0.766), CNFT (20.36 ± 4.53; 15.15 ± 2.56; p < 0.051) or CNFL (28.91 ± 2.95; 25.50 ± 5.67; p < 0.144) in stroke patients with white matter ischemia compared to stroke patients without white matter ischemia.
Conclusion
Corneal confocal microscopy identifies greater corneal nerve fibre abnormalities in patients admitted with stroke, which is present in patients with and without dysglycemia. It may therefore reflect the consequence of vascular risk factors independent of glycemic status. However, the extent of corneal nerve fibre pathology does not differ in relation to the severity of neurological disability or extent of pathology on MRI. Larger, longitudinal follow up studies are required to determine the prognostic ability and utility of CCM as a surrogate imaging biomarker for stratifying patients at risk of stroke.
References
1. Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes care. 2013;36(11):3646–51.
2. Petropoulos IN, Manzoor T, Morgan P, Fadavi H, Asghar O, Alam U, et al. Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology. Cornea. 2013;32(5):e83–e9.
3. Petropoulos IN, Alam U, Fadavi H, Marshall A, Asghar O, Dabbah MA, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Investigative ophthalmology & visual science. 2014;55(4):2071–8.
4. Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes care. 2014;37(9):2643–6.
5. Tavakoli M, Kallinikos P, Iqbal A, Herbert A, Fadavi H, Efron N, et al. Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabetic medicine: a journal of the British Diabetic Association. 2011;28(10):1261–7.
6. Azmi S, Ferdousi M, Petropoulos IN, Ponirakis G, Alam U, Fadavi H, et al. Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes. Diabetes care. 2015;38(8):1502–8.
7. Tavakoli M, Ferdousi M, Petropoulos IN, Morris J, Pritchard N, Zhivov A, et al. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: A multinational normative data set. Diabetes care. 2015;38(5):838–43.
8. Dabbah M, Graham J, Petropoulos I, Tavakoli M, Malik R. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Medical image analysis. 2011;15(5):738–47.
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Roadside Observational Surveys of Restraint Use by Young Children in Qatar: Initial Results and Recommendations
المؤلفون: Shahnaz MalikIntroduction
In a report by the WHO Eastern Mediterranean Region 1, the non-use of child restraints for children was identified as a key risk factor that can be addressed by the adoption and enforcement of legislation that will increase their use. Currently, there are no child restraint laws in Qatar. The objective of the study is to report baseline data on child restraint use and to provide evidence to inform the passage of child passenger restraint laws in Qatar.
Methodology
This roadside observational survey was conducted as part of the Young Kids in Safe Seats Project funded by the Qatar Foundation. Trained observers conducted roadside observations of passenger restraint use in vehicles with children, less than 5 years, at 12 sampling sites. Standard data was collected per observation: seating position, restraint used and appropriateness of restraint used.
Results
Of 2232 observations of young child passengers; 41% were properly restrained, 21% improperly restrained and 38% unrestrained, 10.9% were on an adult's lap. The most common seating location was right 2nd row followed by left 2nd row. These 2 locations also had the highest rates of proper restraint use. The positions with the lowest restraint use were the front and 2nd row middle seat. One in 9 children observed was illegally seated in the front row, most on the lap of an adult [38.3%] or unrestrained [34.4%].
Conclusions
This is the first observational study in Qatar that measures child restraint rates in children younger than 5. Less than half of these children are traveling safely. Priority areas for intervention include: enforcement of existent laws banning children in the front seat, education about the risks for children in an adult's lap and encouraging the proper use of age/size appropriate restraint systems. These findings can inform the development of national child passenger restraint laws.
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A Five-Year Time Trend Analysis of Road Traffic Injuries [Rtis] and Deaths among Infants and Toddlers in Qatar
المؤلفون: Shahnaz MalikBackground
Road Traffic Injuries (RTIs) are the leading cause of death in Qatar1, but the epidemiology of these injuries in the infant (0–1 years) and toddler (2–4 years) [IAT] population has not been reported. This study aimed to document and analyze the epidemiology of RTIs in IATs of Qatar and make recommendations for targeted and age-specific recommendations to improve road safety for this population.
Methods
A retrospective analysis of data on child RTIs and RTI deaths admitted to the Hamad Medical Corporation [HMC] Trauma Center or Mortuary in Doha, Qatar, from 2008–2014, was conducted. Temporal trends in the nature of RTI's and RTI deaths, road user types and mortality rates were calculated and analyzed for the years that age-group population size was available.
Results
There were 189 severe RTIs and 15 RTI deaths during the study period. Males made up 80% of the injured and 60% of fatalities. The average age of the injured was 3 years and for fatalities was 2.8 years. Pedestrians [53%] and unrestrained passengers [43%] made up the majority of the injured. There have been steady declines in severe RTI and RTI death rates from 2008 to 2012 [25.9 to 22.2 RTIs per 100,000 and 0.9 to 4.0 RTI deaths per 100,000], but these rates are still two times higher than those for IAT in other high-income countries [HICs] like the United States and Germany2.
Conclusions
RTIs and RTI death rates in IAT in Qatar have been declining but proven programs for improved safety of child pedestrians and passengers must be implemented if it is to approximate those in other HICs. This includes programs around child restraint use and improving pedestrian environments and practices/supervision for IAT.
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High-Throughput Discovery of Cancer Cell Surface Interactions by Pairing cDNA Phage Display and Next Generation Sequencing
المؤلفون: Simeon Andrews and Joel MalekDetermining the complement of binding partners for a given protein is one of the most common questions in the field of biochemistry. Understanding complex protein interaction networks enables predictions about putative drug targets and the effects of mutations. Among the many techniques used to study protein-protein interactions, cDNA phage display stands out as a relatively unbiased method of finding protein interaction partners. By inserting cDNA fragments into the phage genome, we can cause the phage to express these cDNA fragments as peptides on its surface, thus physically linking a protein fragment with the DNA that encodes it. Limited work has previously been done with cDNA-encoding phage libraries, mainly focused on very strong interactions.
Cell lines MDA-MB-231 and MCF-7, derived from human breast tumors, model more and less aggressive cancers, respectively. An understanding of their surface interactions could provide insight into the biology of aggressive cancers, and identify new targets for therapy.
Using phage cDNA libraries encoding millions of fragments from cDNA libraries, we have probed the surface of breast cancer cell lines. These cells were exposed to the phage cDNA libraries, followed by brief washing; this selects for the phage particles that bind selectively to the cells. Importantly, these gentle washes should permit the detection of low-energy interactions as well as higher affinity ones. The selected libraries can then be analyzed by next generation sequencing (NGS) technology. NGS permits the recording of tens of millions of cDNA sequences from each library. As a result, we can quantify the differences in the phage binding to aggressive versus non-aggressive cell lines. This allows us to discover cell surface markers of aggressiveness in cancer, and informs us of native cell surface interactions.
We have shown that phage display, paired with next generation sequencing, can provide quantitative information on the complement of proteins that bind to cancer cells. Two rounds of selection are sufficient to identify potential markers of cell phenotypes, or possible targets for future therapy. In our initial screening, we found hundreds of sequences that were specific to one cell line versus the other. Although these sequences are likely valid, we determined that the majority do not correspond to native protein sequences. This was due to the construction of the original (purchased) phage library. The insertion of the cDNA into the phage had been, of necessity, somewhat random, resulting in a large fraction of phages with cDNA sequences that were out of frame. Given that phages expressing truncated proteins have a growth advantage over phages expressing longer cDNAs, these truncated proteins rapidly overtook expanding libraries.
We have expanded this work by the creation of our own phage cDNA libraries. cDNA from the MCF-7 cell line was created, sheared, and inserted into a phage we generated. This new phage DNA encodes a biotin signal after the cDNA sequence. By using streptavidin beads to select for biotinylated phages, we can greatly increase the fraction of in-frame cDNAs in the phage pool. We have shown this selection is effective, while still leaving a diverse library. Selection of these frame-correct libraries has now revealed much more informative selections against mammalian cell surfaces. As an unbiased approach, cDNA phage display on cancer cells promises to uncover substantial new biology.
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Patient Counseling Practices among Community Pharmacists in Qatar
المؤلفون: Bridget Javed, Nadir Kheir and Adil YousifBackground
Patient counseling is a term used in the field of pharmacy to describe the communication that takes place between a pharmacist and a patient in regards to his or her medication therapy. Patient counseling is deemed to be the professional responsibility of pharmacists. Patients require education on the proper use of medications to improve therapeutic outcomes and avoid treatment failure. 1 Pharmacists are in an excellent position to provide this type of education and counseling to patients, and are readily accessible to the public as a first point of contact for patients with medical inquiries. 2 Several studies have shown that counseling provided by pharmacists can prevent medication related problems, improve patient compliance with medications, and contribute to positive therapeutic outcomes. 3, 4 Patient counseling practices among Arab countries are not clearly identified in literature or mandated by governing authorities or agencies. The reason may be the low expectation by the public of the pharmacist who for so long had confined their role to filling and selling medications. Many studies have identified various aspects such as the busyness of the pharmacies and the education, age, and attitude of the pharmacists as barriers for the provision of counseling. 4 The assessment of these barriers in addition to patient characteristics will assist in further evaluating and understanding pharmacist's counseling practices in community pharmacies. Since patient counseling is an essential element of patient care, investigating the current state of patient counseling practices in Qatar is necessary. One of the methods that help to gain an accurate assessment of pharmacist's counseling practices is to observe pharmacists in their natural environment without prior knowledge to the minimize the Hawthorne effect. 5 Therefore, to lessen the potential Hawthorne effect (change in someone's behavior due to the knowledge that s/he is being observed), this research project will utilize simulated patients (also known as mystery shopper) to examine the counseling practices of community pharmacists in Qatar. The objectives of this research project are to evaluate the quality of patient counseling practices by community pharmacists in Qatar and to determine if an association exists between the content of patient counseling and the characteristics of community pharmacists, patients, and community pharmacies.
Methods
This is an observational cross sectional study to evaluate the community pharmacist's counseling practices in Qatar using simulated patients. Two patient scenarios were created to assess the counseling provided by the pharmacist to the patients with diabetes and asthma. Two simulated patients of Arab decent fluent in Arabic and two simulated patients of non-Arab decent fluent in English were recruited for this study. Each simulated patient was randomly assigned to either the diabetes or asthma scenario. Each simulated patient entered the community pharmacy and observed the number of customers to assess for busyness of the pharmacy. The simulated patient then asked to speak to the pharmacist and requested their assigned medication. Prompting questions were initiated by the patient after each pharmacist was provided with the opportunity to counseling the patient. The simulated patient then purchased the medication to authenticate the interaction and left the pharmacy. Immediately following the interaction, the simulated patient completed a form that assessed the pharmacist's counseling ability. Once completed, the simulated patient returned to the same the pharmacist to explain the purpose of the study. Consent was obtained from the pharmacist and a survey written in English or Arabic was administered only to those who provided consent. The written survey included questions related to pharmacist demographics (gender, age, native language, pharmacy degree received, country of pharmacy education, graduation year, and practice experience), pharmacist's perception on patient counseling (barriers and importance), and pharmacy characteristics (number of staff, availability of a counseling area, and busyness of the pharmacy).
Results
One hundred and twenty-nine pharmacists consented to participate in this study. The majority of pharmacists were young male pharmacists with at least 2 years of practice experience in Qatar. Most pharmacists have received their pharmacy degree from India and Egypt. Most of the community pharmacies had one pharmacist per shift and no private patient counseling area. In the diabetes scenario (n = 64), the male simulated patient received significantly better counseling from the pharmacist when compared to the female simulated patient. The pharmacist's knowledge regarding diabetes was considered poor with over 60% of pharmacists referring the patient to the physician. For the asthma scenario (n = 65), the male simulated patient received significantly better counseling from the pharmacist compared to the female simulated patients. Only 6% of the pharmacists were able to properly demonstrate the correct inhaler technique to patients. However, more than 50% of the pharmacists were are able educate the simulated patient on the role of the asthma medications. Overall, the pharmacist's gender, age, native language, pharmacy degree, country of pharmacy education, and years of practice experience did not seem to have an effect on the quality of counseling provided to patients. Better counseling was provided by the community pharmacists to the simulated patients when the pharmacy was not busy. Not having a private counseling area in the pharmacy was a significant barrier leading to lower counseling practices among community pharmacists. Some other barriers related to patient counseling identified by pharmacist include time, no access to patient medication records, and patients not interested in the counseling provided by the pharmacist.
Conclusion
The findings from this study suggest the current counseling practices among community pharmacists in Qatar is substandard. Development of continuing education programs for practicing pharmacists to enhance their communication skills and knowledge to improve counseling practices is strongly advocated. These educational programs will need to be tailored to meet the needs of the pharmacists to address the fundamental communication skills that each pharmacist should possess for practice. In addition, pharmacy laws and regulations need to be updated to meet the changes in the pharmacy profession from dispensing to a patient centered care focus. Community pharmacies need to be equipped with a counseling area, mandatory drug information resources, and the ability to maintain medication profiles for each patient. Pharmacy regulations should also consider mandating all pharmacists to provide counseling for each patient.
References
Resnik DB et al. The conflict between ethics and business in community pharmacy: what about patient counseling? Journal of Business Ethics 2000;28:179–186.
Taylor J. OTC counseling: review of pharmacist performance. Medscape Pharmacists [serial online] 2001 Aug [cited 2009 Dec 21]; 2(2). Available from URL: http://www.medscape.com.
American Society of Health-System Pharmacists. ASHP guidelines on pharmacist-conducted patient education and counseling. Am J Hosp Phar 1997;54:431–4.
Svarstad BL, Bultman DC, Mount JK. Patient counseling provided in community pharmacies: Effects of state regulation, pharmacist age, and busyness. J Am Pharm Assoc 2004;44:22–29.
Puspitasari HP, et al. A review of counseling practices on prescription medicines in community pharmacies. Res Soc Admin Pharm 2009;5:197–210.
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Genotype and Phenotype Correlation of Breast Cancer in BRCA Carriers and Non-Carriers
المؤلفون: Hekmet Bugrein and Salha Mohammed BujassoumBreast cancer is both genetically and histopathologically heterogeneous disease, the biological basis for this heterogeneity is unknown, although there are some distinct phenotype-genotype correlations. Approximately 5% to 10% of breast cancer is hereditary and BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast cancers. BRCA1 and BRCA2 mutant cells have defects in the DNA repair and chromosomal instability with marked defects in cell division [9]. In the literatures BRCA1 and BRCA2 associated breast cancers have different clinical, histological, immune-phenotypic features [6]. To validate the effect of BRCA 1 or BRCA 2 germ line mutation on breast cancer aggressiveness and on the clinical features, we analyzed, correlate the genotype, and compared histological and molecular status and clinical variables of 31 breast cancer patients with BRCA gene mutations carriers and histopathological and molecular characters of breast cancer in 50 patients affected in the same age group but with no pathogenic mutations or variants of unknown significant (VUS) in either BRCA1 or BRCA2 genes. This is a retrospective study and involved cases assessed on the hereditary breast and ovarian cancer clinic between 2013–2015 at the National Center of Cancer Care and Research (NCCCR) in the State of Qatar.
Methods
A retrospective review of medical records was conducted to determine the clinical characteristics, the molecular results of BRCA testing and the tumor characteristics from the histopathology reports in addition to a new review of the tumor blocks. All of the cases were evaluated at the high risk hereditary breast and ovarian cancer clinic at the national center of cancer care and research (NCCCR) in state of Qatar between 2013–2015.
Results
(81) patients with breast cancers were diagnosed at ages 50 year and below, (50) patients were BRCA negative, and (31) patients were BRCA positive, (21) were BRCA1 mutation carriers, (8) patients were BRCA2 mutation carriers and (2) carried mutations in both BRCA1 and BRCA2 genes. On BRCA1,2 gene sequencing and MLPA the most detected mutation in BRCA gene is small frame shift deletion or insertion in one or more Exons, and protein truncation. In this study age group carriers and non-carriers are young (50 and below) but BRCA mutation detected with higher incidence in younger ages, Histopathology of invasive ductal carcinoma (IDC) was detected in (93.5%) of BRCA gene mutation carriers with (74%) high nuclear grade 3, and a higher proliferative rate were detected in non carriers control group nuclear grade 3 in 36% of cases and high proliferative rate in 31%. Triple negative (48.6%), Triple positive (16%), ER PR positive. Her 2 negative (26%) and ER PR negative Her 2 positive (9.6%) in BRCA carriers. In non carriers TN in 17%, triple positive 13%, ER PR positive Her 2 negative 44%, ER PR negative Her 2 positive 13%.
Conclusion
These results suggest that tumors associated with BRCA mutations are more likely to be basal sub type, has more aggressive behavior (invasive, grade 3, Triple negative) affect younger age group, patient presented in more advanced stage further analysis needed to determined clinical outcomes in BRCA positive compare to control, in regards to local and systemic relapse, overall survival. however will continue to build up our data base for better characterization of our hereditary breast cancer cases at clinical and molecular level and use this information for future development of targeted anti-cancer agents use.
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Prospective Study of Incidence and Predictors of Peripheral IV Catheter–Induced Complications
المؤلفون: Mostafa Abolfotouh, Mahmoud Salam, Ala'a Bani Mustafa, David White and Hanan BalkhyBackground
Peripheral intravenous catheters (PIVs) are invasive catheters that may endure risks of clinical complications affecting health care outcomes and patient satisfaction. Patients requiring frequent PIV insertions due to an extended length of stay of one week or more would undergo multiple PIV pricks during their course of hospitalization. The combined factors of multiple PIV insertions and extended hospital stay make chronic patients especially at a higher risk for phlebitis and subsequently infection No studies in the literature review discussed the phlebitis rates and risks when toxic medications were infused using a peripheral catheter. The aim of this study was to determine the pattern and incidence of PIV complications among patients admitted to a tertiary care military health care facility in central region of Kingdom of Saudi Arabia. This was achieved through the following objectives: (1) Estimation of the cumulative incidence and incidence density for major PIV complications (catheter occlusion, dislodgment, infiltration, and phlebitis) during a period of 1 month, (2) Identification of significant risk factors for PIV complications such as patient related characteristics (gender, age, co-morbidities) or catheter related characteristics (catheter size, dressing, site of insertion, type of infusion, dwell times), and (3) Determination of the time line for the occurrence of various PIV complications.
Methods
An observational prospective cohort study investigated PIV pattern and complications among 359 adults with 842 PIV catheters, admitted to various wards at KAMC with a total of 2505 catheter days. Data on patient characteristics (age, gender, and health complaints) and PIV characteristics (Catheter size, duration, insertion site, nature of PIV infusate, and type of dressing) was collected. PIV catheters-related clinical outcomes (Pain, Phlebitis, leaking and others) were recorded on 12–hour intervals, using the Visual Inspection Phlebitis (VIP) scale. Phlebitis was defined as the presence of two or more signs of pain, tenderness, warmth, erythema, swelling, or a palpable cord, with or without purulent drainage from the catheter insertion site. Infusion Phlebitis scale can range from (0), indicating no symptoms of phlebitis, to (5), with signs of purulent drainage, redness, and a palpable cord greater than 3 inches. Infiltration was defined as permeation of intravenous fluid into the interstitial compartment, causing swelling of the tissue around the site of the catheter. All PIV catheters were changed for a score of 2 or more, determined by the presence of a cold/warmth skin region around the insertion site, pain, redness, and/or edema extending from 1 to 2 inches above the PIV site. Incidence density (DI) and cumulative incidence (CI) of complications were calculated. Regression analyses were applied to determine the significant predictors of complications. Significance limits were set at P < 0.05.
Results
One half of all patients were 65 years and above, with no significant sex difference. The majority of patients (76.88%) had medical chief admission complaints, whereas (51.53%) were admitted in cardiac wards. Complicated catheters were found in 141(39.3%) patients, with 273 complications (32.4/100 catheters), 190 complicated catheters (CI = 22.56/100 catheters & DI = 75.84/1000 catheter days). Phlebitis ranked first among complications, with a CI of (17.58%), followed by pain (7.60%), leaking (3.92%) and dislodgement (2.38%), and extravasations and occlusion (0.48% each). When the analysis was based on failure per 1000 device days, and after adjusting for all possible confounders, female gender remained as a significant predictor of higher incidence of overall complications (p = 0.00001), phlebitis (p = 0.000003) as well as other complications (p = 0.0.0003). Insertion in fore/upper arm was a significant predictor of both phlebitis (0.024) and other complications (0.049), while medical infusion was a significant predictor of phlebitis (0.02) and overall complications (0.006).
Conclusion
Incidence of complications in this study is comparable with figures in previous studies, however, better insertion techniques may be sought to lower the incidences of PIV complications, thus extending their onset beyond day 3. Changing catheters is recommended when clinically indicated rather than routinely post 72 hours of insertion which in return minimizes the frequency of insertions per patient and subsequently complications.
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A New Monte Carlo Tools to Simulate PET Scanner based on FLUKA
المؤلفون: Yassine ToufiquePositron Emission Tomography system is a functional medical imaging technique providing 3D images of the living processes inside the body relying on isotopes. These systems are used to study animal models of human disease. It has been found that significant benefits in spatial resolution, sensitivity, image quality, and quantification were achievable using preclinical systems. The physics of PET systems is based on the detection in coincidence of the two 511-keV rays, produced by an electron-positron annihilation, and emitted in opposite directions, as dictated by the conservation of energy and momentum. The radioactive nuclei used as sources of emission of positrons for PET systems are mainly 11C, 13N, 15O, and 18F, which are produced in cyclotrons and decay with half-lives of 20.3 min, 9.97 min, 124 sec, and 110 min, respectively. These radio-nuclides can be incorporated in a wide variety of radiopharmaceuticals that are inhaled or injected, leading to a medical diagnosis based on images obtained from a PET system. Traditionally, Monte Carlo codes (MC) are powerful tools for the research and development of new scanners and advanced image reconstruction algorithms. Among the benefits from extensive use of MC simulations we can highlight the design of new PET scanners, the development and assessment of image reconstruction algorithms and other applications, such as the Effect of inter-crystal scatter on estimation methods for random coincidences and image reconstruction algorithms assessment. Simulations make it feasible not only to refine the design parameters of PET scanners, but they also help to identify obstacles concerning count rate, resolution, sensitivity, etc. There are different Monte Carlo codes that simulate the transport of radiation through matter, such as FLUKA, GEANT4, MCNP, EGS4 and PENELOPE. All of them have been widely employed in the field of nuclear imaging and internal dosimetry. In this work we present and validate a new PET-dedicated Monte Carlo tool. This tools is based on FLUKA and implemented on FLAIR the GUI of FLUKA. FLUKA is a multi-purpose particle physics code for calculations of particle transport and interaction with matter. It is used in a wide range of applications in high energy experimental physics and engineering including accelerator driven systems, shielding, detector or target design, neutrino physics, dosimetry, activation and medical physics etc. this tools is an easy-to-use application which allows comprehensive simulations of PET systems within FLUKA. The developed tools include a PET scanner geometry builder and a dedicated scoring routine for coincident event determination. The geometry builder allows the efficient construction of PET scanners with nearly arbitrary parameters. We also present recent medically-oriented developments for Flair, which allows to import DICOM files and convert them into FLUKA voxel geometry or into a density map of radioactive isotopes, which could be employed as source in a convenient way. The coincidence events from the scoring can be saved in standard output formats, including list mode and binary sinogram. Such coincidence events can be further 2D- or 3D-reconstructed using Filtered back-projection (FBP) or Maximum Likelihood Expectation Maximization (MLEM) algorithms. In the MLEM method, the user can specify the size of the voxel as well as the size of the reconstructed image. Another source of flexibility is the possibility of adding new functionalities: a user can write a Python, C++ and FORTRAN routine and add it to Flair. This paper describes the PET tools and shows the results of extensive validations and comparisons of simulations against real measurements from commercial acquisition systems.
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Predicting Potential Functional Modules in Biological Networks Through Context-Sensitive Random Walk Based Network Querying
المؤلفون: Byung-Jun Yoon and Hyundoo JeongNetwork querying algorithms provide computational means to identify conserved network modules in large-scale biological networks that are similar to known functional modules, such as pathways or molecular complexes. Two main challenges for network querying algorithms are the high computational complexity of detecting potential isomorphisms between graphs and ensuring the biological significance of the query results. In this work, we propose a novel network querying algorithm that can enhance the biological significance of the query results through the use of a context-sensitive random walk (CSRW) model. In order to identify conserved subnetwork regions in the target network that are similar to a given query network, the algorithm estimates the node correspondence between the query and the target networks based on the CSRW model. Inspired by the pair hidden Markov model (pair-HMM) that has been widely used in comparative sequence analysis, the CSRW model can effectively capture the similarities between graphs by explicitly accounting for potentially inserted and deleted network nodes. Based on the estimated CSRW node correspondence scores, our algorithm first identifies high-scoring regions (referred to as the seed networks) in the target network that bear considerable similarity with (part of) the query. The seed networks are further extended by maximally minimizing the network conductance, which can effectively identify nearby nodes (e.g., proteins) that may share similar functions with other nodes in the current seed. Finally, the query result is pruned by removing irrelevant nodes based on an extension reward score, thereby improving the consistency of the final query result. Through extensive numerical simulations based on 938 real biological complexes, we show that our proposed algorithm yields accurate query results with enhanced biological significance.
References
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Spirin, V., Mirny. L.A.: Protein complexes and functional modules in molecular networks. Proc. Natl. Acad. Sci. USA 100, 12123–12128 (2003).
Sharan, R., Ulitsky, I., Shamir, R.: Network-based prediction of protein function. Mol. Syst. Biol. 3, 88 (2007).
Cook, S.A.: The complexity of theorem-proving procedures. Proceedings of the third annual ACM sym- posium on theory of computing, pp 151–158 (1971).
Jeong, H., Yoon, B.-J.: Effective Estimation of node-to-node correspondence between different graphs. IEEE Signal Processing Letters 22, 661–665 (2015).
Jeong, H., Yoon,B.-J.: Accurate multiple network alignment through context-sensitive random walk. BMC Systems Biology 9, S7 (2015).
Kelley, B.P., Yuan, B., Lewitter, F., Sharan, R., Stockwell, B.R., Ideker, T.: Path BLAST: a tool for alignment of protein interaction networks. Nucleic Acids Res. 32, W83–W88 (2004).
Shlomi, T., Segal, D., Ruppin, E., Sharan, R.: QPath: a method for querying pathways in a protein- protein interaction network. BMC Bioinformatics 7, 199 (2006).
Dost, B., Shlomi, T., Gupta, N., Ruppin, E., Bafna, V., Sharan, R.: QNet: a tool for querying protein interaction networks. J. Comput. Biol. 15, 913–925 (2008).
Bruckner, S., Hffner, F., Karp, R.M., Shamir, R., Sharan, R.: TORQUE: topology-free querying of protein interaction networks. Nucleic Acids Res. 37, W106–W108 (2009).
Bruckner, S., Hffner, F., Karp, R.M., Shamir, R., Sharan, R.: Topology-free querying of protein inter- action networks. J. Comput. Biol. 17, 237–252 (2010).
Sahraeian, S.M.E., Yoon, B.-J.: RESQUE: Network reduction using semi-Markov random walk scores for efficient querying of biological networks. Bioinformatics 28, 2129–2136 (2012).
Huang, Q., Wu, L.Y., Zhang, X.S.: An efficient network querying method based on conditional random fields. Bioinformatics 27, 3173–3178 (2011).
Huang, Q., Wu, L.Y., Zhang, X.S.: Corbi: a new R package for biological network alignment and querying. BMC Systems Biology 7, S6 (2013).
El-Kebir, M., Brandt, B.W., Heringa, J., Klau, G.W.: Natalie Q: A web server for protein-protein inter- action network querying. BMC Systems Biology 8, 40 (2014).
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Qatar Birth Cohort: Prevention Program of Risk Factors for Reproductive Health, Pregnancy and Child Health- A “Crossomics” Study
المؤلفون: Eman T Sadoun, Eleni Fthenou, Manolis Kogevinas and Faleh Mohamed AliBackground
Qatar demonstrated high incidence of low birth weight (8.8%), preterm deliveries (8.5%), and stillbirths rate (6.85) (Rahman et all, 2013). In addition, Qatari pregnant women are 1.2 times more likely to have a low birth weight newborn compared to other Arab women, where Gestational Diabetes (13.4%–20.8%) and Gestational Hypertension (15.2%–21.6%) were the leading maternal complications observed.). The WHO Qatar STEPS survey (2012) on chronic disease risk factors reported that 42.5% of the women in reproductive age have high risk factor for developing chronic diseases, while 68% are overweight with high blood pressure, elevated total cholesterol levels and fasting glucose. In addition to these data, the International Association of the study of Obesity has ranked Qatar sixth globally for prevalence of obesity.
Methods/Design
This is a prospective five year cohort study developed by SCH. Pregnant women (n = 2500) and offspring will be, respectively, recruited during certain critical periods of fetal development and the first years of life. The genetic, environmental exposures and potential human health risks (including cancer, immune, metabolic and cardiovascular diseases, neurodevelopmental abnormalities, asthma, and birth outcomes) will be investigated via specific questionnaires and collection of biological samples. The study comprises an extensive range of “omics” analyses for the in-depth investigation of the impact of the genome-exposome synergy in the establishment of adverse birth outcomes and early childhood diseases. This is a multidisciplinary study where SCH is collaborating with various research institutions such as PHCC, QU, WCMC-Q, QBRI, QBB, QEERI, TAMU-Q, Sidra, and HMC.
Discussion
Human epidemiological studies and animal research data propose a concept of fetal developmental programming whereby intrauterine environment is believed to trigger adaptations preparing the fetus in a particular range of environments. In this context intrauterine exposures have been referred to as the “fourth factor” in the causation of human disease. Consequently, the design of birth-cohort study is crucial for investigating the complex multidimensional molecular mechanisms associated with genetic, environmental and socioeconomic determinants, and their contribution to the development of chronic diseases and birth defects. This first birth-cohort in the state of Qatar has been launched by SCH with the main objective of evaluating the association of these exposures with the fetal development, reproductive outcomes, endocrine related outcomes, neurodevelopment, and obesity and with the occurrence of chronic diseases including asthma and allergies, metabolic syndrome and endocrine disorders that appear first in childhood but may perpetuate to future health problems. The main outcome of this multi-disciplinary project is to address the national concern of low reproductive health. The identification and quantification of the gene-environmental interaction affecting fetal growth and child health, shall provide evidence-based data to assist policy makers at SCH to develop better primary prevention programs and evidence based healthcare policies concerning Maternal Health, Reproductive Health, Pregnancy and Child Health in Qatar.
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Spatial Covariate Adjusted Survival Rates for Middle East Respiratory Syndrome (Mers) Coronavirus in the Arabian Peninsula
المؤلفون: Oyelola Abdulwasiu AdegboyeIntroduction
The frequent outbreaks of novel or emerging infectious diseases are alarming. There is a need for urgent and appropriate intervention that can be adapted quickly for such diseases. Middle East respiratory syndrome coronavirus (MERS-CoV) previously known as novel CoV is a viral infection that causes severe acute respiratory illness. MERS-CoV is a respiratory pathogen and contagious that is contracted via close contact with infected subject. It appears to have been transmitted from camels to humans, recent studies have revealed an association among the virus found in humans and that found in camels (Drosten, et al., 2014). The epidemic that started in 2012 in the Kingdom of Saudi Arabia has spread to many countries, mostly in the Middle East and North Africa, and more recently South Korea. The new epidemic started when the virus crossed from an infected individual who had recently traveled to the Middle East and subsequently began spreading between people via direct contact while in some cases the infection crossed from animal to human. This has exposed the general populace and especially the healthcare workers to greater risk. Similar to the reaction during other infection outbreaks, such as SARS and Ebola virus, many countries have issued travel restrictions and advisories to the affected countries because of fear of international spread of the disease. The rate at which the outbreak is evolving cannot be overemphasized and the geographical extension of its spread is widening. Neighborhoods constitute a key determinant of socioeconomic disparities and health habits, and therefore there is a high risk that people at geographical proximity to the infection are particularly vulnerable. Additionally, people with preexisting chronic medical conditions are more prone to being infected by the illness or developing a severe case resulting in fatality (Assiri, et al., 2013). Strong links between healthcare facilities and the outbreak of the disease has been found in Jeddah, where the majority of patients were in contact with other patients or health care facilities (Oboho, et al., 2015). Elsewhere, the transmission of MERS-CoV in household contacts revealed that an outcome of approximately 5% as the rate of secondary transmission occurred at home (Assiri, et al., 2013). In spite of the many research conducted on MERS-CoV, very few have investigated the effect of ecological factors on the transmission of the disease. Moreover, very little is known on the possibility of airborne transmission of the virus and discussion is still on going on this issue. Airborne transmission of the pathogen may also occur through dust and movement of people, equipment and animals within infected countries which may contribute to the spread of the virus. Additionally, the effect of alternating temperature highs and lows may imply seasonality that could alter the transmission and survivability of the virus. Objectives During infectious disease outbreaks, transmission of disease may form networks of infected individuals because of the way virus crossed from infected individual to susceptible individual. See figure 1a for a subset of the infection network for MERS disease used in this study. The infected individuals may form network of individuals connected by source of infection (contact) as direct or indirection connection. The study intends to (1) explore and investigate the relationship between the intensity of the disease in a given region and environmental variables, (2) We sought to evaluate the risk factors of and trends in mortality as a result of MERS-CoV infection in a large cohort of patients between June 6, 2012 and May 19, 2015. Use covariate adjustment to correctly assess the disease-risk factor associated with the survival outcome, (3) It also aims to understand the dynamic pattern of the disease over different temporal and spatial scales. A functional spatial time series method of estimating the death rate in the outbreaks will be formulated. Spatial time series analysis of disease outbreaks are versatile tools for studying and understanding transmission and spread of a disease and may be useful in the different frontiers of its upsurge and in the possibility of its containment or eradication. And lastly, (3) a flexible dependence model that reflect the relationship among infected individuals in the same network.
Figure 1: (Top) Network for subset of the MERS data. The numbers represent the identification number of the patient while the arrow represents the infection direction. (Bottom) Showing the patients that were infected by patient 27.
Figure 2: Number of patients infected by each main contact (patient ID). Preliminary Exploratory Analysis This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in the Arabian Peninsula between June 6, 2012 and May 19, 2015.
Table 1 presents the summary of data used in this study. Of the 958 cases recorded during the study period more than 90% (866) of the disease incidence occurred in the Kingdom of Saudi Arabia while Kuwait has the least incidence of 3. Seventeen percent of those infected with MERS disease were heath care worker. The fatality for the disease is about 0.35 among the total population. The mean age of the infected persons was 50.22 ± 18.37 years, with large percentage (55%) reported that they had some kind of comorbidity. Spatial analyses of disease outbreaks are versatile tools for studying and understanding transmission and spread of a disease.
Figure 3 shows the spread of MERS disease across the Arabian Peninsula within the study period. Majority of the disease incidence occurred in KSA and closed countries.
Table 1. Summary of the MERS data Country No. of Patients No. of Male/female No. with comorbidity Age at incidence % of HCW % fatal Mean/median mean SD KSA 866 565/284 469 49.66/50 49.66 ± 18.54 153 302 UAE 70 50/18 49 54/56 54 ± 15.33 9 30 Qatar 12 9/3 5 59.1/58 59.1 ± 15.99 1 3 Kuwait 3 1/2 3 54/43 54 ± 27.22 0 1 Oman 7 7/0 2 56.28/60 56.28 ± 17.54 1 3 Total 958 632/307 528 50.22/50.5 50.22 ± 18.37 164 339
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Eeg Profile & Yield in Evaluation of First Non-Febrile Seizures in Children-First Observational Study in Qatar
المؤلفون: Abdulhafeez Mohamed KhairIntroduction
Seizures are among the most common neurological disorders in the pediatric age group. Up to 10% of children might experience at least one episode suggestive of seizure activity in their life. It is thought that 5% of all medical attendances to emergency department are related to seizures. Whether the first non-febrile seizure is the kick start of long term epilepsy is always a question that physicians & families encounter. Ordering Electroencephalogram (EEG) for children with first non-febrile seizure is a subject of continuous debate.
Objectives
To collect demographic background data for children (1 month to 14 years) who presented with the first non-febrile seizure, To determine the prevalence & pattern of EEG abnormalities in Children (1 month to 14 years) with first non-febrile seizure, To estimate the possible yield of EEG in first non-febrile seizure as possible predictor of seizure recurrence or future epilepsy, and To collect possible evidence sufficient to make a recommendation for the use versus abandoning use of routine EEG in children with first episode of non-febrile seizure.
Methods
In a retrospective observational study around (400) children who were admitted with first non-febrile seizure to the Pediatric Emergency Centers (PECs) and their seizure were defined using the international league against epilepsy (ILAE) between January 2012 to December 2013 were studied. EEG was requested for 76 patients. Their EEG were reviewed and interpreted by pediatric neurology consultants. Patients’ demographic data and EEG records are then analyzed.
Results & Conclusion
Epileptic seizure should be diagnosed clinically and EEG is just a helpful tool. Utility of EEG is debatable in childhood first non-febrile seizure. EEG is helpful but interpretation should be individualized. EEG alone is not very good predictors of seizure recurrence or overall prognosis. Larger scale studies with longer follow up are needed.
Learning points
This is the first epidemiological study in Qatar in regard to children with epilepsy. It has given almost matching results in regard to background factors & yield of diagnosis in this small country with unique population constituents. This study however has formed the first step towards establishing pediatric epilepsy database project in Qatar. Recruiting of more patients & follow up studies are the future visions of this study.
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Nuclear Positioning is Important for the Survival of Mechanically Active Sensory Cells in the Cochlea
المؤلفون: Henning Horn, Brian Burke and Colin StewartHearing loss is a common sensory deficit that can affect all levels of society. The two age groups where hearing loss is most likely to be identified is in newborns and in the elderly. Newborn screens have been very effective in finding individuals affected by hearing loss. The general hearing loss incidence in newborns is 0.2%, with roughly 50% of all cases being hereditary. A recent study in Qatar found that the incidence of hearing loss in newborns was as high as 5.2% 1, 25 times higher than the general global incidence. Much of this increase can be attributed to hereditary forms of hearing loss, as the rate of consanguinity in Qatar is high 1,2. The elderly are the other population group where hearing loss is often identified. Globally, the hearing loss incidence for people over 50 is around 40%, with men showing a higher incidence than women 3,4. In Qatar, 66% of the Qatari population over the age of 50 suffers hearing loss, compared to ∼35% for the non-Qatari populations 5. The gender distribution of hearing loss within the Qatari population is also different from the global trend, with the incidence being 75% for women and 59% percent for men5. Therefore, the incidence of hearing loss is dramatically higher in the Qatari population than it is globally, and presents an important health issue that should be addressed. We have previously shown that the outer nuclear membrane protein Nesprin 4 is essential for hearing in humans and in mice. Nesprin 4 is expressed in the sensory outer hair cells (OHCs) of the cochlea and is important for the proper nuclear positioning and survival of these cells. In the absence of functional Nesprin 4, the nuclei are apically mispositioned and the OHCs die. OHCs act as cochlear amplifiers, augmenting sound signals by up to 100-fold6. This amplification is achieved, at least in part, through electromotility, a somatic cell motility that causes cell length changes in response to depolarization or hyperpolarization of the cell. Electromotility is mediated by SLC26A5/prestin, a membrane protein enriched in the lateral membranes of OHCs7. Prestin-mediated electromotility develops postnatally in mice, with full activity occurring at 12–14 days after birth. We observed that the majority of OHCs in mice lacking Nesprin 4 die around this time and predicted that the mislocalized nucleus was incompatible with electromotility. To test this hypothesis we generated double-null mice for Nesprin 4 and prestin and examined the fate of OHCs in these animals. We found that loss of prestin rescues the loss of OHCs in Nesprin 4-null animals, indicating that while a mispositioned nucleus is incompatible with electromotility, it does not affect cell viability independent of mechanical stress. Others have previously shown that animals heterozygous for the prestin allele exhibit a reduced electromotility. We predicted that a reduction in electromotility should yield a partial rescue of OHCs in Nesprin 4-null animals. When we examine the Nesprin 4-null/prestin heterozygous animals, we did indeed observe a partial rescue of OHCs. Together, these results indicate that proper nuclear positioning mediated by Nesprin 4 in OHCs is essential for these cells to survive the mechanical stress of electromotility.
References
1. Bener, A., EIHakeem, A. A. M. & Abdulhadi, K. Is there any association between consanguinity and hearing loss. Int J Pediatr Otorhinolaryngol 69, 327–333 (2005).
2. Girotto, G. et al. Consanguinity and Hereditary Hearing Loss in Qatar. Hum Hered 77, 175–182 (2014).
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Down-Regulation of Erk and Sirt1 Signaling May Lead to Reduced Fgf-21 Sensitivity in a Mouse Model of Diabetes
المؤلفون: Yasser Majeed, Rohit Upadhyay, Arun Lakshmanan, Christopher Triggle and Hong DingIntroduction
Fibroblast Growth Factor 21 (FGF-21) belongs to the FGF family of growth factors. FGF-21 regulates various aspects of glucose and lipid metabolism and is anti-diabetic. For example, FGF-21 administration or transgenic overexpression alleviates hyperglycemia and hyperlipidemia in obese mice, reduces body weight, and protects against fatty liver disease. FGF-21 signals via the FGF receptors and signaling also requires an accessory protein called β-klotho. Downstream FGF-21 effectors include ERK and Sirt1. FGF-21 is primarily secreted by adipocytes and hepatocytes and its expression is increased by agonists of PPARα (e.g. fenofibrate) and AMPK (e.g. metformin). Here, we used a mouse model of diabetes and investigated changes in FGF-21 and related signaling proteins in liver and adipose tissue. The role of microRNAs as potential regulators of FGF-21 signaling was also assessed.
Methods
WT or leptin receptor mutant (db/db) mice were used in this study. Mice were identified by genotyping and blood glucose levels were monitored (to confirm hyperglycemia in db/db mice). All animal experiments were performed using an IACUC-approved protocol. Mice were euthanized and liver and perivascular adipose tissue were collected and snap-frozen for later analysis. Blood was collected from anesthetized mice. Western blotting and quantitative PCR were performed using standard protocols. Data were analyzed using GraphPad software and t-tests and ANOVA analysis were used for statistical comparisons.
Results
WT and leptin receptor mutant (db/db) mice were treated with metformin (100 mg/kg/day) for 6–8 weeks. Western blot experiments in liver lysates revealed that metformin treatment significantly increased FGF-21 protein expression in WT mice. However, metformin failed to elevate FGF-21 in db/db mice. Metformin also significantly increased the expression of β-klotho protein in the liver of WT mice, but not in db/db mice. There was also an increase in FGF-21 and β-klotho gene expression after metformin treatment in WT mice, but not in db/db mice. ERK and Sirt1 are downstream molecules required for FGF-21 signaling. Experiments revealed that there was a significant decrease in ERK phosphorylation in db/db liver. Metformin treatment of WT as well as db/db mice also further reduced ERK phosphorylation in liver. Expression of Sirt1 protein was also reduced in db/db liver and further decrease was observed after metformin treatment. To investigate mechanisms involved in down-regulation of ERK and Sirt1, experiments were focused on microRNA 34a (miR34a), which is known to regulate both ERK and Sirt1 expression. A significant increase in circulating plasma miR34a was observed in db/db mice. Short treatment with metformin (1–3 days) produced a further increase (>10-fold) in circulating plasma miR34a in db/db mice. To identify the tissue source for miR34a synthesis and release into circulation, experiments were performed in perivascular adipose tissue (PVAT). Experiments revealed a significant increase in miR34a, but no further increase after metformin treatment in PVAT from db/db mice, suggesting that PVAT was not a likely source for miR34a release.
Conclusions
The data suggest up-regulation of FGF-21 and β-klotho in livers of db/db mice but a concomitant reduction in its downstream effectors, ERK and Sirt1. This may lead to compromised FGF-21 sensitivity in diabetes. Down-regulation of ERK and Sirt1 may result from elevated circulating miR34a levels.
Acknowledgements
The project was funded by NPRP grants (6-428-3-113 and 5-149-3-040) from QNRF.
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