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By Z. Malir. Ottawa University.

By combining and analysing information about our genome , with clinical and diagnostic information and then comparing that with data from others , patterns can be identifed . In the early 20th century we saw the frst connection between genetic inheritance and susceptibility to disease . It recognises that complex diseases should no longer be considered as a single entity . One disease may have many different forms , or subtypes , resulting from the complex interaction of our biological make-up and the diverse pathological and physiological processes in our bodies . These will not only vary between patients who have the same disease but also within an individual patient as they get older and their body changes . As we integrate and analyse genomic and other data , we can fnd common factors and causes of variation, resulting in the discovery of new pathways of disease, changing how diseases are thought of and treated. All patients with the same condition receive the same frst line treatment even though it may be only 30 to 60% effective. This can be used for a wide range of cancers such as melanoma (skin cancer), leukaemia, colon, brain and breast cancers. It may also mean that patients with different types of cancer may, on the basis of the genomic diagnosis, receive similar treatments. It will create the opportunity to fnd new purposes for, and better use of, existing medicines including generics and biosimilars. It will also help us to use other non-pharmacological treatments, and even, in some patients, simple dietary or lifestyle interventions. Within Specialised Services for example, personalised medicine will be a key aspect of the strategic approach to meeting the health and wellbeing challenge, bringing a more preventative approach to these vital, but often rare and expensive treatments. It is the integration and analysis of this information that forms the powerhouse for personalised medicine. Building an integrated informatics system across a healthcare system is diffcult: weve tried in the past and struggled, but the challenges are not insurmountable. The scale of the interdependency between integrated informatics and delivering personalised medicine cannot be overstated. The information that comes from a single human genome produces enough information to fll a stack of paperback books over 60 meters high, so the data storage requirements are vast. The foundations for this step change in health care are already being put in place. The Project is coordinated by Genomics England, who have procured whole genome sequencing services and analytical providers. They have created a unique database that enables approved researchers, clinicians, and industry to work on de-identifed data to enhance clinical interpretation and answer arising research questions. Knowledge from the Project will enable clinical teams to better characterise an individuals condition, learn from others with the same disease and connect seemingly different conditions with the same underlying genomic cause. Whole Genomes Sequencing returned a molecular diagnosis, setting them free to make decisions about the treatment options for their child. Now that we have this doagnosis there are things we can do differently straight away. A special diet means her medication can decrease and her epilepsy be more easily controlled. Earlier detection will open up the prospect of new treatment options and support people to make informed lifestyle choices. This will create the potential to reduce the growing burden of disease, particularly for long term conditions such as cardiovascular diseases, cancer, chronic respiratory diseases and diabetes. More precise diagnoses Currently a diagnosis is made based on tests and investigations of a patients symptoms. But whilst two patients might share the same symptoms, the cause of them could be different. Knowledge of each individuals complex molecular and cellular processes, informed by other clinical and diagnostic information, will enable us to fully understand the abnormal function and determine the true cause of the symptoms. This ability to diagnose more precisely can be optimised when coupled with new and improved technologies such as those that provide rapid and real time results and those that can be used at the point of care. Patients and health professionals can make shared decisions about medicines and adjust dosing in real time. Targeted and personalised interventions Personalised medicine offers the opportunity to move away from trial-and-error prescribing to optimal therapy frst time round. Currently key pharmaceutical interventions are effective in only 30-60% of patients due to differences in the way an individual responds to and metabolises medicines. Knowledge of the genetic variants responsible for individual drug response can be used to create an individuals pharmacogenomic profle, identifying optimal treatment. We are already beginning to see the development of simple point of care tests, based on genomic knowledge, which enable clinicians in a wide variety of settings to identify the best therapy. This marks the beginning of an end to the frustrating and costly practice of trial-and-error prescribing. The development and regulatory approval of so called companion diagnostics - a diagnostic test, device or imaging tool used as a companion to a therapeutic drug - is already making this a reality. Warfarin Warfarin is a common and effective treatment to prevent blood clots, but patients show a 40-fold difference in dose needed. The current trial and error approach to discover the right dose for an individual means some suffer signifcant problems as their treatment is worked out. Appropriate testing can be used so people get the right dose sooner cutting side- effects and improving outcomes. The ability to predict and prevent their occurrence has signifcant potential to reduce burden on accident and emergency units and to signifcantly improve a patients experience. However about 1 in 17 people have a bad reaction to the drug which, at worst, can be fatal due to a variation in their immune system. All patients now have a specifc genomic test before they start taking Abacavir, which identifes those who would have an allergic reaction. A more participatory role for patients The ability for a clinician to discuss with their patients information about individual genomic characteristics, lifestyle and environmental factors, and interpret personal data from wearable technology will drive a new type of conversation. It might also lead patients to consider preventative measures when there is high likelihood of a disease developing. This is a new era of medicine and it requires new knowledge amongst professionals, patients and the public to have confdence in using the information available to them. Diabetes when less can be more The standard approach to newly-diagnosed Type 1 diabetes is to treat it with regular insulin injections. However there are other forms of diabetes that can appear clinically like Type 1 diabetes, but have different underlying causes and can be treated much more simply. A simple genetic test can identify some patients who can be better treated using tablets or even some patients who are best managed by no treatment at all. We can strengthen our ability to design appropriate health and care for our local populations through a more sophisticated understanding of the impact of age, gender and ethnicity or lifestyle factors that infuence the onset of disease. This will enable us to be far smarter in the way that we manage and leverage the limited resources that we have. New partnerships will be central in driving forward a personalised medicine approach bringing together clinical practice, academic rigour, industry skills and the active involvement of patients and patient groups. Personalised medicine with science and innovation at its core is integral to making the vision a reality. The potential benefts of personalised medicine are signifcant, and the changes are inevitable, but we must rise to the challenge in a considered and proactive way. We will need to embed systematically the approach into mainstream healthcare whilst ensuring the ethical, equality and economic implications are fully recognised and addressed. We must ensure that patients and the public are confdent in the use of these technologies and that we can mitigate any potential concerns, particularly in the area of data security and confdentiality. We will need to ensure that the system develops appropriate education and training, effective digital and informatics, with deepening patient involvement and empowerment. The potential is signifcant, and there are real and tangible developments that will take place over the coming decade. Genomic technologies are an increasingly large part of the evolution of modern medicine and our understanding of genomic implications is growing. And informatics advances are making discoveries and connections at an enormous pace. This is the dawn of a new era in medicine that will need to move and evolve at the scale and pace of scientifc and technological advances if real improvements for patients and the public are going to be made. We have been working with the Academy of Medical Sciences to develop exemplar clinical pathways in key priority areas, such as diabetes and cardiovascular disease, where there is a real opportunity to improve outcomes for patients and our population. We will continue to work with the Academy as well as with the Academy of Medical Royal Colleges, its constituent colleges and other professional groups, to build the evidence base and clinical understanding. It is not a simple task; there are a number of challenges including ethical, equitable and economic implications that we will need to address. Over the coming months we will be working with our partners, patients and the public, and leading experts to develop our approach. Approaching Customs, I noticed the intensity and seriousness on the faces of the customs officers whose responsibility were to check passports and question passengers. As I moved closer to the front of the line, I noticed someone reading a foreign newspaper. The man was reading about the Middle Eastern conflict, a clash fueled by religious intolerance. While there I worked, studied their religions, ate their food, traveled and contracted malaria. Despite all of Ghanas economic hardships, the blending of Christianity, Islam, and traditional religion did not affect the health of the country. When I reached the front of the line, the customs officer glanced at my backpack and with authoritative curiosity asked me, What are you studying? In my quest to understand where I fit into society, I used service to provide a link between science and my faith. Science and religion are fundamentally different; science is governed by the ability to provide evidence to prove the truth while religions truth is grounded on the concept of faith. Physicians are constantly balancing the reality of a persons humanity and the illness in which they are caring for. The physicians I have found to be most memorable and effective were those who were equally as sensitive and perceptive of my spirits as they were of my symptoms. Therefore, my desire to become a physician has always been validated, not contradicted by my belief system. Being a servant is characterized by leading by 2 example and striving to be an advocate for equity. As a seventh grade math and science teacher in the Philadelphia public school system, everyday is about sacrifice and service. I sacrifice my time before, during and after-school; tutoring, mentoring and coaching my students. I serve with vigor and purpose so that my students can have opportunities that many students from similar backgrounds do not have. Although I had been diagnosed with asthma, I had not had an attack since I was in middle school. Consequently, the physicians attributed my attacks to high stress, lack of sleep, and poor eating habits. It had become clear to me that my unrelenting drive to provide my students with a sound math and science education without properly balancing teaching and my personal life negatively impacted my ability to serve my students. I believe this experience taught me a lesson that will prove to be invaluable as a physician. Establishing an equilibrium between my service and my personal life as a physician will allow me to remain connected to the human experience; thus enabling me to serve my patients with more compassion and effectiveness. Throughout my travels and experiences I have seen the unfortunate consequences of not having equitable, quality health care both domestically and abroad. Illness marks a point in many peoples lives where they are most vulnerable, thus making a patients faith and health care providers vital to their healing process. My pursuit to blend the roles of science and religion formulate my firm belief that health care providers are caretakers of Gods children and have a responsibility to all of humanity. Nevertheless, I realize my effectiveness and success as a physician will be predicated mostly on my ability to harmonize my ambition with my purpose. Therefore, I will always answer bewildered looks with the assurance that my faith and my abilities will allow me to serve my patients and achieve what I have always strived for and firmly believe in, balance. We never made it to see a horror movie; but our night was nothing close to mundane, when we became innocent victims to gang crossfire. As we descended my front door stairs two gunshots were fired and one person fell to the floor. I vividly recall holding him in my arms, and while he lost blood I almost lost my mind. While this event started me on my quest to become a medical doctor, at that moment all I could envision was a life of despondency. According to author Jennifer Holloway, tragedy is a substance which can ignite the soul. As fast as despondency had filled my heart, it was now gone; I was consumed by anger, frustration and motivation to change my lifes direction. By the end of the year I excelled as the top student in biology, received the Inorganic Chemistry Achievement Award and was encouraged to become a tutor in general biology and chemistry. Questions raised by students challenged my understanding of scientific concepts and their application in patient care. While shadowing doctors, I was introduced to triaging, patient diet monitoring and transitioning from diagnosis to treatment.

Inkjet droplet diameter may vary wet granulation due to the fact that drying at room between 10-100 micrometers and its volume temperature or applied heat may be required in order between 1-300 picoliters [32 ,73 ,97] . Suitable viscosities and surface given to size related flowability and cohesion issues tensions of the drug inks must be paired in order to [115] . Using a film substrate on which a single , Bone implants coated with antibacterial continuous layer of liquid or suspension is formulation using inkjet printing were also reported deposited is sometimes considered 2D [46 ,86] [85] . Similarly , the printed droplets solutions to print visible unique patterns (geometric can be freeze-dried using liquid nitrogen [19 ,33] . Though beeswax based, solid dosage forms were proposed the majority of resins usually employed in this in order to investigate the manipulation and method are toxic or carcinogenic, thus not suitable prediction of drug release models [59]. The in 4D (four dimensions), as they can timely alter microneedle triangular base had equal 150 their shape and drug release potential after micrometers sides, while the microneedles implantation or ingestion when differences in pH or themselves were 500 micrometers tall [10]. The 3D printed One of the most important benefits of 3D printing is pieces can have any geometry [89]. Warping and shrinking of the printed object especially if to operate and there are a large number platform is not thermostated or if the printing chamber is open, allowing the printed object to of producers, this is now the most cool down too suddenly [32,46]. Prerequisite filament formulation is necessary, as no pharmaceutical grade commercial ones are No use of solvents, improved sturdiness available [6,58]. The same bulk filament can be used for Distortion of the filament around the extrusion feeding gears or failure to grip and advance the the preparation of different doses and/or filament may appear, if it doesnt have a consistent diameter [107,115]. Post-printing drying of the printed piece may be necessary and incidental shrinking may alter its physicochemical properties [6,32,77]. For the same reasons, multi-drug, multi-compartment devices could prove difficult to attain [77]. Internal porosity is highly controllable Post-processing is usually required in order to remove the powder residue adhering to the printed [6]. The printed structures have an increased fragility due to high porosity [6,57,77]. Easier production of porous structures Increased risk of agglomeration towards the center of the printed structure [77]. Clogging of the print head may also arise due to nucleation or crystal development in Enables printing down to picoliter supersaturated solutions [95]. Satellite drop formation is an undesired issue determined by a combination of factors, both ink and hardware dependant [87,95]. Touching of the printhead to the substrate may lead to smearing of the drug ink, thus causing unexpected doses in the final printlet [7]. Today, 2014, 17(5): 247-252, Conventional dispensing could shift from traditional doi. Of note, none of these drugs The understanding of this pathogenic mechanism, were able to induce disease remission in all treated along with advances in biopharmaceutical technology patients or even low disease activity - a fact which (recombinant deoxyribonucleic acid technique), lead proves the complexity of the disease process. Likewise, mast cells protein coded on chromosome 22q11 and is account for a significant percent of the local production ubiquitously expressed on somatic cells. A meta-analysis from 2016 by Kunwar tract infections, oral herpes and diarrhoea which et al. The efficacy analysis on individual the available results from the first two studies molecules revealed that secukinumab and ixekizumab revealed a similar pattern. Clinical trials have analysis of individual side effects revealed an revealed that it has a good safety profile and that the increased risk of infection. There are at least three possible responses after 3 months with brodalumab was not explanations for this observation: the causal pathogenic significantly different compared to placebo. Since Crohns disease is more frequently associated Journal of immunology, 1999; 162(1): 494-502. Clin Exp necrosis factor inhibitor-methotrexate combination Rheumatol, 2018; 36(1): 50-55. Arthritis & with disease-modifying anti rheumatic drugs in rheumatology, 2017; 69(6): 1144-1153. Archivum immunologiae et treatment for 48 weeks in a phase ii study in therapiae experimentalis, 2015; 63(3): 215-221. Rheumatology, 2016; results of secukinumab in patients with rheumatoid 55(1): 49-55. Arthritis research, 2001; monoclonal antibody, in rheumatoid arthritis patients 3(3): 168-177. Immunology, 2014; disease and ulcerative colitis show unique cytokine 141(3): 353-361. Rheumatology, poor clinical outcome in rheumatoid arthritis are 2014; 53(10): 1896-1900. Journal of immunology, 1993; 150(12): 5445- safety of subcutaneous and intravenous loading dose 5456. The Journal of rheumatology, 2016; 43(3): cooperation between interleukin-17 and tumor 495-503. Clinical rheumatology, Iwakura Y, Th17 functions as an osteoclastogenic 2012; 31(7): 1145-1146. Unfortunately, the irrational use of antibiotics has rendered some pathogens resistant towards anti-microbial agents. Since pigs are the main source of this bacterium, extensive research has been done on pork products compared to other foods, though the presence of Yersinia in other foods have also been reported. For the treatment of acute gastroenteritis, as one of the most common symptoms of bacterial infections, several antibiotics are prescribed. Three species of Yersinia from the Enterobacteriaceae family, are human pathogens and Y. Rezumat Apariia agenilor patogeni rezisteni la mai multe medicamente a devenit o problem important n tratamentul bolilor infecioase i intoxicaiilor. Din pcate, utilizarea iraional a antibioticelor a fcut ca anumii ageni patogeni s fie rezisteni la substanele antimicrobiene. Astzi, infeciile cauzate de tulpini rezistente la antibiotice sunt dificil de tratat. Deoarece porcii sunt principala surs a acestei bacterii, s-au fcut cercetri ample cu privire la produsele din carne de porc, n comparaie cu alte alimente, dei prezena Yersinia n alte alimente a fost de asemenea raportat. Pentru tratamentul gastroenteritelor acute, ca unul dintre cele mai frecvente simptome ale infeciilor bacteriene, sunt prescrise mai multe antibiotice. Trei specii de Yersinia din familia Enterobacteriaceae sunt ageni patogeni umani i Y. Their motility is due to the existence of the importance of detection of virulence genes in parallel peritrichous flagella. In this literature search, we used the disease outbreaks and enhancement of animals growth following combination of keywords: (Antibiotic and food consumption. Globally, it is accepted that or Antibiogram) and (Yersinia or Yersinia increased resistance towards antibiotics correlates enterocolitica) and Food in the title and abstract well with inappropriate administration of these of the articles. Duplicate publications, irrelevant agents to animals (for production or veterinary care) topics and book chapters were excluded and were and humans [10]. It is assumed that, by Results and discussion 2050, approximately 10 million deaths may annually occur due to antimicrobial resistance, with an Antimicrobial resistance of Y. Although yersinosis is seldom treated trimethoprim-sulfamethoxazole, while exhibited the with anti-microbials, immunodeficient individuals highest levels of resistance towards ampicillin, need medication. In a research conducted by towards antibiotics is at least in part, induced by - Novoslavskij et al, all tested Y. There is strains exhibited resistance to ampicillin and an alarming growing prevalence of Y. But, the Meat and meat products as the main sources of food- afore mentioned application has led to increased borne infectious diseases are crucial parts of the bacterial resistance to many antibiotics [27, 28]. The most frequently found species in dairy clindamycin, but were sensitive to chloramphenicol products were Y. All* clindamycin tobramycin and imipenem Turkey 2015 [29] *All: All strains of Yersinia enterocolitica Antimicrobial resistance of Y. However, In a study that evaluated resistance pattern in sea- these isolates were resistant towards cephalothin food-borne Y. In a study, A small number of 57 O serogroups are regarded as Lucero-Estrada C et al found all the Y. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistancethe legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever- increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs. In this review, we focus on the underlying principles and ecological factors that affect drug resistance in bacteria. Notable global examples include hospital and genes emerged in military hospitals in the 1930s4. Similarly, Acinetobacter baumanii and Pseudomonas aeruginosa3,1618 (Box 2, Mycobacterium tuberculosis with resistance to streptomycin emerged World Health Organization website). Fueled by increasing antimicrobial use, the frequency of individuals in hospitals in the United States and elsewhere for more resistance escalated in many different bacteria,especially in developing than a decade24,25. At present, the newly developed drugs daptomycin, countries where antimicrobials were readily available without pre- linezolid and the streptogramin combination, dalfopristin/quino- scription. Center for Adaptation Genetics and Drug Resistance, Departments of Molecular Biology and Microbiology and of Medicine, Tufts University School of Medicine, aeruginosa and A. Correspondence should be addressed to one, antibiotics, which seriously challenges the treatment of immuno- S. Resistant (and presumably the costs) as compared with drug-susceptible strains can be traced from the community to the hospital and vice infections88. A cost comparison of treating methicillin-resistant versa, indicating that drug resistance is no longer localized. Drug resistance emerges only when the two It noted that the antimicrobial resistance selected in one year will components come together in an environment or host, which can lead persist, and subsequent years will bear the burden of the resistance to a clinical problem. If community infections are considered, the costs are involved in essential physiological or metabolic functions of the bacte- even greater, particularly for combination therapies of multiple 1 rial cell (Table 1). Enterobacter and Klebsiella,destroy even the latest generations of peni- But how do bacteria acquire resistance? Ofparticular note is the increase in mobilethe genes for resistance traits can be transferred among strains bearing metallo--lactamases that inactivate carbapenems bacteria of different taxonomic and ecological groups by means of drugs that are often the last resort in serious infections of Gram-neg- mobile genetic elements such as bacteriophages, plasmids, naked ative bacteria31,32. And, like the antibiotics themselves, resistance recently recommended fluoroquinolones. This process was responsible for the initial emer- Resistance in pneumococci continues to be an ever-increasing gence of penicillin and tetracycline resistance in N. The global threat that curtails treatment of pneumonias and ear infections, organism later acquired transposons bearing genes with high-level particularly in children. One study has predicted that multidrug resistancewill over- mutations in the target enzymes (topoisomerases) and an increase ride single-drug resistance in the present decade37. This phenomenon was found to occur after the prolonged use of tetracycline for urinary tract infections53 and for Mechanism of action Antibiotic families 54 acne. Competitive inhibition of folic Sulfonamides; trimethoprim acid synthesis This phenomenon reflects the linkage of different resistance genes on the same transposon or plasmid. Bacteria that are already resistant to one growth- inhibitory agent seem to be favored in recruiting additional resistance Chromosomal mutants of S. Asmall increase in the minimum inhibitory concentration to an antimicrobial should alert clinical Loss of resistance is slow microbiologists in hospitals and communities to an incipient prob- Resistant bacteria may rapidly appear in the host or environment after lem of resistance. Although still classified as susceptible, a strain antibiotic use, but they are slow to be lost, even in the absence of the with decreased susceptibility to a drug heralds the eventual emer- selecting antibiotic. This phenomenon reflects the minimal survival gence of higher-level resistance and should galvanize efforts towards cost to the emerging resistant strains. In addition, as discussed above, altering the use of that antimicrobial in that environment. Some transposons contain integronsmore complex transposons that contain a site for integrating different antibiotic resistance genes and other gene cassettes in tandem for expression from a single promoter91. Originally discovered among Gram-negative bacteria, integrons have been since located in Gram-positive commensal floraa newly found reservoir of these unique genetic elements92. A model of resistance gene spread is the tet(M) tetracycline resistance gene, which is commonly located on the transposon Bacteriophage Tn916 (ref. It has been found in Gram-positive and Gram- Transposon negative bacteria, aerobic and anaerobic bacteria, and in all Plasmid environmental and biological niches94. The pneumococci have shown that the chromosomal location of the resistance determinant is not a safeguard against its spread. Bacteria themselves are mobile and can easily travel from person to person and between countries. Resistant pneumococci in Iceland and in the United States have been shown to be the progeny of strains that initially appeared in Spain85. Thus, countries and Chromosome citizens worldwide have become part of a global microbial ecology, tn tn sharing and spreading the consequences of antimicrobial resistance. Some are directed at the antibiotic itself: enzymes such as -lactamases destroy penicillins and cephalosporins, and modifying enzymes inactivate chloramphenicol Antibiotic-resistance Antibiotic- and aminoglycosides such as streptomycin and gentamicin. For example, the -lactamases now number in the hundreds and more than 20 different resistance determinants mediate an efflux of tetracyclines100. In addition, more than one type of mechanism may provide resistance to the same antibiotic; for Chromosome Antibiotic- example, tetracycline resistance can be effected by either efflux or altering Antibiotic ribosome protection101. Although most fluoroquinolone resistance enzyme stems from chromosomal mutations in the gyrase target or from drug efflux, a plasmid-mediated resistance to fluoroquinolones has been recently described102. Multidrug resistance can be specified by chromosomal genes for regulatory proteins such as MarA and SoxS. These proteins promote drug resistance by controlling the expression of other chromosomal genes, Bacterial cell such as those involved in drug efflux61. Ecologically speaking, it is the density of antibiotic usage that Some studies have, however, tracked a decline in resistance frequen- enhances resistance selection and its effects. Asignificant countrywide reversal involves the total amount of antibiotic being applied to a geographi- of macrolide resistance in S. Nonetheless, resistance generally becomes a factory of resistant bacteria that enter the environment.

In the long-term follow up of the ran- opment of type 2 diabetes during follow up (27) . After a total physical activity (4 cohorts) and incidence of type 2 diabetes median 4 . The greatest relative benets were attained ventions were not part of the intervention and between-group at low levels of activity , but further benets can be recognized at changes were negligible . Future research is needed to consider healthy diets are consistently associated with a 20% reduced risk the dose-response relationship of physical activity and type 2 dia- of future type 2 diabetes (28) . While the nature of diets associ- betes prevention in ethnically diverse populations . A dosage of 850 mg twice Diets Emphasizing Specic Foods daily for an average of 2 . These the consumption of whole grains was inversely associated with inci- data suggest that metformin may be more effective in women with dent type 2 diabetes over a median 7 . The results of this study suggested that 26% of the consumed greater than 2 servings of whole grains per day had a diabetes prevention effect could be accounted for by the pharma- 43% reduced risk of incident type 2 diabetes compared with women cologic action of metformin (which did not persist when the drug who consumed no whole grain (29) . The benets of metformin on diabetes pre- Dairy vention persisted for up to 10 years (18) . Nonlinear inverse asso- metformin and 29% by healthy behaviour interventions over 10 years ciations were observed for total dairy products and yogurt, with most of follow up (35). More subjects in the voglibose group achieved normoglycemia than in the placebo group The Diabetes Reduction Assessment with Ramipril and (66. Treatment with rosiglitazone resulted in a 60% an intensive lifestyle modication program (diet and exercise) on reduction in the primary composite outcome of diabetes or death the prevention of diabetes in 3,305 individuals with obesity (43). Compared to placebo, orlistat treatment was associated receive pioglitazone or placebo and were followed for 2. A total of 3,876 people with recent ischemic stroke Subjects were randomized to 1 of 4 liraglutide doses (1. Surveillance for diabetes onset during the trial was accom- 96% with liraglutide 1. The study did not provide information with comorbidities, were randomized 2:1, using a telephone or web- whether this effect would be sustained. One thousand one hundred Despite the favourable effects of thiazolidinediones on delay- and twenty-eight (50%) completed the study up to week 160, after ing the development of type 2 diabetes, the multiple potential withdrawal of 714 (47%) in the liraglutide group and 412 (55%) in adverse effects and warnings in this class of medication make it dif- the placebo group. Taking the different diagnosis frequencies between the treat- a 5-year study with a mean follow up of 3. Overall, there ment groups into account, the time to onset of diabetes over 160 was a 25% reduction in the risk of progression to diabetes when the weeks among all randomized was 2. The limitations included the fact that withdrawn individu- placebo at reducing the progression to type 2 diabetes (5. Thirty-ve trials (43,407 participants) with variable risk in addition to healthy behaviour interventions, although there was of bias were included. One must keep in mind that the measures of preven- Bariatric Surgery tion must be delivered in a culturally sensitive manner to these populations. Many limitations exist in this paper, including not all sub- jects being randomized and biases in publication (15). Additionally, At a macro-level, the type 2 diabetes epidemic has been attrib- the cost-benet analysis for bariatric surgery as a primary tool to uted to urbanization and environmental transitions, including sed- prevent diabetes is unclear. Hence, more data is needed before rec- entary occupations, increased mechanization, improved ommending bariatric surgery routinely to prevent diabetes. In recent decades, men and women around the globe (and in Canada) have gained Diabetes Prevention in High-Risk Ethnicities weight, largely due to changes in dietary patterns and decreased physical activity levels. The reasons for this are multifactorial and include is important to recognize that the health sector on its own cannot genetic susceptibility, altered fat distribution (more visceral fat with accomplish population-wide changes. New strategic relationships greater insulin resistance) and higher prevalence of metabolic syn- with groups that have an impact on health (e. Many of them develop diabetes at a younger age and often construction industry) are needed to help create an environment have complications at the time of diagnosis due to long-standing, more conducive to an active lifestyle and healthy eating habits. As a result, there may be a benet of delay- Major legislative and other regulatory measures may be required ing the onset of diabetes in this population. The Indian Diabetes similar to those needed to address illness arising from tobacco usage. Progression to dia- mandating nutrition labelling of restaurant foods and regulating betes in the control group was high (55%) over 3 years (50). In a recent systematic review and meta-analysis (52), ventions and metformin compared with the control group. Participants were randomized to standard lifestyle advice type 2 diabetes risk in a meta-analysis (53) and a pooled analysis (control) or a 6-month, culturally tailored, United States Diabetes of European cohorts (54). The primary outcome paign recommending (i) limited intake of free sugars to <10% of total of diabetes incidence was assessed biannually and compared across daily calorie intake, and (ii) limited intake of sugar-sweetened study arms using an intention-to-treat analysis. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention TrialType 1. Hydrolyzed infant formula and early beta- cell autoimmunity: A randomized clinical trial. The effectiveness of school-based strategies for the primary prevention of obesity and for promoting physical activity and/or nutrition, the major modiable risk factors for type 2 diabetes: A review of reviews. Lifestyle interven- interventions that includes moderate weight loss and regular physical activ- tions for patients with and at risk for type 2 diabetes: A systematic review and ity of a minimum of 150 minutes per week over 5 days a week should be meta-analysis. In individuals at risk for type 2 diabetes, dietary patterns may be used to type 2 diabetes with lifestyle intervention or metformin. Effects of weight loss, weight cycling, and weight loss maintenance on diabetes incidence and change in cardiometabolic traits in the Diabetes Prevention Program. Early response to preventive strate- may be used to reduce the risk of type 2 diabetes [Grade A, Level 1A (17,33) gies in the Diabetes Prevention Program. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: A 23-year follow-up study. The effect of medical nutrition therapy by a registered dietitian nutritionist in patients with prediabetes participating Dr. Prebtani reports support from Novo Nordisk, Eli Lilly, in a randomized controlled clinical research trial. J Acad Nutr Diet 2014;114:1739 Boehringer Ingelheim, Sano and Janssen, outside the submitted 48. A journey into a Mediterranean diet personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and type 2 diabetes: A systematic review with meta-analyses. The prospective impact of food pricing tion with incident type 2 diabetes: The Womens Health Initiative Observa- on improving dietary consumption: A systematic review and meta-analysis. Association between sugar-sweetened beverages betes: A systematic review and dose-response meta-analysis of cohort studies. Diabetologia betes mellitus: A systematic review and dose-response meta-analysis of pro- 2013;56:152030. The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: The Diabetes Prevention Program outcomes study 10-year follow-up. Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: A randomized clinical trial. Citations identified through Additional citations identified Diabetes Care 2015;38:518. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: A randomised controlled trial. Effect of ramipril on the inci- Citations after duplicates removed dence of diabetes. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Voglibose for prevention of type 2 dia- for eligibility N=155 betes mellitus: A randomised, double-blind trial in Japanese individuals with N=346 impaired glucose tolerance. Effects of liraglutide in the treatment of N=191 obesity: A randomised, double-blind, placebo-controlled study. Clinical review: Effect of vitamin D3 supple- mentation on improving glucose homeostasis and preventing diabetes: A sys- tematic review and meta-analysis. The Indian Diabetes Prevention Programme shows that lifestyle modication and metformin prevent type 2 dia- (2009). Can J Diabetes 42 (2018) S27S35 Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage: www. The person with diabetes should be an active participant in their telehealth (telephone, web-based or virtual) diabetes support and visits. Recall: Develop a system to remind your patients and caregivers of timely Any of the above strategies may be facilitated with telehealth technologies. In Canada, there is a care gap between the clinical goals out- Remember you are the most important member of the team. Since almost 80% of the medical care be ready to share in decision making regarding how you will care for your of people with diabetes takes place in primary care, there has been diabetes and health. Be prepared to share any issues that may affect tice and community that encourage high-quality chronic disease your ability to care for your diabetes on a daily basis, including any fears or anxiety you may have. Also, bring your glucose components facilitate planning and coordination among health- meter and insulin pen device if you use one. This model aims to trans- form the care of people with chronic illnesses from acute and reactive to proactive, planned and population-based. The most important member of the diabetes health- on this evidence to include the following 6 components that work care team is the person living with diabetes. Organizations that provide diabetes care in accor- pital visits than patients who are not (35,36). Initially, it appeared as if only profession, continue to be integral members of the team. A variety of individual and community health-care and based in primary care, reduced overall mortality as well as drug support systems, particularly psychological support, can also improve and hospital costs (27). These components facilitate planning and coordination among providers, while helping people play an informed role in managing their own care. This model has evolved from the Wagner original (1999) to the Expanded Care Model (85). Shared care Joint participation of primary care provider [rst contact and ongoing health care: family physician, general practitioner or nurse practitioner] and specialty care physician in the planned delivery of care, informed by an enhanced information exchange over and above routine discharge and referral notices. Shared care can also refer to the sharing of responsibility for care between the person with diabetes and provider or team. Team-based care Care by a multidisciplinary and interprofessional team with specic training in diabetes. Continuous quality improvement Techniques for examining and measuring clinical processes, designing interventions, testing their impacts and then assessing the need for further improvement. Self-management support Self-management education Self-management support is dened as activities that support the A systematic intervention that involves active participation by the person with diabetes in self-monitoring implementation and maintenance of behaviours for ongoing (physiologic processes) and/or decision making (managing). Decision support Audit and feedback Integration of evidence-based guidelines into the ow of clinical Summary of provider or group performance on clinical or process indicators delivered to clinicians to practice. Benchmarking Feedback on the performance of a person with diabetes or physician, which is ranked against that of a peer group. Clinician education May include didactic, academic detailing, online, customized cases with feedback. Evidencebased guidelines Adherence to guidelines may be facilitated by embedding into electronic medical records with reminders (see below) or with the use of clinical ow sheets. Clinical information systems Clinician reminders The part of an information system that helps organize patient and Paper-based or electronic system to prompt health-care professionals to recall patient-specic information population data to facilitate ecient and effective care. In general, the person with diabetes should be facilitating the relay but may come from other team members. Patient registry A list of people sharing a common characteristic, such as diabetes. May be paper-based, but increasingly is electronic, from a simple spreadsheet to one embedded in an electronic health record. Patient reminders Any effort to remind people about upcoming appointments or aspects of self-care (e. A meta-analysis involving people with both type 1 and type 2 care physician), monitoring, care coordination (where the manager diabetes showed a signicant 0. A systematic review of modify treatment with or without prior approval from the primary pharmacist-led disease management found resource use was gen- care physician had the greatest impact on A1C lowering. Flexibility in the opera- experience, the better the outcomes compared to primary care tion of the team is important. Furthermore, the outcomes when team member, active participation of professionals from more these nurse case managers were used was equivalent or better than than 1 discipline and role expansion, have been associated with primary care providers (40). The greatest body of evi- gies that have been associated with positive outcomes are the del- dence for improved clinical outcomes in diabetes is with promo- egation of prescribing authority and the monitoring of complications tion of self-management, team changes and case management using decision support tools (33,34,38). They are often the principal medical contact for the as process outcomes, medication use and screening for complica- person with diabetes and have a comprehensive overview of all tions: promotion of self-management, team changes, case man- health issues and social supports (51). Another laborative, shared care is the ideal approach to organizing care for recent systematic review showed that education of the person with individuals with diabetes. Generally, sonalized goal setting (17,48) (see Self-Management Education and it is the person with diabetes who is facilitating the relay. Community partner- ventions, particularly those that used interactive computer tech- ships should be considered as a means of obtaining better care for nology to provide recommendations and immediate feedback of people with diabetes. For example, in addition to the diabetes health- personally tailored information, were shown to be the most effec- care team, peer- or lay leader-led self-management groups have been tive in improving outcomes of people with diabetes (67). Incorporation of evidence-based treatment algo- health regions also have developed diabetes strategies, diabetes rithms has been shown in several studies to be an integral part of service frameworks and support diabetes collaboratives.

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