Abstract Crohn’s disease (CD), a chronic inflammatory condition of the digestive tract, poses significant challenges in terms of disease prognosis and treatment selection. Biomarkers have the potential to predict CD outcomes and guide clinical decision-making. This review aims to summarize the current literature on promising biomarkers associated with CD outcomes and their potential clinical implications. The identification of reliable biomarkers for CD outcomes is of paramount importance in tailoring treatment strategies, monitoring disease activity, and predicting the risk of complications. Clinical prognostic factors traditionally used to assess disease severity, and the likelihood of complications have limitations in accuracy and predictive value. Thus, there is a need for more precise biomarkers, particularly in newly diagnosed and treatment-naive patients. Pharmacogenomic markers, such as TPMT and NUDT15 polymorphisms, have been utilized to identify patients at risk of adverse events with thiopurine therapy. Several biomarkers, including HLA haplotypes, oncostatin M expression, and transcriptomic profiles, have shown associations with response to anti-TNF therapy. Confocal laser endomicroscopy and single-cell analyses hold promise in predicting treatment response to specific therapies. The identification of biomarkers associated with post-operative recurrence in CD is crucial, as it could lead to changes in management algorithms. Several promising microbiome signatures and proteomic profiles have been identified. In conclusion, biomarkers have the potential to revolutionize the management of CD by providing valuable prognostic information and guiding treatment decisions. However, further research and validation are necessary to establish their clinical utility and integration into routine practice.
{"title":"Biomarkers That Predict Crohn’s Disease Outcomes","authors":"Pablo A Olivera, Mark S Silverberg","doi":"10.1093/jcag/gwad024","DOIUrl":"https://doi.org/10.1093/jcag/gwad024","url":null,"abstract":"Abstract Crohn’s disease (CD), a chronic inflammatory condition of the digestive tract, poses significant challenges in terms of disease prognosis and treatment selection. Biomarkers have the potential to predict CD outcomes and guide clinical decision-making. This review aims to summarize the current literature on promising biomarkers associated with CD outcomes and their potential clinical implications. The identification of reliable biomarkers for CD outcomes is of paramount importance in tailoring treatment strategies, monitoring disease activity, and predicting the risk of complications. Clinical prognostic factors traditionally used to assess disease severity, and the likelihood of complications have limitations in accuracy and predictive value. Thus, there is a need for more precise biomarkers, particularly in newly diagnosed and treatment-naive patients. Pharmacogenomic markers, such as TPMT and NUDT15 polymorphisms, have been utilized to identify patients at risk of adverse events with thiopurine therapy. Several biomarkers, including HLA haplotypes, oncostatin M expression, and transcriptomic profiles, have shown associations with response to anti-TNF therapy. Confocal laser endomicroscopy and single-cell analyses hold promise in predicting treatment response to specific therapies. The identification of biomarkers associated with post-operative recurrence in CD is crucial, as it could lead to changes in management algorithms. Several promising microbiome signatures and proteomic profiles have been identified. In conclusion, biomarkers have the potential to revolutionize the management of CD by providing valuable prognostic information and guiding treatment decisions. However, further research and validation are necessary to establish their clinical utility and integration into routine practice.","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"60 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134949095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanjay K Murthy, M Ellen Kuenzig, Joseph W Windsor, Priscilla Matthews, Parul Tandon, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Gilaad G Kaplan, Kate Lee, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Saketh Meka, Roxana S Chis, Sarang Gupta, Eric Cheah, Tal Davis, Jake Weinstein, James H B Im, Quinn Goddard, Julia Gorospe, Jennifer Loschiavo, Kaitlyn McQuaid, Joseph D'Addario, Ken Silver, Robyn Oppenheim, Harminder Singh
Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD.","authors":"Sanjay K Murthy, M Ellen Kuenzig, Joseph W Windsor, Priscilla Matthews, Parul Tandon, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Gilaad G Kaplan, Kate Lee, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Saketh Meka, Roxana S Chis, Sarang Gupta, Eric Cheah, Tal Davis, Jake Weinstein, James H B Im, Quinn Goddard, Julia Gorospe, Jennifer Loschiavo, Kaitlyn McQuaid, Joseph D'Addario, Ken Silver, Robyn Oppenheim, Harminder Singh","doi":"10.1093/jcag/gwad006","DOIUrl":"https://doi.org/10.1093/jcag/gwad006","url":null,"abstract":"<p><p>Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S83-S96"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gilaad G Kaplan, M Ellen Kuenzig, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Sara Ghandeharian, Noelle Rohatinsky, Jake Weinstein, Tyrel Jones May, Mira Browne, Nazanin Jannati, Sahar Tabatabavakili, James H B Im, Saketh Meka, Sonya Vukovic, Tal Davis, Quinn Goddard, Julia Gorospe, Taylor Stocks, Léa Caplan, Najla Kanaan, Daniel Stuart, Tesa Ramsay, Kelly J Robinson, Diane Charron-Bishop, Eric I Benchimol
The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: COVID-19 and IBD.","authors":"Gilaad G Kaplan, M Ellen Kuenzig, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Sara Ghandeharian, Noelle Rohatinsky, Jake Weinstein, Tyrel Jones May, Mira Browne, Nazanin Jannati, Sahar Tabatabavakili, James H B Im, Saketh Meka, Sonya Vukovic, Tal Davis, Quinn Goddard, Julia Gorospe, Taylor Stocks, Léa Caplan, Najla Kanaan, Daniel Stuart, Tesa Ramsay, Kelly J Robinson, Diane Charron-Bishop, Eric I Benchimol","doi":"10.1093/jcag/gwad019","DOIUrl":"https://doi.org/10.1093/jcag/gwad019","url":null,"abstract":"<p><p>The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S76-S82"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lesley A Graff, Rose Geist, M Ellen Kuenzig, Eric I Benchimol, Gilaad G Kaplan, Joseph W Windsor, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Juan-Nicolás Peña-Sánchez, Laura E Targownik, Nazanin Jannati, Tyrel Jones May, Tasbeen Akhtar Sheekha, Tal Davis, Jake Weinstein, Ghaida Dahlwi, James H B Im, Jessica Amankwah Osei, Noelle Rohatinsky, Sara Ghandeharian, Quinn Goddard, Julia Gorospe, Shira Gertsman, Michelle Louis, Richelle Wagner, Colten Brass, Rhonda Sanderson, Charles N Bernstein
Psychiatric disorders are 1.5 to 2 times more prevalent in persons with inflammatory bowel disease (IBD) than in the general population, with pooled prevalence estimates of 21% for clinical anxiety and 15% for depression. Rates are even higher when considering mental health symptoms, as nearly one-third of persons with IBD experience elevated anxiety symptoms and one-quarter experience depression symptoms. Rates of these symptoms were much higher during periods of disease activity, more common in women than men, and more common in Crohn's disease than ulcerative colitis. There is robust evidence of the detrimental effects of comorbid depression and anxiety on the subsequent course of IBD based on longitudinal studies tracking outcomes over time. However, psychiatric disorders and IBD have bidirectional effects, with each affecting risk of the other. Elevated mental health concerns have been consistently associated with greater healthcare utilization and costs related to IBD. There is some signal that low resilience in adolescence could be a risk factor for developing IBD and that enhancing resilience may improve mental health and intestinal disease outcomes in IBD. Psychological therapies used to treat anxiety and depression occurring in the context of IBD have been shown to significantly improve the quality of life for persons with IBD and reduce anxiety and depression. There is less evidence in regard to the impact of psychotropic medications on mental health or disease outcomes in persons with IBD. There is consensus, however, that mental health must be addressed as part of comprehensive IBD care for children and adults.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Mental Health and Inflammatory Bowel Disease.","authors":"Lesley A Graff, Rose Geist, M Ellen Kuenzig, Eric I Benchimol, Gilaad G Kaplan, Joseph W Windsor, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Juan-Nicolás Peña-Sánchez, Laura E Targownik, Nazanin Jannati, Tyrel Jones May, Tasbeen Akhtar Sheekha, Tal Davis, Jake Weinstein, Ghaida Dahlwi, James H B Im, Jessica Amankwah Osei, Noelle Rohatinsky, Sara Ghandeharian, Quinn Goddard, Julia Gorospe, Shira Gertsman, Michelle Louis, Richelle Wagner, Colten Brass, Rhonda Sanderson, Charles N Bernstein","doi":"10.1093/jcag/gwad012","DOIUrl":"https://doi.org/10.1093/jcag/gwad012","url":null,"abstract":"<p><p>Psychiatric disorders are 1.5 to 2 times more prevalent in persons with inflammatory bowel disease (IBD) than in the general population, with pooled prevalence estimates of 21% for clinical anxiety and 15% for depression. Rates are even higher when considering mental health symptoms, as nearly one-third of persons with IBD experience elevated anxiety symptoms and one-quarter experience depression symptoms. Rates of these symptoms were much higher during periods of disease activity, more common in women than men, and more common in Crohn's disease than ulcerative colitis. There is robust evidence of the detrimental effects of comorbid depression and anxiety on the subsequent course of IBD based on longitudinal studies tracking outcomes over time. However, psychiatric disorders and IBD have bidirectional effects, with each affecting risk of the other. Elevated mental health concerns have been consistently associated with greater healthcare utilization and costs related to IBD. There is some signal that low resilience in adolescence could be a risk factor for developing IBD and that enhancing resilience may improve mental health and intestinal disease outcomes in IBD. Psychological therapies used to treat anxiety and depression occurring in the context of IBD have been shown to significantly improve the quality of life for persons with IBD and reduce anxiety and depression. There is less evidence in regard to the impact of psychotropic medications on mental health or disease outcomes in persons with IBD. There is consensus, however, that mental health must be addressed as part of comprehensive IBD care for children and adults.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S64-S75"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wael El-Matary, Matthew W Carroll, Colette Deslandres, Anne M Griffiths, M Ellen Kuenzig, David R Mack, Eytan Wine, Jake Weinstein, Rose Geist, Tal Davis, Justin Chan, Rabia Khan, Priscilla Matthews, Gilaad G Kaplan, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James H B Im, Quinn Goddard, Julia Gorospe, Jules Verdugo, Samantha A Morin, Taylor Morganstein, Lisa Banning, Eric I Benchimol
Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-Children and Adolescents with IBD.","authors":"Wael El-Matary, Matthew W Carroll, Colette Deslandres, Anne M Griffiths, M Ellen Kuenzig, David R Mack, Eytan Wine, Jake Weinstein, Rose Geist, Tal Davis, Justin Chan, Rabia Khan, Priscilla Matthews, Gilaad G Kaplan, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James H B Im, Quinn Goddard, Julia Gorospe, Jules Verdugo, Samantha A Morin, Taylor Morganstein, Lisa Banning, Eric I Benchimol","doi":"10.1093/jcag/gwad016","DOIUrl":"https://doi.org/10.1093/jcag/gwad016","url":null,"abstract":"<p><p>Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S35-S44"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seth R Shaffer, M Ellen Kuenzig, Joseph W Windsor, Alain Bitton, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Parul Tandon, Joëlle St-Pierre, Navneet Natt, Tal Davis, Jake Weinstein, James H B Im, Eric I Benchimol, Gilaad G Kaplan, Quinn Goddard, Julia Gorospe, Maxime Bergevin, Ken Silver, Dawna Bowles, Margaret Stewart, Marsha Pearlstein, Elizabeth H Dawson, Charles N Bernstein
Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-IBD in Seniors.","authors":"Seth R Shaffer, M Ellen Kuenzig, Joseph W Windsor, Alain Bitton, Jennifer L Jones, Kate Lee, Sanjay K Murthy, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Parul Tandon, Joëlle St-Pierre, Navneet Natt, Tal Davis, Jake Weinstein, James H B Im, Eric I Benchimol, Gilaad G Kaplan, Quinn Goddard, Julia Gorospe, Maxime Bergevin, Ken Silver, Dawna Bowles, Margaret Stewart, Marsha Pearlstein, Elizabeth H Dawson, Charles N Bernstein","doi":"10.1093/jcag/gwad013","DOIUrl":"https://doi.org/10.1093/jcag/gwad013","url":null,"abstract":"<p><p>Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S45-S54"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Ellen Kuenzig, James H B Im, Stephanie Coward, Joseph W Windsor, Gilaad G Kaplan, Sanjay K Murthy, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Tyrel Jones May, Sahar Tabatabavakili, Rohit Jogendran, Jake Weinstein, Rabia Khan, Elias Hazan, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Kate Mason, Jack Kerr, Naji Balche, Anna Sklar, Laura E Targownik
People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one's ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn's and Colitis Canada's 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Indirect (Individual and Societal) and Direct Out-of-Pocket Costs.","authors":"M Ellen Kuenzig, James H B Im, Stephanie Coward, Joseph W Windsor, Gilaad G Kaplan, Sanjay K Murthy, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Tyrel Jones May, Sahar Tabatabavakili, Rohit Jogendran, Jake Weinstein, Rabia Khan, Elias Hazan, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Kate Mason, Jack Kerr, Naji Balche, Anna Sklar, Laura E Targownik","doi":"10.1093/jcag/gwad009","DOIUrl":"https://doi.org/10.1093/jcag/gwad009","url":null,"abstract":"<p><p>People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one's ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn's and Colitis Canada's 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S16-S22"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Ellen Kuenzig, Stephanie Coward, Laura E Targownik, Sanjay K Murthy, Eric I Benchimol, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James H B Im, Rohit Jogendran, Saketh Meka, Jake Weinstein, Tyrel Jones May, Manisha Jogendran, Sahar Tabatabavakili, Elias Hazan, Malini Hu, Jessica Amankwah Osei, Rabia Khan, Grace Wang, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Kate Mason, Jack Kerr, Naji Balche, Anna Sklar, Gilaad G Kaplan
Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn's disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Direct Health System and Medication Costs.","authors":"M Ellen Kuenzig, Stephanie Coward, Laura E Targownik, Sanjay K Murthy, Eric I Benchimol, Joseph W Windsor, Charles N Bernstein, Alain Bitton, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James H B Im, Rohit Jogendran, Saketh Meka, Jake Weinstein, Tyrel Jones May, Manisha Jogendran, Sahar Tabatabavakili, Elias Hazan, Malini Hu, Jessica Amankwah Osei, Rabia Khan, Grace Wang, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Kate Mason, Jack Kerr, Naji Balche, Anna Sklar, Gilaad G Kaplan","doi":"10.1093/jcag/gwad008","DOIUrl":"https://doi.org/10.1093/jcag/gwad008","url":null,"abstract":"<p><p>Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn's disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S23-S34"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Holly Mathias, Noelle Rohatinsky, Sanjay K Murthy, Kerri Novak, M Ellen Kuenzig, Geoffrey C Nguyen, Sharyle Fowler, Eric I Benchimol, Stephanie Coward, Gilaad G Kaplan, Joseph W Windsor, Charles N Bernstein, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Kate Lee, Sara Ghandeharian, Nazanin Jannati, Jake Weinstein, Rabia Khan, James H B Im, Priscilla Matthews, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Michelle Louis, Naji Balche, Peter Dobranowski, Ashley Patel, Linda J Porter, Robert M Porter, Alain Bitton, Jennifer L Jones
Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56-66.) and pandemic-exacerbated health system resource limitations have resulted in significant variability in access to high-quality, evidence-based, person-centered specialty care for Canadians living with IBD. Individuals with IBD have identified long wait times, gaps in biopsychosocial care, treatment and travel expenses, and geographic and provider variation in IBD specialty care and knowledge as some of the key barriers to access. Care delivered within integrated models of care (IMC) has shown promise related to impact on disease-related outcomes and quality of life. However, access to these models is limited within the Canadian healthcare systems and much remains to be learned about the most appropriate IMC team composition and roles. Although eHealth technologies have been leveraged to overcome some access challenges since COVID-19, more research is needed to understand how best to integrate eHealth modalities (i.e., video or telephone visits) into routine IBD care. Many individuals with IBD are satisfied with these eHealth modalities. However, not all disease assessment and monitoring can be achieved through virtual modalities. The need for access to person-centered, objective disease monitoring strategies, inclusive of point of care intestinal ultrasound, is more pressing than ever given pandemic-exacerbated restrictions in access to endoscopy and cross-sectional imaging. Supporting learning healthcare systems for IBD and research relating to the strategic use of innovative and integrative implementation strategies for evidence-based IBD care interventions are greatly needed. Data derived from this research will be essential to appropriately allocating scarce resources aimed at improving person-centred access to cost-effective IBD care.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Access to and Models of Care.","authors":"Holly Mathias, Noelle Rohatinsky, Sanjay K Murthy, Kerri Novak, M Ellen Kuenzig, Geoffrey C Nguyen, Sharyle Fowler, Eric I Benchimol, Stephanie Coward, Gilaad G Kaplan, Joseph W Windsor, Charles N Bernstein, Laura E Targownik, Juan-Nicolás Peña-Sánchez, Kate Lee, Sara Ghandeharian, Nazanin Jannati, Jake Weinstein, Rabia Khan, James H B Im, Priscilla Matthews, Tal Davis, Quinn Goddard, Julia Gorospe, Kate Latos, Michelle Louis, Naji Balche, Peter Dobranowski, Ashley Patel, Linda J Porter, Robert M Porter, Alain Bitton, Jennifer L Jones","doi":"10.1093/jcag/gwad007","DOIUrl":"https://doi.org/10.1093/jcag/gwad007","url":null,"abstract":"<p><p>Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56-66.) and pandemic-exacerbated health system resource limitations have resulted in significant variability in access to high-quality, evidence-based, person-centered specialty care for Canadians living with IBD. Individuals with IBD have identified long wait times, gaps in biopsychosocial care, treatment and travel expenses, and geographic and provider variation in IBD specialty care and knowledge as some of the key barriers to access. Care delivered within integrated models of care (IMC) has shown promise related to impact on disease-related outcomes and quality of life. However, access to these models is limited within the Canadian healthcare systems and much remains to be learned about the most appropriate IMC team composition and roles. Although eHealth technologies have been leveraged to overcome some access challenges since COVID-19, more research is needed to understand how best to integrate eHealth modalities (i.e., video or telephone visits) into routine IBD care. Many individuals with IBD are satisfied with these eHealth modalities. However, not all disease assessment and monitoring can be achieved through virtual modalities. The need for access to person-centered, objective disease monitoring strategies, inclusive of point of care intestinal ultrasound, is more pressing than ever given pandemic-exacerbated restrictions in access to endoscopy and cross-sectional imaging. Supporting learning healthcare systems for IBD and research relating to the strategic use of innovative and integrative implementation strategies for evidence-based IBD care interventions are greatly needed. Data derived from this research will be essential to appropriately allocating scarce resources aimed at improving person-centred access to cost-effective IBD care.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S111-S121"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanjay K Murthy, Adam V Weizman, M Ellen Kuenzig, Joseph W Windsor, Gilaad G Kaplan, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Nasruddin Sabrie, Sarang Gupta, Gurmun Brar, Rabia Khan, James H B Im, Tal Davis, Jake Weinstein, Joëlle St-Pierre, Roxana Chis, Saketh Meka, Eric Cheah, Quinn Goddard, Julia Gorospe, Jack Kerr, Kayla D Beaudion, Ashley Patel, Sophia Russo, Jonathan Blyth, Stephanie Blyth, Diane Charron-Bishop, Laura E Targownik
The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes.
{"title":"The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape.","authors":"Sanjay K Murthy, Adam V Weizman, M Ellen Kuenzig, Joseph W Windsor, Gilaad G Kaplan, Eric I Benchimol, Charles N Bernstein, Alain Bitton, Stephanie Coward, Jennifer L Jones, Kate Lee, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Nasruddin Sabrie, Sarang Gupta, Gurmun Brar, Rabia Khan, James H B Im, Tal Davis, Jake Weinstein, Joëlle St-Pierre, Roxana Chis, Saketh Meka, Eric Cheah, Quinn Goddard, Julia Gorospe, Jack Kerr, Kayla D Beaudion, Ashley Patel, Sophia Russo, Jonathan Blyth, Stephanie Blyth, Diane Charron-Bishop, Laura E Targownik","doi":"10.1093/jcag/gwad015","DOIUrl":"https://doi.org/10.1093/jcag/gwad015","url":null,"abstract":"<p><p>The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes.</p>","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"6 Suppl 2","pages":"S97-S110"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}