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Prevalence and Implications of Frailty in Older Adults With Incident Inflammatory Bowel Diseases: A Nationwide Cohort Study.
Kochar, B, Jylhävä, J, Söderling, J, Ritchie, CS, , , Ludvigsson, JF, Khalili, H, Olén, O
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;(10):2358-2365.e11
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Abstract
BACKGROUND AND AIMS We aimed to compare the risk of frailty in older adults with incident inflammatory bowel disease (IBD) and matched non-IBD comparators and assess the association between frailty and future hospitalizations and mortality. METHODS In a cohort of patients with incident IBD ≥60 years of age from 2007 to 2016 in Sweden identified using nationwide registers, we defined frailty using Hospital Frailty Risk Score. We compared prevalence of frailty in patients with IBD with age, sex, place of residency- and calendar year-matched population comparators. In the IBD cohort, we used Cox proportional hazards modeling to examine the associations between frailty risk and hospitalizations or mortality. RESULTS We identified 10,590 patients with IBD, 52% female with a mean age of 71 years of age, matched to 103,398 population-based comparators. Among patients with IBD, 39% had no risk for frailty, 49% had low risk for frailty, and 12% had higher risk for frailty. Mean Hospital Frailty Risk Score was 1.9 in IBD and 0.9 in matched comparators (P < .01). Older adults with IBD at higher risk for frailty had a 20% greater risk for mortality at 3 years compared with those who were not frail. Compared with nonfrail older patients with IBD, patients at higher risk for frailty had increased mortality (hazard ratio [HR], 3.22, 95% confidence interval [CI], 2.86-3.61), all-cause hospitalization (HR, 2.42; 95% CI, 2.24-2.61), and IBD-related hospitalization (HR, 1.50; 95% CI, 1.35-1.66). These associations were not attenuated after adjusting for comorbidities. CONCLUSIONS Frailty is more prevalent in older adults with IBD than in matched comparators. Among older patients with IBD, frailty is associated with increased risk for hospitalizations and mortality.
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Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies.
Chan, SSM, Chen, Y, Casey, K, Olen, O, Ludvigsson, JF, Carbonnel, F, Oldenburg, B, Gunter, MJ, Tjønneland, A, Grip, O, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;(5):1048-1058
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BACKGROUND AND AIMS It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. CONCLUSIONS In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19.
Ludvigsson, JF
Acta paediatrica (Oslo, Norway : 1992). 2021;110(3):914-921
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The long-term effects of COVID-19 is becoming increasingly documented in adults. Symptoms such as fatigue, headache and depression have all been reported, however data on the possible long-term effects of COVID-19 in children is scarce. The aim of this systematic review and case report was to describe the long-term effects of COVID-19 in five children and support this with other reports in the literature. The results showed that of the five case reports of long COVID, four were girls aged 9-15 years. All subjects reported symptoms lasting between 6-8 months. Most common symptoms were fatigue, difficulty breathing and heart issues. The systematic literature review did not find any publications which documented long COVID in children. It was concluded that children may experience long COVID symptoms and girls may be more susceptible. This study could be used by healthcare professionals to understand that children may also be affected by long COVID and that patients should be monitored for symptoms for at least 6-8 months.
Abstract
AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce. METHODS This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020. RESULTS The five children with potential long COVID had a median age of 12 years (range 9-15) and four were girls. They had symptoms for 6-8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children. CONCLUSION Children may experience similar long COVID symptoms to adults and females may be more affected.
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Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
Ludvigsson, JF
Acta paediatrica (Oslo, Norway : 1992). 2020;109(6):1088-1095
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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was also previously known as 2019-nCoV. This study is a systematic literature review which summarises the findings on the current knowledge of COVID-19 in children. The review includes 45 scientific papers and letters. Results showed that children have so far accounted for 1%-5% of diagnosed cases. Children often are asymptomatic, have milder disease than adults, and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent. Authors conclude that the disease course in paediatric COVID-19 was milder than in adults, children had a better prognosis and deaths were extremely rare.
Abstract
AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990-2014.
Kalman, TD, Everhov, ÅH, Nordenvall, C, Sachs, MC, Halfvarson, J, Ekbom, A, Ludvigsson, JF, Myrelid, P, Olén, O
The British journal of surgery. 2020;(11):1529-1538
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BACKGROUND Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated. METHODS In this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990-1995 and 1996-2000 with use of inpatient registries, 2001, and 2002-2008 and 2009-2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan-Meier method. RESULTS Among 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990-1995 to 40·4 per cent in 1996-2000 (P < 0·001), and again from 19·8 per cent in 2002-2008 to 17·3 per cent in 2009-2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990-1995 to 16·0 per cent in 1996-2000 (P = 0·009). After 2000, no further significant decreases were observed. CONCLUSION The 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy.
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The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register.
Shrestha, S, Olén, O, Eriksson, C, Everhov, ÅH, Myrelid, P, Visuri, I, Ludvigsson, JF, Schoultz, I, Montgomery, S, Sachs, MC, et al
Scandinavian journal of gastroenterology. 2020;(4):430-435
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Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown.Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals.Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis.Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
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Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients.
Everhov, ÅH, Sachs, MC, Malmborg, P, Nordenvall, C, Myrelid, P, Khalili, H, Elmberg, M, Ekbom, A, Askling, J, Jakobsson, G, et al
Scandinavian journal of gastroenterology. 2019;(1):55-63
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AIM: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time. METHODS We examined International Classification of Diseases coding in patients with ≥2 IBD diagnostic listings in the National Patient Register 2002-2014 (n = 44,302). RESULTS 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children). CONCLUSIONS IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children.
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Intestinal failure after necrotising enterocolitis: incidence and risk factors in a Swedish population-based longitudinal study.
Sjoberg Bexelius, T, Ahle, M, Elfvin, A, Björling, O, Ludvigsson, JF, Andersson, RE
BMJ paediatrics open. 2018;(1):e000316
Abstract
BACKGROUND AND OBJECTIVE Paediatric intestinal failure (IF) is a disease entity characterised by gut insufficiency often related to short bowel syndrome. It is commonly caused by surgical removal of a large section of the small intestine in association with necrotising enterocolitis (NEC), which usually affects premature infants. This study investigated the incidence and risk of IF in preterm infants with or without NEC. DESIGN A matched cohort study to investigate the incidence and risk factors for IF in a population-based setting in Sweden from 1987 to 2009 using the Swedish Patient Register. PARTICIPANTS Infants with a diagnosis of NEC (n=720) were matched for gestational age and year of birth with reference individuals without NEC (n=3656). The study cohort was censored at death, IF or at end of follow-up (2 years of age). We calculated HRs with 95%CIs for IF using Cox regression, adjusting for pertinent perinatal factors. RESULTS IF was 15 times more common in the infants with NEC compared with the reference infants (HR=7.2, with 95% CI 3.7 to 14.0). Other risk factors for IF were small for gestational age, extreme preterm birth and abdominal surgery. Neonatal mortality in infants with NEC decreased from 20.6% in 1987-1993 to 10.4% in 2007-2009. CONCLUSION IF was more common in the infants with NEC but was also linked to extreme preterm birth, a history of abdominal surgery and small for gestational age. IF was more common at the end of the study period, indicating that it increases when more preterm infants with NEC survive the neonatal period.
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Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis.
Mahadev, S, Laszkowska, M, Sundström, J, Björkholm, M, Lebwohl, B, Green, PHR, Ludvigsson, JF
Gastroenterology. 2018;(2):374-382.e1
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BACKGROUND & AIMS Anemia is common in patients with celiac disease (CD) and a frequent mode of presentation. Guidelines recommend screening patients with iron-deficiency anemia (IDA) for CD. However, the reported prevalence of CD in patients with IDA varies. We performed a systematic review to determine the prevalence of biopsy-verified CD in patients with IDA. METHODS We performed a systematic review of articles published in PubMed Medline or EMBASE through July 2017 for the term "celiac disease" combined with "anemia" or "iron deficiency." We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of CD. Meta-regression was used to assess subgroup heterogeneity. RESULTS We identified 18 studies composed of 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of CD was 4.8% (n = 143). Using a weighted pooled analysis, we found a prevalence of biopsy-confirmed CD of 3.2% (95% confidence interval = 2.6-3.9) in patients with IDA. However, heterogeneity was high (I2 = 67.7%). The prevalence of CD was not significantly higher in studies with a mean participant age older or younger than 18 years or in studies with a mixed-sex vs female-predominant (≥60%) population. On meta-regression, year of publication, female proportion, age at CD testing, and prevalence in the general population were not associated with the prevalence of CD in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of CD was 5.5% (95% confidence interval = 4.1-6.9). CONCLUSIONS In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of CD. This prevalence value justifies the practice of testing patients with IDA for CD.
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Celiac disease and non-celiac gluten sensitivity.
Lebwohl, B, Ludvigsson, JF, Green, PH
BMJ (Clinical research ed.). 2015;:h4347
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Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.