Summary
Background
Appendicitis is a common disease with a lifespan risk of approximately 8%. The full range of specific causes for the disease remains elusive, but an aberrant microbiota have been ...identified as a potential risk factor.
Aim
To investigate if use of antibiotics in a paediatric population increases the risk of appendicitis in childhood and adolescence
Methods
We conducted a cohort study from 1 January 1995 to 31 December 2014. A total of 1 385 707 children (0‐19 years of age) including 7 406 397 antibiotic prescriptions and 11 861 cases of appendicitis were included. Primary outcome was appendicitis requiring appendectomy according to previous use of antibiotics. Appendicitis and appendectomy were identified from nationwide hospital records, and exposure to antibiotics was identified from nationwide prescription register. Rate ratios (RRs) with 95% confidence intervals were estimated from Poisson and logistic regression models.
Results
Children who received at least one course of antibiotics were at increased risk of developing appendicitis compared to unexposed children (adjusted RR 1.72 95% confidence interval 1.61‐1.85), mean age of developing appendicitis was 9.8 years (SD 4.1 years). The RR of appendicitis increased by 1.04 (1.04‐1.04) per antibiotic course. A higher risk of appendicitis was observed in children exposed to antibiotics within the first 6 months of life (RR 1.46 1.36‐1.56) and children exposed to broad‐spectrum antibiotics (RR 1.33 1.27‐1.39). After adjustment for number of antibiotic courses, the association between early age of antibiotic exposure and risk of appendicitis and the association between exposure to broad‐spectrum antibiotics and the risk of appendicitis both disappeared.
Conclusion
Children who receive antibiotics are at increased and dose‐dependent risk of appendicitis. The underlying mechanisms merit further investigation.
Summary
Background
Escalation to anti‐tumour necrosis factor (anti‐TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing ...thiopurine at escalation is unclear.
Aim
To assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation.
Methods
We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti‐TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti‐TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD‐related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).
Results
Of the 10,352 anti‐TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti‐TNF. After anti‐TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti‐TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10‐1.36), particularly for IBD‐related hospitalization (aHR: 1.14; 95% CI: 1.00‐1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13‐1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02‐1.34) and UC (aHR: 1.32; 95% CI: 1.12‐1.55).
Conclusions
In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti‐TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.
Continuing thiopurine therapy at the time of anti‐TNF initiation (versus discontinuing thiopurine) decreased the risk of adverse outcomes, including new corticosteroid use, IBD‐related hospitalization, IBD‐related surgery, and death in this nationwide cohort study of 2,630 patients with IBD. Particularly, it reduced hospitalization and new corticosteroid use, key goals in the management of IBD.
Since information about macro- and micronutrient intake among vegans is limited we aimed to determine and evaluate their dietary and supplementary intake.
Seventy 18-61 years old Danish vegans ...completed a four-day weighed food record from which their daily intake of macro- and micronutrients was assessed and subsequently compared to an age-range-matched group of 1,257 omnivorous individuals from the general Danish population. Moreover, the vegan dietary and supplementary intake was compared to the 2012 Nordic Nutrition Recommendations (NNR).
Dietary intake differed significantly between vegans and the general Danish population in all measured macro- and micronutrients (p < 0.05), except for energy intake among women and intake of carbohydrates among men. For vegans the intake of macro- and micronutrients (including supplements) did not reach the NNR for protein, vitamin D, iodine and selenium. Among vegan women vitamin A intake also failed to reach the recommendations. With reference to the NNR, the dietary content of added sugar, sodium and fatty acids, including the ratio of PUFA to SFA, was more favorable among vegans.
At the macronutrient level, the diet of Danish vegans is in better accordance with the NNR than the diet of the general Danish population. At the micronutrient level, considering both diet and supplements, the vegan diet falls short in certain nutrients, suggesting a need for greater attention toward ensuring recommended daily intake of specific vitamins and minerals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Importance
Observational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in ...clinical trials.
Objective
To compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD.
Design, Setting, and Participants
This active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022.
Interventions
Treatment with vedolizumab or TNF antagonists.
Main Outcomes and Measures
The primary effectiveness outcome was treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy. Secondary effectiveness outcomes were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score–matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors.
Results
The study compared 377 older patients with IBD with incident use of vedolizumab (202 women 53.6%; mean SD age, 61.2 8.3 years; 177 46.9% with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women 54.6%; mean SD age, 61.3 8.1 years; 182 48.3% with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio HR, 1.31; 95% CI, 1.02-1.69), including higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43;
P
= .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.
Conclusions and Relevance
In this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage.
Phosphatidylcholine (PC), the most abundant of the phospholipids, has several metabolic functions in organs such as the liver and the intestine, important structural- and signaling functions in ...biological membranes, and might have a role in the effects of Roux-en-Y gastric bypass (RYGB), an operation known to ameliorate metabolic diseases, including type 2 diabetes. We hypothesized that serum PC, as a reflection of phospholipid metabolism, changes after RYGB, and that changes are related to weight loss and possibly to changes in glucose metabolism (reflected in the HbA1c-level) as well as to changes in serum Apo A1, Apo B and Apo B/Apo A1 ratio.
In a cohort of 220 RYGB patients, we studied changes in serum PC after RYGB in relation to serum Apo A1 and Apo B, the main apolipoproteins in HDL- and LDL/VLDL-particles, respectively, up to 2 years following RYGB-surgery.
Serum PC reached its lowest levels 3 months postoperatively to later rebound to preoperative levels 24 months after RYGB. No difference was seen between patients with or without type 2 diabetes. Serum Apo A1 showed a similar pattern whereas serum Apo B concentrations stayed low after the initial decrease after RYGB. As a result, the Apo B / Apo A1 ratio constantly decreased during follow-up. There was a strong positive correlation between PC and Apo A1, and between PC and Apo B, but none between Apo A1 and Apo B. After RYGB surgery, both PC and Apo A1, but not Apo B, correlated positively to weight loss. In relation to total cholesterol, the molar ratio between serum PC and plasma cholesterol increased steadily after RYGB.
We conclude that changes in PC and apolipoproteins after RYGB are highly dynamic, reflecting a large plasticity and capability of accommodating lipid metabolism including PC-, cholesterol- and apolipoprotein metabolism imposed by RYGB surgery, independent of glucose tolerance. We suggest that after RYGB and major weight loss, PC and Apo A1 might have a special role in the altered metabolism of lipoproteins.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundAlthough short adult height is generally associated with increased risks of type 2 diabetes mellitus (T2DM), there are large inconsistencies across studies. The aims of this study were to ...describe and quantify currently available evidence on the association between adult height and T2DM, to examine whether the reported associations differ by sex, and to examine the shapes of the height and T2DM associations.MethodsRelevant literature was identified using PubMed (1966–May 2018), EMBASE (1947–May 2018) and Google Scholar (May 2018). We identified cross-sectional and cohort studies with original publications on human subjects, which were included in a random-effects meta-analysis.ResultsFrom 15 971 identified sources, 25 studies met the inclusion criteria for the systematic review (N=401 562 individuals). From these 25 studies, 16 (9 cross-sectional studies and 7 cohort studies) were included in the meta-analysis (n=261 496 individuals). The overall random-effects meta-analysis indicated an inverse association between adult height and T2DM (effect estimate=0.88, 95% CI 0.81 to 0.95). No sex differences in the associations between adult height and T2DM were found (effect estimate for men: 0.86, 95% CI 0.75 to 0.99; effect estimate for women: 0.90; 95% CI 0.80 to 1.01; p value for sex interaction=0.80). Due to lack of data, results on the shape of the association between height and T2DM were inconclusive.ConclusionsShorter height is associated with an increased risk of T2DM and the association does not significantly differ by sex. The currently available data are insufficient to support conclusions regarding the shape of the association between height and T2DM.Trial registration number CRD42017062446.
The colon hosts gut microbes and glucagon-like peptide 1 secreting cells, both of which influence glucose homeostasis. We tested whether colectomy is associated with development of type 2 diabetes. ...Using nationwide register data, we identified patients who had undergone total colectomy, partial colectomy, or proctectomy. For each colectomy patient, we selected 15 non-colectomy patients who had undergone other surgeries. Compared with non-colectomy patients, patients with total colectomy (n = 3,793) had a hazard ratio (HR) of clinically recorded type 2 diabetes of 1.40 (95% confidence interval CI, 1.21 to 1.62; p<0.001). Corresponding HRs after right hemicolectomy (n = 10,989), left hemicolectomy (n = 2,513), and sigmoidectomy (n = 13,927) were 1.08 (95% CI, 0.99 to 1.19; p=0.10), 1.41 (95% CI, 1.19 to 1.67; p<0.001) and 1.30 (95% CI, 1.21 to 1.40; p<0.001), respectively. Although we were not able to adjust for several potential confounders, our findings suggest that the left colon may contribute to maintenance of glucose homeostasis.
Elevated plasma levels of C-reactive protein (CRP), a marker of inflammation, are associated with an increased risk of cancer, but it is unclear whether this association is causal. We examined ...whether four common single-nucleotide polymorphisms (SNPs) in the CRP gene that are associated with altered plasma CRP levels are causally associated with an increased risk of cancer. The study population included participants in a prospective study (n = 10 215) and a cross-sectional study (n = 36 403) of the adult general population in Denmark, all of whom were genotyped for the CRP SNPs. The association between plasma CRP levels measured by a high-sensitivity turbidimetry assay and the risk of cancer was examined for 8224 participants in the prospective study. The hazard ratio of cancer for a doubling of the plasma CRP level was 1.09 (95% confidence interval CI = 1.03 to 1.14). The nine most common genotype combinations of the four CRP SNPs were associated with up to a 72% increase (95% CI = 58% to 87%) in CRP levels but not with an increased risk of cancer. The estimated causal odds ratio for cancer associated with a genetically induced doubling in CRP level was 0.94 (95% CI = 0.81 to 1.08). This finding suggests that elevated CRP levels do not cause cancer.
To review studies examining the appendiceal microbiota and microbial changes in acute appendicitis.
After a systematic literature search, 11 studies examining the appendiceal microbiota (414 samples) ...using non-culture-based methods were included.
The appendiceal microbiota showed decreased α-diversity compared with fecal microbiota. Inflamed and uninflamed appendices showed differences in β-diversity, and there was an increased abundance of oral-associated bacteria in inflamed versus uninflamed appendices.
The appendiceal microbiota exhibits lower α-diversity than the fecal microbiota, with an increased abundance of oral-associated bacteria. Compared with uninflamed appendices, the appendix microbiota in acute appendicitis also showed increased abundance of oral-associated bacteria, but no bacterial profile unique to either complicated or uncomplicated appendicitis was found.
Aims/hypothesis
Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and ...follow-up examinations (18, 36 and 48 months of follow-up).
Methods
From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (
n
= 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6–24 months previously (
n
= 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at ~18 months (both cohorts) and at ~48 months (cohort 1) or ~36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe.
Results
Using ADA 2011 glycaemic categories, 33% (
n
= 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (
n
= 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean ± SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m
2
; fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants’ clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (
n
= 517) were treated by lifestyle modification and 34% (
n
= 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m
2
; fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants’ clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l.
Conclusions/interpretation
The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.
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