Predictors of Complicated Disease Course in Children and Adults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN.

BACKGROUND: Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC. METHODS: Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together. RESULTS: A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course. CONCLUSION: In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.

Prognostic factors of complicated disease course are vital for clinical decision-making of early escalation to intensive treatment. In this nationwide cohort, one-third of children and one-fifth of adults with UC developed complicated disease course. Disease course was predicted particularly by routinely collected laboratory tests, age, extraintestinal manifestations, and type of induction therapy at diagnosis.

Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN.

BACKGROUND: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators. METHODS: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching. RESULTS: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02). CONCLUSION: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy.

Predictors of Complicated Disease Course in Adults and Children With Crohn's Disease: A Nationwide Study from the epi-IIRN.

BACKGROUND: Since data on predictors of complicated Crohn's disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD. METHODS: Data of patients with CD were retrieved from Israel's 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for >1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results. RESULTS: A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score -0.41; 95% CI, -1.42 to 0.43 in complicated disease vs -0.24; 95% CI, -1.23 to 0.63] in favorable disease; P < .001). CONCLUSIONS: In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children.

Prognostic factors of complicated disease course are vital for considering early escalation to biologics. In this nationwide cohort, complicated disease course was apparent in approximately one-fourth of patients and was predicted particularly by routinely collected laboratory tests, age, and type of induction therapy at diagnosis.

The epidemiology of inflammatory bowel diseases during the COVID-19 pandemic: comparison of two nationwide cohorts.

BACKGROUND: We aimed to explore the epidemiology of inflammatory bowel diseases (IBD) in association with the COVID-19 pandemic in two countries with different lockdown policies. METHODS: We utilized nationwide IBD cohorts in Israel and Sweden to explore the incidence of IBD during the pandemic compared to three years prior (2017- 2019). We examined temporal trends through the presence of inflection points by Joinpoint regression analysis and reported average monthly percentage changes (AMPC). RESULTS: A total of 155,837 patients with IBD were included (Israel, 58,640; Sweden, 97,197). The annual incidence of IBD was stable until 2019 in both countries and since, it decreased in Israel (AAPC of -16.6% [95%CI -19.9% to -10.0%]) and remained stable in Sweden (AAPC of -3.5% [95%CI -11.6% to 3.7%]). When exploring the monthly incidence during the pandemic, in Israel the rate remained stable until November 2020 (AMPC 2.3% [95%CI -13.4% to 29.9%]) and then decreased sharply (AMPC -6.4% [95%CI-20.8% to 17.0%]) until February 2021 and -20.1% [95%CI -38.9% to -4.7%]) from February 2021), while in Sweden, which had a less stringent lockdown policy, it decreased slightly until July 2020 (AMPC -3.3% [95%CI -21.6% to 20.3%]), but increased thereafter (AMPC 13.6% [95%CI -12.6% to 27.0%]). The change of incidence rate in Sweden occurred mainly in elderly-onset patients, the only population with significant restrictions during the pandemic. CONCLUSION: The incidence of IBD decreased during the pandemic in association with lockdowns, more so in Israel, which had more stringent policies. Future studies are needed to determine the long-term effect of the pandemic on IBD.

Durability of Adalimumab and Infliximab in Children With Crohn's Disease: A Nationwide Comparison From the epi-IIRN Cohort.

BACKGROUND: In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy. METHODS: We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models. RESULTS: Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4). CONCLUSION: Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy.

Prevalence and Outcomes of No Treatment Versus 5-ASA in Ulcerative Colitis: A Nationwide Analysis From the epi-IIRN.

BACKGROUND: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients. METHODS: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment. RESULTS: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy. CONCLUSIONS: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC.

The rate of no maintenance treatment (NMT) decreased in the last years, but in a propensity score­matched analysis, 5-aminosalicylic acid monotherapy did not demonstrate any therapeutic advantage over NMT. NMT seems to be a viable option in a subset of patients with mild ulcerative colitis.

Residence in Peripheral Regions and Low Socioeconomic Status Are Associated With Worse Outcomes of Inflammatory Bowel Diseases: A Nationwide Study From the epi-IIRN.

BACKGROUND: Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes. METHODS: We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use. RESULTS: A total of 28 216 IBD patients were included: 15 818 (56%) Crohn's disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P < .001; and 18% vs 12% in ulcerative colitis; P < .001), and higher surgery rates (12% vs 7%; P < .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes. CONCLUSIONS: We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk.

In a novel nationwide population study, we found that patients with inflammatory bowel disease living in peripheral regions and those with lower socioeconomic status had significantly worse inflammatory bowel disease outcomes, notably higher corticosteroid dependency, higher surgery rate, and higher repeat surgery rate.

Durability of the First Biologic in Patients with Crohn's Disease: A Nationwide Study from the epi-IIRN.

BACKGROUND: In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy. METHODS: We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses. RESULTS: A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001]. CONCLUSION: Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.

Antibiotic Stewardship for Community-Acquired Pediatric Pharyngitis: A Pre-Post Intervention Study.

BACKGROUND: Group A Streptococcus (GAS), the predominant bacterial pathogen of pharyngitis, is sometimes difficult to distinguish clinically from viral pharyngitis. Despite the high prevalence of viral pharyngitis in children, antibiotic treatment is common. OBJECTIVES: To investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with GAS pharyngitis (GAS-P) at a large pediatric community clinic. METHODS: Antibiotic prescription data were collected from October 2016 to March 2017 (pre-intervention period) and from October 2017 to March 2018 (post-intervention period). The intervention was a one-day seminar for primary care pediatricians on the diagnosis and treatment of GAS-P in children according to national guidelines. RESULTS: The overall prevalence of testing differed between the two time periods. There was a decrease in children who did not undergo any testing (from 68% to 63%), an increase in streptococcal rapid antigen detection testing (28% to 32%), and a slight increase in throat cultures (3% to 4%) (P = 0.02). There was no change in the types of antibiotics prescribed before and after the intervention (P = 0.152). CONCLUSIONS: The ASP resulted in a slight reduction in the percentage of children who did not undergo laboratory testing for GAS-P and a slight reduction in the percentage of children who received antibiotic treatment. The ASP did not reduce the use of broad-spectrum antibiotics and macrolides.

Association of Antibiotic Use with Durability of Biologic Agents in Inflammatory Bowel Disease: a Report from the epi-IIRN.

BACKGROUND: Different antibiotic classes were reported to have variable effects on immunogenicity towards anti-tumour necrosis factor [TNF] agents. However, the impact of antibiotic administration on biologic treatment durability was not investigated. We aimed to assess the association between antibiotic treatment and persistence of different classes of biologic therapy in inflammatory bowel disease [IBD] patients. METHODS: Data from the epi-IIRN, a nationwide registry of all Israeli IBD patients were analysed. All patients who filled a prescription of either infliximab, adalimumab, vedolizumab, or ustekinumab, were included. Treatment cessation was defined as drug discontinuation of at least 6 months. Macrolides, cephalosporins, fluoroquinolones, and penicillins with beta-lactamase inhibitors were selected as primary exposure variables. Survival analysis was performed using marginal structural models for each drug separately. RESULTS: In all 13 513 IBD patients, with a total of 39 600 patient-years, were included. Significant differences of overall treatment persistence were demonstrated, with highest persistence rates for ustekinumab and the lowest for infliximab treatment. Macrolides were found to be significantly associated with reduced risk of infliximab cessation (adjusted hazard ratio [aHR] 0.72, 95% CI 0.62-0.89]. Fluoroquinolones and cephalosporins were associated with an elevated risk of adalimumab treatment cessation [aHR 1.33, 95% CI 1.22-1.46; and aHR 1.20, 95% CI 1.08-1.34, respectively]. No significant effects of the studied antibiotics were observed in ustekinumab and vedolizumab users. CONCLUSIONS: Specific antibiotic classes are associated with duration of anti-TNF treatment, but not with durability of vedolizumab or ustekinumab treatments. Further research is required to study the effect of specific antibiotics on response to biologics.

Thiopurines Have Longer Treatment Durability than Methotrexate in Adults and Children with Crohn's Disease: A Nationwide Analysis from the epi-IIRN Cohort.

BACKGROUND: Thiopurines and methotrexate have long been used to maintain remission in Crohn's disease [CD]. In this nationwide study, we aimed to compare the effectiveness and safety of these drugs in CD. METHODS: We used data from the epi-IIRN cohort, including all patients with CD diagnosed in Israel. Outcomes were compared by propensity-score matching and included therapeutic failure, hospitalisations, surgeries, steroid dependency, and adverse events. RESULTS: Of the 19264 patients diagnosed with CD since 2005, 3885 [20%] ever received thiopurines as monotherapy and 553 [2.9%] received methotrexate. Whereas the use of thiopurines declined from 22% in 2012-2015 to 12% in 2017-2020, the use of methotrexate remained stable. The probability of sustaining therapy at 1, 3, and 5 years was 64%, 51%, and 44% for thiopurines and 56%, 30%, and 23% for methotrexate, respectively [p <0.001]. Propensity-score matching, including 303 patients [202 with thiopurines, 101 with methotrexate], demonstrated a higher rate of 5-year durability for thiopurines [40%] than methotrexate [18%; p <0.001]. Time to steroid dependency [p = 0.9], hospitalisation [p = 0.8], and surgery [p = 0.1] were comparable between groups. These outcomes reflect also shorter median time to biologics with methotrexate (2.2 [IQR 1.6-3.1 years) versus thiopurines (6.6 [2.4-8.5]; p = 0.02). The overall adverse events rate was higher with thiopurines [20%] than methotrexate [12%; p <0.001], including three lymphoma cases in males, although the difference was not significant [4.8 vs 0 cases/10 000 treatment-years, respectively; p = 0.6]. CONCLUSION: Thiopurines demonstrated higher treatment durability than methotrexate but more frequent adverse events. However, disease outcomes were similar, partly due to more frequent escalation to biologics with methotrexate.

The Association of Inflammatory Bowel Disease with Coeliac Disease and Coeliac Autoimmunity in Children and Adults: A Nationwide Study from the epi-IIRN.

BACKGROUND AND AIMS: Given the paucity of population-based data on the association between inflammatory bowel diseases [IBD], coeliac disease [CeD], and coeliac autoimmunity [CeA] we aimed to study the associations in a nationwide study. METHODS: Using health administrative data for all four health maintenance organisations in Israel, covering 98% of the population, we explored the prevalence of CeD in children and adults with IBD versus non-IBD matched controls. CeD was defined by three ICD-9 codes and CeA by positivity for tissue transglutaminase antibodies. RESULTS: In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 603 non-IBD controls. Among IBD patients, 319 [0.93%] had CeD versus 294 [0.31%] non-IBD controls (odds ratio [OR] = 2.97, 95% confidence interval [CI] 2.54-3.48; p <0.001). CeA was identified in 575 [1.67%] IBD patients vs 158 [0.17%] controls [OR = 10.06, 95% CI 8.43-12; p <0.001]. The prevalence of CeD was higher in paediatric-onset IBD (87/5243 [1.66%]) than adult-onset IBD (232/29 132 [0.79%]; p <0.001). CD patients had a higher prevalence of CeD (229/19 264 [1.19%]) than UC patients (90/15 111 [0.56%]; OR = 2.01, 95% CI 1.57-2.56; p <0.001). The diagnosis of CeD preceded the diagnosis of IBD in 241/319 cases [76%]. The time to treatment escalation was shorter in patients with both IBD and CeD than in patients with IBD without CeD [p = 0.017]. CONCLUSION: CeD and CeA are more prevalent in IBD patients, especially in paediatric-onset IBD and in CD. The diagnosis of CeD usually precedes that of IBD. Having CeD is associated with more intensified treatment for IBD.

Inflammatory bowel disease among first generation immigrants in Israel: A nationwide epi-Israeli Inflammatory Bowel Disease Research Nucleus study.

BACKGROUND: Israel has a high rate of Jewish immigration and a high prevalence of inflammatory bowel disease (IBD). AIM: To compare IBD prevalence in first-generation immigrants vs Israel-born Jews. METHODS: Patients with a diagnosis of IBD as of June 2020 were included from the validated epi-IIRN (Israeli IBD Research Nucleus) cohort that includes 98% of the Israeli population. We stratified the immigration cohort by IBD risk according to country of origin, time period of immigration, and age group as of June 2020. RESULTS: A total of 33544 patients were ascertained, of whom 18524 (55%) had Crohn's disease (CD) and 15020 (45%) had ulcerative colitis (UC); 28394 (85%) were Israel-born and 5150 (15%) were immigrants. UC was more prevalent in immigrants (2717; 53%) than in non-immigrants (12303, 43%, P < 0.001), especially in the < 1990 immigration period. After adjusting for age, longer duration in Israel was associated with a higher point prevalence rate in June 2020 (high-risk origin: Immigration < 1990: 645.9/100000, ≥ 1990: 613.2/100000, P = 0.043; intermediate/low-risk origin: < 1990: 540.5/100000, ≥ 1990: 192.0/100000, P < 0.001). The prevalence was higher in patients immigrating from countries with high risk for IBD (561.4/100000) than those originating from intermediate-/low-risk countries (514.3/100000; P < 0.001); non-immigrant prevalence was 528.9/100000. CONCLUSION: Lending support to the environmental effect on IBD etiology, we found that among immigrants to Israel, the prevalence of IBD increased with longer time since immigration, and was related to the risk of IBD in the country of origin. The UC rate was higher than that of CD only in those immigrating in earlier time periods.

Pediatric Antibiotic Stewardship for Community-Acquired Pneumonia: A Pre-Post Intervention Study.

We aimed to investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with community-acquired pneumonia (CAP). Antibiotic purchasing data were collected for children aged 3 months to 18 years diagnosed with CAP from November 2016 to April 2017 (pre-intervention period) and from November 2017 to April 2018 (post-intervention period). The intervention was a 1-day seminar for primary care pediatricians on the diagnosis and treatment of CAP in children according to national guidelines. There was a substantial decrease in the use of azithromycin after the intervention. In younger children, there was a 42% decrease, alongside an increased use of amoxicillin (P < .001). In older children, there was a smaller, non-statistically significant decrease in the use of azithromycin (P = .45). Our data demonstrate that the implementation of an ASP was associated with a reduction in the use of broad-spectrum antibiotics and macrolides and increased guideline adherence for the safe treatment of CAP.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN.

BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Trends and socioeconomic disparities in diabetes prevalence and quality of care among Israeli children; 2011-2018.

BACKGROUND: Despite Israel's universal health coverage, disparities in health services provision may still exist. We aimed to assess socioeconomic disparities in diabetes prevalence and quality of care among Israeli children, and to assess whether these changed over time. METHODS: We used repeated cross-sectional analyses in the setting of the National Program for Quality Indicators in Community Healthcare. The data were derived from electronic medical records from Israel's four health maintenance organizations. The study population included all Israeli children aged 2-17 years in 2011-2018 (2018: N = 2,404,856). Socio-economic position (SEP) was measured using Central Bureau of Statistics data further updated by a private company (Points Business Mapping Ltd), and grouped into 4 categories, ranging from 1 (lowest) to 4 (highest). We used logistic regression to assess the association of SEP with diabetes prevalence, diabetes clinic visits, hemoglobin A1C (HbA1C) testing, and poor glycemic control (HbA1c > 9%), and assessed whether these changed over time. RESULTS: Diabetes prevalence increased with age and SEP, with a total of 3019 children with diabetes. SEP was positively associated with visiting a specialized diabetes clinic (age and sex adjusted Odds Ratio (aORSEP 4 vs. 1 2.45, 95% Confidence Interval (CI) 1.67-3.69)). Although children in higher SEPs were less likely to undergo HbA1c testing (aORSEP 4 vs. 1 0.54, 95% CI 0.40-0.72), they were also less likely to have poor glycemic control (aORSEP 4 vs. 1 0.25, 95% CI 0.18-0.34). Disparities were especially apparent among children aged 2-9 (6.5% poor glycemic control in SEP 4 vs. 38.2% in SEP 1). Poor glycemic control decreased over time, from 44.0% in 2011 to 34.1% in 2018. CONCLUSIONS: While poor glycemic control rates among children have improved, they remain high compared to rates in adults. Additionally, substantial socioeconomic gaps remain. It is eminent to study the causes of these disparities and develop policies to improve care provided to children in the lower SEP levels, to promote health equity.

Area-level socioeconomic disparity trends in nutritional status among 5-6-year-old children in Israel.

OBJECTIVE: This study aimed to assess area-level socioeconomic position (SEP) disparities in nutritional status, to determine whether disparities differed by sex and to assess whether nutritional status and disparities changed over time. DESIGN: We used repeated cross-sectional data from a national programme that evaluates the quality of healthcare in Israel to assess children's nutritional status. SETTING: The study included all Israeli residents aged 7 years during 2014-2018 (n=699 255). METHODS: SEP was measured based on the Central Bureau of Statistics' statistical areas, and grouped into categories, ranging from 1 (lowest) to 10 (highest). We used multivariable multinomial regression to assess the association between SEP and nutritional status and between year and nutritional status. We included interactions between year and SEP to assess whether disparities changed over time. RESULTS: Children in SEP 1, comprised entirely of children from the Bedouin population from Southern Israel, had drastically higher odds of thinness compared with those in the highest SEP (Girls: OR 5.02, 99% CI 2.23 to 11.30; Boys: OR 2.03, 99% CI 1.19 to 3.48). Odds of obesity were highest in lower-middle SEPs (ORSEP 5 vs 10 1.84, 99% CI 1.34 to 2.54). Prevalence of overweight and obesity decreased between 2014 and 2018, normal weight increased and thinness did not change. SEP disparities in thinness decreased over time in boys but showed a reverse trend for girls. No substantial improvement was seen in SEP disparities for other weight categories. CONCLUSIONS: Our study demonstrates the need to consider initiatives to combat the considerable SEP disparities in both thinness and obesity.

Birth Outcomes of Women Using a Midwife versus Women Using a Physician for Prenatal Care.

INTRODUCTION: Few studies have compared midwife-led and physician-led care in the United States. Our objective was to compare the frequency of birth interventions and maternal and neonatal outcomes between women who received prenatal care from a midwife and those who received care from a physician, among women who were low risk when they initiated prenatal care. METHODS: We performed a retrospective cohort study of women giving birth at a large public hospital who had at least one prenatal visit before 20 weeks' gestation in the years 2012 through 2015. We classified women according to prenatal care provider type (midwife vs physician) at first prenatal visit and compared birth outcomes between the groups, using intent-to-treat analyses. We used modified Poisson regression to calculate adjusted risk ratios (aRRs) for common outcomes and logistic regression with Firth's bias correction to produce adjusted odds ratios (aORs) for rare outcomes. As a sensitivity analysis, we performed a matched propensity score analysis to account for potential confounding by indication. RESULTS: Midwives provided care to 8.2% of the women; physicians provided care to 91.8% of the women. Women in midwifery care were less likely to be black, have Medicaid insurance, or have a history of pregnancy complications or previous cesarean births compared with women who received care from physicians. Women in midwifery care had lower risks of cesarean (aRR, 0.66; 95% CI, 0.57-0.78) and preterm birth (aRR, 0.58; 95% CI, 0.42-0.79), with no increased odds of neonatal intensive care unit admissions, neonatal deaths, or severe maternal morbidity. Women in midwifery care had increased odds of postpartum hemorrhage and shoulder dystocia (aOR, 3.26; 95% CI, 1.40-7.58, and aOR, 1.80; 95% CI, 1.01-3.22, respectively); however, these did not remain significant in the propensity score analysis. DISCUSSION: Among women with low-risk pregnancies, midwifery care was associated with substantially fewer preterm births and labor interventions.

Hospital Supplementation Differentially Impacts the Association Between Breastfeeding Intention and Duration Among Women With and Without Gestational Diabetes Mellitus History.

BACKGROUND: Little is known about how in-hospital supplementation with water, infant formula, or sugar water affects the relationship between breastfeeding intentions and duration, and whether this differs by gestational diabetes mellitus (GDM) history. Our study objectives were to assess the associations between GDM and exclusive breastfeeding intentions, hospital supplementation, and breastfeeding duration, including whether hospital supplementation mediates the association between exclusive breastfeeding intentions and breastfeeding duration. STUDY DESIGN AND METHODS: Using data from the Infant Feeding Practices Study II (2005-2007), we included women with GDM (n = 160) and women without GDM or prepregnancy diabetes (no diabetes mellitus [NDM]) (n = 2,139). We used multivariable logistic and linear regressions to determine the associations between GDM history and exclusive breastfeeding intentions, and between breastfeeding intentions, hospital supplementation, and breastfeeding duration, by GDM. We used mediation analysis to assess whether hospital supplementation mediated the association between exclusive breastfeeding intention and breastfeeding duration, also by GDM. All analyses were adjusted for prepregnancy body mass index. RESULTS: GDM was associated with lower odds of intending to exclusively breastfeed (adjusted odds ratio [AOR] 0.71; 95% confidence interval [CI, 0.51-0.99]). GDM and NDM women who did not intend to exclusively breastfeed had similarly increased odds of hospital supplementation (GDM: AOR 3.52; 95% CI [1.44-8.57], NDM: AOR 3.66; 95% CI [2.93-4.56]). Breastfeeding duration was similar by exclusive breastfeeding intentions and by hospital supplementation, regardless of GDM. Hospital supplementation partially mediated the association between breastfeeding intentions and duration in NDM women, but it did not mediate the association in women with GDM. CONCLUSIONS: Breastfeeding intentions, rather than hospital supplementation, are particularly important for women with GDM to optimize breastfeeding outcomes.