Introduction

Current Literature examining how Ramadan affects gastrointestinal disorders indicates that individuals with inflammatory bowel disease (IBD) generally face a low likelihood of worsening symptoms, although older men with ulcerative colitis (UC) are more susceptible to exacerbations during fasting. Moreover, individuals with duodenal ulcers have a heightened risk of experiencing bleeding following fasting during Ramadan (1).

Aims & Methods

Aim: To study the impact of ‘Ramadan’ on Inflammatory bowel disease (IBD) activity in an Emirati cohort.
Methods: We designed a retrospective cohort study of adults (> 16 years) with IBD seen at our tertiary care IBD referral center in Abu Dhabi, the United Arab Emirates (UAE) for IBD related emergencies, IBD related hospitalizations and in-person clinic visits during Ramadan, the Islamic lunar calendar month of fasting vs. during the preceding month of Shaban in the year 2023. Exposure of interest was the month (30 days) of ‘Ramadan’ and the unexposed cohort was the month (30 days) of ‘Shaban’. Chi-square testing was used to compare emergency department (ED) visits and hospitalizations. Logistic regression was used to assess the impact of Ramadan vs. Shaban on the risk of active clinical disease during in-person clinic visits. Statistical analysis was performed using R (version 4.0.2) and a p-value of <0.05 was considered statistically significant. IRB approval was in place for this study.

Results

A total of 294 encounters in the cohort (130 in Ramadan vs. 164 in Shaban) During Ramadan, 12 of 130 (9%) IBD encounters were ED visits for an IBD related emergency vs. 4 of 164 (2%) patients during Shaban (X² = 5.25, 95%CI 0.06-0.13, P=0.02). During Ramadan, 16 of 130 (12%) IBD encounters led to hospitalization vs. 16 of 164 (10%) during Shaban (X²=0.26, 95%CI -0.054-0.1, P=0.61). In Ramadan, during 33/77 (43%) in-person clinic visits, patients had active disease vs. 24/106 (23%) in Shaban (X²=7.59, 95%CI 0.055-0.35, P=0.006). Logistic regression model adjusted for age and gender demonstrated that during Ramadan, the risk (likelihood) of active clinical disease was approximately 3 times higher compared to during Shaban (OR 2.70, 95% CI 1.41-5.25, P= 0.003).

Conclusion

This is the first study examining the effect of the fasting month of ‘Ramadan’ on disease activity among Emirati patients with IBD. We found that during Ramadan, there was higher likelihood of ED visits, hospitalizations and active clinical disease when compared to during Shaban. This risk was profound and statistically significant regarding ED visits and likelihood of active clinical disease. There may be several factors underlying these significant findings. For example, in the UAE during Ramadan, there are limited meal and drink options during the day, there occurs a sudden drastic change in diet patterns and there are limited working hours that reduce access to the IBD Clinic. IBD practices in the UAE could try to mitigate the risk of flares during Ramadan by increased dietary and lifestyle counseling of patients in preparation for the month, encourage patients to hydrate adequately and perhaps by increasing access when needed to the IBD clinic during Ramadan.

References

1. Tibi S, Ahmed S, Nizam Y, et al. (March 31, 2023) Implications of Ramadan Fasting in the Setting of Gastrointestinal Disorders. Cureus 15(3): e36972. doi:10.7759/cureus.36972

Introduction

Vit D is a known immunomodulator and is essential in maintaining immune balance as well as controlling processes observed in inflammatory disorders like ulcerative colitis (UC) [1,2].

Aims & Methods

Aim: We previously completed a study looking at the effect of vitamin-D on Crohn's disease activity and noted a marginal beneficial effect. In this study, we sought to investigate the association between Vitamin D (VitD) levels and Ulcerative Colitis (UC) activity in the Emirati patient population of the United Arab Emirates (UAE).
Methods: We designed a retrospective cohort study using a sample population of patients (16-85 years) with UC, who were followed for at least one year in the Division of Gastroenterology at our tertiary care center in Abu Dhabi, between January 2021 and October 2023. Demographics were collected on patients retrospectively identified in the EMR. Eligibility criteria were applied that included patients who had their VitD levels recorded at baseline and whose disease outcomes were measured between 1-12 months post-baseline visit. VitD was documented as a continuous variable and dichotomized into low vs. adequate level categories. The primary outcome was clinical disease activity measured dichotomously. Summary statistics were calculated. Unadjusted logistic regression analysis was employed to examine the association between VitD level as a continuous variable and when categorized into low vs. adequate levels on clinical disease activity in UC. Multivariable logistic regression looked at the independent effect of VitD levels by adjusting for covariates of effect size >20%. Statistical analysis was performed using R (version 4.0.2) and a p-value of <0.05 was considered statistically significant. IRB approval was in place for this study.

Results

We identified 89 patients with UC. Of these, 75 met our eligibility criteria, out of which 47 had their Vit D levels recorded at baseline, and 18 were noted to be deficient. 34 (45%) were women. The mean age of the cohort was 36 years. Detailed summary statistics were done. Unadjusted logistic regression analysis revealed that VitD did not appear to impact disease activity. However, in the multivariable logistic regression analysis, when the model was adjusted for variables with an effect size of greater than 20% (age, BMI, duration of disease, steroid use), a marginal association between VitD as a continuous variable and active clinical disease was observed (OR 0.96 95%CI 0.93-0.99 P=0.039).

Conclusion

This is the first study looking at the impact of VitD on Emirati patients with UC. While there are previous studies in other cohorts that have suggested an association between VitD level and disease activity in UC, it appears that having adequate VitD levels, similar to our experience with Emirati patients with CD has a positive effect. The results of this study highlight the need for IBD practices in the UAE to consider VitD level sampling at baseline and replacement when necessary but discourage the frequent use or overuse of VitD testing in the UC population in the UAE.

References

1.Gubatan, J., Mitsuhashi, S., Longhi, M. S., Zenlea, T., Rosenberg, L., Robson, S., & Moss, A. C. (2018). Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis. Cytokine, 103, 38–45. https://doi.org/10.1016/j.cyto.2017.12.023
2.Dash, K. R., Panda, C., Das, H. S., Mishra, D., Behera, S. K., Parida, P. K., & Mohapatra, D. (2021). Association of Vitamin D Level With Disease Severity and Quality of Life in Newly Diagnosed Patients of Ulcerative Colitis: A Cross-Sectional Analysis. Cureus, 13(7), e16481. https://doi.org/10.7759/cureus.16481

Introduction

Inflammatory bowel diseases (IBD) may impact the daily life in affected patients in various dimensions including quality of life and work productivity. Suboptimal disease management and limited efficacy of available treatment options can cause inadequate disease control (IDC) resulting in disease progression and negative long-term outcomes. Here, we aim to assess the rates of IDC in daily clinical practice and the related economic burden.

Aims & Methods

IBD-PODCAST is a global cross-sectional, multicenter, non-interventional study assessing signs of residual disease activity according to STRIDE II-criteria¹ in patients with ulcerative colitis (UC) or Crohn’s disease (CD). Analysis included patient- and physician-reported measures as well as retrospectively assessed components of the medical record of the last 12 months. In accordance with the recent STRIDE-II recommendations¹, pre-defined indicators (‘red flags’) of IDC were assessed incl. clinical parameters, biomarkers, endoscopy and imaging studies and patient questionnaires such as the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and the Work Productivity and Activity Impairment Questionnaire (WPAI)). In addition, reported Health care resource utilization (HCRU) was assessed.

Results

From 04/2022 to 11/2022, 438 patients with IBD (UC: n=228; CD: n=210) were included at 21 German IBD centers. Parameters of IDC were identified in 43.8% (92/210) CD patients and in 39.9% (91/228) UC patients. More specifically, impaired quality of life (SIBDQ <50) was identified as the most common indicator of IDC, followed by steroid overuse and failure to achieve clinically meaningful improvement (>50% reduction of symptoms since therapy initiation) across both indications. Patients with IDC showed substantial impairments in WPAI such as work time missed (CD: 13.4% IDC vs. 2.6% ADC (adequate disease control) and UC: 10.5% IDC vs. 3.0% ADC). HCRU was substantially increased in the IDC group reflected by increased ER visits, hospitalization and surgery rates.

Table 1. HCRU in patients with IBD according to disease control status

Conclusion

In a substantial proportion of patients with IBD, inadequate disease control was associated with impaired quality of life, lower work productivity and more frequent health care utilization. Our data underlines the continued need for improved disease management and more treatment options in IBD patients.

References

1. Turner D, et al.; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-1583.

Disclosure

A. Dignass has received fees for participation in clinical trials and for review activities, such as data monitoring boards, statistical analysis and endpoint committees from Abivax, AbbVie, Arena, Celgene/Bristol Myers Squibb, Falk, Gilead, Janssen and Pfizer; consultancy fees from AbbVie, Amgen, Biogen, Boehringer-Ingelheim, Celgene/Bristol Myers Squibb, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, High5Immunology, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts and Vifor; and payment for lectures including service on speaker bureaus from AbbVie, Amgen, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Gilead/Galapagos, Janssen, Lilly, MSD, Onkowissen, Pharmacosmos, Pfizer, Streamed-Up, Takeda, Tillotts and Vifor.
D. Bettenworth is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, DGVS, Diaplan, Doctorflix, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopharma, Viatris and Vifor Pharma.
C. Schmidt obtained consulting fees from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Ewopharma, Galapagos, Janssen-Cilag, MSD Sharp & Dohme, Norgine, Pfizer, Shield Therapeutics, and Takeda, lecture fees and travel support AbbVie, Alanta Health Group, Berlin Chemie, Biogen, CED Service, Celltrion, Ewopharma, Dr. Falk, Ferring, Galapagos, Janssen-Cilag, med update, Merckle, MSD Sharp & Dohme, Norgine, Novartis, Olympus, Pentax, Pfizer, Shire, Shield Therapeutics, and Takeda, and research support from Abbvie, Pentax and Olympus.
A. Marek and S. Rath are AbbVie employees and may own AbbVie stock or options.
AbbVie sponsored the study; contributed to the design; participated in the collection, analysis, and interpretation of data; in writing, reviewing, and approval of the final version.
The data collection and statistical analysis was supported by Labcorp Drug Development, which was funded by AbbVie.
No honoraria or payments were made for authorship.

Introduction

Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in IBD population. The ileo-psoas muscle (IP) muscle has already been used in the literature for the assessment of sarcopenia, however, as it is a deep muscle and it needs experienced operators for a proper measurement. Therefore, diaphragm muscle (DM) more superficial and easily assessed, was examined to check its correlation with IP.

Aims & Methods

The aim of this work was to evaluated the correlation of positivity SARC-F score with ultrasound (US) measure of the IP and DM.
A total of 50 IBD patients with significant suspected sarcopenia with SARC-F score positive ≥4, were enrolled. IP and DM US were detected in the enrolled patients. The transverse diameter of the right IP was evaluated. We defined "reliable" the measurements of the IP that fulfilled all of the following criteria: all anatomical boundaries could be clearly identified (superior margin of the iliac crest and lumbar vertebrae); the maximum diameter of the psoas between each of the three measurements did not deviate from the other two by more than 5 mm. Moreover, we calculated the US psoas/height ratio as the average of the psoas diameter divided by the patient's height (mm/m). For DM, an extended space between the axillary line and the hemi clavicular line was used, in the diaphragmatic thickness between the hyperechogenic limiting. Diameters during expiration and during inspiration were assessed, then diaphragmatic expansion was evaluated. We calculated the diaphragm/height ratio (mm/m) as well. The correlation between IP and DM ratio was researched by using the Pearson correlation test. Age and sex were taken into consideration as confounders in a linear regression model, using the psoas/height ratio and these confounders as independent variables and the diaphragm index as dependent variable.

Results

The mean of the three US IP measured diameters was 30.37 mm, the psoas/height ratio was 17.92 mm/m. The mean maximum inspiration DM diameter was 20.4 mm (± 5 mm), the mean minimum expiration DM diameter was 10.7 mm (± 35 mm). The mean difference between the two diameters was 9.7 mm (± 3,4 mm). The diaphragm/height ratio was 0.59 mm/m (±0.21 mm/m). A significant correlation was identified between IP and DM ratio, with a Pearson coefficient r = 0.3568 (p-value <0.05). A consistent association was found between the two indices, with diaphragm/height ratio increasing linearly with the psoas/height ratio (OR: 0.018; p-value: 0.008). Multivariate analysis showed that age and sex were not significantly associated with the diaphragm/height ratio (p-value >0.05).

Conclusion

The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. IP US is confirmed to correlate with sarcopenia. DM can be used more easily and correlates with IP. This research could take a significant implications for disease management in IBD patients and underscores the importance of further investigations to validate these findings in larger cohorts. This study will continue to expand the cohort under evaluation.

Introduction

Malnutrition is a common condition of patients with inflammatory bowel disease (IBD) and could be associated with sarcopenia i.e. a reduced muscle mass and strength. Recent data suggest that the prevalence of sarcopenia is, respectively, 52% and 37% in Crohn's disease (CD) and ulcerative colitis (UC). It is well demonstrated that sarcopenic IBD patients have two to three times higher risk of lost of response to biotechnology drugs than non-sarcopenic patients.

Aims & Methods

Consecutive IBD patients accessing the IBD outpatient service were enrolled. Detailed data regarding the characteristics of MC and CU populations, current therapy and disease activity are reported. Each patient was interviewed about the frequency (none, low, high) and the kind (aerobic or anaerobic) of the physical activity they were practicing.
At the enrolment, nutritional assessments were performed by body mass index (BMI) evaluation according with the World Health Organization recommendations, global subjective assessment by the MUST (Malnutrition Universal Screening Tool) index according with the European Society for Clinical Nutrition and Metabolism and the Global Leadership Initiative on Malnutrition [GLIM]. Moreover, the SARC-F questionnaire, recommended by the scientific consensus EWGSOP 2 to identify individuals at risk for sarcopenia was administrated. A SARC-F value ≥ 4 was significant of sarcopenia. Finally, the quality of life was assessed using the inflammatory bowel disease questionnaire (IBDQ). Univariate and multivariate analysis was conducted between BMI, MUST, SARC-F and IBDQ values and patient characteristics (age, current therapy, disease activity and physical activity).

Results

A total of 321 IBD patients (158 CD and 163 UC), 56.07% male, with a mean age of 44.78 years were enrolled. Sixty-seven patients (20.87%) reported a current smoking habit. A mean BMI of 70.37 kg, was calculated. Regarding malnutrition, 199 patients (61.99%) were considered at low risk (MUST=0), 75 subjects (23.36%) at medium risk (MUST=1), 47 (14.64%) at high risk (MUST ≥2). A SARC-F value ≥4 was evaluated in 50 patients (15.58%). A reduction in quality of life, understood as IBDQ < 209, was found in 45 (14.02%) patients. Females and males presented a significantly different prevalence of sarcopenia (chi2: 9.69; p-value: 0.002).
Univariate analysis shows a significant protective role of male sex (OR vs. female sex: 0.33; p-value: 0.018) in the risk of sarcopenia; older subjects had a slightly higher sarcopenic risk (OR: 1.04; p-value <0.001). The risk was associated with corticosteroid therapy (OR 1,03, p-value <0.001), with increasing MUST (OR 1,65, p-value <0.001) and with the IBDQ decreases (OR 2,1; p-value<0.001).
Multivariate analysis confirmed an higher incidence of sarcopenia in female subjects of advanced age with active-stage disease (R²: 0.88, p-value<0.0001), furthermore female patients with active-stage disease who did not engage in physical activity had a greater impairment in quality of life, regardless of age (R²: 0.75, p-value<0.0001). Aerobic and anaerobic physical activity played a protective role in the onset of sarcopenia regardless of sex and age (R²: 0.82, p-value<0.0001).

Conclusion

In our cohort of patients, sarcopenia was present in only 18.94%. Male sex was found to be a protective factor for sarcopenia. Disease status is firmly linked to the risk of sarcopenia. Regular physical activity has been shown to have a protective role for good quality of life and it was related with a lower risk of sarcopenia. This study will continue to expand the cohort taken into account.

Introduction

The appropriateness of lower gastrointestinal (GI) endoscopy in patients with inflammatory bowel disease (IBD) is a key issue in endoscopic practice, especially given limited healthcare resources, the growing demand for endoscopic procedures, and the increasing prevalence of IBD. While numerous studies have examined the appropriateness of endoscopy, particularly upper GI endoscopic procedures, in general gastrointestinal disorders,^{[1, 2]} there is a relative lack of literature specifically addressing the appropriateness of lower GI endoscopy in patients with IBD.^{[3, 4]}

Aims & Methods

This study aimed to evaluate the appropriateness of lower GI endoscopic examinations in patients with IBD at a tertiary referral center. Secondary objectives were identifying reasons for inappropriateness and assessing the presence of clinically significant pathological findings in inappropriate procedures. This was a prospective, observational, monocentric study including all adult patients affected by IBD who underwent lower GI endoscopy at a tertiary referral center between September 2024 and April 2025, with a confirmed IBD diagnosis for at least six months. Data collected included IBD subtype, endoscopic procedure appropriateness based on the 2023 ECCO Guidelines,^[5] and endoscopic/histological findings.

Results

Among 406 endoscopic procedures, 26 were excluded from the analysis due to inappropriate timing resulting from patients lost to follow-up. Therefore, a total of 380 IBD patients were included (mean age 52.9 ± 15.1 years; 57% male). Among them, 135 (35.5%) had Crohn’s disease (CD), 176 (46.3%) ulcerative colitis (UC), 60 (15.8%) ileal pouch, and 9 (2.4%) unclassified IBD (IBD-U). Lower endoscopic procedures included colonoscopy (256, 67.4%), rectosigmoidoscopy (61, 16.1%), pouchoscopy (60, 15.8%), and trans-stomal ileoscopy (3, 0.8%). Overall, 308 procedures (81.1%) were deemed appropriate. Appropriateness was higher in CD (115/135, 85.2%), in UC (147/176, 83.5%) and IBD-U (8/9, 88.9%), and lower in ileal pouch (38/60, 63.3%). Between the different endoscopic procedures, rectosigmoidoscopy showed the highest appropriateness (56/61, 91.8%), followed by colonoscopy (213/256, 83.2%), pouchoscopy (38/60, 63.3%), and trans-stomal ileoscopy (1/3, 33.3%). Among the 72 inappropriate procedures (18.9%), 23 (31.9%) were performed too early, 20 (27.8%) too late, 27 (37.5%) were unwarranted, and 2 (2.8%) were improper endoscopic procedures. Most early procedures were prescribed by physicians (78.3%), while the remaining (21.7%) were requested by patients. Despite being considered inappropriate, 27 of the 72 examinations (37.5%) revealed endoscopic pathological findings, and 17 (23.6%) led to clinically relevant conclusions (based on both endoscopic and histological findings), including 4 cases of dysplasia. It is noteworthy that, among the inappropriate examinations that led to clinically relevant conclusions, almost 60% were performed either too early or were considered unwarranted, while only the remaining 40% were performed too late.

Conclusion

The appropriateness of lower gastrointestinal endoscopy in patients affected by IBD was found to be nearly 80% in a tertiary referral center. Notably, among the examinations classified as inappropriate, roughly 24% revealed clinically relevant findings based on both endoscopic and histological report. A greater spread and awareness among physicians of the latest international guidelines on IBD management could improve the appropriateness of endoscopic procedure prescriptions, while reducing waiting lists and related healthcare costs.

References

1. Tursi A, Palieri AP, Lattarulo V, Elefante A, Gigliobianco A, Spinazzola D, Elisei W, Papa A. How we can improve the appropriateness of ambulatory gastrointestinal endoscopy: the lesson of the COVID-19 outbreak. Eur J Gastroenterol Hepatol. 2023 Oct 1;35(10):1149-1153. doi: 10.1097/MEG.0000000000002626. Epub 2023 Jul 28. PMID: 37665614.
2. Bohara TP, Laudari U, Thapa A, Rupakheti S, Joshi MR. Appropriateness of Indications of Upper Gastrointestinal Endoscopy and its Association With Positive Finding. JNMA J Nepal Med Assoc. 2018 Jan-Feb;56(209):504-509. PMID: 30058633; PMCID: PMC8997324.
3. Manes G, Imbesi V, Ardizzone S, Cassinotti A, Bosani M, Massari A, Porro GB. Appropriateness and diagnostic yield of colonoscopy in the management of patients with ulcerative colitis: a prospective study in an open access endoscopy service. Inflamm Bowel Dis. 2008 Aug;14(8):1133-8. doi: 10.1002/ibd.20434. PMID: 18314901.
4. Manes G, Imbesi V, Ardizzone S, Cassinotti A, Bosani M, Massari A, Bianchi Porro G. Use of colonoscopy in the management of patients with Crohn's disease: appropriateness and diagnostic yield. Dig Liver Dis. 2009 Sep;41(9):653-8. doi: 10.1016/j.dld.2008.10.006. Epub 2008 Nov 25. PMID: 19036651.
5. Gordon H, Biancone L, Fiorino G, et al. ECCO Guidelines on Inflammatory Bowel Disease and Malignancies. J Crohns Colitis. 2023;17(6):827-854. doi:10.1093/ecco-jcc/jjac187

Introduction

The management of patients with inflammatory bowel disease (IBD) during the coronavirus disease 2019 (COVID-19) pandemic has been a challenge, as immunosuppressant therapies comprise the cornerstone of IBD treatment and social distancing is recommended to diminish the virus spread. The aim of this study is to investigate the impact of COVID-19 on the therapeutic decisions and management of patients with IBD.

Aims & Methods

Records from patients diagnosed with ulcerative colitis (UC), Crohn’s disease (CD) and unclassified-IBD (IBD-u), under follow-up by a single IBD center, were retrospectively screened from March 2020 to May 2021. Primary and secondary outcomes were predetermined to be changes in therapeutic decisions and monitoring respectively, during the pandemic.

Results

A total of 201 patients were included in the study [125 (62%) UC, 69 (34%) CD and 7 (3%) IBD-U]. Patients with UC were treated with 5-aminosalicylic acid [(5-ASA), 89], infliximab [(IFX), 21], combination therapy with 5-ASA and azathioprine (AZA), (11) and adalimumab [(ADA), 4)]. To avoid hospital environment, two patients under IFX (10%) switched to subcutaneous home-infusions with ADA and in eight patients treated with IFX (38%), infusion intervals increased to ten weeks (drug holiday). No complications were observed. Patients with CD were treated with IFX (39), ADA (12), vedolizumab (8), AZA (4), combination therapy with AZA or methotrexate (4) and ustekinumab (2). To avoid hospital environment, two patients under IFX (5%) switched to subcutaneous home-infusions with ADA and in 12 patients treated with IFX (30%), infusion intervals increased to ten weeks (drug holiday). One patient in clinical remission discontinued IFX and received AZA. Although a significant number of outpatient visits, endoscopic procedures and non-urgent surgeries were postponed, two patients with CD (IFX) required emergency surgery which was performed without delay. Patients’ monitoring was carried out through telemedicine (remote monitoring, intangible prescription and drug home delivery).

Conclusion

The vast majority of patients treated with biologics did not discontinue maintenance therapy and a significant number extended intravenous infusion intervals. The setting of this critical and unprecedented situation has led to significant changes in decision making in IBD management, based on patients’ preferences aiming an efficient and safer care.