Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.

AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 ± 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered ≥80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal.

Parasympathetic Versus Sympathetic Changes in Heart Rate Variability After a Multimodal Integrative Medicine Intervention for Frontline COVID-19 Personnel.

OBJECTIVE: Frontline healthcare providers (HCPs) working in COVID-19 hospital departments need to deal with considerable physical and emotional stress on a daily basis. We conducted a pilot study to examine changes in heart rate variability (HRV) in frontline COVID-19 personnel after an integrative medicine (IM) intervention. METHODS: HCPs working in isolated COVID-19 inpatient departments underwent a single 30-minute individually tailored IM sessions combining various IM modalities (acupuncture, mind-body, and/or manual-movement modalities, including anthroposophic medicine). HRV parameters were compared during the first IM session at 3-minute intervals, at the beginning of treatments, and after 20 minutes. Root mean square of successive RR interval differences (RMSSD) was measured, as were domains of time (standard deviation of NN intervals, percentage of successive RR intervals that differ by more than 50 milliseconds) and frequency (low frequency/high frequency [LF/HF] ratio). Preintervention and postintervention concerns were assessed using the Measure Yourself Concerns and Well-being questionnaire, with posttreatment free-text narratives analyzed for clusters of emotional- and spiritual-related keywords (ESKs). RESULTS: A total of 114 HCPs underwent an IM treatment session, and their HRV values were measured, of which 75 (65.8%) expressed ESKs. The RMSSD increased only in the ESK-expressing group ( p < .001). LF/HF ratios decreased in both groups, with HF power increasing in the ESK-expressing ( p = .043) and LF power decreasing in the non-ESK-expressing groups ( p = .004). CONCLUSIONS: Increased parasympathetic activity was observed in all HCPs after the IM intervention, particularly among those expressing ESKs. LF/HF parameters suggest different relaxation-associated mechanisms, with increased HF (regulated predominantly by parasympathetic tone) in the ESK-expressing and decreased LF (regulated partially by sympathetic tone) in the nonexpressing group. Additional research needs to explore the relationship between subjective effects of the IM intervention and physiological mechanisms of relaxation in HCPs working in stressful environments. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05104827.

Sensing the lightness: a narrative analysis of an integrative medicine program for healthcare providers in the COVID-19 department.

OBJECTIVES: The research addressing physical and emotional exhaustion among healthcare providers (HCPs) in COVID-19 departments is limited. We examined the impact of integrative medicine (IM) intervention for HCPs working in isolated COVID-19 in-patient departments, addressing concerns and well-being. METHODS: HCPs working in 3 isolated COVID-19 in-patient departments underwent 40-min IM treatment sessions (including acupuncture, manual movement, and/or mind-body modalities) provided by integrative oncology practitioners. The MYCAW (Measure Yourself Concerns and Well-being) questionnaire examined HCP concerns and free-text narratives following IM treatments. Data were qualitatively analyzed using ATLAS.Ti software for systematic coding. RESULTS: A total of 181 HCPs underwent 305 IM treatments. Narrative themes focused on physical symptoms (primarily pain and fatigue) and emotional concerns, including perceived communication barriers with patients, and reflections on well-being and insights following IM treatments. HCPs reported feeling a sense of "relief" which was likely related to the 3 main effects of the IM intervention: a sense of "being cared for" and treated; experiencing emotional, sometimes spiritual effects of the treatment; and the feeling of relaxation, combined with the relief of pain. Qualitative analysis identified clusters of emotional and spiritual-related keywords such as "calming," "release," "relaxation," and "disengagement" following the first IM session (119 of 181 narratives, 65.7%). CONCLUSIONS: HCPs working in isolated COVID-19 departments reported improved well-being and the addressing of their concerns following IM treatment sessions provided during their work shift. Further research is needed to explore the impact of IM on HCP burnout and resilience in palliative care settings.

High Prevalence of Acromegaly in Different Industrial Areas: A Population-based Study from Haifa and Western Galilee District in Northern Israel.

BACKGROUND: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty. OBJECTIVES: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel. METHODS: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected. RESULTS: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/106 inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m2 .Obesity, with a BMI ≥ of 30 kg/m2, was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%). CONCLUSIONS: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

COVID-19 Pandemic and Ramadan Fasting among Patients with Type 2 Diabetes Mellitus.

BACKGROUND: This year Ramadan occurs during the global coronavirus disease-2019 (COVID-19) pandemic. Data has shown that patients with type 2 diabetes mellitus (T2DM) are prone to severe disease with COVID-19 and with increased mortality. Acute complications such as dehydration, starvation ketosis, ketoacidosis, and the increased risk of coagulopathy and thrombosis should be considered particularly during this pandemic period. Fasting during Ramadan this year and the COVID-19 pandemic is more challenging, not only for patients with T2DM but also for healthcare providers. We present healthcare providers with important aspects to consider during the COVID-19 pandemic for patients with T2DM who intend to fast during Ramadan and other fasting days.

[AMIODARONE-INDUCED THYROTOXICOSIS - RISK FACTORS AND PREDICTORS OF OUTCOME: A RETROSPECTIVE STUDY].

BACKGROUND: Amiodarone induced thyrotoxicosis (AIT) occurs with considerable incidence and is associated with significant morbidity and mortality. Factors that predict poor prognosis in this disease have not yet been sufficiently investigated. OBJECTIVES: We examined the characteristics and short-term clinical outcomes of patients with AIT (up to six months from diagnosis). We evaluated the relationship between T3 and T4 levels at time of presentation and complications associated with AIT. METHODS: A retrospective epidemiological study was conducted reviewing all cases diagnosed with thyrotoxicosis and amiodarone consumption of patients treated in the Carmel Medical Center between the years 2004-2008. We examined the characteristics of patients who tend to develop AIT. In addition, we examined whether T3 and T4 levels at the time of presentation were a predictor of a poor prognosis. Three major complications associated with AIT were defined as primary outcomes within six months of diagnosis: 1. mortality; 2. development of AIT-related complications that required hospitalization; 3. the need for thyroidectomy. RESULTS: A total of 400 patients were diagnosed with thyrotoxicosis and consumed amiodarone. However, only 39 patients met the definition of AIT. The composite outcome of mortality, AIT-related complications and thyroidectomy were found in the vast majority of patients (94.8%, 37 out of 39 participants); 3 (7.6%) died and 35 (89.7%) were hospitalized with AIT-related complications and 8 (20.5%) required thyroidectomy. We found a statistically significant relationship between high T4 levels (above 64.3 mcg/dL or above 3 times the upper limit of the norm) and the composite of two main endpoints: mortality and the need for thyroidectomy in the first half year of diagnosis (P=0.009). CONCLUSIONS: AIT is associated with significant morbidity and mortality. An elevated level of free T4 reflects the severity of AIT. In patients with significantly increased T4 values, an early surgical intervention should be considered.

[DOES INCIDENTAL CALCIUM DEPOSITION IN NON-CARDIAC CT SCANS PREDICT CARDIOVASCULAR MORBIDITY AND MORTALITY IN YOUNG ADULTS - A RETROSPECTIVE STUDY].

INTRODUCTION: Calcium score (CS) in cardiac CT scans represents an effective tool in the early diagnosis of cardiovascular disease. Few studies evaluated the value of incidental arterial calcification (AC) in non-cardiac CT scans, especially in young adults with no prior cardiovascular disease. AIMS: To examine the relationship between arterial calcifications and the incidence of cardiovascular events. METHODS: A retrospective study in patients aged 40-51 years old with no history of cardiovascular disease who underwent chest CT scans between 1.9.2012-31.8.2013 for reasons not related to cardiovascular disease. We assessed the presence of AC in the aorta and coronary arteries and its association with the rates of coronary catheterization for acute coronary syndrome (ACS), cardiac mortality and emergency room (ER) visits or hospitalizations for cardiovascular disease. Furthermore, we examined the association between AC and atherosclerotic risk factors. RESULTS: A total of 407 patients underwent CT scans for non-cardiovascular reasons within the timeframe specified; 308 were included in the study, 150 men and 158 women with average follow-up period of 7.2+0.29 years. There was an increased frequency in ACS and coronary catheterizations in patients with a positive AC compared to those with null AC (11.6% vs. 0.5% respectively, P= 0.0001, OR = 29.1). A positive AC was found more in men than women (35% vs. 20.9% respectively, P=0.006, OR=2.18). Patients with a positive AC had more ER and hospital admissions (33.7 % vs. 14.4% respectively, P<0.0001, OR=3). Patients with diabetes, hypertension and hyperlipidemia exhibited higher rates of positive AC. CONCLUSIONS: Although multivariate analysis is still to be conducted, it seems that AC is associated with cardiovascular morbidity and increased incidence of coronary catheterizations. Primary preventive strategies in patients with positive AC may reduce cardiovascular morbidity and mortality.

An Intervention to Reduce the Time Interval Between Hospital Entry and Emergency Coronary Angiography in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. OBJECTIVES: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. METHODS: In March 2013 the authors launched a seven-component intervention program:  Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory Education program for the emergency department staff Dissemination of information regarding the urgency of the PPCI decision Activation of the catheterization team by a single phone call Reimbursement for transportation costs to on-call staff who use their own cars Improvement in the quality of medical records Investigation of failed cases and feedback. RESULTS: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. CONCLUSIONS: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival.

Glucose Promotes EMMPRIN/CD147 and the Secretion of Pro-Angiogenic Factors in a Co-Culture System of Endothelial Cells and Monocytes.

Vascular complications in Type 2 diabetes mellitus (T2DM) patients increase morbidity and mortality. In T2DM, angiogenesis is impaired and can be enhanced or reduced in different tissues ("angiogenic paradox"). The present study aimed to delineate differences between macrovascular and microvascular endothelial cells that might explain this paradox. In a monoculture system of human macrovascular (EaHy926) or microvascular (HMEC-1) endothelial cell lines and a monocytic cell line (U937), high glucose concentrations (25 mmole/L) increased the secretion of the pro-angiogenic factors CD147/EMMPRIN, VEGF, and MMP-9 from both endothelial cells, but not from monocytes. Co-cultures of EaHy926/HMEC-1 with U937 enhanced EMMPRIN and MMP-9 secretion, even in low glucose concentrations (5.5 mmole/L), while in high glucose HMEC-1 co-cultures enhanced all three factors. EMMPRIN mediated these effects, as the addition of anti-EMMPRIN antibody decreased VEGF and MMP-9 secretion, and inhibited the angiogenic potential assessed through the wound assay. Thus, the minor differences between the macrovascular and microvascular endothelial cells cannot explain the angiogenic paradox. Metformin, a widely used drug for the treatment of T2DM, inhibited EMMPRIN, VEGF, and MMP-9 secretion in high glucose concentration, and the AMPK inhibitor dorsomorphin enhanced it. Thus, AMPK regulates EMMPRIN, a key factor in diabetic angiogenesis, suggesting that targeting EMMPRIN may help in the treatment of diabetic vascular complications.

Clinical outcomes of clostridioides difficile infection in the very elderly.

BACKGROUND: Clostridioides difficile infection (CDI) causes considerable morbidity, mortality, and economic cost. Advanced age, prolonged stay in healthcare facility, and exposure to antibiotics are leading risk factors for CDI. Data on CDI clinical outcomes in the very elderly patients are limited. METHODS: A retrospective cohort study of patients hospitalized between 2016 and 2018 with CDI. We evaluated demographic clinical and laboratory parameters. Major clinical outcomes were evaluated including duration of hospital stay, admission to intensive care unit (ICU), in-hospital mortality, 30 days post-discharge mortality, and readmission/mortality composite outcome. We compared patients aged up to 80 years (elderly) to those of 80 years old or more (very elderly). RESULTS: Of 196 patients included in the study, 112 (57%) were very elderly with a mean age of 86 versus 67 years in the elderly group. The duration of hospital stays, and intensive care unit admission frequency were significantly reduced in the very elderly (13 vs. 22 days p = 0.003 and 1.8% vs. 10.7% p = 0.01, respectively). No significant difference was found in the frequencies of in-hospital and in 30 days post-discharge mortality. CONCLUSIONS: In our cohort, the duration of hospital stay seemed to be shorter in the very elderly with no increase of in-hospital and post-discharge mortality. Although admitted less frequently to ICU, the in-hospital survival of the very elderly was not adversely affected compared to the elderly, suggesting that very advanced age per se should not be a major factor to consider in determining the prognosis of a patient with CDI.

The risk factors for uveitis among psoriatic arthritis patients: a population-based cohort study.

OBJECTIVE: To assess the frequency of uveitis in patients with psoriatic arthritis (PsA) in the era of biologics and to identify risk factors associated with uveitis. METHODS: A retrospective matched cohort study was conducted within the database of a large healthcare provider. Newly diagnosed 6147 adult PsA patients between 2005 and 2020 were matched by the index date of PsA diagnosis, age, sex, and ethnicity to 23,999 randomly selected controls. This cohort was used to examine the association between PsA and uveitis. An additional analysis was conducted within the PsA group to identify uveitis risk factors, using two analytic approaches: a retrospective cohort study and a nested case-control study. RESULTS: Uveitis was diagnosed in 107 patients in the PsA group (1.7%) vs 187 (0.8%) patients in the control group (adjusted HR, 2.38, 95% CI 1.80-3.15, p<0.005) and was similar when the analysis was confined to patients without past uveitis. Uveitis was diagnosed more in females (2.1% vs 1.3%, HR 1.61, 95% CI 1.09-2.40, p<0.05), and was acute in all cases. Anterior uveitis was documented in 41.1% of the cases, 64.5% unilateral, and 9.3% bilateral. In the PsA group, using nested case control approach, only past uveitis [adjusted OR 136.4 (95% CI 27.38-679.88), p<0.005] and treatment with etanercept [adjusted OR 2.57 (95% CI 1.45-4.57), p=0.001] were independently associated with uveitis. Only one PsA patient with uveitis (out of 107) required systemic oral treatment with prednisone, while the rest of the patients were treated with topical glucocorticosteroids only. CONCLUSION: PsA is associated with increased risk of uveitis. Past uveitis and treatment with etanercept were associated with higher risk of uveitis. Key Points • Psoriatic arthritis (PsA) is a major risk factor for uveitis with hazard ratio of 2.38 compared to healthy individuals without PsA. • Among PsA patients, the past event of uveitis and treatment with etanercept are risk factors for uveitis. • Uveitis in patients treated with biologics for their PsA requires topical therapy only in most of the cases.

Recognition and killing of human and murine pancreatic beta cells by the NK receptor NKp46.

Type 1 diabetes is an incurable disease that is currently treated by insulin injections or in rare cases by islet transplantation. We have recently shown that NKp46, a major killer receptor expressed by NK cells, recognizes an unknown ligand expressed by ß cells and that in the absence of NKp46, or when its activity is blocked, diabetes development is inhibited. In this study, we investigate whether NKp46 is involved in the killing of human ß cells that are intended to be used for transplantation, and we also thoroughly characterize the interaction between NKp46 and its human and mouse ß cell ligands. We show that human ß cells express an unknown ligand for NKp46 and are killed in an NKp46-dependent manner. We further demonstrate that the expression of the NKp46 ligand is detected on human ß cells already at the embryonic stage and that it appears on murine ß cells only following birth. Because the NKp46 ligand is detected on healthy ß cells, we wondered why type 1 diabetes does not develop in all individuals and show that NK cells are absent from the vicinity of islets of healthy mice and are detected in situ in proximity with ß cells in NOD mice. We also investigate the molecular mechanisms controlling NKp46 interactions with its ß cell ligand and demonstrate that the recognition is confined to the membrane proximal domain and stalk region of NKp46 and that two glycosylated residues of NKp46, Thr(125) and Asn(216), are critical for this recognition.

Complementary and integrative medicine intervention in front-line COVID-19 clinicians.

OBJECTIVE: To assess the impact of a multidisciplinary complementary and integrative medicine (CIM) intervention on physical and emotional concerns among front-line COVID-19 healthcare providers (HCPs). METHODS: A multimodality CIM treatment intervention was provided by integrative practitioners to HCPs in three isolated COVID-19 departments. HCPs' two main concerns were scored (from 0 to 6) before and following the CIM intervention using the Measure Yourself Concerns and Wellbeing questionnaire. Postintervention narratives identified reflective narratives specifying emotional and/or spiritual keywords. RESULTS: Of 181 HCPs undergoing at least one CIM treatment, 119 (65.7%) completed post-treatment questionnaires. While HCPs listing baseline emotional-related concerns benefited from the CIM intervention, those who did not express emotional or spiritual concerns improved even more significantly following the first session, for both leading concerns (p=0.038) and emotional-related concerns (p=0.023). Nevertheless, it was shown that following subsequent treatments HCPs who expressed emotional and spiritual concerns improved more significantly than those who did not for emotional-related concerns (p=0.017). CONCLUSIONS: A CIM intervention for front-line HCPs working in isolated COVID-19 departments can significantly impact emotional-related concerns, more so after the first treatment and among HCPs not using emotional-spiritual keywords in post-treatment narratives. Referral of HCPs to CIM programmes for improved well-being should avoid referral bias to those not expressing emotional/spiritual concerns.

Inducing regulated necrosis and shifting macrophage polarization with anti-EMMPRIN antibody (161-pAb) and complement factors.

Treatment of solid tumors is often hindered by an immunosuppressive tumor microenvironment (TME) that prevents effector immune cells from eradicating tumor cells and promotes tumor progression, angiogenesis, and metastasis. Therefore, targeting components of the TME to restore the ability of immune cells to drive anti-tumoral responses has become an important goal. One option is to induce an immunogenic cell death (ICD) of tumor cells that would trigger an adaptive anti-tumoral immune response. Here we show that incubating mouse renal cell carcinoma (RENCA) and colon carcinoma cell lines with an anti-extracellular matrix metalloproteinase inducer polyclonal antibody (161-pAb) together with complement factors can induce cell death that inhibits caspase-8 activity and enhances the phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase-like domain (MLKL). This regulated necrotic death releases high levels of dsRNA molecules to the conditioned medium (CM) relative to the necrotic death of tumor cells induced by H2 O2 or the apoptotic death induced by etoposide. RAW 264.7 macrophages incubated with the CM derived from these dying cells markedly enhanced the secretion of IFNß, and enhanced their cytotoxicity. Furthermore, degradation of the dsRNA in the CM abolished the ability of RAW 264.7 macrophages to secrete IFNß, IFNγ-induced protein 10 (IP-10), and TRAIL. When mice bearing RENCA tumors were immunized with the 161-pAb, their lysates displayed elevated levels of phosphorylated RIPK3 and MLKL, as well as increased concentrations of dsRNA, IFNß, IP-10, and TRAIL. This shows that an antigen-targeted therapy using an antibody and complement factors that triggers ICD can shift the mode of macrophage activation by triggering regulated necrotic death of tumor cells.

Immune modulation in type 1 diabetes mellitus using DiaPep277: a short review and update of recent clinical trial results.

In type 1 diabetes mellitus, autoimmune T-cells mount an attack on insulin producing beta-cells eventually causing hyperglycemia. It is hypothesized, that to prevent and treat this disease, one must interfere with the autoimmune process. To avoid hazardous side effects, this intervention should not cause a global immune suppression but immune modulation. DiaPep277 (peptide 277) is a 24 amino acid peptide derived from positions 437-460 in HSP60. It has recently been shown to have an immune modulatory effect on diabetogenic T cells in animal models of diabetes. It has also been recently implicated as a possible auto-antigen in type 1 diabetes. Promising results in animal models led to phase 1 to 3 human clinical trials in patients with type 1 diabetes, the results of which are the focus of this review. A combined analysis of all the adult phase II studies revealed that DiaPep277 significantly inhibits the decline in stimulated C-peptide secretion (thus preserving endogenous insulin secretion). This effect was more pronounced in patients with a high beta-cell reserve at the start of the treatment. Furthermore, opposite trends in glycemic control of DiaPep277 treated patients where noted as opposed to placebo treated patients. The phase III study has began more than 2 years ago in 40 medical centers worldwide, and thus far recruited over 350 patients around the world. If DiaPep277 will prove to be efficacious, it will cause a paradigm shift in the treatment of type 1 diabetes, from treating the subsequent insulin deficiency to addressing the initial autoimmune process that is at the heart of the disease.

Treat-to-target concept implementation for evaluating rheumatoid arthritis patients in daily practice.

OBJECTIVE: We aimed to assess the implementation of the treat-to-target (T2T) concept in rheumatoid arthritis (RA) patients in daily practice. METHODS: All RA patients visiting one of the 7 academic medical centers in Israel in June 2015 with at least 3 previous clinic visits were included in this study. A common questionnaire was used to collect data from patients' medical records, and two independent rheumatologists evaluated the collected data for the implementation of the T2T concept. The associations between T2T implementation and the categorical and continuous variables were assessed. RESULTS: The study included 724 patients with a mean (standard deviation) age of 62.6 (13.97) years and 575 (80.4%) of them were women. Four centers used more than one scoring method, with Disease Activity Score-28 and Clinical Disease Activity Index) being most commonly used. Only 276 (38.1%) patients had disease score results in ≥3 visits, and the T2T recommendations were implemented for 245 (33.8%) of the 724 patients. The rate of implementation was higher in younger (p=0.028) rheumatoid factor-positive patients (p=0.011) and varied between centers (11.1%-87% p<0.0001). T2T implementation did not correlate to gender, place of residence, education, tobacco use, treatment regimens, and presence of erosions or comorbidities. CONCLUSION: The T2T concept was implemented on only 33.8% of patients and was not affected by RA disease severity. Further studies are needed to determine the reasons for this deviation from the T2T standard of care for RA as well as its consequences.