Multicenter Non-interventional Study Research Articles

Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

#1426 Association of intradialytic hypertension and mortality in a cohort of Spanish population

Abstract Background and Aims Intradialytic hypertension (IH) has been identified as an independent mortality risk factor in hemodialysis (HD) patients. The are a lack of a standardized definition of (IH). Recently, a definition of IH ≥30% of baseline sessions with an increase in pre-to post-HD systolic blood pressure (SBP) of ≥10 mmHg had the highest adjusted risk of mortality, compared with other threshold-based definitions (Singh AT, et al. Hypertension 2022;79:855–62) in American population. The aim of these study is to evaluate this definition of IH in our Spanish population. Method We conduct a retrospective multicenter non-interventional study in a Spanish cohort of patients receiving HD (3 sessions PER week) between 1-July 2021 and 30-June 2023 in Fresenius Medical Care Spain. Pre-post-HD SBP, HD parameters and blood test data were averaged over the 90-day exposure period from 1-April-2021 to 30-Jun- 2021. Cox models were fit to examine the association of ID ≥10 mmHg with all-cause mortality in the univariate and multivariate model adjusted for potential confounding variables. Results 3221 patients met the inclusion criteria, 59.6% men, median age 74 years. The mean of SBP pre HD systolic during the exposure period was 140.6 ± 21 mmHg. The mean follow-up was 22 months. 1620 (50.3%) met the definition of IH,379 (22.4%) of patients with IH died during the follow-up period, compared with 302 of 1587 (19%) individuals who did not meet criteria for IH. In the cox multivariate model, patients with IH, had a significant association with mortality HR: 1.19 [1.01-1.41]) p < 0.05 in a model adjusted for age, Charlson Index, weight loss, vintage, ultrafiltration, vascular access, OL-HDF and malnutrition, among others (Table 1). Conclusion Patients with IH (defined as ≥30% of baseline sessions with an increase in pre-to post-HD systolic blood pressure of ≥10 mmHg) have been associated with all-cause mortality (HR 1.19 [1.01-1.41]) in Spanish HD population, similar to previous studies in the American population.

Abstract PO4-18-12: MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411)

Abstract Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support will be provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Nina Ditsch, Antonio Esgueva, Neslihan Cabıoğlu, Dawid Murawa, Nuh Zafer Canturk, Isabel Rubio, Jana de Boniface, Andreas Karakatsanis, Rajiv Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael P. Lux, Tove Tvedskov, Lina Pankratjevaite, Michalis Kontos, Florentia Peintinger, Aoife Lowery, Marjolein Smidt, Lia Rebaza, Maria Vasconcelos, Bahadir M. Gulluoglu, Bilge Aktas Sezen, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Maria Luisa Gasparri, Séverine Alran, SVS Deo, Mah Muneer Khan, James Harvey. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-12.

Abstract PO2-16-08: Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China

Abstract Background: CHASE001 (NCT05544123), a prospective, non-interventional multicenter study exploring real-world treatment and referral behavior of Chinese county patients (pts) with HER2+ or HR+/HER2– breast cancer is ongoing since September 2022. A prespecified interim analysis (IA) on 750 HER2+ and HR+/HER2- early breast cancer (eBC) was reported at the ESMO Congress 2023. In the 2nd IA from CHASE001, adjuvant treatment selection for patients with HR+/HER2- eBC will be evaluated. Methods: The study was designed to enroll 2500 pts, including four cohorts (HER2+ eBC, HR+/HER2-eBC, HER2+ advanced BC, and HR+/HER2- aBC). In this IA, HR+/HER2- eBC pts after surgery were included. Descriptive statistics reported patient demographics, clinical and disease characteristics and treatment patterns. To investigate the factors associated with chemotherapy-free regimen, non-anthracycline chemotherapy regimen and ovarian function suppression (OFS), univariate and multivariate logistic regression analyses were conducted. Results: At data cutoff (May 17, 2023), 697 HR+/HER2- eBC pts (median age 52 years, 45.77% pT2, 50.93% pN0, 56.10% G2) were included from 26 institutions in China county areas, 338 (48.49%) were premenopausal. 584 (83.79%) received adjuvant chemotherapy, with a few (47/584, 8.05%) initially developing their treatment plan at a higher level hospital (national or provincial tertiary hospital). AC-T (309/584, 52.91%) was the most commonly used regimen. 181 (30.99%) pts received non-anthracycline chemotherapy regimen (mainly TC), and pts with N0, age≥65 years and ki67 < 20% had the strongest association to this regimen (multivariate OR=0.082, 95%CI [0.037,0.179], OR=0.463, 95%CI [0.250,0.859], and OR=0.642, 95%CI [0.418,0.985], respectively). Interestingly, on univariate analysis pts initially diagnosed in a higher level hospital were significantly associated with non-anthracycline regimen (P=0.0109), however on multivariate analysis it was no longer significant. 483 pts received endocrine therapy, including 234 (48.45%) premenopausal pts. The most commonly used endocrine regimen for premenopausal pts was OFS/OFS+ (122/234, 52.14%) ,of which half (61, 50%) were prescribed OFS+TAM/TOR; followed by TAM/TOR monotherapy (69/234, 29.49%). The proportions of patients classified as low, intermediate, and high clinical risk for recurrence (investigator assessed)were 33.62%, 42.67% and 23.71%. The OFS rate were 39.74% in low, 61.62% in intermediate and 70.91% in high risk pts, respectively. Multivariable analyses found that high clinical risk, age < 45 years and ki67 < 20% were strongly associated with the use of OFS (OR=0.210, 95%CI [0.066,0.674], OR=0.327, 95%CI [0.165,0.649], and OR=0.405, 95%CI [0.194,0.845], respectively). For postmenopausal pts, AI monotherapy (84.74%) was the most commonly used endocrine regimen. Conclusions: To our knowledge, this is the first real-world study evaluating the treatment patterns and referral behavior of BC pts in China counties. The 2nd IA results presented showed the current systemic adjuvant treatment preferences and influence factors from a large sample of HR+/HER2- eBC pts in China counties, which were generally consistent with China BC treatment guidelines. Table 1. Utilization of adjuvant systemic therapy regimens in 697 HR+/HER2− eBC pts, China counties AC-T: (dd)doxorubicin/epirubicin, cyclophosphamide, followed by (dd)paclitaxel/docetaxel; TC: paclitaxel/docetaxel, cyclophosphamide; AC: doxorubicin/epirubicin, cyclophosphamide; TAC: docetaxel, doxorubicin/epirubicin, cyclophosphamide; TAM: tamoxifen; OFS: ovarian function suppression; AI: aromatase inhibitors; TOR: toremifene; CDK4/6i: cyclin-dependent kinase 4/6 inhibitors; “Other” category includes various therapies used in <1% of patients each Citation Format: Yinghua Ji, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, Wenbo He, Wei Liang, Qiuli Meng, Yun Ren, Guoxiang Luo, Hongjian Wang, Hui Liu, Zien Qin, Yingguo Tian, Huali Tang, Hongmei Liu, Jun Luo, Zengfeng Yu, Guinv Hu, Jianzhi Gao, Xiang Tan, Yi Liu, Yuanjiang Zhang, Ming Wang, Min Zhang, Ping Lu. Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-08.

Results of a non-interventional multicenter study of management of patients with non-radiological axial spondyloarthritis in real-life clinical practice in the Russian Federation (NiSpAR)

NiSpAR is a non-interventional, multicenter study whose aim was to describe a cohort of patients with non-radiological axial spondyloarthritis (nr-axSpA) and approaches to its diagnosis in the Russian Federation.Material and methods. The study involved 20 research centers in different regions of the Russian Federation. The work consisted of two phases: retrospective data collection 12 months before enrolment in the study and prospective observation of patients in whom the diagnosis of nr-axSpA was confirmed (104 weeks).The study included 272 patients who met the inclusion and exclusion criteria (Full Analysis Set, FAS). The mean age of the FAS-population was 38.7±11.0 years. The diagnosis of nr-axSpA was confirmed in 159 (58.5 %) of the 272 patients. Of the remaining 113 (41.5%) participants, 57 (50.4%) did not have the information required to confirm the diagnosis, 34 (30.1%) did not have pelvic radiographs, and 22 (19.5%) did not fulfil the ASAS criteria for nr-axSpA.Results and discussion. The mean age of patients with nr-axSpA was 37.6±10.4 years, more than half of them (52.8%) were women. The median disease duration was 36 [12; 80] months. In half of the patients the disease duration was more than 2 years, in more than one third – less than 2 years. The median CRP and ESR values were 5.0 [2.0; 12.0] mg/l and 11.0 [5.0; 18.0] mm/h, respectively. The BASDAI averaged 3.5±2.0 and was >4 in more than half of the cases (64.2%). The mean ASDAS-CRP value reached 2.6±1.1. Only 1 in 5 participants (20.8%) had low axSpA activity, while in 61.1% it was high (44.7%) or very high (16.4%). An inactive state was found in a small number of patients (9.4%). Twenty two (13.8%) patients had treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) in anamnesis, and 21 (13.2%) patients were still taking them.Conclusion. The results of the retrospective phase of the study show that in real-life clinical practice in the Russian Federation there is a continued positive trend towards improving the diagnosis of nr-axSpA. The median duration of the disease at the time of enrolment in the study was 3 years. The frequency of use of magnetic resonance imaging has increased by more than 1.8 times. At the same time, practitioners still have difficulties in establishing the diagnosis of nr-axSpA and a shortage of bDMARDs for treatment of these patients.

Birth Register for Deep Endometriosis (BiRDeE): first analysis and recommendations

ObjectiveRecent research has shed light on the impact of endometriosis on complications during pregnancy, but very few studies address the influence of deep endometriosis (DE) on delivery and peripartum parameters. For this reason, an international birth register for DE was established to aid in counseling affected women on delivery mode and individual risks. Material and methodsThe BiRDeE study (Birth Register for Deep Endometriosis) is an international noninterventional multicenter study based on a patient register of women with singleton live births after diagnosis of DE (both operated on and non-operated). This first extracted data was analysed using descriptive statistics and logistic regression. ResultsAt the time point of data extraction (January 2023), 10 study centres created 209 records of which 165 were closed and suitable for analysis. Cesarean section was performed in 49.1% of patients with a high rate of elective CS due to known deep endometriosis. The median gestational age at delivery was 40 weeks of pregnancy (IQR 39–41) with a preterm delivery rate of 10.9%. In four cases, Apgar scores at 5 min were less than seven; there were no cases with an umbilical artery pH < 7.00 (lowest NapH value was 7.08). No bladder or bowel injuries (beside OASIS) were reported so far. ConclusionDeep endometriosis per se is not a contraindication for vaginal delivery. Based on the currently available data, the choice of delivery method should be made together with the patient after adequate information about benefits and possible complications. Neonatal outcomes are encouraging.

REBISTART: Adherence of Patients with Multiple Sclerosis to Treatment with Subcutaneous Interferon Beta in the Context of a Patient Support Program.

Treatment adherence is a critical success factor in the disease-modifying therapy (DMT) of multiple sclerosis (MS). The REBISTART study prospectively evaluated adherence in patients using components of a patient support program (PSP). The 12-month non-interventional multicenter study examined the real-world adherence to subcutaneously (sc) injected interferon beta-1a (Rebif®). Patient-assessed adherence was measured by a visual analog scale (VAS) and the Morisky Medication Adherence Scale (MMAS). Objective adherence data were obtained by readouts from the RebiSmart® injection device. Of 333 patients, 70.9% used the nursing service as the core component of the PSP. Self-assessed VAS-based adherence was stable over time at 94.0-96.3%. Similarly, MMAS score (maximum 4) was 3.8-3.9 at all visits, also reflecting high self-assessed adherence. In 269 patients using the RebiSmart® injection device, mean readout-based objective adherence was similarly high (93.0-98.4% throughout visits). At last available visit, VAS-based adherence was independent of participation in the PSP nursing service (93.1% with participation versus 91.7% without it). Adherence was also independent of injection method or disease-related measures, including fatigue, depression, cognition, and quality of life. The most frequent reason for the premature discontinuations (38.7% of patients) was "change of treatment" (10.0%). We suggest that subgroups that may specifically benefit from PSP include patients who live alone, use multiple comedications, and are affected by cognitive impairment, depression, and/or fatigue. Further studies should investigate the potential usefulness of PSPs in these populations. Very high adherence rates independent of the PSP nursing service over 1year of treatment indicate that IFN beta-1a sc is an easy-to-use and well-tolerated disease-modifying drug. Vfa.de: No. 892. https://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_892 .

174 (PB-081) Poster - MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 0555941 1)

174 (PB-081) Poster - MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 0555941 1)

Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC): a retrospective non-interventional multicenter patient chart data study

Objectives The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. Methods This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. Results The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. Conclusions In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428.

Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary

Patients with suspected head and neck squamous cell carcinoma of unknown primary (HNSCCUP) may undergo tonsillectomy and tongue base mucosectomy (TBM) to help identify clinicoradiologically occult primary disease. It is hypothesized that when these diagnostic specimens are analyzed, conventional histopathological (CH) techniques risk missing small primary tumors that may be hidden in the tissue blocks. To establish the outcomes of a step serial sectioning (SSS) histopathological technique vs CH when analyzing diagnostic tissue specimens from TBM and tonsillectomy performed for HNSCCUP. The MOSES prospective multicenter noninterventional cohort study was conducted over a 25-month period from November 2019 at secondary and tertiary care ear, nose, and throat departments in the United Kingdom and included adults with clinicoradiologically occult HNSCCUP who were undergoing TBM. Conventional histopathological techniques performed on TBM and tonsillectomy specimens at participating centers, followed by SSS performed at the central laboratory. Identification of cancer on central histopathological review of TBM and tonsillectomy specimens. Tissue from 58 eligible patients was analyzed (median [range] age, 58 [47-82] years; 10 women [17%]), with 20 480 sections cut in the laboratory and 4096 sections directly examined by a pathologist (median [range], 64 [28-135] per patient). The overall identification rate for TBM following SSS according to study protocol was 50.0% (95% CI, 37.5%-62.5%) and by subgroups was 42.9% (95% CI, 21.4%-67.4%) when performed following a negative bilateral tonsillectomy, 46.7% (95% CI, 24.8%-69.9%) at the same time as bilateral tonsillectomy, and 57.1% (95% CI, 36.5%-75.5%) following historic tonsillectomy. Conventional histopathological techniques at central review identified 2 undiagnosed primary tumors and revised the diagnosis of 2 other cases (1 nonmalignant and another down staged). Step serial sectioning identified a single additional tumor: an ipsilateral synchronous tongue base tumor for which a contralateral tumor had been identified on CH. Multifocal disease was seen in 5 (8.6%); all were human papillomavirus-related and in the tongue base. In this multicenter cohort study of patients undergoing TBM for HNSCCUP, SSS was associated with added considerable histopathological workload with minimal additional diagnostic benefit. A second opinion for conventional histological techniques may be more beneficial. Synchronous primary disease should be considered when planning diagnostic oropharyngeal surgery for these patients.

Characterization of postoperative LASIK ectasia features on higher-order aberration excimer ablation maps

BackgroundTo characterize anterior corneal higher-order aberration (HOA) excimer ablation map patterns in postoperative LASIK ectasia (POE) and to examine correlations between newly identified corneal HOA ablation map features of POE and known topographic indices.MethodsProspective multicenter non-interventional descriptive study. A total of 28 eyes from 22 POE patients were enrolled. The postoperative HOA ablation map was derived from Topolyzer Vario corneal imaging at the time of POE diagnosis. Features that recurred were identified and then analyzed. Correlations to Orbscan indices were studied.ResultsAn arrangement of two elliptical paracentral ablation islands, deep inferior and shallow superior, in direct mirror-like opposition to each other, were identified on all HOA maps. The paracentral islands were accompanied by peripheral ablation crescents. The deep paracentral inferior island ‘hot spot’ coincided with the topographical apical POE cone and was highly reproducible in angular position (249.3 ± 17.3°). There was significant variation in ablation depth (shallow superior island: 11.5 ± 6.9 μm and deep inferior island: 32.5 ± 18.8 μm). The superior crescents had high variability in depth (34.8 ± 18.9 μm). Strong correlations were found between the corneal irregularity index and the ablation depth difference between the deep and shallow paracentral islands (R = 0.96; P < 0.0001).ConclusionThe corneal HOA excimer ablation map revealed a recurring, distinct, easily recognizable pattern in POE eyes. Validated Orbscan POE indices and HOA ablation map islands showed a strong correlation. It is possible to extract useful information from the corneal HOA ablation map, potentially making it suitable for diagnosing and monitoring POE although more studies are needed.

NOVEMA® NIGHT (diphenhydramine + naproxen) in patients with pain and insomnia: results of a multicenter non-interventional observational study

Pain and sleep disorders are interrelated problems that significantly affect patients’ quality of life (QoL) and daily functioning.Objective: to evaluate the efficacy and safety of the use of the combination of diphenhydramine + naproxen (NOVEMA® NIGHT) in patients with acute pain syndrome or exacerbation of chronic pain syndrome and sleep disorders.Material and methods. The study included 4365 outpatients with acute pain (musculoskeletal pain, post-traumatic pain, headache) and sleep disorders who took naproxen 275 mg, 1 tablet in the morning and diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) for 5 days before bedtime. Pain intensity, using a visual analogue scale (VAS), and sleep disorders were assessed before and after treatment; QoL was assessed after treatment using a five-point scale.Results. During treatment, a reduction or complete regression of pain was observed in 92% of cases (60 [50; 61] points on the VAS before treatment versus 10 [0; 20] after treatment; p&lt;0.0001) and normalisation of sleep in most patients: faster falling asleep – in 81% (χ2=9650.2; p&lt;0.0001), an increase in total sleep duration – in 75.5% (χ2=7351.2; p&lt;0.0001), a decrease in the number of nocturnal awakenings – in 84% of patients (χ2=10,568; p&lt;0.0001). At the end of treatment course, the majority of patients rated their quality of life as 4 out of 5 possible points (4 [4; 5]): 41% of patients – “high quality of life”; 48% – “above average”; 11% – “average”; 0.09% – “below average”). None of the patients had a low QoL. The therapy was well tolerated and no patient discontinued treatment due to adverse events (AEs).Conclusion. Short-term treatment (5 days) with naproxen 275 mg and a combination of diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) at bedtime effectively reduces the pain syndrome associated with insomnia. This therapy significantly improves patients’ QoL and has a low risk of AEs, so that we can recommend NOVEMA® NIGHT as an additional analgesic for patients with concomitant sleep disorders.

Results of a non-interventional observational multicenter study of the management of patients with axial psoriatic arthritis in real-life clinical practice (NiSaXPA)

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

Combination of serum and peritoneal 1.3-beta-d-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study

BackgroundIntra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-d-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC.MethodsThis prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-d-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements.ResultsBetween 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54–72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5–1578.0] pg/ml) compared to non-IAC patients (133 [16.0–831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0–9.0] pg/ml) than in non-IAC patients (3 [3.0–3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0–211.0] pg/ml) than in non-IAC patients (50 [23.0–141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%.ConclusionIn critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure.Trial registration: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).Graphical abstract

Real World Clinical Characteristics, Treatment Patterns and Outcomes of R/R B-Cell ALL Adult Patients in Latin America

Introduction. Acute lymphoblastic leukemia (ALL) frequently affects mainly children and young adults. ALL has seen important progresses in diagnosis techniques and treatment approaches in the last decade. However, in some developing countries, there are inequalities in ALL management, such as heterogeneous access to diagnosis technologies (e.g., cytogenetic and molecular profiling) and access to target therapies treatments. To date, there is scarce data on those impacts in treatment patterns and real-world outcomes of adult relapsed/refractory (R/R) B-cell ALL (R/R ALL) patients in Latin America (LA). Therefore, this study aims to describe treatment patterns, clinical characteristics, and outcomes of R/R ALL adult patients treated in LA. Methods. This was a retrospective multicenter non-interventional study to evaluate treatment patterns, clinical characteristics and outcomes conducted in Argentina, Brazil, and Colombia. The study included patients ≥ 18 years old at diagnosis with confirmed R/R ALL between January 1, 2015, to December 31, 2019 that received at least one line of treatment for R/R ALL. Data collected from medical records was considered for the analysis, which was descriptive in nature, as no hypothesis has been tested. Results: A total of 71 patients diagnosed with R/R ALL were included in the study (23 from Argentina, 27 from Brazil, and 21 from Colombia). Table 1 shows the demographics and clinical characteristics. The median age at diagnosis was 31 years (Q1-Q3: 24.0-46.0), 56.3% were male, and 50% were White/Caucasian patients. At diagnosis, the most common comorbidities were diabetes, hypertension, gastrointestinal disease, and thyroid disease, with 11% each. At diagnosis, most patients presented with poor or intermediate cytogenetic risk prognosis, in 55.1% and 31.6%, respectively. Most of the patients presented with good performance status, 50.9% ECOG 0 and 36.8% ECOG 1. As for treatment patterns, patients received up to six treatment lines (LOT-1 to LOT-6), with a median of 2.0 LOTs (Q1-Q3: 1.5-3.0) within the R/R setting. Fifty-three (74.6%) out of the 71 patients enrolled in the study received two lines of R/R treatment (up to LOT-2), and 27 patients (38%) received 3 lines (up to LOT-3). The median treatment duration of LOTs were 3.4 months (Q1-Q3: 1.14 - 5.7), 1.4 months (Q1-Q3: 0.62 - 2.6) and 0.9 months (Q1-Q3: 0.4 - 2.1) for LOT-1, -2 and -3, respectively. The most frequently used treatment regimens at LOT-1 were the Hyper-CVAD (22.9%), BFM (20.0%) and GRAAL (15.7%). The most reported reasons for patients discontinuing their regimen in LOT-1 were progression of disease (37.5%), followed by adverse events (25%). For LOT-2 discontinuation, adverse events and/or toxicity (33.3%) were most frequently reported, followed by progression of the disease (25%). Of the total number of R/R ALL patients, 26 (36.6%) underwent stem cell transplantation (SCT), with a median time from diagnosis to transplantation of 9.6 months. All those patients (n=26) received allogeneic hematological SCT (100%), and haploidentical donors were most common (42.3%), followed by identical (matched) related (34.6%), mismatched unrelated donor (15.4%), and identical (matched) unrelated donors (7.7%). For R/R ALL patients, the median overall survival (mOS) was 18.96 months, with a probability of survival of 66.6% at 1 year, 32.3% at 3 years, and 16.2% at 5 years. Philadelphia Chromosome (Ph) molecular results were reported in 53 patients: 38 (71.7%) were Ph- and 15 (28.3%) were Ph+. The mOS in Ph+ patients was 31.5 months, numerically longer than the 17.7 months seen in Ph- patients (p = 0.500); however, the Kaplan-Meiers crossed over and separation was not clearly evident within the follow-up period (Figure 1). Conclusions: This study enabled a better understanding of R/R ALL in LA in the real-world. Data from this study demonstrate the high heterogenicity within first salvage (LOT-1) treatment patterns in R/R ALL, likely due to no established single standard of care in the region and highlights that only a fraction of the patients undergo SCT, which should be the treatment goal following induction therapy. In addition, our study reinforces already published data that overall survival on R/R ALL adult patients remain poor. Consistent guidelines and access to new treatments and are needed to remove inequalities in the management of ALL in LA.

Efficacy and safety of netakimab therapy in patients with moderate and severe psoriasis in real clinical practice

Rationale. Data from randomized clinical trials (RCTs) may differ from the results of the efficacy and safety of medicines in the conditions of daily work.&#x0D; Purpose: to obtain data on the long-term efficacy and safety of the use of the genetically engineered biological drug netakimab in real clinical practice.&#x0D; Methods. In everyday clinical practice, a multicenter non-interventional observational study BCD-085-NIS-01 (ORION) was conducted, which involved 260 adult patients with moderate to severe psoriasis. It has been shown that therapy with GIBA netakimab using a standard dose of 120 mg and a regimen in patients with psoriasis is effective for 104 weeks.&#x0D; Results. It was established that the survival rate of genetically engineered biological therapy of netakimab, when analyzing data of 104 weeks of observation, remains high both in bionaive patients and in persons who have previously received treatment for this dermatosis using monoclonal antibodies.&#x0D; The long-term safety profile of netakimab in real clinical practice is comparable to data previously obtained in RCTs and remains favorable for follow-ups up to 2 years.&#x0D; Keywords. Psoriasis; treatment; genetically engineered biological preparations; efficiency; safety

Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients’ coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.

A clinical decision support system to predict the efficacy for EGFR-TKIs based on artificial neural network.

The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) was affected by numerous factors. In the study, we developed and validated an artificial neural network (ANN) system based on clinical characteristics and next-generation sequencing (NGS) to support clinical decisions. A multicenter retrospective non-interventional study was conducted. 240 patients from three hospitals with advanced non-small cell lung cancer (NSCLC) and EGFR mutation were tested by NGS before the first treatment. All patients received formal EGFR-TKIs treatment. Five different models were individually trained to predict the efficacy of EGFR-TKIs based on one medical center with 188 patients. Two independent cohorts from other medical centers were collected for external validation. Compared with logistic regression, four machine learning methods showed better predicting abilities for EGFR-TKIs. The inclusion of NGS tests improved the predictive power of models. ANN performed best on the dataset with mutations TP53, RB1, PIK3CA, EGFR mutation sites, and tumor mutation burden (TMB). The prediction accuracy, recall and AUC were 0.82, 0.82, and 0.82, respectively in our final model. In the external validation set, ANN still showed good performance and differentiated patients with poor outcomes. Finally, a clinical decision support software based on ANN was developed and provided a visualization interface for clinicians. This study provides an approach to assess the efficacy of NSCLC patients with first-line EGFR-TKI treatment. Software is developed to support clinical decisions.

Changes in serotype distribution of &lt;i&gt;Streptococcus pneumonia&lt;/i&gt; circulating among children in the Russian Federation after 13-valent pneumococcal conjugate vaccine introduction.

During a prospective multicenter non-interventional observational study, a comparative assessment was made of the serotype structure of pneumococci circulating among healthy children under the age of 5 years and children of the same age group with signs of respiratory infections in the periods 2016-2018 and 2020-2022. Data on the serotype structure of pneumococci in the period from 2016-2018 were obtained from our previous works. In 2020-2022 the study included 2066 healthy children and 603 children with respiratory infections. Streptococcus pneumoniae and their DNA were detected in nasopharyngeal swabs by classical culture and molecular methods. Typing was carried out by molecular methods. On the territory of the Russian Federation, pneumococci belonging to the serotypes included in the 13-valent vaccine are being forced out of circulation and replaced by non-vaccine serotypes. Before the introduction of mass antipneumococcal vaccination (until 2015), the 13-valent conjugate vaccine covered from 66.2% to 92% of pneumococci, after the start of mass anti-pneumococcal vaccination in the period 2016-2018, coverage decreased to 57.3%. Between 2020 and 2022, coverage was less than 40%. The main “non-vaccine” serotypes/serogroups circulating in the Russian Federation are 15AF, 11AD, 23A, 9LN and 16F.

MELODY (Methods for Localization of Different Types of Breast Lesions): A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).

TPS626 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com ). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 20 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Clinical trial information: NCT05559411 .