Multicenter Non-interventional Study Research Articles

CTNI-71. TTFIELDS IN ROUTINE CLINICAL CARE OF NEWLY DIAGNOSED GBM PATIENTS IN GERMANY – FIRST REPORT ON THE FULLY ENROLLED TIGER STUDY POPULATION

Abstract OBJECTIVE Glioblastoma (GBM) is widely treated with surgery, chemoradiation and TTFields in combination with chemotherapy. Since the introduction of TTFields to first-line GBM treatment, prescribing physicians in Germany are interested to gain additional knowledge on the use in clinical practice. The TIGER study was designed to assess the therapy decision making process, safety and efficacy of TTFields in clinical routine, as well as evaluating quality of life (QoL) within 4 months after start of therapy, treatment compliance and duration. METHODS This multi-center prospective non-interventional study in Germany (NCT03258021) included newly diagnosed GBM patients eligible for TTFields therapy. Within the study, after receiving introduction to TTFields therapy, patients could decide for or against receiving TTFields. The study was designed to recruit 500 patients for each group, with and without TTFields. Demographic data, QoL and reasons for therapy decision 2–4 months after treatment start are assessed using the EORTC-QLQ-C30/BN-20 and a TTFields questionnaire, respectively, with 18 months follow-up. RESULTS At the last data cut-off (31st March, 2020), the median follow-up was 11 months (range: 0–28 months) and 581 (82%) of the 710 recruited patients in the trial had decided for TTFields therapy. According to preliminary analysis, this patient population represents a typical GBM population regarding median age (59 years, range: 19.0–85.0), gender (37 % female), median KPS (90, range: 40–100) and MGMT promoter methylation status (44% methylated). In this population 49 % received complete resection, 33 % partial resection and 19 % biopsy. CONCLUSION The TIGER study allows prospective and systematic analysis of TTFields treatment decision making and use of typical GBM patient population in routine clinical care. In addition, the study allows the evaluation of compliance and treatment duration. Here, we will present an updated analysis of the TIGER study.

A Preliminary Analysis of FLAM (Italian Non-Interventional Multi-center Study of FLT3 mutated AML patients): FLT3 Receptor Gene Mutational Analysis and FLT3 Inhibitors Administration in the Real-Life Clinical Practice

A Preliminary Analysis of FLAM (Italian Non-Interventional Multi-center Study of FLT3 mutated AML patients): FLT3 Receptor Gene Mutational Analysis and FLT3 Inhibitors Administration in the Real-Life Clinical Practice

Nosocomial SARS-CoV-2 infection in urology departments: Results of a prospective multicentric study.

ObjectiveTo evaluate the coronavirus disease 2019 perioperative infection rate and mortality rate of patients undergoing urological surgeries during the early pandemic period in Spain.MethodsThis was a non‐interventional multicenter prospective study carried out from 9 March to 3 May 2020 in two urology departments in Madrid, Spain. Clinical, microbiological and radiological data of patients who underwent surgery were collected from computerized medical records.ResultsA total of 148 patients were included in the study, and 141 were analyzed for nosocomial infection risk, after excluding previous and concomitant severe acute respiratory syndrome coronavirus type 2 infections. Elective surgeries represented 76.6% of the procedures, whereas emergent surgeries represented 23.4%. Preoperative screening was carried out with polymerase chain reaction test in 34 patients, all were negative. A total of 14 patients also had chest X‐ray (not suspicious in all cases). Three patients (2.1%) developed severe acute respiratory syndrome coronavirus type 2 nosocomial infection (symptoms developed between the third day after surgery to the 14th day after hospital discharge). Time from admission to a compatible clinical case was 5.5 days (4–12 days). Two patients underwent surgery with concomitant diagnosis of coronavirus disease. The mortality rate due to severe acute respiratory syndrome coronavirus type 2 infection is 0.7%, and the specific mortality rate in patients undergoing surgery with community‐acquired coronavirus disease 2019 infection was 50% (1/2).ConclusionsThe nosocomial severe acute respiratory syndrome coronavirus type 2 infection rate was low in patients undergoing urological surgical procedures during the peak of the pandemic in Madrid. With appropriate perioperative screening, urological surgical activity can be carried out in safety conditions.

Safety and efficacy of aflibercept in FOLFIRI regime in treatment of metastatic colorectal cancer in real clinical practice: results of Russian prospective multicentre observational study SAFETRAP

Aim. The main objective of the prospective multicentre observational study is to describe adverse events occurred during treatment with aflibercept plus FOLFIRI therapy in real life practice. In despite of broad use of aflibercept in Federal oncological centers, this regimen is still perceived by healthcare professionals (HCPs) as having worse safety profile in comparison with other antiangiogenic agents. Taking into account limited experience of using aflibercept in Russia it s critically important to evaluate and document adverse events occurred with treatment in aflibercept plus FOLFIRI regimen in patients with metastatic colorectal cancer (mCRC) in real-life practice. Methods. The physician selection was performed as a random process. Twenty sites with experience in treatment of mCRC patients were selected. The investigators were encouraged to enroll all patients meeting eligibility criteria in consecutive manner. Total number of included patients into the study patient was 101. Data were evaluable for 91 patients. 14 of 91 (15.4 %) patients didn ’t meet inclusion criteria and were excluded from the per protocol analysis: 10 patients didn ’t receive oxaliplatin within the last line of therapy preceding inclusion into the study and in 4 patients progression occurred more than 6 months after the end of adjuvant therapy. Results. Overall, 265 treatment emergent adverse events (TEAEs) occurred in the 77 patients analysed per protocol. In total, 23 grade 3 and 5 grade 4 TEAEs were reported by 16 and 4 patients, respectively. The most common TEAEs were nausea (68 events in 31 [40.3 %j patients), diarrhea (43 events in 25 [32.5 %j patients), hypertension (36 in 20 [26.0 %] patients), neutropenia (29 events in J5 [J9.5 %] patients), asthenia (28 events in 12 [15.6 %]patients). Three cases of grade 1-2 stomatitis were reported in 2 (2.6 %) patients. And one patient reported grade 1 epistaxis during the study. There was no case of gastrointestinal perforation, fistula development, ulceration, arterial or venous thromboembolism. During this study seven serious adverse events were documented in 5 (6.5 %) patients of 77. The reason for treatment discontinuation in 5 (11.1 %) of 45 cases was adverse event. No death, classified as related to any component of therapy, was reported in this study. Conclusion. This national (Russian) prospective multicentre non-interventional study conducted in patients with mCRC in daily practice suggests that aflibercept plus FOLFIRI has a manageable safety profile in line with VELOUR phase III study.

The multicenter observational non-interventional study of combination anti-tuberculosis drugs used in treatment of pulmonary tuberculosis patients

The objective of the study:to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods.13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results.Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer.

The efficiency of treatment with a combined chondroitin sulfate and glucosamine hydrochloride drug for knee and hip osteoarthritis: intermediate results of a Russian observational study

Objective: to assess pain dynamics, daily functional activity of joints, quality of life, and treatment satisfaction in patients with knee and hip osteoarthritis (KOA and HOA), who long take a combined glucosamine (GA) and chondroitin sulfate (CS) drug in routine clinical practice.Patients and methods: An interim analysis of data from an open multicenter prospective non-interventional study that is being conducted in the Russian Federation was carried out. The study included patients with Kellgren–Lawrence Stages I–III KOA or HOA, who were treated with a combined GA and CS drug (Theraflex®). The interim analysis was based on the data obtained at 16–24 weeks of treatment (Visit 2) in 542 patients (50% of the total sample).Results and discussion. A study group included patients with KOA (n=399) or HOA (n=143) from 43 centers in Russia. At visit 2, the KOA/HOA patients showed positive changes in all subscales of the Knee disability and Osteoarthritis Outcome Score (KOOS/Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaires compared to the baseline level. The proportion of patients with a ≥20% increase in different subscale scores ranged from 42.6 to 67.4% for KOA and from 47.6 to 66.4% for HOA.Most (89.1%) patients took Theraflex® for ≥3 months. 76,1% of patients were satisfied with treatment efficiency. Adverse events (AEs) related to treatment were recorded in 16 (3.0%) patients and included mainly gastrointestinal tract disorders in 12 (2.2%) cases.Conclusion. The results obtained at 16–24 weeks of Theraflex® treatment are indicative of a decrease in the frequency and intensity of pain and other symptoms of OA, as well as increases in joint functional activity and quality of life in patients with KOA or HOA after the first cycle of therapy. The majority of the patients were satisfied with the treatment. The incidence of drug-related AEs was low, while their nature was consistent with information on the drug's side effects.

Observational Study of Clinical Practice in Patients with Pancreatic Adenocarcinoma in Greece.

Background During the last decade, significant improvement was made in systemic therapy of pancreatic adenocarcinoma (PAC). The impact of this progress in everyday clinical practice has not been fully described yet. The aim of the study was to investigate the pattern followed by Greek Medical Oncologists regarding the treatment of patients with PAC. Methods This observational, noninterventional multicenter study recorded clinical data from the files of 200 active patients (alive and under treatment or follow-up) for a two-year period (November 2015 until November 2017) from 20 oncology centers around Greece. Results In total, 51 (25.5%) patients underwent radical surgical resection of PAC, and 40 (78.4%) of them received adjuvant and 1 (2.0%) neoadjuvant chemotherapy. The median time to recurrence was 7.9 months, and median overall survival (OS), 20.2 months. First-line chemotherapy was administered to 193 (96.5%) patients. The majority of patients were treated with the combination of nab-paclitaxel-gemcitabine (NPG), 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX), or gemcitabine monotherapy. Of them, 39.5% responded to the treatment. Median OS and PFS were 14.1 months and 7.0 months, respectively. Second-line treatment was administered to 112 patients. The majority received NPG, FOLFIRINOX/capecitabine, oxaliplatin, irinotecan (CAPOXIRI), or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (CAPOX). Median OS with second-line treatment was 8.6 months, and median PFS, 5.5 months. The most common chemotherapy sequences were NPG as first-line followed by FOLFIRINOX/CAPOXIRI as second-line, NPG followed by FOLFOX/CAPOX, NPG followed by other regimens, and FOLFIRINOX/CAPOXIRI followed by NPG. Conclusion This study described the significant improvement in prognosis of PAC patients receiving palliative chemotherapy and the relatively high rate of receipt of second-line chemotherapy, according to real-world data. However, due to the nonrandomized nature of the study, any comparison between different chemotherapy regimens should be regarded with caution.

Seasonal allergic rhinitis and its control with antihistamines in an outpatient practice.

Allergic rhinitis (AR) is a significant social and medical problem of modern healthcare. The treatment of patients with AR is based on a stepwise approach, the purpose of which is to fully control the symptoms. The first stage drugs of choice are oral non-sedative antihistamines of the second generation. A study was conducted to evaluate the effectiveness of Allerway and drugs containing cetirizine to control the symptoms of seasonal AR (SAR) in an outpatient practice. The data obtained in the framework of a multicenter prospective noninterventional study (the short name of the study is LEVADA) were analyzed. Data were collected at 5 centers using scales for assessement of the symptoms of allergic rhinitis: rTNSS, miniRQLQ, visual analog scale and the Epworth sleepiness scale. The dynamics of SAR symptoms was assessed using the rTNSS scale (24 hours) after 7 and 14 days of treatment. A total of 100 patients were included in the study; 97 patients completed the study. Of these, 46 (47.42%) were women and 51 (52.57%) were men aged 18 years. The average duration of the diagnosis of SAR in patients before inclusion in the study in the Allerway group was 97.485.51 months (about 8 years), in the cetirizine group 107.0114.62 months (about 8.9 years), p=0.641. The efficacy of regressing the intensity of SAR symptoms on the rTNSS scale was demonstrated to be (average and average error) 2.920.11 points in the group of patients taking Allerway and 2.930.11 points in the group of patients taking cetirizine. After 7 days, there was an increase in the proportion of patients with a complete absence of the main symptoms of SAR: nasal congestion, rhinorrhea, itching in the nose. In the group of patients taking Allerway in 44 out of 49 patients (89.8%), it was noted that on average, after 39.414.35 minutes, symptom relief was observed in 42 of 48 (87.5%) patients, and in patients taking cetirizine, relief of rhinitis symptoms was noted during 44.013.76 minutes. An improvement in the quality of life was noted by reducing the severity of symptoms on the miniRQLQ scale by 44.315.29 points in the Allerway group and by 45.013.03 in the group receiving cetirizine. It was shown that the use of Allerway (at a dose of 5 mg, once a day) and preparations containing cetirizine (at a dose of 10 mg, with a single dose per day), allows to achieve a positive clinical effect in the treatment of patients with SAR (seasonal allergic rhinitis) in outpatient practice within 7 and 14 days with a high level of safety and compliance.

Evaluation of the efficacy and safety of injectable glycosaminoglycan-peptide complex (GPC) in patients with osteoarthritis: a multicenter observational study GLADIOLUS (GPC in the treatment of osteoarthritis: a follow-up study of pain relief and local symptom reduction)

Glycosaminoglycan-peptide complex (GPC) is a popular injectable extended-release symptomatic agent (ERSA) in Russia for the treatment of osteoarthritis (OA). To date, no large-scale studies of GPC used in real clinical practice have been conducted in our country.Objective: to evaluate the efficacy and safety of GPC in the treatment of OA in real clinical practice.Patients and methods. A multicenter observational non-interventional study was performed to evaluate the efficacy of GPC (Rumalon® , a cycle of intramuscular injections thrice weekly; a total of 25 injections). A study group consisted of 2,955 patients (75.4% female) aged 61.4±11.8 years) with knee and hip OA, and generalized OA (GOA) with the previous inefficacy of oral ERSAs, moderate/severe pain, and the need for regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). 414 (14%) patients received a GPC and diacerein combination 100 mg/day. The investigators assessed the dynamics of pain during movement and at rest, functional disorders (on a numeric rating scale (NRS) of 0–10), as well as the need for NSAIDs at 12 weeks after starting the GPC cycle.Results and discussion. 98.5% of the patients completed their GPC treatment cycle. The therapy decreased the intensity of pain at rest from 4 [3; 5] to 1 [0; 2] and during movement from 6 [5; 7] to 2 [1; 3] and reduced the severity of functional disorders from 5 [4; 6] to 1 [0; 3]. The number of patients with a good response to therapy (a≥50% decrease in symptom severity) for pain at rest and during movement was 55.6 and 53.5%, respectively; and for functional disorders was 50.8%. 68.1% of patients stopped taking NSAIDs. The GPC and diacerein combination was more effective than GPC monotherapy: the number of patients with a ≥50% decrease in movement pain was 62.8 and 54.3%, respectively (p <0.001). GPC was well tolerated. During treatment, there were skin allergic reactions (0.3%), moderate injection-site pain (0.37%), and adverse reactions (ARs) related to the gastrointestinal tract (8%) and cardiovascular system (6%) (which were likely to be caused by NSAIDs). There were no serious ARs that were life-threatening and required hospitalization.Conclusion. GPC allows successful control of the main symptoms of knee and hip OA and GOA, by reducing pain, and those of functional disorders, and the need for NSAIDs. The GPC and diacerein combination is more effective than GPC monotherapy. GPC therapy is well tolerated and very rarely causes ARs.

Risk Factors for Failure of Direct Restorations in General Dental Practices

The aim of this retrospective noninterventional multicenter practice-based study was to analyze factors influencing the survival of direct restorations. Records from patients who visited 5 private practices regularly were searched for the presence of direct restorations. Data were recorded from 7,858 patients with 27,407 direct restorations being detected at least 6 mo before the last recall visit. Multilevel Cox proportional hazard models were used to evaluate the association between clinical factors and time until failure. Within 228 mo, 5,493 failures could be observed. Median survival time was 207 mo. The annual failure rates were 3.8%, 4.0%, 4.6%, 4.9%, and 3.9% for class I, II, III, IV, and V restorations, respectively. Class II and IV restorations showed a 1.1-times (95% CI, 1.0 to 1.2) and 1.2-times (95% CI, 1.1 to 1.2) higher failure rate than class I restorations (P ≤ 0.029). Patients aged <20 y and >60 y showed up to a 1.4-times higher failure rate than patients aged 20 to 60 y (P ≤ 0.015). Restorations that underwent check-up twice a year or more showed a significantly higher failure rate than those that did so less than twice a year (P < 0.001). Furthermore, the dentists significantly influenced time until failure (P < 0.001). Regarding the restorative material, composites showed up to a 2.1-times longer time until failure than GIC (P ≤ 0.020). Moderate failure rates were observed for direct restorations in the private practice setting after up to 18.5 y. Within the limitations of the present study, several factors on the levels of practice (i.e., dentist), patient (i.e., age), and tooth (i.e., restorative material, restored surfaces according to the classification of Black) were significant predictors for the failure rate. Therefore, treatment decision should take into account most relevant factors (German Clinical Trials Register DRKS00015228).

Artificial intelligence as an emerging diagnostic approach in paediatric pulmonology.

Artificial intelligence as an emerging diagnostic approach in paediatric pulmonology.

Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib \u2013 results from a non-interventional multi-center study

BackgroundGemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash.MethodsThis multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade ≥ 2), duration of erlotinib treatment (≤8 weeks, > 8 weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0–1, 2) and age (≤65 years, > 65 years).ResultsWithin the full analysis set (FAS; N = 270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade ≥ 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11 months with an OS of 9.93 months in rash-positive and 8.68 months in rash-negative patients. Median PFS was 5.06 months for rash-positive and 4.11 months for rash-negative patients. PFS was longer in patients with rash grade ≥ 2 and in older patients (> 65 years). Examination using a multivariate Cox proportional model revealed that an age > 65 years was associated with longer OS (hazard ratio 0.640; p = 0.0327) and PFS (hazard ratio 0.642; p = 0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3.ConclusionsComparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade ≥ 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals.Trial registrationClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013.

Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party.

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multicenter, prospective, non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult patients with systemic sclerosis undergoing a first autologous hematopoietic stem cell transplant between December 2012 and February 2016 were prospectively included in the study. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty patients with systemic sclerosis were included. The median duration of the follow-up was 24 (range, 6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulin conditioning for all, with CD34+ selection in 35 patients. At 2 years, the progression- free survival rate was 81.8%, the overall survival rate was 90%, the response rate was 88.7% and the incidence of progression was 11.9%. The 100-day non-relapse mortality rate was 6.25% (n=5) with four deaths from cardiac events, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (P<0.001). By multivariate analysis, baseline skin score >24 and older age at transplantation were associated with lower progression-free survival (hazard ratios 3.32 and 1.77, respectively). CD34+-cell selection was associated with better response (hazard ratio 0.46). This study confirms the efficacy of autologous stem cell transplantation, using nonmyeloablative conditioning, in real-life practice for severe systemic sclerosis. Careful cardio-pulmonary assessment to identify organ involvement at the time of the patient’s referral, reduced cyclophosphamide doses and CD34+-cell selection may improve outcomes. The study was registered at ClinicalTrials.gov: NCT02516124.

Topical drugs for the treatment of non-streptococcal acute tonsillopharyngitis in children: results of a multicenter study

Acute tonsillopharyngitis (ATP) is a very common disease in children. In non-streptococcal ATP, systemic antibiotics are usually not indicated, but topical antimicrobial therapy is advisable. To evaluate the effectiveness of the combination of cetylpyridinium chloride with gramicidin C in the form of a spray in children with ATP in a prospective multicenter non-interventional study. The groups of patients did not differ significantly in terms of demographic indicators and initial clinical manifestations. Body temperature initially did not differ, but was significantly lower in the main group after 1 (p=0.003) and 4 (p=0.04) days. The sore throat pain intensity decrease in the main group significantly exceeded this indicator in the control group after 1 (p<0.001) and 4 (p <0.001) days. Initially, swallowing pain was observed in all patients, after 4 days the complaint was significantly less frequent in the main group (p<0.001). The total assessment of objective data was significantly lower in the main group after 4 (p<0.001) and 8 (p<0.001) days. No adverse effects of pharmacotherapy were observed. The study showed high efficacy and safety of the cetylpyridinium chloride and gramicidin C (in the form of a spray) combination for non-streptococcal ATP in children aged 6-15 years.

Tolerability, compliance, quality of life, and clinical outcome during treatment with quinine sulfate in patients with nocturnal calf cramps. A multicenter non-interventional study (NIS) in adults

Frequent and painful nocturnal leg cramps (NLC) require an effective therapy to improve quality of life and sleep performance in patients. In a multicenter, prospective, non-interventional study (NIS) data on the effectiveness, tolerability and safety of quinine sulfate were collected in daily medical management in adult patients with frequent and painful nocturnal leg cramps. In total 596 patients were included into the study. Of these, 568 patients finished the study as planned (95.3%). Number, duration and pain intensity of NLC were reduced in the majority of patients after 2 weeks of therapy with quinine sulfate 200 mg OD. Physicians rated global assessment of treatment effect as "good" and "very good" in 535 patients (92.4%) which was concurrent with the patients' rating ("good" and "very good" by 534 patients = 92.2%), based on the full analysis set of 579 patients. Furthermore, quality of life and sleep were improved. Adverse drug reactions were reported in 35/592 patients (5.9%). Severe adverse events were not observed. The total incidence of therapy-associated adverse effects was comparable in the subgroup of patients with concomitant ß-blocker therapy (149/592 patients, 25.2%; totally 10%, subgroup 10.1%). Efficacy and tolerability of quinine sulfate were evaluated as "very good" or "good" by the majority of physicians and patients. The present NIS confirms effectiveness and tolerability of the therapy with quinine sulfate in daily clinical routine for adult patients with frequent and painful nocturnal leg cramps.

Effectiveness and safety of biosimilar follitropin alfa in women undergoing routine ovarian stimulation with a GnRH antagonist: results from a german multi-centre non-interventional study

Effectiveness and safety of biosimilar follitropin alfa in women undergoing routine ovarian stimulation with a GnRH antagonist: results from a german multi-centre non-interventional study

Die Dauer von Ethikvoten in Deutschland - am Beispiel einer nicht-interventionellen Beobachtungsstudie mit 44 teilnehmenden Zentren (PROSa)

BackgroundThe bureaucratic and administrative burden for obtaining the obligatory Institutional Review Board (IRB) approval, which confirms the ethical integrity of a scientific project, is high. In order to participate in multicenter studies, most participating centers in Germany require a local second approval. We investigated the variation in the time it took the participating centers of a non-interventional multicenter study to obtain this approval. MethodsDescriptive investigation of the amount of time it takes to gain an IRB approval for a multicenter observational study on the quality of life of sarcoma patients conducted throughout Germany. Stratified analyses were carried out on the basis of potential predictors of this duration and reasons for requests for revisions by the IRB were identified. Results44 applications for ethics approval were submitted to 26 IRBs. To obtain the 25 second approvals took 53.6 days on average (standard deviation 49.8 days, median 34 days). While State Medical Chambers needed an average of 20.3 days for a local second approval, university hospitals needed 72.4 days. 81.3 % of the university IRBs and 33.3% of the IRB of the State Medical Chambers made specific requests. Ten IRBs followed the recommendations of the primary approval without undertaking their own assessment (average 41.3 days), five IRBs examined the application in an abbreviated procedure (51.4 days), and ten examined it thoroughly (67.1 days). ConclusionSubmitting ethics approval applications for observational studies in a clinical setting involved considerable effort and long waiting times in 2017 and 2018. Simplified review procedures or a waiver of examination by local IRBs do not necessarily mean shorter processing times. In general, there is a continued need for further progress.

OR44: The Self-Evaluation of Food Intake (Sefi®) as a Screening Test for Malnutrition in General Practice: Prospective Non-Interventional Multicenter Study

OR44: The Self-Evaluation of Food Intake (Sefi®) as a Screening Test for Malnutrition in General Practice: Prospective Non-Interventional Multicenter Study

The prevalence of hypogonadism in men with type 2 diabetes mellitus in clinical practice

BACKGROUND: Hypogonadism is a common complication in men with type 2 diabetes mellitus (DM), but its prevalence remains unknown.&#x0D; AIMS: To estimate the prevalence of hypogonadism in men with type 2 DM.&#x0D; MATERIALS AND METHODS: Male patients with type 2 DM were enrolled into a single-cohort contemporaneous multicenter non-interventional screening study. The study period was from November 2017 through August 2018. Assessments included total testosterone, luteinizing hormone (LH), sex hormone-binding globulin, HbA1c levels. Levels of free testosterone were calculated by Vermeullen method.&#x0D; RESULTS: TheThe median of age of 400 included men was 56 years [51; 58], total testosterone was 12.3 [9.2; 16.5] nmol/l, free testosterone 270 [217; 334] pmol/l, HbA1c 7,1% [6.1; 8.6]. Hypogonadism was found in 135 men (33.7%). The total testosterone level in that group was 7.9 [6.8; 9.8] nmol/l, and free testosterone 192 [164; 227] pmol/l. In hypogonadism-free men their levels were 15,1 [12,4; 18,6] nmol/l and 311 [270; 364] pmol/l, respectively. In most patients with hypogonadism LH level was low, but within normal ranges, and significantly lower than in men without hypogonadism 3.2 [2.1; 4.7] IU/L vs 3.8 [2.7; 4.9] IU/L, respectively (p=0.007). Most commonly hypogonadism was with normal LH levels (92,6%, median LH level 3.2 [2.2; 4.3] IU/L, p0,001). The frequency of hypogonadism with high LH level (10.2 [9.2; 14.7] IU/L) and low LH level (1.0 [0.6; 1.1] IU/L) was 4.4% and 3.0%, respectively.&#x0D; CONCLUSIONS: The prevalence of hypogonadism in men with type 2 DM was found to be 33.7%. Normal levels of LH are typical for this type of patients with hypogonadism.

Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination

To study the influence of human papillomavirus (HPV) virions present in different sperm fractions of male partners of women undergoing IUI on fertility outcome. Prospective noninterventional multicenter study. Inpatient hospital fertility centers. Seven hundred thirty-two infertile couples undergoing 1,753 IUI cycles with capacitated sperm. None. Biochemical and clinical pregnancy rate in IUI cycles with HPV-positive or HPV-negative semen. Five hundred seventy-three infertile couples undergoing 1,362 IUI cycles were enrolled. Work-up of the 1,362 sperm samples that were used for IUI generated 3,444 separate sperm fractions. Each of the sperm fractions was tested with quantitative polymerase chain reaction for 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68). HPV prevalence in sperm was 12.5%/IUI cycle. When infectious HPV virions were detected in sperm, a significant decrease in clinical pregnancies was observed when compared with HPV-negative cycles (2.9% vs. 11.1 %/cycle). Above a ratio of 0.66 HPV virions/spermatozoon no pregnancies occurred (sensitivity 100%, specificity 32.5%). Women inseminated with HPV-positive sperm had 4 times fewer clinical pregnancies compared with women who had HPV-negative partners. Detection of HPV virions in sperm is associated with a negative IUI outcome and should be part of routine examination and counseling of infertile couples. 2017-004791-56.