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Background: Chemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN. Methods: QUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1-V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of = 30% and = 50% pain reduction. Results: Median age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of = 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of = 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions. Conclusion: In this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice. [ABSTRACT FROM AUTHOR]

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN.MethodsQUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1–V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of ≥ 30% and ≥ 50% pain reduction.ResultsMedian age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of ≥ 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of ≥ 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions.ConclusionIn this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice.

Abstract Introduction Plaque psoriasis is a chronic relapsing inflammatory skin disease that is associated with extensive disease burden that often requires long-term therapy. Treatment of psoriasis with 4 weeks of the aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD; Enstilar®, LEO Pharma) has been demonstrated to be effective, well tolerated, and associated with high patient satisfaction. Cal/BD foam is approved as a first-line treatment in multiple countries, where several non-interventional studies (NIS) have corroborated the beneficial efficacy and safety profiles determined in the randomized clinical trials. Heterogenicity in these NIS, however, prevents the use of a data pooling strategy for comparisons of effectiveness outcomes across different patient populations. Methods Therefore, here, we report on a post hoc analysis of effectiveness data consolidated from six prospective NIS to discern any differences in improvement in signs and symptoms of psoriasis attributable to Cal/BD foam treatment across the countries. In addition, we provide real-world experience of clinicians with Cal/BD foam treatment, factoring in changes in usage since these NIS were performed in their local markets. Results This post hoc analysis of Cal/BD foam NIS brings together data outside of randomized clinical trials from six countries to provide real-world evidence in 1388 patients showing that 4 weeks of Cal/BD foam is an effective and safe treatment option with quick onset of action for patients with psoriasis. Conclusion These results show that regardless of NIS location, Cal/BD foam remains a well-tolerated, efficacious option for patient care that could be used as a first-line topical therapy for mild-to-severe psoriasis.

Introduction: Plaque psoriasis is a chronic relapsing inflammatory skin disease that is associated with extensive disease burden that often requires long-term therapy. Treatment of psoriasis with 4 weeks of the aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD; Enstilar®, LEO Pharma) has been demonstrated to be effective, well tolerated, and associated with high patient satisfaction. Cal/BD foam is approved as a first-line treatment in multiple countries, where several non-interventional studies (NIS) have corroborated the beneficial efficacy and safety profiles determined in the randomized clinical trials. Heterogenicity in these NIS, however, prevents the use of a data pooling strategy for comparisons of effectiveness outcomes across different patient populations. Methods: Therefore, here, we report on a post hoc analysis of effectiveness data consolidated from six prospective NIS to discern any differences in improvement in signs and symptoms of psoriasis attributable to Cal/BD foam treatment across the countries. In addition, we provide real-world experience of clinicians with Cal/BD foam treatment, factoring in changes in usage since these NIS were performed in their local markets. Results: This post hoc analysis of Cal/BD foam NIS brings together data outside of randomized clinical trials from six countries to provide real-world evidence in 1388 patients showing that 4 weeks of Cal/BD foam is an effective and safe treatment option with quick onset of action for patients with psoriasis. Conclusion: These results show that regardless of NIS location, Cal/BD foam remains a well-tolerated, efficacious option for patient care that could be used as a first-line topical therapy for mild-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. Methods: This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. Results: Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. Conclusions: LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients. [ABSTRACT FROM AUTHOR]

Purpose: data analysis of Russia’s first register of neovascular age-related macular degeneration (nAMD) — a web-based system for clinical monitoring of nAMD patients designed to collect and accumulate the data on such patients, their demographic, social and clinical characteristics, on the existing practice of treating nAMD, assessing the effectiveness of anti-VEGF therapy and the burden inflicted by the disease. Material and methods. A non-interventional, multicenter prospective study (CRTH258ARU01) was undertaken, which involved primary collection and reuse of data. The study is referred to as “the Russian register of patients with neovascular age-related macular degeneration”. The patients’ case histories served as the primary source of information as the data contained therein were entered by the doctors into electronic individual registration cards (eIRC). The eIRC were used remotely for dynamic clinical observations and data analysis. 61 ophthalmologists from 34 Russia’s scientific or medical organizations engaged in diagnosing, follow-up and treatment of nAMD patients contributed to the register. The data for the register were collected from December 20, 2020 to December 5, 2022. The register has data on 2665 patients (3460 eyes). Results. The mean age (± standard deviation) of patients at the time of inclusion in the registry was 73.0 ± 8.8 years; the majority of patients (66.2%) were female. The average yearly number of follow-up visits per patient was 3.4 ± 2.7, while the average yearly number of injections of anti-VEGF drugs per eye was 2.0 ± 1.7. Conclusion. With the creation of the register, the main goals of the study have been achieved. On the other hand, the register showed that a significant share of nAMD patients/eyes evaded medical observation, and that the patients’ adherence to treatment was insufficient, which had a notable negative impact on the results of therapy in real clinical practice

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.

Abstract Background To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. Methods CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. Results Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1–39.6] and 29.5% [26.7–32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6–25-7], 8.4% [6.8–10.0], 5.0% [3.5–6.5] and 3.9% [2.6–5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. Conclusions In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit.

Abstract Introduction Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. Methods This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. Results Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician’s Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. Conclusions LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.

BackgroundHalf (49%) of clinically diagnosed allergic rhinitis (AR) patients are sensitized to house dust mite (HDM). If allergen avoidance and symptomatic medication fail, allergen immunotherapy may be indicated.ObjectiveWe investigated safety and tolerability of HDM-sublingual immunotherapy by HDM-SLIT tablets in Dutch daily clinical practice.MethodsDaily intake of 12 SQ-HDM SLIT-tablet was investigated in a prospective, multicenter, observational study (EUPAS43753). It comprised 4 consultations in 1 year. Data on safety, tolerability, treatment satisfaction, symptomatic medication, compliance, and clinical effectiveness (Control of Allergic Rhinitis and Asthma Test; CARAT) were collected. Descriptive and longitudinal regression data analysis were performed.ResultsAdult patients (n = 415), mean (SD) age 36.6 (12.2) years, 61.4% female and 36% asthmatic were included. The preponderance (65.1%) experienced adverse events (AEs). These, mostly mild (67%), AEs comprised: oral allergic reactions (58.6%), respiratory (12.4%) and gastrointestinal symptoms (9.4%). Sixty (14.5%) patients stopped due to AEs and 76 (18.3%) for non-AE reasons. CARAT scores improved clinically significant by 6 points and symptomatic medication use decreased from 96.1% to 77.4%. Most patients (74.5%) tolerated the treatment and were compliant (>86.5%). The majority of patients (62.4%) and investigators (69.4%) were satisfied with treatment.ConclusionsHDM SLIT-tablet is a safe and well-tolerated AR treatment. AEs occur often but are mostly mild and decreasing during the first year. CARAT scores improved and symptomatic medication use decreased suggesting better control of AR with treatment. Compliance, tolerability, and treatment satisfaction are good. However, patient follow-up and compliance remain important points of attention when initiating treatment.

Background: To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. Methods: CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. Results: Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1–39.6] and 29.5% [26.7–32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6–25-7], 8.4% [6.8–10.0], 5.0% [3.5–6.5] and 3.9% [2.6–5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. Conclusions: In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit. [ABSTRACT FROM AUTHOR]

Background: Dizziness is a common leading symptom in bilateral vestibulopathy (BVP) and functional dizziness (FD), with significant negative effects on functional ability and quality of life. Vertigoheel is a widely used non-prescription drug for the treatment of vertigo. In order to generate systematic data for Vertigoheel in BVP and FD, we conducted a non-interventional study assessing vertigo symptoms. Methods: This study was conducted as an open-label, prospective, monocentric, non-interventional case series (ClinicalTrials.gov identifier NCT05897853). Patients with BVP and FD received Vertigoheel according to market approval for an observational period of 2 months. Change from baseline after 2 months was assessed for the following endpoints: Dizziness Handicap Inventory (DHI) as the primary endpoint, quality of life (QoL) by EQ-5D-5L, and body sway by static posturography. Patients with FD were additionally assessed for depression and anxiety by PHQ-9 and GAD-7 questionnaires. Patients with BVP were assessed for vestibular function by video head impulse testing and caloric testing. Adverse events and other safety-related observations were evaluated. Results: Of 41 patients with FD and 13 with BVP, two with FD and none with BVP dropped out before the follow-up visit. Both patient groups showed significantly improved disability caused by dizziness after 2 months: In BVP, the DHI decreased on average by 13.2 points from 45.4 to 32.2 (p < 0.001). In FD, the DHI decreased on average by 12.0 points from 46.5 to 34.5 (p < 0.001). In patients with FD, significant improvements were also observed for the secondary endpoints QoL, anxiety, and depression. No significant change was observed for posturography readouts. In patients with BVP, there were no statistically significant improvements for the secondary endpoints QoL, posturography, or vestibular function within the observation period. The study found no evidence of a safety risk. Conclusion: The study provides evidence for Vertigoheel's clinical safety and limited evidence - because of the non-interventional design - for its effectiveness in BVP and FD that are considered disease entities with high medical need for new treatment options. The results may serve as the basis for randomized placebo-controlled trials. [ABSTRACT FROM AUTHOR]

Abstract Background There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice. Methods Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria. Results A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2). Conclusions This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials. Trial registration ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.

Abstract Background Precision oncology, defined as treatment of patients with targeted therapies matched to specific molecular alterations, has entered routine clinical practice. Particularly in patients with advanced cancer or hematologic malignancies, for whom no further standard therapies are available, this approach is increasingly applied as last resort option outside of the approved indication. However, data on patient outcomes are not systematically collected, analyzed, reported, and shared. We have initiated the INFINITY registry to provide evidence from routine clinical practice to fill this knowledge gap. Methods INFINITY is a retrospective, non-interventional cohort study conducted at approximately 100 sites in Germany (office-based oncologists/hematologists and hospitals). We aim to include 500 patients with advanced solid tumors or hematologic malignancies who received a non-standard targeted therapy based on potentially actionable molecular alterations or biomarkers. INFINITY aims to provide insights into the use of precision oncology in routine clinical practice within Germany. We systematically collect details on patient and disease characteristics, molecular testing, clinical decision-making, treatment, and outcome. Discussion INFINITY will provide evidence on the current biomarker landscape driving treatment decisions in routine clinical care. It will also provide insights on effectiveness of precision oncology approaches in general, and of specific drug class/alteration matches used outside their approved indications. Trial registration The study is registered at ClinicalTrials.gov, NCT04389541.

BackgroundDizziness is a common leading symptom in bilateral vestibulopathy (BVP) and functional dizziness (FD), with significant negative effects on functional ability and quality of life. Vertigoheel is a widely used non-prescription drug for the treatment of vertigo. In order to generate systematic data for Vertigoheel in BVP and FD, we conducted a non-interventional study assessing vertigo symptoms.MethodsThis study was conducted as an open-label, prospective, monocentric, non-interventional case series (ClinicalTrials.gov identifier NCT05897853). Patients with BVP and FD received Vertigoheel according to market approval for an observational period of 2 months. Change from baseline after 2 months was assessed for the following endpoints: Dizziness Handicap Inventory (DHI) as the primary endpoint, quality of life (QoL) by EQ-5D-5L, and body sway by static posturography. Patients with FD were additionally assessed for depression and anxiety by PHQ-9 and GAD-7 questionnaires. Patients with BVP were assessed for vestibular function by video head impulse testing and caloric testing. Adverse events and other safety-related observations were evaluated.ResultsOf 41 patients with FD and 13 with BVP, two with FD and none with BVP dropped out before the follow-up visit. Both patient groups showed significantly improved disability caused by dizziness after 2 months: In BVP, the DHI decreased on average by 13.2 points from 45.4 to 32.2 (p

To investigate the tolerability and safety of two sublingual tree pollen extracts approved in 2018, a non-interventional study (NIS) was performed. This NIS was an 8-month observational study conducted at 84 sites throughout Germany. Study participants received either a sublingual liquid allergen extract of birch pollen (SBPE) or a liquid allergen extract consisting of a mixture of birch, hazel, and alder tree pollen (STPE). Data from 432 patients were analyzed for the occurrence of adverse events and patient compliance. At least one local reaction occurred in 69 (22.2%) patients, whereas systemic reactions were only observed in 27 (6.3%) patients. STPE-treated patients developed systemic reactions more frequently than SBPE-treated patients (SBPE: 9 (4.3%) vs. STPE: 18 (8.0%)). Only one patient developed a systemic grade III reaction. Severe systemic grade IV reactions were not observed. A total of 348 (98.6%) of the patients who completed all visits were satisfied or very satisfied with the sublingual immunotherapy (SLIT), and 322 (71%) patients completed all visits. Both investigated products were well tolerated by the patients and demonstrated a good safety profile. AEs were observed less frequently than in the preceding clinical phase III trial, and no new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada. Methods Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression – Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population. Results Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration. Conclusions AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms. Trial registration NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

Abstract Background Rituximab has become a standard treatment for non‐Hodgkin lymphoma. Clinical studies have demonstrated the efficacy of rituximab in combination with standard chemotherapies in the treatment of follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) patients. This non‐interventional study aimed to evaluate the effectiveness and safety of subcutaneous (SC) rituximab in routine clinical practice. Methods Adult patients with previously untreated CD20 positive DLBCL or FL who received rituximab SC and chemotherapy as first‐line treatment were observed between 07/2014 and 07/2019 at 99 institutions in Germany. Primary endpoint was the (unconfirmed) complete remission (CR/CRu) rate. Primary outcome was analyzed inferentially; other variables were evaluated descriptively. Results Overall 583 patients (247 FL; 336 DLBCL) were evaluated. CR/CRu rates were 51.4% (95% CI: 45.2; 57.6) in the FL set and 48.5% (95% CI: 43.2; 53.8) in the DLBCL set. Regarding progression‐free survival in the FL group, the probability of being event‐free was 94.2% in the first year and 86.2% in the second year. An overall response was achieved in 85.8% (FL) and 85.4% patients (DLBCL). Patient satisfaction at the end of study with the time saving simplification of the SC vs. intravenous route was 98% for FL and 97% for DLBCL. 45.3% of FL and 47.0% of DLBCL patients experienced an adverse event of grade ≥3. Serious adverse events of grade ≥3 occurred in 27.9% FL and 32.4% DLBCL patients, with the highest incidences for leucopenia, anemia, nausea, and fatigue. No new safety signals were detected. Conclusions The results confirmed the effectiveness and safety of rituximab SC in both the FL and the DLBCL group. Satisfaction of patients and nurses with SC administration was high.

Background: There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice. Methods: Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria. Results: A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2). Conclusions: This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials. Trial registration: ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017. [ABSTRACT FROM AUTHOR]

Background: Precision oncology, defined as treatment of patients with targeted therapies matched to specific molecular alterations, has entered routine clinical practice. Particularly in patients with advanced cancer or hematologic malignancies, for whom no further standard therapies are available, this approach is increasingly applied as last resort option outside of the approved indication. However, data on patient outcomes are not systematically collected, analyzed, reported, and shared. We have initiated the INFINITY registry to provide evidence from routine clinical practice to fill this knowledge gap. Methods: INFINITY is a retrospective, non-interventional cohort study conducted at approximately 100 sites in Germany (office-based oncologists/hematologists and hospitals). We aim to include 500 patients with advanced solid tumors or hematologic malignancies who received a non-standard targeted therapy based on potentially actionable molecular alterations or biomarkers. INFINITY aims to provide insights into the use of precision oncology in routine clinical practice within Germany. We systematically collect details on patient and disease characteristics, molecular testing, clinical decision-making, treatment, and outcome. Discussion: INFINITY will provide evidence on the current biomarker landscape driving treatment decisions in routine clinical care. It will also provide insights on effectiveness of precision oncology approaches in general, and of specific drug class/alteration matches used outside their approved indications. Trial registration: The study is registered at ClinicalTrials.gov, NCT04389541. [ABSTRACT FROM AUTHOR]

This article is devoted to an ethical review of planned real-world studies. The legal basis of such examinations has also been considered. Most real-world studies are non-interventional, so the ethical review of such studies is similar to that of observational studies.

Introduction: Pelvic hypoperfusion caused by atherosclerosis has been proposed as a cause of lower urinary tract dysfunction including overactive bladder syndrome (OAB). Limited data indicate that OAB patients with concomitant diabetes or hypertension, known risk factors of atherosclerosis, may exhibit greater baseline OAB symptoms and slightly smaller therapeutic responses to treatment, but the impact of a combined presence of diabetes and hypertension has not been reported. Therefore, we have explored whether the combined presence of both comorbidities is associated with greater baseline OAB symptoms than that of either comorbidity alone. Secondary questions were exploration of the impact of either comorbidity on baseline symptoms, and of the impact of either comorbidity alone and their combination on therapeutic responses. Methods: Data from two non-interventional studies applying treatment with propiverine ER 30 or 45 mg/d for 12 weeks were analyzed. Results: Number of urgency episodes in the combination group was greater than with each comorbidity alone. The impact of comorbidities on baseline intensity of incontinence, frequency or nocturia or Patient Perception of Bladder Condition was less consistent or absent. Either comorbidity alone was associated with a smaller % improvement of symptoms, and their combination had a greater effect than either alone. However, all attenuations associated with comorbidity were small relative to the overall improvement. Conclusions: We conclude that comorbidities of diabetes and hypertension have detectable effects on OAB symptoms and treatment responses, but the small magnitude of these alterations does not justify changing existing paradigms for the clinical management of OAB. [ABSTRACT FROM AUTHOR]

Background: Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada. Methods: Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression – Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population. Results: Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration. Conclusions: AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms. Trial registration: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N. [ABSTRACT FROM AUTHOR]

Background: Rituximab has become a standard treatment for non‐Hodgkin lymphoma. Clinical studies have demonstrated the efficacy of rituximab in combination with standard chemotherapies in the treatment of follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) patients. This non‐interventional study aimed to evaluate the effectiveness and safety of subcutaneous (SC) rituximab in routine clinical practice. Methods: Adult patients with previously untreated CD20 positive DLBCL or FL who received rituximab SC and chemotherapy as first‐line treatment were observed between 07/2014 and 07/2019 at 99 institutions in Germany. Primary endpoint was the (unconfirmed) complete remission (CR/CRu) rate. Primary outcome was analyzed inferentially; other variables were evaluated descriptively. Results: Overall 583 patients (247 FL; 336 DLBCL) were evaluated. CR/CRu rates were 51.4% (95% CI: 45.2; 57.6) in the FL set and 48.5% (95% CI: 43.2; 53.8) in the DLBCL set. Regarding progression‐free survival in the FL group, the probability of being event‐free was 94.2% in the first year and 86.2% in the second year. An overall response was achieved in 85.8% (FL) and 85.4% patients (DLBCL). Patient satisfaction at the end of study with the time saving simplification of the SC vs. intravenous route was 98% for FL and 97% for DLBCL. 45.3% of FL and 47.0% of DLBCL patients experienced an adverse event of grade ≥3. Serious adverse events of grade ≥3 occurred in 27.9% FL and 32.4% DLBCL patients, with the highest incidences for leucopenia, anemia, nausea, and fatigue. No new safety signals were detected. Conclusions: The results confirmed the effectiveness and safety of rituximab SC in both the FL and the DLBCL group. Satisfaction of patients and nurses with SC administration was high. [ABSTRACT FROM AUTHOR]

Abstract Background Tropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide array of tumors. Larotrectinib is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. ON-TRK aims to evaluate the safety profile of larotrectinib in a broader population and over extended time periods. Methods ON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib that will describe the safety and effectiveness of larotrectinib in real-world practice conditions. Adult patients will be grouped by tumor type and followed for at least 2 years. Patients

Abstract Background Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD). Methods Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019. Results A total of 106 patients with GD (15.1% children aged

Mean voided volume (MVV) is a non-invasive indicator of urinary bladder capacity and frequently used as secondary or even primary endpoint in clinical studies of bladder function, particularly in the context of overactive bladder syndrome. We have analyzed previously reported results from two large, non-interventional studies (n = 1335 and 745 patients with overactive bladder syndrome treated with 30–45 mg propiverine ER) to address two questions: How does MVV relate to other typically used parameters of overactive bladder syndrome (primary aim)? Is MVV a normally distributed variable (secondary aim)? We found that distribution of MVV at baseline and after treatment exhibits a skewed distribution and deviates from a normal distribution, albeit not to a major extent. Basal MVV was weakly to moderately inversely correlated to numbers of urgency, incontinence and nocturia episodes (Spearman’s correlation coefficient 0.2224–0.2960) and somewhat stronger but still only moderately to micturition frequency (0.3296–0.3505). Associations of similar strength were found for absolute and % treatment-associated changes of MVV. MVV was not associated with age and only inconsistently with gender. We conclude that MVV should not be treated as a normally distributed variable and propose that at least partly different (patho)physiological factors may regulate MVV as compared to urgency, incontinence, frequency and nocturia. This should be considered in the choice of primary endpoint in clinical studies.

While animal studies have suggested an association between the presence of hypertension and the presence and/or severity of overactive bladder syndrome (OAB) symptoms, little clinical data is available. We have conducted a prespecified secondary analysis of a non-interventional study involving 4450 OAB patients being treated with solifenacin to explore the existence of an association between OAB and hypertension using three parallel and overlapping definitions of hypertension to enhance robustness of analysis. Regardless of definition, patients with hypertension were older and had greater OAB symptom severity in univariate analyses. In multiple regression models including age as explanatory covariate, most relationships held up but effect sizes of concomitant hypertension on OAB severity were small (odds ratios <1.35 in all cases) and were deemed to be unlikely of clinical relevance. % Changes in symptom severity were somewhat smaller in univariate analysis, but effect sizes were small. We conclude that OAB and arterial hypertension are associated but effect sizes are too small to justify adaptation of clinical practice for OAB patients with concomitant hypertension. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical trials have demonstrated the effectiveness of pazopanib as a primary treatment for metastatic renal cell carcinoma (mRCC). The approval of tyrosine kinase inhibitors and checkpoint-inhibitors represented further progress in the mRCC treatment landscape. Yet, with the recent changes in treatment options, there are scarce real-world data on these substances, including pazopanib. The PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. This study included 376 mRCC patients who received first-line treatment with pazopanib and assessed the treatment's effectiveness, safety, and resultant quality of life. The median time on the drug for the study population was 10.0 months; for primary treatment with pazopanib, it was 6.3 months. The median overall survival (mOS) for the entire study population was 35.9 months. No new safety signals were detected. PAZOREAL provides valuable real-world data for the primary treatment of mRCC with pazopanib. The approval of tyrosine kinase inhibitors and checkpoint inhibitors represented a remarkable progression in the therapeutic landscape for the treatment of metastatic renal cell carcinoma (mRCC). Yet, in the ever-evolving landscape of mRCC treatment, real-world data on these agents, including pazopanib, are scarce. The non-interventional PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. The multicentric study included 376 mRCC patients who received first-line treatment with pazopanib and assessed time on the drug (primary endpoint), overall survival, best responses, disease control rates, as well as safety signals and health-related quality of life. The median overall time on the drug was 10.0 months, with first-line pazopanib having a median time on drug of 6.3 months. The median overall survival was 35.9 months. The disease control rate for first-line pazopanib was 56.9%. No new safety signals were detected. PAZOREAL provides valuable real-world data for first-line treatment with pazopanib. [ABSTRACT FROM AUTHOR]

Introduction: The non-interventional study (NIS) KORALLE evaluated the effectiveness and safety of bevacizumab in patients with metastatic colorectal carcinoma (mCRC) treated with bevacizumab in combination with fluoropyrimidine-based chemotherapy in the first-line setting and beyond first progression in routine clinical practice. Methods: This prospective, multicenter NIS observed adult patients with mCRC who started first-line bevacizumab therapy. The planned maximum duration of observation per patient was 21 months. The primary effectiveness variable was progression-free survival in the first-line therapy setting (PFS-1). Secondary effectiveness variables included PFS after first progression as well as overall survival and overall response rate. All analyses were carried out descriptively for the full analysis population set (FAS). Effectiveness analyses were also assessed for predefined subgroups based on therapy goals. Results: Between December 2012 and July 2016, 2,429 eligible patients were observed at 314 sites in Germany. In the first-line setting in the FAS, the median PFS-1 was 10.3 months (95% CI: 9.9; 10.8), the median overall survival was 16.9 months (95% CI: 16.3; 17.5), and the overall response rate (ORR-1) was 44.2% (95% CI: 41.6%; 46.8%). Effectiveness results of all subgroups were similar to the FAS. Overall, 80.9% of patients experienced any adverse events, 36.6% of patients experienced serious adverse events, and 8.8% of patients experienced fatal adverse events. Conclusion: The NIS KORALLE provided broad real-world evidence on effectiveness and safety of bevacizumab. Despite different treatment intentions, the combination of bevacizumab plus fluoropyrimidine-based chemotherapy was similarly effective in all subgroups in routine clinical practice. The safety information reported in this study is consistent with the known safety profile of bevacizumab. [ABSTRACT FROM AUTHOR]

Aim: The multicentre non-interventional AVANTI study assessed safety, effectiveness and patient-reported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice. Methods: Eligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians’ discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC). Results: Between November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumab–capecitabine were less likely to have de novo disease and more likely to have TNBC, age ≥60 years and prior anthracycline/taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9–13.2) months (12.8 with bevacizumab–paclitaxel, 10.5 with bevacizumab–capecitabine); median OS was 23.9 (95% CI 22.2–25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade ≥3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall. Conclusions: In routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance.

While animal studies have suggested an association between the presence of hypertension and the presence and/or severity of overactive bladder syndrome (OAB) symptoms, little clinical data is available. We have conducted a pre-specified secondary analysis of a non-interventional study involving 4450 OAB patients being treated with solifenacin to explore the existence of an association between OAB and hypertension using three parallel and overlapping definitions of hypertension to enhance robustness of analysis. Regardless of definition, patients with hypertension were older and had greater OAB symptom severity in univariate analyses. In multiple regression models including age as explanatory covariate, most relationships held up but effect sizes of concomitant hypertension on OAB severity were small (odds ratios

Background: Functional gastrointestinal disorders (FGIDs) of the upper and lower digestive system in children and adolescents present with heterogeneous gastrointestinal symptoms and are a common reason for specialist consultations. The herbal medicinal preparation STW-5 has already shown efficacy and safety in clinical studies with more than 7000 adult participants suffering from functional dyspepsia (FD) or irritable bowel syndrome (IBS). Here, we evaluate with a prospective observational study the effectivity and safety of STW-5 in children with FGID under real-life conditions and interpret these data versus the background of controlled clinical studies in a predominantly adult population. Methods: This prospective observational study included 980 children (age 3–14 years) with FGID. For inclusion, Rome III criteria were recommended to apply. The inclusion of the patients for treatment with STW-5 followed routine clinical practice. Patients were treated for approximately 1 week. The presence and severity of symptoms was documented at the study start and at the end of treatment period utilizing the adapted gastrointestinal symptom score (GIS). Other target parameters included global effectivity and tolerability assessments as well as adverse events. Results: The average patient age was 7.6 ± 2.9 years. Most of the patients were treated for IBS (n = 418; 43 %) or FD (n = 259; 26 %), with a mean baseline GIS of 16.1 ± 8.9. During the treatment period, the GIS decreased 76 % to 3.8 ± 4.2. The decrease in symptoms was similar for different age groups, gender, and indications. Patients with a shorter duration of complaints had a lower GIS at study end (p

Abstract Background There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials. Methods Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters. Results The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6–17.9 years) and glycated hemoglobin 7.3% (6.6–8.4%) [56 mmol/mol (49–68 mmol/mol)]. Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval [CI] 32.7–36.8) and 31.8% (95% CI 29.7–33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively. Conclusions In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).

Background: Tropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide array of tumors. Larotrectinib is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. ON-TRK aims to evaluate the safety profile of larotrectinib in a broader population and over extended time periods.Methods: ON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib that will describe the safety and effectiveness of larotrectinib in real-world practice conditions. Adult patients will be grouped by tumor type and followed for at least 2 years. Patients < 18 years old will be enrolled under a 'pediatric' cohort regardless of tumor type and will be followed for 5 years to evaluate the risk of potential long-term adverse effects of larotrectinib on their growth and development. The effectiveness of larotrectinib in the overall study population as well as in patient subgroups will also be evaluated. Procedures avoided in patients with infantile fibrosarcoma (e.g., amputation) and the number of patients who were able to undergo surgery with a curative intent (excluding amputation) because of the use of larotrectinib will be described. Larotrectinib treatment patterns in real-world practice, including dosing and duration of treatment, will be described.Discussion: The FDA Accelerated Approval Program allows for earlier approval of and patient access to drugs that treat serious conditions and fill an unmet medical need. This study is designed to fulfill post-approval requirements set by the FDA as well as post-marketing requirements set forth by local regulatory bodies and is part of the risk management plan for the EMA.Study Registration: This study is registered at ClinicalTrials.gov ( NCT04142437 ).Protocol Version: v2.5, 25 March 2021. [ABSTRACT FROM AUTHOR]

There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-naïve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was + 1.25 and + 1.35 in US and international patients, respectively. Conclusion: Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH. Trial registration: NA. What is Known: • Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies. • The PAtients TReated with Omnitrope® (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope®. What is New: • Omnitrope® is well tolerated and effective in US patients, and those from other countries. • Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes. [ABSTRACT FROM AUTHOR]

Background: Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD).Methods: Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019.Results: A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients.Conclusions: The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa. [ABSTRACT FROM AUTHOR]

Arschang Valipour,1 Sergey Avdeev,2 Adam Barczyk,3 Valentina Bayer,4 Zvi Fridlender,5 Mariela Georgieva,6 Ondřej Kudela,7 Alexey Medvedchikov,8 Ramona Miron,9 Maria Sanzharovskaya,8 Virginija Šileikienė,10 Jurij Šorli,11 Marc Spielmanns,12 Zsuzsanna Szalai13 1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Vienna Health Care Group, Klinik Floridsdorf, Vienna, Austria; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 3Wydział Nauk Medycznych Śląskiego Uniwersytetu Medycznego, Katowice, Poland; 4Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 6Medical Center “Sv.ivan Rilski” OOD, Vidin, Bulgaria; 7Department of Pneumology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic; 8Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 9Clinical Pneumophtysiology Hospital Iasi, Iasi, Romania; 10Faculty of Medicine, Clinic of Chest Diseases, Immunology and Allergology, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania; 11Bolnišnica Topolšica, Topolšica, Slovenia; 12Zürcher RehaZentrum Wald, Wald, Switzerland; 13Petz Aladar County Teaching Hospital, Gyor, HungaryCorrespondence: Arschang ValipourDepartment of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Vienna Health Care Group, Klinik Floridsdorf, Brünner Straße 68, 1210 Vienna, AustriaTel +43 1 277 00-72201Fax +43 1 277 00 99 2208Email arschang.valipour@gesundheitsverbund.atBackground: The Clinical COPD Questionnaire (CCQ) is a simple patient-reported tool to measure clinical control of chronic obstructive pulmonary disease (COPD).Objective: This open-label, single-arm, non-interventional study (NCT03663569) investigated changes in CCQ score during treatment with tiotropium/olodaterol in clinical practice.Methods: Data were included from consenting COPD patients, enrolled in Bulgaria, Czech Republic, Hungary, Israel, Lithuania, Poland, Romania, Russia, Slovenia, Switzerland and Ukraine, who were receiving a new prescription for tiotropium/olodaterol according to the treating physician in a real-world environment. The primary endpoint was the occurrence of therapeutic success, defined as a 0.4-point decrease in CCQ score after treatment with tiotropium/olodaterol for approximately 6 weeks.Results: Overall, 4819 patients were treated; baseline and Week 6 CCQ scores were available for 4700 patients, mostly classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B (51.6%) or D (42.7%). After 6 weeks’ treatment, 81.4% (95% confidence interval [95% CI] 80.24– 82.49) of patients achieved therapeutic success; mean improvement in overall CCQ score was 1.02 points (95% CI 1.00– 1.05). Improved CCQ score was seen in 92.2% of patients (95% CI 91.43– 92.98), 2.5% had no change and 5.3% showed a worsening. When stratified by prior treatment, the greatest benefit was seen in treatment-naïve patients, with 85.7% achieving therapeutic success, compared with 79.5% of those pretreated with long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) and 74.2% of those pretreated with LABA or long-acting muscarinic antagonist (LAMA) monotherapy. Overall, rescue medication decreased by 1.25 puffs/day (95% CI 1.19– 1.31) versus baseline. In total, 29 patients (0.6%) reported drug-related adverse events and 7 patients reported serious adverse events (0.15%).Conclusion: In 4700 COPD patients, 6 weeks’ treatment with tiotropium/olodaterol, as initial treatment or follow-up to LAMA or LABA monotherapy or LABA/ICS, improved CCQ and decreased rescue medication use. The adverse event profile was consistent with the known safety profile of tiotropium/olodaterol.Keywords: tiotropium, olodaterol, COPD, CCQ, Clinical COPD Questionnaire, non-interventional study

Most patients with advanced basal cell carcinomas (BCCs) may not benefit sufficiently from standard treatment comprising surgery and radiation. Vismodegib, an oral selective hedgehog pathway inhibitor, is approved for treatment of patients with locally advanced BCC inappropriate for surgery or radiotherapy, or for patients with symptomatic metastatic BCC. In order to enhance understanding of the effectiveness, safety and utilization of vismodegib in clinical practice in Germany, a non-interventional study, JONAS, was conducted. A total of 53 patients with locally advanced BCC who initiated treatment with vismodegib between 2016 and 2018 were included in the study, which was embedded in the German ADOReg skin cancer registry. Duration of response, the primary endpoint, was 12.4 months, progression-free survival 32.2 months and overall response rate 77.4%. Most adverse events were mild to moderate. Overall, results confirmed previous findings, demonstrating favourable responses and manageable safety of vismodegib in patients with locally advanced BCC in clinical practice.

Background: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low‐dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real‐world evidence is scarce. Patients and Methods: POSEIDON was a prospective non‐interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. Results: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression‐free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. Conclusion: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real‐world setting. Registered at clinicaltrials.gov (NCT02075996). [ABSTRACT FROM AUTHOR]

Most patients with advanced basal cell carcinomas (BCCs) may not benefit sufficiently from standard treatment comprising surgery and radiation. Vismodegib, an oral selective hedgehog pathway inhibitor, is approved for treatment of patients with locally advanced BCC inappropriate for surgery or radiotherapy, or for patients with symptomatic metastatic BCC. In order to enhance understanding of the effectiveness, safety and utilization of vismodegib in clinical practice in Germany, a non-interventional study, JONAS, was conducted. A total of 53 patients with locally advanced BCC who initiated treatment with vismodegib between 2016 and 2018 were included in the study, which was embedded in the German ADOReg skin cancer registry. Duration of response, the primary endpoint, was 12.4 months, progression-free survival 32.2 months and overall response rate 77.4%. Most adverse events were mild to moderate. Overall, results confirmed previous findings, demonstrating favourable responses and manageable safety of vismodegib in patients with locally advanced BCC in clinical practice. [ABSTRACT FROM AUTHOR]

Background: STEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. Methods: Postmenopausal women with HR+, HER2− ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end. Results: Overall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval [CI]: 8.6–10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3–11.5 months) and 8 months (4.7–10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0–14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9–12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%). Conclusions: Real-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2− ABC recurring/progressing on/after NSAIs.

Aim. This observational (non-interventional) study was aimed at obtaining data on practitioners’ commitment to prescribing rifaximin-α therapy to patients with uncomplicated diverticular disease (UDD), to assess patients’ adherence to such prescriptions, as well as to assess physicians’ and patients’ satisfaction with this drug under the conditions of outpatient practice.Materials and methods. 27 research physicians in 22 research centres located in 15 Russian cities and 250 patients participated in an open, prospective multicentre observational study. The observation lasted for 6 months with an interim assessment after 3 months. Physicians’ prescription of rifaximin-α (dose, duration of administration, number of prescribed courses) was evaluated, as well as patients’ compliance expressed as the ratio of the actual number of taken pills to the number of prescribed pills during each course according to the MMAS-4 scale. Such symptoms, as abdominal pain, constipation, diarrhea, flatulence and tenesmus were evaluated using a 4-score scale. At the end of the study, physicians’ and patients’ satisfaction with the treatment was evaluated using a 5-score scale.Results. One fifth — 52 patients (20.8%)—had received rifaximin-α therapy prior to inclusion in the study. Most frequently, rifaximin-α therapy was prescribed monthly at a dose of 400 mg 2 times a day for 7 days. 67.6% of patients received 6 courses of treatment during the study period. The proportion of patients who received more than one course of treatment over 6 months was 97.6%. During almost all treatment courses (97.5%), patients’ compliance was more than 80%. The total score of symptom intensity decreased from 5.6 at the inclusion visit, to 2.2 points at the second visit and to 0.9 points at the end of the observation. A statistically significant (p

Abstract Background Multiple sclerosis (MS) is a chronic disease that requires lifelong treatment. A highly effective drug not only for relapsing but also for progressive forms of MS with a favorable safety profile is needed to further improve overall patient outcomes. Ocrelizumab, a recombinant humanized monoclonal antibody that selectively targets CD20-expressing B-cells, is the first drug indicated for the treatment of adult patients with relapsing forms of MS (RMS) and primary progressive MS (PPMS). Its safety and effectiveness profile has yet to be studied in a large, real-world setting. CONFIDENCE aims to further characterize the safety profile of ocrelizumab in routine clinical practice. In addition, real-world effectiveness data will be collected to complement the efficacy data documented in the pivotal clinical trials. Methods CONFIDENCE is a non-interventional, prospective, multicenter, long-term study collecting primary data from 3000 RMS and PPMS patients newly treated with ocrelizumab and 1500 patients newly treated with other selected MS disease-modifying therapies (DMTs). Treatment must be in accordance with the local label and follow routine practice. Data will be collected at approximately 250 neurological centers and practices across Germany. The recruitment period of 30 months started in April 2018. The observation period per patient is planned 7.5 to 10 years, depending on the date of inclusion, regardless of whether patients discontinue treatment. Visits follow routine practice and will be documented approximately every 6 months. The primary endpoint is the incidence and type of uncommon adverse events and death. Statistical analyses will be mainly descriptive and exploratory. Discussion CONFIDENCE is a large, non-interventional, post-authorization safety study that assesses long-term safety and effectiveness of ocrelizumab and other DMTs in a real-world setting. Data collected in CONFIDENCE will also be integrated into studies that have been developed to fulfil international regulatory requirements.

BackgroundIn children and adults with acute respiratory tract infections (ARTI), elevations of serum liver enzyme activities are frequently observed in clinical practice. However, epidemiological data particularly in the pediatric population are very limited. The aim of this study was to assess the incidence of hepatic involvement, to identify the viruses and to analyze risk factors in children and adolescents with ARTI in a real-world setting.MethodsWe report on a prospective, multicenter, non-interventional study with 1,010 consecutive patients aged 1–17 years with ARTI who consulted a physician within 5 days after onset of symptoms. Laboratory blood tests and PCR virus detection in nasopharyngeal lavage were performed at first presentation and after 3–7 days. Patients with elevated activities of serum liver enzymes (ASAT, ALAT, and γ-GT) were determined in local laboratories and values were normalized by dividing by the individual upper limit of the normal range (ULN). The resulting index (1 means above ULN) allowed to compare results from laboratories with different reference ranges.ResultsLaboratory test results of 987 patients were available at first visit. 11.1% (95% CI: 9.2–13.3%) exhibited an elevation of ASAT, ALAT, and/or γ-GT activities. Virus DNA or RNA was identified in nasopharyngeal lavages of 63% of the patients. 12.2% of patients with positive PCR and 9.7% of those with negative PCR (p = 0.25) had elevated serum liver enzyme activities. The highest rates were observed in patients with a positive result for influenza B virus (24.4%) followed by human metapneumovirus (14.6%), and human coronavirus (others than SARS-CoV-2) (13.6%). The rate of children and adolescents with ARTI and elevation of serum liver enzyme activities correlated with the virus species and with overweight of the patients but did not differ in patients with or without previous medication intake.ConclusionElevated enzyme activities are present in about 10% of children and adolescents with ARTI. In our cohort, these elevations were mild to moderate; probably resulting from an inflammation process with hepatic involvement.

The multicentre non-interventional AVANTI study assessed safety, effectiveness and patient-reported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice. Eligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians' discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC). Between November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumab–capecitabine were less likely to have de novo disease and more likely to have TNBC, age ≥60 years and prior anthracycline/taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9–13.2) months (12.8 with bevacizumab–paclitaxel, 10.5 with bevacizumab–capecitabine); median OS was 23.9 (95% CI 22.2–25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade ≥3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall. In routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance. • AVANTI assessed 1st-line bevacizumab-based therapy for LR/MBC in routine practice. • Median progression-free and overall survival were 12.6 and 23.9 months respectively. • Treatment satisfaction was rated as good or better by 77% of patients at week 54. • Physician- and patient-rated treatment satisfaction showed high concordance. • Effectiveness and safety were consistent with experience from phase III trials. [ABSTRACT FROM AUTHOR]

Objective: The aim of this investigation was to evaluate the performance of Straumann Bone Level SLActive implants in various clinical situations in daily dental practice for up to 3 years. Method and Materials: This was a prospective, multicenter, non-interventional study in which implants were placed within approved indications in any situation deemed suitable by the treating clinician. No implant placement or loading protocol was specified, and implants were placed according to the routine treatment protocols at each participating center. Results: In this analysis, data were available from 342 implants in 233 patients in three countries (USA, Canada, and Switzerland). One or two implants were placed in the majority of patients (70.8% and 19.3%, respectively), mostly in the maxilla (71.3%); almost half (47.7%) were placed in the esthetic zone. Implant placement after 4 to > 16 weeks of healing was preferred in Switzerland (92.0%), while 42.0% of implants were placed immediately in the USA and Canada. A flapless procedure was performed in 25.2% of cases in the USA and Canada, compared to 0.5% in Switzerland. Cumulative implant survival and success rates after 3 years were 97.5% and 93.5%, respectively. Conclusion: Straumann Bone Level Implants can achieve favorable outcomes and high survival rates after 3 years in daily dental practice. The survival and success rates were comparable with those achieved in formal controlled clinical trials. [ABSTRACT FROM AUTHOR]