Routine Clinical Practice In Europe Research Articles

The safety of a low protein diet in older adults with advanced chronic kidney disease.

A low protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD. The EQUAL study is a prospective, observational study, including patients ≥65 years, incident estimated glomerular filtration rate <20 ml/min/1.73m², in six European countries with follow-up up till six years. Nutritional status was assessed by 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (gram protein/kilogram/bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease by ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights. Out of 1738 adults (631 prescribed LPD at any point during follow-up) there were 1319 with repeated SGA measurements of which 267 (20%) declined in SGA ≥ 2 points and 565 (32.5%) died. There was no difference in survival or decline in nutritional status for patients prescribed LPD ≤0.8 g/kg ideal bodyweight (Odds Ratio (OR) for mortality 1.15 (95% Confidence interval (CI) 0.86-1.55) and OR for decline in SGA 1.11 (95% CI 0.74-1.66) in the adjusted models. In patients prescribed LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and higher age >75 years, lower SGA, and higher comorbidity burden for both mortality and nutritional status decline. In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.

Systematic analysis of combined oral contraceptive prescription patterns in psychotropic drug users across twelve European countries

ObjectiveTo investigate prescription patterns of combined oral contraceptives (COC) among psychotropic drug users compared to non-psychotropic drug users in routine clinical practice in Europe. Study designA pooled analysis of three large, prospective, multinational cohort studies including women with a new prescription of COC from 12 European countries. We calculated standardized mean differences (SMD) to investigate whether the status of psychotropic drug use (use/no use) or the psychotropic drug class (psycholeptics/psychoanaleptics) is associated with the healthcare professional’s choice of a specific type of COC progestin. ResultsOur analysis comprised 143,069 non-psychotropic drug users and 2174 psychotropic drug users. Progestins with the highest frequency in the cohorts were levonorgestrel (non-psychotropic drug users: 33.8%; psychotropic drug users: 32.4%), nomegestrol/nomegestrol acetate (non-psychotropic drug users: 19.1%; psychotropic drug users: 26.4%), and drospirenone (non-psychotropic drug users: 15.9%; psychotropic drug users: 14.8%). SMD analysis indicated no substantial differences in COC prescription patterns between the two cohorts. However, we observed association signals for users of the herbal antidepressant St. John’s wort in that those individuals more often received a prescription for drospirenone and less frequently for nomegestrol/nomegestrol acetate compared to non-psychotropic drug users. ConclusionsPsychotropic drug user status does not seem to affect healthcare professionals’ decisions when prescribing COC. However, limited evidence suggests that the risk for drug interactions might differ by progestin type, and some COC might be more suitable for psychotropic drug users than others. Specific guidelines should be conveyed to healthcare professionals to assist them in contraceptive counseling. ImplicationsWith exception of St. John’s wort, our analysis showed no differential prescription behavior of combined oral contraceptives in psychotropic drug users and non-users. However, healthcare professionals should carefully consider psychotropic drug use in contraceptive counseling as it is still unclear whether drug interactions exist when co-administered with certain oral contraceptives.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry

PurposeTo evaluate the proportion, predictors and outcomes of neovascular age-related macular degeneration (nAMD) patients treated with a high burden of vascular endothelial growth factor (VEGF) inhibitor injections (IVT) after two years in routine clinical practice. DesignRetrospective analysis of data from a prospectively designed observational outcomes registry, Fight Retinal Blindness! project, of patients treated in European centers. ParticipantsTreatment-naïve eyes (one eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed three treatment burden groups defined by the mean interval of the three closest injections to the 24-month visit: (1) those with a high treatment burden had injection intervals ≤ 42 days, (2) those with a low treatment burden had injection intervals between 43 and 83 days and those with tolerable treatment burden had injection intervals between 84 and 365 days. MethodsMultinomial regression was used to evaluate baseline risk predictors of patients requiring a high treatment burden. Main Outcome MeasuresThe proportion of patients that experienced a high treatment burden at 2 years and its predictors. ResultsWe identified 2,038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (Q1, Q3) of 13 (10, 17) injections. The proportion of patients with a high treatment burden was 25% (516 patients) at 2 years. Younger patients (Odds ratio (OR), 0.97; 95%CI, 0.96-0.99; P<0.01) were more likely to have high treatment burden, while eyes with type 3 CNV at baseline were significantly less likely (OR, 0.26; 95%CI, 0.13-0.52; P<0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95%CI, 1.34-11.01; P=0.01) and persistent active intraretinal (OR, 1.56; 95%CI, 1.18-2.06; P<0.01) or subretinal fluid only (OR, 2.21; 95%CI, 1.52-3.21; P<0.01) after the loading phase had a higher risk of high treatment burden at 2 years. ConclusionsHigh treatment burden is common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40 percent discontinuing treatment within 2 years.

Interim Baseline Characteristics of Adult Patients with Immune Thrombocytopenia Enrolled in the Observational Multicenter Phase 4 Adopt Study to Evaluate the Use and Effectiveness of Avatrombopag

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts and increased bleeding rate. Current first-line ITP treatments include corticosteroids and immunoglobulins. If first-line therapy fails, subsequent treatment options include the thrombopoietin receptor agonists (TPO-RAs). Avatrombopag (AVA), the most recently approved TPO-RA, is a small molecule, administered orally with no food-type restrictions, and no significant hepatotoxicity. AVA was approved by FDA in 2019 and EMA in 2021, for the treatment of chronic ITP in adult patients who are refractory to other treatments. The Phase 4 ADOPT study (NCT04943042) will generate data on the real-world effectiveness and safety of AVA in routine clinical practice in Europe. Described here are the interim baseline characteristics of patients enrolled in the ADOPT study. Study objective and methods: ADOPT is a multicenter, observational study with the primary objective to describe the real-world effectiveness of AVA treatment over a prospective period of 12 months. Prospective data will be collected at routine clinical visits. In addition, retrospective data will be collected from patients' medical records for up to 12 months prior to AVA treatment start. Eligible patients must be ≥18 years of age, have provided informed consent, have an established and well documented ITP diagnosis, and are treated with, or initiating treatment with AVA for ITP, at enrollment. Exclusion criteria include enrollment in other clinical interventional studies, or intake of an investigational medicinal product, ≤3 months prior to inclusion. The primary endpoint is the cumulative number of weeks with a platelet count ≥30×10 9/L. Platelet counts during rescue medication use and within 4 weeks after stopping a rescue medication or following splenectomy are considered non-response and thus not included in the primary endpoint cumulative number. Secondary endpoints supporting the primary objective include cumulative number of weeks with a platelet count ≥50×10 9/L, patients (n [%]) with a platelet count ≥30×10 9/L and ≥50×10 9/L for at least 8 consecutive weeks, patients (n [%]) experiencing WHO bleeding grade ≥2, patients (n [%]) requiring rescue medication, and time from AVA treatment start to platelet count ≥30×10 9/L and ≥50×10 9/L. Additional secondary endpoints are AVA dose and dosing frequency, reason for ITP treatment discontinuation or change from one ITP treatment to another (prior to and during the study), use of concomitant ITP medications, physicians' satisfaction with outcome of AVA treatment (5-point scale), physician assessment of clinically meaningful effects (Clinical Global Impression of Change scale), healthcare resource use, as well as a number of patient reported outcomes (PROs). Secondary safety endpoints include serious adverse events and adverse events of special interest (thromboembolic events [TEEs] and significant bleeding events). Results: Fifty-six patients have been enrolled in the study as of July 2023, and demographic and baseline characteristics information were available for 39 patients (Table 1). The mean age (SD) was 52.2 (18.10) years and 20 patients were male (51.3%). Nine patients had a baseline PC &amp;lt;30x10 9/L. Eight patients (20.5%) reported newly diagnosed/persistent ITP with &amp;lt;12 months disease duration since diagnosis; 31 (79.5%) had chronic ITP. A majority of patients (n=22; 56.4%) had no previous exposure to TPO-RAs. One patient was splenectomized (2.6%), and seven had experienced prior TEEs (17.9%). Conclusions: This baseline interim data set from the ADOPT Phase 4 study provides important insight into the types of ITP patients who are being prescribed avatrombopag across European centers. More than half of enrolled patients were TPO-RA naïve, and over 20% did not have chronic ITP although the mean duration of ITP was 7.6 years and median duration of 4 years at the time of first AVA treatment. Though previous clinical trials excluded patients with newly diagnosed/persistent ITP and prior TEEs, this real-world evidence study does not exclude such patients. We look forward to presenting safety and efficacy data, as well as multiple PROs, from this observational study at future scientific meetings. Study status: The study was initiated in January 2022, will include approximately 60 sites in Europe, and enroll 150 patients in total.

Lipid management in patients with high and very high cardiovascular risk: Data from routine clinical practice in Europe (SANTORINI study)

Lipid management in patients with high and very high cardiovascular risk: Data from routine clinical practice in Europe (SANTORINI study)

213P Real-world clinical outcomes associated with first-line palbociclib and aromatase inhibitor therapy among patients with HR+/HER2- advanced breast cancer in Europe

Palbociclib (PB), a cyclin-dependent kinase 4/6 inhibitor, has become a standard of care in HR+/HER2- advanced/metastatic breast cancer (ABC) in Europe since EMA approval in 2016. This study examines clinical characteristics and outcomes in ABC patients treated with PB and an aromatase inhibitor (AI) in routine clinical practice in Europe. A multicenter retrospective medical record review collected data on adult patients with HR+/HER2- ABC in Europe who received first-line PB+AI between September 2016 and July 2020. Sites screened all patients who received PB+AI during the study time frame and abstracted data for patients who met all eligibility criteria. We report here results from Germany, Spain and the UK; data from 4 additional European countries will be reported when data collection is complete. Study measures were descriptively analyzed, with the Kaplan-Meier method used to estimate real-world progression-free survival (rwPFS). Data were abstracted and analyzed for 668 patients from 47 sites. Median age at ABC diagnosis was 64.4 years (33.8% ≥70 yo), 99.6% were female, 82.9% were white, and median follow-up was 32.7 months. Of females (665), 14.1% were premenopausal at first-line PB+AI initiation. 38.5% of patients had de novo disease. At ABC diagnosis, 24.9% had bone only disease and 46.7% had visceral disease (Table). Objective response and clinical benefit rate were 35.8% and 80.7%, respectively. The median rwPFS (95% CI) was estimated to be 31.8 (27.7-35.4) months (Table). Table: 213PN%Total number of patients668100.0Age (years) at ABC diagnosis<5010115.150-6934151.1≥7022633.8Clinical stage at initial BC diagnosisStage I–III (resectable)38056.9Stage III–unresectable182.7Stage IV23935.8Unknown314.6Disease-free intervalDe novo25738.5≤12 months15222.8>12 months22133.1Unknown385.7Performance status at first-line016124.1117626.3≥2588.7Not recorded27340.9Objective response rate23935.8rwPFS, Kaplan–Meier estimateMonths (95% CI)Median31.8 (27.7-35.4)rwPFS rate% (95% CI)12 months77.2(73.8-80.3)24 months59.5(55.5-63.2)36 months45.2(41.0-49.4) Open table in a new tab This real-world study affirms the favorable clinical outcomes demonstrated for first-line PB+AI in the previous clinical trials and supports its utilization as frontline treatment for this patient population. This study presents pooled analysis of 3 European countries and variability in practice patterns and disease management may exist among countries.

A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers

PurposeThe combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT.MethodsA questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods.ResultsThe response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3–100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter “cumulative equivalent minutes at 43 °C” (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order.ConclusionThere is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

Initiation of bone-targeted agents in patients with bone metastases and breast or castrate-resistant prostate cancer actively treated in routine clinical practice in Europe.

Guidelines recommend starting bone-targeted agents (BTA), such as zoledronic acid and denosumab, as soon as bone metastases (BMs) are definitively diagnosed in all patients with breast cancer (BC) or castration-resistant prostate cancer (CRPC) whether they are symptomatic or not. Data were analyzed from 1364 patients with BC and 1161 patients with CRPC who had BMs and were receiving anti-cancer therapy in hospitals across six European countries (Belgium, France, Germany, Italy, Spain and the UK). The 731 physicians (medical oncologists or urologists) provided insights in the decision-making factors driving their management of bone health for these patients, and the patient medical records indicated how these decisions were reflected in routine clinical practice. Within three months of a BM diagnosis, 74% of BC and 51% of CRPC patients had initiated treatment with a BTA. Around 12% of BC and 23% of CRPC patients did not receive a BTA following BM diagnosis. Irrespective of the tumour type (BC or CRPC), most physicians prescribed either denosumab or zoledronic acid as first BTA therapy. Physicians reported bone pain as a major decision-making factor to initiate a BTA. The presence of bone complications at BM diagnosis and bone pain at BM diagnosis were found to be significant predictive factors for a BTA initiation, irrespective of tumour type. Despite European Society for Medical Oncology (ESMO) guidance on bone protection irrespective of symptomatic disease, not all patients with BMs received a BTA following a BM diagnosis. This suggests that clinical judgements and patients' communication of their pain to their physicians contributed to the decision to prescribe bone protection therapy in cancer patients.

A European, multicentre, observational, post-authorisation safety study of oral sulphate solution: compliance and safety.

Background and study aims Oral sulphate solution (OSS) is a sulphate-based, low-volume bowel cleansing preparation taken in two doses of 500 mL, each followed by 1000mL of water or clear liquid. The primary objective of this observational study was to document compliance with the recommended hydration guidelines in a representative sample of the European population. Patients and methods Prospective, non-interventional, multicentre study (NCT02630680, EUPAS9361) in patients prescribed OSS for colonoscopy preparation in routine clinical practice in Europe. Patients were included according to pre-agreed consecutive enrolment rules. Patients recorded the volume of OSS and water or clear liquid intake, and occurrence of adverse events (AEs). Compliance with hydration was calculated as a ratio of actual volume of water/clear liquid taken versus prescribed 2,000 mL, and non-compliance defined as < 75 % intake. Colon cleansing level was assessed on a 4-point scale. Results Between October 2015 and January 2017, 1,281 patients were recruited in 16 centres in four European countries (safety population n = 1,206; registry population n = 1,177). Of patients, 94.5 % were ≥ 75 % and 86.8 % 100 % compliant with hydration guidelines. Patients took an average of 96.8 % of the recommended OSS volume; 46 patients (3.9 %) were non-compliant. Colon cleansing levels were good-to-excellent in 87.6 % of patients. Three hundred and twenty-nine patients (27.3 %) experienced 758 treatment-related AEs, mostly gastrointestinal (82.9 %), all were mild-to-moderate. Non-compliant patients had no AEs suggestive of dehydration. Conclusion In this non-interventional study in a real-life setting, treatment compliance with hydration guidelines was good-to-excellent in 94.5 % of patients receiving OSS. The safety profile of OSS was similar to the prescribing information. TRIAL REGISTRATION: Observational study EUPAS9361 at www.encepp.eu

Cardiovascular (CV)-Related Hospitalizations and Associated Costs Among US Patients in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in Routine Clinical Practice

Cardiovascular (CV)-Related Hospitalizations and Associated Costs Among US Patients in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in Routine Clinical Practice

Cytogenetic and Molecular Response with First- and Second-Generation Tyrosine Kinase Inhibitor (TKI) Therapy in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML)

Introduction: SIMPLICITY (NCT01244750) is an ongoing observational study of patients (pts) with CP-CML receiving first-line (1L) imatinib (IM), dasatinib (DAS), or nilotinib (NIL) in routine clinical practice in Europe and the United States (US). The study aimed to assess the effectiveness and safety of TKIs for pts with CP-CML outside the clinical trial setting. Here, we analyze the clinical outcomes (complete cytogenetic response [CCyR] and major molecular response [MMR]) associated with the CML risk level in SIMPLICITY pts with CP-CML receiving first-generation (1G: IM) or second-generation (2G: DAS/NIL) TKI therapy. Methods: Clinical outcomes after 1L TKI initiation were assessed by CyR (karyotype analysis or fluorescence in situ hybridization) and polymerase chain reaction MR tests. Proportions of pts achieving CCyR and MMR are presented for those with at least one recorded response test during 1L TKI therapy. Outcomes were stratified by CML risk level (Hasford scoring; low [≤780] and intermediate/high risk [≥781]), and the differences between 1L 1G and 2G TKI cohorts analyzed. Statistical comparisons for continuous variables were made using t-tests and the Mann-Whitney U test, and chi-square test for categorical variables. Multivariate logistic regression models, adjusted for age, gender, region, risk level (low vs intermediate/high), and baseline (BL) comorbidities, were used to determine if generation of TKI therapy (1G/2G) was associated with clinical response (CCyR or MMR) after start of 1L TKI. Performance and timing of CyR and MR tests were at the discretion of oncologists, limiting the analysis of outcomes and comparisons of CCyR and MMR rates. Results: There were 1,241 pts (IM: n=416; DAS: n=417; NIL: n=408) at database lock (October 2018); only 391 (31.5%) pts with CP-CML receiving 1L TKI were identified to have the elements needed for a Hasford risk assessment documented at diagnosis (IM: n=140; DAS: n=119; NIL: n=132). CML risk assessment (Hasford score) was significantly more common in Europe (68.7% vs 11.7% in the US, p&lt;0.0001). No significant difference in risk score was observed across the different 1L TKI groups (p=0.7012). Of the 130 (33.2%) pts with recorded CyR test results, no significant differences in BL demographics were observed except for median age at start of 1L TKI and BL cardiovascular and gastrointestinal (GI) comorbidities (Table 1). A higher percentage of pts on 2G TKIs achieved CCyR compared with 1G TKI in both low (88.1% vs 79.2%) and intermediate/high (73.0% vs 44.4%) CML risk categories, with statistical significance reached in the intermediate/high-risk group (p=0.0209). Multivariate logistic regression analysis (Figure 1) showed that pts were approximately 3 times more likely to achieve CCyR if receiving 2G TKIs (odds ratio [95% confidence interval]: 2.93 [1.21, 7.13] vs 1G, p=0.0177). Other predictors of CCyR were low baseline CML risk (5.75 [2.00, 16.50] vs intermediate/high CML risk, p=0.0011) and treatment at European centers (2.72 [1.03, 7.18] vs US centers, p=0.0431). MR test results were recorded in 358 (91.6%) pts; median number of MR tests was significantly higher in Europe (8 vs 5 in the US, p&lt;0.0001). No significant differences in pt demographics were observed except for age at start of 1L TKI and BL GI comorbidities (Table 1). A higher percentage of pts on 2G TKIs achieved MMR compared with 1G TKI in the low (82.0%vs 74.6%) and intermediate/high (87.0% vs 72.4%) CML risk groups, with significance reached in the latter cohort (p=0.0185). Multivariate logistic regression analysis showed that TKI generation was the sole predictor of MMR achievement; pts were approximately twice as likely to achieve MMR with 2G TKIs as with 1G TKI (OR: 2.13 [1.23, 3.70], p=0.0070) (Figure 1). Conclusions: Despite treatment guidelines recommending 2G TKI therapy for pts with higher CML risk, our analysis of SIMPLICITY pts showed no differences in 2G versus 1G TKI use in low and intermediate/high risk groups. Here, the use of 2G TKIs, compared with 1G TKI, was a significant predictor for achieving either CCyR or MMR, thereby validating the clinical response benefits of 2G TKIs regardless of BL CML risk. These findings emphasize the importance of adhering to treatment guidelines when making decisions on the generation of TKI, first (IM) or second (DAS/NIL), to be used in the 1L treatment of pts with CP-CML, particularly in higher risk pts. Disclosures Cortes: Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Sun Pharma: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; BiolineRx: Consultancy. Chen:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment, Equity Ownership. Goldberg:Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; COTA: Equity Ownership; Bristol-Myers Squibb: Consultancy. Mauro:Bristol-Myers Squibb: Consultancy; Novartis Oncology: Consultancy, Research Funding; Takeda: Consultancy; Pfizer: Consultancy.

Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe.

AimTo evaluate the impact of Vesomni/Urizia/Volutsa, a fixed‐dose combination tablet containing 6 mg solifenacin (antimuscarinic) and 0.4 mg tamsulosin (α‐blocker), on health‐related quality of life (HRQoL) and treatment satisfaction in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in routine clinical practice.MethodsEUROPA was a noninterventional study of men with LUTS/BPH not responding to monotherapy who were prescribed Vesomni in routine clinical practice. Data were collected retrospectively (1 year) and prospectively (1 year). Assessments were performed at baseline, weeks 4 to 8, weeks 9 to 18 (optional), weeks 19 to 39 (optional), and Weeks 40 to 52. The primary endpoint was change from baseline in HRQoL, as assessed by the Overactive Bladder Questionnaire (OAB‐q) symptom bother subscale score. Change from baseline in OAB‐q total and coping, sleep, and social interaction subscale scores, treatment satisfaction‐visual analog scale (TS‐VAS), International Prostate Symptom Score (IPSS), and European Quality of Life 5‐Dimension‐5‐Level (EQ‐5D‐5L) questionnaire were also evaluated.ResultsFive hundred and eighty‐nine patients were enrolled. The mean changes in adjusted mean (95% confidence interval [CI]) OAB‐q symptom bother subscale scores were −16.40 (−24.31, −8.49) at weeks 4 to 8 and −19.59 (−28.26, −10.92) at weeks 40 to 52; at weeks 40 to 52, changes were clinically meaningful in 84.6% of patients. Adjusted mean (95% CI) change from baseline to weeks 40 to 52 were 15.02 (7.35, 22.69), 19.37 (10.86, 27.89), 18.65 (7.44, 29.86), 9.85 (3.90, 15.81), and 16.09 (9.07, 23.11) for concern, coping, sleep, social interaction, and total, respectively. TS‐VAS, IPSS, and EQ‐5D‐5L all improved, and treatment persistence at weeks 40 to 52 was 77.1%. Urinary retention was reported in four (0.7%) patients.ConclusionsVesomni was well‐tolerated and improved HRQoL and treatment satisfaction in patients with LUTS/BPH.

Relationship of glycaemic control and hypoglycaemic episodes to 4-year cardiovascular outcomes in people with type 2 diabetes starting insulin.

AimsTo examine the relationships between glycated haemoglobin (HbA1c) and cardiovascular (CV) events in people beginning insulin in routine clinical practice in Europe, North America and Asia in a non‐interventional study, the Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy (CREDIT) study.MethodsData on 2999 people were collected prospectively over 4 years from physician reports. The primary outcome was the composite of stroke or myocardial infarction (MI) or CV‐specific death. Events were blindly adjudicated. The relative hazards of CV events were described from Cox proportional hazards models incorporating patient risk factors, with updated average HbA1c as a time‐dependent covariate. The relationship of severe and symptomatic hypoglycaemia (collected during the 6 months before yearly ascertainment) with CV and all‐cause mortality was examined.ResultsA total of 147 primary events were accrued during up to 54 months of follow‐up. In all, 60 CV‐specific deaths, 44 non‐fatal MIs and 57 non‐fatal strokes occurred, totalling 161 events. There was a significant positive relationship between updated mean HbA1c and primary outcome: hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.12–1.40; p < 0.0001]. CV death [HR 1.31 (95% CI 1.10–1.57); p = 0.0027] and stroke [HR 1.36 (95% CI 1.17–1.59); p < 0.0001] were both strongly associated with HbA1c, while MI was not [HR 1.05 (95% CI 0.83–1.32)]. One or more severe hypoglycaemic episodes affected 175 participants, while 1508 participants experienced one or more symptomatic hypoglycaemic events. We found no relationship between severe/symptomatic hypoglycaemic events and CV‐specific/all‐cause death.ConclusionsOngoing poorer glucose control was associated with CV events; hypoglycaemia was not associated with CV‐specific/all‐cause death.

AB0532 Effect of prior therapy on the efficacy and safety of abatacept: 6-month analysis of the action study

BackgroundRandomized controlled trials have demonstrated the long-term efficacy and favourable safety of abatacept (ABA) in RA patients (pts).1 Previously we reported 6-month (mth) results of an interim analysis of German...

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures. Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥ 3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39). The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.

Coronary endothelial function: a clinical role for PET?

Coronary endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis and is also independently associated with future cardiac events. Quantification of myocardial blood flow (MBF) can assist in the diagnosis of diffuse coronary artery disease (CAD), heart failure and microvascular disease [1, 2]. In the absence of coronary stenoses, a reduced coronary flow reserve (CFR) reflects dysfunction of the coronary microcirculation. Positron emission tomography (PET) plays an important role in the assessment of MBF due to four major characteristics: (1) high sensitivity, (2) excellent temporal resolution, (3) the possibility to label molecules without altering their chemical properties and (4) the short half-life of isotopes. The most common method of quantifying MBF involves the acquisition of dynamic images with the cyclotron-produced radiopharmaceuticals 13N-ammonia and 15O-water. An alternative method is the generator-produced 82Rb. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yoshinaga and colleagues present some interesting data comparing the quantitative analysis of coronary endothelial function with 82Rb and 15O-water PET [3]. MBF was assessed at rest and during a cold pressor test (CPT) with 82Rb and 15O-water PET in controls and smokers. They found a reduced CPT to rest ratio in smokers compared with controls for both radiopharmaceuticals. They concluded that 82Rb is a reliable method in comparison to 15O-water PET and that 82Rb may be applicable for risk assessment in subjects with coronary risk factors. The usefulness of 82Rb is proven in this study; however, the study included in total 19 subjects, and there will be a need for studies with larger sample sizes. A wide pallet of pathological disorders like hyperlipidaemia, hypertension, diabetes and smoking attenuate the vasomotor response to NO and reveals the widespread distribution of underlying causes that can result in endothelial dysfunction. In other words, MBF assessment provides a way to document how risk factors translate into measurable damage to the coronary circulation. In my opinion, it is time to get MBF PET ready for the future, because of the open access to 82Rb now in Europe. The use of 82Rb would give advantages compared to 13N-ammonia and 15O-water PET: no need for a cyclotron, 24-h/day access, fast acquisition protocols allowing high throughput, evaluation of stunning by using rest and stress gating modality and a better visual quality compared to 15O-water. Also absolute quantification of MBF is possible with 82Rb and validated [4, 5] and the important parameter of CFR for prognosis can be calculated [6]. Due to the wide range of the 82Rb positron, the resolution is reduced. An important issue of concern is the cost-effectiveness of 82Rb, especially compared to the widely used SPECT technique. The 82Rb generator needs to be replaced every 4–6 weeks, rendering this technique relatively expensive, with a price in the region of 25,000 euros. Industry should put maximal effort into reducing the price of the generator, so that 82Rb may finally facilitate a breakthrough of cardiac PET myocardial perfusion imaging (MPI) for routine clinical practice in Europe. The first studies on the clinical utility of 82Rb MPI were reported almost 25 years ago [7], and accurate data of 82Rb MPI are available in the literature linked to outcomes [8, 9]. Although 82Rb is now widely available in the USA, this tracer is moderately available in Europe; however, a dawn is coming. Industrial 82Rb supply for Europe is growing and may lead to a wider implementation of 82Rb. Nevertheless, and although the use of 82Rb has been already described in a number of reports in the literature, the merit of the present study is that it encourages us to benefit from the substantial superiority of the PET technique for instance over SPECT, resulting in good image quality even in obese patients. The superiority over SPECT can be expected regarding accuracy, study duration, staff radiation exposure, reduced patient dose, patient discomfort and potentially economic benefit. These are all important implications, which may not have been fully appreciated in Europe so far. A clinical role of MBF PET should be highlighted now, because of the easier access to 82Rb.

The Cost of Relapse for Patients with a Manic/Mixed Episode of Bipolar Disorder in the EMBLEM Study

Bipolar disorder (BD) is characterized by episodes of mania and depression. The debilitating symptoms during an acute episode require intensive treatment, frequently leading to inpatient psychiatric care, which places significant demands on health and social care systems and incurs substantial costs. However, no study to date has estimated the economic impact of relapse. To estimate the direct costs associated with relapse in the treatment of BD following an acute manic or mixed episode over a 21-month follow-up period in routine clinical practice in Europe, using data from a large, prospective, observational study. EMBLEM was a prospective, observational study on the outcomes of patients with a manic/mixed episode of BD conducted in 14 European countries. Patients eligible for analysis were those enrolled in the 21-month maintenance phase of the study, following the 3-month acute phase. Relapse was defined as achieving any one of the following criteria: (i) at least a one-point increase in Clinical Global Impression - Bipolar Disorder (CGI-BP) overall score from the previous visit, with a final rating of > or =4; (ii) inpatient admission for an acute episode of BD; or (iii) psychiatrists' confirmation of relapse. Data on healthcare resource use were recorded retrospectively for the four respective periods (3-6, 6-12, 12-18 and 18-24 month visits). Multivariate analyses were performed to compare the cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who relapsed during the 21-month maintenance phase and those who never relapsed. A sensitivity analysis was also conducted to examine the 6-month costs during relapse. The analyses were adjusted for patient characteristics and took account of non-Normality of the cost data by using a log link function. UK unit costs were applied to resource use. The analysis was repeated after multiple imputation for missing data. All costs were presented as year 2007/08 values. A total of 1379 patients completed all visits during the maintenance phase and were eligible for inclusion in the present analysis. Of these, over half (54.3%) experienced relapse during this period. A total of 792 patients without any missing data were eventually included in the final cost model. Costs incurred by patients who relapsed during the 21-month maintenance phase were approximately double those incurred by patients who never relapsed (pounds sterling 9140 vs pounds sterling 4457; p < 0.05). Of the cost difference, 80.3% was accounted for by inpatient stay. Estimates on the economic impact were higher (pounds sterling 11,781 vs pounds sterling 4789; p < 0.05) in the additional analysis with imputed missing data. The impact of relapse was even greater in the 6-month cost comparison. The average 6-month costs for patients who relapsed were found to be about three times higher than for those who did not relapse (pounds sterling 4083 vs pounds sterling 1298; p < 0.05). Our findings confirm the significant economic impact of relapse in BD patients after an acute manic or mixed episode, even when considering direct costs only. Such costs were dominated by inpatient stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and the associated costs will differ by country.

Effectiveness and safety of recombinant human erythropoietin beta in maintaining common haemoglobin targets in routine clinical practice in Europe: the GAIN study

ABSTRACTObjective: The Gain effectiveness in Anaemia treatment wIth NeoRecormon (epoetin beta) study (GAIN) evaluated the effectiveness and safety of recombinant human erythropoietin beta in correcting and/or maintaining common haemoglobin (Hb) targets in routine clinical practice in Europe.* NeoRecormon is a registered trade name of F. Hoffmann-La Roche, Basel, SwitzerlandResearch design and methods: European 18-month observational, prospective clinical practice study across 217 centres from 13 countries. During a 3-month retrospective period, patients received any erythropoiesis stimulating agent (ESA). For the subsequent 18-month study phase, patients receiving intravenous (IV) epoetin beta or any other ESA were recommended to be switched to subcutaneous (SC) epoetin beta. Presence of anti-erythropoietin antibodies (AEAB) and related outcomes was investigated before and during the study.Clinical trial registration: ClinicalTrials.gov number: NCT00551603.Main outcome measures: Correction and maintenance of Hb levels within recommended target range and mean dose requirement to correct and maintain target Hb levels.Results: A total of 4264 patients on haemodialysis received an ESA for treatment of renal anaemia. During the study period, the number of patients who maintained Hb levels in the recommended target range of 10–12 g/dL increased from 57% to 62%. Administration of SC epoetin beta resulted in a 24% lower mean dose requirement to maintain target Hb levels compared to IV administration (p < 0.001). Considerable differences were observed between countries in the study. No patients developed pure red cell aplasia associated with AEAB during observation.Conclusion: This observational study suggests that haemodialysis patients who are receiving any ESA via SC or IV administration for treatment of their renal anaemia can be safely and effectively switched to SC epoetin beta to achieve or maintain the currently recommended Hb targets. SC required a lower dose than IV administration to maintain similar efficacy, thereby potentially lowering the drug costs.Trial registration: ClinicalTrials.gov identifier: NCT00551603.

Acute stroke: we have the treatments and we have the evidence – we need to use them

Despite huge global burden, stroke disease has traditionally received little attention in the general medical press. We review a series of four acute stroke research articles published in a themed issue of the Lancet. Claiborne-Johnston and coworkers presented a scoring system to stratify risk of stroke following transient ischaemic attack. Chalela and colleagues demonstrated that magnetic resonance imaging is superior to computed tomography in detecting acute ischaemic stroke and that fears of missing intracranial haemorrhage are unfounded. The SITS-MOST (Safe Implementation of Thrombolysis in Stroke – Monitoring Study) group reported positive experience of translating acute stroke thrombolysis trials into routine clinical practice in Europe, and the PROSIT (Project on Stroke Services in Italy) group studied acute effects of admission to a dedicated stroke unit. The message from all of these reports is that evidence-based, successful management of acute stroke is possible, and that investment in health infrastructure and changing mind sets of health practitioners to improve stroke care will deliver benefits.