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Objective The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). Methods A keyword-based literature search was conducted, and 26 publications were included. Results Overall, 7–31% of patients had LN at SLE diagnosis; 31–48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40–76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3–11% and 6–19%, respectively, in patients with SLE and LN. Conclusions Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

Background and Aims Anaemia is a frequent complication in patients with chronic kidney disease (CKD). The aim of this literature review was to understand the prevalence and burden of anaemia associated with CKD, with a further focus on Europe. Method A targeted literature review was conducted to identify publications on prevalence estimates (search: January 2015 to August 2018), and a systematic literature review was performed to identify publications on humanistic and healthcare resource use (HRU) burden (search: from database inception to July 2018) using MEDLINE®, Embase®, Cochrane Library, and conference proceedings. These were complemented by grey literature searches. Citations were screened per predefined criteria to include observational studies and reviews. Case series/reports and conceptual model studies were excluded. The study population included patients with anaemia associated with CKD, irrespective of CKD stage, dialysis status, or modality. All searches were funded by GSK. Results After applying all inclusion and exclusion criteria, 18 publications were retained that contained prevalence data, of which 9 provided European data. Based on 9 publications, the prevalence of anaemia associated with CKD in European adults was reported to range from 12.8% to 61.5% (Figure). Prevalence was higher in older individuals (aged >60 years) and increased with more advanced CKD stages. However, the methodology used to identify anaemia was not consistent across studies. Anaemia was identified based on varying thresholds of haemoglobin (Hgb) levels per different clinical guidelines (Kidney Disease Improving Global Outcomes [KDIGO], N=4; World Health Organization [WHO], N=2; European Best Practice Guidelines [EBPG], N=3), use of anaemia treatment, or Hgb thresholds without a reference to a specified guideline. Most studies focused on later-stage CKD patients (3 − 5), with only 2 studies reporting rates for stage 1 and 2 patients. A total of 50 publications provided data on humanistic and HRU burden, 6 of which provided European data. The literature on humanistic and HRU burden showed adults with anaemia associated with CKD had significantly poorer health-related quality of life (HRQoL) compared with those without anaemia, with significantly lower Kidney Disease Quality of Life (KDQoL) scores reflecting poorer HRQoL observed in the following domains: symptoms/problems, effect of kidney disease, and burden of kidney disease. This finding was consistent irrespective of instrument used for HRQoL assessment. However, tools used were not specific to anaemia or anaemia associated with CKD, and publications did not mention whether thresholds for clinical meaningfulness had been identified and/or met. Publications on HRU in anaemia associated with CKD in Europe were sparse (N=1): this single published study reported increased HRU in CKD patients with anaemia compared with CKD patients without anaemia. Conclusion Prevalence rates of anaemia associated with CKD reported in Europe vary, with increased prevalence in later stages of CKD. Anaemia negatively impacts patient QoL and leads to increased HRU in patients with CKD. More data are needed to characterise anaemia in earlier stages of CKD and across different populations (e.g. patients with particular comorbidities or undergoing different types of dialysis) in European countries. Due to varied definitions of anaemia, it would be of interest to evaluate the extent of underdiagnosis and its impact on prevalence rates.

A systematic literature review was conducted to quantify populations of patients with primary breast cancer in whom bone metastases were detected at study start or during follow-up. Searches were performed in PubMed and EMBASE using terms related to breast cancer and bone metastases. Articles had to have been published 01/01/99–31/12/13, and to report data on the proportion of patients with bone metastases among patients with breast cancer. In total, 156 articles were included in the meta-analysis. A median of 12% of patients with stage I–III breast cancer developed bone metastases during a median follow-up of 60 months. Of patients who developed metastatic disease during follow-up, 55% (median) had bone metastases. Of those with metastatic breast cancer at study start, 58% (median) had bone metastases. These data help to inform on the global burden of bone metastases by defining patient populations that are at risk of developing bone metastases., SCOPUS: re.j, info:eu-repo/semantics/published

Background Traditional methods for assessing prescriber knowledge can take several years to deliver results. This study was undertaken to obtain insights into the potential for using existing online communities to educate prescribers on therapy-related safety risks. Objective The aim of this study was to describe approaches to measuring prescribers’ knowledge of safety risk (osteonecrosis of the jaw) outlined in the European Medicine Agency’s summary of product characteristics for denosumab (XGEVA®). Methods Short multiple-choice online instruments were administered as (1) a two-round cross-sectional survey fielded in January 2013–May 2015 (traditional, nine European countries, study duration: 3 years), (2) a survey targeting the online Medscape community (seven European countries, study duration: 3 weeks), and (3) a continuing medical education module with pre-/post-assessment in an online Medscape community (Medscape Education, USA). All respondents were oncologists; treated five or more patients with bone metastases from solid tumours in the previous 3 months; and prescribed denosumab within the previous 12 months. Medscape (a WebMD company, New York, NY, USA) is the leading online medical information resource, serving approximately 3 million physicians worldwide and 400,000 within Europe. Results In the traditional 29-month study, 420 (n = 210 per round; 14% of screened physicians) individuals participated. Knowledge levels exceeded 75% correct on five questions (incidence of osteonecrosis of the jaw, concomitant risk factors and prevention of osteonecrosis of the jaw during denosumab treatment, importance of ensuring oral hygiene, and care for patients who have or develop osteonecrosis of the jaw) with less awareness of optimal osteonecrosis of the jaw treatment. The Medscape survey (n = 207; 32.1% of 645 eligible) provided similar results in a 3-week post-survey launch. The Medscape Education study (n = 264) documented knowledge acquisition. Conclusions Assessments that target physicians through online platforms where they seek information about drug-related safety risks may result in increased efficiencies, informing regulators about prescribers’ knowledge of safe use within weeks rather than years. Online communities or professional societies may provide venues in which to implement knowledge-acquisition surveys tied to training/education modules that address safety topics. Electronic supplementary material The online version of this article (doi:10.1007/s40290-017-0196-4) contains supplementary material, which is available to authorized users.

Purpose Unaffected women who carry BRCA1 or BRCA2 mutations face difficult choices about reducing their breast cancer risk. Understanding their treatment preferences could help us improve patient counseling and inform drug trials. The objective was to explore preferences for various risk-reducing options among women with germline BRCA1/2 mutations using a discrete-choice experiment survey and to compare expressed preferences with actual behaviors. Methods A discrete-choice experiment survey was designed wherein women choose between hypothetical treatments to reduce breast cancer risk. The hypothetical treatments were characterized by the extent of breast cancer risk reduction, treatment duration, impact on fertility, hormone levels, risk of uterine cancer, and ease and mode of administration. Data were analyzed using a random-parameters logit model. Women were also asked to express their preference between surgical and chemoprevention options and to report on their actual risk-reduction actions. Women aged 25–55 years with germline BRCA1/2 mutations who were unaffected with breast or ovarian cancer were recruited through research registries at five clinics and a patient advocacy group. Results Between January 2015 and March 2016, 622 women completed the survey. Breast cancer risk reduction was the most important consideration expressed, followed by maintaining fertility. Among the subset of women who wished to have children in future, the ability to maintain fertility was the most important factor, followed by the extent of risk reduction. Many more women said they would take a chemoprevention drug than had actually taken chemoprevention. Conclusions Women with BRCA1/2 mutations indicated strong preferences for breast cancer risk reduction and maintaining fertility. The expressed desire to have a safe chemoprevention drug available to them was not met by current chemoprevention options. Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4332-3) contains supplementary material, which is available to authorized users.

Background Organ system involvement in systemic lupus erythematosus (SLE) is highly variable. Better understanding of the symptom and organ involvement patterns in patients with SLE may facilitate making more accurate prognoses and individualized management decisions. This analysis aimed to categorize patients with SLE into clusters according to their organ system involvement. Methods This was a secondary, descriptive analysis (208683) that utilized survey data collected from adult patients with SLE and their physicians, enrolled in the 2015 Adelphi Real World Disease Specific Programme (US and Europe) (205086). Latent class modeling based on current organ involvement was used to generate clusters of patients with similar manifestations; characteristics of each cluster were compared using the chi-square test for categorical variables and Kruskal-Wallis test for ordered/numeric outcomes. Results Overall, 1376 patients (n=1196 [87.0%] female; mean [standard deviation (SD)]) age, 42.1 [13.6] years) were included in the analysis. Four patient clusters were generated: Cluster 1 (n=250, 18.2%), lowest overall organ burden (predominantly mucocutaneous); Cluster 2 (n=670, 48.7%), joint and skin SLE (predominantly mucocutaneous and musculoskeletal) with limited renal/hematologic involvement; Cluster 3 (n=150, 10.9%), highest frequency of renal/hematologic involvement; Cluster 4 (n=306, 22.2%), highest frequency of mucocutaneous, musculoskeletal, constitutional, cardiorespiratory and neuropsychiatric involvement, but without renal involvement. Key results are summarized in the table 1. Significant between-cluster differences were observed for disease severity (p Conclusions This analysis provides important insights on potential clinically meaningful subsets of SLE (per organ system involvement) using real-world evidence. The highest disease burden was observed in Clusters 3 and 4, confirming the extensive impact of SLE irrespective of renal involvement. Limitations included the absence of serological findings or disease activity indices for cluster formation or comparison. Funding Source(s): Study funded by GlaxoSmithKline; ownership of data retained by Adelphi Real World.

Background Despite recent advances in the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), understanding of their pathogenesis and the interrelation between disease states remains incomplete. A pragmatic review (GSK study LS3178) was conducted to map disease severity and progression of renal involvement in SLE, focusing on: LN development among patients with SLE, within-LN progression, and progression to end-stage renal disease (ESRD). Methods A keyword based literature search was conducted using PubMed, Google and Google Scholar and supplemented with a bibliography search relevant to the focus area. The following publications were screened and prioritized for inclusion: high quality; published after 2010; addressed a topic of focus or an information gap; data were from the USA or Europe. High-quality pre-2010 and non-USA/Europe publications were permitted. Results Overall, 248 citations were identified (keyword based search, n=117; bibliography search, n=131). Following full text screening, 144 publications were considered relevant to the review and 26 were selected for inclusion (21 primary studies, 3 narrative reviews and 2 systematic literature reviews). An overview of the results is provided in the Figure. This review identified that 726% of patients had LN at the time of SLE diagnosis, and 3148% of patients with SLE developed LN in the disease course, most (8090%) within 5 years of diagnosis. Class IV nephritis was the most common LN class found at first (3560%) and repeat (3563%) biopsy and had the worst prognosis. Histological transformation from one LN class to another was reported in 4076% of patients, most commonly in patients with nonproliferative lesions in the first biopsy. Overall, the proportion of patients who subsequently developed ESRD was 36% (SLE) and 428% (LN). Limited data existed for time to progression within LN and from SLE/LN to ESRD, and for renal signs present before LN diagnosis. Conclusions This review highlights risk factors for developing LN and progressing from SLE/LN to ESRD. Male patients, patients of non white ethnicities, and patients of a younger age at SLE diagnosis had the highest risk for developing LN and progressing from SLE/LN to ESRD. Of the renal parameters, elevated serum creatinine was identified as the best predictor of worsening disease state. A higher risk of worse outcomes is seen in the earlier SLE/LN disease stages, demonstrating the importance of early diagnosis and the need for effective disease modifying treatments for SLE and LN. Funding Source(s): Study funded by GSK.

There is limited comparative evidence of the outcomes of different types of surgical management in patients with malignant melanoma in Europe. To address that gap we conducted a systematic literature review to summarize studies reporting outcomes of surgical procedures in patients with malignant melanoma in Europe. Medline was searched for European studies published in English, between 2004 and 2014 reporting surgical outcomes in adults with cutaneous malignant melanoma. We identified 23 studies that evaluated 18 332 patients treated surgically between 1979 and 2009 from 11 European countries. Most of the studies (21/23) were observational; the two remaining studies were randomized controlled trials (RCTs). Studies compared the effect of a range of surgical interventions on a range of clinical outcomes, more commonly overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Wider excisions were not associated with improved survival in patients with melanoma thickness ≥2 mm in both studies (RCTs), however, recent results based on long-term follow-up data associate 3 cm excision margins (vs. 1 cm) with favourable survival outcomes. There was some evidence that complete lymph node dissection after positive sentinel lymph node offers survival benefits over therapeutic lymph node dissection. Sentinel lymph node biopsy was not shown to be associated with significant OS benefits, however, it was overly related with higher rates of DFS/RFS. This review highlights the difficulties of making comparisons between different types of surgical procedures for malignant melanoma. As surgery remains the main treatment, this is an important field, and further evidence, particularly from RCTs, is needed.

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted five-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with five-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stage I and IV patients, respectively. In addition to stage, male gender, age, and circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments. This article is protected by copyright. All rights reserved.

There is anecdotal evidence of variation in the treatment of patients with metastatic melanoma. We aimed to describe the decision-making process physicians use to define resectability and injectability in patients with metastatic melanoma, and to identify patient characteristics associated with unresectable and injectable lesions. Physicians in Germany, France and the UK who manage patients with metastatic melanoma completed a questionnaire and case report forms on lesion resectability and injectability. In total, 122 physicians participated in the study, collecting data on 1,193 patients. Physicians' resection history was the main factor impacting their resection decisions; those who had frequently performed resections in the past were more likely to consider a lesion resectable than those who had rarely performed resections. A physician's decision to resect varied according to field of expertise; 46% of oncologists rarely performed resections, but this was the case for only 10% of dermatologists and 26% of dermato-oncologists. Another important factor affecting resectability status was the number of in-transit lesions; 49% of patients with three or more in-transit lesions were considered resectable compared with 73% of patients with fewer than three in-transit lesions. Lesion location impacted on injectability status; cutaneous and regional lymph node lesions were often considered injectable, whereas distant lesions in the bone, brain, lung, and liver were considered uninjectable. Assessment of resectability status was influenced by physicians' resection history; this varied according to field of expertise, and may reflect the lack of clear guidance on resection for patients with advanced melanoma.

Aims and background With the recent emergence of immunotherapies and novel targeted treatments for advanced and metastatic melanoma such as selective B-Raf inhibitors and checkpoint inhibitors, the treatment landscape in Europe has changed considerably. The aim of this review was to provide an overview of current treatment pathways in Europe for the treatment of advanced melanoma, unresectable stage III–IV. Methods A literature search of four databases was conducted to identify publications reporting on the treatment patterns of advanced and metastatic melanoma (stage III–IV) in European populations. Results Seven full-text publications and two conference abstracts reported on observational studies of melanoma treatment practices in France, Italy and the United Kingdom. Treatment patterns were identified for two time periods: 2005–2009 and 2011–2012. Common treatments reported for both periods included chemotherapy with dacarbazine, fotemustine or temozolomide. The main differences between the two periods were the introduction and prescription of immunotherapy ipilimumab and targeted therapy vemurafenib between 2011 and 2012. Across the three countries studied, the types of treatments prescribed between 2005 and 2009 were relatively similar, however, with noticeable differences in the frequency and priority of administration. Conclusion Treatment practices for advanced melanoma vary markedly across different European countries and continue to evolve with the introduction of new therapies. The results of this review highlight a considerable evidence gap with regards to recent treatment patterns for advanced melanoma in Europe, especially post-2011 after the introduction of novel therapeutic agents, and more recently with the introduction of programmed cell death 1 inhibitors.

Introduction Giant-cell tumor of bone (GCTB) is a locally aggressive histologically benign neoplasm with a less common malignant counterpart. Longitudinal data sources on GCTB are sparse, limited to single institution case series or surgical outcomes studies. The Swedish Cancer Registry is one of the few national population-based databases recording GCTB, representing a unique source to study GCTB epidemiology. We estimated incidence rate (IR) and overall mortality rates based on registry data. Materials and methods We identified patients with a GCTB diagnosis in the Swedish Cancer Registry from 1983 to 2011: benign (ICD-7 196.0–196.9; PAD 741) and malignant (PAD 746). Results were stratified by age at diagnosis, gender, and anatomical lesion location. Results The cohort included 337 GCTB cases (IR of 1.3 per million persons per year). The majority (n = 310) had primary benign GCTB (IR of 1.2 per million per year). Median age at diagnosis was 34 years (range 10–88) with 54% (n = 183) females. Malignant to benign ratio for women was 0.095 (16/167) and for men 0.077 (11/143). Incidence was highest in the 20–39 years age group (IR of 2.1 per million per year). The most common lesion sites were distal femur and proximal tibia. Mortality at 20 years from diagnosis was 14% (n = 48) and was slightly higher for axial (17%; n = 6) and pelvic (17%; n = 4) lesions. Recurrence occurred in 39% of primary benign cases and 75% of primary malignant cases. Conclusions In our modern population-based series primary malignant cases were uncommon (8%), peak incidence 20–39 years with slight predominance in women. Recurrence rates remain significant with overall 39% occurring in benign GCTB, and 75% in malignant form. The linkage between databases allowed the first population based estimates of the proportion of patients who received surgery at initial GCTB diagnosis, and those who also received subsequent surgeries.

Antibacterials are frequently associated with idiosyncratic drug-induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and amoxicillin/clavulanate (AMC) on DILI. We conducted a systematic review (SR) and meta-analysis (MA) with studies retrieved from PubMed, Cochrane Library Plus, Web of Knowledge, clinicaltrials.gov, Livertox and Toxline (1980-2014). We searched for macrolides, AMC and MeSH and synonym terms for DILI. We included all study designs except case reports/series, all population ages and studies with a placebo/non-user comparator. We summarized the evidence with a random-effects MA. Quality of the studies was appraised with a checklist developed for SR of adverse effects. Heterogeneity and publication bias were assessed with different exploratory tools. We finally included 10 (two randomized clinical trials, six case-control, one cohort and one case-population studies) and 9 (case-population excluded) articles in the SR and MA, respectively. The overall summary relative risk of DILI for macrolides was 2.85 [95% confidence interval (CI) 1.81-4.47], p < 0.0001, I(2) = 57%. Three studies were perceived to be missing in the area of low statistical significance. Year of study and selected exposure window partly explained the variability between studies. For AMC, the risk of DILI was 9.38 (95% CI 0.65-135.41) p = 0.3, I2 = 95%. In conclusion, although spontaneous reports and case series have long established an association between macrolides and AMC with acute liver injury, these SR and MA have assessed the magnitude of this association. The low incidence of DILI and the therapeutic place of these antibiotics might tilt the balance in favour of their benefits.

ObjectiveTo examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE.MethodsThis retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the ‘index date’. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods.ResultsOf the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, pConclusionsIn this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.

Background: Since the FDA (Food and Drug Administration) report on antiepileptic drugs (AEDs) and suicide risk was released (2008), several studies have been published on this controversial relationship. This systematic review (SR) gives an updated approach to this health issue. Summary: We searched 6 databases. We ultimately included 11 publications: 4 cohort studies, 1 case-crossover study, 2 community case-control studies, and 4 SRs. Overall, 1 SR described studies already included; 3 studies reported a 2- to 4-fold overall increase in risk; 1 study reported an increased risk of suicide among epilepsy patients on AEDs with high risk of depression; 1study showed a protective effect among epilepsy patients; 2 studies were conducted with patients with bipolar disorder (1 showed a protective effect, whereas the other showed a 3-fold increase in risk of suicide), and the other 3 studies reported results for single AEDs. Several biases affected the published results. Key Messages: There is no clear evidence of an association between the use of AEDs and an increased risk of suicide because of the heterogeneity in the studies at the clinical and methodological level. A future study should cover all indications for use, retrieve information from a healthcare database, and include a defined set of covariates to avoid bias.

The Swedish Cancer Registry (founded in 1958) constitutes a unique resource for epidemiological studies of giant cell tumor of bone with potential for use for population-based studies of incidence over time. The aim of this study was to provide what we believe is the first modern population-based assessment of the incidence trends of giant cell tumor, a unique osteoclastogenic lytic stromal tumor with both benign and malignant histological forms, and to compare the findings with data from the same registry on osteosarcoma, a tumor that may display similar histological characteristics.Cases were identified with use of codes for pathological bone tumor (International Classification of Diseases [ICD]-7 196). Specific morphological coding distinguishes benign (PAD 741) from malignant giant cell tumor (PAD 746) and osteosarcoma (PAD 766).During the period of 1958 to 2011, 4625 bone tumors were reported, including 505 giant cell tumors (383 benign and 122 malignant) and 1152 osteosarcomas. From 1958 to 1982 the ratio of malignant to benign giant cell tumors was 1.3, whereas from 1983 to 2011 the ratio inverted to 0.09, suggesting a change in the reporting or diagnosis of malignant or benign cases. Cases of giant cell tumor diagnosed from 1983 to 2011 displayed an age and sex distribution (median age at diagnosis, 34.0 years; 54% female) that were consistent with those in large published case series but differed from those in 1958 to 1982 (median age at diagnosis, 31.5 years; 48% female). The most current data (1983 to 2011) showed the giant cell tumor incidence in Sweden to be 1.3 per million per year, while the osteosarcoma incidence was 2.3 per million per year.Early Swedish Cancer Registry data (1958 to 1982) revealed a higher proportion of malignant giant cell tumors than seen in large sequential case series and a distinct age and sex profile compared with more recent data (1983 to 2011). This likely represents changes in the diagnostic workup and introduction of multidisciplinary review of giant-cell-containing tumors around 1982. Recent data may reflect the impact of expert centralized biopsy and multidisciplinary case review and more comprehensive reporting of benign giant cell tumors.

Background After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany. Methods Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses. Results Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of “concomitant LABA and ICS users” increased from 52.0 to 57.6% within the study period, whereas for “LABA users without ICS” a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present. Conclusions Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS. Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0051-x) contains supplementary material, which is available to authorized users.

Aim: Giant-cell tumour of the bone (GCTB) is a locally aggressive and histologically benign neoplasm with a less common malignant counterpart. Sources of data on GCTB are sparse, and most published data are from individual case reports or case series. The Swedish Cancer Registry is one of the few national population-based databases that routinely records GCTB; representing a unique source to study the epidemiology of GCTB. The primary goal was to estimate the incidence rate (IR) and mortality rates of GCTB as recorded in the registry. Methods: We identified patients with a GCTB diagnosis in the Swedish Cancer Registry from 1983-2011: benign (ICD-7 196.0-196.9; PAD 741) and malignant (PAD 746). Results were stratified by age at diagnosis, gender, and anatomical lesion location. Mortality was described for patients diagnosed 1997-2011. Results: The cohort included 337 GCTB cases, corresponding to an IR of 1.3 per million persons per year. The majority (n=310) were primary benign (b)GCTB with population IR of 1.2 per million per year. Median age was 34 years (range 10–88) with 54% (n=183) female. Malignant to benign ratio was higher among women 0.095 (16/167) than men 0.077(11/143). Incidence was highest in the 20–29 years age group with an IR of 2.5 per million per year. The most common lesion site for both bGCTB and malignant (m)GCTB was the lower extremity (Table). Overall mortality at 14 years since diagnosis was 9% (n=14) and was higher for pelvic lesions (n=2; 15%). bGCTB mGCTB N Incidence * N Incidence * Age 0–19 43 0.67 2 0.03 20–39 133 1.86 15 0.21 40–59 90 1.31 5 0.07 60+ 44 0.74 5 0.08 Location Axial 33 0.13 2 0.01 Pelvic 19 0.07 4 0.02 Upper extremity 81 0.32 4 0.02 Lower extremity 143 0.56 13 0.05 Non-spec 34 0.13 4 0.02 * per million, per year Conclusions: This population-based, retrospective cohort study confirmed that GCTB is a rare disease in Sweden. Consistent with the published literature, malignant cases were uncommon (8%), peak incidence between 20–39 years, slight predominance in women, and most common lesion location was lower extremity. Further work is ongoing to elucidate risk factors associated with outcomes of patients with GCTB. Disclosure: J. Amelio: JA is employed by and owns stock in Amgen; J. Sandberg: JS is employed at IMS and are consultants for Amgen; R. Hernandez: RH is employed by and own stocks in Amgen; P. Sobocki: PS is employed at IMS and are consultants for Amgen; S. Stryker: SS is employed by and owns stock in Amgen; J. Engellau: JE is a board member of Genovis Inc. He has participated advisory board meetings for Amgen and lectured for Amgen on the topic GCTB; B. Bach: BB is employed by and owns stock in Amgen; A. Liede: AL is employed by and owns stock in Amgen

Aim: Giant Cell Tumour of the Bone (GCTB) is a rare, histologically benign but locally aggressive neoplasm of the bone that also has a less common malignant form. There are limited data on the epidemiology of GCTB as few population-based cancer registries record incidence of benign bone tumours. The Swedish Cancer Registry (SCR) was introduced in 1958 as a national and compulsory registration of all patients diagnosed with a malignancy, including GCTB. The objective of this study was to evaluate reported trends in the incidence of GCTB, compared to osteosarcoma (an osteolytic and osteoblastic malignant tumour with distinctive histology that may contain multinuclear giant cells). Methods: Patients were identified in the SCR with tumour of bone codes (ICD-7 196). Specific and verified morphological coding distinguishes benign GCTB (PAD 741) from malignant GCTB (PAD 746) and osteosarcoma (PAD 766). Results: There were 4625 bone tumours reported to the SCR between 1958-2011, including 505 GCTB (383 benign, 122 malignant) and 1152 osteosarcoma. Osteosarcoma was more common than GCTB (2.3 to 1 ratio) and had a peak incidence in the second decade of life, whereas GCTB peak incidence was between ages 20 and 40. There was a subtle decline in the incidence of osteosarcoma, whereas the distribution of malignant and benign GCTB inverted around 1982 with fewer malignant and more benign cases reported in the SCR. The ratio of malignant to benign GCTB before 1982 was 1.3 (95/73) and 1983 forward was 0.09 (27/310). The incidence rate of benign GCTB in Sweden was 1.1 per million per year in recent data (1992-2011). Conclusions: The reporting of GCTB to the SCR has improved over the last 50 years. GCTB trends in Sweden can be attributed to the formation of the Scandinavian Sarcoma Group (SSG) in 1979. The SSG introduced centralized treatment and review of sarcoma patients thereby reducing misclassification of sarcoma and confirming that malignant GCTB is rare. The SCR remains one of the few national registries that routinely capture GCTB and is a robust source for epidemiology studies in this disease, although validation studies are needed to further confirm benign and malignant classification. Disclosure: A. Liede: Employed by Amgen Inc, including stock ownership; J. Sandberg: Employed by IMS Health, consultant for Amgen Inc.; J. Amelio: Employed by Amgen Ltd, including stock ownership; R.K. Hernandez: Employed by (and stock ownership) Amgen Inc.; P. Sobocki: Employed by IMS Health, consultant for Amgen Inc.; H.C.F. Bauer: Advisory board member (osteosarcoma) with Eli Lilly; B. Bach: Employed by Amgen Inc. including stock ownership; J. Engellau: Member of advisory board for Amgen and Genovis Inc. Also, lectured for Amgen Ltd (on giant cell tumor of bone).