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Aim To understand the psychosocial experience of children and identify their primary support needs following a type 1 diabetes diagnosis. Methods A systematic review and narrative synthesis of the literature in this area was conducted. Results A total of 32 studies were included in the review. At diagnosis, the majority of children experienced high distress, including grief, anxiety, anger, irritation and injection anxiety. The intensity of this reaction decreased rapidly over the following weeks. At diagnosis, rates of depressive symptoms, anxiety, stress disorders and suicidal ideation were elevated. The initial reaction tended to peak shortly after diagnosis and declined over the following year. Thereafter, symptoms of depression and anxiety appeared to increase once again, corresponding with the children's experience of diabetes management and implications as being more difficult and upsetting. Injection anxiety, distress and depressive symptoms persisted for a smaller group of children. Conclusion The initial high prevalence of depressive symptoms following diagnosis is transitional and should be regarded as a normal adaptive response. To facilitate this adaptive process, specific child-centred support should be prioritized as an integrated part of early diabetes care. Our findings point to five inter-related support needs following a type 1 diabetes diagnosis: (1) children need time to adjust to the diagnosis; (2) children need supportive relationships; (3) children need an opportunity for meaningful participation and appropriate protection; (4) children need to engage and explore; and (5) children need to feel supported, but not different.

Introduction Risk stratification tools provide valuable information to inform treatment decisions. Existing algorithms for patients with multiple myeloma (MM) were based on patients with newly diagnosed disease, and these have not been validated in the relapsed setting or in routine clinical practice. We developed a risk stratification algorithm (RSA) for patients with MM at initiation of second-line (2L) treatment, based on data from the Czech Registry of Monoclonal Gammopathies. Methods Predictors of overall survival (OS) at 2L treatment were identified using Cox proportional hazards models and backward selection. Risk scores were obtained by multiplying the hazard ratios for each predictor. The K-adaptive partitioning for survival (KAPS) algorithm defined four groups of stratification based on individual risk scores. Results Performance of the RSA was assessed using Nagelkerke’s R2 test and Harrell’s concordance index through Kaplan–Meier analysis of OS data. Prognostic groups were successfully defined based on real-world data. Use of a multiplicative score based on Cox modeling and KAPS to define cut-off values was effective. Conclusion Through innovative methods of risk assessment and collaboration between physicians and statisticians, the RSA was capable of stratifying patients at 2L treatment by survival expectations. This approach can be used to develop clinical decision-making tools in other disease areas to improve patient management. Funding Amgen Europe GmbH. Electronic supplementary material The online version of this article (10.1007/s40487-019-00100-5) contains supplementary material, which is available to authorized users.

Multiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease-related factors change between diagnosis and the initiation of second-line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K-adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)-4 (highest risk) were 61·6, 29·6, 14·2 and 5·9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations. ispartof: BRITISH JOURNAL OF HAEMATOLOGY vol:187 issue:4 pages:447-458 ispartof: location:England status: published

Using the theoretical framework of Guido Möllering conceptualising trust as a mental process composed of three elements—expectation, interpretation and suspension—we examined the role of trust in relation to young children’s (age ≤ 7 years) psychosocial needs when diagnosed with type 1 diabetes. Based on qualitative interviews with health care professionals (HPCs) from paediatric diabetes clinics in all regions of Denmark, we identified four main themes: trust through meaningful interaction, trust as a key factor at the time of diagnosis, trust in a long-term perspective and caregivers as the bridge to trust. We conclude that trust between young children and HCPs is central to children’s psychosocial experience, as well as a primary need, when children are diagnosed with type 1 diabetes. Trusting relationships counteract children’s experience of fear, anxiety and needle phobia and reinforce HCPs’ experience of providing good psychosocial as well as medical care. The present study offers insights into how trust can positively affect young children’s experience of diagnosis. This study also points out some key barriers to and facilitators of creating trusting relationships. This research is a first step towards a greater understanding that can inform collective future guidelines on the psychosocial care of young children.

Objectives and designA novel risk stratification algorithm estimating risk of death in patients with relapsed multiple myeloma starting second-line treatment was recently developed using multivariable Cox regression of data from a Czech registry. It uses 16 parameters routinely collected in medical practice to stratify patients into four distinct risk groups in terms of survival expectation. To provide insight into generalisability of the risk stratification algorithm, the study aimed to validate the risk stratification algorithm using real-world data from specifically designed retrospective chart audits from three European countries.Participants and settingPhysicians collected data from 998 patients (France, 386; Germany, 344; UK, 268) and applied the risk stratification algorithm.MethodsThe performance of the Cox regression model for predicting risk of death was assessed by Nagelkerke’s R2, goodness of fit and the C-index. The risk stratification algorithm’s ability to discriminate overall survival across four risk groups was evaluated using Kaplan-Meier curves and HRs.ResultsConsistent with the Czech registry, the stratification performance of the risk stratification algorithm demonstrated clear differentiation in risk of death between the four groups. As risk groups increased, risk of death doubled. The C-index was 0.715 (95% CI 0.690 to 0.734).ConclusionsValidation of the novel risk stratification algorithm in an independent ‘real-world’ dataset demonstrated that it stratifies patients in four subgroups according to survival expectation.

Purpose Describe temporal changes in use of myelosuppressive chemotherapy, primary prophylactic colony-stimulating factor, and neutropenia-related hospitalization, in commercially insured patients. Methods Using a large commercial administrative database, we identified annual cohorts of adult patients diagnosed with breast or lung cancer, or non-Hodgkin lymphoma and initiating myelosuppressive chemotherapy during 2005–2017. We described yearly changes in proportions of myelosuppressive chemotherapy by febrile neutropenia risk category (high, intermediate, unclassified) and proportion of prophylactic colony-stimulating factor use and unadjusted incidence of neutropenia-related hospitalization in the first cycle of myelosuppressive chemotherapy. Results Annual cohorts included 4383–5888 eligible patients during 2005–2017. The proportion of eligible patients aged ≥ 65 years increased from 26.0% in 2005 to 58.2% in 2017. Myelosuppressive chemotherapy use with regimens with high risk for febrile neutropenia increased from 15.1% in 2005 to 31.0% in 2017; and regimens with intermediate risk for febrile neutropenia decreased from 63.7% to 48.1% in 2017. Prophylactic colony-stimulating factor use increased from 41.6% in 2005 to 54.3% in 2017. Crude incidence of neutropenia-related hospitalization for all cancers increased from 2.0% to 3.1%, with a substantial increase in neutropenia-related hospitalization observed among non-Hodgkin lymphoma patients (2.8% to 8.5%) during 2005–2017. Conclusion Among adult patients with breast and lung cancer, and non-Hodgkin lymphoma receiving myelosuppressive chemotherapy, use of regimens with high risk for febrile neutropenia increased, as did the use of prophylactic colony-stimulating factors after 2005. Incidence of neutropenia-related hospitalization increased slightly, particularly among non-Hodgkin lymphoma patients. Further studies are required to understand this increasing trend of neutropenia-related hospitalization, changing patient-level risk factors, and febrile neutropenia management.

Altres ajuts: This analysis and the development of this manuscript were funded by Amgen (Europe) GmbH. Medical writing support, funded by Amgen (Europe) GmbH, was provided by Oxford PharmaGenesis, Oxford, UK. Editorial support was provided by Carine Thual of Amgen (Europe) GmbH. In ENDEAVOR, carfilzomib and dexamethasone (Kd56) demonstrated significant improvement in progression-free survival (PFS) compared with bortezomib and dexamethasone (Vd). Both agents were administered until disease progression; the EU label for Vd, however, stipulates a maximum of eight treatment cycles. Here, matching-adjusted treatment comparison was used to compare efficacy of Kd56 with Vd, if Vd was administered for 8 cycles (Vd-8). Data from ENDEAVOR and CASTOR trials (which compared daratumumab, bortezomib, and dexamethasone with Vd-8) were used. Hazard ratios of PFS were estimated for Vd vs. Vd-8 and Kd vs. Vd-8. For cycles 1-8, risk reduction in PFS for Kd56 vs. Vd-8 was equal to that estimated in ENDEAVOR (HR: 0.53; 95% CI 0.44-0.65). Beyond eight cycles, risk reduction in PFS for Kd56 and Vd-8 was estimated to be 60% (HR: 0.40; 95% CI 0.26-0.63). The analysis suggested that PFS benefit of Kd56 over Vd increases when Vd is given for eight cycles only.

Background Australia has a maternal mortality ratio of 6.8/100000 live births, a rate akin to other developed countries and consistent with the high level care provided within the Australian health care system. With maternal mortality at very low levels assessment of severe maternal morbidity is increasingly being used as an indicator of quality of care and to identify areas for improvement in maternity services. The WHO maternal ‘near miss’ criteria is a standardised tool has been increasingly used worldwide to assess maternal morbidity and standards of maternity care. The aim of this study was to determine the rate and aetiology of maternal ‘near misses’ at King Edward Memorial Hospital (KEMH) using the WHO near miss criteria. Methods Cases of maternal ‘near miss’ were prospectively identified at KEMH using the WHO near miss criteria over a period of 6 months (1st December 2014 to 31st May 2015). A descriptive analysis of the results was undertaken. Results During the study there were 2773 live births with 19 women who had ‘near miss’ presentations. There were no maternal deaths. The maternal ‘near miss’ index rate was 7/1000 live births. The main causes of obstetric ‘near miss’ were obstetric haemorrhage, pre-eclampsia and early pregnancy complications. Conclusion The rate of maternal ‘near miss’ at KEMH was 7/1000 live births and post-partum haemorrhage was identified as the most common aetiology, consistent with other studies in developed countries. Further research comparing currently utilised local, state and national morbidity systems would allow further validation of the WHO near miss criteria in Australian settings. The study presented in this publication was undertaken at King Edward Memorial Hospital, 374 Bagot Rd., Subiaco WA 6008. Electronic supplementary material The online version of this article (10.1186/s12884-018-1862-6) contains supplementary material, which is available to authorized users.

Introduction Real-world data on patient outcomes and treatment patterns in multiple myeloma (MM) are limited. Materials and Methods The present noninterventional, observational, retrospective analysis of prospectively collected Czech patient medical record data from the Registry of Monoclonal Gammopathies estimated real-world outcomes in adults with a diagnosis of symptomatic MM made between May 2007 and June 2014. Results In total, 2446 patients had initiated first-line treatment. The median overall survival since the diagnosis (primary endpoint) was 50.3 months (95% confidence interval, 46.1-54.5 months) and decreased with each successive treatment line. A similar trend was observed for progression-free survival and the depth of response. In line with European guidelines and clinical practice, bortezomib-, thalidomide-, and lenalidomide-based regimens were most commonly used across all treatment lines (42.3%, 28.9%, and 18.4%, respectively). In the first line, bortezomib and thalidomide were used most often, with lenalidomide the most commonly used agent in the relapse setting (second to fourth lines). Exploratory analyses revealed that younger age (≤ 65 years), lower international staging system stage, and previous stem cell transplantation were associated with significant improvements in overall and progression-free survival, especially in the early treatment lines. Conclusion The present study is the first analysis of Czech data from the Registry of Monoclonal Gammopathies, and it provides important insights into the real-world management of MM for physicians and healthcare providers.

Temporary abdominal closure (TAC) techniques are routinely used in the open abdomen. Ideally, they should prevent evisceration, aid in removal of unwanted fluid from the peritoneal cavity, facilitate in achieving safe definitive fascial closure, as well as prevent the development of intra-abdominal complications. TAC techniques used in the open abdomen were compared with negative pressure wound therapy (NPWT) to identify which was superior. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines involving Medline, Excerpta Medica, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Clinicaltrials.gov. All studies describing TAC technique use in the open abdomen were eligible for inclusion. Data were analyzed per TAC technique in the form of a meta-analysis. A total of 225 articles were included in the final analysis. A meta-analysis involving only randomized controlled trials showed that NPWT with continuous fascial closure was superior to NPWT alone for definitive fascial closure [mean difference (MD): 35% ± 23%; P = 0.0044]. A subsequent meta-analysis involving all included studies confirmed its superiority across outcomes for definitive fascial closure (MD: 19% ± 3%; P < 0.0001), perioperative (MD: -4.0% ± 2.4%; P = 0.0013) and in-hospital (MD: -5.0% ± 2.9%; P = 0.0013) mortality, entero-atmospheric fistula (MD: 22.0% ± 1.8%; P = 0.0041), ventral hernia (MD: -4.0% ± 2.4%; P = 0.0010), and intra-abdominal abscess (MD: -3.1% ± 2.1%; P = 0.0044). Therefore, it was concluded that NPWT with continuous fascial traction is superior to NPWT alone.

Background: Patient (pt) involvement in treatment decisions or 'shared decision making' has been associated with increased pt satisfaction, increased compliance to advice from health professionals, enhanced treatment adherence and overall improved treatment outcomes. Methods: A multinational non-interventional cross-sectional survey was designed and aimed to enrol approximately 1,000 adult pts with multiple myeloma (MM) through Myeloma Patients Europe's (MPE) member network across 12 participating countries: France, Israel, Netherlands, United Kingdom (UK), Sweden, Germany, Hungary, Austria, Finland, Switzerland, Poland and Romania. Patient advocacy organizations were asked to disseminate a URL link for the survey to pts by posting the link on their website, e-mailing the link to pt members on their mailing list or through social media. The primary survey objective was to describe pt confidence in making an informed treatment decision. Main secondary objectives were to describe how pt confidence in making an informed treatment decision was associated with types of information, importance of information and sources of information. Pts fulfilling the following criteria were included: adults who had started MM treatment and received at least one dose, who were able to self-report diagnosis of MM and recall the decision-making process at the start of their most recent line of treatment, and who were able and willing to complete an online questionnaire lasting approximately 30 minutes. Results: Out of 4325 pts who accessed the online survey link, 1559 pts fulfilled eligibility criteria and were included in the primary analysis, of which 1081 provided fully completed surveys. France, Israel, Netherlands, and UK were the largest recruiters with over 200 pts each. Median age of respondents was 54-64 years. Time since diagnosis was 0-4 years for over half of pts (53.1%), and ≥16 years since diagnosis for 4.8% of pts. The majority of pts had received 1 line (40.1%, n=592) of anti-MM treatment, 20.5% (n=303) of pts had received 2 lines, 16.0% (n=236) of pts had received 3 lines, and 19.9% (n=294) reported having received 4 or more lines of treatment. Last treatment decision was taken 2 years ago for another 25.5% of respondents. Of the 1112 pts who responded to the question for the primary objective, half of pts (54.4%, n=605) reported being very confident in their most recent treatment decision, and 37.2% (n=414) of pts reported being somewhat confident. Similarly, over half of pts (56.8%, n=634/1116) felt that they were 'very involved' in their last treatment decision, 28.4% (n=317/1116) reported being 'somewhat involved'. Confidence in making an informed treatment decision did not appear to differ by lines of therapy, primary treating physician, type of clinic primarily treated at, or whether help from a carer was received. In terms of types of information received, pts most commonly received information on location of treatment (84.5%, n=1037), mode of administration (83.0%, n=1019), frequency of treatment (77.7%, n=953) and common side effects (72.2%, n=886), and least commonly received information on overall survival (OS) benefit (38.4%, n=471) and how long until MM returns (30.9%,n=379) or healthcare provider costs (20.0%, n=245). Information relating to treatment effectiveness (OS benefit, likelihood treatment would work, how long until MM returns) were reported as the most important types of information amongst those who received them, followed by types relating to treatment tolerability (how safe the treatment is). Operational aspects of treatment (mode of administration, location of treatment and healthcare provider costs) were considered the least important type of information. Receiving the types of information perceived as most important by pts was significantly associated with increased pt confidence in making an informed treatment decision. Conclusion: The most important types of information to pts with MM are related to treatment effectiveness and tolerability. However, effectiveness seems to be communicated to pts less frequently than tolerability and this may be due to the uncertainty surrounding this type of information. However, the survey results suggest some elements on effectiveness should be considered to be shared with pts to increase their confidence in making an informed treatment decision. Disclosures Brescianini: Amgen: Current Employment, Current equity holder in publicly-traded company. Desgraz:Amgen: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Plate:Pfizer: Research Funding, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; ASCO: Membership on an entity's Board of Directors or advisory committees; ESMO: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Myeloma Patients Europe: Current Employment; Novartis: Research Funding, Speakers Bureau; Mundipharma: Research Funding, Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; GSK: Research Funding, Speakers Bureau; Oncopeptides: Research Funding, Speakers Bureau. Morgan:Amgen, BMS, GSK, Janssen, Karyopharm, MundiPharma, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Takeda: Research Funding, Speakers Bureau; Myeloma Patients Europe: Current Employment. Vallejo:Amgen, BMS, GSK, Janssen, Karyopharm, MundiPharma, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Takeda: Research Funding; Myeloma Patients Europe: Current Employment. Wetten:Amgen: Current Employment, Current equity holder in publicly-traded company. DeCosta:Amgen Ltd: Current Employment, Current equity holder in publicly-traded company. Suzan:Amgen: Current Employment, Current equity holder in publicly-traded company.

BackgroundHealth education is particularly important for people with mental illness because they are at higher risk of becoming overweight or obese and developing type 2 diabetes than are members of the general population. However, little is known about how to provide health education activities that promote engagement and motivation among people with mental illness.MethodsThis study used ethnographic methods to examine barriers and facilitators of effective health education targeting people with mental illness by applying the concept of flow as a theoretical framework. Flow refers to immersion in an activity and is related to motivation. Data were collected through participant observation during eight health-educating activities and were thematically analysed using the concept of flow. Fieldwork was carried out between May and July 2015 in Denmark.ResultsBarriers to flow included: 1) information overload, particularly of biomedical rationales for behaviour change; 2) a one-size-fits-all approach that failed to address the needs and preferences of the target group; and 3) one-way communication allowing little time for reflection. Educators promoted a state of flow when they spoke less and acted outside of a traditional expert role, thus engaging participants in the activity. Flow was facilitated when educators were attentive and responsive to people with mental illness, and when they stimulated reflection about health and health behaviour through open-ended questions, communication tools and in small group exercises.ConclusionsThis study suggests that more focus should be paid to training of educators in terms of skills to involve and engage people with mental illness in health education activities.

Background People living with HIV/AIDS (PLWHA) often experience psychological stress associated with disease management. This meta-analysis examines the benefits of yoga interventions on psychological distress among PLWHA. Methods Included were studies that (a) evaluated a yoga intervention in PLWHA; (b) provided between-group or within-group changes; and (c) assessed a psychological, physiological, or biomedical outcome. Results Seven studies sampling 396 PLWHA (M age = 42 years, SD = 5 years; 40% women) met inclusion criteria. PLWHA who received yoga interventions reported significant improvements in perceived stress (d+ = 0.80, 95% Confidence Interval [CI] = 0.53, 1.07), positive affect (d + = 0.73, 95% CI = 0.49, 0.98), and anxiety (d+ = 0.71, 95% CI = 0.27, 1.14) compared to controls. Conclusion Yoga is a promising intervention for stress management. However, the literature is limited by the small number of studies. Randomized controlled trials with objective measures of HIV-related outcomes are needed to further evaluate the benefits of yoga.

Introduction: Despite increasing evidence that aerobic exercise and cognitive training improve cognitive function among patients with cognitive impairment and dementia, few studies have focused on the effect of a combination of these approaches. This study will explore whether combining aerobic training (AT) with mindfulness training (MT), an intervention promoting the moment-to-moment awareness of physical sensations, affective states, and thoughts, improves cognitive function in individuals at risk of dementia. The primary objective is to determine the feasibility and acceptability of the intervention(s). The secondary objective is to obtain estimates of effect sizes on cognitive function and on possible mediators. Methods and analysis: Forty participants with at least 2 risk factors for dementia will be randomized (2 × 2 factorial design) to either AT (3 sessions/week for 12 weeks), MT (1 session/week for 8 weeks), both, or usual care. Assessments of cognitive function (attention, executive function, episodic, and working memory); physical activity (accelerometry), aerobic capacity (6-minute walk test), waist-to-hip ratio, blood pressure, social support (Multidimensional Scale of Perceived Social Support), depression (Hospital Anxiety and Depression Scale), and mindfulness (Five Facets of Mindfulness) will be conducted at baseline, end of treatment, and 6-months postbaseline. Rates of retention, attendance, and program satisfaction will be calculated for each of the 4 groups to determine the feasibility and acceptability of each intervention. Ethics and dissemination: This study has full ethical approval by The Miriam Hospital Institutional Review Board and adheres to the Standard Protocol Items: Recommendations for Interventional Trials reporting recommendations. If results from this exploratory, proof-of-concept study support our hypotheses, we will conduct a large randomized controlled trial (RCT) to determine the efficacy of combined MT and AT in improving cognitive function in individuals at risk of dementia. Results from the study will be disseminated through peer-reviewed journals and conference presentations. Registration details: http://www.clinicalstrials.gov identifier NCT03289546.

Prophylaxis for febrile neutropenia (FN) is recommended for the duration of myelosuppressive chemotherapy in high-risk patients; yet, granulocyte-colony-stimulating factor (G-CSF) discontinuation occurs frequently in clinical practice. The objective of this study was to investigate the incidence of FN in real-world settings and the extent and impact of early pegfilgrastim discontinuation. This prospective, observational study enrolled patients with any-stage non-Hodgkin’s lymphoma (NHL) or breast cancer initiating a new chemotherapy course with a high (> 20%) FN risk, with pegfilgrastim in cycle 1. During routine clinical visits, data were collected on FN events, discontinuation of pegfilgrastim (defined as administration of G-CSF other than pegfilgrastim for ≥ 1 cycle) and all G-CSF (and reasons), neutropenic complications and adverse drug reactions (ADRs). Overall, 943 patients were enrolled; 844 met the eligibility criteria (full analysis set) and 814 (86%) completed the study. Twenty-eight patients (3%) had 31 FN events (NHL, n = 17; breast cancer, n = 11). Twenty-six patients (3%) discontinued pegfilgrastim. Forty-four patients (5%) discontinued G-CSF. The most common reason for pegfilgrastim discontinuation was physician preference for daily G-CSF (n = 14 [2%]), and for discontinuation of all G-CSFs was reduced FN risk (n = 14 [2%]). Patients who continued G-CSF prophylaxis were less likely to experience neutropenic complications (odds ratio [95% confidence interval]: 0.26 [0.09–0.80]). Suspected ADRs to pegfilgrastim occurred in 43 patients (5%) and serious ADRs in 5 (1%). FN rates were consistent with previous reports with pegfilgrastim in clinical practice. No new ADRs were observed. G-CSF discontinuation was uncommon but appeared to increase the likelihood of neutropenic complications.

Aims: To assess the real-world healthcare resource utilization (HRU) and costs associated with different treatment regimens used in the management of patients with relapsed multiple myeloma in the UK, France, and Italy. Methods: Retrospective medical chart review of characteristics, time to progression, level of response, HRU during treatment, and adverse events (AEs). Data collection started on June 1, 2015 and was completed on July 15, 2015. In the 3 months before record abstraction, eligible patients had either disease progression after receiving one of their country’s most commonly prescribed regimens or had received the best supportive care and died. Costs were calculated based on HRU and country-specific diagnosis-related group and/or unit reference costs, amongst other standard resources. Results: Physicians provided data for 1,282 patients (387 in the UK, 502 in France, 393 in Italy) who met the inclusion criteria. Mean [median] total healthcare costs associated with a single line of treatment were €51,717 [35,951] in the UK, €37,009 [32,538] for France, and €34,496 [42,342] for Italy, driven largely by anti-myeloma medications costs (contributing 95.0%, 90.0%, and 94.2% of total cost, respectively). During active treatment, the highest costs were associated with lenalidomide- and pomalidomide-based regimens. Mean cost per month was lowest for patients achieving a very good partial response or better. Unscheduled events (i.e. not considered part of routine management, whether or not related to multiple myeloma, such as unscheduled hospitalization, AEs, fractures) accounted for 1–9% of total costs and were highest for bendamustine. Limitations: The use of retrospective data means that clinical practice (e.g. use of medical procedures, evaluation of treatment response) is not standardized across participating countries/centers, and some data (e.g. low-grade AEs) may be incomplete or differently adjudicated/reported. The centers involved may not be fully representative of national practice. Conclusions: Drug costs are the main contributor to total HRU costs associated with multiple myeloma. The duration of active treatment may influence the average total costs, as well as response, associated with a single line of therapy. Improved treatment outcomes, and reductions in unscheduled events and concomitant medication use may, therefore, reduce the overall HRU and related costs of care in multiple myeloma.

Registry data are important for monitoring the impact of new therapies on treatment algorithms and outcomes, and for guiding clinical decision making in multiple myeloma (MM). This observational study analyzed real-world data from patients in the Population-based HAematological Registry for Observational Studies who were treated for symptomatic MM from 2008 to 2013 in the Netherlands. The primary endpoint was overall survival (OS) from initiation of first-line treatment. Secondary endpoints included OS and progression-free survival per treatment line, treatment patterns, and treatment response. Between 2008 and 2013, 917, 583, 283, and 139 patients had initiated first, second, third, and fourth treatment lines, respectively. Thalidomide-based regimens were the most frequently used first-line treatment (66%); bortezomib- and lenalidomide-based regimens were most often used in the second line (41% and 27%, respectively). The median OS (95% confidence interval) ranged from 37.5 months (34.8–41.8 months) in the first line to 9.2 months (6.2–12.3 months) in the fourth line. Univariate analyses showed that survival benefits were most apparent in younger patients (65 vs >65 years). These analyses provide important real-world information on treatment patterns and outcomes in patients with MM.

We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd). Patients with relapse ≤1 year after initiating the most recent prior line of therapy were categorized as early relapsers, and patients with relapse after >1 year were categorized as late relapsers. The median progression-free survival (PFS) in ASPIRE for early relapsers was 21.4 months for KRd vs 10.7 months for Rd (hazard ratio [HR]: 0.714; 95% confidence interval [CI]: 0.508-1.004; P = 0.0257), and for late relapsers was 29.7 months for KRd vs 18.2 months for Rd (HR: 0.675; 95% CI: 0.533-0.854; P = 0.0005). The overall response rate (ORR) for early relapsers was 83.2% for KRd vs 54.8% for Rd, and for late relapsers was 89.0% for KRd vs 69.7% for Rd. The median PFS in ENDEAVOR (Kd vs Vd) for early relapsers was 13.9 months vs 5.7 months (HR: 0.598; 95% CI: 0.423-0.846; P = 0.0017), and for late relapsers was 22.2 months vs 10.2 months (HR: 0.486; 95% CI: 0.382-0.620; P < 0.0001). The ORR (Kd vs Vd) for early relapsers was 63.4% vs 49.1% and for late relapsers was 81.8% vs 66.8%. In conclusion, patients with relapsed or refractory multiple myeloma who received carfilzomib-containing regimens had improved PFS and ORR compared with control groups, regardless of whether they had an early or late relapse following the most recent prior therapy.

Sonography is an accurate and commonly used method of determining the presence, location, and acuity of deep vein thrombosis (DVT). A retrospective data analysis of 284 venous examinations was performed to determine if imaging presets increase the ability to detect an acute DVT. There were no significant differences between the outcomes of three modalities of sonographic imaging. If a patient had a prior DVT, the likelihood of observing another DVT using only two-dimensional imaging, resolution presets, or the B-color option was approximately nine times greater than for a patient who did not have a prior DVT. Sex, age, body mass index, ethnicity, and comorbidities of diabetes and/or hypertension were not significant predictors of observing a DVT. Using a resolution-enhancing preset that increases the overall frequency range to reduce artifacts and improve border definition and/or using the B-color preset to tint the overall image did not improve the likelihood of detecting an acute DVT during a lower extremity venous duplex sonogram.

Treatment of non-Hodgkin lymphoma (NHL) requires chemotherapy regimens with significant risk of febrile neutropenia (FN). For patients at ≥20% FN risk, guidelines recommend primary prophylaxis (PP) with granulocyte-colony stimulating factor (G-CSF). This study assessed whether G-CSF use in NHL was in line with recommendations in routine practice. This was a retrospective, observational study of adult NHL patients receiving first-line (R)CHOP-like chemotherapy and G-CSF support between June 2010 and 2012, in Italy. The primary outcome was whether G-CSF was provided as PP, which was defined as G-CSF initiation on days 1–3 after chemotherapy, ≥3 days’ use for daily G-CSFs and continued prophylaxis from cycle 1 across all cycles. Secondary prophylaxis was defined as continued prophylaxis from cycle 2 or later, and all other use was defined as Suboptimal. The analysis included 199 patients, 61% of whom had diffuse large B cell lymphoma and 21% follicular lymphoma. (R)CHOP-21 was given to 52% of patients and (R)CHOP-14 to 32%. Overall, 29% of patients received PP, while two-thirds received Suboptimal G-CSF. Of patients receiving daily G-CSF, 3% received PP and 94% received Suboptimal use; with pegfilgrastim, 65% received PP and 26% Suboptimal use. FN occurred in 13 patients (7%) and grade 3/4 neutropenia in 43%. Chemotherapy dose delays occurred in 22% and dose reductions in 18% of patients. Delivery of G-CSF, particularly daily G-CSFs, was not in accordance with guideline or product label recommendations in a large proportion of NHL patients receiving chemotherapy in Italy.

VACTERL syndrome is a multisystem congenital anomaly. The potential findings include vertebral, anorectal, and cardiac anomalies; tracheoesophageal fistula/esophageal atresia; and renal and limb anomalies. This case report presents a pregnant woman in her early 30s presenting with multiple fetal anomalies suggesting this diagnosis.

Panitumumab monotherapy is approved for KRAS wild-type (WT) metastatic colorectal cancer (mCRC) progressing after standard chemotherapy. This study evaluated first-line panitumumab plus FOLFIRI in patients with mCRC.In this phase II, single-arm study, panitumumab (6 mg/kg) and FOLFIRI [irinotecan (180 mg/m(2)) and leucovorin (400 mg/m(2)) followed by a 5-fluorouracil 400 mg/m(2) bolus and a 2,400-3,000 mg/m(2) continuous infusion] were administered every 14 days until progression. Data were analysed descriptively overall and by tumour KRAS status.KRAS data were available for 145/154 (94%) patients: 59% KRAS WT and 41% mutant (MT); mean follow-up was 39.5 versus 35.8 weeks, respectively. Objective responses occurred in 49% of patients: 56% versus 38% in the KRAS WT versus MT groups [(18% difference (95% CI 1-35%); odds ratio 2.1 (95% CI 1.0-4.4)]; median duration of response was 13.0 versus 7.4 months. More patients in the WT group underwent R0 resection (8% vs. 5%); median progression-free survival also favoured this group (8.9 vs. 7.2 months). The most common adverse events (any grade) were integument toxicities (98%), diarrhoea (79%) and stomatitis/oral mucositis (51%).As expected, consistently favourable efficacy was observed in patients with KRAS WT versus MT tumours receiving first-line panitumumab plus FOLFIRI treatment.

Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy. This prospective, observational study describes physicians' approaches toward assessing FN risk in patients receiving chemotherapy regimens with an intermediate (10-20 %) FN risk. In the baseline investigator assessment, physicians selected factors considered important when assessing overall FN risk and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP). Physicians then completed patient assessments using the same lists of factors. The final FN risk scores and whether G-CSF PP was planned were reported. The final analysis included 165 physicians and 944 patients. The most frequently considered factor in both assessments was chemotherapy agents in the backbone (88 % of investigator and 93 % of patient assessments). History of FN (83 %), baseline laboratory values (76 %) and age (73 %) were commonly selected at baseline, whereas tumor type (72 %), guidelines (62 %) and tumor stage (43 %) were selected most during patient assessments. Median investigator-reported FN risk threshold for G-CSF PP was 20 % (range 10-85 %). G-CSF PP was planned in 82 % of patients with an FN risk at or above this threshold; therefore, almost one-fifth of qualifying patients would not receive G-CSF PP. Physicians generally follow guidelines, but also consider individual patient characteristics when assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may optimize the use of G-CSF PP, which may minimize the incidence of FN in patients undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov Identifier: NCT01813721. Funding for this support was provided by Amgen (Europe) GmbH.

Objectives This open, multinational study examined the efficacy and tolerability of telithromycin (HMR 3647), the first ketolide antibacterial agent, at an oral dose of 800 mg once daily for seven to ten days (further validated using pharmacokinetic analysis) as an empiric therapy in adults with mild to moderate community-acquired pneumonia (CAP). Methods A total of 240 patients (aged 18–79 years; median 40 years) with clinical signs and symptoms of CAP (radiologically confirmed) were enrolled in the study and received at least one dose of study medication. Sputum and blood samples for bacteriologic documentation were collected within 48 h prior to enrollment. Clinical and bacteriological outcomes were assessed 17–21 days (test of cure visit) and 31–36 days (late post-therapy visit) after treatment initiation. Adverse events were assessed by spontaneous reporting and investigator observation. Results At the test of cure visit, 92.9% (95% CI: 88.4–96.1; n = 197) of patients achieved clinical cure in the per-protocol (PP) population. In the modified intent-to-treat (mITT) population, the cure rate was 79.6% (95% CI: 73.9–84.5; n = 240), including 12.5% of undetermined cases categorized as failures. Clinical cure (PP population) remained high in patients ≥65 years (85.7%), and in patients with a Fine score ≥III (92.1 %). Among those patients for whom bacteriologic data were available, the majority had a satisfactory outcome (88.9% in the bacteriologic PP; n = 45). Bacterial eradication rates were similarly high (85.5% and 82.7% for the mITT and PP populations, respectively). All patients with infections as a result of atypical/intracellular pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila had a clinical outcome of cure. Treatment was well tolerated. Adverse events were mainly gastrointestinal in origin and mild in intensity. Conclusion An oral dose of telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated first-line treatment for mild to moderate CAP in adults.

Objective To compare the efficacy and safety of two different doses of levofloxacin with amoxycillin/clavulanic acid in the treatment of community-acquired pneumonia. Methods A double-blind, randomized (1:1:1), double-dummy, three-arm parallel design, multicenter study was conducted in adult patients with mild-to-moderate community-acquired pneumonia. In total, 518 patients were randomized to receive levofloxacin 500 mg once daily, levofloxacin 500 mg twice daily or amoxycillin/clavulanic acid 625 mg three times daily for 7–10 days. Results The clinical cure rates post-therapy (2–5 days after the end of treatment) in the intent-to-treat population were 84.2% (144/171) in the levofloxacin once-daily group, 80.2% (142/177) in the levofloxacin twice-daily group and 85.7% (144/168) in the amoxycillin/clavulanic acid group. In the per-protocol population, the clinical cure rates post-therapy were 95.2% (138/145), 93.8% (137/146) and 95.3% (141/148), respectively. The total pathogen eradication rates were 97.8%, 100% and 97.5%, respectively. Both drugs were equally well tolerated and no major adverse events were observed. Conclusions Levofloxacin was effective, safe and well tolerated in the treatment of mild-to-moderate community-acquired pneumonia. A complementary analysis indicated that there was no difference in therapeutic outcome between levofloxacin 500 mg once daily and twice daily. Levofloxacin 500 mg once daily, for 7–10 days, is an effective and safe treatment for mild-to-moderate community-acquired pneumonia in adults.

This retrospective study compared the prenatal ultrasound (US) diagnosis with autopsy findings in 61 intact fetuses following induced abortion and 36 fragmented fetuses from dilatation and evacuation (D&E). In intact fetuses, complete agreement between US diagnosis and autopsy findings was achieved in 65.6% of cases in the central nervous system (CNS) and 47.5% in other somatic organ systems (SOS). There were major differences between US and autopsy findings involving the CNS in 6.5% of cases and SOS in 27.9%. Correlation was better for evaluation of renal anomalies (complete agreement in 63.6% of 11 suspected cases, 2 false-positive and no false-negative cases) than congenital heart disease (complete agreement in 27.3% of 11 suspected cases, 5 false-positive and 3 false-negative cases). In D&E specimens, a prenatal diagnosis of neural tube defect (NTD) was confirmed in 90% of cases. However, due to fragmentation of fetal parts, the US diagnosis in the CNS could not be confirmed totally (69.4%) or partially (2.8%) in fetuses with chromosomal abnormalities (ChA) or multiple congenital anomalies (MCA). Nonetheless, the US diagnosis of SOS was confirmed in six cases on D&E, including Meckel-Gruber syndrome, cystic hygroma, renal agenesis with contralateral renal dysplasia, cardiac defect, fetal hydrops, and tracheal atresia. Our results show that a thorough autopsy of an intact fetus after abortion is necessary to confirm prenatal diagnosis and allow proper management and counseling. The pathologic examination of D&E specimens can reliably confirm the US diagnosis of NTD, but it is very limited in identifying other fetal anomalies.

Obsessive-compulsive Disorder (OCD) is a pervasive anxiety disorder characterized by ego-dystonic features associated with intrusive thoughts and ritualistic behaviors. Traditionally, most etiological studies have focused on the maladaptive and dysfunctional cognitive processes associated with the disorder. More recently, with the development of neuroimaging techniques and advanced pharmacological interventions, additional support for the hypothesis of a biological basis for the disorder has increased. The present literature review brings some of the evidence for a neurobiological foundation of OCD into perspective and examines neuroimaging studies, the possibility of serotinergic dysregulation in individuals with OCD, and the role of the basal ganglia in the etiology and course of this debilitating disorder.

MM is a heterogeneous disease. The International Staging System (ISS) and the revised-ISS (R-ISS) can be used to stratify patients in terms of risk of mortality in newly-diagnosed MM (NDMM) however; there is less understanding of the predictors of OS in the relapsed setting. This retrospective analysis of the Registry of Monoclonal Gammopathies database, which covers ~80% of all Czech patients with MM, was designed to explore how predictors of OS differ between initiation of first- and second-line treatments, in order to further understand patient heterogeneity as the disease progresses. Eligible patients initiated first-line treatment for symptomatic MM between May 2007 and April 2016. Factors considered prognostic of OS in both NDMM and relapsed/refractory MM were identified from targeted literature searches. Predictors of OS in second-line treatment included historical parameters that reflect outcomes to previous therapy. OS data was then fitted with multiple Cox-regression models. Backward selection was performed using Akaike's Information Criterion (AIC) as selection criterion. Patient characteristics at both first- (N=3027) and second-line (N=1418) treatment initiation are presented in Table 1. Comparison of these characteristics shows that as patients progress, on average their profile becomes less severe (e.g. ISS stage III 28% vs 20% in first- and second-lines, respectively), mainly explained by the dropout rate between first- and second-line treatment (Raab et al 2016) as patients either died or did not continue therapy due to adverse prognosis. Median OS (95% CI) from initiation of first- and second-line treatment was 49.9 (46-54) and 27.6 (25-30) months. Results of OS predictive variables are shown in Table 2. Predictors of OS differ between initiation of first-line versus second-line therapy, both in terms of type of predictor as well as strength. At initiation of first-line, calcium level, bone lesions and bone marrow aspiration cytology were not significant predictors of OS, however they became significant at initiation of second-line or were selected by backward selection procedure. At initiation of second-line, historical parameters defining outcomes of prior treatments remained strong predictors, however only refractory status to prior bortezomib [HR=1.626 (1.267-2.087 p=0.0001)] and time to next treatment (TTnT) [HR=1.280 (1.051-1.559, p=0.014)] were significant predictors of OS. The significance of prediction of age and Eastern Cooperative Oncology Group (ECOG) performance status remained in both settings, with a lower impact of age in second-line treatment. Data for cytogenetics was not collected for initiation of second-line, however it is included in the R-ISS component. Although only measured at diagnosis, it remained a significant predictor in both settings (N.B. this variable had 82% missing values). Restaging of ISS at initiation of second-line was predictive, especially for those ISS III vs ISS I, HR=1.56 (1.23-1.97 p=0.0002). Additionally, lactate dehydrogenase (LDH), which is also a component of R-ISS was significant in both settings with as stronger effect in second-line. Elements normally considered predictive of OS at initiation of second-line did not appear in the final model: prior stem-cell transplant status or time-to-progression of previous therapy, perhaps explained by age and TTnT, respectively. Creatinine level was not significant at initiation of second-line, perhaps as patients with renal impairment during first-line treatment may not receive second-line treatment. This real-world analysis of data from Czech patients revealed that predictors of OS differ between initiation of first- and second-line treatments. Prediction of OS in the relapsed setting should consider patient-related factors (age, ECOG), factors reflecting the disease activity and severity (LDH, bone lesion, calcium level) as well as historical elements, including those that were dependent on patient experience in the first treatment line (treatment response and duration of response). Additionally, there seems to be value in reclassification of patients in terms of severity at the relapse setting in order to improve prognosis and treatment selection in the relapsed setting. Disclosures Hájek: Takeda: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; BMS: Honoraria; Janssen: Honoraria. Jiri:Amgen: Consultancy. Walter:Amgen: Consultancy. Maarten:Amgen: Consultancy. Lucy:Amgen: Employment, Other: Amgen Stock. Marco:Amgen: Employment, Other: Holds Amgen Stock. Lucie:Amgen: Consultancy. Sebastian:Amgen: Employment, Other: Holds Amgen Stock.

Risk stratification tools in multiple myeloma (MM), such as the International Staging System (ISS) and the revised-ISS (R-ISS), have improved understanding of survival expectations using the strongest known predictors at time of diagnosis. Given their value at diagnosis, these have been used to define risk after first relapse in clinical trials and standard practice. Although these tools have not been validated in this setting, their use arises because of the need to better characterize patients in order to define survival expectations and treatment decisions. Once the patient has relapsed, there are additional variables that may need to be considered in order to systematically assess patient risk, understand drivers of disease progression and ensure that treatment strategies are aligned with patient risk. Using data from the Czech Registry of Monoclonal Gammopathies (RMG), this study assessed predictors of overall survival (OS) and developed a new Risk Stratification Tool (RST) to predict OS at time of treatment decision after first relapse (TTD1). The RST was developed by estimating the strongest predictors of OS at both diagnosis and TTD1 to define the final parameters for inclusion. The cut-offs for each parameter reflect conventional cut-offs used in clinical practice and some were supported by evidence using a K-adaptive Partitioning for Survival (KAPS) approach, which stratified data based on distinct survival expectations. The hazard ratio (HR) of the selected predictors was used to assign a score per parameter at a patient level where missing data were entered with a contribution equal to 1. Using the full RMG data set at TTD1 (N=1418) the (KAPS) method was run to define 4 distinct group of patients based on survival expectations. The RST consists of 4 dimensions and 12 item questions based on the strongest predictors of survival at TTD1, "Patient Factors" (age and Eastern Cooperative Oncology Group (ECOG) performance status), "Existing Stratification Factors (R-ISS at diagnosis and ISS at TTD1), "Disease Factors" (calcium level, number of bone lesions, extramedullary disease, thrombocyte count, clonal cells in bone marrow aspiration cytology, lactate dehydrogenase [LDH]) and "Treatment history" (refractory to prior therapy, time-to-next-treatment [from initiation of treatment of first anti-myeloma drug to initiation of treatment at first relapse]) (Table 1). Subsequently, we explored each group based on distribution of frailty-driven measures (age and ECOG) and aggressiveness of the disease (rest of parameters) to understand what is driving stratification. Figure 1 shows the KM curve of survival after TTD1 for each of the 4 groups estimated by KAPS. The new analysis shows strong differentiation in survival expectations between the 4 groups (Table 2), showing significantly different OS for all groups compared with reference. The median OS and Confidence Intervals per group did not overlap, supported by the positive association of HR across groups. The distribution of the Total Score (Figure 2) is between 1 and 2, which shows sufficient sensitivity to differentiate these groups by survival expectations. The RST can then be split into Frailty Score and Aggressiveness Score (Figure 3a & b) to understand what is driving disease severity. The distribution of these two scores shows that group 1 consists of low patient frailty and low disease aggressiveness, whereas group 4 shows high on both elements. Group 2 has an increased score for frailty and marginal increase in aggressiveness compared with group 1, and group 3 stratification is driven by an increase in aggressiveness over group 2. The analysis showed that predictors, patient's experience of prior treatment and level of disease impact at the point of treatment decision after first relapse provided an initial framework to demonstrate strong differentiation between groups based on patient severity and what is driving patient risk (patient frailty vs aggressiveness of disease). The RST has shown promising results when applied to the RMG, however further validation of this work is required using other real-world and clinical trials data. Nevertheless, this analysis is a first step in systematically assessing patient risk to improve the selection of treatments based on improved understanding of patient profiles. Disclosures Hájek: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; BMS: Honoraria; Takeda: Consultancy; Celgene: Consultancy, Research Funding. Bouwmeester:Amgen: Consultancy. Treur:Amgen: Consultancy. DeCosta:Amgen: Employment, Other: Holds Amgen Stock. Campioni:Amgen: Employment, Other: Holds Amgen Stock. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Raab:BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Schoen:Amgen: Employment, Other: Holds Amgen Stock. Szabo:Amgen: Employment, Other: Holds Amgen Stock. Lucie:Amgen: Consultancy. Gonzalez-McQuire:Amgen: Employment, Other: Holds Amgen Stock.

The ISS stratifies survival risk in patients with MM based on β2-microglobulin and albumin levels. The R-ISS is an improved stratification tool, which also uses chromosomal abnormalities (CA) and lactate dehydrogenase (LDH). It was developed based on clinical trial data in the first-line setting but, has not been validated outside clinical trials or for use in the relapsed setting. Using data from the RMG, we assessed the real-world validity of the R-ISS at diagnosis. Additionally, as it is standard practice to re-stage patients after first relapse, we explored the value of re-estimating ISS stage in the relapsed setting and exploring the carry on effect of R-ISS from diagnosis. Re-estimation of R-ISS at relapse is not possible as standard practice often does not include CA measurement at first relapse. Assessment of improvement in stratification was based on visual comparison of median OS, hazard ratios (HR) and confidence intervals. Eligible patients were diagnosed with symptomatic MM between May 2007 and April 2016. A Cox regression model and Kaplan-Meier analyses assessed the performance of the ISS and R-ISS for stratifying patients based on survival both at diagnosis and at first relapse. Overall, there were 3027 patients at diagnosis however only 493 were included in these analyses due to unavailable CA values (84% of patients). ISS and R-ISS stage distribution at diagnosis was ISS I 31.2%, II 29.1% and III 39.6%; and R-ISS I 12% II 57% and III 31% (Table 1). Median overall survival (OS) in months (95% confidence interval [CI]), from diagnosis was 73.5 (68.0-NE), 40.5 (31.0-50.0) and 29.0 (20.9-37.2) in patients with ISS stage I, II and III, respectively, and not reached (NR), 46.6 (39.2-54.1) and 26.0 (18.2-33.8) in patients with R-ISS stage I, II and III, respectively. Table 2 shows HR, which indicate OS assessed in alternative ways was significantly different among the three stages for both ISS and R-ISS. R-ISS provided refined stratification than ISS alone, since R-ISS stage III classified patients with higher risk than ISS III alone, (shorter median OS, narrower CI, and stronger HR vs. ISS I and II). From the original sample of 493 patients at diagnosis, only 250 went on to receive further treatment after first relapse. The median OS months (95% CI) after first relapse was 46.4 (32.0-60.8), 22.8 (13.4-32.1) and 14.9 months (9.0-20.8) in patients staged as ISS stage I, II and III at diagnosis, respectively. In patients staged as R-ISS stage I, II and III at diagnosis it was NR, 25.6 (20.8-30.3) and 10.4 (6.7-14.2), respectively. Data to enable re-estimation of ISS and R-ISS at first relapse were available for 187 patients (R-ISS re-stratification was using CA data at diagnosis only). Median OS months (95% CI) from first relapse was 32.2 (15.5-49.0), 25.6 (11.5-39.6) and 10.8 (8.6-13.0) in patients at ISS stage I, II and III, respectively, and 23.3 (NE-NE), 28.4 (20.8-36.0) and 9.7 (6.5-12.9) in patients at R-ISS stage I, II and III, respectively. The HRs comparing OS from first relapse stratified by ISS at diagnosis indicated that re-estimating ISS did not improve stratification (Table 2). For R-ISS, compared with staging patients at diagnosis, staging at first relapse resulted in refined stratification between stage II and III, however assessment of HRs comparing to stage I was difficult owing to small sample sizes. Re-estimation of R-ISS stage at first relapse resulted in 26% of patients having their stage reclassified; the main drivers of reclassification to a lower R-ISS risk group were β2-microglobulin and albumin levels, and to a higher risk group, LDH levels. Our real-world data show that, at diagnosis R-ISS provides refined risk stratification compared with ISS. Further refinement seemed to be added by restaging at first relapse using R-ISS, not ISS however, CA measurements are not currently routinely measured at first relapse, limiting the practical utility of the R-ISS at this stage. Therefore, re-estimating R-ISS stage after first relapse may enable physicians improve estimation of patient prognosis. Both ISS and R-ISS have been developed for use at diagnosis when there is less evidence to predict prognosis, therefore risk stratification after first relapse should also consider other historical patient, disease and treatment factors contributing to improved risk stratification and improved treatment selection and outcomes. Disclosures Hájek: Novartis: Consultancy, Research Funding; Celgene: Research Funding; Amgen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bouwmeester:Amgen: Consultancy. Treur:Amgen: Consultancy. Lucy:Amgen: Employment, Other: Amgen Stock. Campioni:Amgen: Employment, Other: Holds Amgen Stock. Delforge:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Raab:BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Schoen:Amgen: Employment, Other: Holds Amgen Stock. Szabo:Amgen: Employment, Other: Holds Amgen Stock. Gonzalez-McQuire:Amgen: Employment, Other: Holds Amgen Stock.

Background The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India. Methods Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml). Results A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ≥ 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05). Conclusions Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.

Disease control has increasingly shifted towards large scale, disease specific, public health interventions. The emerging problems of HIV, hepatitis, malaria, typhoid, tuberculosis, childhood pneumonia, and meningitis have made community based trials of interventions a cost effective long term investment for the health of a population. The authors conducted this study to explore the complexities involved in obtaining informed consent to participation in rural north India, and how people there make decisions related to participation in clinical research.

This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period.This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis.This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P/=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P.05), including nasal congestion in the evening reflective assessment (P.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality.The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Noncardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP.To test the efficacy of a potent acid-suppressing agent as a diagnostic test in the evaluation of NCCP and to compare it with three commonly used tests.Eighteen men and 24 women, aged 22 to 77 years, who presented with recurrent chest pain complaints of a noncardiac etiology, as determined by rest/stress perfusion imaging with technetium Tc99m sestamibi (MIBI), were enrolled in a prospective, double-blinded, placebo-controlled, crossover trial using high-dose omeprazole. Thirty-seven patients completed both arms of the trial. Findings were compared with those of endoscopy, manometry, and ambulatory 24-hour two-channel esophageal pH monitoring. All patients underwent initial diagnostic upper endoscopy, esophageal manometry, and 24-hour pH monitoring. Patients were then randomly assigned to either placebo or omeprazole (40 mg/d orally twice daily) for 14 days, washed out for 21 days, and then crossed over. Patient's symptoms were determined using a Visual Analogue Scale to measure the severity of chest pain before and after each period.Seventy-one percent of patients in the omeprazole arm reported improved chest pain, whereas only 18% in the placebo arm did. Abnormal results on manometry (20%), 24-hour pH monitoring (42%), or endoscopy with visual evidence of esophagitis (26%) were found less frequently. Combination of the three tests did not significantly increase their usefulness. In NCCP patients with GERD, as defined by positive results on a 24-hour pH test or presence of esophagitis on endoscopy, omeprazole treatment led to a response in 95% of patients, whereas 90% of GERD-positive patients treated with placebo did not respond. Of NCCP patients determined to be GERD negative, 39% responded to omeprazole.Omeprazole as a first diagnostic tool in the evaluation of MIBI-negative NCCP is sensitive and specific for determining the cause of NCCP. Endoscopy, manometry, and 24-hour pH monitoring were not only less sensitive in diagnosing NCCP, but they were significantly more expensive.

Aim: For chemotherapy regimens with intermediate FN risk (10–20%), physicians should assess patient risk factors to determine whether overall risk is >20% and G-CSF PP is indicated1. This study described factors considered important by physicians when assessing FN risk and deciding to use G-CSF PP in pts receiving intermediate-FN-risk chemotherapy. Methods: This prospective observational study (NCT01813721) was conducted in Europe, Australia and Canada. Before pt enrolment, investigators reported their own FN risk threshold at which they usually give G-CSF PP, and selected and ranked factors they considered important when assessing overall FN risk and deciding to give G-CSF PP (investigator baseline assessment). For each enrolled pt, their overall FN risk score and the same factors were assessed before starting chemotherapy (patient assessment), and whether G-CSF PP was planned was reported. Results: The final analysis included 165 investigators (67% medical oncologists) and 944 pts (median age 61 years, range 20–94) with breast cancer (42%), lung cancer (39%) or NHL (19%). Stage IV disease was reported in 34% of pts; 1% had a history of FN. Table 1 lists factors most often ranked for FN risk assessment and G-CSF PP decision. The median investigator-reported FN risk threshold was 20% and the pt median overall FN risk score was 18%. G-CSF PP was planned in 82% pts with an overall FN risk score≥the investigator's threshold and in 19% pts with an overall risk score Top 5 most frequently listed factors deemed important by investigators in the overall FN risk assessment and the G-CSF PP decision, at baseline and for each individual patient Factors considered in overall FN risk assessment, % (95% CI) Factors considered in G-CSF PP decision, % (95% CI) Investigator assessment (n = 165) Patient assessment (n = 944) Investigator assessment (n = 165) Patient assessment (n = 944) Chemotherapy agents in the backbone 88 (82–93) Chemotherapy agents in the backbone 93 (88–96) Outcome of FN risk assessment 89 (83–93) Outcome of FN risk assessment 79 (71–84) Prior history of FN 83 (76–89) Tumour type 72 (61–82) Age 80 (71–87) Guidelines 67 (53–79) Baseline laboratory values 76 (68–83) Guidelines 62 (48–74) Baseline laboratory values 74 (64–82) Treatment intent 67 (59–74) Age 73 (64–81) Tumour stage 43 (34–53) Guidelines 71 (61–78) Age 51 (43–60) Prior chemotherapy 71 (62–78) Age 39 (32–48) Treatment intent 69 (61–77) ECOG/Karnofsky performance status 36 (28–45) CI, confidence interval; ECOG, Eastern Cooperative Oncology Group. Conclusions: The most frequently considered factors were chemotherapy regimen for assessing FN risk and FN risk assessment outcome for decision to initiate G-CSF PP. Other factors were selected less consistently at the investigator and pt level. A standardised approach to risk factor assessment may improve guideline adherence and G-CSF use. 1Aapro et al. (2011) Eur J Cancer;47:8–32 Disclosure: G. Freyer: Consultant for Amgen France; E. Kalinka-Warzocha: Received honoraria from Amgen for clinical trials. Given lectures for Amgen; M. Marinca: Has spoken in speaker bureaus for Amgen Romania; L. Decosta: Employed by Amgen and holds stock; Z. Szabo: Employed by Amgen and holds stock. All other authors have declared no conflicts of interest.

A study was conducted to determine whether laser-induced fluorescence could detect high grade dysplasia in Barrett's esophagus. Four-hundred-ten nm laser light was used to induce autofluorescence of Barrett's mucosa in 36 patients during routine endoscopy. The spectra were analyzed using the Differential Normalized Fluorescence (DNF) Index technique to differentiate high grade dysplasia from either low grade or non-dysplastic mucosa. Each spectrum was classified as either premalignant or benign using two different DNF indices. Analyzing the fluorescence spectra from all patients using one DNF Index, 96% of non- dysplastic Barrett's samples classified as benign tissue. All low grade dysplasia samples classified as benign. Ninety percent of high grade dysplasia samples classified as premalignant. Twenty-eight percent of mixed low grade/focal high grade dysplasia samples classified as premalignant. In summary, high grade dysplasia in Barrett's esophagus patients can be detected by endoscopic laser-induced fluorescence spectroscopy using differential normalized fluorescence technique.

3545 Background: Pmab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is approved in Europe as monotherapy for pts with chemotherapy-refractory, EGFR-expressing, KRAS wild-type (WT) mCRC. Methods: Ptsreceived pmab (6 mg/kg) and FOLFIRI every 2 weeks. Eligibility criteria included histologically confirmed mCRC (no prior systemic treatment for metastatic disease), ECOG PS 0–2 and availability of tumor tissue for biomarker analysis. The primary endpoint was objective response rate and secondary endpoints included progression-free survival and safety. All analyses are descriptive, this abstract discusses resections. Results: A total of 154 pts were enrolled. At time of primary analysis (June 09), KRAS evaluable samples were available for 94% (n = 145) of pts: 86 (59%) pts had KRAS WT tumors and 59 (41%) pts had KRAS mutant (MT) tumors. Demographics in the primary analysis set (all KRAS evaluable pts) by KRAS WT and MT were: 78%/54% male; median age (range) 63.5...

1.1. The literature on the subject of pneumothorax of the newborn infant is reviewed; 67 cases have been collected and studied. 2.2. Of these, only 46 have been directly associated with birth. 3.3. Two additional instances at the time of birth are reported, one unique in that subcutaneous emphysema and pneumoperitoneum were also present. 4.4. There appear to be two clinical types of pneumothorax in the newborn infant: one arising suddenly, pneumothorax abrupta, demanding prompt treatment; the other more gradual and less severe, pneumothorax lenta, with good prognosis irrespective of treatment. 5.5. Resistance to the flow of air through the treacheal catheter during insufflation is suggestive of pneumothorax. 6.6. The danger of producing pneumothorax by improper insufflation is stressed. 7.7. Pneumothorax is a condition that probably occurs much more frequently than the literature indicates. Obstetricians should be mindful of its possibility, especially when any method of artificial respiration has been employed.