Electronic Case Report Form Research Articles

The efficacy and stability of an information and communication technology-based centralized monitoring system of adherence to immunosuppressive medication in kidney transplant recipients: study protocol for a randomized controlled trial

BackgroundImmunosuppression non-adherence in kidney transplant recipients (KTRs) not only increases the risk of medical intervention due to acute rejection and graft loss but burdens the socioeconomic system in the form of increased healthcare costs. An aggressive preemptive effort by healthcare professionals, geared to ensure adherence to immunosuppressants in KTRs, is significant and imperative.Methods/designThis study was designed as a prospective, open-label, multicenter, randomized controlled study aimed at evaluating the efficacy and stability of an information and communication technology (ICT)-based centralized monitoring system in boosting medication adherence in KTRs. One hundred fourteen KTRs registered throughout the year 2017 to 2018 are randomized into either the ICT-based centralized home monitoring system or to ambulatory follow-up. The planned follow-up duration is 6 months. The ICT-based centralized home monitoring system described consists of a smart pill box equipped with personal identification system, a home monitoring system, an electronic Case Report Form (eCRF) system, and a comprehensive clinical trial management system (CTMS). It alerts both patients and medical staff with texts and pill box alarms if there is a dosage/dosing time error or a missed dose. Medication adherence and transplant outcomes for the follow-up period are compared between the two groups, while patient satisfaction as well as the stability and cost-effectiveness of the ICT-based monitoring system are to be evaluated.DiscussionThis on-going study is expected to determine if consistent use of the ICT-based centralized monitoring system described could maximize mediation adherence and subsequently enhance transplant outcomes in KTRs. Further, it would lay the foundation for successful implementation of this ICT-based monitoring system for effective management of medication adherence in KTRs.Trials registrationClinicalTrials.gov, Identifier: NCT03136588. Registered on 20 April 2017.

Pilot Project «All-Russian Registry of Patients with Severe Bronchial Asthma.» The First Results in a Children’s Group of Patients (Moscow’s Observation Program)

The article presents the first results of the pilot observation program «The All-Russian Severe Asthma Patient Registry» which was started in Moscow. Objectives. The objective of this initiative is the accumulation of clinical data on patients with severe bronchial asthma in the Russian Federation. Methods. The chosen method was a registry, the rights holders of which were 3 professional associations — Interregional Public Organization «Russian Respiratory Society», Public Organization «Union of Pediatricians of Russia», All-Russian Public Organization «Association of Allergologists and Clinical Immunologists». Results. The results of the pilot project are presented by the data analysis of electronic case report forms of 36 children (totally, the project included 100 patients, 64 adults and 36 children) enrolled in the program from June to December 2016. Using the registry, a detailed analysis of the clinical characteristics of a group of children with severe atopic bronchial asthma was carried out, the results of a pharmacoepidemiological evaluation of therapy were given. Obtained by the researchers, a high frequency of the assignment of a genetically engineered biologic drug of omalizumab meets the international recommendations but does not reflect the all-Russian reality and can be explained by inclusion in the registry of pediatric patients observed only in the Federal State Autonomous Institution «National Scientific and Practical Center of Children’s Health» of the Ministry of Health of the Russian Federation. Conclusion. To determine true indicators that characterize bronchial asthma in children in the Russian Federation it is necessary, undoubtedly, to expand the geography of project participants.

Series: Pragmatic trials and real world evidence: Paper 8. Data collection and management

Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the challenges in designing and conducting pragmatic trials and their specific methodological, operational, regulatory, and ethical implications. The present final paper of the series discusses the operational and methodological challenges of data collection in pragmatic trials. A more pragmatic data collection needs to balance the delivery of highly accurate and complete data with minimizing the level of interference that data entry and verification induce with clinical practice. Furthermore, it should allow for the involvement of a representative sample of practices, physicians, and patients who prescribe/receive treatment in routine care. This paper discusses challenges that are related to the different methods of data collection and presents potential solutions where possible. No one-size-fits-all recommendation can be given for the collection of data in pragmatic trials, although in general the application of existing routinely used data-collection systems and processes seems to best suit the pragmatic approach. However, data access and privacy, the time points of data collection, the level of detail in the data, and the lack of a clear understanding of the data-collection process were identified as main challenges for the usage of routinely collected data in pragmatic trials. A first step should be to determine to what extent existing health care databases provide the necessary study data and can accommodate data collection and management. When more elaborate or detailed data collection or more structured follow-up is required, data collection in a pragmatic trial will have to be tailor-made, often using a hybrid approach using a dedicated electronic case report form (eCRF). In this case, the eCRF should be kept as simple as possible to reduce the burden for practitioners and minimize influence on routine clinical practice.

Efficacy and safety of eribulin in patients with triple negative metastatic breast cancer: Real life experience.

e12580 Background: Eribulin demonstrates improved overall survival compared to standard treatments, Her2-negative and TNBC patients have the most survival benefit. We sought to describe treatment patterns of eribulin and clinical outcomes among TNBC patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between January 1, 2014 and January 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records (electronic or paper-based) and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 52 TNBC patients were considered by 10 providers. A median of age at start of eribulin was 47,5 (39-55) yrs and ECOG status 0-1 were assessed. Most of the pts (92,3%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of BC treatment to 14 (26,9%) pts, 3rd line – to 9 (17,3%), the 4thand later lines – to 29 (55,8%) pts. Objective response occurred in 5 (9,6%) pts. Stable disease registered in 24 (46,1%) pts. Median PFS was 3,0 months (95% CI 1,9-8,55). Overall the drug was well tolerated. The most common type of toxicity was hematologic. Neutropenia gr II was observed in 8 (15,4) pts and III-IV gr in 6 (11,5%), two cases of febrile neutropenia were registered. 4 (7,7%) pts experienced fatigue gr II. Peripheral neuropathy gr II was observed in 4 (7,7%) pts. Dose reduction due to toxicity was performed in 8 (15,4%) pts. Treatment was never withdrawn due to toxicity. Conclusions: This is the first real-life study of clinical outcomes, for patients initiating eribulin therapy for TNBC in community oncology practices throughout the Russian Federation. . Our experience with Eribulin in TNBC patients confirms it efficacy and safety in all lines of treatment, including intensively pretreated patients in this hard-to-treat population.

Efficacy and safety of eribulin in patients with metastatic breast cancer at early and late application: Real-life experience.

e12579 Background: We sought to describe treatment patterns of eribulin and clinical outcomes associated with early and late use among anthracycline and taxane-pretreated patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between Jan1, 2014 and Jan 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 113 MBC patients were considered by 16 providers. A median age was 53 (44-58) yrs and ECOG status 0-1 were assessed. 57 (50,5%) pts were ER/PR-positive, 37 (32,7%) – triple-negative, 19 (16,8%) – HER2-positive (in combination with trastuzumab). Most of the pts (96,5%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of MBC treatment to 36 (32%) pts (early application), the 3rd and later lines (late application) – to 77 (68%) pts. Clinical response rate (ORR and SD ≥ 6 months) was 44% among early line treated patients (first and second-line combined) and 38% among late line eribulin treated patients. Median PFS was 4,89 months (95% CI 2,84-8,00) among early users and 3,96 months (95% CI 2,04-7,99) among later users. The effectiveness in early eribulin application group was higher, but difference was not statistically significant. Tolerability of the drug was good: withdrawn due to toxicity had 3,5%, dose reduction – 13, 3% of pts. The most common type of toxicity was hematological with neutropenia Gr II in 12 (10,6%) of pts and Gr III – in 8 (7,1%) of pts and 2 pts had febrile neutropenia. 6 (5,3%) pts experienced fatigue Gr II. Peripheral neuropathy Gr II was observed in 8 (7,1%) of pts. Conclusions: This is the first real-life description of clinical outcomes, for patients initiating eribulin therapy for MBC throughout the Russian Federation. Our experience with Eribulin in MBC patients confirms it efficacy and safety in early lines of treatment and intensively pretreated patients.

The cost of Clostridium difficile infection (CDI) in hospital in Italy

Objective To describe characteristics, resource utilization and cost for patients experiencing a primary episode of CDI and recurrent CDI. Methods A retrospective observational cohort study was conducted. CDI data were collected with an electronic case report form (CRF) from five Hospitals in Italy. Hospitals collected all resource use attributable to CDI during the period 2011-2014. All resource use from initial presentation to the healthcare provider for CDI symptoms, until resolution of infection attributable to CDI in each enrolled patient was included. The patient cohort was analysed both as a whole and in stratified subgroups (by age, gender and co-morbidities). The impact of CDI on hospital length of stay (LOS) was used to calculate CDI-attributable costs. The total cost of a CDI episode was estimated by multiplying each resource used by its unit cost (national tariffs and market prices); finally, the mean cost/patient was calculated across the cohort. Results In total, data were collected for 488 adult infected patients (mean age 76.0 years [SD ± 15.48]; female 56.6%). Five hundred and three (503) episodes were evaluated (mean number per patient: 1.03 [SD ± 0.23]). LOS attributable to CDI was 14.6 days (SD ± 13.14). Attributable cost per adult patient was €10,224.08 (SD ± €8,963.86), with the majority of the cost being due to hospitalization. The mean cost of a recurrent episode of CDI was €9,504.87 [SD ± €8,614.11]. Conclusions These findings show that the economic burden of CDI is considerable in Italy. The most important cost driver was the LOS attributable to CDI.

Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post-marketing study (J-STEP/EL Study).

Aims/IntroductionAlthough sodium‐glucose cotransporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, they are associated with concerns about specific adverse drug reactions. We carried out a 1‐year post‐marketing study of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus.Materials and MethodsThis was a prospective, observational and multicenter post‐marketing study carried out in the context of routine clinical practice. The study included all type 2 diabetes patients aged ≥65 years who started treatment with tofogliflozin during the first 3 months after its launch on 23 May 2014.ResultsOf 1,535 patients registered, 1,507 patients whose electronic case report forms were collected and who had at least one follow‐up visit were included in the safety analysis. A total of 270 of 1,507 patients (17.92%) had at least one adverse drug reaction to tofogliflozin. The incidences of adverse drug reactions of special interest, namely, polyuria/pollakiuria, volume depletion‐related events, urinary tract infection, genital infection, hypoglycemia and skin disorders were 2.92, 3.85, 2.06, 1.33, 1.06 and 2.39%, respectively. Among those patients evaluable for clinical effectiveness, the mean change in glycated hemoglobin and bodyweight from baseline to last visit was −0.46% (P < 0.0001) and −2.71 kg (P < 0.0001), respectively.ConclusionsThe present study showed that the incidence of adverse drug reactions to tofogliflozin in this study of elderly patients aged ≥65 years differed little from the incidence in the preapproval clinical trials. It was shown that tofogliflozin significantly decreased glycated hemoglobin levels.

Contemporary dual-mobility cup regional and private register: methodology and results.

The dual-mobility cup (DMC) was introduced in 1979. Due to lack of referenced publications, this interesting and innovating concept was ignored during close to 20years. However, 180 studies (level III or IV) have now been published. Evidence-based medicine is based on level I studies. Over the past three decades, the role of national registries developed with the intention of surveying orthopaedic implants. In 2012, we developed, registered, and implemented a specific database for contemporary DMC. Data are collected with an electronic case-report form, and this evaluation is limited to a single product line . From May 2012 to December 2016, 2090 cases of Quattro cup implantation have been registered; results of the first 636 primary cases with a minimum follow-up of three years were previously reported (series 1). Of the 1454 remaining cases, dislocation rate only was monitored (series 2) and results are reported here. In series1 comprising 553 degenerative diseases and 83 proximal femoral fractures (PFF), one dislocation (1.2%) occurred in PFF and none in degenerative disease. Survivorship (infection excluded) at three years was 99.8%. In series 2 (1315 degenerative diseases; 139 PFFs), dislocation rate was 0.27% (four cases). In neither series did we observe any intraprosthetic dislocation. Results of this private regional register confirm the high efficiency of DMC to decrease dislocation rate (0.23%). Few outcomes of DMC in primary total hip arthroplasty (THA) are published in national registries. The Swedish Hip Arthroplasty Register has reported on 287 primary DMC hips of 78,098 THAs. No dislocations were reported. We conclude that DMC decreases dislocation rate, and the national registry of Lithuania also reports a significant decrease in the rate of revision for dislocation in the DMC group. These data-available online-allow us to monitor DMC in real time, although they lack short-term follow-up.

Abstract P5-15-16: Utilization and outcomes of eribulin in triple negative metastatic breast cancer: Real-world findings

Abstract Background Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs) and a significant proportion of all BC deaths. Eribulin is approved for the treatment of metastatic BC (MBC) after treatment with two prior regimens. A pooled analysis of two phase III studies of eribulin in women with TNBC patients found a 26% reduction in the risk of death vs. controls. Treatment patterns of eribulin and clinical outcomes associated with early vs. late use among TNBC patients treated in community oncology practices have not been evaluated. Methods Physicians from the Cardinal Health Oncology Research Network completed an electronic case report form (CRF) on up to 7 TNBC patients treated with eribulin between 01/01/11 and 12/31/13. Adult female patients with pathologically confirmed metastatic disease and not participating in any interventional clinical trial were included. Providers indicated the usage of chemotherapy, either alone or in combination, by line of therapy (LOT) up to the LOT of eribulin initiation. Reported data points include: clinical parameters (eg, site of metastases, ECOG performance status, and comorbidities), treatment events (eg, LOT start/end date and rationale for discontinuation), and outcomes (eg, clinical response and date of death). Dosing, adverse events, use of supportive care medications, and hospitalization were also captured during eribulin treatment. Use of eribulin in LOT 1/LOT 2 was considered early; LOT 3+ was considered late. All comparisons are univariate. Results An interim analysis was performed on 123 TNBC patients (planned sample size of 250) collected from 26 providers. Patient mean age at eribulin treatment initiation was 55.0 years. Mean follow-up duration was 27 mo (SD = 11.9) from initiation of first line metastatic treatment until date of last visit, death, or loss to follow-up. Overall, 74.0% were deceased, 85.4% had received at least 3 LOTs in the metastatic setting, and 45.4% were stage IV at diagnosis. Most women were prescribed eribulin in a later LOT (61.8%), 3 (2.4%) patients received eribulin in LOT1 and 44 in LOT2 (36.7%). Among patients with known treatment start and end dates (87.0%), mean duration of treatment (DOT) was 6.2 mo (SD = 3.3), median 5.8 mo among early recipients and 5.5 mo (SD = 5.7), median 4.1 mo, among later recipients (p = 0.39). Early users were more likely (p = 0.05) to have a complete/partial response (71.1% vs. 47.7%) and less likely to have progressive disease (7.1% vs. 12.3%). In comparing eribulin users to all other therapies, eribulin users had a significantly longer DOT in LOT2 (5.9 vs. 4.7 mo, p = 0.01) and LOT3 (5.8 vs. 3.6 mo, p = 0.03). In LOT3, eribulin users were significantly more likely to have complete/partial response (54.2% vs. 18.8%) and less likely to have to have progressive disease (4.2% vs. 37.5%) compared to all other observed LOT3 therapies. Conclusions This interim analysis indicates longer DOT for patients treated with eribulin for TNBC in LOT2 and LOT3 and a more favorable response rate compared to all other agents used in each LOT, respectively, among patients treated in community oncology practices. Full results will be available at the conference. Citation Format: Kish JK, Mougalian SS, Copher R, McAllister L, Zhixiao W, Broscious M. Utilization and outcomes of eribulin in triple negative metastatic breast cancer: Real-world findings [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-16.

INVOLVEMENT OF STAKEHOLDERS IN THE REPORTING PROCESS OF SERIOUS ADVERSE EVENTS DURING CLINICAL TRIALS IN A SUB-SAHARAN RESEARCH CENTER, LAMBARÉNÉ, GABON

BackgroundThe pharmacovigilance of medical products for human use should start during the clinical development and continues after licensure. In developed countries, regulatory agencies are actively involved in all steps of...

Pre-Exposure Prophylaxis (PrEP) as an Additional Tool for HIV Prevention Among Men Who Have Sex With Men in Belgium: The Be-PrEP-ared Study Protocol.

BackgroundPre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent HIV. With the approval of Truvada as daily PrEP by the European Commission in August 2016, individual European Member states prepare themselves for PrEP implementation following the examples of France and Norway. However, context-specific data to guide optimal implementation is currently lacking.ObjectiveWith this demonstration project we evaluate whether daily and event-driven PrEP, provided within a comprehensive prevention package, is a feasible and acceptable additional prevention tool for men who have sex with men (MSM) at high risk of acquiring HIV in Belgium. The study’s primary objective is to document the uptake, acceptability, and adherence to both daily and event-driven PrEP, while several secondary objectives have been formulated including impact of PrEP use on sexual behavior.MethodsThe Be-PrEP-ared study is a phase 3, single-site, open-label prospective cohort study with a large social science component embedded in the trial. A total of 200 participants choose between daily or event-driven PrEP use and may switch, discontinue, or restart their regimen at the 3-monthly visits for a duration of 18 months. Data are collected on several platforms: an electronic case report form, a Web-based tool where participants register their sexual behavior and pill use, a more detailed electronic self-administered questionnaire completed during study visits on a tablet computer, and in-depth interviews among a selected sample of participants. To answer the primary objective, the recruitment rate, (un)safe sex behavior during the last 6 months, percentage of reported intention to use PrEP in the future, retention rates in different regimens, and attitudes towards PrEP use will be analyzed. Adherence will be monitored using self-reported adherence, pill count, tenofovir drug levels in blood samples, and the perceived skills to adhere.ResultsAll participants are currently enrolled, and the last study visit is planned to take place around Q3 2018.ConclusionsAs PrEP is not yet available in Belgium for use, this study will provide insights into how to optimally implement PrEP within the current health care provision and will shape national and European guidelines with regard to the place of PrEP in HIV prevention strategies.ClinicalTrialEU Clinical Trial 2015-000054-37; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000054-37/BE (Archived by WebCite at http://www.webcitation.org/6nacjSdmM).

Global, Prospective, Non-Interventional, Observational Study of Presentation, Treatment Patterns, and Outcomes in Multiple Myeloma Patients: The Insight-MM Study

Global, Prospective, Non-Interventional, Observational Study of Presentation, Treatment Patterns, and Outcomes in Multiple Myeloma Patients: The Insight-MM Study

Bleeding Events and Safety Outcomes in Patients with Hemophilia a with Inhibitors: A Prospective, Multicenter, Non-Interventional Study

Bleeding Events and Safety Outcomes in Patients with Hemophilia a with Inhibitors: A Prospective, Multicenter, Non-Interventional Study

The design, rationale, and baseline characteristics of a nationwide cohort registry in China: blood pressure and clinical outcome in TIA or ischemic stroke.

BackgroundThe relationship between poststroke blood pressure (BP) and clinical outcomes in ischemic stroke (IS) is still controversial. However, there is no large BP database for IS or transient ischemic attack (TIA) in China. This study aims to describe the rationale, study design, and baseline characteristics of a nationwide BP database in IS or TIA patients in China.Materials and methodsThe BOSS (blood pressure and clinical outcome in TIA or ischemic stroke) study was a hospital-based, prospective cohort study aiming to assess BP parameters and clinical outcome in IS/TIA patients. BP parameters were based on office BP, ambulatory BP, and home BP. Clinical outcomes included stroke recurrence, combined vascular events, and disability. Electronic case-report forms were used to record baseline and follow-up data. The patients were followed up for clinical outcomes at 3 months through face-to-face interview and at 12 months by telephone.ResultsBetween October 2012 and February 2014, the BOSS registry recruited 2,608 patients from 61 hospitals, with a mean age of 62.5 years, 32.4% of whom were female, 88.9% with an entry diagnosis of IS, and 86% diagnosed with hypertension. The rates of patients lost-to-follow-up were 3.1% at 3 months and 5.1% at 1 year; 93% of patients completed ambulatory BP monitoring during hospitalization and 94.7% finished a 3-month BP diary.ConclusionThe BOSS registry will provide important evidence about BP management in the acute phase and secondary prevention for IS/TIA patients.

PRM208 - Important Methodological Considerations and Strategies for Resolution for Multinational Retrospective Chart Review Studies

In the absence of secondary sources of health care data, chart review studies are necessary to fulfill peri- and post-approval evidence gaps such as informing on patient profiles, treatment effectiveness, and clinical and safety outcomes. Multinational studies (conducted in more than one country) are essential in understanding how to best address global medical needs; however the conduct of these studies poses its own set of challenges. Our objective was to explore the design and operational challenges and strategies to overcome these challenges in order to ensure successful conduct of multinational chart review studies. Fourteen recent multinational chart review case studies were evaluated to describe lessons learned in terms of key methodological considerations and strategies for resolution. Eight studies (57%) were comprised of 3 or more countries and 7 studies (50%) were comprised of European countries only. Across studies, common scientific and operational considerations included identifying country-specific ethics and privacy regulations (including patient informed consent) and accounting for variance in treatment patterns and safety reporting. Recommendations include pilot-testing the case report form (CRF) in participating countries to ensure data points of interest are available, sufficient staff training on study purpose, outcomes and electronic CRF navigation, and creation of detailed training materials and guidelines for data abstraction. Additionally, in order to ensure uniformity of data collection across sites, the use of a standardized data collection tool and the implementation of quality control guidelines for data cleaning and query resolution is recommended. Multinational chart reviews are an effective methodology for capturing tailored, patient-level data and offer an important opportunity to inform on global clinical data. While the conduct of multinational chart review studies can be challenging due to inter-country variance, careful consideration of key design and operational challenges can allow for successful study implementation.

PS 08-24 SAFETY AND EFFICACY OF FIMASARTAN IN ELDERLY PATIENTS WITH ARTERIAL HPERTENSION (1 YEAR FOLLOW-UP DATA FROM K-MetS STUDY)

Objective: The objective of this study was to determine the safety and efficacy of fimasartan in elderly patients (age ≥60 year-old) with hypertension by measuring clinic and home blood pressure and compare with non-elderly patients. Design and Method: K-MetS study was a nation-wide prospective observational study including primary care clinic to tertiary care hospital about antihypertensive treatment including fimasartan. Among the 6,399 study population, elderly patients (age ≥60 year-old) who were treated for 1 year with fimasartan (30–120 mg daily) were recruited, and the data were systematically collected using electronic case report forms. Written informed consent forms were obtained from all patients. Results: A total of 2,363 elderly patients [1,109 (46.9%) males; mean age 67.3 ± 5.7 years] were evaluated. Overall, fimasartan reduced systolic blood pressure (SBP) from 144.15 ± 17.25 to 127.75 ± 12.87 mmHg and diastolic blood pressure (DBP) from 85.10 ± 10.41 to 76.84 ± 8.36 mmHg (all p < 0.0001). The heart rate was reduced from 72.65 ± 10.25 to 71.55 ± 9.2 beats/min within 1-year fimasartan-including antihypertensive treatment (p < 0.0001). This efficacy of fimasartan was consistent regardless of patient's sex, underlying medical condition or co-morbidities in elderly patients. Adverse events were reported in 37 (0.016%) patients. There were no dose dependencies for adverse events. Non-of these events lead to drug discontinuation. The goal achievement rate (combined SBP/DBP < 140/ 90 mmHg) and the responder rate (DBP to <90 mmHg or a reduction of ≥10 mmHg) were 1,914 subjects (81.0%) and 2253 subjects (95.3%), respectively without differences from none-elderly patients. 1-year fimasartan treatment efficacy was gradually progress over 1-year treatment especially for SBP reduction in home BP data. Conclusions: 1-year treatment of fimasartan in eldely patients reduced clinic and home BP to normal level. There were no serious adverse events that lead to drug discontinuation. The safety and efficacy of fimasartan were found to be excellent beyond the target BP achievement in a large elderly patient population.

Professional Practices and Diagnostic Issues in Neuroendocrine Tumour Pathology: Results of a Prospective One-Year Survey among French Pathologists (the PRONET Study)

Introduction: Many changes have recently occurred in the practice of neuroendocrine tumour (NET) pathology. We therefore aimed to evaluate how pathologists have adapted their daily practice to the most recent international guidelines for diagnostic and prognostic evaluation. Procedures: A 12-month prospective study (PRONET) was carried out among French pathologists between August 2010 and July 2011. Data were collected using an anonymous electronic case report form. Observations: Five hundred laboratories were invited, 149 accepted to participate, 80 were active and 59 provided eligible cases. A total of 1,340 cases were collected. The primary tumour was gastroenteropancreatic in 58.1% of cases and thoracic in 18.1%; it was from another site in 9.7%; 12.3% of cases were metastases of unknown origin. Pathological diagnosis was made from the examination of surgical samples in 58.1% of cases, biopsy specimens in 33.5%, endoscopic resections in 3.1% and cytological preparations in 4.2%. For the demonstration of the neuroendocrine nature of the tumour, chromogranin A and synaptophysin were tested in, respectively, 97.1 and 82.8% of cases. The differentiation status was definitely provided in 95.7% of cases. Mitotic count was attempted in 80.1% of cases and Ki67 index in 80.7%. In gastroenteropancreatic (GEP)-NETs, histological grading was available in 95.9% of the cases. WHO classification was available or feasible in 94.1% of GEP-NETs and 93.8% of thoracic NETs. TNM staging was performed according to International Union against Cancer in 74.8% of GEP-NETs and according to European Neuroendocrine Tumour Society in 55.6%. Conclusions: The PRONET study shows that the current recommendations and diagnostic procedures are satisfactorily respected by most pathologists in daily practice.

The Cooking and Pneumonia Study (CAPS) in Malawi: Implementation of Remote Source Data Verification.

BackgroundSource data verification (SDV) is a data monitoring procedure which compares the original records with the Case Report Form (CRF). Traditionally, on-site SDV relies on monitors making multiples visits to study sites requiring extensive resources. The Cooking And Pneumonia Study (CAPS) is a 24- month village-level cluster randomized controlled trial assessing the effectiveness of an advanced cook-stove intervention in preventing pneumonia in children under five in rural Malawi (www.capstudy.org). CAPS used smartphones to capture digital images of the original records on an electronic CRF (eCRF). In the present study, descriptive statistics are used to report the experience of electronic data capture with remote SDV in a challenging research setting in rural Malawi.MethodsAt three monthly intervals, fieldworkers, who were employed by CAPS, captured pneumonia data from the original records onto the eCRF. Fieldworkers also captured digital images of the original records. Once Internet connectivity was available, the data captured on the eCRF and the digital images of the original records were uploaded to a web-based SDV application. This enabled SDV to be conducted remotely from the UK. We conducted SDV of the pneumonia data (occurrence, severity, and clinical indicators) recorded in the eCRF with the data in the digital images of the original records.Result664 episodes of pneumonia were recorded after 6 months of follow-up. Of these 664 episodes, 611 (92%) had a finding of pneumonia in the original records. All digital images of the original records were clear and legible.ConclusionElectronic data capture using eCRFs on mobile technology is feasible in rural Malawi. Capturing digital images of the original records in the field allows remote SDV to be conducted efficiently and securely without requiring additional field visits. We recommend these approaches in similar settings, especially those with health endpoints.

The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC): 2010–2015

BackgroundCentral and East European (CEE) patients with acute coronary syndromes (ACS) have worse outcomes than US and West European patients, including higher mortality rates. The aim of the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) was to define patient and treatment characteristics in order to examine whether differences in clinical and ethnic factors or healthcare organization may mediate the observed disparities in outcomes. Methods and resultsBetween October 2010 and December 2015, 14,326 patients with ACS were prospectively enrolled. Of these patients 8650 (60%) had ST-segment elevation myocardial infarction (STEMI). Patients were enrolled from 41 centers in 12 countries in Europe. Standardized electronic case report forms were completed by trained study coordinators, and included fields relating to demographic factors, medical history and processes of inpatient care, supplemented with a detailed baseline interview on time delays to hospital admission. Blood sampling for genetic data were obtained at hospital discharge. Prospective individual patient follow-up was carried out with a focus on patient health (symptoms) and vital status. Thirty day follow-up was 100% complete. Difficulties were found for recruitment of patients at 6months. Publications are available at ClinicalTrials.gov: NCT01218776. ConclusionsISACS-TC is a novel ACS registry with detailed information on CEE patients' clinical, demographic, treatment, and metabolic characteristics and health status. The concurrent enrollment of patients from some European Union founding members provides greater generalizability of the data. ISACS-TC may help to make an additional improvement in clinical outcomes of countries with economy in transition.

Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial

In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.