Showing papers on "Case report form published in 2013"

Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH

Abstract: Data describing real-life management and treatment of community-acquired pneumonia (CAP) in Europe are limited. REACH ( NCT01293435 ) was a retrospective, observational study collecting data on the management of EU patients hospitalized with CAP. The purpose of this study was to understand patient and disease characteristics in patients hospitalized with CAP and to review current clinical practices and outcomes. Patients were aged ≥18 years, hospitalized with CAP between March 2010 and February 2011, and requiring in-hospital treatment with intravenous antibiotics. An electronic Case Report Form was used to collect patient, disease and treatment variables, including type of CAP, medical history, treatment setting, antibiotics administered and clinical outcomes. Patients (N = 2,039) were recruited from 128 centres in ten EU countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Turkey, UK). The majority of patients were aged ≥65 years (56.4%) and had CAP only (78.8%). Initial antibiotic treatment modification occurred in 28.9% of patients and was more likely in certain groups (patients with comorbidities; more severely ill patients; patients with healthcare-associated pneumonia, immunosuppression or recurrent episodes of CAP). Streamlining (de-escalation) of therapy occurred in 5.1% of patients. Mean length of hospital stay was 12.6 days and overall mortality was 7.2%. These data provide a current overview of clinical practice in patients with CAP in EU hospitals, revealing high rates of initial antibiotic treatment modification. The findings may precipitate reassessment of optimal management regimens for hospitalized CAP patients.

The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan

Abstract: Background: The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis. Objective: In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies. Methods: Our statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. We reviewed the data collected by the research team as specified in the study protocol and detailed in the study case report form. We describe information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation, other related therapies and other relevant data with appropriate comparisons between groups. We define the primary, secondary and tertiary outcomes for the study, with description of the planned statistical analyses. Results: We have developed a statistical analysis plan with a trial profile, mock-up tables and figures. We describe a plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies and adverse events. We describe the primary, secondary and tertiary outcomes with identification of subgroups to be analysed. Conclusion: We have developed a statistical analysis plan for the ARISE study, available in the public domain, before the completion of recruitment into the study. This will minimise analytical bias and conforms to current best practice in conducting clinical trials.

Study of therapeutic hypothermia (32 to 35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial): outcome of the pilot phase of the trial

Abstract: Background: Clinical trials in traumatic brain injury (TBI) are challenging. Previous trials of complex interventions were conducted in high-income countries, reported long lead times for site setup and low screened-to-recruitment rates. In this report we evaluate the internal pilot phase of an international, multicentre TBI trial of a complex intervention to assess: design and implementation of an online case report form; feasibility of recruitment (sites and patients); feasibility and effectiveness of delivery of the protocol. Methods: All aspects of the pilot phase of the trial were conducted as for the main trial. The pilot phase had oversight by independent Steering and Data Monitoring committees. Results: Forty sites across 12 countries gained ethical approval. Thirty seven of 40 sites were initiated for recruitment. Of these, 29 had screened patients and 21 randomized at least one patient. Lead times to ethics approval (6.8 weeks), hospital approval (18 weeks), interest to set up (61 weeks), set up to screening (11 weeks), and set up to randomization (31.6 weeks) are comparable with other international trials. Sixteen per cent of screened patients were eligible. We found 88% compliance rate with trial protocol. Conclusion: The pilot data demonstrated good feasibility for this large international multicentre randomized controlled trial of hypothermia to control intracranial pressure. The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered.

Bisphosphonate-Related Osteonecrosis of Jaw in the Adjuvant Breast Cancer Setting: Risks and Perspective

Abstract: Bisphosphonate-related osteonecrosis of jaw (BONJ) is a rare adverse effect of antiresorptive treatments (primarily zoledronic acid and more recently denusomab) to my knowledge first described 10 years ago. The definition of BONJ includes the presence of necrotic bone for more than 6 weeks in an area of the oral cavity normally covered by mucosa, prior or current bisphosphonate use, and no prior history of radiation to the head and neck. The risks of BONJ increase with more frequent scheduling (ie, monthly) and prolonged durations of administration (ie, 2 years) of intravenous bisphosphonates, and the major risk factor for BONJ is dental extractions or procedures that expose bone during antiresorptive therapy. Principally, this led to the recommendation that, before initiating bisphosphonates, a dental evaluation and, if needed, dental work be completed before starting these drugs. Small nonrandomized cohort studies suggest that the incidence of BONJ is decreased with dental screening before initiating intravenous (IV) bisphosphonates. There is no evidence that routine dental health maintenance increases the risks of BONJ, and patients should be encouraged to have routine care during treatment with these drugs. The precise mechanism(s) of BONJ or why it is confined to the jaw, predisposing risk factors other than dental extractions, optimal treatments, and more importantly, the shortand long-term outcomes and health-related quality of life of patients who develop BONJ are largely unknown. Some, but not all, recent studies suggest that genetic polymorphisms in genes related to bone metabolism, collagen, or aromatase may predispose patients to BONJ. As is true of other rare but serious complications of cancer treatment, health professionals tend to overestimate or underestimate the risks, depending on their specialty (eg, dentists or medical oncologists), general knowledge of BONJ, and anecdotal experience. In addition, recent small studies in patients seen in either dental or cancer clinics suggest that awareness and education about BONJ is lacking. Rathbone et al, on behalf of the Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial investigators, have made an important contribution by providing the incidence and outcomes of BONJ in a prospective randomized controlled trial of zoledronic acid in more than 3,000 women with localized breast cancer receiving adjuvant systemic therapy and assessing the oral health-related quality of life in a small subset of them. Several aspects of the trial are noteworthy. The trial opened in 2003, which is the same year that BONJ was first described. In 2004, the protocol and consent was amended to exclude women with active dental issues or recent jaw surgery, consent was reaffirmed for all prior trial enrollees, educational materials were provided to all trial participants and investigators, and suspected cases of BONJ were reported as serious adverse events in real time to the trial coordinating center. These then triggered requests for additional information, and the final case determinations were adjudicated by the study team, which included an oral surgeon. Thus to the extent possible, investigators and trial participants were made aware of the potential of BONJ. However, we do not know whether a standard approach to case ascertainment of BONJ was performed at every clinic visit for all women enrolled onto the trial. For example, in recently closed Cancer and Leukemia Group B (CALGB) trial 70604 (ClinicalTrials.gov trial number NCT00869206) trial participants were queried about dental problems, visits, and procedures they had had in the past 1 to 12 months, and the information was recorded in the monthly case report form. Without such a standard approach to case ascertainment, the potential bias of underor over-reporting suspected cases of BONJ is possible. The schedule of zoledronic acid in the AZURE trial was intensive, with one 4-mg dose administered every 3 to 4 weeks for 5 to 6 months, followed by one dose every 3 to 6 months for 46 months, or a total of 19 doses in 5 years. This schedule approximates the 24 once-permonth zoledronic acid doses typically used to treat women with breast cancer and skeletal metastases. It is interesting to note that, in the Austrian Breast Cancer Study Group (ABCSG) trial-12, in which more than 1,800 premenopausal women received goselerin and were randomly assigned to either tamoxifen or anastrozole with or without zoledronic acid, treatment with zoledronic acid reduced the risk of local recurrence, bone metastases, and distant metastases (overall hazard ratio, 0.68; 95% CI, 0.51 to 0.91; P .009). The schedule of zoledronic acid in the ABCSG trial was one 4-mg dose every 6 months for 3 years or a total of 6 doses, and there were no reports of BONJ (median follow-up, 62 months). In the AZURE trial, the overall cumulative incidence of BONJ at 108 months was 2.1% (95% CI, 0.9% to 3.3%) and, extrapolating from Figure 1 of the article, was about 1.1% at 36 months. This is JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 21 JULY 2

The A1chieve study: Mapping the Ibn Battuta trail.

Abstract: Ibn Battuta (1304-69), the Moroccan explorer, was famous for his observational skills, as well as his multifaceted acumen. His travels extended from Morocco, his homeland, across North Africa, Arabia, and the Arabian Gulf, to India and beyond. His observations, recorded in the book Rihla (The Journey) provide an accurate account of the world that he inhabited seven centuries ago.[1] This supplement of the Indian Journal of Endocrinology and Metabolism traces Ibn Battuta's trail in ways more than one. The huge geographical spread of the articles mentioned in this issue corresponds to his epic journey. The number of subjects studied, the number of clinical trial sites and countries represented, remind us of Ibn Battuta's travels. The sheer number of original papers, and the amount of data presented, try to live up to the voluminous Rihla. The wide spectrum of analyses reported upon the full variety of insulin analogues used in this trial seem similar to the equally vast cultures reported by Ibn Battuta long ago. Observational studies are non-interventional studies that are conducted to ascertain the efficacy and safety of therapies in the post-marketing period. The main feature of these studies is to collect safety data in a large cohort of patients as a representative of the whole population.[2] Just as Ibn Battuta's observations give us an accurate, vivid account of life in his times, observational studies today describe the real-life picture of health and disease. While observational studies have been carried out with insulin analogues there has been no large scale study with all three viz., basal, bolus and premix insulin analogues. A1chieve study was a 24-week, international, prospective, multicentre, non-randomized, observational study in type 2 diabetes mellitus (T2DM) patients, which evaluated safety and effectiveness of insulin analogues viz., insulin aspart (NovoRapid®, Novo Nordisk), insulin detemir (Levemir®, Novo Nordisk, Denmark) and biphasic insulin aspart 30 (NovoMix 30®, Novo Nordisk), alone or in combination with OADs in routine clinical practice. The A1chieve study was carried out in more than 60,000 patients from 28 countries across four continents (Asia, Africa, Latin America and Europe). The robust methodology and statistical analysis, coupled with the Brobdingnagian subject pool, has made the A1chieve study a landmark in modern diabetology. This Afro-Asian results supplement details the results from 43 regions of India, the Arabian Gulf, Morocco, Tunisia and Libya. This editorial describes, in brief, the methodology of A1chieve study.[3] This applies to the study conducted across the nations and continents. The study was conducted in accordance with the principles of declaration of Helsinki and good clinical practice (GCP) guidelines. Before the commencement of the study, ethics committee approval and informed consent from all participants, was obtained. Patients with type 2 diabetes who had not used any of the study insulin's previously, and who had been started on one of the study insulin's or excipients within past 4 weeks of study commencement, were recruited. People with hypersensitivity to study insulin's and women who were either pregnant or breast feeding or planning to conceive within 6 months of the study, were excluded. Participants were free to withdraw at any time during the study. If they withdrew, the data collected was used for analysis until the point when consent was withdrawn. The primary objective was to assess number of serious adverse drug reactions (SADRs) including major hypoglycemic events recorded from baseline to final visit. All serious adverse events (SAEs) and adverse drug reactions (ADRs) were also recorded. An ADR was defined as an adverse event for which the reporting physician suspected a possible or probable relationship to a study drug. Minor hypoglycaemic episodes and nocturnal hypoglycaemia were also assessed. Major hypoglycaemic events were defined as events with severe central nervous system symptoms, consistent with hypoglycaemia, for which the person was unable to self-treat, and accompanied by plasma glucose < 3.1 mmol/L or 56 mg/dL, or reversal of symptoms after either food intake or glucagon or intravenous glucose administration. Minor hypoglycaemia was any event, with or without symptoms of hypoglycaemia, with a plasma glucose reading below 3.1 mmol/L or 56 mg/dL and the participant was able to self-treat. Nocturnal hypoglycaemia was defined as a symptomatic event consistent with hypoglycaemia that occurred during sleep between bedtime after the evening insulin injection and before getting up in the morning. Efficacy of the study drugs was determined by measuring change in HbA1c, fasting plasma glucose (FPG), and post-prandial glucose at interim visit and final visit compared with baseline. Body weight, blood pressure, and serum lipids were also recorded at final visit to identify any cardiovascular risk. Furthermore, effect on health related quality of life (HRQoL) of the participants was also evaluated. The insulin therapies were prescribed by the physician in routine clinical practice. The data was collected at baseline, interim (around 12 weeks from baseline) and final (around 24 weeks from baseline) visit. The time period of 4 weeks past baseline visit, was defined as a pre-study period. Data was collected from the physician's clinical notes, and participant's recall and self-monitoring diary/meter at each visit and transferred to a standard case report form (CRF). HRQoL was measured using the EQ-5D questionnaire at baseline and after 24 weeks of therapy with insulin analogues. Statistical analyses were performed for the entire cohort and for the entire cohort classified as insulin-naive or prior insulin users. For the change in hypoglycaemia from baseline, the percentage of patients reporting at least one event was analyzed using Fisher's exact test. The change from baseline in HbA1c, FPG, PPPG, SBP, body weight, blood lipids and HRQoL was analyzed using a paired t-test using baseline and end-of-study values. Data analyses were performed by Novo Nordisk using SAS (version 9.1.3). In this study, we present the data for subgroups having 5 or more patients only. The aim of A1chieve study was not only to focus on the safety and efficacy of study insulin but also to gather data for future health economic analysis. Moreover further analyses may confer benefits to vulnerable population such as the elderly and/or those with co-morbidities since such groups are generally excluded from randomized controlled trials (RCTs). This supplement of the Indian Journal of Endocrinology and Metabolism is proud to follow in Ibn Battuta's trail, presenting robust multinational data, to a discerning international audience.