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- [Results of the Czech National Colorectal Cancer Screening Programme - Colonoscopy Examinations.] [JOURNAL ARTICLE]
- Klin Onkol 2014; 27(Supplementum 2):98-105.
Introduction: Colorectal cancer (CRC) is one of the most common cancers, and the Central European countries have the highest CRC burden worldwide. CRC screening has repeatedly been proven capable of decreasing CRC mortality and incidence rates. The nationwide Colorectal Cancer Screening Programme in the Czech Republic involves the colonoscopic examination as a dia-gnostic method (for patients with a positive FOBT result - screening colonoscopy - SC), or as a screening method (primary screening colonoscopy - PSC). The aim of this article is to present the results of colonoscopic examinations performed as part of the Czech screening programme. Material and Methods: For the purpose of quality assurance, the Czech programme has been equipped since 2006 with an information system called the Colorectal Cancer Screening Registry, which collects and evaluates data on preventive colonoscopies performed in the colonoscopy screening centres. Performance indicators, as specified in the European Guidelines (and adapted for the Czech programme), are employed to assess preventive colonoscopies performed in the Czech Republic. Results: Since 2006, more than 110,000 SCs and almost 20,000 PSCs were recorded. Approximately 95% of SCs and almost 98% of PSC were classified as total, i.e. examining the entire colonic mucosa up to the caecum. The positive predictive value of FOBT for adenomas has increased slightly and continuously over time, and was 39.7% in 2013. In PSC, the adenoma detection rate (ADR) has recently increased compared to previous years, and was 27.3% in 2013. CRC was detected in 3.7% of individuals undergoing an SC examination and in 1.0% of individuals undergoing a PSC examination. The programme safety is controlled based on the monitoring of complications during colonoscopies; these can occur either during dia-gnostic colonoscopy (perforation in 0.03% of cases since 2006) or during endoscopic polypectomy (perforation in 0.12% of cases, bleeding in 0.73% of cases since 2006). Conclusion: Our results confirm that the quality of colonoscopic examinations corresponds to the international standards and that this is not an obstacle to a positive impact of CRC screening on the Czech population, which has a high colorectal cancer burden.Key words: colorectal neoplasms - mass screening - colonoscopy - quality indicators - health care This study was supported by the project 36/14/NAP "Development and implementation of methodology for the evaluation of effectiveness of personalised invitations of citizens to cancer screening programmes" as part of the programme of the Czech Ministry of Health "National action plans and conceptions". The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biomedical papers.Submitted: 12. 9. 2014Accepted: 17. 10. 2014.
- Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction. [JOURNAL ARTICLE]
- Cytotherapy 2014 Dec 4.
Cell therapy is promising as an exploratory cardiovascular therapy. We have recently developed an investigational new drug named Stempeucel (bone marrow-derived allogeneic mesenchymal stromal cells) for patients with acute myocardial infarction (AMI) with ST-segment elevation. A phase I/II randomized, double-blind, single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo (multiple electrolytes injection).Twenty patients who had undergone percutaneous coronary intervention for AMI were randomly assigned (1:1) to receive intravenous Stempeucel or placebo and were followed for 2 years.The number of treatment-emergent adverse events observed were 18 and 21 in the Stempeucel and placebo groups, respectively. None of the adverse events were related to Stempeucel according to the investigators and independent data safety monitoring board. There was no serious adverse event in the Stempeucel group and there were three serious adverse events in the placebo group, of which one had a fatal outcome. Ejection fraction determined by use of echocardiography showed improvement in both Stempeucel (43.06% to 47.80%) and placebo (43.44% to 45.33%) groups at 6 months (P = 0.26). Perfusion scores measured by use of single-photon emission tomography and infarct volume measured by use of magnetic resonance imaging showed no significant differences between the two groups at 6 months.This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention. The optimal dose and route of administration needs further evaluation in larger clinical trials (http://clinicaltrials.gov/show/NCT00883727).
- Unsuccessful trial accrual and human subjects protections: An empirical analysis of recently closed trials. [JOURNAL ARTICLE]
- Clin Trials 2014 Dec 4.
Ethical evaluation of risk-benefit in clinical trials is premised on the achievability of resolving research questions motivating an investigation.To determine the fraction and number of patients enrolled in trials that were at risk of not meaningfully addressing their primary research objective due to unsuccessful patient accrual.We used the National Library of Medicine clinical trial registry to capture all initiated phases 2 and 3 intervention clinical trials that were registered as closed in 2011. We then determined the number that had been terminated due to unsuccessful accrual and the number that had closed after less than 85% of the target number of human subjects had been enrolled. Five factors were tested for association with unsuccessful accrual.Of 2579 eligible trials, 481 (19%) either terminated for failed accrual or completed with less than 85% expected enrolment, seriously compromising their statistical power. Factors associated with unsuccessful accrual included greater number of eligibility criteria (p = 0.013), non-industry funding (25% vs 16%, p < 0.0001), earlier trial phase (23% vs 16%, p < 0.0001), fewer number of research sites at trial completion (p < 0.0001) and at registration (p < 0.0001), and an active (non-placebo) comparator (23% vs 16%, p < 0.001).A total of 48,027 patients had enrolled in trials closed in 2011 who were unable to answer the primary research question meaningfully. Ethics bodies, investigators, and data monitoring committees should carefully scrutinize trial design, recruitment plans, and feasibility of achieving accrual targets when designing and reviewing trials, monitor accrual once initiated, and take corrective action when accrual is lagging.
- Editor's Choice - Safety of Carotid Endarterectomy After Intravenous Thrombolysis for Acute Ischaemic Stroke: A Case-Controlled Multicentre Registry Study. [Journal Article]
- Eur J Vasc Endovasc Surg 2014 Dec; 48(6):620-5.
Few studies have been published on the safety of carotid endarterectomy (CEA) after intravenous thrombolysis (IVT). Registry reports have been recommended in order to gather large study groups.A retrospective, registry based, case controlled study on prospectively gathered data from Sweden, the capital region of Finland, and from Denmark, including 30 days of follow up.The study group was a consecutive series of 5526 patients who had CEA for symptomatic carotid artery stenosis during a 4.5 year period. Among these, 202 (4%) had IVT prior to surgery, including 117 having CEA within 14 days, and 59 within 7 days of thrombolysis. IVT as well as CEA were performed following established guidelines. The median time from index symptom to CEA was 12 days (range 0-130, IQR 7-21).The 30 day combined stroke and death rate was 3.5% (95% CI 1.69-6.99) for those having IVT + CEA, 4.1% (95% CI 3.46-4.39) for those having CEA without previous IVT (odds ratio 0.84 [95% CI 0.39-1.81]), 3.4% (95% CI 1.33-8.39) for those having IVT + CEA within 14 days, and 5.1% (95% CI 1.74-13.91) for those having IVT + CEA within 7 days.Data on the time from symptoms to CEA in patients not having IVT, Rankin score, degree of stenosis, and cerebral imaging were not available. Despite its weaknesses, this study reasserts that CEA can be performed within the recommended 2 weeks of the onset of symptoms and IVT without increasing the risk of peri-operative stroke or death. Centres and vascular registries are recommended to continue monitoring changes in patient characteristics, lead times, and major complications after CEA in general, with a special focus on those who have undergone a prior thrombolysis.
- Building a More Connected DSMB: Better Integrating Ethics Review and Safety Monitoring. [Journal Article]
- Account Res 2015; 22(2):81-105.
Data and Safety Monitoring Boards (DSMBs) have become an increasingly common feature of clinical trial oversight, yet a paucity of legal or ethical frameworks govern these Boards' composition or operation, or their relationship with other actors with monitoring responsibilities. This paper argues that prevailing structural gaps are impeding harmonized systems for monitoring the ongoing ethical acceptability of clinical trials. Particular tensions stem from DSMBs' sweeping discretion in deciding whether and when to recommend that a trial should be terminated or amended based on safety and efficacy information. This discretion becomes especially challenging in light of DSMBs' monopoly over emerging trial data, which prevents Institutional Review Boards, sponsors, and investigators from participating in certain pivotal and ethically charged decisions. To address these disconnects, I advocate for strengthened pre-trial and post-trial communication in addition to innovative strategies to support DSMB decision making through the life of a trial.
- Underinsurance Before the Implementation of the Affordable Care Act: From the Research Involving Outpatient Settings Network (RIOS Net). [Journal Article]
- J Am Board Fam Med 2014 Nov-Dec; 27(6):855-7.
As the Affordable Care Act (ACA) is implemented and many uninsured become insured, rates of underinsurance may persist or increase. This study was designed to estimate the rate of underinsurance in primary care safety net clinics serving low income, multiethnic populations in New Mexico.Data were collected from 2 primary care clinics in an urban setting during a 2-week period in 2011 and 2012. Voluntary, anonymous, self-administered surveys were distributed to adult patients waiting to be seen by their doctor. Surveys were available in English and Spanish.Of those insured, 44% were underinsured. The underinsured comprised higher proportions of patients who were Hispanic, young, and poor; 39% reported fair or poor health, 23% reported that their health suffered from an inability to seek care because of cost, and 53% had either Medicaid or state coverage insurance. Patients with an income of ≤$25,000 were 8 times more likely to be underinsured.A high level of underinsurance was found in these safety net clinics. Because millions of Americans gain health care insurance benefits, monitoring whether the current reform provides adequate health care coverage or whether those with new and existing health care insurance are underinsured is critical.
- Laboratory Medicine Handoff Gaps Experienced by Primary Care Practices: A Report from the Shared Networks of Collaborative Ambulatory Practices and Partners (SNOCAP). [Journal Article]
- J Am Board Fam Med 2014 Nov-Dec; 27(6):796-803.
The majority of errors in laboratory medicine testing are thought to occur in the pre- and postanalytic testing phases, and a large proportion of these errors are secondary to failed handoffs. Because most laboratory tests originate in ambulatory primary care, understanding the gaps in handoff processes within and between laboratories and practices is imperative for patient safety. Therefore, the purpose of this study was to understand, based on information from primary care practice personnel, the perceived gaps in laboratory processes as a precursor to initiating process improvement activities.A survey was used to assess perceptions of clinicians, staff, and management personnel of gaps in handoffs between primary care practices and laboratories working in 21 Colorado primary care practices. Data were analyzed to determine statistically significant associations between categorical variables. In addition, qualitative analysis of responses to open-ended survey questions was conducted.Primary care practices consistently reported challenges and a desire/need to improve their efforts to systematically track laboratory test status, confirm receipt of laboratory results, and report results to patients. Automated tracking systems existed in roughly 61% of practices, and all but one of those had electronic health record-based tracking systems in place. One fourth of these electronic health record-enabled practices expressed sufficient mistrust in these systems to warrant the concurrent operation of an article-based tracking system as backup. Practices also reported 12 different procedures used to notify patients of test results, varying by test result type.The results highlight the lack of standardization and definition of roles in handoffs in primary care laboratory practices for test ordering, monitoring, and receiving and reporting test results. Results also identify high-priority gaps in processes and the perceptions by practice personnel that practice improvement in these areas is needed. Commonalities in these areas warrant the development and support of tools for use in primary care settings.
- Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer-CALGB 40302 (Alliance). [Journal Article]
- J Clin Oncol 2014 Dec 10; 32(35):3959-66.
CALGB 40302 sought to determine whether lapatinib would improve progression-free survival (PFS) among women with hormone receptor-positive metastatic breast cancer treated with fulvestrant.Eligible women had estrogen receptor-positive and/or progesterone receptor-positive tumors, regardless of human epidermal growth factor receptor 2 (HER2) status, and prior aromatase inhibitor treatment. Patients received fulvestrant 500 mg intramuscularly on day 1, followed by 250 mg on days 15 and 28 and every 4 weeks thereafter, and either lapatinib 1,500 mg or placebo daily. The study planned to accrue 324 patients and was powered for a 50% improvement in PFS with lapatinib from 5 to 7.5 months.At the third planned interim analysis, the futility boundary was crossed, and the data and safety monitoring board recommend study closure, having accrued 295 patients. At the final analysis, there was no difference in PFS (hazard ratio [HR] of placebo to lapatinib, 1.04; 95% CI, 0.82 to 1.33; P = .37); median PFS was 4.7 months for fulvestrant plus lapatinib versus 3.8 months for fulvestrant plus placebo. There was no difference in overall survival (OS) (HR, 0.91; 95% CI, 0.68 to 1.21; P = .25). For HER2-normal tumors, median PFS did not differ by treatment arm (4.1 v 3.8 months). For HER2-positive tumors, lapatinib was associated with longer median PFS (5.9 v 3.3 months), but the differential treatment effect by HER2 status was not significant (P = .53). The most frequent toxicities were diarrhea, fatigue, and rash associated with lapatinib.Adding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic.
- Radiation therapy digital data submission process for national clinical trials network. [Journal Article]
- Int J Radiat Oncol Biol Phys 2014 Oct 1; 90(2):466-7.
- Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. [Journal Article, Research Support, Non-U.S. Gov't]
- Stroke 2014 Nov; 45(11):3187-93.
On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke.We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included.The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488).Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset.http://www.clinicaltrials.gov. Unique identifier: NCT01120301.