Inference for Clinical Trials with Some Protocol Amendments

ABSTRACT

The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually documented by protocol amendments. However, the actual patient population after protocol amendments could deviate from the originally targeted patient population. In addition, protocol amendments made based on accrued data of the on-going trial may distort the sampling distribution of the statistic designed for the case of no protocol change. In this article, we model the population deviations due to protocol amendments using some covariates and study how to develop a valid statistical inference procedure. An example concerning an asthma trial is presented for illustration.     

Effect of exposure factors on image quality in screening mammography

IntroductionThe aim of this research was to study the effect of exposure factors on image quality for digital screening mammography units in Kuwait which use Tungsten (W) targets with Rhodium (Rh) and Silver (Ag) as filters.MethodsMammography Accreditation Phantom Model 015 was imaged using a Hologic Selenia Digital mammography unit with W targets and Rh and Ag filters. Four images, each at 26, 28, 30, and 32 kVp, were obtained using each target-filter combination (W/Rh and W/Ag). The images were evaluated by five senior technologists for the number of specks, fibers and masses visible on each image. Statistical analysis was carried out using non-parametric tests at p = 0.05 level.ResultsThere were significant changes in the visibility of fibers and specks between different kVp values with W/Rh (p < 0.001). However, with W/Ag combination, significant differences were observed in the fibers only (p < 0.001). Among the kVp values used, 28 kV emerged as the optimal value. Comparison of images obtained with the two filter materials, led to significant differences in the visibility of fibers and specks (p < 0.008). At 32 kVp, there were significant differences in the visibility of specks only (p < 0.008).ConclusionA W/Rh target-filter combination provides better image quality than that provided by W/Ag. In particular, 30 and 32 kVp X-ray beams produce higher quality images than the lower kV values.     

18F-FDG PET/CT in the diagnosis of prosthetic valve endocarditis

Prosthetic valve endocarditis is a major diagnostic challenge in clinical practice, due to the lower sensitivity of the modified Duke criteria and a higher percentage of cases with negative or inconclusive echocardiography results. The delay in establishing medical and surgical treatment increases the morbidity/mortality rate. New imaging techniques and 18F-FDG PET/CT in particular have meant a significant advance in cases of high clinical suspicion and negative or inconclusive echocardiography, increasing the overall sensitivity of the modified Duke criteria.We report the case of a male patient with prosthetic valve endocarditis, where 18F-FDG PET/CT provided the diagnostic key, determining the origin of the endocarditis and avoiding treatment delay.     

Hepatocellular Carcinoma and Liver Transplantation: State of the Art

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in chronic liver disease and cirrhosis. The incidence of HCC is growing worldwide.With respect to any other available treatment for liver cancer, liver transplantation (LT) has the highest potential to cure. LT allows for removal at once of both the tumor (“seed”) and the damaged-hepatic tissue (“soil”) where cancerogenesis and chronic liver disorders have progressed together. The Milan criteria (MC) have been applied worldwide to select patients with HCC for LT, yielding a 4-year survival rate of 75%. These criteria represent the benchmark for patient selection and are the basis for comparison with any other suggested criteria.However, MC are often considered to be too restrictive, and recent data show that between 25% and 50% of patients with HCC are currently transplanted beyond conventional indications. Consequently, any unrestricted expansion of selection criteria will increase the need for donor organs, lengthen waiting periods, increase drop-out rates, and impair outcomes on intention-to-treat analysis. Management of HCC recurrence after LT is challenging. There are a few reports available regarding the safety and efficacy of sorafenib for HCC recurrence after LT, but the data are heterogeneous. A multi-center prospective randomized controlled trial comparing placebo with sorafenib is advised. Alternatively, a meta-analysis of patient survival with sorafenib for HCC recurrence after LT could be helpful to characterize the therapeutic benefit and safety of sorafenib.Here, we review the use of LT for HCC, with particular emphasis on the selection criteria for transplantation in patients with HCC and management of HCC recurrence after LT.     

Melde- und Informationssystem für bedeutsame Vorkommnisse bei Strahlenanwendungen in der Medizin: Struktur,Zuständigkeiten und Meldekriterien

The increasing frequency and complexity of medical radiation exposures to humans inevitably result in higher risks of harmful unintended or accidental radiation exposures. To ensure a high level of protection and its continuous improvement, the Directive 2013/59/Euratom thus requires to systematically record and analyze both events and near-miss events as well as, in the case of their significance, to disseminate information regarding lessons learned from these events promptly and nationwide to improve radiation protection in medicine. These requirements have been transposed into German legislation by the new radiation protection law and radiation protection ordinance that entered into force simultaneously on December 31^th, 2018. The reporting and information system as provided by these regulations as well as the tasks, duties and powers of the parties involved are presented in the first part of this review article. In the second part, the established application-specified criteria for the significance – and thus the notification requirement - of (near-miss) events are itemized and explicated.     

Update: medical treatment of onychomycosis

The diagnosis of onychomycosis should be made clinically and mycologically: clinically, by one of seven subtypes of onychomycosis, and mycologically, by evidence of dermatophytes or verified presence of molds and/or yeasts. Dermatophytes are usually considered as pathogens, whereas non‐dermatophyte molds and yeasts are saprophytes. Basic anamnesis and close inspection should be performed to eliminate combined diseases (e.g., onychomycosis and trauma). The gold standard treatment for onychomycosis is basically systemic. Combination with topical agents, such as nail lacquer and/or chemical nail avulsion, produces better results than systemic treatment alone. Topical treatment as monotherapy is not efficient, excluding minor cases. Terbinafine is superior to itraconazole for dermatophyte onychomycosis. Evaluation of the outcome of clinical cure, mycological cure and total cure should be based on the well‐defined worldwide criteria; otherwise, comparison of results is impossible due to lack of uniformity in different studies. In case of treatment failure, the reasons for each failure should be carefully considered.     

MBO管理法在神经外科临床护理带教中的应用研究

目的分析运用MBO管理法（目标管理法）在神经外科临床护理带教中的应用效果，探索更为有效的护理带教方法。方法将2012年5月-2013年3月在我院神经外科实习的护理学员96名纳入研究对象，随机分为观察组（n=48）和对照组（n=48）。对照组：按照传统带教方法，随机完成大纲要求的教学内容。观察组：采用MBO模式，根据神经外科特点、总目标和护理实习的大纲要求，结合学员的实际考核情况，制定针对个人的带教目标和培训内容，制定日、周计划。4周内每周都要达到预定的目标。4周结束后对学员进行考核。观察并比较两组理论、操作、健康教育及满意度。结果观察组护理学员实行目标管理后，理论、操作、健康教育考评成绩及满意度明显高于对照组，两组比较差异有显著意义（P〈0．05）。结论将MBO法运用于神经外科临床护理学员带教中，对新护理学员和带教老师均提出了明确的目标要求，强化了老师带教意识，促进了学员的自控管理能力，提高了神经外科临床护理学员的整体水平。