Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it

Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Overexpression of anti-apoptotic Bcl-2 plays a role in prostate cancer progression, particularly in transformation to androgen-independent disease. Androgen-independent prostate cancers have been shown to harbor Bcl-2 gene copy number gains frequently suggesting that this genetic alteration might play a role in Bcl-2 overexpression. The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown.

Potential biomarkers for hepatoblastoma: Results from the SIOPEL-3 study

Hepatoblastoma (HB) is a rare malignant liver tumour found in infants. Many heterogenous histological tumour subtypes exist. Although survival rates have improved dramatically in recent years with the use of platinum-based chemotherapy, there still exists a subset of HB that does not respond to treatment. There are currently no tumour biomarkers in use and in this study we aim to evaluate potential biomarkers to aid identification of relapse cases that would otherwise be overlooked by current prognostication. This may identify patients that would benefit from more aggressive therapy and could improve overall survival rates. We used immunohistochemistry to analyse the expression of β-catenin, E-cadherin, Cyclin D1, Ki-67 and alpha-fetoprotein (AFP) protein in tumours from 91 patients prospectively enroled into the SIOPEL 3 clinical trial. The relationship between these biomarkers and clinicopathologic features and patient survival were statistically analysed. We identified one biomarker, Cyclin D1, which has a correlation with mixed epithelial/mesenchymal HB approaching significance (P=0.07). Survival analysis using these markers has revealed two potential prognostic indicators; Cyclin D1 and Ki-67 (P=0.01, 0.01).

Neurological outcome, working capacity and prognostic factors of patients with SCIWORA

STUDY DESIGN: Retrospective case review. OBJECTIVES: In the present study, the neurological outcome, retirement and prognostic factors of patients with spinal cord injury without radiographic abnormality (SCIWORA) were evaluated. SETTING: Swiss national work accident insurance database. METHODS: The medical histories of 32 patients who were insured by the Swiss Accident Insurance Fund (SUVA) and had SCIWORA between 1995 and 2004 were evaluated thoroughly. Moreover, all available magnetic resonance imaging (MRI) scans were evaluated. RESULTS: At the last follow-up, none of the patients had complete spinal cord injury, only 4 patients had severe deficits and 12 patients had normal motor and sensory function in the neurological examination. However, only 7 out of 32 patients had returned to full-time work and 10 out of 32 patients were fully retired. Both the presence of spinal cord change (ρ=0.51) and higher maximum spinal cord compression (ρ=0.57) in MRI scan correlated with the likelihood for retirement; older age (ρ=0.38) and physical load of work (ρ=0.4) correlated with retirement to a lesser extent. CONCLUSION: Although the neurological outcome of SCIWORA is mostly good, the retirement rate is high. Presence of spinal cord change and severity of cord compression are the best predictors for the degree of retirement.

Validation of prognostic factors and survival of patients with multiple myeloma in a real-life autologous stem cell transplantation setting: a Swiss single centre experience

High-dose chemotherapy with subsequent autologous stem cell transplantation (ASCT) is an important treatment option in younger patients with multiple myeloma (MM). We analysed the outcome of patients treated at our institution outside the clinical trials framework and tried to identify risk factors prognostic for survival.

Prognostic value of microvascular invasion in predicting the cancer specific survival and risk of metastatic disease in renal cell carcinoma: a multicenter investigation

While microvascular invasion is an accepted risk factor in various cancers, its prognostic role in renal cell carcinoma is still unclear. Therefore, a large multicenter study examining the experience of 5 international institutions was performed to evaluate the prognostic value of microvascular invasion in the occurrence of metastases and cancer specific survival.

PRO_10--a new tissue-based prognostic multigene marker in patients with early estrogen receptor-positive breast cancer

Clinicopathological and molecular factors determine the prognosis of breast cancer. PRO_10 is a prognostic score based on quantitative RT-PCR of 10 proliferation-associated genes obtained from formalin-fixed, paraffin-embedded breast cancer tissues. We revalidated PRO_10 in patients treated in a non-trial setting.

The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma

The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis was performed on five poorly differentiated HCC cell lines compared with non-neoplastic hepatic controls and a set of three cholangiolar carcinoma (CC) cell lines. The gene with the highest upregulation was HLXB9. HLXB9 is a gene of the homeobox genfamily important for the development of the pancreas. RT-PCR confirmed the upregulation of HLXB9 in surgical specimens of carcinoma tissue, suggesting its biological significance. Interestingly, HLXB9 upregulation was primary observed in poorly differentiated HCC with a pseudoglandular pattern compared with a solid pattern HCC or in moderate or well-differentiated HCC. Additional the expression of translated HLXB9, the protein HB9 (NCBI: NP_001158727), was analyzed by western blotting. Expression of HB9 was only detected in the cytoplasm but not in the nuclei of the HCC cells. For validation CC were also investigated. Again, we found an upregulation of HLXB9 in CC cells accompanied by an expression of HB9 in the cytoplasms of these tumor cells, respectively. In conclusion, homeobox HLXB9 is upregulated in poorly differentiated HCC with a pseudoglandular pattern. The translated HB9 protein is found in the cytoplasm of these HCC and CC. We therefore assume HLXB9 as a possible link in the understanding of the development of HCC and CC, respectively.

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise.

[Complex umbilical cord vein pulsations in cases with twin-twin transfusion syndrome: prognostic implications]

Umbilical vein pulsations (UV-P) are due to various etiologies. The aim of the present study was to investigate the incidence and type of UV-P in monochorionic twins with twin-twin transfusion syndrome (TTTS).

The prognostic utility of the SYNTAX score on 1-year outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial

This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents.