Assessing additional benefit in noninferiority trials.

A method for simultaneously assessing noninferiority with respect to efficacy and superiority with respect to another endpoint in two-arm noninferiority trials is presented. The procedure controls both the average type I error rate for the intersection-union test problem and the frequentist type I error rate for the noninferiority test by α while allowing an increased level for the superiority test. For normally distributed outcomes, two methods are presented to deal with the uncertainty about the correlation between the endpoints which defines the adjusted levels. The operating characteristics of these procedures are investigated. Furthermore, the sample size required when applying the proposed method is compared with that of alternative procedures. Application of the method in the situation of binary endpoints and mixed normal and binary endpoints, respectively, is sketched. An illustrative example is provided demonstrating implementation of the proposed approach in a clinical trial.

Original and repair bond strength of fiber-reinforced composites in vitro.

OBJECTIVE: A great benefit of FRC technology is that, in case of minor failure events, restorations can be repaired or reinserted. However, various FRC materials are available, that differ in matrix composition and fiber pre-treatment. The aim of this investigation was, therefore, to evaluate original and repair bond strength of FRC materials. METHODS: Five fully pre-impregnated, unidirectional FRCs were selected, one semi-interpenetrating polymer network FRC and four cross-linked-polymer FRCs. The primary endpoint was the evaluation of shear bond strength (SBS) between FRC and composite resin, which was performed by a universal testing machine. For each FRC specimens were divided into control (original SBS, resin to fresh FRC with oxygen inhibition layer (OIL), n=30) and test groups (repair SBS, resin to FRC after removal of OIL and adhesive infiltration, n=30). RESULTS: The cross-linked-polymer FRC GrandTec(®) (12.4±5.4 MPa) yielded the highest control SBS, followed by the semi-interpenetrating polymer network FRC (everStick(®), 9.2±3.5 MPa). With everStick(®), repair led to a significant increase in the test SBS (14.6±5.8 MPa, p=0.01). SIGNIFICANCE: Control SBS was best with GrandTec(®) indicating that the material is superior in direct clinical application. Test SBS was significantly increased with everStick(®) which points at potential reparability and advantages in semi-direct or indirect fabrication of fiber-reinforced fixed partial dentures.

Cytotoxicity of coated and uncoated fibre-reinforced composites.

OBJECTIVE: Currently, there are many fibre-reinforced composites (FRCs) available which differ in the type and volume fraction of fibres, pre-treatment of fibres and matrix composition. The aims of this in vitro investigation were to determine whether there is a difference in biocompatibility of FRCs and if coating FRCs with resin composites influences their cytotoxic potential. MATERIALS AND METHODS: Five different FRC materials were tested which were either uncoated or coated with flowable or viscous resin composite. Artificial saliva extracts were prepared according to USP-XXIII and ISO-10993 to determine cytotoxicity by testing cell viability and growth of primary human gingival fibroblasts (HGF) using MTT assay, LIVE/DEAD(®) assay and cell proliferation assay. The influence of eluates on fibres of the cytoskeleton was investigated by vimentin, tubulin and actinin immunostainings. A two-way ANOVA followed by Scheffe's post-hoc test, which included the factors FRC material and coating procedure, was performed to assess cytotoxicity. RESULTS: All extracts of FRC materials displayed minor cytotoxic potential on HGF cell viability, cell proliferation and integrity of the cytoskeleton. The type of FRC material significantly influenced cell viability (MTT assay) (p < 0.0001), whereas neither the presence of a coating nor the type of coating material resulted in altered cell viability. Distribution and organization of cytosolic fibres was not affected after HGF exposure to eluates. CONCLUSIONS: There is a lack of knowledge about the leaching behaviour of commonly available fully pre-impregnated FRCs and their interactions with coating materials. The coating of FRCs with resin composite materials did not impact biocompatibility.

Sample size calculations for noninferiority trials with Poisson distributed count data.

Clinical trials with Poisson distributed count data as the primary outcome are common in various medical areas such as relapse counts in multiple sclerosis trials or the number of attacks in trials for the treatment of migraine. In this article, we present approximate sample size formulae for testing noninferiority using asymptotic tests which are based on restricted or unrestricted maximum likelihood estimators of the Poisson rates. The Poisson outcomes are allowed to be observed for unequal follow-up schemes, and both the situations that the noninferiority margin is expressed in terms of the difference and the ratio are considered. The exact type I error rates and powers of these tests are evaluated and the accuracy of the approximate sample size formulae is examined. The test statistic using the restricted maximum likelihood estimators (for the difference test problem) and the test statistic that is based on the logarithmic transformation and employs the maximum likelihood estimators (for the ratio test problem) show favorable type I error control and can be recommended for practical application. The approximate sample size formulae show high accuracy even for small sample sizes and provide power values identical or close to the aspired ones. The methods are illustrated by a clinical trial example from anesthesia.

Neurosensory alterations and function of the temporomandibular joint after high oblique sagittal split osteotomy: an alternative technique in orthognathic surgery.

The current most common technique for repositioning of the mandible, bilateral sagittal split osteotomy (BSSO), was first described by Obwegeser and Dal Pont in the early1960s, and has since been modified several times. However, there is always a risk of damaging the inferior alveolar nerve. We have studied 50 consecutive patients who had high oblique sagittal split osteotomy (HSSO) as an alternative to avoid damage to the nerve. The patients were evaluated for sensory alterations and function of the temporomandibular joint (TMJ). Healing of both wound and bone were complete and uneventful in all 50 patients. Mean (SD) sagittal movement of the mandible was 6.6 (2.9)mm and length of the osteotomy line was 11.0 (3.1)mm. No patient had either temporary or permanent alteration in sensitivity. Pinprick tests showed no significant changes between the preoperative and postoperative readings (p>0.16) or in the chronological results (p>0.23). No disorders of the TMJ developed. Mean (SD) mouth opening 6months postoperatively was 41.6 (8.6)mm. The lateral excursion increased postoperatively by 1.86mm to the left and by 0.76mm to the right. Protrusion increased by 0.66mm. HSSO is therefore a suitable alternative to BSSO as it avoids injury to the inferior alveolar nerve without compromising the TMJ. Ossification was uneventful though bony attachment was less than with the classic BSSO.

A general approach for sample size calculation for the three-arm 'gold standard' non-inferiority design.

In the three-arm 'gold standard' non-inferiority design, an experimental treatment, an active reference, and a placebo are compared. This design is becoming increasingly popular, and it is, whenever feasible, recommended for use by regulatory guidelines. We provide a general method to calculate the required sample size for clinical trials performed in this design. As special cases, the situations of continuous, binary, and Poisson distributed outcomes are explored. Taking into account the correlation structure of the involved test statistics, the proposed approach leads to considerable savings in sample size as compared with application of ad hoc methods for all three scale levels. Furthermore, optimal sample size allocation ratios are determined that result in markedly smaller total sample sizes as compared with equal assignment. As optimal allocation makes the active treatment groups larger than the placebo group, implementation of the proposed approach is also desirable from an ethical viewpoint.

Fixed implant-retained rehabilitation of the edentulous maxilla: 11-year results of a prospective study.

OBJECTIVES: The aim of the present study was to assess long-term survival and success rates of implants in the edentulous maxilla restored with an implant-supported fixed prosthesis. MATERIALS AND METHODS: Seventeen edentulous patients received six to eight implants and implant-supported fixed prostheses by one surgeon. Yearly recalls were conducted by two examiners over a period of 11 years. Survival and success rates (biological complications) were determined; marginal bone loss was examined radiographically. Furthermore, microbiological tests as well as test for interleukin-1 composite genotype were assessed and potential risk factors were evaluated. RESULTS: After a mean time of 11.26 years, 15 patients of 17 could be reexamined. Out of 94 implants, three were lost in one patient. Mean marginal bone loss reached 0.88 mm, two patients (at seven implants) showed bone loss of ≥3.2 mm. Survival rate of implants reached 96.8%. Success rates on implant level hit 92.6% according to the criteria of Albrektsson and colleagues and 83.0% in accordance with Karoussis and colleagues. One prosthesis had to be renewed. CONCLUSION: Within the limitation of this study, restoration of the edentulous maxilla with an implant-supported fixed prosthesis represents an effective tool for rehabilitation over a period of 11 years.

Dental fear in children and adolescents: a comparison of forms of anxiety management practised by general and paediatric dentists.

BACKGROUND. About 11% of children and adolescents suffer from dental fear. These young people run an increasing risk of undergoing more invasive treatments. AIM. We researched the management of dental anxiety in young patients by general and paediatric dentists as well as by trained and untrained dentists. DESIGN. Eight hundred dentists in Germany were interviewed via e-mail regarding their experience, treatment techniques, information material and complications during the treatment of fearful children. We also examined how difficult dentists judge the treatment of anxious children and how often they participate in continuing education courses. RESULTS. Paediatric dentists applied a greater spectrum of management techniques than general dentists. They used more often psychotherapeutic interventions and anxiety assessment questionnaires. Dentists who frequently attend in continuing education courses judged the treatment to be less difficult and also used psychotherapeutic interventions more often. CONCLUSIONS. German paediatric dentists and dentists who take continuing education courses utilise a broader range of techniques to manage dental anxiety. They may be eminently suited to treat children with severe forms of anxiety. Therefore, dentists who treat young patients should participate in education programmes so as to reduce both the anxiety of their patients and their own anxiety.