Overview of periodontal clinical trials utilizing anti-infective or host modulating agents

In ants, antennal movements support the stimulus perception of olfactory and mechanosensory sensilla, most of which are located on the distal part of the antenna. In addition, sensory hair plates, campaniform sensilla, and Janet's organ provide the ant with proprioceptive information about the position, velocity, and acceleration of their antennae. We describe the morphology of these proprioceptors and their afferent neurons with special reference to the trap-jaw ant genus Odontomachus. All these sensory neurons terminate in the dorsal lobe, the part of the brain that also contains antennal motor neurons and that controls antennal movements. Neurons originating from campaniform sensilla and Janet's organ send additional collaterals into the subesophageal ganglion. Particularly fast antennal movements occur during protective withdrawal of the antenna. Under natural conditions, antennal retraction in Odontomachus always precedes the rapid mandible strike. We have found no indication of monosynaptic coupling between the antennal proprioceptive afferents and the trigger motor neurons that release the mandible strike. Instead, complex neuronal interactions in the involved neuromeres are more likely to control the timing of the two reflexes. The normal behavioral sequence of antennal retraction can be reversed by artificially releasing the mandible strike earlier than normal. The significance of fast antennal reflexes and of proprioceptive control is discussed.     

Overview of randomized trials in laparoscopic inguinal hernia repair

Purified phenolic glycolipid (PGL-1) from Mycobacterium leprae was used to detect IgG antibodies against PGL-1 in leprosy patients in an enzyme-linked immunosorbent assay (ELISA). A total of 698 sera were screened; they came from patients suffering from leprosy, autoimmune disease, myeloma, tuberculosis and sexually transmitted diseases (STDs). Cases with miscellaneous diseases and persons undergoing AIDS screening were also included. Sera from lepromatous and tuberculoid leprosy patients gave positivity rates of 60.5% and 41.7%, respectively. In non-leprosy cases, the PGL-1 ELISA showed an overall positivity rate of 6.9%; this was greatest in patients with tuberculosis (43.8%) followed by autoimmune diseases (40.9%) and miscellaneous cases including liver diseases (37.9%). This study emphasizes that PGL-1 ELISA has a low predictive value for diagnosis of active infection by Mycobacterium leprae. Positive reactions in a significant percentage of patients with autoimmune disease are intriguing and need indepth study.     

Self-designing clinical trials

I present a method of sequential analysis for randomized clinical trials that allows use of all prior data in a trial to determine the use and weighting of subsequent observations. One continues to assign subjects until one has 'used up' all the variance of the test statistic. There are many strategies to determine the weights including Bayesian methods (though the proposal is a frequentist design). I explore further the self-designing aspect of the randomized trial to note that in some cases it makes good sense (i) to change the weighting on components of a multivariate endpoint, (ii) to add or drop treatment arms (especially in a parallel group dose ranging/efficacy/safety trial), (iii) to select sites to use as the trial goes on, (iv) to change the test statistic and (v) even to rethink the whole drug development paradigm to shorten drug development time while keeping current standards for the level of evidence necessary for approval.     

Therapy and clinical trials

Little is know about intraosseous migration of nonerupting teeth, a rare natural condition of horizontal tooth movement and impaction. It occurs only in the mandible and involves primarily the second premolar or the canine. When the second premolar is the affected tooth, it always is found distal to its normal position. The origins of the second premolar intraosseous migration phenomenon are obscure and usually no treatment is recommended. Intraosseous migration involving the canine is commonly called transmigration because the affected canine moves mesially across the mandibular symphysis to the opposite side of the mandible. Analysis of 50 published cases of canine transmigration indicated higher occurrence in women and no sidedness preference. In over 80% of the studied cases, the canine remained nonerupted and, of the 24 cases receiving some treatment, all but two underwent extraction of the anomalous canine. The canine transmigration phenomenon appears to show signs of having some genetic determinants.     

Multiple-outcome meta-analysis of clinical trials

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.     

Role of clinical trials in memory clinics

The main points of a workshop on the place of clinical trials in the memory clinics in France are reproduced schematically. The efficiency of these centres has been tested at the time of the numerous clinical trials performed in France on Alzheimer's disease. In parallel, several difficulties have been pointed out: inhomogeneity of the technical approaches, official role of psychologists in the hospital teams, integration of clinical research to individual care. A particular effort should be oriented towards specific research on the different types of dementia, on early stages, on information for both media and authorities as well as on specific technical and methodological problems.     

The use of equipoise in clinical trials

We present two new microfabricated cantilever-beam force transducers. The transducers were fabricated from thin silicon-nitride films, and were used respectively to measure forces generated by two small-muscle preparations: the single myofibril, and the single actin filament in contact with a myosin-coated surface. A simple resonance method was developed to characterize the transducers. Because of the high reproducibility of lever dimensions and the consistency of the modulus of elasticity, few calibration measurements sufficed to characterize the stiffness of all the levers on a single wafer.