Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD-VIVIAD.

BACKGROUND: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. METHODS: This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. RESULTS: To be expected early 2023 CONCLUSION: This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498650.

Environmental Distractions during Unsupervised Remote Digital Cognitive Assessment.

The current demand for cognitive assessment cannot be met with traditional in-person methods, warranting the need for remote unsupervised options. However, lack of visibility into testing conditions and effort levels limit the utility of existing remote options. This retrospective study analyzed the frequency of and factors associated with environmental distractions during a brief digital assessment taken at home by 1,442 adults aged 23-84. Automated scoring algorithms flagged low data capture. Frequency of environmental distractions were manually counted on a per-frame and per-trial basis. A total of 7.4% of test administrations included distractions. Distractions were more frequent in men (41:350) than women (65:1,092) and the average age of distracted participants (51.7) was lower than undistracted participants (57.8). These results underscore the challenges associated with unsupervised cognitive assessment. Data collection methods that enable review of testing conditions are needed to confirm quality, usability, and actionability.

Psychometric Evaluation of the Neuropsychological Test Battery in Individuals with Normal Cognition, Mild Cognitive Impairment, or Mild to Moderate Alzheimer's Disease: Results from a Longitudinal Study.

BACKGROUND: The Neuropsychological Test Battery (NTB) is a combination of widely used clinical neuropsychological tests measuring memory and executive function and was designed to overcome some of the limitations of the traditionally used Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog). A previously reported account indicated high levels of NTB reliability in patients with mild-to-moderate Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVES: We examined capacity of the Neuropsychological Test Battery (NTB) and its component subtests to measure cognitive change over time. Correlations with other cognitive and functional assessments were also determined. Design, Settings, Participants: This was a multicentre, prospective, non-interventional, longitudinal cohort study involving patients with mild-to-moderate AD (n=196), MCI (n=70), or cognitively normal control participants (NC, n=75). INTERVENTION: The NTB, as well as other Clinical Outcome Assessments including, ADAS-Cog, other cognitive measures, functional/behavioral questionnaires, health outcome questionnaires, and resource utilization tools were administered. RESULTS: Mean change from baseline for the NTB composite score and the six individual NTB subtests showed greater reductions in performance over time in the AD and MCI groups, compared with NC group. The ADAS-Cog was found to be more sensitive to change than the NTB in all three populations. CONCLUSIONS: The NTB showed high correlation with the ADAS-Cog and appears to be a sensitive and reliable assessment tool for measuring cognitive decline in patients with mild-to-moderate AD. However, the ADAS-Cog was found to be more sensitive to change over time in both the AD and MCI populations.

Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.

Evidence suggests that 30-50% of patients suffering from major depressive disorder (MDD) are classified as suffering from treatment resistant depression (TRD) as they have an inadequate response to standard antidepressants. A key feature of this patient population is the increased incidence of co-morbid symptoms like anxiety and pain. Recognizing that current standards of care are largely focused on monoaminergic mechanisms of action (MOAs), innovative approaches to drug discovery for TRD are targeting glutamate hyperfunction. Here we describe the in vitro and in vivo profile of GRN-529, a novel negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5). In cell based pharmacology assays, GRN-529 is a high affinity (Ki 5.4 nM), potent (IC50 3.1 nM) and selective (>1000-fold selective vs mGluR1) mGluR5 NAM. Acute administration of GRN-529 (0.1-30 mg/kg p.o.) had dose-dependent efficacy across a therapeutically relevant battery of animal models, comprising depression (decreased immobility time in tail suspension and forced swim tests) and 2 of the co-morbid symptoms overrepresented in TRD, namely anxiety (attenuation of stress-induced hyperthermia, and increased punished crossings in the four plate test) and pain (reversal of hyperalgesia due to sciatic nerve ligation or inflammation). The potential side effect liability of GRN-529 was also assessed using preclinical models: GRN-529 had no effect on rat sexual behavior or motor co-ordination (rotarod), however it impaired cognition in mice (social odor recognition). Efficacy and side effects of GRN-529 were compared to standard of care agents (antidepressant, anxiolytic or analgesics) and the tool mGluR5 NAM, MTEP. To assess the relationship between target occupancy and efficacy, ex vivo receptor occupancy was measured in parallel with efficacy testing. This revealed a strong correlation between target engagement, exposure and efficacy across behavioral endpoints, which supports the potential translational value of PET imaging to dose selection in patients. Collectively this broad spectrum profile of efficacy of GRN-529 supports our hypothesis that negative allosteric modulation of mGluR5 could represent an innovative therapeutic approach to the treatment of TRD. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

WAY-318068: a novel, potent and selective noradrenaline re-uptake inhibitor with activity in rodent models of pain and depression.

BACKGROUND AND PURPOSE: Antidepressants, which raise the CNS concentrations of 5-HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity. EXPERIMENTAL APPROACH: In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one). KEY RESULTS: WAY-318068 is a potent and effective inhibitor of the NET with a K(i) of 8.7 nM in a binding assay, and an IC(50) of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits. CONCLUSIONS AND IMPLICATIONS: Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain.

Development of an international spinal injury prevention module: application of the international classification of external cause of injury to spinal cord injury.

STUDY DESIGN: An end-user response survey and assessments of inter-rater reliability before and after training. OBJECTIVES: Evaluate the spinal cord injury (SCI) application of the international classification of external cause of injury (ICECI) in a mixed group of untrained and trained coders to assess agreement, refine coding and training methodology. SETTING: An interactive coding workshop for an international group of coders with varying previous training. METHODS: Evaluate content validity (qualitative survey) and inter-rater reliability (kappa estimate of agreement) of the ICECI in a variety of injury scenarios presented within a computerized data-entry and training module. The results of this evaluation are compared with an earlier published gold standard. RESULTS: The ICECI is a flexible data coding system that appears to work with reasonable content validity in the regions assessed with English-language coders. Training appeared to narrow the difference between the inexperienced and trained coders. This is reflected in a borderline tendency for lower kappa scores pre-training compared with an earlier examined group of expert coders (P=0.073) but no difference in kappa scores after training (P=0.67). Computer-based training on a face-to-face level with computerized data entry appears an effective tool for training coders to use the ICECI. CONCLUSIONS: This report shows that using electronic data-entry and training assistance, inexperienced coders using the SCI-ICECI computerized system quickly approach the levels of agreement of trained coders in related data systems. The content validity of the training data set is adequate but needs to include more cases representative for use in SCI.

Causes of injuries resulting in hospitalisation in Australia: assessing coder agreement on external causes.

OBJECTIVE: To assess extent of coder agreement for external causes of injury using ICD-10-AM for injury-related hospitalisations in Australian public hospitals. METHODS: A random sample of 4850 discharges from 2002 to 2004 was obtained from a stratified random sample of 50 hospitals across four states in Australia. On-site medical record reviews were conducted and external cause codes were assigned blinded to the original coded data. Code agreement levels were grouped into the following agreement categories: block level, 3-character level, 4-character level, 5th-character level, and complete code level. RESULTS: At a broad block level, code agreement was found in over 90% of cases for most mechanisms (eg, transport, fall). Percentage disagreement was 26.0% at the 3-character level; agreement for the complete external cause code was 67.6%. For activity codes, the percentage of disagreement at the 3-character level was 7.3% and agreement for the complete activity code was 68.0%. For place of occurrence codes, the percentage of disagreement at the 4-character level was 22.0%; agreement for the complete place code was 75.4%. CONCLUSIONS: With 68% agreement for complete codes and 74% agreement for 3-character codes, as well as variability in agreement levels across different code blocks, place and activity codes, researchers need to be aware of the reliability of their specific data of interest when they wish to undertake trend analyses or case selection for specific causes of interest.

Accuracy of external cause-of-injury coding in hospital records.

OBJECTIVE: To appraise the published evidence regarding the accuracy of external cause-of-injury codes in hospital records. DESIGN: Systematic review. DATA SOURCES: Electronic databases searched included PubMed, PubMed Central, Medline, CINAHL, Academic Search Elite, Proquest Health and Medical Complete, and Google Scholar. Snowballing strategies were used by searching the bibliographies of retrieved references to identify relevant associated articles. SELECTION CRITERIA: Studies were included in the review if they assessed the accuracy of external cause-of-injury coding in hospital records via a recoding methodology. METHODS: The papers identified through the search were independently screened by two authors for inclusion. Because of heterogeneity between studies, meta-analysis was not performed. RESULTS: Very limited research on the accuracy of external cause coding for injury-related hospitalisation using medical record review and recoding methodologies has been conducted, with only five studies matching the selection criteria. The accuracy of external cause coding using ICD-9-CM ranged from approximately 64% when exact code agreement was examined to approximately 85% when agreement for broader groups of codes was examined. CONCLUSIONS: Although broad external cause groupings coded in ICD-9-CM can be used with some confidence, researchers should exercise caution for very specific codes until further research is conducted to validate these data. As all previous studies have been conducted using ICD-9-CM, research is needed to quantify the accuracy of coding using ICD-10-AM, and validate the use of these data for injury surveillance purposes.

Orthodontic treatment for prominent upper front teeth in children.

BACKGROUND: Prominent upper front teeth are an important and potentially harmful type of orthodontic problem. This condition develops when the child's permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. When treatment is provided during adolescence the orthodontist may provide treatment with various orthodontic braces, but there is currently little evidence of the relative effectiveness of the different braces that can be used. OBJECTIVES: To assess the effectiveness of orthodontic treatment for prominent upper front teeth, when this treatment is provided when the child is 7 to 9 years old or when they are in early adolescence or with different dental braces or both. SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched. The handsearching of the key international orthodontic journals was updated to December 2006. There were no restrictions in respect to language or status of publication. Date of most recent searches: February 2007. SELECTION CRITERIA: Trials were selected if they met the following criteria: design - randomised and controlled clinical trials; participants - children or adolescents (age < 16 years) or both receiving orthodontic treatment to correct prominent upper front teeth; interventions - active: any orthodontic brace or head-brace, control: no or delayed treatment or another active intervention; primary outcomes - prominence of the upper front teeth, relationship between upper and lower jaws; secondary outcomes: self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, number of attendances required to complete treatment. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Group's statistical guidelines were followed and mean differences were calculated using random-effects models. Potential sources of heterogeneity were examined. MAIN RESULTS: The search strategy identified 185 titles and abstracts. From this we obtained 105 full reports for the review. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review.Early treatment comparisons: Three trials, involving 432 participants, compared early treatment with a functional appliance with no treatment. There was a significant difference in final overjet of the treatment group compared with the control group of -4.04 mm (95% CI -7.47 to -0.6, chi squared 117.02, 2 df, P < 0.00001, I(2) = 98.3%). There was a significant difference in ANB (-1.35 mm; 95% CI -2.57 to -0.14, chi squared 9.17, 2 df, P = 0.01, I(2) = 78.2%) and change in ANB (-0.55; 95% CI -0.92 to -0.18, chi squared 5.71, 1 df, P = 0.06, I(2) = 65.0%) between the treatment and control groups. The comparison of the effect of treatment with headgear versus untreated control revealed that there was a small but significant effect of headgear treatment on overjet of -1.07 (95% CI -1.63 to -0.51, chi squared 0.05, 1 df, P = 0.82, I(2) = 0%). Similarly, headgear resulted in a significant reduction in final ANB of -0.72 (95% CI -1.18 to -0.27, chi squared 0.34, 1 df, P = 0.56, I(2) = 0%). No significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances. Adolescent treatment (Phase II): At the end of all treatment we found that there were no significant differences in overjet, final ANB or PAR score between the children who had a course of early treatment, with headgear or a functional appliance, and those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (-5.22 mm; 95% CI -6.51 to -3.93) and ANB (-2.27 degrees; 95% CI -3.22 to -1.31, chi squared 1.9, 1 df, P = 0.17, I(2) = 47.3%) for adolescents receiving one-phase treatment with a functional appliance versus an untreated control.A statistically significant reduction of ANB (-0.68 degrees; 95% CI -1.32 to -0.04, chi squared 0.56, 1 df, P = 0.46, I(2) = 0%) with the Twin Block appliance when compared to other functional appliances. However, there was no significant effect of the type of appliance on the final overjet. AUTHORS' CONCLUSIONS: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.

Measuring cognitive change in Alzheimer's disease clinical drug trials.

In the following paper the cognitive measures used in clinical trials of drugs for Alzheimer's disease are reviewed. The potential benefits of employing innovative tests that map cognitive domains poorly indexed by traditional measures such as the ADAS-cog are considered. Finally, issues pertaining to the cognitive breadth of any proposed new instrument are discussed, as well as the clinical relevance of cognitive change.

Species-specific in vitro pharmacological effects of the cannabinoid receptor 2 (CB2) selective ligand AM1241 and its resolved enantiomers.

BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.

Natural rubber latex allergy: implications for the orthodontist.

Natural rubber latex (NRL) allergy can have potentially serious consequences, and reports of orthodontic patients reacting to NRL have increased significantly over recent years. It is therefore important for the orthodontist to know how to manage patients with an NRL allergy and how to deal with possible reactions to NRL. Safe and effective practice depends on recognizing patients who are at risk of NRL allergy, and an awareness of materials and equipment that contain NRL and the availability of suitable NRL-free alternatives.

Delay and failure to publish dental research.

OBJECTIVE: To investigate the incidence and time taken to full publication of abstracts presented at dental scientific meetings. DESIGN: A retrospective observational study. SETTING: All abstracts from the 1993 proceedings of the European Orthodontic Society (EOS) and European Organisation for Caries Research (ORCA) and a 10% random sample of abstracts from the International Association for Dental Research (IADR) conferences. METHODS: A cross-referenced Medline search of abstract title and authors was undertaken to determine whether abstracts had been published as full papers. Searches were censored 1 year prior to and 5 years post publication as an abstract. Publication rate was compared between abstracts presented orally and as posters. MAIN OUTCOME MEASURES: Publication as a full paper and time taken to publication. RESULTS: 546 abstracts were investigated. 252 abstracts (46.1%) were found as full reports. Median time to publication of all abstracts was 18 months (IQR 9, 30 months). 99 of the oral abstracts (57%) and 153 (41%) of the poster abstracts were published. Relative Risk Oral vs Poster=1.37 CI (1.19, 1.55). CONCLUSION: More than half of the research presented at EOS, IADR and ORCA in 1993 remained unpublished 5 years after presentation at the conference. Oral presentations were published more frequently than poster presentations.

Diagnosis based injury severity scaling: investigation of a method using Australian and New Zealand hospitalisations.

OBJECTIVE: To assess the performance of the International Classification of Diseases (ICD) based injury severity score, ICISS, when applied to two versions of the 10th edition of ICD, ICD-10 and ICD-10-AM. DESIGN: ICISS was assessed on its ability to predict threat to life using logistic regression modelling. Models used ICISS and age as predictors and survival as the outcome. SETTING: Australia and New Zealand. Patients or SUBJECTS: Hospitalisations with an ICD-10-AM principal diagnosis in the range S00-T89 from 1 July 1999 to 30 June 2001 (Australia) or 1 July 1999 to 31 December 2001 (New Zealand). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The models were assessed in terms of their discrimination, measured by the concordance score, and calibration, measured using calibration curves and the Hosmer-Lemeshow statistic. RESULTS: 523 633 Australian and 124 767 New Zealand hospitalisations were selected, including 7230 and 1565 deaths respectively. Discrimination was high in all the fitted models with concordance scores of 0.885 to 0.910. Calibration results were also promising with all calibration curves being close to linear, though ICISS appeared to underestimate mortality somewhat for cases with an ICISS score less than 0.6. Overall ICISS performed better when applied to the Australian than the New Zealand hospitalisations. Australian and New Zealand hospitalisations were very similar. ICISS was also only a little more successful when ICD-10-AM rather than mapped ICD-10 was used. CONCLUSIONS: ICISS appears to be a reasonable way to estimate severity for databases using ICD-10 or ICD-10-AM. It is also likely to work well for other clinical variants of ICD-10.

How readable are orthodontic patient information leaflets?

OBJECTIVE: To assess the readability of published orthodontic patient information leaflets (PILs) and their eligibility for the Plain English Campaign's Crystal Mark. DESIGN: A retrospective, observational study. SETTING: PILs available from professional organizations and commercial companies. MATERIALS AND METHODS: Twenty-six orthodontic PILs were assessed. The entire text of each leaflet was reproduced in Microsoft Word, 2000. Readability statistics were obtained via the 'Tools' menu. The design elements of each leaflet were assessed. The leaflets were sent to the Plain English Campaign for assessment of their eligibility for the Crystal Mark. OUTCOME MEASURES: Leaflet and sentence length, passive percentage, Flesch Reading Ease score, Flesch Kincaid Grade Level, design percentage and eligibility for the Plain English Campaign's Crystal Mark. RESULTS: Overall, nearly half of the leaflets (42.3%) were rated as 'fairly difficult' or 'difficult' to read. However, the BOS PILs were significantly better than the AAO leaflets in all but one outcome with the BOS leaflets being rated as 'standard' or 'fairly easy' to read, meaning that 70-80% of the UK population would be able to understand them. None of the PILs were eligible for the Plain English Campaign's Crystal Mark. CONCLUSIONS: The orthodontic PILs assessed were difficult to read and none were eligible for the Plain English Campaign's Crystal Mark. However, the BOS leaflets were much easier to read and better designed than those produced by the AAO making them a useful tool to improve patients' understanding of different treatment options and allowing them to be used in the informed consent process.

Clinical trials in orthodontics II: assessment of the quality of reporting of clinical trials published in three orthodontic journals between 1989 and 1998.

AIMS: To test the hypothesis that the quality of reporting of orthodontic clinical trials is insufficient to allow readers to assess the validity of the trial. DESIGN: A retrospective observational study. SETTING: The American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), the British Journal of Orthodontics (BJO) and European Journal of Orthodontics (EJO). DATA SOURCE: Clinical trials published between 1989 and 1998. METHOD: A hand search was performed to identify all clinical trials. The concealment of allocation, whether the trial was randomized, double blind, and whether there was a description of withdrawals and dropouts was recorded. RESULTS: One hundred and fifty-five trial reports were identified of which 4 (2.6%) were adequately concealed, 85 (54.8%) were described as being randomized, 10 (6.5%) as double-blind, and 44 (28.4%) gave a description of withdrawals and drop-outs from the trial. The type of randomization was considered appropriate in 78 (50.3%) reports and in 57 (36.8%) reports the level of blinding was considered appropriate. When assessed for the risk of bias in the reported trials,(1) one trial (0.6%) had a low risk of bias, 17 (11%) a moderate risk, and 137 (88.4%) a high risk. CONCLUSIONS: In general the quality of reporting orthodontic clinical trials was insufficient to allow readers to assess the validity of the trials. Reporting of clinical trials could be improved by orthodontic journals adopting the CONSORT statement(2,)(3) to ensure that all relevant information is provided.

Clinical trials in orthodontics I: demographic details of clinical trials published in three orthodontic journals between 1989 and 1998.

AIM: To test the hypothesis that there is insufficient evidence available, from clinical trials, to allow evidence-based decisions to be made on the effectiveness of orthodontic treatment. OBJECTIVES: To identify reports of orthodontic clinical trials and assess their demographic characteristics. DESIGN: A retrospective, observational study. SETTING: The American Journal of Orthodontics and Dentofacial Orthopedics, British Journal of Orthodontics, and European Journal Orthodontics. DATA SOURCE: Clinical trials published between 1989 and 1998. METHOD: A hand-search was performed to identify all clinical trials. The journal and year of publication, research method, interventions, and sample size of the trials reported were recorded. RESULTS: One-hundred-and-fifty-five trial reports were identified of which 56 (36.1%) were published from 1989 to 1993 and 99 (69%) from 1994 to 1998. Ninety-nine (69%) reports were published in the AJO-DO, 18 (11.6%) in the BJO and 38 (24.5%) in the EJO. Eighty-five (54.8%) were reports of randomized controlled trials and 70 (45.2%) of controlled clinical trials. The interventions most frequently assessed were bonding materials (21.9%), growth modification treatments (21.3%), and oral hygiene procedures (9.0%). The median sample size was 32 (IQR 19.5, 50). CONCLUSION: There is sufficient evidence available from clinical trials to warrant doing systematic reviews of orthodontic clinical trials to aid decision-making.

Publication bias: raising awareness of a potential problem in dental research.

With the development of evidence-based dentistry it is important to consider how accurate and representative our published pool of evidence is. In this article we will describe publication bias and discuss the causes and potential effects it may have upon the pool of scientific evidence available in dentistry.