Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease Suggest Disease Modification Potential.

BACKGROUND: Alzheimer's Disease (AD) patients homozygous for the APOE4 allele (APOE4/4) have a distinct clinical and biological phenotype with high levels of beta amyloid (Aß) pathology and toxic Aß oligomers. Tramiprosate, an oral agent that inhibits Aß monomer aggregation into toxic oligomers, was evaluated in two Phase 3 Mild to Moderate AD studies which did not show efficacy in the overall population. Re-analyses of these trials showed the most consistent clinical benefits in APOE4/4 patients. We analyzed efficacy in the APOE4/4 patients with Mild disease. OBJECTIVES: To determine the optimal stage of AD for future trials in APOE4/4 homozygotes. DESIGN: Two randomized, double-blind, placebo-controlled parallel-arm multi-center studies of 78-weeks duration. SETTING: Academic Alzheimer's disease centers, community-based memory clinics, and neuropsychiatric research sites. PARTICIPANTS: Participants included 2,025 AD patients with MMSE 16-26. Approximately 13-15% had APOE4/4 genotype (N= 147 and 110 per study), mean age 71.1 years, 56% females. Almost all were on stable symptomatic drugs. INTERVENTION: Randomized subjects received oral placebo, 100mg BID, or 150mg BID of tramiprosate. MEASUREMENTS: Co-primary outcomes were change from baseline in the ADAS-cog11 and CDR-SB. Disability assessment for dementia (DAD) was a secondary outcome. RESULTS: In APOE4/4 homozygotes receiving 150mg BID tramiprosate, efficacy in the traditional Mild AD patients (MMSE 20-26) was higher than the overall group (MMSE 16-26) and efficacy in the Mild patients (MMSE 22-26) was highest. Tramiprosate benefits compared to placebo on ADAS-cog, CDR-SB, and DAD were 125%, 81% and 71%, respectively (p<0.02). The Mild subgroup (MMSE 22-26) showed cognitive stabilization with no decline over 78 weeks, both ADAS-cog and DAD effects increased over time. Tramiprosate safety in APOE4/4 patients was favorable. Most common adverse events were nausea, vomiting, depression and decreased weight. CONCLUSIONS: The Mild subgroup of APOE4/4 AD patients (MMSE 22-26) showed larger benefits on the high dose of tramiprosate than the overall Mild and Moderate group. Consistent with its preclinical effects on Aß oligomers, tramiprosate seemed to stabilize cognitive performance, supporting its disease modification potential. Confirmatory studies using ALZ-801, an improved pro-drug formulation of tramiprosate, will target APOE4/4 patients with Mild AD.

Tract-Specific Diffusion Tensor Imaging in Cervical Spondylotic Myelopathy Before and After Decompressive Spinal Surgery: Preliminary Results.

PURPOSE: Diffusion tensor imaging (DTI) metrics of the cervical spinal cord in patients with cervical spondylotic myelopathy (CSM) were compared to those measured in healthy volunteers, using tract-specific region of interests (ROIs) across all cervical intervertebral disc levels. METHODS: Magnetic resonance (MR) imaging of the cervical spinal cord was performed in four patients with CSM and in five healthy volunteers on a 3-T MR scanner. Region-specific fractional anisotropy (FA) and mean diffusivity (MD) were calculated on axial imaging with ROI placement in the anterior, lateral, and posterior regions of the spinal cord. FA and MD were also calculated on sagittal acquisitions. Nonparametric statistical tests were used to compare controls and patients before and after surgery. RESULTS: FA values were significantly lower (p = 0.050) and MD values were significantly higher (p = 0.014) in CSM patients measured at level of maximal compression before surgery than in healthy controls in lateral and posterior ROIs, respectively. In posterior ROIs, MD values were significantly higher in patients before surgery compared to controls at all levels except C7-T1. CONCLUSION: Patients with CSM may demonstrate region-specific changes in DTI metrics when compared to healthy controls. Changes in DTI metrics may also occur at levels remote from site of compression.

Evaluation of the Walking Index for Spinal Cord Injury II (WISCI-II) in children with Spinal Cord Injury (SCI).

STUDY DESIGN: Mixed methods were used in this study. The appropriateness of the levels of the Walking Index for Spinal Cord Injury II (WISCI-II) for application in children was critically reviewed by physical therapists using the Modified Delphi Technique, and the inter- and intra-rater reliability of the WISCI-II in children was evaluated. OBJECTIVES: To examine the construct validity, and to establish reliability of the WISCI-II related to its use in children with spinal cord injury (SCI). SETTING: United States of America. METHODS: Using a Modified Delphi Technique, physical therapists critically reviewed the WISCI-II levels for pediatric utilization. Concurrently, ambulatory children under age 18 years with SCI were evaluated using the WISCI-II on two occasions by the same therapist to establish intra-rater reliability. One trial was photographed and de-identified. Each photograph was reviewed by four different physical therapists who gave WISCI-II scores to establish inter-rater reliability. Summary and descriptive statistics were used to calculate the frequency of yes/no responses for each WISCI-II level question and to determine the percent agreement for each question. Inter- and intra-rater reliability was calculated using interclass correlation coefficients (ICCs) with 95% confidence intervals (CI). RESULTS: Construct validity was confirmed after one Delphi round during which at least 80% agreement was established by 51 physical therapists on the appropriateness of the WISCI-II levels for children. Fifty-two children with SCI aged 2-17 years completed repeated WISCI-II assessments and 40 de-identified photographs were scored by four physical therapists. Intra- and inter-rater reliability was high (ICC=0.997, CI=0.995-0.998 and ICC=0.97, CI=0.95-0.98, respectively). CONCLUSION: This study demonstrates support for the use of the WISCI-II in ambulatory children with SCI. SPONSORSHIP: This study was funded by the Craig H Neilsen Foundation, Spinal Cord Injury Research on the Translation Spectrum, Senior Research Award #282592 (Mulcahey, PI).

Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Individuals with Early Alzheimer's Disease: Amyloid Imaging Positron Emission Tomography and Safety Results from a Phase 2 Study.

BACKGROUND: ACC-001 is an investigational therapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease. OBJECTIVES: To evaluate safety, immunogenicity, impact on brain amyloid, and other exploratory endpoints in participants receiving ACC-001. DESIGN: Randomized, phase 2, interventional study. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT01227564. PARTICIPANTS: Individuals with early Alzheimer's disease (Mini-Mental State Examination scores ≥25, a global Clinical Dementia Rating of 0.5, and evidence of elevated baseline brain amyloid burden). INTERVENTION: Participants were randomized to ACC-001 3 µg or 10 µg with QS-21 adjuvant (50 µg), or placebo. MEASUREMENTS: The primary endpoint was change in brain amyloid burden by 18F-florbetapir positron emission tomography in composite cortical standard uptake value ratio. RESULTS: A total of 63 participants were randomized and 51 completed the study. At week 104, no significant differences were observed in 18F-florbetapir positron emission tomography composite cortical standard uptake value ratio between either ACC-001 dose compared with placebo. In both ACC-001 + QS-21 treatment groups, following the initial immunization, the anti-amyloid-beta geometric mean titers increased after each subsequent vaccination and then declined, with less apparent decline after the later compared with earlier immunizations. The majority of treatment-emergent adverse events in the ACC-001 + QS-21 groups were injection site reactions, which occurred at a greater rate in active treatment groups than in the placebo group. No amyloid-related imaging abnormalities of edema or effusion were reported. CONCLUSION: No statistically significant differences were observed between groups in the change from baseline brain amyloid burden despite apparently robust systemically measured anti-amyloid-beta antibody response at both dose levels. Insufficient antibody titers, poor quality immune response, short duration of treatment, or small sample size may have resulted in these findings. The safety and tolerability profile was acceptable.

Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

This study was designed to evaluate whether subjects with amyloid beta (Aß) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aß pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aß+) or negative (Aß-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aß+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aß+ MCI subjects demonstrated greater worsening compared with Aß- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aß+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aß+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aß+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aß+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aß+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aß- subjects do.

Rivastigmine transdermal system for the treatment of mild to moderate Alzheimer's disease.

Today patients with mild to moderate Alzhiemer's disease (AD) have a treatment approach choice: oral or transdermal delivery. The aim of this review was to provide a concise, comprehensive overview of the clinically relevant safety, tolerability and efficacy information available for the rivastigmine transdermal system. Relevant articles were identified through a MEDLINE search of publications in the past 3 years using the terms 'rivastigmine' and 'transdermal' or 'patch'. Efficacy, safety and tolerability of the rivastigmine patch vs. placebo were established in a large, international, 24-week, double-blind, randomised clinical trial and subsequent 28-week open-label extension study. Drug exposure with the 9.5 mg/24 h rivastigmine patch was not significantly different to that provided by an oral capsule dose of 12 mg/day. Most frequently observed adverse events were gastrointestinal. In the primary study, incidences of nausea, vomiting and diarrhoea were: 5%, 3% and 3% respectively in the placebo group; 7%, 6% and 6% in the 9.5 mg/24 h rivastigmine patch group; and 23%, 17% and 5% in the 12 mg/day capsule group. Most patients experienced no, slight or mild application-site skin reactions. De novo patients or those taking oral rivastigmine or donepezil may tolerate a switch to rivastigmine patch. By providing drug exposure that is not significantly different to the highest recommended rivastigmine capsule dose (12 mg/day), with less fluctuation over 24 h, rivastigmine patch offers similar efficacy with an improved tolerability profile. The rivastigmine patch provides a viable treatment option for patients with mild to moderate AD.

Safety and tolerability of rivastigmine transdermal patch compared with rivastigmine capsules in patients switched from donepezil: data from three clinical trials.

OBJECTIVES: To compare the safety and tolerability of switching patients with mild-to-moderate Alzheimer's disease from donepezil to either rivastigmine capsule or transdermal patch. METHODS: Three studies investigated the switch from donepezil to rivastigmine; study US13 was a 26-week, single-arm, immediate-switch study; US18 was a 26-week, sequential cohort study (both studies evaluated rivastigmine capsules 3-12 mg/day); study US38 was a 25-week, randomised, parallel-group, open-label study which investigated switch (immediate or after 7 days' withdrawal) from donepezil to rivastigmine transdermal patch (4.6 mg/24 hr). Safety outcomes included adverse events (AEs), discontinuations caused by AEs and serious AEs (SAEs). RESULTS: Patient groups receiving rivastigmine patch (n = 261) or capsules (n = 331) had mean +/- SD ages of 77.3 +/- 8.0 and 78.1 +/- 7.8 years, dementia durations of 3.9 +/- 2.6 and 3.6 +/- 2.2 years and Mini-Mental State Examination scores of 18.3 +/- 4.00 and 17.9 +/- 4.4 respectively. Overall, 184 (70.5%) and 276 (83.4%) patients experienced at least one AE, and 23 (8.8%) and 55 (16.6%) patients experienced an SAE with the rivastigmine patch and capsules respectively. Of the patients who experienced an AE, 10 (3.8%) and 109 (32.9%) experienced nausea, and 11 (4.2%) and 80 (24.1%) experienced vomiting with the rivastigmine patch and capsules respectively. Discontinuations because of AEs occurred in 64 (19.3%) patients receiving capsules and 38 (14.6%) patients in the transdermal patch group. The most common reasons for discontinuation with the transdermal patch were application site reaction and disease progression, and nausea and vomiting with the capsules. CONCLUSIONS: The rivastigmine transdermal patch appears to have better tolerability than rivastigmine capsules, with fewer gastrointestinal AEs and discontinuations because of these AEs. Simple daily rotation of patch location will likely reduce the frequency of skin reactions. This post hoc analysis was carried out by Novartis Pharmaceuticals Corporation. Data for the analysis were collected from the US13 study (CENA713B US13), the US18 study (CENA713B US18) and the US38 study (CENA713D US38).

Switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch.

Oral cholinesterase inhibitors (ChEIs) are associated with side effects such as nausea and vomiting. The use of transdermal patches for ChEI delivery may help to minimize these problems. The objective of this review was to consider available data from patients switching from oral ChEIs to transdermal rivastigmine treatment, and to suggest practical guidelines for patients wishing to do this. Literature database and reference list searches were performed to identify suitable publications. Data from two clinical trials and a series of open observational studies, in which patients were switched to the rivastigmine patch from oral rivastigmine, donepezil tablets, or galantamine, were evaluated. Adverse events were tabulated. In the studies reported here, nausea was reported in up to 3.2% and vomiting in up to 1.9% of patients switching to the rivastigmine patch from oral rivastigmine. Similar rates (up to 3.8% of patients for nausea and 0.8% of patients for vomiting) were reported when switching to the rivastigmine patch from donepezil tablets, and no nausea or vomiting was reported in a case study of patients switching to the rivastigmine patch from galantamine tablets. Switching regimes used in clinical trials appeared well tolerated. Data support recommendations for patients on high rivastigmine capsule doses to switch directly to the 9.5 mg/24 h rivastigmine patch, while those on lower oral rivastigmine doses should start on the 4.6 mg/24 h patch for 4 weeks before increasing to the 9.5 mg/24 h patch. This latter regimen is recommended for patients on other oral cholinesterase inhibitors if switching is medically indicated or requested by the patient or the caregiver.

DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD. METHOD: Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint. RESULTS: Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points. CONCLUSIONS: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.

Spinal cord injury.

PURPOSE: This article is an overview of the newer therapeutic interventions employed in the care of the spinal cord injured individual and the theoretical rationale supporting them. ISSUE: Spinal Cord Injury (SCI) care was, until recently, a maintenance type treatment, addressing systems mostly affected by complications of the original injury (e.g. bladder, skin, spasiticity). CONCLUSION: With the recent advances in the neuroscience field, more aggressive interventions geared at secondary injury prevention, neuronal regeneration and functional restoration are emerging.

The use of palatal rugae for the assessment of anteroposterior tooth movements.

Currently, cephalometric superimpositions are the accepted means for the assessment of orthodontic tooth movement. The present investigation evaluated the use of palatal rugae as reference points for the measurement of tooth movement, in a manner comparable with cephalometric superimpositions. The sample consisted of pretreatment and posttreatment maxillary study models and lateral cephalometric radiographs from 33 patients who had received orthodontic treatment that involved the extraction of the maxillary first permanent premolars. The mean age at the start of treatment was 13 years 11 months, and the average time between records was 35 months. The anteroposterior movement of the maxillary first molars and central incisors was evaluated with the use of 2 cephalometric variables and 12 study model variables that were reduced to 6 by the combining of the left and right sides. No statistical differences were found between the mean molar movement that was measured cephalometrically and the mean molar movement that was relative to the medial and lateral ends of the first and second palatal rugae or relative to the medial end of the third palatal ruga. Also, no statistical differences were found between the mean incisor movement that was measured cephalometrically and the mean incisor movement that was relative to the medial and lateral end of the third palatal ruga. These findings suggest that ruga landmarks can be used as reliably as cephalometric superimpositions to assess anteroposterior molar movements.

A relatively minor adult case becomes significantly complex: A lesson in humility.

A 41-year-old white woman with no particular concerns about facial esthetics was first seen with bilateral Class II molar relationship, a Class I right canine, and a Class II left canine. Overjet was 3 mm and overbite was 0.5 mm, with no incisor contact. A maxillary right premolar was missing for unknown reasons and all 4 third molars had previously been extracted. The maxillary midline was 2 mm to the right of the facial midline, and the mandibular midline was 3.5 mm to the left of the maxillary midline. There was 7 mm of crowding in the maxillary arch and 6 mm of crowding in the mandibular arch, with an increased curve of Spee. The patient had a well-positioned maxilla, a retrognathic mandible with increased convexity, a Class II denture base relationship, and a vertical facial pattern. The treatment plan consisted of extracting the maxillary left first premolar and the mandibular left central incisor. After 4 months of treatment, an open bite from second premolar to second premolar was noted. After 6 months of treatment, the patient expressed concern with her chin position and mentalis hyperactivity. It was apparent that the orthodontic treatment had resulted in molar extrusion, which the musculature was not able to withstand. Treatment continued and the case was set up for posterior maxillary impaction and mandibular advancement surgical procedures.

Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.

OBJECTIVE: To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment. METHODS: This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.

Electrical stimulation in spinal cord injury.

The use of electricity to stimulate nerves or muscles is nothing new. In the 18th century Galvani recognized that electricity could be converted into "nerve force". Numerous applications of electrical stimulation have been explored, most notably cardiac pacing, cochlear implants or transcutaneous electrical nerve stimulation (TENS) units for pain control. Spinal cord injury (SCI), with its "transecting lesion" that leaves intact nervous system below the injury completely disconnected from the centers that exert motor control provides the ideal opportunity for electrical stimulation use. Multiple applications are being investigated, including those for aerobic conditioning/cardiovascular exercise, cough and breathing assistance, improving bowel and bladder control, erection and ejaculation, hand grasp, spasticity management, neuro-muscular reeducation, standing and walking, etc. This review will focus on innovative and technologically advanced applications of electrical stimulation in the management of patients with spinal cord injury.

A comparison of the effects of rectangular and round arch wires in leveling the curve of Spee.

A prospective randomized clinical study was designed to evaluate the effects of full continuous arch wires, rectangular in cross section, on the axial inclination of lower incisors. The intention of rectangular arch wires is to counteract the labial crown moment usually produced during leveling the curve of Spee with full arch mechanics. Patients were randomly assigned to 2 groups. Group 1 (N = 12) received round arch wires throughout the leveling stage. Group 2 (N = 16) started with flat 0.016 x 0.022 nickel titanium arch wires progressing to 0.016 x 0.022 stainless steel. The preadjusted 0.018 x 0.025 edgewise appliance was used in all cases. Lateral cephalometric radiographs and mandibular study models were taken before treatment and when the curve of Spee was leveled (or in some cases when the overbite was considered clinically acceptable). In group 1, the lower incisor proclined a mean of 6.75 degrees +/- 4.85 degrees (P <.01) and in group 2 it proclined a mean of 6.10 degrees +/- 3.95 degrees (P <.01). However, no significant difference in proclination was detected between the 2 groups. Statistically significant, but low, correlations were demonstrated between change in lower incisor axial inclination and relief of crowding r = 0.45) and change in mandibular arch depth r = 0.54), which was in turn inversely correlated with change in intercanine width r = -0.45). In both groups, the lower incisors proclined with uncontrolled tipping that can probably be attributed to the intrusive force introduced by the arch wire being labial to the center of resistance of the lower incisors. The ability of the rectangular arch wires to control labial proclination following leveling of the curve of Spee, as used in this study, was not supported.

Mandibular asymmetry and condylar position in children with unilateral posterior crossbite.

The purpose of this retrospective study was to determine if condylar position in children with functional unilateral crossbites was different from that found in children with Class I noncrossbite malocclusions and if there was a change in condylar position after correction of the crossbite by palatal expansion. Mandibular asymmetry in children with functional unilateral posterior crossbite was also compared to that of a Class I noncrossbite group. Thirty-one children aged 6 to 14 years (mean, 9.3 years; standard deviation, 2.2) with functional unilateral crossbites were compared to 31 children aged 9.5 to 14.1 years (mean, 11.9 years; standard deviation, 1.3) exhibiting Angle Class I noncrossbite malocclusions. Pretreatment submentovertex radiographs were used to study mandibular skeletal, dental, and positional asymmetries with reference to cranial floor and mandibular coordinate systems. In addition, the anterior, superior, and posterior joint spaces were measured to determine differences between the groups with the use of pretreatment and posttreatment horizontally corrected tomograms of the temporomandibular joints. Finally, the distances of the mesiobuccal cusp of the upper first molar relative to the buccal groove of the lower first molar were measured in both groups before treatment. Univariate analyses revealed that the mandibles of children in the functional unilateral posterior crossbite group exhibited asymmetry in both anteroposterior and transverse dimensions when compared with the Class I noncrossbite group (P <. 05). These asymmetries were the result of a functional deviation of the mandible that was present in all subjects in the crossbite group. This deviation was manifested occlusally by a Class II subdivision on the crossbite side as indicated from the study model analysis (P <.05). Examination of condylar position as evidenced by horizontally corrected tomograms demonstrated a large standard deviation, resulting in an inability to detect any significant differences within or between groups at both T1 and T2 (P >.05). This study raised the question of the appropriateness of measuring joint spaces for routine diagnostic purposes.

Methodologies for evaluating long-term stability of dental relationships after orthodontic treatment.

A comprehensive review of literature which considers methodologies for studying long-term occlusal stability is presented. This article focuses on the evaluation of plaster study models because occlusal changes are best reflected in longitudinal casts. Of particular interest is the assessment of crowding in the dentition and the various physical and mathematical procedures used to evaluate the measurement of space available. Indices used to assess the overall occlusal results of treatment are also presented.

Effectiveness and duration of orthodontic treatment in adults and adolescents.

The purpose of this investigation was to compare the effectiveness and duration of orthodontic treatment in adults and adolescents with a valid and reliable occlusal index. Another aim was to evaluate variables that may influence the effectiveness and duration of orthodontic treatment in general. Pretreatment and posttreatment study models were scored using the Peer Assessment Rating Index. The difference in scores between pretreatment and posttreatment stages reflects the degree of improvement and therefore the effectiveness of treatment. Variables that reflect patient compliance were recorded from written treatment records from three private orthodontic practices. The sample consisted of 32 adults (mean age, 31.3 years) and 40 adolescents (mean age, 12.9 years), all of whom had four premolars extracted as part of the treatment strategy. The results indicated that there were no statistically significant differences (P > .05) between adults and adolescents regarding treatment effectiveness (occlusal improvement) and treatment duration. Multiple regression techniques revealed that the number of broken appointments and appliance repairs explained 46% of the variability in orthodontic treatment duration and 24% of the variability in treatment effectiveness. Furthermore, orthodontic treatment of the buccal occlusion and overjet explained 46% of the variability in treatment duration.

Analysis of change in arch form with premolar expansion.

The arch forms of 38 cases (53 nonextraction and 23 extraction arches) in which expansion, while maintaining arch form, was the objective of the practitioner, were analyzed before treatment, after treatment, and an average of 6 to 8 years after retention. The cubic spline was used to fit a curve representing arch form. By superimposing the spline curves, changes in arch form were analyzed with the variables rebound change (RC), rebound index (RI), rebound number (RN), and stability number (SN). Traditional linear intraarch dimensions were also analyzed. Analysis of variance was used to determine differences between the maxillary and mandibular arches and between the extraction and nonextraction cases. Pearson correlation coefficients between spline variables and arch width variables were also computed. There was significantly more expansion in the maxillary arch than the mandibular arch during treatment, irrespective of extraction or nonextraction strategies. In the nonextraction cases, a greater amount of net expansion was achieved for all dimensions for the maxillary arch as compared with the mandibular arch. Overall, a relatively high stability in arch form was found. The findings suggest that stability may not be related to the amount of change produced during treatment. Significant expansion can be gained throughout the premolar regions and may be expected to be stable. The order of greatest net arch width gained was for the second premolars followed by first premolars, molars, and then the canines. The intercanine widths for both arches decreased toward pretreatment values, but were more stable in the maxillary arch in nonextraction cases. The cubic spline permits measurement of change in arch form both during treatment and retention periods.

Efficacy of intraarch mechanics using differential moments for achieving anchorage control in extraction cases.

A prospective survey was conducted to test the hypothesis that maximum anchorage can be achieved in the maxillary arch by controlling forces and moments using intraarch mechanics while retracting canines into first premolar extraction sites. The sample consisted of 24 patients (mean age 18 years, 9 months) who required the extraction of two maxillary first premolars, with or without extractions in the mandibular arch. Movements of the first molars, canines, and incisors were evaluated with 6 cephalometric variables and 10 study model variables. T tests were used to assess differences between pretreatment and postretraction tooth positions. Cephalometrically, the maxillary first molars (left and right sides combined) moved mesially ONLY 0.7 mm (SD 0.43; p < 0.008). All other cephalometric variables showed no significant differences between the two time points. From the study models, the molars moved mesially ONLY 0.5 mm on both the right and left sides (right side SD = 0.43 and left side SD = 0.38; p < 0.005), while the canines were retracted on average 5.8 mm on the right side and 5.6 mm on the left. The molars and canines showed significant mesiopalatal and distolingual rotations, respectively. Many of the study model and cephalometric variables were significantly correlated to one another. This study questions the need to use adjunctive appliances, which directs a distal force to the posterior teeth, if horizontal molar anchorage control is a treatment objective. By controlling forces and moments, using intraarch mechanics while retracting maxillary canines into first premolar extraction sites, minimal molar anchorage loss occurred.