Large Multisite Clinical Trial Research Articles

Harmonizing multisite data with the ComBat method for enhanced Parkinson's disease diagnosis via DAT-SPECT.

Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson's disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as "combatting batch effects when combining batches of gene expression microarray data" (ComBat). We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges's g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination. Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.

CHALLENGES AND OPPORTUNITIES FOR RECRUITMENT AND RETENTION OF OLDER HISPANICS FOR CLINICAL RESEARCH

Abstract Older Hispanics represented 9% of the population over 65 years of age in the USA in 2019. That number is expected to increase to 21% by 2060. Representation of older Hispanics in clinical research is not proportional to the projected increase of older Hispanics. I will discuss the lessons learned on recruitment and retention of older Hispanics and their family caregivers from a large multi-site pragmatic clinical trial I am a part of and a small pilot project I am co-leading. The pragmatic trial compares a health-system-based approach and a community-based approach to dementia care. For this pragmatic trial, 2,176 dyads of persons living with dementia and their family caregivers were recruited. More than 20% of participating dyads belong to underrepresented racial and ethnic groups and 8.8% identified as Hispanic. The pilot project tests the cultural adaptation of the Patient Priorities Care (PPC) approach for older Hispanics. For the pilot project, we recruited 5 older Hispanics with multiple chronic conditions (MCC) and 20 Hispanics with MCC and dementia. I will describe the recruitment strategies used in each study, the barriers we faced, and the approaches we think worked best for the recruitment of Hispanics. I will also reflect on the challenges we currently face to conduct pragmatic trials that include older Hispanics and the opportunities for improvement.

77 Feasibility and Effectiveness of a Telehealth-Delivered Inductive Reasoning Training Program for Older Adults

Objective:Inductive reasoning training has been found to be particularly effective at improving inductive reasoning, with some evidence of improved everyday functioning and driving. Telehealth may be useful for increasing access to, reducing time and travel burdens of, and reducing the need for physical spaces for cognitive training. On the other hand, telehealth increases technology burden. The present study investigated the feasibility and effectiveness of implementing an inductive reasoning training program, designed to mimic the inductive reasoning arm used in a large multi-site clinical trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)), via telehealth (using Zoom and Canvas as delivery platforms).Participants and Methods:31 older adult participants (mean age = 71.2, range = 65-85; mean education = 15.5, range = 13-18; 64.5% female; 87.1% white) received 10-sessions of telehealth-delivered inductive reasoning training over 5 weeks. Comparison groups (inductive reasoning trained and no-contact controls) were culled from the in-person ACTIVE trial via propensity matching. All participants completed three pretest and posttest inductive reasoning measures (Word Series, Letter Series, Letter Sets), as well as a posttest measure assessing participant perceptions of the telehealth intervention. In addition, at the end of each of the ten training sessions, participants received a final inductive reasoning assessment.Results:Telehealth participants provided high levels of endorsement suggesting that the telehealth training program was useful, reliable, easy to use and interact on, and employed a useable interface. Participants were generally satisfied with the training program. With regard to performance, telehealth participants demonstrated greater gains than untrained controls on Letter Series [F(1, 116) = 9.81, p = 0.002, partial eta-squared = 0.084] and Letter Sets [F(1, 116) = 8.69, p = 0.004, partial eta-squared = 0.074], but did not differ in improvement on Word Series [F(1, 116) = 1.145, p = 0.287, partial eta-squared = 0.010]. Furthermore, telehealth participants evinced similar inductive reasoning gains as matched inperson inductive reasoning trained participants on Letter Series [F(1, 116) = 1.24, p = 0.226, partial eta-squared = 0.01] and Letter Sets [F(1, 116) = 1.29, p = 0.259, partial eta-squared = 0.01], but demonstrated fewer gains in Word Series performance [F(1, 116) = 25.681, p = < 0.001, partial eta-squared = 0.181]. On the end-of-session reasoning tests, telehealth-trained participants showed a similar general pattern of improvement across the ten training sessions and did not differ significantly from in-person trained comparison participants.Conclusions:Cognitive training via telehealth evinced similar gains across nearly all measures as its in-person counterpart. However, telehealth also led to substantial challenges regarding the telehealth training platform. Despite these challenges, participants reported perceiving increased competence with computer use, peripherals (mice, trackpad), and videoconferencing. These may be ancillary benefits of such training and may be maximized if more age-friendly learning management systems are investigated. Overall, this study suggests that telehealth delivery may be a viable form of cognitive training in inductive reasoning, and future studies could increase performance gains by optimizing the online training platform for older adults.

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults.

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the "Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts" (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer's Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer's Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults.

Hold that pose: capturing cervical dystonia's head deviation severity from video

ObjectiveDeviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system—the Computational Motor Objective Rater (CMOR)—to quantify multi‐axis directionality and severity of head posture in CD using only conventional video camera recordings.MethodsCMOR is based on computer vision and machine learning technology that captures 3D head angle from video. We used CMOR to quantify the axial patterns and severity of predominant head posture in a retrospective, cross‐sectional study of 185 patients with isolated CD recruited from 10 sites in the Dystonia Coalition.ResultsThe predominant head posture involved more than one axis in 80.5% of patients and all three axes in 44.4%. CMOR's metrics for head posture severity correlated with severity ratings from movement disorders neurologists using both the TWSTRS‐2 and an adapted version of the Global Dystonia Rating Scale (rho = 0.59–0.68, all p <0.001).ConclusionsCMOR's convergent validity with clinical rating scales and reliance upon only conventional video recordings supports its future potential for large scale multisite clinical trials.

Workshops of the eighth international brain–computer interface meeting: BCIs: the next frontier

ABSTRACT The Eighth International Brain–Computer Interface (BCI) Meeting was held June 7–9, 2021 in a virtual format. The conference continued the BCI Meeting series’ interactive nature with 21 workshops covering the breadth of topics in BCI (also called brain–machine interface) research. Some workshops provided detailed examinations of methods, hardware, or processes. Others focused on BCI applications or user groups. Several workshops continued consensus building efforts designed to create BCI standards and improve comparisons between studies and the potential for meta-analysis and large multi-site clinical trials. Ethical and translational considerations were the primary topic for some workshops or an important secondary consideration for others. The range of BCI applications continues to expand, with more workshops focusing on approaches that can extend beyond the needs of those with physical impairments. This paper summarizes each workshop, provides background information and references for further study, summarizes discussions, and describes the resulting conclusion, challenges, or initiatives.

Immediate Sample Fixation Increases Circulating Tumour Cell (CTC) Capture and Preserves Phenotype in Head and Neck Squamous Cell Carcinoma: Towards a Standardised Approach to Microfluidic CTC Biomarker Discovery.

Simple SummaryCirculating tumour cells (CTCs) have shown potential to act as markers of disease and prognosis in head and neck squamous cell carcinoma (HNSCC). However, there are a number of methods and devices reported to isolate and characterise CTCs. Translating CTC markers to clinical practice, for patient benefit, requires a reliable, reproducible and standardised approach. We report the benefit of the Parsortix microfluidic CTC enrichment platform in HNSCC. We demonstrate consistent cell capture rates between 10 and 100 cells/mL of whole blood. Analysis of gene expression with unfixed cells before and after Parsortix enrichment demonstrated a cell stress response and downregulation of key genes. We highlight the benefit of using a fixative blood collection tube (Transfix) to increase cell capture rate and preserve the CTC marker expression profile. Such evidence is crucial when designing sample processing protocols for large cohort multi-centre clinical trials investigating CTCs in any cancer type.Introduction: Research demonstrates strong evidence that circulating tumour cells (CTCs) can provide diagnostic and/or prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC) and a potential tool for therapeutic stratification. However, the question still remains as to the optimum method of CTC enrichment and how this can be translated into clinical practice. We aimed to evaluate the Parsortix microfluidic device for CTC enrichment and characterisation in HNSCC, seeking to optimise a sample collection and processing protocol that preserves CTC integrity and phenotype. Method: Spiking experiments of the FaDu and SCC040 HNSCC cell lines were used to determine the Parsortix capture rate of rare “CTC-like” cells. Capture rates of cancer cells spiked into EDTA blood collections tubes (BCTs) were compared to the Transfix fixative BCT and Cytodelics whole blood freezing protocol. The Lexogen Quantseq library preparation was used to profile gene expression of unfixed cells before and after microfluidic enrichment and enriched cell line spiked Transfix blood samples. An antibody panel was optimised to enable immunofluorescence microscopy CTC detection in HNSCC patient Transfix blood samples, using epithelial (EpCAM) and mesenchymal (N-cadherin) CTC markers. Results: Across a spiked cell concentration range of 9–129 cells/mL, Parsortix demonstrated a mean cell capture rate of 53.5% for unfixed cells, with no significant relationship between spiked cell concentration and capture rate. Samples preserved in Transfix BCTs demonstrated significantly increased capture rates at 0 h (time to processing) compared to EDTA BCTs (65.3% vs. 51.0%). Capture rates in Transfix BCTs were maintained at 24 h and 72 h timepoints, but dropped significantly in EDTA BCTs. Gene expression profiling revealed that microfluidic enrichment of unfixed cell lines caused downregulation of RNA processing/binding gene pathways and upregulation of genes involved in cell injury, apoptosis and oxidative stress. RNA was successfully extracted and sequenced from Transfix preserved cells enriched using Parsortix, demonstrating epithelial specific transcripts from spiked cells. In a proof-of-concept cohort of four patients with advanced HNSCC, CTCs were successfully identified and visualised with epithelial and epithelial-mesenchymal phenotypes. Conclusion: We have optimised a protocol for detection of CTCs in HNSCC with the Parsortix microfluidic device, using Transfix BCTs. We report a significant benefit, both in terms of cell capture rates and preserving cell phenotype, for using a fixative BCT- particularly if samples are stored before processing. In the design of large cohort multi-site clinical trials, such data are of paramount importance.

Long-acting buprenorphine injectables: Opportunity to improve opioid use disorder treatment among rural populations

The opioid epidemic continues with escalating overdose deaths further exacerbated by the coronavirus pandemic, despite having efficacious medication treatments for opioid use disorder (MOUD). Most persons with OUD remain undiagnosed, without ever receiving MOUD, and even among those who initiate MOUD, retention is infrequently longer than 6 months (Williams et al., 2019). Treatment access remains particularly problematic in rural areas that often have few providers and limited resources (Ghertner, 2019). There are two new injectable long-acting buprenorphine (LAB) formulations recently approved in the United States and abroad (Lofwall et al., 2018; Walsh et al., 2017; Haight et al., 2019). They hold promise to improve treatment access and retention by decreasing risks of nonadherence, diversion and misuse and may be particularly attractive during a pandemic in order to minimize provider and pharmacy contacts (Roberts et al., 2020) and help improve access to care in rural areas. There are several ongoing evaluations of LAB injectables in large multi-site randomized clinical trials sponsored by the National Institute on Drug Abuse and Veterans Administration Office of Research and Development in settings with special populations that exist in both urban and rural settings. Understanding the potential clinical benefits of LAB injectables along the care continuum, particularly for rural areas is essential to successful implementation in the complex healthcare system.

Clinical trials proposed for the VA Cooperative Studies Program: Success rates and factors impacting approval

The process by which funding organizations select among the myriad number of proposals they receive is a matter of significant concern for researchers and the public alike. Despite an extensive literature on the topic of peer review and publications on criteria by which clinical investigations are reviewed, publications analyzing peer review and other processes leading to government funding decisions on large multi-site clinical trials proposals are sparse. To partially address this gap, we reviewed the outcomes of scientific and programmatic evaluation for all letters of intent (LOIs) received by the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) between July 4, 2008, and November 28, 2016. If accepted, these LOIs represented initial steps towards later full proposals that also underwent scientific peer review. Twenty-two of 87 LOIs were ultimately funded and executed as CSP projects, for an overall success rate of 25%. Most proposals which received a negative decision did so prior to submission of a full proposal. Common reasons for negative scientific review of LOIs included investigator inexperience, perceived lack of major scientific impact, lack of preliminary data and flawed or confused experimental design, while the most common reasons for negative reviews of final proposals included questions of scientific impact and issues of study design, including outcome measures, randomization, and stratification. Completed projects have been published in high impact clinical journals. Findings highlight several factors leading to successfully obtaining funding support for clinical trials. While our analysis is restricted to trials proposed for CSP, the similarities in review processes with those employed by the National Institutes of Health and the Patient Centered Outcomes Research Institute suggest the possibility that they may also be important in a broader context.

Immersive Virtual Reality to Improve Outcomes in Veterans With Stroke: Protocol for a Single-Arm Pilot Study.

BackgroundOver the last decade, virtual reality (VR) has emerged as a cutting-edge technology in stroke rehabilitation. VR is defined as a type of computer-user interface that implements real-time simulation of an activity or environment allowing user interaction via multiple sensory modalities. In a stroke population, VR interventions have been shown to enhance motor, cognitive, and psychological recovery when utilized as a rehabilitation adjunct. VR has also demonstrated noninferiority to usual care therapies for stroke rehabilitation.ObjectiveThe proposed pilot study aims to (1) determine the feasibility and tolerability of using a therapeutic VR platform in an inpatient comprehensive stroke rehabilitation program and (2) estimate the initial clinical efficacy (effect size) associated with the VR platform using apps for pain distraction and upper extremity exercise for poststroke neurologic recovery.MethodsThis study will be conducted in the Comprehensive Integrated Inpatient Rehabilitation Program at the James A Haley Veterans’ Hospital. Qualitative interviews will be conducted with 10 clinical staff members to assess the feasibility of the VR platform from the clinician perspective. A prospective within-subject pretest-posttest pilot design will be used to examine the tolerability of the VR platform and the clinical outcomes (ie, upper extremity neurologic recovery, hand dexterity, pain severity) in 10 veteran inpatients. A VR platform consisting of commercially available pain distraction and upper extremity apps will be available at the participants’ bedside for daily use during their inpatient stay (approximately 4-6 weeks). Clinician interviews will be analyzed using qualitative descriptive analysis. Cohen d effect sizes with corresponding 95% CIs will be calculated for upper extremity neurologic recovery, hand dexterity, and pain. The proportion of participants who achieve minimal clinically important difference after using the VR platform will be calculated for each clinical outcome.ResultsThis study was selected for funding in August 2020. Institutional review board approval was received in October 2020. The project start date was December 2020. The United States Department has issued a moratorium on in-person research activities secondary to COVID-19. Data collection will commence once this moratorium is lifted.ConclusionsOur next step is to conduct a large multi-site clinical trial that will incorporate the lessons learned from this pilot feasibility study to test the efficacy of a VR intervention in inpatient rehabilitation and transition to home environments. When VR is used in patients’ rooms, it serves to provide additional therapy and may reduce clinician burden. VR also presents an opportunity similar to home-based practice exercises. VR can be implemented in both clinical settings and people’s own homes, where engagement in ongoing self-management approaches is often most challenging. This unique experience offers the potential for seamless transition from inpatient rehabilitation to the home.International Registered Report Identifier (IRRID)PRR1-10.2196/26133

Study protocol of coaching end-of-life palliative care for advanced heart failure patients and their family caregivers in rural appalachia: a randomized controlled trial

BackgroundHeart failure (HF) afflicts 6.5 million Americans with devastating consequences to patients and their family caregivers. Families are rarely prepared for worsening HF and are not informed about end-of-life and palliative care (EOLPC) conservative comfort options especially during the end stage. West Virginia (WV) has the highest rate of HF deaths in the U.S. where 14% of the population over 65 years have HF. Thus, there is a need to investigate a new family EOLPC intervention (FamPALcare), where nurses coach family-managed advanced HF care at home.MethodsThis study uses a randomized controlled trial (RCT) design stratified by gender to determine any differences in the FamPALcare HF patients and their family caregiver outcomes versus standard care group outcomes (N = 72). Aim 1 is to test the FamPALcare nursing care intervention with patients and family members managing home supportive EOLPC for advanced HF. Aim 2 is to assess implementation of the FamPALcare intervention and research procedures for subsequent clinical trials. Intervention group will receive routine standard care, plus 5-weekly FamPALcare intervention delivered by community-based nurses. The intervention sessions involve coaching patients and family caregivers in advanced HF home care and supporting EOLPC discussions based on patients’ preferences. Data are collected at baseline, 3, and 6 months. Recruitment is from sites affiliated with a large regional hospital in WV and community centers across the state.DiscussionThe outcomes of this clinical trial will result in new knowledge on coaching techniques for EOLPC and approaches to palliative and end-of-life rural home care. The HF population in WV will benefit from a reduction in suffering from the most common advanced HF symptoms, selecting their preferred EOLPC care options, determining their advance directives, and increasing skills and resources for advanced HF home care. The study will provide a long-term collaboration with rural community leaders, and collection of data on the implementation and research procedures for a subsequent large multi-site clinical trial of the FamPALcare intervention. Multidisciplinary students have opportunity to engage in the research process.Trial registrationClinicalTrials.gov NCT04153890, Registered on 4 November 2019

Optimizing the Delivery of Home-Based Palliative Care: Experiences from PCORI’s Ongoing Large Multi-Site Clinical Trials (FR472)

Optimizing the Delivery of Home-Based Palliative Care: Experiences from PCORI’s Ongoing Large Multi-Site Clinical Trials (FR472)

1.3 The Impact of Tobacco, Alcohol, and Cannabis Use on Treatment Outcomes Among Patients Experiencing First-Episode Psychosis: Data From the National RA1SE Early Treatment Program (ETP) Study

The goal of this session is to examine the effect of recent tobacco, alcohol, and cannabis use on treatment outcomes among participants experiencing first-episode psychosis (FEP); these participants were enrolled in a large multisite clinical trial called Recovery After an Initial Schizophrenia Episode—Early Treatment Program (RAISE-ETP).

A Physical Therapist–Administered Physical Activity Intervention After Total Knee Replacement: Protocol for a Randomized Controlled Trial

The definitive treatment for knee osteoarthritis is a total knee replacement, which results in a clinically meaningful improvement in pain and physical function. However, evidence suggests that physical activity (PA) remains unchanged after total knee replacement (TKR). The objective of this study is to investigate the efficacy, fidelity, and safety of a physical therapist-administered PA intervention for people after TKR. This study will be a randomized controlled trial. The setting is an outpatient physical therapy clinic. The participants are 125 individuals who are over the age of 45 and are seeking outpatient physical therapy following a unilateral TKR. In addition to standardized physical therapy after TKR, the intervention group will receive, during physical therapy, a weekly PA intervention that includes a wearable activity tracking device, individualized step goals, and face-to-face feedback provided by a physical therapist. The control group will receive standardized physical therapy alone after TKR. The efficacy of the intervention will be measured as minutes per week spent in moderate to vigorous PA at enrollment, at discharge, and at 6 months and 12 months after discharge from physical therapy. The fidelity and safety of the intervention will be assessed throughout the study. Participants will not be masked, PA data will be collected after randomization, and the trial will be conducted at a single site. The goal of this randomized controlled trial is to increase PA after TKR. A protocol for investigating the efficacy, fidelity, and safety of a physical therapist-administered PA intervention for people after TKR is presented. The findings will be used to support a large multisite clinical trial to test the effectiveness, implementation, and cost of this intervention.

Outcomes for adolescents who comply with long-term psychosocial treatment for ADHD.

We conducted a large (N = 216) multisite clinical trial of the Challenging Horizons Program (CHP)-a yearlong afterschool program that provides academic and interpersonal skills training for adolescents with attention-deficit/hyperactivity disorder. Intent-to-treat analyses suggest that, as predicted, the CHP resulted in significant reductions in problem behaviors and academic impairment when compared to community care. However, attendance in the CHP ranged from zero to 60 sessions, raising questions about optimal dosing. To evaluate the impact of treatment compliance, complier average causal effect modeling was used to compare participants who attended 80% or more of sessions to an estimate of outcomes for comparable control participants. Treatment compliers exhibited medium to large benefits (ds = 0.56 to 2.00) in organization, disruptive behaviors, homework performance, and grades relative to comparable control estimates, with results persisting 6 months after treatment ended. However, compliance had little impact on social skills. Students most in need of treatment were most likely to comply, resulting in significant benefits in relation to comparable control participants who experienced deteriorating outcomes over time. Difficulties relating to dose-response estimation and the potentially confounding influence of treatment acceptability, accessibility, and client motivation are discussed. (PsycINFO Database Record

Evaluation of the impact of preoperative assessment on length of stay after a total hip arthroplasty

Introduction To investigate if preoperative assessment delivered by occupational therapists, physiotherapists and social workers for people awaiting a total hip arthroplasty decreased the length of stay in hospital postoperatively. Method A retrospective data review was conducted on all patients who had a primary total hip arthroplasty across a 6-month period. A total of 101 patients (mean age 67.16 years) was included in this evaluation. Clinical notes were used to determine which patients attended or did not attend preoperative assessment. Statistical modeling was used to analyse the association of a series of variables and time spent in hospital after a total hip arthroplasty. Results There was no significant difference in the length of stay for patients who attended preoperative assessment ( P &lt; 0.05) while patients who were medically unfit, lived alone and/or required a care package experienced a significantly higher length of stay ( P &lt; 0.05). Conclusion These results do not support the British Orthopaedic Association’s recommendation that preoperative assessment delivered by allied health professionals helps reduce length of stay. However, it identifies variables which could be managed potentially to reduce length of stay. A large multisite clinical trial is required to determine if preoperative assessment reduces length of stay for people undergoing this surgical procedure.

Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment.

To estimate differences in post-treatment psychosocial functioning among treatment 'failures' (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment 'successes' (i.e. non-heavy drinkers). Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies and Behavioral Interventions) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity), comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. Eleven US academic sites in COMBINE, 27US treatment sites local to nine research sites in Project MATCH. A total of 962 individuals in COMBINE (69% male, 77% white, mean age: 44years) treated January 2001 to January 2004 and 1528 individuals in Project MATCH (75% male, 80% white, mean age: 40years) treated April 1991 to September 1994. In COMBINE, we analyzed health, quality of life, mental health symptoms and alcohol consequences 12 months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms and alcohol consequences 15 months post-baseline. Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment 'failures', characterized by high-, average- and low-functioning individuals. The high-functioning treatment 'failures' generally performed better across measures of psychosocial functioning at follow-up than participants designated treatment 'successes' by virtue of being abstainers or light drinkers. Current United States Food and Drug Administration guidance to use heavy drinking as indicative of treatment 'failure' fails to take into account substantial psychosocial improvements made by individuals who continue occasionally to drink heavily post-treatment.

E32 A 36 Month Longitudinal Magnetic Resonance Spectroscopy Study In Pre-manifest And Early Huntington Disease Subjects From The Track-hd Study

<h3>Background</h3> TRACK-HD is a multi-national longitudinal observational study of Huntington Disease (HD). Magnetic Resonance Spectroscopy (MRS) utilises MRI technology to measure brain metabolites. <h3>Aims</h3> Using MRS we aimed to define patterns of change in specific metabolite concentrations that reflect disease onset or progression in brain regions affected in HD. <h3>Methods</h3> Age and gender-matched subjects from a single TRACK-HD site (Vancouver) were evaluated by MRS at four visits over 36 months. Early HD was defined as UHDRS-TFC Stage 1 or 2, Pre-manifest HD (Pre-HD) individuals scored &lt;5 on UHDRS-TMS and controls were gene negative spouses or family members. The MRS protocol involved single voxel spectroscopy in the LEFT putamen using a 3T Philips Achieva MRI Scanners. Metabolites reported include: N-acetyl Aspartate (NAA) a marker of neuronal integrity; Creatine, a marker of brain energy metabolism; Choline, a marker for neuronal membrane turnover; Glutamate, a major CNS excitatory neurotransmitter; and Myo-inositol (mI), an astrocyte marker. MRS spectra were fit using the LCModel program, and metabolite concentrations were normalised to the unsuppressed water signal. <h3>Results</h3> At all time points, decreased putaminal NAA concentration was observed in Pre-HD and Early HD; the decrease in NAA concentration was independent of grey matter volume loss (putamen atrophy), showed longitudinal consistency, and correlated with motor performance at baseline. Putaminal mI concentration was increased in early HD at all time points. Additional findings for other metabolites will be presented. <h3>Conclusions</h3> We identify here a potentially useful role for MRS in measuring disease progression and disease onset in HD. These MRS measures are biologically relevant endpoints that should be further evaluated in large multi-site clinical trials.

Therapist focus on ambivalence and commitment: A longitudinal analysis of Motivational Interviewing treatment ingredients.

The present study examines two core therapeutic principles of Motivational Interviewing (MI) with alcohol and other substance use disorders. Specifically, therapist focus on client ambivalence and commitment to change, as well as a more general indicator of goal assessment, were tested as process predictors of subsequent alcohol use across four sessions of Motivational Enhancement Therapy. Participants were adult alcohol users involved in a large multisite clinical trial (Project MATCH; two arms Aftercare [AC] and Outpatient [OP]). A series of multilevel models examined the effect of proposed MI ingredients on alcohol use (percent days abstinent; drinks per drinking day) over a 12-week treatment period, and whether these effects interacted with time and client baseline motivation. Therapist effort to elicit client commitment to change alcohol use was associated with greater rates of abstinence among both AC and OP participants, and reduced drinking quantity among OP participants. However, therapist focus on ambivalence was associated with greater drinking quantity among OP participants, and when motivation was low, among AC participants. Goal assessment was a marginal to nonsignificant predictor across outcomes, and all interactions with time were nonsignificant. Therapist-reported treatment foci are important to subsequent patterns of drinking within a multisession MI, but the role of ambivalence and discrepancy is worthy of further clinical and empirical consideration.

Time to initiation of treatment for neonatal abstinence syndrome in neonates exposed in utero to buprenorphine or methadone

BackgroundThe recommended standard of care calls for treating opioid-dependent pregnant women with methadone and observing neonates exposed in utero for five to seven postnatal days to see if treatment for neonatal abstinence syndrome (NAS) is needed. Data from a large multi-site randomized clinical trial comparing buprenorphine vs. methadone for the treatment of opioid dependence during pregnancy suggest buprenorphine-exposed neonates had less severe NAS, but may require pharmacologic treatment for NAS later than methadone-exposed neonates. The present study examined whether time to pharmacologic treatment initiation differed in a relatively large non-blinded clinical sample of buprenorphine- vs. methadone-exposed neonates treated for NAS. MethodsMedical records for 75 neonates exposed to buprenorphine (n=47) or methadone (n=28) in utero who required treatment for NAS were examined. Time elapsed between birth and initiation of pharmacologic treatment was calculated for each neonate and time to treatment initiation compared between groups. ResultsMedian time to treatment initiation (hours:minutes, IQR) was significantly later in buprenorphine- vs. methadone-exposed neonates (71:02, 44:21–96:27 vs. 34:12, 21:00–55:41, respectively, p<.001). Estimates of mean time to treatment initiation from parametric analyses that adjusted for maternal and neonatal characteristics were very similar (73:10 (95% CI: 61:00–87:18) vs. 42:36 (95% CI: 33:06–53:30), respectively, p=.0005). This difference was not dependent on maternal age or neonatal sex, gestational age, or birth weight. ConclusionsThese findings confirm results from randomized clinical trials, adding generality to the observation that buprenorphine-exposed neonates require treatment significantly later than methadone-exposed neonates.