Primary Clinical Outcome Measure Research Articles

Does seeking knowledge of depression make a difference? A randomized study to examine the efficacy of psychoeducational intervention with patients suffering from non-psychotic depression

Aims: The primary objective of the study is to assess the efficacy of a systematic patient-centered psychoeducation program on knowledge seeking of depression and on the clinical outcomes, in patients with non-psychotic major depressive disorder. Method: 52 consenting patients with confirmed diagnosis of major depression were randomly assigned to a group (n = 32) who received systematized psychoeducation for depression, and to a waiting group (n = 20) who received standard care. The intervention group received systematic education consisting of (i) Reading material, "depression manual", and (ii) individual or groups educational sessions. The primary clinical outcome measures included the clinician rated quick inventory of depressive symptomatology (QIDS-C) and the self-rated quick inventory of depressive symptomatology (QIDS-SR). Patients in both groups completed QIDS-SR, and the knowledge seeking behavior instrument (KSI), at baseline, at 4th, 8th and 12th weeks. Results: At 12th week, there was significant (p less than 0.01) reduction in the (QIDS-CR) and the (QIDS-SR) scores in both the intervention and waiting group patients. However, there were significant differences between the two groups, with the superiority for the intervention group in reduction of depressive symptoms. The number of hours spent in knowledge seeking as measured by the (KSI), correlated negatively with the scores of QIDS-SR, and QIDS-CR. Conclusion: Systematized education may lead to significant reduction in clinical symptomatology, and to improved knowledge seeking behavior.

Development of a group and family‐based cognitive behavioural therapy program for youth at risk for psychosis

The onset of psychosis typically occurs during adolescence or early adulthood and can have a detrimental impact on social and cognitive development. Cognitive behavioural therapy (CBT) shows promise in reducing the risk of psychosis. Teaching families to apply CBT with their offspring may bolster therapeutic gains made in time-limited treatment. We developed a comprehensive group-and-family-based CBT (GF-CBT) program that aims to facilitate psychosocial recovery, decrease symptoms and prevent transition to psychosis in youth at risk. GF-CBT is grounded in ecological systems and cognitive theories, resilience models and research on information processing in delusions. The theoretical rationale and description of GF-CBT are presented together with a pilot study that evaluated the program's feasibility and explored participants' outcomes. Youth ages 16-21 at risk for psychosis and their families participated in an open trial with pre, post and 3-month follow-up assessments conducted by an independent evaluator. The Comprehensive Assessment of At-Risk Mental States was the primary clinical outcome measure. All enrolled participants (n = 6) completed GF-CBT and all remitted from at-risk mental state (ARMS). As a group participants showed statistically significant decreases in attenuated psychotic symptoms, negative symptoms, depression, cognitive biases and improvements in functioning. Family members showed significant improvements in use of CBT skills, enhanced communication with their offspring, and greater confidence in their ability to help. Gains were maintained at follow-up. GF-CBT may delay or prevent transition to psychosis in youth at risk, and potentially facilitate recovery from ARMS. More rigorous, controlled research is needed to further evaluate this program.

Baseline Serum Interleukin-6 Predicts Cardiovascular Events in Incident Peritoneal Dialysis Patients

The utility of local and systemic interleukin 6 (IL-6) as a prognostic marker in incident peritoneal dialysis (PD) patients remains to be fully defined. The present study aimed to explore the capacity of systemic IL-6 concentrations to predict cardiovascular events (CVEs) and mortality in PD patients, and to evaluate the influence of neutral-pH PD solutions low in glucose degradation products (GDPs) on systemic IL-6. The study included 175 incident participants from the balANZ trial with at least one stored serum sample. A composite CVE score was used as the primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe, respectively, the trend of serum IL-6 over time and its ability to predict composite CVE. A significant increase in serum IL-6 from baseline to 24 months was observed in the study population (mean difference: 1.68 pg/mL; p = 0.006). The type of PD solution received by patients exerted no significant effect on serum IL-6 (p = 0.12). Composite CVE was significantly and independently associated with baseline serum IL-6 (incidence rate ratio per picogram per milliliter: 1.06; 95% confidence interval: 1.02 to 1.10; p = 0.003). Baseline serum IL-6 was a significant independent predictor of composite CVE. Serum IL-6 concentrations increased with increasing PD duration and were not significantly modified with the use of biocompatible fluid over the study period. The present study is the first to link systemic IL-6 concentrations with CVE outcomes in incident PD patients.

Design of an international multicentre RCT on group schema therapy for borderline personality disorder.

BackgroundBorderline personality disorder (BPD) is a severe and highly prevalent mental disorder. Schema therapy (ST) has been found effective in the treatment of BPD and is commonly delivered through an individual format. A group format (group schema therapy, GST) has also been developed. GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness. An important question is how GST compares to treatment as usual (TAU) and what format for delivery of schema therapy (format A; intensive group therapy only, or format B; a combination of group and individual therapy) produces the best outcomes.Methods/DesignAn international, multicentre randomized controlled trial (RCT) will be conducted with a minimum of fourteen participating centres. Each centre will recruit multiple cohorts of at least sixteen patients. GST formats as well as the orders in which they are delivered to successive cohorts will be balanced. Within countries that contribute an uneven number of sites, the orders of GST formats will be balanced within a difference of one. The RCT is designed to include a minimum of 448 patients with BPD. The primary clinical outcome measure will be BPD severity. Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms, schemas and schema modes, social functioning and quality of life. Furthermore, an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective. Lastly, additional investigations will be carried out that include an assessment of the integrity of GST, a qualitative study on patients’ and therapists’ experiences with GST, and studies on variables that might influence the effectiveness of GST.DiscussionThis trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST. By combining an evaluation of clinical effectiveness, an economic evaluation and additional investigations, it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical, economic, and stakeholders’ perspectives.Trial registrationNetherlands Trial Register NTR2392. Registered 25 June 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0319-3) contains supplementary material, which is available to authorized users.

The Utah Remote Monitoring Project: improving health care one patient at a time.

The expanding role of technology to augment diabetes care and management highlights the need for clinicians to learn about these new tools. As these tools continue to evolve and enhance improved outcomes, it is imperative that clinicians consider the role of telemonitoring, or remote monitoring, in patient care. This article describes a successful telemonitoring project in Utah. This was a nonrandomized prospective observational preintervention-postintervention study, using a convenience sample. Patients with uncontrolled diabetes and/or hypertension from four rural and two urban primary care clinics and one urban stroke center participated in a telemonitoring program. The primary clinical outcome measures were changes in hemoglobin A1C (A1C) and blood pressure. Other outcomes included fasting lipids, weight, patient engagement, diabetes knowledge, hypertension knowledge, medication adherence, and patient perceptions of the usefulness of the telemonitoring program. Mean A1C decreased from 9.73% at baseline to 7.81% at the end of the program (P<0.0001). Systolic blood pressure also declined significantly, from 130.7 mm Hg at baseline to 122.9 mm Hg at the end (P=0.0001). Low-density lipoprotein content decreased significantly, from 103.9 mg/dL at baseline to 93.7 mg/dL at the end (P=0.0263). Other clinical parameters improved nonsignificantly. Knowledge of diabetes and hypertension increased significantly (P<0.001 for both). Patient engagement and medication adherence also improved, but not significantly. Per questionnaires at study end, patients felt the telemonitoring program was useful. Telemonitoring improved clinical outcomes and may be a useful tool to help enhance disease management and care of patients with diabetes and/or hypertension.

Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients

This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures – the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry – further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials.

Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT)

IntroductionMany patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy....

Platelet-Rich Plasma for the Treatment of Chronic Plantar Fasciopathy in Adults

Plantar fasciopathy (PF) is a common source of pain and disability that is often refractory to conservative management. There are no uniformly effective standard-of-care treatments for chronic recalcitrant PF. Corticosteroid injection is considered a viable treatment option when traditional therapies fail, but is limited by suboptimal long-term efficacy and potential adverse effects. Platelet-rich plasma (PRP) is an emerging injection-based treatment for various chronic degenerative soft-tissue diseases. It is postulated to promote native tissue regeneration; however, consistent scientific evidence remains lacking. A prospective case series, including 24 consecutive PF cases, was conducted to report patient-rated pain and disability following PRP injection. Foot and Ankle Ability Measure (FAAM) scores were the primary clinical outcome measure. Foot-Single Assessment Numeric Evaluation (Foot-SANE) scores, Short Form-12 Health Survey version 2 (SF-12v2) questionnaires, and PRP treatment satisfaction surveys were secondary outcome measures. Statistical analysis compared baseline and 32 weeks post-injection time points. Patients receiving PRP injection reported clinically and statistically significant improvement in all outcome measures during this interval. There were no serious adverse events associated with treatment. PRP is considered a safe therapeutic option with the ability to decrease heel pain in patients with chronic PF refractory to appropriate conservative management.

Does obesity increase the rate of recurrent herniated nucleus pulposus after lumbar microdiscectomy?

Introduction Given the rising incidence of obesity in the adult population, it is more than likely that orthopaedic surgeons will be treating more obese patients with lumbar disc pathologies. The relationship between obesity and recurrent herniated nucleus pulposus (HNP) following microdiscectomy remains unclear. Objectives To investigate the relationship between obesity and recurrent HNP following lumbar microdiscectomy. Methods A retrospective review of case notes from 2008–2011 was conducted for all patients that underwent one level lumbar microdiscectomy, performed by a single surgeon. The standard criteria for microdiscectomy were used. Patient demographics, including Body Mass Index (BMI), collected from notes. Obese patients classified as BMI >/= 30. The primary clinical outcome measure was evidence of recurrent HNP on post operative MRI scan requiring further surgery. Results A total of 283 patients were available for analysis: 190(67%) were in the non-obese group and 93 (32.9%) in the obese group. The average BMI was 28.1 and the average length of stay was 1.3days. Dural leak was seen in 11 patients(3.9%) out of which 8(4.2%) occurred in the non-obese group and 3(3.2%) in the obese group [p=0.04]. Recurrent symptomatic HNP was seen in 27(9.5%) patients confirmed by MRI scan. 19(10%) were in the non-obese group and 8(8.6%) in the obese group [p>0.8]. Conclusion Obesity was not a predictor of recurrent HNP after lumbar microdiscectomy and did not have increased complication rates compared to the non-obese group.

Cost-effectiveness of a stepped-care intervention to prevent major depression in patients with type 2 diabetes mellitus and/or coronary heart disease and subthreshold depression: design of a cluster-randomized controlled trial

BackgroundCo-morbid major depression is a significant problem among patients with type 2 diabetes mellitus and/or coronary heart disease and this negatively impacts quality of life. Subthreshold depression is the most important risk factor for the development of major depression. Given the highly significant association between depression and adverse health outcomes and the limited capacity for depression treatment in primary care, there is an urgent need for interventions that successfully prevent the transition from subthreshold depression into a major depressive disorder. Nurse led stepped-care is a promising way to accomplish this. The aim of this study is to evaluate the cost-effectiveness of a nurse-led indicated stepped-care program to prevent major depression among patients with type 2 diabetes mellitus and/or coronary heart disease in primary care who also have subthreshold depressive symptoms.Methods/designAn economic evaluation will be conducted alongside a cluster-randomized controlled trial in approximately thirty general practices in the Netherlands. Randomization takes place at the level of participating practice nurses. We aim to include 236 participants who will either receive a nurse-led indicated stepped-care program for depressive symptoms or care as usual. The stepped-care program consists of four sequential but flexible treatment steps: 1) watchful waiting, 2) guided self-help treatment, 3) problem solving treatment and 4) referral to the general practitioner. The primary clinical outcome measure is the cumulative incidence of major depressive disorder as measured with the Mini International Neuropsychiatric Interview. Secondary outcomes include severity of depressive symptoms, quality of life, anxiety and physical outcomes. Costs will be measured from a societal perspective and include health care utilization, medication and lost productivity costs. Measurements will be performed at baseline and 3, 6, 9 and 12 months.DiscussionThe intervention being investigated is expected to prevent new cases of depression among people with type 2 diabetes mellitus and/or coronary heart disease and subthreshold depression, with subsequent beneficial effects on quality of life, clinical outcomes and health care costs. When proven cost-effective, the program provides a viable treatment option in the Dutch primary care system.Trial registrationDutch Trial Register NTR3715

Intra-articular hylastan versus steroid for knee osteoarthritis

To assess the efficacy and safety of one and two intra-articular (IA) injections of the new viscosupplement, hylastan, compared with a single IA corticosteroid injection for pain due to knee osteoarthritis (OA). Hylastan is a high-molecular-weight hyaluronan derivative prepared from bacterial fermented sodium hyaluronate that was developed to remain in the joint for longer than most other viscosupplements. This 6-month, double-blind, randomized, parallel group, multicenter trial enrolled patients aged ≥40 years who met American College of Rheumatology criteria for knee OA and had continued pain despite conservative treatment. Patients were randomized 1:1:1 to one of three arms: 2 × 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 × 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). Participants and evaluators were blinded to treatment. The primary clinical outcome measure was change from baseline in WOMAC A pain score over all postbaseline visits to Week 26. Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A: 2 × 4 mL hylastan -0.9 (-1.0, -0.7); 1 × 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all P < 0.0001 versus baseline. Changes in secondary outcomes (OMERACT-OARSI and WOMAC A responder rates, patient/clinical observer global assessments, and WOMAC A1 walking pain) were similar in all three arms. Target knee adverse events were comparable for all treatments. Both IA hylastan injection regimens were effective in relieving pain with an acceptable safety profile. IA hylastan did not show a difference versus IA corticosteroid; therefore, the hypothesis of superior pain relief was not met. Further research is needed to compare the efficacy and safety of hylastan with other viscosupplements.

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial

BackgroundMany older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial.MethodsA 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life.DiscussionThe EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses.Trial registrationClinical Trials NCT01740635.

The management of elderly diabetic Saudi patients with acute coronary syndrome

Background and Purpose:Elderly Diabetics (DM) who present with Acute Coronary Syndrome (ACS) constitute a very high risk group. We present the pattern of management of elderly patients (>65 years) in the Kingdom of Saudi Arabia (KSA) in comparison to the international data extrapolated from a Multicenter International Diabetes-Acute Coronary Syndromes (MIDAS).Materials and Methods:DM patients presenting with unstable angina or non-ST-segment elevation myocardial infarction (MI) at the time of admission to the hospital were collectively enrolled into the MIDAS study. A total of 3624 patients were enrolled; 142 were from Saudi Arabia. Primary clinical outcome measure was in-hospital death or MI. We present the data of KSA based on the age of the patients in comparison to the international registry.Results:Baseline characteristics were typical for DM presenting with ACS, with mean age of 67 ± 15 years, males, constituted 36% of patients while 94% of patients were DM type 2. There was marked underutilization of glycoprotein IIb/IIIa inhibitors in those aged over 65 years with a decrease from 22.5 to 12.7 in KSA (Odds ratio 0.56) patients. The percentage of early coronary angiography approach in KSA was less than that of the international data with further reduction of the percentage in Saudi elderly population (from 49.3% to 25.5% with Odds ratio 0.52).Conclusions:In elderly Saudi diabetic patients admitted with ACS, there is tendency for underutilization of GP IIb/IIIa, early coronary angiography, and revascularization that needs to be addressed.

Prospective randomized study of cervical arthroplasty and anterior cervical discectomy and fusion with long-term follow-up: results in 74 patients from a single site

The purpose of this study was to evaluate the long-term results of cervical total disc replacement (TDR) and anterior cervical discectomy and fusion (ACDF) in the treatment of single-level cervical radiculopathy. The results of 2 separate prospective, randomized, US FDA Investigational Device Exemption pivotal trials (Bryan Disc and Kineflex|C) from a single investigational site were combined to evaluate outcomes at long-term follow-up. The primary clinical outcome measures included the Neck Disability Index (NDI), visual analog scale (VAS), and neurological examination. Patients were randomized to receive cervical TDR in 2 separate prospective, randomized studies using the Bryan Disc or Kineflex|C cervical artificial disc compared with ACDF using structural allograft and an anterior plate. Patients were evaluated preoperatively; at 6 weeks; at 3, 6, and 12 months; and then yearly for a minimum of 48 months. Plain radiographs were obtained at each study visit. A total of 74 patients were enrolled and randomly assigned to either the cervical TDR (n = 41) or ACDF (n = 33) group. A total of 63 patients (86%) completed a minimum of 4 years follow-up. Average follow-up was 6 years (72 months) with a range from 48 to 108 months. In both the cervical TDR and ACDF groups, mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the minimum 48-month follow-up (p < 0.001). Similarly, the median VAS pain scores improved significantly by 6 weeks and remained significantly improved throughout the minimum 48-month follow-up (p < 0.001). There were no significant differences between groups in mean NDI or median VAS scores. The range of motion (ROM) in the cervical TDR group remained significantly greater than the preoperative mean, whereas the ROM in the ACDF group was significantly reduced from the preoperative mean. There was significantly greater ROM in the cervical TDR group compared with the ACDF group. There were 3 reoperations (7.3%) at index or adjacent levels in the cervical TDR group; all were cervical laminoforaminotomies. There were 2 adjacent-level reoperations in the cervical TDR group (4.9%). There was 1 reoperation (3.0%) in the ACDF group at an index or adjacent level (a second ACDF at the adjacent level). There was no statistically significant difference in overall reoperation rate or adjacent-level reoperation rate between groups. Both cervical TDR and ACDF groups showed excellent clinical outcomes that were maintained over long-term follow-up. Both groups showed low index-level and adjacent-level reoperation rates. Both cervical TDR and ACDF appear to be viable options for the treatment of single-level cervical radiculopathy.

Inflammatory Cytokine and Chemokine Expression is Associated With Heterotopic Ossification in High-Energy Penetrating War Injuries

Heterotopic ossification (HO) develops frequently after modern high-energy penetrating war injuries. The purpose of this prospective study was to identify and characterize the unique cytokine and chemokine profile associated with the development of HO as it pertained to the systemic inflammatory response after penetrating combat-related trauma. Patients with high-energy penetrating extremity wounds were prospectively enrolled. Surgical debridement along with the use of a pulse lavage and vacuum-assisted-closure device was performed every 48-72 hours until definitive wound closure. Wound bed tissue biopsy, wound effluent, and serum were collected before each debridement. Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue was analyzed quantitatively for bacterial colonization. Correlations between specific wound and patient characteristics were also analyzed. The primary clinical outcome measure was the formation of HO as confirmed by radiographs at a minimum of 2 months of follow-up. Thirty-six penetrating extremity war wounds in 24 patients were investigated. The observed rate of HO in the study population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum follow-up of 2 months. An elevated injury severity score was associated with the development of HO (P = 0.006). Wound characteristics that correlated with the development of HO included impaired healing (P = 0.005) and bacterial colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1) and wound effluent (IP-10 and MIP-1α) cytokine and chemokine bioprofiles were individually associated and suggestive of the development of HO (P < 0.05). A severe systemic and wound-specific inflammatory state as evident by elevated levels of inflammatory cytokines, elevated injury severity score, and bacterial wound colonization is associated with the development of HO. These findings suggest that the development of HO in traumatic combat-related wounds is associated with a hyper-inflammatory systemic response to injury. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Minimally invasive trans-sacral approach to L5-S1 interbody fusion: Preliminary results from 1 center and review of the literature

BackgroundLumbar interbody fusion has long been used for the treatment of painful degenerative spinal conditions. The anterior approach is not feasible in some patients, and the posterior approach is associated with a risk of neural complications and possibly muscle injury. A trans-sacral technique was developed that allows access to the L5-S1 disc space. The purposes of this study were to investigate the clinical outcome of trans-sacral interbody fusion in a consecutive series of patients from 1 center and to perform a comprehensive review of the literature on this procedure. MethodsA literature search using PubMed was performed to identify articles published on trans-sacral axial lumbar interbody fusion (AxiaLIF). Articles reviewed included biomechanical testing, feasibility of the technique, and clinical results. The data from our center were collected retrospectively from charts for the consecutive series, beginning with the first case, of all patients undergoing fusion using the AxiaLIF technique. In most cases, posterior instrumentation was also used. A total of 41 patients with at least 6 months' follow-up were included (mean follow-up, 22.2 months). The primary clinical outcome measures were visual analog scales separately assessing back and leg pain and the Oswestry Disability Index. Radiographic assessment of fusion was also performed. ResultsIn the group of 28 patients undergoing single-level AxiaLIF combined with posterior fusion, the visual analog scale scores assessing back and leg pain and mean Oswestry Disability Index scores improved significantly (P < .01). In the remaining 13 patients, back pain improved significantly with a trend for improvement in leg pain. Reoperation occurred in 19.5% of patients; in half of these, reoperation was not related to the anterior procedure. ConclusionsA review of the literature found that the AxiaLIF technique was similar to other fusion techniques with respect to biomechanical properties and produced acceptable clinical outcomes, although results varied among studies. Clinical relevanceThe AxiaLIF approach allows access to the L5-S1 interspace without violating the annulus or longitudinal ligaments and with minimal risk to dorsal neural elements. It may be a viable alternative to other approaches to interbody fusion at the L5-S1 level. It is important that the patients be selected carefully and surgeons are familiar with the presacral anatomy and the surgical approach.

Revisiting The Multiple Sclerosis Functional Composite: proceedings from the National Multiple Sclerosis Society (NMSS) Task Force on Clinical Disability Measures

This article describes proceedings from a meeting of the National Multiple Sclerosis Society (NMSS) Task Force on Clinical Disability Measures (the TF). The TF was appointed by the NMSS Research Programs Advisory Committee with the goal of pooling and analyzing existing datasets to explore the utility of novel disability outcome measures based on the Multiple Sclerosis Functional Composite (MSFC) approach. The TF seeks to determine the suitability of the MSFC approach as a primary clinical outcome measure for registration trials in MS. The TF met in Washington, DC, Dec. 14 and 15, 2011, and provided unanimous support for a collaborative approach involving representatives from academic medicine, the pharmaceutical industry, regulatory agencies, the NMSS and the Critical Path Institute. There was also unanimous agreement that analysis of existing datasets would be useful in making progress toward the objective. The TF placed high value on determining the clinical meaning of individual component measures for the MSFC, and in establishing optimal analysis methods for MSFC so that scores would be more interpretable than the originally recommended z-score method. The background for a collaborative project aimed at developing an improved disability outcome measure is described in this paper.

Abstract 3438: Intracranial Arterial Occlusion and Extent of Hypoattenuation on CT Angiography Source Images may Modify the Benefit of Thrombolysis

Background: CT angiography source images (CTASI) improve diagnostic accuracy for ischemic brain infarction compared to non-contrast CT (NCCT). We studied whether CTASI alone or combined with the CTA occlusion status may improve patient selection for thrombolysis in an extended time window. Methods: We prospectively observed patients presenting with anterior circulation ischemic stroke within 12 hours from symptom onset and an NIHSS score ≥ 3. All patients underwent cranial NCCT and CTA. Patients were treated with intravenous and/or intra-arterial thrombolysis at the discretion of the treating stroke neurologist and neuroloradiologist. We determined intracranial occlusion status and applied the Alberta Stroke Program Early CT Score (ASPECTS) to CTASI. Primary clinical outcome measure was independent outcome at 3 months, defined as mRS scores 0-2. We calculated unadjusted risk ratios to assess the effect of thrombolysis on functional outcome in patients with: 1) minor ischemic changes on CTASI (CTASI-ASPECTS &gt;5) and 2) patients with minor ischemic changes on CTASI and middle cerebral artery (MCA) occlusion. Results: We enrolled 102 patients with a mean age of 71 +/- 12 years, median onset-to-CTA time of 112,5 (range 37-898) min, a median NIHSS score of 9.5 (3-39), and a median CTASI-ASPECTS of 8. Sixty-two patients (61%) received any thrombolysis (56 IV, 5 IV/IA, 1 IA). MCA occlusion was present in 57 patients (56%), 80/101 (80%) assessable patients had a CTASI-ASPECTS &gt;5 and 37/101 (37%) patients had a CTASI-ASPECTS &gt;5 in the presence of a MCA occlusion. At 3 months, 52 (51%) patients had an independent functional outcome. When patients with CTA-SI ASPECTS &gt; 5 received thrombolysis, 30/46 (65%) achieved an independent functional outcome, whereas 20/35 (57%) without thrombolysis were functionally independent (RR 1.1, CI 95 0.8-1.6). In patients with CTASI-ASPECTS &gt; 5 and additional MCA-occlusion, 13/24 (54%) with thrombolysis and 3/13 (23%) without thrombolysis achieved an independent functional outcome (RR 2.3, CI 95 0.8-6.8). Conclusion: In our non-randomized study, the extent of CTASI hypoattenuation alone did not identify patients benefiting from thrombolysis. In the presence of an MCA-occlusion, however, CTASI might identify patients with benefit from thrombolysis in an extended time window.

Evaluating the transferability of a hospital-based childhood obesity clinic to primary care: a randomised controlled trial

The Care Of Childhood Obesity (COCO) clinic at the Bristol Royal Hospital for Children (BRHC) uses a multidisciplinary approach comprising a consultant, dietitian, and exercise specialist. The clinic has demonstrated efficacy in managing children's weight but similar clinics are scarce in the UK. This pilot randomised controlled trial (RCT) aimed to examine the feasibility of undertaking a fully powered RCT and to gauge whether the COCO model could be effective as a nurse-led clinic in primary care settings. Patients were randomised to a hospital-based childhood obesity clinic or a nurse-led clinic in a primary care setting in south-west England. Children aged 5-16 years with a body mass index (BMI) ≥98th centile were referred by GPs to the consultant in charge of the COCO clinic at BRHC. Referred children were clinically screened for suitability and invited into the study. Consenting families were randomised to BRHC or a primary care clinic (PCC) and offered five appointments over 12 months. Clinical effectiveness was measured by change in body mass index standard deviation score (BMI SDS) at 12 months. Other measures included: treatment adherence, quality of life (QOL), and satisfaction. Feasibility was examined by assessing referral, screening, and recruitment data. A total 152 patients were referred by GPs: 31 (20%) were screened out; 45 (30%) declined to participate. Seventy-six (50%) patients were randomised and 68 provided baseline data (PCC = 42; BRHC = 26); 52 provided outcome data (PCC = 29; BRHC = 23). Mean change in BMI SDS was PCC -0.17 (95% confidence interval [CI] = -0.27 to -0.07); BRHC -0.15 (95% CI = -0.26 to -0.05). QOL, adherence, and satisfaction data indicated similar positive patterns in both trial arms. Screening and recruitment data indicate that primary care is a clinically appropriate setting and acceptable to families. The primary clinical outcome measure (reduction in BMI SDS), along with secondary outcome measures, indicate that primary care has the potential to be effective in providing weight management for children, using the COCO model.

A Pilot Study of Mifepristone in Combat-Related PTSD

Background. We obtained pilot data to examine the clinical and neuroendocrine effects of short-term mifepristone treatment in male veterans with PTSD. Methods. Eight male veterans with military-related PTSD completed a randomized, double-blind trial of one week of treatment with mifepristone (600 mg/day) or placebo. The primary clinical outcome measures were improvement in PTSD symptoms and dichotomously defined clinical responder status as measured by the CAPS at one-month follow-up. Additional outcome measures included self-reported measures of PTSD symptom severity, CAPS-2 symptom subscale scores, and morning plasma cortisol and ACTH levels. Results. Mifepristone was associated with significant improvements in total CAPS-2 score. At one-month follow-up, all four veterans in the mifepristone group and one of four veterans in the placebo group achieved clinical response; three of four veterans in the mifepristone group and one of four veterans in the mifepristone group remitted. Mifepristone treatment was associated with acute increases in cortisol and ACTH levels and decreases in cytosolic glucocorticoid receptor number in lymphocytes. Conclusions. Further controlled trials of the effects of mifepristone and their durability are indicated in PTSD. If effective, a short-term pharmacological treatment in PTSD could have myriad uses.