Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

PURPOSE: The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). METHODS: Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. RESULTS: In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. CONCLUSION: These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Protease: Serpin complexes to assess contact system and intrinsic pathway activation.

Mounting evidence suggests that a variety of disease states are pathophysiologically related to activation of the contact system in vivo. The plasma contact system is composed of a cascade of serine proteases initiated by surface activation of factor XII, which can then proceed through a procoagulant pathway by activating the intrinsic coagulation factor XI, or a proinflammatory pathway by activating prekallikrein. Serpins are the primary endogenous inhibitors of the contact system, which irreversibly inhibit their respective protease(s), forming a stable complex. We modified an existing assay strategy for detecting these complexes in plasma using ELISAs and determined the effect of preanalytical variation caused by anticoagulant selection and processing time. The assays were sensitive and specific to inherited deficiency of individual contact factors. We conclude that these assays are robust and represent a relatively simple approach to the assessment of contact factor activation in plasma samples.

Identifying and responding to trial implementation challenges during multisite clinical trials.

INTRODUCTION: The National Drug Abuse Treatment Clinical Trials Network (CTN) was initiated by the National Institute on Drug Abuse (NIDA) in 2000 with the aim of improving substance use treatment and reducing the time between the discovery of effective treatments and their implementation into clinical practice. While initial trials were conducted almost exclusively in specialty addiction treatment settings, the CTN began evolving strategically in 2010 to conduct research in general medical settings, including healthcare systems, primary care settings, emergency departments, and pharmacies, to broaden impact. The advantages of a research network like the CTN is not only the collective content expertise that investigators contribute to the network, but the collective experience gained by conducting studies in the network and then applying those lessons to future studies. OBJECTIVE: To summarize trial implementation challenges encountered, and the process by which solutions were identified and implemented, within one of the last early-phase CTN Stage II behavioral intervention studies conducted in a specialty addiction treatment setting. METHOD AND RESULTS: We describe the implementation of the CTN-0037 STimulant Reduction Intervention using Dosed Exercise (STRIDE) trial. Issues encountered during study implementation are categorized into four major areas, described in terms useful to future study teams: 1) study team infrastructure challenges, 2) participant- and site- level challenges, 3) intervention-related challenges, and 4) longitudinal study design challenges. Potential consequences of identified problems and the solutions developed to manage these problems are discussed within the context of these four areas. We propose how to extend these implementation lessons and apply them in other healthcare settings to expand the CTN. CONCLUSIONS: Effective study management allows for flexible, collaborative solutions to expected and unexpected obstacles to study success. Implementation strategies derived from the first 15 to 20 years of CTN studies are a result of working with providers and participants, and the ongoing collaboration among CTN investigators and network staff. Timely identification and response to problems during study implementation are critical to the success of a trial, regardless of its design. We believe a collaborative approach to identifying and responding to study implementation challenges will increase the likelihood of successful adoption of relevant, efficacious interventions. As the CTN continues to expand, the wealth of successful trial implementation strategies developed during the first 20 years of the CTN need to be applied and adapted to studies in broader network settings, and considered in conjunction with more formalized implementation science processes that are currently available.

Age differences in outcomes among patients in the "Stimulant Abuser Groups to Engage in 12-Step" (STAGE-12) intervention.

Emerging adults (roughly 18-29years) with substance use disorders can benefit from participation in twelve-step mutual-help organizations (TSMHO), however their attendance and participation in such groups is relatively low. Twelve-step facilitation therapies, such as the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12), may increase attendance and involvement, and lead to decreased substance use. AIMS: Analyses examined whether age moderated the STAGE-12 effects on substance use and TSMHO meeting attendance and participation. DESIGN: We utilized data from a multisite randomized controlled trial, with assessments at baseline, mid-treatment (week 4), end-of-treatment (week 8), and 3- and 6- months post-randomization. PARTICIPANTS: Participants were adults with DSM-IV diagnosed stimulant abuse or dependence (N=450) enrolling in 10 intensive outpatient substance use treatment programs across the U.S. ANALYSIS: A zero-inflated negative binomial random-effects regression model was utilized to examine age-by-treatment interactions on substance use and meeting attendance and involvement. FINDINGS: Younger age was associated with larger treatment effects for stimulant use. Specifically, younger age was associated with greater odds of remaining abstinent from stimulants in STAGE-12 versus Treatment-as-Usual; however, among those who were not abstinent during treatment, younger age was related to greater rates of stimulant use at follow-up for those in STAGE-12 compared to TAU. There was no main effect of age on stimulant use. Younger age was also related to somewhat greater active involvement in different types of TSMHO activities among those in STAGE-12 versus TAU. There were no age-by-treatment interactions for other types of substance use or for treatment attendance, however, in contrast to stimulant use; younger age was associated with lower odds of abstinence from non-stimulant drugs at follow-up, regardless of treatment condition. These results suggest that STAGE-12 can be beneficial for some emerging adults with stimulant use disorder, and ongoing assessment of continued use is of particular importance.

Predictors of Functional and Quality of Life Outcomes following Deep Brain Stimulation Surgery in Parkinson's Disease Patients: Disease, Patient, and Surgical Factors.

OBJECTIVE: The primary objective was to evaluate predictors of quality of life (QOL) and functional outcomes following deep brain stimulation (DBS) in Parkinson's disease (PD) patients. The secondary objective was to identify predictors of global improvement. METHODS: PD patients who underwent DBS at our Center from 2006 to 2011 were evaluated by chart review and email/phone survey. Postoperative UPDRS II and EQ-5D were analyzed using simple linear regression adjusting for preoperative score. For global outcomes, we utilized the Patient Global Impression of Change Scale (PGIS) and the Clinician Global Impression of Change Scale (CGIS). RESULTS: There were 130 patients in the dataset. Preoperative and postoperative UPDRS II and EQ-5D were available for 45 patients, PGIS for 67 patients, and CGIS for 116 patients. Patients with falls/postural instability had 6-month functional scores and 1-year QOL scores that were significantly worse than patients without falls/postural instability. For every 1-point increase in preoperative UPDRS III and for every 1-unit increase in body mass index (BMI), the 6-month functional scores significantly worsened. Patients with tremors, without dyskinesia, and without gait-freezing were more likely to have "much" or "very much" improved CGIS. CONCLUSIONS: Presence of postural instability, high BMI, and worse baseline motor scores were the greatest predictors of poorer functional and QOL outcomes after DBS.

Changing the practice learning landscape.

Engagement in real life practice has long been acknowledged as the most effective way to learn a trade or profession and practice learning is consistently highlighted by nursing and midwifery placement students for its impact on both their professional and personal development. The paper examines the current complexities of practice learning that have emerged from educational reform and policy and debates the increased interest in the development of alternative approaches to practice learning in the UK.

Randomized Controlled Trial Comparing Exercise to Health Education for Stimulant Use Disorder: Results From the CTN-0037 STimulant Reduction Intervention Using Dosed Exercise (STRIDE) Study.

OBJECTIVE: To evaluate exercise as a treatment for stimulant use disorders. METHODS: The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. RESULTS: Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education participants. Percent of abstinent days using the eliminate contradiction (ELCON) algorithm was 75.6% (SD = 27.4%) for Exercise and 77.3% (SD = 25.1%) for Health Education. The primary intent-to-treat analysis, using a mixed model controlling for site and the ELCON algorithm, produced no treatment effect (P = .60). In post hoc analyses controlling for treatment adherence and baseline stimulant use, Exercise participants had a 4.8% higher abstinence rate (78.7%) compared to Health Education participants (73.9%) (P = .03, number needed to treat = 7.2). CONCLUSIONS: The primary analysis indicated no significant difference between exercise and health education. Adjustment for intervention adherence showed modestly but significantly higher percent of abstinent days in the exercise group, suggesting that exercise may improve outcomes for stimulant users who have better adherence to an exercise dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141608.

Adverse Maternal and Neonatal Outcomes in Adolescent Pregnancy.

STUDY OBJECTIVE: To investigate the outcomes of adolescent pregnancy. DESIGN: Retrospective cohort study from the Consortium on Safe Labor between 2002 and 2008. SETTING: Twelve clinical centers with 19 hospitals in the United States. PARTICIPANTS: Nulliparous women (n = 43,537) younger than 25 years of age, including 1189 younger adolescents (age ≤ 15.9 years), 14,703 older adolescents (age 16-19.9 years), and 27,645 young adults (age 20-24.9 years). INTERVENTIONS: Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated, controlling for maternal characteristics and pregnancy complications (young adults as a reference group). MAIN OUTCOME MEASURES: Maternal, neonatal outcomes, cesarean indications, and length of labor. RESULTS: Younger adolescents had an increased risk of maternal anemia (aOR = 1.25; 95% CI, 1.07-1.45), preterm delivery at less than 37 weeks of gestation (aOR = 1.36; 95% CI, 1.14-1.62), postpartum hemorrhage (aOR = 1.46; 95% CI, 1.10-1.95), preeclampsia or hemolysis, increased liver enzyme levels, and low platelet syndrome (aOR = 1.44; 95% CI, 1.17-1.77) but had a decreased risk of cesarean delivery (aOR = 0.49; 95% CI, 0.42-0.59), chorioamnionitis (aOR = 0.63; 95% CI, 0.47-0.84), and neonatal intensive care unit admission (aOR = 0.80; 95% CI, 0.65-0.98). Older adolescents had an increased risk of maternal anemia (aOR = 1.15; 95% CI, 1.09-1.22), preterm delivery at less than 37 weeks of gestation (aOR = 1.16; 95% CI, 1.08-1.25), and blood transfusion (aOR = 1.21; 95% CI, 1.02-1.43), but had a decreased risk of cesarean delivery (aOR = 0.75; 95% CI, 0.71-0.79), chorioamnionitis (aOR = 0.83; 95% CI, 0.75-0.91), major perineal laceration (aOR = 0.82; 95% CI, 0.71-0.95), and neonatal intensive care unit admission (aOR = 0.89; 95% CI, 0.83-0.96). Older adolescents were less likely to have a cesarean delivery for failure to progress or cephalopelvic disproportion (aOR = 0.89; 95% CI, 0.81-0.98). For adolescents who entered spontaneous labor, the second stage of labor was shorter (P < .01). CONCLUSION: Adolescents were less likely to have a cesarean delivery. Failure to progress or cephalopelvic disproportion occurred less frequently in older adolescents. Adolescents who entered spontaneous labor had a shorter second stage of labor.

Do They Stand a Chance? Vaginal Birth after Cesarean Section in Adolescents Compared to Adult Women.

STUDY OBJECTIVE: To determine the rate of elective repeat cesarean delivery (CD), vaginal birth after cesarean (VBAC) attempt, and VBAC success in adolescent mothers presenting for delivery of a second child after a prior CD compared to their adult counterparts. DESIGN: Retrospective cohort study analyzing data from the Consortium on Safe Labor Database which includes data for 228,668 deliveries from 2002 to 2008. SETTING: 19 hospitals within 12 institutions in the United States. PARTICIPANTS: 10,791 women age ≤ 35 (428 adolescents, age ≤ 19 and 10,363 adults age 20-35) with history of prior CD presenting for delivery of a second child. METHODS: The database was accessed for information on patient characteristics, prenatal comorbidities, and delivery data. Rates of repeat CD, VBAC attempt, and VBAC success were calculated. Multiple logistic regression was applied to identify predictors of VBAC success. RESULTS: Adolescents had a lower overall repeat CD rate and higher VBAC attempt rate compared to adults (80.61% vs 85.32%, P = .0072; 40.42% vs 30.09%, P < .0001 respectively). VBAC success was similar between adolescents and adults (47.98% vs 48.78% P = .8368). Delivery at a teaching hospital and greater gestational age were predictive of VBAC success. Gestational diabetes mellitus, induction of labor, and higher maternal body mass index were predictive of VBAC failure. Adolescence was not an independent predictor of VBAC outcome. CONCLUSIONS: Adolescents are more likely to attempt VBAC and are likely to be as successful as their adult counterparts. Adolescents should be encouraged to attempt a trial of labor after prior CD when appropriate to lower the risks of lifelong maternal morbidity from numerous repeat CDs.

Gender-based Outcomes and Acceptability of a Computer-assisted Psychosocial Intervention for Substance Use Disorders.

BACKGROUND: Digital technologies show promise for increasing treatment accessibility and improving quality of care, but little is known about gender differences. This secondary analysis uses data from a multi-site effectiveness trial of a computer-assisted behavioral intervention, conducted within NIDA's National Drug Abuse Clinical Trials Network, to explore gender differences in intervention acceptability and treatment outcomes. METHODS: Men (n=314) and women (n=192) were randomly assigned to 12-weeks of treatment-as-usual (TAU) or modified TAU+Therapeutic Education System (TES), whereby TES substituted for 2hours of TAU per week. TES is composed of 62 Web-delivered, multimedia modules, covering skills for achieving and maintaining abstinence plus prize-based incentives contingent on abstinence and treatment adherence. Outcomes were: (1) abstinence from drugs and heavy drinking in the last 4weeks of treatment, (2) retention, (3) social functioning, and (4) drug and alcohol craving. Acceptability was the mean score across five indicators (i.e., interesting, useful, novel, easy to understand, and satisfaction). RESULTS: Gender did not moderate the effect of treatment on any outcome. Women reported higher acceptability scores at week 4 (p=.02), but no gender differences were detected at weeks 8 or 12. Acceptability was positively associated with abstinence, but only among women (p=.01). CONCLUSIONS: Findings suggest that men and women derive similar benefits from participating in a computer-assisted intervention, a promising outcome as technology-based treatments expand. Acceptability was associated with abstinence outcomes among women. Future research should explore characteristics of women who report less satisfaction with this modality of treatment and ways to improve overall acceptability.

Clinical and programming pattern of patients with impending deep brain stimulation power failure: a retrospective chart review.

BACKGROUND: It is important to prevent complications of implanted pulse generators (IPG) depletion by replacing the IPG in time. METHODS: We reviewed the charts of all patients with deep brain stimulation treated movement disorders who were seen at our institution over a period of 6 months. Among these, we retained for analyses those who had undergone IPG replacement within the previous 3 years. RESULTS: A total of 55 IPG replacements (from 38 patients) were reviewed. Electrodes were implanted in the subthalamic nucleus in all Parkinson's disease patients, in the ventral intermedius nucleus of the thalamus in all essential tremor patients and in the globus pallidus interna in all dystonia patients. Replacements were preceded by a voltage increase due to worsened symptoms in 27.3% (15/55); 25.5% (14/55) had full IPG depletion or had too low IPG reserve to allow for any voltage adjustment; and 21.7% (12/55) did not get a needed voltage increase either for safety reasons (eg: concern for increase in falls with higher voltages) or because the surgery date for IPG replacement was close. Only 25.5% (14/55) remained clinically well-controlled prior to IPG replacement, all of whom had IPG longevity estimates available. Clinical deterioration was noted prior to IPG replacement in 100% of patients without available longevity estimates versus 61% of patients with available longevity estimates (p < 0.001). CONCLUSION: Despite best efforts, clinical deterioration prior to IPG replacement can be seen frequently. Routine estimation of IPG life, along with symptom assessment at every follow-up visit may prevent it.

Educating nurses for the twenty-first century abilities-based outcomes and assessing student learning in the context of democratic professionalism.

This article describes recent work in implementing a framework of abilities-based learning outcomes and related practices for assessing student learning in a Canadian Baccalaureate nursing degree program. The authors describe steps in implementing an abilities-based paradigm for nursing education, and subsequently developing an assessment framework based on abilities-based learning outcomes. The discussion reviews theoretical and policy-level influences involved in this initiative. The curriculum work is also discussed in terms of current trends in higher education emphasizing the assessment of student learning. The discussion concludes by linking these efforts to recent calls for a paradigm shift in the preparation of professionals, noting how the assessment of student learning can contribute to democratic professional formation in nursing.

Clinical and sociodemographic characteristics associated with suicidal ideation in depressed outpatients.

OBJECTIVE: To identify clinical and sociodemographic characteristics associated with suicidal ideation (SI) among patients seeking care for depression in routine primary and psychiatric care settings. METHODS: We examined data from 4041 treatment-seeking outpatients with major depressive disorder (MDD) to compare baseline sociodemographic and clinical characteristics of those with and without SI, and the presence or absence of baseline depressive symptoms and psychiatric comorbidities in those with SI. RESULTS: SI was significantly (P < 0.01) associated with numerous sociodemographic characteristics (that is, lower level of education, Caucasian or African American, male, unemployed, and treated in psychiatric care) and clinical features (that is, previous suicide attempt, younger age of MDD onset, greater baseline depressive symptom severity, greater number of depressive symptoms, and presence of agoraphobia and [or] generalized anxiety disorder). Elevated levels of SI at baseline were associated with decreased remission rates. CONCLUSIONS: Consistent with past findings, increased rates of SI were associated with greater depressive symptom severity as well as other features suggestive of severity of illness. Our results confirm previous findings of associations between SI and panic and (or) phobic symptoms and anxiety, but did not confirm previous findings of an association between SI and alcohol or drug use and (or) dependence. While selective serotonin reuptake inhibitor monotherapy appeared significantly helpful in reducing SI during the course of treatment, the presence of SI at baseline was found to be a associated with decreased treatment response, with patients reporting SI at the start of treatment being less likely to achieve remission. CLINICAL TRIAL REGISTRATION NUMBER: Sequenced Treatment Alternatives to Relieve Depression, NCT00021528.

Falls related to accidental deactivation of deep brain stimulators in patients with Parkinson's disease living in long term care facilities.

This case series highlights three patients with Parkinson's disease residing at nursing home facilities whose deep brain stimulators were accidentally deactivated for varying lengths of time, which was associated with an increase in falls. In all three cases, neither the patients nor the caregivers were aware of the random deactivations/reactivations. We propose a specific care plan for these patients that includes further education of caregivers regarding deep brain stimulators and regular checks of the review device, especially when there is concern about a patient's mobility or balance that is out of character.

Name that neurotransmitter: using music to teach psychopharmacology concepts.

The purpose of this article is to discuss the use of music (i.e., two original songs, "Neurotransmitter Twitter" and "Parkinson's Shuffle") to teach aspects of psychopharmacology to students in the course Psychiatric/Mental Health Nursing. Songs were incorporated in both the clinical and classroom settings. This innovative teaching method allowed students the opportunity to revisit the information through multiple exposures of the content for reinforcement and enhancement of student learning in a fun, creative approach. Brain-based research will be discussed, along with the process of development.

Amantadine induced reversible corneal edema.

Amantadine is becoming more commonly used for Parkinson's disease (PD), particularly for its efficacy in treating the drug-induced dyskinesias. Corneal edema is a known but unusual side effect of amantadine therapy, rarely reported in the neurological literature. We report amantadine-induced reversible corneal edema in a patient with advanced PD.

Effect of the dose volume of perfluorocarbon when starting partial liquid ventilation.

OBJECTIVE: Very preterm neonates are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit any lung disease but giving 30 mL/kg of perfluorocarbon when starting PLV increases cortical cerebral blood flow velocity. We aimed to determine if varying the initial dose of perfluorocarbon alters the effect on cerebral blood flow velocity when starting PLV. METHODS: In this randomised, controlled trial with historical comparison 24 preterm lambs received one of three loading doses of intratracheal perfluorocarbon liquid over 20 min when starting PLV: 20, 30 or 40 mL/kg. Data on respiratory mechanics, haemodynamics and cerebral blood flow velocity, measured with laser Doppler, were collected continuously for 30 min from the start of dosing. RESULTS: Cortical cerebral blood flow velocity increased over time in all three groups (two-way ANOVA, P= 0.007). There was no difference between groups (two-way ANOVA, P= 0.26). There was no difference between groups in cortical cerebral blood flow velocity variability (P= 0.68), blood pressure (P= 0.96) or heart rate (P= 0.46). The was no statistically significant difference in PaCO(2) between groups measured at baseline and at 30 min after starting PLV (P= 0.51). CONCLUSIONS: Cortical cerebral blood flow velocity and its variability are not affected by varying doses of tracheal perfluorocarbon (20, 30 or 40 mL/kg) at the start of PLV in preterm lambs.

A modified cementing technique using BoneSource to augment fixation of the acetabulum in a sheep model.

BACKGROUND AND PURPOSE: Our aim was to assess in an animal model whether the use of HA paste at the cement-bone interface in the acetabulum improves fixation. We examined, in sheep, the effect of interposing a layer of hydroxyapatite cement around the periphery of a polyethylene socket prior to fixing it using polymethylmethacrylate (PMMA). METHODS: We performed a randomized study involving 22 sheep that had BoneSource hydroxyapatite material applied to the surface of the acetabulum before cementing a polyethylene cup at arthroplasty. We studied the gross radiographic appearance of the implant-bone interface and the histological appearance at the interface. RESULTS: There were more radiolucencies evident in the control group. Histologically, only sheep randomized into the BoneSource group exhibited a fully osseointegrated interface. Use of the hydroxyapatite material did not give any detrimental effects. In some cases, the material appeared to have been fully resorbed. When the material was evident in histological sections, it was incorporated into an osseointegrated interface. There was no giant cell reaction present. There was no evidence of migration of BoneSource to the articulation. INTERPRETATION: The application of HA material prior to cementation of a socket produced an improved interface. The technique may be useful in humans, to extend the longevity of the cemented implant by protecting the socket interface from the effect of hydrodynamic fluid flow and particulate debris.