Focusing on recovery goals improves motivation in first-episode psychosis.

INTRODUCTION: Diminished motivation (e.g., low drive, curiosity, and engagement in activities) is associated with robust impairment in psychosocial functioning in schizophrenia, yet even the most effective evidence-based interventions rarely effect meaningful change in motivation. Individual Resiliency Training (IRT) is a psychosocial treatment for individuals following a first episode of psychosis, supporting motivation through recovery goal setting and pursuit. The extent to which such an approach might improve motivation over time is unknown. METHOD: We tested the impact of exposure to IRT modules focused on goal setting and attainment on motivation and functional outcomes among participants in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP). In the sample of 404 individuals with a first episode of psychosis receiving treatment across 34 community sites, we ran mixed-effect models with group (exposed to four or more goal-focused IRT sessions vs. Community Care (CC)), time (baseline, six- and 12-month follow-up), and the group-by-time interaction as predictors of motivation, role and social functioning. We also ran these analyses with those exposed to three or fewer goal-focused IRT sessions compared to CC. RESULTS: Controlling for gender, ethnicity, baseline cognition, and total number of outpatient mental health visits, exposure to four or more goal-focused IRT sessions was associated with greater improvements in motivation and role functioning compared to CC; effects were not observed for social functioning. Participants receiving three or fewer goal-focused IRT sessions did not differ from those in CC in these outcomes. Further, sensitivity analysis showed that general exposure to IRT was not associated with differential outcomes. CONCLUSIONS: Findings suggest that sufficient focus on recovery goal setting and support in psychosocial intervention for first-episode psychosis may have specific impact on motivation.

Intraabdominal continuous negative pressure therapy for secondary peritonitis: an observational trial in a maximum care center.

Background: Acute secondary peritonitis is afflicted with a high morbidity and mortality. Intensive care therapy, antibiotics and surgical procedures are mandatory. Continuous negative pressure therapy (cNPT) seems to be beneficial but it is unclear which patients will benefit most from this procedures.Methods: We performed a prospective observational trial including all patients that needed to undergo an exploratory laparotomy for the suspicion of acute secondary peritonitis and were treated with cNPT in one year.Results: Thirty nine patients fitted the criteria. Median hospitalization length was 40 days. The vacuum therapy treatment was applied for a median of 4 days. The subgroup analysis between patients, who received the cNPT-dressing for one time (Group A) and patients, in whom the cNPT was continued after first relaparotomy (Group B) showed no differences concerning patients' characteristics. The Mannheimer Peritonitis Index (MPI) during the first operation was significantly correlated with the number of dressing changes (Spearman's rho 0.518, p = .002).Conclusions: Fast acting in acute secondary peritonitis for elimination of the source, abdominal lavage, derivation of the exsudat and interdisciplinary treatment is the treatment of choice. The MPI could be beneficial for the decision process of using cNPT.

Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study.

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

Opportunities for Integrating Physical Health Within Assertive Community Treatment Teams: Results from Practitioner Focus Groups.

This qualitative study assessed the experiences of assertive community treatment (ACT) team members regarding the integration of physical and mental health self-management for persons with serious mental illness. Three focus groups elicited information from participants concerning barriers, strategies, and recommendations. Findings from inductive analyses revealed six overarching themes: (1) collaboration with primary care, (2) improvements in engagement, (3) team-focused roles, (4) education and training, (5) recommendations for system level barriers, and (6) systems collaboration. Participant recommendations suggest that ACT teams are well positioned to integrate mental and physical health treatment, but further research is needed to support integrated care.

Hypoxia causes increased monocyte nitric oxide synthesis which is mediated by changes in dimethylarginine dimethylaminohydrolase 2 expression in animal and human models of normobaric hypoxia.

BACKGROUND: Tissue hypoxia is a cardinal feature of inflammatory diseases and modulates monocyte function. Nitric oxide is a crucial component of the immune cell response. This study explored the metabolism of the endogenous inhibitor of nitric oxide production asymmetric dimethylarginine(ADMA) by monocyte dimethylarginine dimethylaminohydrolase 2(DDAH2), and the role of this pathway in the regulation of the cellular response and the local environment during hypoxia. METHODS: Peritoneal macrophages were isolated from a macrophage-specific DDAH2 knockout mouse that we developed and compared with appropriate controls. Cells were exposed to 3% oxygen followed by reoxygenation at 21%. Healthy volunteers underwent an 8 h exposure to normobaric hypoxia with an inspired oxygen percentage of 12%. Peripheral blood mononuclear cells were isolated from blood samples taken before and at the end of this exposure. RESULTS: Intracellular nitrate plus nitrite(NOx) concentration was higher in wild-type murine monocytes after hypoxia and reoxygenation than in normoxia-treated cells (mean(SD) 13·2(2·4) vs 8·1(1·7) pmols/mg protein, p = 0·009). DDAH2 protein was 4·5-fold (SD 1·3) higher than in control cells (p = 0·03). This increase led to a 24% reduction in ADMA concentration, 0·33(0.04) pmols/mg to 0·24(0·03), p = 0·002). DDAH2-deficient murine monocytes demonstrated no increase in nitric oxide production after hypoxic challenge. These findings were recapitulated in a human observational study. Mean plasma NOx concentration was elevated after hypoxic exposure (3·6(1.8)µM vs 6·4(3·2), p = 0·01), which was associated with a reduction in intracellular ADMA in paired samples from 3·6(0.27) pmols/mg protein to 3·15(0·3) (p < 0·01). This finding was associated with a 1·9-fold(0·6) increase in DDAH2 expression over baseline(p = 0·03). DISCUSSION: This study shows that in both human and murine models of acute hypoxia, increased DDAH2 expression mediates a reduction in intracellular ADMA concentration which in turn leads to elevated nitric oxide concentrations both within the cell and in the local environment. Cells deficient in DDAH2 were unable to mount this response.

Impact of heart rate on admission on mortality and morbidity in acute ischaemic stroke patients - results from VISTA.

BACKGROUND AND PURPOSE: Elevated heart rate (HR) is associated with worse outcomes in patients with cardiovascular disease. Its predictive value in acute stroke patients is less well established. We investigated the effects of HR on admission in acute ischaemic stroke patients. METHODS: Using the Virtual International Stroke Trials Archive (VISTA) database, the association between HR in acute stroke patients without atrial fibrillation and the pre-defined composite end-point of (recurrent) ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) and vascular death within 90 days was analysed. Pre-defined secondary outcomes were the composite end-point components and any death, decompensated heart failure and degree of functional dependence according to the modified Rankin Scale after 90 days. HR was analysed as a categorical variable (quartiles). RESULTS: In all, 5606 patients were available for analysis (mean National Institutes of Health Stroke Scale 13; mean age 67 years; mean HR 77 bpm; 44% female) amongst whom the composite end-point occurred in 620 patients (11.1%). Higher HR was not associated with the composite end-point. The frequencies of secondary outcomes were 3.2% recurrent stroke (n = 179), 0.6% TIA (n = 35), 1.8% MI (n = 100), 6.8% vascular death (n = 384), 15.0% any death (n = 841) and 2.2% decompensated heart failure (n = 124). Patients in the highest quartile (HR> 86 bpm) were at increased risk for any death [adjusted hazard ratio (95% confidence interval) 1.40 (1.11-1.75)], decompensated heart failure [adjusted hazard ratio 2.20 (1.11-4.37)] and worse modified Rankin Scale [adjusted odds ratio 1.29 (1.14-1.52)]. CONCLUSIONS: In acute stroke patients, higher HR (>86 bpm) is linked to mortality, heart failure and higher degree of dependence after 90 days but not to recurrent stroke, TIA or MI.

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

An investigation of the relationship between therapist characteristics and alliance in group therapy for individuals with treatment-resistant auditory hallucinations.

BACKGROUND: Alliance is a well-studied construct; however, little research has investigated predictors of alliance in a group context. AIMS: This study investigates the relationship between therapist characteristics and group alliance in 65 individuals with schizophrenia receiving outpatient group therapy for treatment-resistant auditory hallucinations. METHODS: Raters coded 120 sessions of cognitive behavioral therapy or supportive therapy for therapist warmth and friendliness, therapist exploration and negative therapist attitude. Alliance was assessed at week six. RESULTS: Higher average levels of therapist warmth and friendliness and lower average levels of negative therapist attitude in sessions one to five were associated with stronger alliance at week six at the trend level (p < 0.10). Therapist exploration did not predict alliance at week six. Higher negative therapist attitude at treatment engagement was associated with higher post-treatment symptom scores. CONCLUSIONS: Our results suggest that therapist attributes but not therapist techniques are associated with client's perceptions of alliance and that negative therapist behaviors are associated with higher symptom levels at post-treatment. Implications for clinical practice are discussed.

Goal-directed fluid therapy using uncalibrated pulse contour analysis and balanced crystalloid solutions during hip revision arthroplasty: a quality implementation project.

BACKGROUND: To implement a goal-directed fluid therapy (GDFT) protocol using crystalloids in hip revision arthroplasty surgery within a quality management project at a tertiary hospital using a monocentric, prospective observational study. METHODS: Adult patients scheduled for elective hip revision arthroplasty surgery were screened for inclusion in this prospective study. Intraoperatively stroke volume (SV) was optimized within a previously published protocol using uncalibrated pulse contour analysis and balanced crystalloids. Quality of perioperative GDFT was assessed by protocol adherence, SV increase as well as the rate of perioperative complications. Findings were then compared to two different historical groups of a former trial: one receiving GDFT with colloids (prospective colloid group) and one standard fluid therapy (retrospective control group) throughout surgery. Statistical analysis constitutes exploratory data analyses and results are expressed as median with 25th and 75th percentiles, absolute and relative frequencies, and complication rates are further given with 95% confidence intervals for proportions using the normal approximation without continuity correction. RESULTS: Sixty-six patients underwent GDFT using balanced crystalloids and were compared to 130 patients with GDFT using balanced colloids and 130 controls without GDFT fluid resuscitation. There was a comparable increase in SV (crystalloids: 65 (54-74 ml; colloids: 67.5 (60-75.25 ml) and total volume infused (crystalloids: 2575 (2000-4210) ml; colloids: 2435 (1760-3480) ml; and controls: 2210 (1658-3000) ml). Overall perioperative complications rates were similar (42.4% (95%CI 30.3-55.2%) for crystalloids and 49.2% (95%CI 40.4-58.1%) for colloids and lower compared to controls: 66.9% (95%CI 58.1-74.9)). Interestingly, a reduced number of hemorrhagic complications was observed within crystalloids: 30% (95%CI 19.6-42.9); colloids: 43% (95%CI 34.4-52.0); and controls: 62% (95%CI 52.6-69.9). There were no differences in the rate of admission to the post-anesthesia care unit or intensive care unit as well as the length of stay. CONCLUSIONS: Perioperative fluid management using a GDFT protocol with crystalloids in hip revision arthroplasty surgery was successfully implemented in daily clinical routine. Perioperative complications rates were reduced compared to a previous management without GDFT and comparable when using colloids. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01753050.

Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (ISSHL) is the newest indication approved by the Undersea and Hyperbaric Medical Society's Hyperbaric Oxygen Therapy Committee. Idiopathic sudden sensorineural hearing loss appears to be characterized by hypoxia in the perilymph and therefore the scala tympani and the organ of Corti. A review of the literature reveals more than 100 publications evaluating the use of hyperbaric oxygen (HBO2) for the treatment of ISSHL, including eight randomized controlled trials. The best and most consistent results are obtained when HBO2 is initiated within two weeks of symptom onset and combined with corticosteroid treatment. The average hearing gain is 19.3 dB for moderate hearing loss and 37.7 dB for severe cases. This improvement brings hearing deficits from the moderate/severe range into the slight/no impairment range. This is a significant gain that can markedly improve a patient's quality of life, both clinically and functionally.

The use of diary methods to evaluate daily experiences in first-episode psychosis.

Integrated Coping Awareness Therapy (I-CAT) is an intervention that targets stress reactivity in first-episode psychosis (FEP). This study extends prior outcome research on I-CAT by examining predictors of online daily diary completion among 38 young adults with FEP and treatment group differences in diary ratings. We found no significant predictors of daily diary completion rate and no effect of treatment condition on diary ratings. These results are consistent with Halverson et al. (2021) and suggest that diaries are a valuable method of data collection in FEP.

Outcomes During and After Early Intervention Services for First-Episode Psychosis: Results Over 5 Years From the RAISE-ETP Site-Randomized Trial.

To examine long-term effects of early intervention services (EIS) for first-episode psychosis, we compared Heinrichs-Carpenter Quality of Life (QLS) and Positive and Negative Syndrome Scale (PANSS) scores and inpatient hospitalization days over 5 years with data from the site-randomized RAISE-ETP trial that compared the EIS NAVIGATE (17 sites; 223 participants) and community care (CC) (17 sites; 181 participants). Inclusion criteria were: age 15-40 years; DSM-IV diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified; first psychotic episode; antipsychotic medication taken for ≤6 months. NAVIGATE-randomized participants could receive NAVIGATE from their study entry date until NAVIGATE ended when the last-enrolled NAVIGATE participant completed 2 years of treatment. Assessments occurred every 6 months. 61% of participants had assessments conducted ≥2 years; 31% at 5 years. Median follow-up length was CC 30 months and NAVIGATE 38 months. Primary analyses assumed data were not-missing-at-random (NMAR); sensitivity analyses assumed data were missing-at-random (MAR). MAR analyses found no significant treatment-by-time interactions for QLS or PANSS. NMAR analyses revealed that NAVIGATE was associated with a 13.14 (95%CI:6.92,19.37) unit QLS and 7.73 (95%CI:2.98,12.47) unit PANSS better improvement and 2.53 (95%CI:0.59,4.47) fewer inpatient days than CC (all comparisons significant). QLS and PANSS effect sizes were 0.856 and 0.70. NAVIGATE opportunity length (mean 33.8 (SD = 5.1) months) was not associated (P = .72) with QLS outcome; duration of untreated psychosis did not moderate (P = .32) differential QLS outcome. While conclusions are limited by the low rate of five-year follow-up, the data support long-term benefit of NAVIGATE compared to community care.

Enhancing stress reactivity and wellbeing in early schizophrenia: A randomized controlled trial of Integrated Coping Awareness Therapy (I-CAT).

Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk for exposure to stressful life events which can lead to increased sensitivity to stress and a dysregulated stress response, which are in turn associated with poor long-term functioning. Stress reactivity is thus a promising treatment target in the early stages of SSD. Integrated-Coping Awareness Therapy (I-CAT) is a manualized intervention integrating mindfulness and positive psychology to target a dysregulated stress response in SSD. The current study is a preliminary randomized-controlled trial (RCT) comparing I-CAT (n = 18) with treatment as usual (TAU; n = 18) in individuals in the early stages of SSD. I-CAT was hypothesized to be more effective than TAU on primary outcomes: increasing positive emotions, decreasing negative emotions, reducing stress, and improving functioning and quality of life; and secondary outcomes: reducing symptoms, increasing mindfulness, and improving overall well-being. Excellent therapy attendance rates, low study attrition, and positive participant feedback demonstrated that I-CAT was a feasible and well-tolerated psychosocial intervention. Results suggest I-CAT led to greater reduction in symptoms (i.e., overall, negative, and disorganized symptoms), increased observational mindfulness, increased endorsement of a sense of purpose in life, and preservation of work abilities and school social functioning compared with TAU. Future work should replicate and extend these findings in a larger-scale RCT.

A randomized controlled trial of group cognitive-behavioral therapy vs. enhanced supportive therapy for auditory hallucinations.

There has been little research examining group cognitive-behavioral therapy (CBT) for schizophrenia, especially compared to an active control treatment. The purpose of this study was to investigate the effectiveness of group CBT for auditory hallucinations compared to an enhanced supportive therapy (ST). Sixty five participants with schizophrenia spectrum disorders and persistent hallucinations were randomly assigned to group CBT or enhanced group ST. Primary outcomes focused on beliefs about voices and global auditory hallucinations severity. Secondary outcomes included psychotic symptoms, self-esteem, social functioning, insight, depression, and hospitalization. Controlling for baseline levels, these outcomes were evaluated across post-treatment, 3 month and 12 month follow-ups. Participants who received enhanced ST were less likely to both resist voices and to rate them as less malevolent through 12-month follow-up relative to participants who received CBT. Group CBT was associated with lower general and total symptom scores on the PANSS through 12-month-followup relative to participants who received enhanced ST. Outcomes improved through 12-month follow-up in both therapy groups, with enhanced ST having more specific impact on auditory hallucinations, and CBT impacting general psychotic symptoms.

Loving-kindness meditation to enhance recovery from negative symptoms of schizophrenia.

In this article, we describe the clinical applicability of loving-kindness meditation (LKM) to individuals suffering from schizophrenia-spectrum disorders with persistent negative symptoms. LKM may have potential for reducing negative symptoms such as anhedonia, avolition, and asociality while enhancing factors consistent with psychological recovery such as hope and purpose in life. Case studies will illustrate how to conduct this group treatment with clients with negative symptoms, the potential benefits to the client, and difficulties that may arise. Although LKM requires further empirical support, it promises to be an important intervention since there are few treatments for clients afflicted with negative symptoms.

[Propofol administration systems. Handling, hemodynamics and propofol consumption]. / Propofolapplikationssysteme: Handhabung, Kreislaufverhalten und Propofolverbrauch.

BACKGROUND: During anaesthesia propofol is administered either by manual controlled infusion (MCI) or by target controlled infusion (TCI) techniques. In this study two different TCI systems for propofol administration were evaluated with regard to handling, patient safety, and costs and compared to administration of propofol by the MCI technique. METHODS: In a prospective study, 90 patients scheduled for elective surgery of the nose or nasal sinuses were randomly enrolled in three groups. The two TCI systems were examined in two groups of 30 patients: one group received propofol following the pharmacokinetic TCI model of Schnider (TCI-Schnider) and the other group received propofol following the TCI model of Marsh (TCI-Marsh). A manual perfusion technique (MCI, n=30) was used in the control group. Depth of anesthesia was controlled using the bispectral index (BSI) which was adjusted to fall within the range of 40-55. Hemodynamics, extubation times and time of awaking, rate and quality of propofol dose adjustment, total drug requirements, costs, and quality of recovery were documented. The incidence of postoperative nausea and vomiting (PONV) as well as shivering and patient satisfaction were also documented. RESULTS: Demographics, hemodynamics and perioperative data did not differ between the groups. Propofol consumption within the first 60 min also showed no significant differences. In the course of extended anaesthesia, propofol consumption was significantly less in both TCI groups compared to the control group (MCI) and the TCI-Schnider group also showed less episodes of bradycardia. The necessity of propofol dose adjustment did not differ significantly between the TCI groups. Administration and consumption of anaesthesia co-medication (fentanyl, remifentanil, cisatracurium) did not differ between the groups. CONCLUSION: The investigated propofol administration procedures using the MCI or TCI techniques were safe and easy to handle under BIS monitoring. No differences were found concerning extubation times and time of awaking. During extended anaesthesia procedures (>60 min), propofol consumption was lower with both TCI techniques and thus costs could be saved.

Off-hours use of a smartphone intervention to extend support for individuals with schizophrenia spectrum disorders recently discharged from a psychiatric hospital.

INTRODUCTION: Technology-delivered healthcare interventions may enhance dissemination of evidence-based treatments in low-resource areas. These interventions may be accessed 'on-demand,' including after hours. Patients with schizophrenia do engage with technological aids but when/how they would utilize these tools is not known. METHODS: We conducted a large, prospective, ten-site, longitudinal study of four technology-assisted interventions for patients with schizophrenia spectrum disorders within 60 days of psychiatric hospital discharge, a high risk period. One tool employed was a smartphone intervention called 'FOCUS,' which could be used by patients as needed, providing help in five content areas: medications, mood, social, sleep and voices. Each login was date- and time-stamped as occurring during normal clinic hours, or 'off-hours,' and the pattern of use described. RESULTS: 347 of 368 patients utilized FOCUS during the 6-month study. There were a total of 75,447 FOCUS logins; 35,739 (47.4%) were self-initiated and 38,139 (50.6%) were off-hours. 18,450 of the logins during off-hours were self-initiated (24.5%). No differences in average usage per month were found based on race/ethnicity. A subset of 'high utilizers' (n = 152, 43.8%) self-initiated use of all five FOCUS modules both on- and off-hours. They tended to be women, >35 years old, and had a high school diploma or greater. CONCLUSION: Most patients with schizophrenia spectrum disorders recently discharged from the hospital utilized a smartphone intervention targeted to address troublesome residual symptoms. One quarter of the total smartphone utilization was self-initiated off-hours, indicating the potential utility of this tool to extend support for patients during periods of elevated risk.

Implementation and fidelity assessment of the NAVIGATE treatment program for first episode psychosis in a multi-site study.

The NAVIGATE program was developed for the Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study, which compared NAVIGATE to usual Community Care in a cluster randomized design involving 34 sites and 404 patients. This article describes the approach to training and implementing the NAVIGATE program at the 17 sites (including 134 practitioners) randomized to provide it, and to evaluating the fidelity of service delivery to the NAVIGATE model. Fidelity was evaluated to five different components of the program, all of which were standardized in manuals in advance of implementation. The components included four interventions (Individualized Resiliency Training, Family Education Program, Supported Employment and Education, Personalized Medication Management) and the overall organization (staffing and structure) of the NAVIGATE team. Most of the sites demonstrated acceptable or higher levels of fidelity in their implementation of the four interventions and the organization of the program, with all 17 sites demonstrating at least acceptable overall fidelity to the NAVIGATE program. The results indicate that the NAVIGATE program can be implemented with good fidelity to the treatment model in a diverse array of community mental health care settings serving persons with a first episode psychosis.

Angina pectoris is a stronger indicator of diffuse vascular atherosclerosis than intermittent claudication: Framingham study.

OBJECTIVE: To compare implications of Angina Pectoris (AP) and Intermittent Claudication (IC) as indicators of clinical atherosclerosis in other vascular territories. STUDY DESIGN AND SETTING: Prospective cohort study of cardiovascular disease (CVD) in 5,209 men and women of Framingham, MA, aged 28-62 years at enrollment in 1948-1951, who received biennial examinations during the first 36 years of follow-up. Comparative 10-year incidence of subsequent atherosclerotic CVD in participants with IC and AP relative to a reference sample free of CVD was determined. RESULTS: On follow-up, 95 CVD events occurred in 186 participants with IC and 206 of 413 with AP. After age, sex, and risk-factor adjustment, the proportion acquiring other CVD was 34.0% for IC and 43.4% for AP. Relative to the reference sample, those with IC had a 2.73-fold higher age and sex-adjusted 10-year hazard of CVD (95% CI 2.21, 3.38) and for AP was 3.17 (95% CI 2.73, 3.69). CVD hazard ratios remained more elevated for AP and statistically significant after standard risk factor adjustment. Risk factors accounted for more of the excess CVD risk associated with IC (34.8%) than AP (9.5%). CONCLUSION: AP is as useful as IC as a hallmark of diffuse atherosclerotic CVD and an indication for comprehensive preventive measures.

Magnetic resonance imaging of iron oxide labelled stem cells: applications to tissue engineering based regeneration of the intervertebral disc.

Minimally-invasive monitoring of regeneration in diseased tissue is an important aspect of stem cell therapy. Magnetic resonance imaging (MRI) based tracking of cells labelled with ferumoxides has the potential for non-invasive in vivo detection and longitudinal assessment of implanted cells. Cells labelled with ferumoxides appear as hypointense regions on MR images and thus can be distinguished from the surroundings. Application of this methodology to intervertebral disc degeneration (IVD), and detection of labelled cells implanted into the disc for tissue regeneration was examined. Mesenchymal stem cells labelled with a ferumoxide contrast agent were imaged in vitro to quantitatively characterize the signal intensity loss using MRI relaxation parameters (T1, T2, and T2*). To determine whether labelled cells could be detected within scaffolds suitable for implantation, labelled cells were seeded within both natural and synthetic polymers and imaged using MRI. Labelled cells were loaded within poly(ethylene glycol) hydrogels and imaged in vitro using both MRI and confocal microscopy. Labelled cells were also loaded into fibrin gels, and detected ex vivo within rat IVDs using MRI. Lastly, the effect of ferumoxide labelling on cell viability was investigated. Quantitatively, labelled cells demonstrate the greatest signal intensity loss and contrast on T2*-weighted images. Labelled cells can be detected in both synthetic and natural polymers, and can be distinguished from the native tissue environment of the rat IVD. Finally, labelling does not significantly impair cell viability. Consequently, this technique shows promise as a potential method for in vivo longitudinal tracking of stem cell based regeneration of the IVD.