Outpatient Trial Research Articles

Targeted cognitive training improves auditory and verbal outcomes among treatment refractory schizophrenia patients mandated to residential care

Computerized targeted cognitive training (TCT) of auditory processing has been shown to improve verbal learning in several clinical trials of schizophrenia outpatients. Less is known, however, about the effectiveness of this promising intervention in more chronic, treatment-refractory patients who are treated in non-academic settings. This study aimed to determine whether TCT improves auditory processing, verbal learning, and clinical symptoms in SZ patients mandated to receive care at a locked residential rehabilitation center. Secondarily, potential factors that moderate TCT's effectiveness including age, symptom severity, antipsychotic medication load, and duration of illness were examined. Schizophrenia patients were randomized to treatment as usual (TAU; n = 22) or TAU augmented with TCT (TAU + TCT; n = 24). Outcomes included a measure of auditory perception (Word-In-Noise test, WIN), verbal learning domain scores from the MATRICS Consensus Cognitive Battery (MCCB), and clinical symptoms (Scale for the Assessment of Positive Symptoms, SAPS; Scale for the Assessment of Negative Symptoms, SANS). TCT produced significant improvements in auditory perception (d = 0.67) and verbal learning (d = 0.65); exploratory analyses revealed a statistically significant reduction in auditory hallucinations (d = −0.64). TCT's effects were only weakly, and mostly non-significantly, moderated by age, clinical symptoms, medication, and illness duration. These findings indicate that even highly symptomatic, functionally disabled patients with chronic illness benefit from this emerging treatment. Ongoing studies will examine the predictive utility of neurophysiological biomarkers and other characteristics assessed at baseline.

Randomized Outpatient Trial of Single- and Dual-Hormone Closed-Loop Systems That Adapt to Exercise Using Wearable Sensors.

OBJECTIVEAutomated insulin delivery is the new standard for type 1 diabetes, but exercise-related hypoglycemia remains a challenge. Our aim was to determine whether a dual-hormone closed-loop system using wearable sensors to detect exercise and adjust dosing to reduce exercise-related hypoglycemia would outperform other forms of closed-loop and open-loop therapy.RESEARCH DESIGN AND METHODSParticipants underwent four arms in randomized order: dual-hormone, single-hormone, predictive low glucose suspend, and continuation of current care over 4 outpatient days. Each arm included three moderate-intensity aerobic exercise sessions. The two primary outcomes were percentage of time in hypoglycemia (<70 mg/dL) and in a target range (70–180 mg/dL) assessed across the entire study and from the start of the in-clinic exercise until the next meal.RESULTSThe analysis included 20 adults with type 1 diabetes who completed all arms. The mean time (SD) in hypoglycemia was the lowest with dual-hormone during the exercise period: 3.4% (4.5) vs. 8.3% (12.6) single-hormone (P = 0.009) vs. 7.6% (8.0) predictive low glucose suspend (P < 0.001) vs. 4.3% (6.8) current care where pre-exercise insulin adjustments were allowed (P = 0.49). Time in hypoglycemia was also the lowest with dual-hormone during the entire 4-day study: 1.3% (1.0) vs. 2.8% (1.7) single-hormone (P < 0.001) vs. 2.0% (1.5) predictive low glucose suspend (P = 0.04) vs. 3.1% (3.2) current care (P = 0.007). Time in range during the entire study was the highest with single-hormone: 74.3% (8.0) vs. 72.0% (10.8) dual-hormone (P = 0.44).CONCLUSIONSThe addition of glucagon delivery to a closed-loop system with automated exercise detection reduces hypoglycemia in physically active adults with type 1 diabetes.

Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis

ObjectiveTo evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, Cochrane Library, and grey...

Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial

BackgroundInjectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX. MethodsPatients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX. ResultsRates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores. ConclusionsA 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.

The effects of psychoeducational family intervention on coping strategies of relatives of patients with bipolar I disorder: results from a controlled, real-world, multicentric study.

BackgroundPsychoeducational family intervention (PFI) has been proven to be effective in improving the levels of family burden and patients’ personal functioning in schizophrenia and bipolar disorders (BDs). Less is known about the impact of PFI on relatives’ coping strategies in BD.MethodsA multicenter, controlled, outpatient trial funded by the Italian Ministry of Health and coordinated by the Department of Psychiatry of the University of Campania “Luigi Vanvitelli” has been conducted in patients with bipolar I disorder (BD-I) and their key relatives consecutively recruited in 11 randomly selected Italian community mental health centers. We aim to test the hypothesis that PFI improves problem-oriented coping strategies in relatives of BD-I patients compared to the Treatment As Usual (TAU) group.ResultsThe final sample was constituted of 123 patients and 139 relatives. At baseline assessment (T0), the vast majority of relatives already adopted problem-oriented coping strategies more frequently than the emotion-focused ones. At the end of the intervention, relatives receiving PFI reported a higher endorsement of adaptive coping strategies, such as “maintenance of social interests” (odds ratio [OR]=0.309, CI=0.04–0.57; p=0.023), “positive communication with the patient” (OR=0.295, CI=0.13–0.46; p=0.001), and “searching for information” (OR=0.443, CI=0.12–0.76; p=0.007), compared to TAU relatives, after controlling for several confounders. As regards the emotion-focused coping strategies, relatives receiving the experimental intervention less frequently reported to adopt “resignation” (OR=−0.380, CI=−0.68 to −0.08; p=0.014) and “coercion” (OR=−0.268, CI=−0.46 to −0.08; p=0.006) strategies, compared to TAU relatives.ConclusionPFI is effective in improving the adaptive coping strategies of relatives of BD-I patients, but further studies are needed for evaluating the long-term benefits of this intervention.

Edema caused by continuous epidural hydromorphone infusion: A case report and review of the literature

Intraspinal drug delivery (IDD) therapy has been increasingly employed in patients with intractable, nonmalignant pain. Before implantation of permanent intraspinal pump, an intraspinal opioid screening trial is conducted to demonstrate the efficacy. The patient-controlled continuous epidural opioid infusion trail, performed in an outpatient setting, is widely accepted by many interventional pain specialists. To report a case of severe edema observed during the continuous epidural hydromorphone infusion trial. An otherwise healthy 68-year-old lady with a 5-year history of severe low back pain and bilateral leg pain because of failed back surgery syndrome was referred to our clinic for IDD therapy. A tunneled lumbar epidural catheter was placed at L2-L3 with catheter tip advanced to L1 under fluoroscopic guidance. Satisfactory catheter placement was confirmed by epidurogram. The catheter was then tunneled subcutaneously and connected to a Microject patient-controlled epidural analgesia (PCEA) pump (Codman, Raynham, MA). The pump was programmed to deliver hydromorphone (0.1 mg/ml) at basal rate of 0.3 ml/h. The bolus dose was 0.1 ml with a 60-minute lockout interval. The patient was instructed how to operate the infusion pump. During the following infusion trial, she reported satisfactory analgesia (> 70 percent pain reduction) and was able to wean off her other systemic opioids. However, she developed diffuse edema and gained over 16 pounds during the 5-day infusion trial. Her edema finally resolved 3-4 days after termination of the epidural infusion. Edema may occur and persist during epidural hydromorphone infusion. This report represents the first case report, to the best of our knowledge, describing severe edema in a patient on continuous epidural hydromorphone administration during an outpatient epidural infusion trial.

Home-based Physical Activity Coaching, Physical Activity, and Health Care Utilization in Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial Secondary Outcomes.

Physical inactivity among patients with chronic obstructive pulmonary disease is associated with exacerbations requiring high-cost health care utilization including urgent, emergent, and hospital care. To examine the effectiveness of a behavioral lifestyle physical activity intervention combined with chronic obstructive pulmonary disease self-management education to prevent high-cost health care utilization. This was an analysis of secondary outcomes of the Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial, a two-arm randomized trial of stable adult outpatients with chronic obstructive pulmonary disease recruited from primary care and pulmonary clinics. Following a 6-week self-management education run-in period, participants were randomized to usual care or to a telephone-delivered home-based health coaching intervention over 20 weeks. Secondary outcomes of physical activity and health care utilization were determined by self-report 6, 12, and 18 months after randomization. Associations between treatment allocation arm and these secondary outcomes were examined using log-binomial and Poisson regression models. A total of 325 outpatients with stable chronic obstructive pulmonary disease were enrolled in the trial. Their average age was 70.3 years (standard deviation, 9.5), and 50.5% were female; 156 were randomized to usual care and 149 to the intervention. A greater proportion of participants reported being persistently active over the 18-month follow-up period in the intervention group (73.6%) compared with the usual care group (57.8%) (mean difference, 15.8%; 95% confidence interval, 4.0-27.7%). This association varied by severity of forced expiratory volume in 1 second impairment (P for interaction = 0.09). Those in the intervention group with moderate impairment (forced expiratory volume in 1 second, 50-70% predicted), more frequently reported being persistently active compared with the usual care (86.0 vs. 65.1%; mean difference, 20.9%; 95% confidence interval, 5.7-36.1%). Patients with severe and very severe forced expiratory volume in 1 second impairment (forced expiratory volume in 1 second < 50% predicted) in the intervention group also reported being persistently active more frequently compared with usual care (63.3 vs. 50.8%; mean difference, 12.6%; 95% confidence interval, -4.7 to 29.8). The intervention was associated with a lower rate of lung-related utilization (adjusted rate ratio, 0.38; 95% confidence interval, 0.23-0.63) only among participants with severe spirometric impairment. Our results demonstrate that a feasible and generalizable home-based coaching intervention may decrease sedentary behavior and increase physical activity levels. In those with severe chronic obstructive pulmonary disease, this intervention may reduce lung disease-related health care utilization. Clinical trial registered with www.clinicaltrials.gov (NCT01108991).

Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story

Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial

Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. Bayer AG.

Comparative efficacy of pharmacological and non-pharmacological interventions for the acute treatment of adult outpatients with anorexia nervosa: study protocol for the systematic review and network meta-analysis of individual data

BackgroundOutpatient treatment studies of anorexia nervosa (AN) are notoriously hard to conduct given the ambivalence of the patient group and high drop-out rates. It is therefore not surprising that previous meta-analyses of pharmacological and psychological treatments for outpatient treatment of adult AN have proved to be inconclusive. Network meta-analysis (NMA) has the potential to overcome the limitations of pairwise meta-analysis, as this approach can compare multiple treatments using both direct comparisons of interventions within randomized controlled trials (RCTs) and indirect comparisons across trials based on a common comparator. To date there is no published example of this approach with eating disorders and the current study provides a protocol which will use NMA to advance knowledge about what outpatient therapy works best for which patients with AN by conducting both direct and indirect comparisons of different treatments and the moderating variables.MethodsSearches of electronic data bases will be supplemented with manual searches for published, unpublished and ongoing RCTs in international registries, and clinical trials registries of regulatory agencies and pharmaceutical companies. Two reviewers will independently extract the data and where possible we will access individual data in order to examine moderators of treatment. Two primary outcomes will be selected: changes to body mass index and changes to global eating disorder psychopathology. The secondary outcome is the total number of patients who, at 12-month post-randomization, attained over the previous 28 day period: (i) BMI > 18.5, and (ii) global eating disorder psychopathology to within 1 SD of community norms. We will also provide a statistical evaluation of consistency, the agreement between direct and indirect evidence.ResultsDescriptive statistics across all eligible trials will be provided along with a network diagram, where the size of the nodes will reflect the amount of evidence accumulated for each treatment. We will use a contribution matrix that describes the percentage contribution of each direct meta-analysis to the entire body of evidence.DiscussionFindings will make a major contribution to the literature by summarising individual data across rapidly accumulating outpatient trials of AN using state of the art NMA methodology.Trial registrationPROSPERO registration number: CRD42017064429

Effect of Omecamtiv Mecarbil in Patients with Ischemic and Non-Ischemic Heart Failure with Reduced Ejection Fraction: Results From COSMIC-HF

Introduction: LV systolic dysfunction is a final common pathway of multiple etiologies in the pathogenesis of chronic heart failure (HF). We evaluated the influence of HF etiology (ischemic vs. non-ischemic) on the response to the selective cardiac myosin activator, omecamtiv mecarbil (OM), in patients with HFrEF. Hypothesis: OM would have similar effects in patients with HFrEF regardless of HF etiology. Methods: COSMIC-HF (NCT 01786512) was a Phase 2 multicenter, randomized, double-blind, placebo-controlled trial in outpatients (n = 448) with a history of optimally-treated chronic HF, LVEF ≤40%, and NT-proBNP ≥200 pg/mL (≥1200 pg/mL with atrial fibrillation). In the expansion phase, patients were randomized 1:1:1 to receive placebo (n = 149), OM at 25 mg BID (n = 150), or 25 mg twice daily with pharmacokinetic-guided increases to 50 mg twice daily (n = 149; OM PK-group) for 20 weeks. Interaction terms were used to assess for a differential effect of OM in the OM PK-group by etiology on various study endpoints. Results: In COSMIC-HF, 287 (64%) had ischemic etiology of HF and 161 (36%) had non-ischemic HF etiology. Previous COSMIC-HF results demonstrated nominally statistically significant changes in all pre-specified secondary efficacy endpoints compared to placebo in the OM PK-group at 20 weeks. The current analyses demonstrate similar findings of efficacy in patients regardless of HF etiology (Table). There was no difference in the change from baseline in troponin after 20 weeks of therapy between the ischemic and non-ischemic OM PK-groups. HF etiology did not modify the effectiveness of OM; there were no significant interaction effects of treatment group with HF etiology for any of these variables (Table). Overall and cardiac adverse events were similar between the placebo and PK-titration groups for patients with ischemic (Subject incidence; Overall: Placebo, 58.4% vs. OM, 62.0%; Cardiac: Placebo, 20.2% vs. OM 20.0%) or non-ischemic (Overall: Placebo, 65.0% vs. OM, 71.7%; Cardiac: Placebo, 30.0% vs. OM 23.9%) etiologies. Conclusion: These data from COSMIC-HF suggest that OM produced similar findings with regard to pharmacodynamic response, cardiac function, heart rate, biomarkers, and adverse events in patients with ischemic and non-ischemic etiology of HF.

A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths at Genetic High Risk for Bipolar Disorder.

To determine if acute treatment with aripiprazole (APZ) would be superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering from "cyclotaxia." This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17 years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive either APZ or placebo. Eligible participants had at least one parent with BPD, another first- or second-degree relative afflicted with a mood disorder, and also had not responded to psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1 mg/kg/day and could be increased by approximately 0.05 mg/kg/day at each study visit. Patients were seen weekly for 4 weeks and then every other week thereafter for 12 weeks. The primary outcome measure was mean change from baseline on Young Mania Rating Scale (YMRS) total score. A total of 59 patients (30 APZ, 29 placebo) aged 11.8 (SD = 2.7) years were randomized and returned for at least one postbaseline assessment. The mean total daily doses of active APZ and placebo were 7.1 mg (SD = 3.7) and 7.4 mg (SD = 4.2), respectively. At the 12-week time point, APZ was superior to placebo on the primary outcome measure (p < 0.005). Most adverse events were mild and transient in nature. There was a significant difference in weight gain from baseline between patients who received APZ (2.3 kg [SD = 3.3]) and those who received placebo (0.7 kg [SD = 1.8]). This double-blind trial found that APZ was significantly more efficacious than placebo in reducing symptoms of mania in children and adolescents with cyclotaxia.

The Evolution of Personalized Behavioral Intervention Technology: Will It Change How We Measure or Deliver Rehabilitation?

Telehealth access, mobile communication, instrumented devices, and wearable sensing technologies can be configured by internet connectivity to hover like an invisible personal drone, curating continuous data about physical activity, mental state, and physiology, even body and environmental chemistry, during everyday life.1,2 The figurative drone can gather ground truth via direct observation of disabled persons after a stroke during their daily activities or rehabilitation practice, then transmit measurements of interest to clinicians and researchers with high accuracy in real time. The technology can be configured to ask about and record in-the-moment self-reports about mood, pain, social interaction, activity, and other personal events. After stroke, it can enable patients to receive rehabilitation in their homes and communities when little or no therapy would otherwise be available. Telerehabilitation includes tools for standard telemedicine in which personalized health care is delivered at a distance by, for example, videoconferencing. Mobile health (mHealth) supports these remote interactions between patients and clinicians with smartphone-based text messaging, video streaming, e-mail, health-related apps, and other wireless technologies, such as wearable motion and heart rate sensors. Instrumented exercise and practice devices with radio connectivity to the internet can also stream a record of training and progress. The conceptual bases for such applications to outpatient rehabilitation and clinical trials are subsumed under the motor learning theory that dominates stroke rehabilitation practices. That is, an adequate dose of repetitive practice at relevant tasks that are increasingly challenging and optimized by behavioral reinforcement, along with exercise for strengthening and conditioning, will best support training-induced neuroplasticity and potentially improve outcomes.3 Usual outpatient rehabilitation tends not to offer feedback and relies on informal or ordinal measures of progress. Feedback from multidimensional mHealth monitoring technologies may better motivate and guide compliance, training intensity, and progression when therapists incorporate sensor-derived ground truth about …

Factors associated with non-persistence to oral and inhaled antiviral therapies for seasonal influenza: a secondary analysis of a double-blind, multicentre, randomised clinical trial

ObjectivesWe aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection.DesignA parallel, three-arm, double-blinded trial randomly...

Safety and Efficacy of an Outpatient Intrathecal Catheter Trialing Method for Targeted Drug Delivery

Background: Chronic pain is a significant health challenge, and targeted drug delivery (TDD) is increasingly utilized to manage patients who have failed several treatment modalities. An intrathecal trial is mandatory prior to permanent implantation, with current guidelines recommending inpatient observation of 23 hours or inpatient admission for a continuous intrathecal infusion opioid trial. Objectives: TDD is an established method of the delivery of opioids, and in this study, we aim to provide a safe methodology using an outpatient protocol. Study Design: The study is designed as a retrospective analysis on all non-malignant chronic pain patients who were candidates for TDD, who underwent an outpatient catheter trial from January 1, 2015 to December 31, 2016. Setting: The study took place in an outpatientbased community practice. Methods: A retrospective chart review and patient experience questionnaire were utilized to assess the safety and efficacy of 98 patients who underwent an intrathecal continuous infusion catheter trial as an outpatient. The patients underwent an intrathecal catheter placement at the L2/3 interlaminar space with the catheter tip at T10, regardless of pathology. The patients were connected to an ambulatory pump and were monitored as an outpatient for up to 3 days. Results: Ninety of the 98 patients had greater than 50% pain relief and proceeded to a permanent intrathecal pump implant. The average effective dose of morphine or hyrdromorphone was 480 mcg/day. Using our outpatient and dosage methodology, 0 patients had serious adverse events which include infection, self-reported or caregiver-reported respiratory difficulty, or an emergency room (ER) visit during the trial. The most common adverse events were postdural- puncture headache (PDPH), which occurred in 41% of the patients, nausea/vomiting in 28% of the patients, and catheter dislodgment in 18% of the patients. Limitations: The sample size can be increased to further prove safety. A multicenter study would also prove to be a benefit. Conclusion: Based on this study, we have devised a safe and efficacious methodology for performing an outpatient intrathecal trial using a continuous infusion catheter, using low doses. Implanted drug delivery systems are being increasingly utilized for chronic non-malignant pain, and this study implements a safe methodology. This study hopes to provide better patient access or an alternative to inpatient intrathecal infusion trials, which can be cumbersome. Key words: Targeted drug delivery, pump trial, intrathecal opioid, intrathecal infusion, outpatient trial, chronic non cancer pain

Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence.

Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. 56 women aged 17-40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes.

Effect of artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a systematic review and meta-analysis of outpatient randomised controlled trials

Closed-loop artificial pancreas systems have been in development for several years, including assessment in numerous varied outpatient clinical trials. We aimed to summarise the efficacy and safety of artificial pancreas systems in outpatient settings and explore the clinical and technical factors that can affect their performance. We did a systematic review and meta-analysis of randomised controlled trials comparing artificial pancreas systems (insulin only or insulin plus glucagon) with conventional pump therapy (continuous subcutaneous insulin infusion [CSII] with blinded continuous glucose monitoring [CGM] or unblinded sensor-augmented pump [SAP] therapy) in adults and children with type 1 diabetes. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from 1946, to Jan 1, 2017. We excluded studies not published in English, those involving pregnant women or participants who were in hospital, and those testing adjunct medications other than glucagon. The primary outcome was the mean difference in percentage of time blood glucose concentration remained in target range (3·9-10 mmol/L or 3·9-8 mmol/L, depending on the study), assessed by random-effects meta-analysis. This study is registered with PROSPERO, number 2015:CRD42015026854. We identified 984 reports; after exclusions, 27 comparisons from 24 studies (23 crossover and one parallel design) including a total of 585 participants (219 in adult studies, 265 in paediatric studies, and 101 in combined studies) were eligible for analysis. Five comparisons assessed dual-hormone (insulin and glucagon), two comparisons assessed both dual-hormone and single-hormone (insulin only), and 20 comparisons assessed single-hormone artificial pancreas systems. Time in target was 12·59% higher with artificial pancreas systems (95% CI 9·02-16·16; p<0·0001), from a weighted mean of 58·21% for conventional pump therapy (I2=84%). Dual-hormone artificial pancreas systems were associated with a greater improvement in time in target range compared with single-hormone systems (19·52% [95% CI 15·12-23·91] vs 11·06% [6·94 to 15·18]; p=0·006), although six of seven comparisons compared dual-hormone systems to CSII with blinded CGM, whereas 21 of 22 single-hormone comparisons had SAP as the comparator. Single-hormone studies had higher heterogeneity than dual-hormone studies (I2 79% vs 66%). Bias assessment characteristics were incompletely reported in 12 of 24 studies, no studies masked participants to the intervention assignment, and masking of outcome assessment was not done in 12 studies and was unclear in 12 studies. Artificial pancreas systems uniformly improved glucose control in outpatient settings, despite heterogeneous clinical and technical factors. None.

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain.

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed. This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

Ten month outcome of cognitive behavioural therapy v. interpersonal psychotherapy in patients with major depression: a randomised trial of acute and maintenance psychotherapy.

Cognitive behaviour therapy (CBT) and interpersonal psychotherapy (IPT) are the most studied psychotherapies for treatment of depression, but they are rarely directly compared particularly over the longer term. This study compares the outcomes of patients treated with CBT and IPT over 10 months and tests whether there are differential or general predictors of outcome. A single centre randomised controlled trial (RCT) of depressed outpatients treated with weekly CBT or IPT sessions for 16 weeks and then 24 weeks of maintenance CBT or IPT. The principle outcome was depression severity measured using the MADRS. Pre-specified predictors of response were in four domains: demographic depression, characteristics, comorbidity and personality. Data were analysed over 16 weeks and 40 weeks using general linear mixed effects regression models. CBT was significantly more effective than IPT in reducing depressive symptoms over the 10 month study largely because it appeared to work more quickly. There were no differential predictors of response to CBT v. IPT at 16 weeks or 40 weeks. Personality variables were most strongly associated with overall outcome at both 16 weeks and 40 weeks. The number of personality disorder symptoms and lower self-directness and reward dependence scores were associated with poorer outcome for both CBT and IPT at 40 weeks. CBT and IPT are effective treatments for major depression over the longer term. CBT may work more quickly. Personality variables are the most relevant predictors of outcome.

Psychoeducational family intervention: Benefits and obstacles reported by mental health professionals

IntroductionDespite several guidelines recommend the use of psychoeducational family interventions (PFIs) as add-on in the treatment of patients with bipolar I disorder (a), their implementation on a large scale remains limited (b).ObjectivesTo identify benefits and obstacles in implementing a PFI in the clinical routine care.MethodsThis was a multicentre, real-world, controlled, outpatient trial, carried out in 11 randomly recruited Italian mental health centres. Mental health professionals received a training on PFI and provided the intervention to patients with bipolar I disorder and their relatives. Difficulties and benefits in performing PFI were collected through an ad-hoc schedule, which was administered at baseline and 5 times during the different stages of the intervention.ResultsMental health professionals report significant improvements in the intervention-related benefits over time (T0 = 5.3 ± 2.0 vs. T5 = 7.9 ± 0.9; P &lt; .0001), in particular in their professional skills (T0 = 6.5 ± 2.3 vs. T5 = 8.0 ± 0.8; P &lt; .01). They also report to be more satisfied with their own work (T0 = 6.6 ± 2.3 vs. T5 = 8.0 ± 1.3; P &lt; .05). The most relevant difficulties were related to the need to integrate the PFI with other work responsibilities and to the lack of time, which did not decrease overtime.ConclusionsPFIs are feasible in routine care for the treatment of patients with bipolar I disorder and their relatives, and main obstacles are related to the organization of mental health centres, and not to the characteristics of the intervention itself.Disclosure of interestThe authors have not supplied their declaration of competing interest.