Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.

INTRODUCTION: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. OBJECTIVE: We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. STUDY DESIGN: We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. RESULTS: In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. DISCUSSION: Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. CONCLUSIONS: Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.

Interventional Radiology Peer Learning Platform and Adverse Event Reporting (IR-PEER): Initial Experience Implementing a Team-based Novel Peer Learning System in Interventional Radiology.

Although the transition from peer review to peer learning has had favorable outcomes in diagnostic radiology, experience with implementing a team-based peer review system in interventional radiology (IR) remains limited. Peer learning systems benefit diverse IR teams composed of multiple clinical roles and could contribute value in archiving events that have potential educational value. With multiple stakeholder input from clinical roles within the IR division at our institution (ie, radiologic technologists, nurses, advanced practice providers, residents, fellows, and attending physicians), we launched a HIPAA-compliant secure IR complication and learning opportunity reporting platform in April 2022. Case submissions were monitored over the subsequent 24 weeks, with monthly dashboard reports provided to departmental leadership. Preintervention and postintervention surveys were used to assess the impact of the peer learning platform and adverse event reporting in IR (IR-PEER) on perceptions of complication reporting in the IR division across clinical roles. Ninety-two peer learning submissions were collected for a weekly average ± standard error of 3.8 ± 0.6 submissions per week, and an additional 26 submissions were collected as part of the division's ongoing monthly complication review conference, for a total of 98 unique total case references. A total of 64.1% of submissions (59 of 92) involved a complication and/or adverse event, and 35.9% of submissions (33 of 92) identified a learning opportunity (no complication or adverse event). Nurses reported that IR-PEER made the complication-reporting process easier (P = .01), and all clinical roles reported that IR-PEER improved the overall process of complication reporting. Peer learning frameworks such as IR-PEER provide a more equitable communication platform for multidisciplinary teams to capture and archive learning opportunities that support quality and safety improvement efforts.

A machine learning algorithm predicting risk of dilating VUR among infants with hydronephrosis using UTD classification.

BACKGROUNDS: Urinary Tract Dilation (UTD) classification has been designed to be a more objective grading system to evaluate antenatal and post-natal UTD. Due to unclear association between UTD classifications to specific anomalies such as vesico-ureteral reflux (VUR), management recommendations tend to be subjective. OBJECTIVE: We sought to develop a model to reliably predict VUR from early post-natal ultrasound. STUDY DESIGN: Radiology records from single institution were reviewed to identify infants aged 0-90 days undergoing early ultrasound for antenatal UTD. Medical records were reviewed to confirm diagnosis of VUR. Primary outcome defined as dilating (≥Gr3) VUR. Exclusion criteria include major congenital urologic anomalies (bilateral renal agenesis, horseshoe kidney, cross fused ectopia, exstrophy) as well as patients without VCUG. Data were split into training/testing sets by 4:1 ratio. Machine learning (ML) algorithm hyperparameters were tuned by the validation set. RESULTS: In total, 280 patients (540 renal units) were included in the study (73 % male). Median (IQR) age at ultrasound was 27 (18-38) days. 66 renal units were found to have ≥ grade 3 VUR. The final model included gender, ureteral dilation, parenchymal appearance, parenchymal thickness, central calyceal dilation. The model predicted VUR with AUC at 0.81(0.73-0.88) on out-of-sample testing data. Model is shown in the figure. DISCUSSION: We developed a ML model that can predict dilating VUR among patients with hydronephrosis in early ultrasound. The study is limited by the retrospective and single institutional nature of data source. This is one of the first studies demonstrating high performance for future diagnosis prediction in early hydronephrosis cohort. CONCLUSIONS: By predicting dilating VUR, our predictive model using machine learning algorithm provides promising performance to facilitate individualized management of children with prenatal hydronephrosis, and identify those most likely to benefit from VCUG. This would allow more selective use of this test, increasing the yield while also minimizing overutilization.

New Frontiers in the Role of Locoregional Therapies in Breast Cancer: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

Emerging evidence regarding the effectiveness of locoregional therapies (LRTs) for breast cancer has prompted investigation of the potential role of interventional radiology (IR) in the care continuum of patients with breast cancer. The Society of Interventional Radiology Foundation invited 7 key opinion leaders to develop research priorities to delineate the role of LRTs in both primary and metastatic breast cancer. The objectives of the research consensus panel were to identify knowledge gaps and opportunities pertaining to the treatment of primary and metastatic breast cancer, establish priorities for future breast cancer LRT clinical trials, and highlight lead technologies that will improve breast cancer outcomes either alone or in combination with other therapies. Potential research focus areas were proposed by individual panel members and ranked by all participants according to each focus area's overall impact. The results of this research consensus panel present the current priorities for the IR research community related to the treatment of breast cancer to investigate the clinical impact of minimally invasive therapies in the current breast cancer treatment paradigm.

The Role of Artificial Intelligence in the Detection and Implementation of Biomarkers for Hepatocellular Carcinoma: Outlook and Opportunities.

Liver cancer is a leading cause of cancer-related death worldwide, and its early detection and treatment are crucial for improving morbidity and mortality. Biomarkers have the potential to facilitate the early diagnosis and management of liver cancer, but identifying and implementing effective biomarkers remains a major challenge. In recent years, artificial intelligence has emerged as a promising tool in the cancer sphere, and recent literature suggests that it is very promising in facilitating biomarker use in liver cancer. This review provides an overview of the status of AI-based biomarker research in liver cancer, with a focus on the detection and implementation of biomarkers for risk prediction, diagnosis, staging, prognostication, prediction of treatment response, and recurrence of liver cancers.

Dietary Risk Factors for Pediatric Kidney Stones: A Case-Control Study.

PURPOSE: Data are scarce regarding dietary risk factors for pediatric nephrolithiasis. Our objective was to perform a case-control study (nonmatched) of the association of dietary nutrients with pediatric urolithiasis. MATERIALS AND METHODS: We obtained dietary information from pediatric urolithiasis patients (from stone clinic in 2013-2016) and healthy controls (well-child visit at primary care in 2011-2012). Survey results were converted to standard nutrient intakes. Children younger than 5 years of age and those with extreme calorie intake values (<500 or >5,000 kcal/day) were excluded. The association of individual nutrients with urolithiasis was assessed by bivariate analysis results and machine-learning methods. A multivariable logistic regression model was fitted using urolithiasis as the outcome. RESULTS: We included 285 patients (57 stones/228 controls). Mean±SD age was 8.9±3.6 years (range 5-20). Of the patients 47% were male. After adjusting for age, sex, body mass index (obese/overweight/normal), calorie intake and oxalate, urolithiasis was associated with higher dietary sodium (OR=2.43 [95% CI=1.40-4.84] per quintile increase, p=0.004), calcium (OR=1.73 [95% CI=1.07-3.00] per quintile increase, p=0.034) and beta carotene (OR=2.01 [95% CI=1.06-4.18] per quintile increase, p=0.042), and lower potassium (OR=0.31 [95% CI=0.13-0.63] per quintile increase, p=0.003). Sensitivity analysis was performed by removing oxalate from the model and limiting the sample to patients aged 5-13 years, with similar results. CONCLUSIONS: In our cohort, higher dietary intake of calcium, sodium and beta carotene, and lower potassium intake were associated with pediatric urolithiasis. This is the first study using a detailed dietary survey to identify dietary risk factors for pediatric urolithiasis. Further research is warranted to delineate the mechanisms and to generate a lower risk diet profile for pediatric urolithiasis.

Point-of-Care Synchronous Virtual Radiology Consultations for Atherosclerotic Disease in Primary Care: A Cluster-Randomized Study.

PURPOSE: Synchronous virtual visits are an emerging model of care, and their feasibility has been demonstrated in radiology. The purpose of this study was to assess the value of point-of-care virtual radiology primary care consultations for atherosclerotic vascular disease management. METHODS: In this institutional review board-approved study, 107 age- and gender-matched patients were assigned to control (n = 62) and intervention (n = 45) arms with the following inclusion criteria: (1) age > 45 years, (2) consult with a primary care physician (PCP), and (3) recent CT of the chest or abdomen demonstrating atherosclerotic calcification. In the intervention arm, virtual real-time radiology consultation with referring PCPs and patients was conducted, with review of CT images focused on the extent of vascular atherosclerosis. Patients in the control arm followed the current standard of care of PCPs' discussing relevant imaging results, if any. RESULTS: Thirty-one patients in the intervention arm and 31 patients in the control arm completed the study (control: 64.5% women; mean age, 68 years; intervention: 67.7% women; mean age, 67 years). Discussion of imaging findings occurred with all patients in the intervention arm (discussion with PCP and virtual consultation with radiologist) and with 45% of patients in the control arm (PCP only; P < .001). All patients in the intervention arm indicated that seeing or discussing their images improved their understanding of their disease, compared with 85% of patients in the control arm (P = .04). In the intervention arm, 10 of 31 patients (32.2%) left the visit with changes in prescriptions for statins or antihypertensive medications, compared with only 4 of 31 patients (13%) in the control arm (P = .04). CONCLUSIONS: Point-of-care radiology virtual visits enhance patient understanding and may influence the longitudinal management of atherosclerotic disease in primary care.

Synchronous Virtual Patient Consultations in Radiology.

We describe our experience in synchronous virtual radiologist consultations, whereby a radiologist at the PACS uses a conferencing platform to join a primary care visit between a patient at home and a referring provider, at home or at clinic, to directly explain imaging results and partner with the referrer in forming management recommendations. We explore the model's significance in the context of patient-centered care. Implementation, obstacles, and potential impact on health care disparities are also discussed.

Top-Down versus Bottom-Up Approach in Children Presenting with Urinary Tract Infection: Comparative Effectiveness Analysis Using RIVUR and CUTIE Data.

PURPOSE: The initial imaging approach to children with urinary tract infection (UTI) is controversial. Along with renal/bladder ultrasound, some advocate voiding cystourethrogram (VCUG), ie a bottom-up approach, while others advocate dimercaptosuccinic acid (DMSA) scan, ie a top-down approach. Comparison of these approaches is challenging. In the RIVUR/CUTIE trials, however, all subjects underwent both VCUG and DMSA scan. Our objective was to perform a comparative effectiveness analysis of the bottom-up vs top-down approach. MATERIALS AND METHODS: We simulated 1,000 hypothetical sets of 500 children using RIVUR/CUTIE data. In the top-down approach, patients underwent initial DMSA scan, and only those with renal scarring underwent VCUG. In the bottom-up approach, the initial study was VCUG. We assumed all children with vesicoureteral reflux (VUR) received continuous antibiotic prophylaxis (CAP). Outcomes included recurrent UTI, number of VCUGs and CAP exposure. We assumed a 25% VUR prevalence in children with initial UTI with sensitivity analysis using 40% VUR prevalence. RESULTS: Median age of the original RIVUR/CUTIE cohort was 12 months. First DMSA scan was performed at a median of 8.2 weeks (IQR 5-11.8) after the index UTI. In the simulated cohort, slightly higher yet statistically significantly recurrent UTI was associated with the top-down compared with the bottom-up approach (24.4% vs 18.0%, p=0.045). On the other hand, the bottom-up approach resulted in more VCUG (100% vs 2.4%, p <0.001). Top-down resulted in fewer CAP-exposed patients (25% vs 0.4%, p <0.001) and lower overall CAP exposure (5 vs 162 days/person, p <0.001). Sensitivity analysis was performed with 40% VUR prevalence with similar results. CONCLUSIONS: The top-down approach was associated with slightly higher recurrent UTI. Compared to the bottom-up approach, it significantly reduced the need for VCUG and CAP.

A Machine Learning Model to Maximize Efficiency and Face Time in Ambulatory Clinics.

INTRODUCTION: Ambulatory appointments are typically scheduled in fixed increments, resulting in suboptimal time utilization. Advanced analytics are rarely applied to address operational challenges in health care. We sought to develop a machine learning model that predicts the time pediatric urologists require to create a more efficient clinic schedule. METHODS: We prospectively collected data from January to April 2018. Variables included demographics and visit level covariates. The primary outcome was defined as in-room doctor time spent. Univariate analysis was performed. Data were split into train/test in a 4:1 ratio. Separate models using random forest were created for new and return visits. Two out-of-sample clinic days were used to compare the patient wait time between fixed-time visits and machine learning model. Patient punctuality simulation was performed 1,000 times for each day. RESULTS: A total of 256 visits (113 new/143 return) were included. Mean age at visit was 6.47 years. In univariate analysis, longer visits were significantly associated with new patients (p <0.01), testing (p <0.01), older patients and diagnoses like voiding dysfunction and neurogenic bladder. Conversely, morning clinic, previous urological surgery (p <0.01), recent postoperation (p <0.01) and diagnoses like penile complaints and hydrocele were associated with shorter visits. On average, our machine learning model predicted doctor time accurately to 3.6 (new patients) and 5.0 minutes (returning patients). In 1,000 simulated days with random patient punctuality machine learning reduced the wait time by 24% to 54%. CONCLUSIONS: Pediatric urologists' clinic time can be accurately predicted with machine learning models. This insight can be incorporated into a robust scheduling model to minimize patient wait time, increase clinical efficiency and likely improve family satisfaction.

Pattern recognition algorithm to identify detrusor overactivity on urodynamics.

AIMS: Detrusor overactivity (DO) of the bladder is a finding on urodynamic studies (UDS) that often correlates with lower urinary tract symptoms and drives management. However, UDS interpretation remains nonstandardized. We sought to develop a mathematical model to reliably identify DO in UDS. METHODS: We utilized UDS archive files for studies performed at our institution between 2013 and 2019. Raw tracings of vesical pressure, abdominal pressure, detrusor pressure, infused volume, and all annotations during UDS were obtained. Patients less than 1 year old, studies with calibration issues, or those with significant artifacts were excluded. In the training set, five representative DO patterns were identified. Candidate Pdet signal segments were matched to representative DO patterns. Manifold learning and dynamic time warping algorithms were used. Five-fold cross validation (CV) was used to evaluate the performance. RESULTS: A total of 799 UDS studies were included. The median age was 9 years (range, 1-33). There were 1,742 DO events that did not overlap with annotated artifacts (cough, cry, valsalva, movements). The AUC of the training sets from the five-fold CV was 0.84 ± 0.01. The five-fold CV leads to an overall accuracy 81.35%, and sensitivity and specificity of detecting DO events are 76.92% and 81.41%, respectively, in the testing set. CONCLUSIONS: Our predictive model using machine learning algorithms provides promising performance to facilitate automated identification of DO in UDS. This would allow for standardization and potentially more reliable UDS interpretation. Signal processing and machine learning interpretation of the other components of UDS are forthcoming.

Novel co-culture plate enables growth dynamic-based assessment of contact-independent microbial interactions.

Interactions between microbes are central to the dynamics of microbial communities. Understanding these interactions is essential for the characterization of communities, yet challenging to accomplish in practice. There are limited available tools for characterizing diffusion-mediated, contact-independent microbial interactions. A practical and widely implemented technique in such characterization involves the simultaneous co-culture of distinct bacterial species and subsequent analysis of relative abundance in the total population. However, distinguishing between species can be logistically challenging. In this paper, we present a low-cost, vertical membrane, co-culture plate to quantify contact-independent interactions between distinct bacterial populations in co-culture via real-time optical density measurements. These measurements can be used to facilitate the analysis of the interaction between microbes that are physically separated by a semipermeable membrane yet able to exchange diffusible molecules. We show that diffusion across the membrane occurs at a sufficient rate to enable effective interaction between physically separate cultures. Two bacterial species commonly found in the cystic fibrotic lung, Pseudomonas aeruginosa and Burkholderia cenocepacia, were co-cultured to demonstrate how this plate may be implemented to study microbial interactions. We have demonstrated that this novel co-culture device is able to reliably generate real-time measurements of optical density data that can be used to characterize interactions between microbial species.

Short-term safety and pharmacokinetic profile of asenapine in older patients with psychosis.

OBJECTIVES: The aim of this study was to assess the short-term tolerability of two titration schedules of sublingual asenapine in older patients with psychosis, not associated with organic brain disease, and to compare asenapine pharmacokinetics in older patients versus younger adults with schizophrenia. METHODS: Patients ≥ 65 years with psychosis without dementia were randomized for 6 weeks to two dose-escalation regimens: 2 days at 2 mg twice daily (BID), 2 days at 5 mg BID, and 10 mg BID thereafter (slow escalation); or 4 days at 5 mg BID and 10 mg BID thereafter (rapid escalation). Clinical and pharmacokinetic assessments were performed in each group. RESULTS: Of 122 randomized patients, 76 (62.3%) completed the trial. The incidence of treatment-emergent adverse events (AEs) was comparable (72.1%) with both regimens. The most frequently reported AEs were hypertension, headache, and somnolence; incidence of extrapyramidal symptom-related AEs was 5.7%. Mean end point weight change was 0.4 kg. For asenapine 5 and 10 mg BID, median times to maximum concentration were 1.00 and 1.06 h, respectively; maximum concentrations (C(max) ) were 4.73 and 7.93 ng/mL; areas under the concentration versus time curve (0-12 h; AUC(0-12) ) were 32.1 and 56.3 ng∙h/mL. CONCLUSIONS: Despite 12-30% increases in asenapine C(max) and AUC(0-12) in older patients compared with previously published findings in younger schizophrenia patients, possibly as a result of slower drug clearance, asenapine was generally well tolerated during both dose-escalation schedules. No dose adjustment appears to be necessary in older patients.

Asenapine as adjunctive treatment for acute mania associated with bipolar disorder: results of a 12-week core study and 40-week extension.

In a 12-week randomized, placebo-controlled study evaluating the efficacy and safety of adjunctive asenapine, bipolar I disorder patients experiencing manic or mixed episodes despite pretreatment with lithium or valproate monotherapy were treated with flexible-dose, twice-daily asenapine 5 or 10 mg (n = 158) or placebo (n = 166). The primary efficacy end point was change from baseline Young Mania Rating Scale (YMRS) total score at week 3. Secondary outcomes included YMRS response and remission and Clinical Global Impression for Bipolar Disorder and Montgomery-Asberg Depression Rating Scale score changes. Patients completing the core study were eligible for a 40-week double-blind extension assessing safety and tolerability. Adjunctive asenapine significantly improved mania versus placebo at week 3 (primary end point) and weeks 2 to 12. The YMRS response rates were similar at week 3 but significantly better with asenapine at week 12. The YMRS remission rates and changes from baseline on Clinical Global Impression for Bipolar Disorder for mania and overall illness were significantly better with asenapine at weeks 3 and 12. No other statistically significant differences on secondary outcomes were observed. Only a small number of patients entered the extension, making firm statistical conclusions on efficacy difficult. Treatment-emergent adverse events reported by 5% or more of asenapine patients and at twice the incidence of placebo were sedation, somnolence, depression/depressive symptoms, oral hypoesthesia, and increased weight in the 12-week core study. Adjunctive asenapine to lithium or valproate was more effective than mood stabilizer monotherapy in the core study and was well tolerated for up to 52 weeks.

Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia.

Two randomized, double-blind, 26-week core studies (Eastern [EH] and Western Hemisphere [WH]) tested the hypothesis that asenapine is superior to olanzapine for persistent negative symptoms of schizophrenia; 26-week extension studies assessed the comparative long-term efficacy and safety of these agents. In the core studies, 949 people were randomized to asenapine (n = 241 and 244) or olanzapine (n = 240 and 224); 26-week completion rates with asenapine were 64.7% and 49.6% (olanzapine, 80.4% and 63.8%) in the EH and WH, respectively. In the EH and WH extensions, respectively (asenapine, n = 134 and 86; olanzapine, n = 172 and 110), 52-week completion rates were 84.3% and 66.3% with asenapine (olanzapine, 89.0% and 80.9%). Asenapine was not superior to olanzapine in change in the 16-item Negative Symptom Assessment Scale total score in either core study, but asenapine was superior to olanzapine at week 52 in the WH extension study. Olanzapine was associated with modest, but significantly greater, changes in PANSS positive subscale score at various assessment times in both core studies and the WH extension study. Incidence of treatment-emergent adverse events was comparable between treatments across studies. Weight gain was consistently lower with asenapine. Extrapyramidal symptom-related adverse event incidence was higher with asenapine (EH: 8.3%; 95% confidence interval [CI], 5.1%-12.5%; WH: 16.4%; 95% CI, 11.9%-21.6%) than olanzapine (EH: 3.3%; 95% CI, 1.4%-6.4%; WH: 12.1%; 95% CI, 8.1%-17.0%), but Extrapyramidal Symptom Rating Scale-Abbreviated total score changes did not significantly differ between treatments. In conclusion, asenapine superiority over olanzapine was not observed in the core studies. Both treatments improved persistent negative symptoms, but discontinuation rates were higher with asenapine.

Training for assessment of negative symptoms of schizophrenia across languages and cultures: comparison of the NSA-16 with the PANSS Negative Subscale and Negative Symptom factor.

BACKGROUND: The 16-item Negative Symptom Assessment scale (NSA-16) has been validated in English-speaking raters. We analyzed the level of agreement achieved among raters of different nationalities using the NSA-16 and the Positive and Negative Syndrome Scale (PANSS) negative subscale and Marder negative factor. METHODS: Raters participating in two international trials were trained in the use of each instrument through lectures and feedback on their ratings of at least one videotaped interview of a schizophrenic patient. Overall and regional (North America, Western Europe, Eastern Europe, South/Central America, and Australia and South Africa combined) kappa values were calculated and mean total scores were compared (1-way analysis of variance) by region for each instrument. In addition, within-scales variance was calculated by item to help identify negative symptoms that were particularly challenging to obtain agreement on across cultures. RESULTS: In the combined group of international raters, the kappa values for ratings of the NSA-16, PANSS negative subscale, and Marder negative factors were 0.89, 0.84, and 0.82, respectively. Kappa values calculated by geographic region ranged from 0.87 to 0.94 for the NSA-16 compared with 0.82 to 0.86 for the PANSS negative subscale and 0.79 to 0.87 for the PANSS Marder negative factor. CONCLUSIONS: Despite cultural and linguistic differences among raters, standardizing measurement of negative symptoms in international clinical trials is possible using available rating scales: NSA-16, PANSS negative subscale, and Marder negative subscale. Agreement among raters was at least as high using the NSA-16 as using the PANSS instruments.

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

BACKGROUND: Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms. METHODS: In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures. RESULTS: Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3. CONCLUSIONS: These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.

Validation of a 4-item Negative Symptom Assessment (NSA-4): a short, practical clinical tool for the assessment of negative symptoms in schizophrenia.

The 16-item Negative Symptom Assessment (NSA-16) scale is a validated tool for evaluating negative symptoms of schizophrenia. The psychometric properties and predictive power of a four-item version (NSA-4) were compared with the NSA-16. Baseline data from 561 patients with predominant negative symptoms of schizophrenia who participated in two identically designed clinical trials were evaluated. Ordered logistic regression analysis of ratings using NSA-4 and NSA-16 were compared with ratings using several other standard tools to determine predictive validity and construct validity. Internal consistency and test--retest reliability were also analyzed. NSA-16 and NSA-4 scores were both predictive of scores on the NSA global rating (odds ratio = 0.83-0.86) and the Clinical Global Impressions--Severity scale (odds ratio = 0.91-0.93). NSA-16 and NSA-4 showed high correlation with each other (Pearson r = 0.85), similar high correlation with other measures of negative symptoms (demonstrating convergent validity), and lesser correlations with measures of other forms of psychopathology (demonstrating divergent validity). NSA-16 and NSA-4 both showed acceptable internal consistency (Cronbach α, 0.85 and 0.64, respectively) and test--retest reliability (intraclass correlation coefficient, 0.87 and 0.82). This study demonstrates that NSA-4 offers accuracy comparable to the NSA-16 in rating negative symptoms in patients with schizophrenia.

A randomized placebo-controlled trial of asenapine for the prevention of relapse of schizophrenia after long-term treatment.

OBJECTIVE: Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind, placebo-controlled trial that followed 26 weeks of open-label treatment. METHOD: Stable schizophrenia patients (DSM-IV-TR criteria) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment, with randomization to continued asenapine or switch to placebo. Time to relapse/impending relapse (primary endpoint, as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale) and discontinuation for any reason (key secondary endpoint) were assessed by survival analyses for asenapine versus placebo. The study was conducted from May 2005 through June 2008. RESULTS: Of 700 enrolled patients treated with open-label asenapine, 386 entered (asenapine, n = 194; placebo, n = 192) and 207 completed (n = 135; n = 72) the double-blind phase. Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo (both P < .0001). Incidence of relapse/impending relapse was lower with asenapine than placebo (12.1% vs 47.4%, P < .0001). The modal dosage of asenapine was 10 mg twice daily in both phases. During the double-blind phase, the incidence of adverse events (AEs) considered serious with asenapine and placebo was 3.1% and 9.9%, respectively; incidence of extrapyramidal symptom-related AEs was 3.1% and 4.7%, respectively. The most frequently reported AEs with asenapine versus placebo were anxiety (8.2%; 10.9%), increased weight (6.7%; 3.6%), and insomnia (6.2%; 13.5%). The incidence of clinically significant weight gain (≥ 7% increase from double-blind baseline) was 3.7% with asenapine and 0.5% with placebo. CONCLUSIONS: Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00150176.