The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.

BACKGROUND: Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. METHODS: Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. RESULTS: Chronic cannabis use was found to be an independent negative predictor of weak swallows (ß=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (ß=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (ß=10.38, P =0.0084). CONCLUSIONS: Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.

Diagnostic Accuracy of the Proton Pump Inhibitor Test in Gastroesophageal Reflux Disease and Noncardiac Chest Pain: A Systematic Review and Meta-analysis.

BACKGROUND: Response to a trial of proton pump inhibitors (PPIs) is currently accepted as a first step in the management of gastroesophageal reflux disease (GERD). However, information on the diagnostic performance of the PPI test is limited. AIM: The aim of this study was to determine the diagnostic accuracy of the PPI test in GERD and noncardiac chest pain (NCCP) and to assess the test performance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD). METHODS: Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard, from January 1, 1950, through February 1, 2021. Subgroup analyses were performed, and the risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: Nineteen studies (GERD=11, NCCP=8) involving 1691 patients were included. In GERD, the PPI test had 79% pooled sensitivity [95% confidence interval (CI), 72%-84%], and 45% pooled specificity (95% CI, 40%-49%). In NCCP, pooled sensitivity and specificity were 79% (95% CI, 69%-86%) and 79% (95% CI, 69%-86%), respectively. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%) and 30% pooled specificity (95% CI, 8%-67%). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%) and 50% pooled specificity (95% CI, 39%-61%). CONCLUSIONS: The PPI test was sensitive in GERD but with suboptimal specificity. The test performed better in GERD-related NCCP. Diagnostic accuracy was comparable in ERD and NERD.

Psychometric Evaluation of The Irritability Scale-Initial Version in Chinese Cancer Patients.

BACKGROUND: Irritability is a common experience of depressed Chinese patients but is understudied and poorly measured. OBJECTIVE: We aimed to assess psychometric properties of a new measure of irritability in Chinese cancer patients across the social and political spectrum. METHODS: The Irritability Scale-Initial Version (TISi) was translated into Chinese and tested in two samples of Chinese cancer patients undergoing treatments: 52 patients in Beijing, China, between 2018 and 2019 and 65 patients in Taipei, Taiwan, in 2020. RESULTS: The Chinese version of TISi demonstrated high internal consistency, high reliability based on the split-half method in the two samples, and satisfactory discriminant validity using the Chinese version of the 17-item Hamilton Rating Scale for Depression and the seven-item depression subscale of the Hospital Anxiety and Depression Scale in the Beijing sample. A confirmatory factor analysis produced factor loadings in both samples, which resembled a sample of American cancer patients. Three TISi items were loaded more highly on the physical instead of the original behavioral subscale in the Beijing sample. A possible influence of cultures was explained. CONCLUSION: The Chinese version of TISi has satisfactory psychometric properties for assessing the level of irritability in Chinese cancer patients. Future large-sample studies are needed to further determine TISi's factorial structure, test-retest reliability, sensitivity to change, and predictive validity for depression in Chinese cancer patients.

Adults with Severe Psychiatric Symptoms in a Community Partial Hospitalization Program: Characteristics and Predictors of Clinical Response.

Mental health wellbeing is a critical element in the overall wellbeing of an individual. Severe mental health issues are directly connected with the individual's functioning and negatively impacts the quality of life. Inpatient psychiatric hospitalization does help significantly in stabilizing the acute serious mental health problems; however, the utility of community partial hospitalization program (PHP) has not been studied extensively. We undertook this study to assess the usefulness of community partial hospitalization program (PHP) in reducing severity of psychosomatic symptoms of patients; to study the epidemiology of the referred patients; and to elucidate the characteristics and predictors of psychosomatic symptom response. 164 patients were assessed by a baseline Behavioral and Symptom Identification Scale-32 (BASIS-32) at a tertiary healthcare center, out of which 82 patients subsequently followed up and were assessed using the same scale and the data was then stratified and compiled. Out of the initial 164 patients, at a 50% adherence rate, 13 patients showed an improvement greater than 30% with a significant co-relation to the race of the patients. Partial Hospitalization Program proved to be moderately effective in improving psychosomatic symptoms, with better results noticed in the White/Caucasian race. We need to consider several variables before generalizing this finding and more studies are needed in this area. However, we are able to highlight this valuable tool in addressing the severe mental health issues in a community-based populations.

Measurement of Irritability in Cancer Patients.

BACKGROUND: Irritability is common among people who are physically ill, but a physical underpinning of irritability is not assessed by existing measures. A measure that assesses multidimensionality of irritability can help nurses and clinicians provide better care for people with cancer and, thus, reduce a risk for developing depression during cancer treatment. OBJECTIVES: We pilot tested a new measure, The Irritability Scale-Initial Version (TISi), for assessing irritability of cancer patients on three dimensions: physical, affective, and behavioral. METHODS: We conducted thee pilot studies to develop the 35-item TISi on a 5-point Likert scale. TISi was tested in 48 early-stage, nonmetastasized breast cancer patients at baseline (before) and 3 months (during chemotherapy). Of these patients, 62.5% received neoadjuvant and 37.5% received adjuvant chemotherapy, but none received hormonal treatment before or during the study. Measures of other correlates, including depression, anxiety, symptom distress, and social disconnectedness, were also administered, and biomarkers of hsCRP, TNF-α, IL-6, and BDNF were obtained from blood draws at both assessments. RESULTS: TISi has a high internal consistency (Cronbach's α = .97), satisfactory test-retest reliability (retest r = .69, intraclass correlation coefficient = .86), and moderate correlation with other constructs over time (r ≈ .40-.70). Its physical subscale significantly correlated with hsCRP (r = .32, p = .025) at baseline and TNF-α (r = .44, p = .002) at 3 months. A confirmatory factor analysis yields three factor loadings that are in line with conceptualization of the subscales. DISCUSSION: The findings support psychometric properties of TISi and its application for assessing cancer patients' irritability in multiple dimensions. Further investigation using a large study sample is necessary for improving construct and criterion validity and reducing item redundancy. CONCLUSION: TISi can be used to measure the level of irritability in cancer patients.

Barrett's esophagus patients are becoming younger: analysis of a large United States dataset.

BACKGROUND: Barrett's esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6-8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. METHODS: This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE's variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. RESULTS: The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (- 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30-39: 2.07%, 40-49: 3.64%, 50-59: 6.89%, 60-69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (- 20.8%, p < 0.001), but increased in the other remaining age groups. CONCLUSIONS: The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients' groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30-39 years old.

Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders.

BACKGROUND & AIMS: As many as 45% of patients with gastroesophageal reflux disease (GERD) still have symptoms after receiving once-daily proton pump inhibitor (PPI) therapy. We aimed to compare reflux characteristics and patterns between responders and non-responders to once-daily PPI therapy using combined impedance-pH monitoring. METHODS: Patients who reported heartburn and/or regurgitation at least twice per week for 3 months while receiving standard-dose PPI therapy were assigned to the PPI failure group (n = 16). Patients who reported a complete resolution of symptoms on once-daily PPIs for at least 4 weeks were assigned to the PPI success group (n = 13). We collected demographic data and subjects completed the short-form 36 and the GERD health-related quality of life questionnaires. Patients then underwent upper endoscopy and combined esophageal impedance-pH monitoring while on PPI therapy. RESULTS: Four patients in the PPI success group (31%) and 4 patients in the PPI failure group (25%) had abnormal results from the pH test (P = 1.00). Most of the patients in the PPI failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI failure and success group. CONCLUSIONS: We found no difference in reflux characteristics between patients with GERD who had successful vs failed once-daily PPI therapy. Most patients in the PPI failure group (75%) had functional esophageal disorders.

Longitudinally Measured Changes in Somnolence Severity With a Visual Analog Scale in a Randomized Lithium Versus Quetiapine-IR Study in Bipolar Disorder.

OBJECTIVE: The aim of this study was to use a visual analog scale (VAS) longitudinally measuring somnolence severity in patients with bipolar disorder. METHODS: A data set of patients with bipolar spectrum disorders who were randomized to lithium or quetiapine-IR for 16 weeks was used. The somnolence severity was measured with a VAS from 0 to 100 (VAS based), and somnolence frequency was recorded according to incident report (incidence based) at each visit. The rates of VAS-based and incidence-based somnolence and changes in somnolence severity from baseline to the end of study were compared between the lithium and quetiapine groups. Longitudinal changes in somnolence severity were analyzed with linear regression analysis. RESULTS: Of 42 patients randomized, only 3 scored 0 on the VAS at baseline. The rates of incidence-based and VAS-based somnolence were similar in the lithium and quetiapine-IR groups. The VAS change scores from baseline to each visit varied in both groups with significant decreases at weeks 6 and 12 in the quetiapine-IR group only. The decrease at week 6 in the quetiapine-IR group was significantly different from that in the lithium group. Patterns of changes in somnolence severity were inconsistent in both groups. A significant interaction between time course and the decrease in VAS scores was observed in the quetiapine-IR group, but not in the lithium group. CONCLUSIONS: Baseline somnolence was highly prevalent in patients with bipolar disorder. The change in somnolence severity was different between lithium-treated and quetiapine-treated patients. Quantifying somnolence longitudinally is important in clinical trials and practice.

Randomized clinical trial of a community navigation intervention to improve well-being in persons living with HIV and other co-morbidities.

Long-term survival of people living with HIV (PLWH) is associated with the development of co-morbid conditions and need for symptom management and other efforts to enhance quality of life. We conducted a longitudinal, randomized trial over 36 months to evaluate the effect of a community-based navigator intervention to provide early palliative care to 179 PLWH and other chronic conditions. Outcomes included quality of life, symptom management, coping ability, social support, self-management, and completion of advance directives. Data were analyzed using SAS mixed effects model repeat measurement. Our navigator program showed variable improvement over time of three outcome variables, self-blame, symptom distress, and HIV self-management. However, the program did not improve overall quality of life, social support, or completion of advance directives.

The vaginal distention model in mice is not a reliable model of simulated birth trauma-induced stress urinary incontinence.

AIMS: Vaginal distention (VD) is a validated model of birth-related trauma in rats. Recently a mouse VD model was reported. Our study was originally conducted to evaluate the impact of age on VD in mice. This manuscript describes the study and reports on the lack of reproducibility of VD models in mice. METHODS: We utilized female C57BL/6 mice. A total of 190, 12-weeks old mice, were randomized into VD and sham groups. We inflated a modified Foley's balloon with 0.3 mL for 1 h inside the mice vagina. Afterwards, we measured the leak point pressure (LPP) at defined timepoints (0, 4, 10, 20, or 40 days). We randomized another 190, 40-week old, C57BL/6 mice into either VD or sham groups. We used an extra 20 mice as age - matched controls. RESULTS: In both 12 and 40 weeks-old mice, LPP was significantly decreased versus the negative controls at day 0. Additionally, in both 12 and 40 weeks-old mice, the decrease in LPP was significantly higher in the VD group compared to the sham group at day 0. However, the LPP results were comparable between VD and sham at any other time point thereafter. Furthermore, there was no significant change in LPP values between instrumented (VD and sham) mice and control mice at any time after day 0. CONCLUSIONS: The VD models previously described is not a reproducible model for the study of VD with large number of mice. Our results, unfortunately, do not support its use to study VD injury in mice.

Mood outcomes of a behavioral treatment for urinary incontinence in prostate cancer survivors.

PURPOSE: This study aimed to assess whether prostate cancer survivors who received a behavioral intervention to urinary incontinence had experienced a significant mood improvement. METHODS: One hundred fifty-three prostate cancer survivors with persistent incontinence were included in this secondary data analysis. They were randomly assigned to usual care or interventions that provided pelvic floor muscle exercises and self-management skills. All subjects had measures of anxiety, depression, and anger at baseline, 3 months (post-intervention), and 6 months (follow-up). Negative binomial regression analysis was performed to examine the group status, daily leakage frequency at 3 months, and their interactions at 3 months as predictors for mood outcomes at 6 months, controlling for demographic and medical variables. RESULTS: The main effect of daily leakage frequency at 3 months significantly predicted anxiety at 6 months (p < .01). The group main effect on any mood outcomes at 6 months was not statistically significant. The interaction between the group and 3-month leakage had a significant effect on anxiety; intervention subjects achieving a significant leakage reduction at 3 months exhibited significantly less anxiety at 6 months than other subjects (p = .04). Age, employment status, and receiving surgery at baseline were significantly associated with less anxiety, depression, and anger at 6 months. CONCLUSIONS: Reduced urinary incontinence significantly predicted less anxiety, especially among the intervention subjects. The findings suggest a significant association between a behavioral therapy of urinary incontinence and anxiety reduction in prostate cancer survivors.

A Pilot Study of the Effectiveness of Lithium Versus Quetiapine Immediate Release Monotherapy in Patients With Bipolar Spectrum Disorders.

OBJECTIVE: The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase. METHODS: Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared. RESULTS: Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups. CONCLUSIONS: The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.

Non-sustained microvolt level T-wave alternans in congenital long QT syndrome types 1 and 2.

BACKGROUND: Patients with long QT syndrome (LQTS) are predisposed to polymorphic ventricular tachycardia (VT) during adrenergic stimulation. Microvolt T-wave alternans (MTWA) is linked to vulnerability to VT in structural heart disease. The prevalence of non-sustained MTWA (NS-MTWA) in LQTS is unknown. METHODS: 31 LQT1, 42 LQT2, and 80 controls underwent MTWA testing during exercise. MTWA tests were classified per standardized criteria, and re-analyzed according to the modified criteria to account for NS-MTWA. RESULTS: LQT1 and LQT2 patients had a significantly higher frequency of late NS-MTWA (26% and 12%) compared to controls (0%). There was no significant difference between the groups with respect to sustained and early NS-MTWA. Late NS-MTWA was significantly associated with QTc. CONCLUSION: LQT1 and LQT2 patients had a higher prevalence of late NS-MTWA during exercise than matched controls. NS-MTWA likely reflects transient adrenergically mediated dispersion of repolarization, and could be a marker of arrhythmic risk in LQTS.

Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.

BACKGROUND: Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. METHODS: High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. KEY RESULTS: Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. CONCLUSIONS: Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.

The Financial and Emotional Impact of Atopic Dermatitis on Children and Their Families.

OBJECTIVE: To examine the personal financial impact of atopic dermatitis (AD) and attempt to correlate cost of AD with emotional impact. STUDY DESIGN: Between March 2011 and December 2013, 82 caretakers of children 6 months to 12 years of age with moderate-to-severe AD were recruited at the time of dermatology clinic visits in Cleveland, Ohio, to complete surveys. The response rate was >95%. Participants were asked questions about direct expenses (medical visits, medications, and other products) and indirect expenses (time missed from work, childcare costs) related to AD in the past 4 weeks. Emotional impact was measured by the Childhood Atopic Dermatitis Impact Scale. RESULTS: The mean monthly personal cost of AD in the month before the office visit was $274 (median $114; IQR $29, $276), with $75 from direct costs (median $45; IQR $20, $110) and $199 from indirect costs (median $0; IQR $0, $208). An average of 34.8% of available monthly money was spent on AD care in the month before the office visit. For patients with Medicaid, there was a significant correlation between monthly adjusted personal cost and Childhood Atopic Dermatitis Impact Scale score (r = 0.548; P < .001); however, this correlation did not exist for patients who had commercial insurance (r = 0.269; P = .166). CONCLUSIONS: Our results illustrate the high emotional and financial burden of childhood AD and provide insight into spending patterns. In addition, our study correlate costs with emotional burden of AD for lower-income patients.

Association of Spirituality With Mental Health Conditions in Ohio National Guard Soldiers.

Research exploring spirituality in military populations is a relatively new field with limited published reports. This study used the Spiritual Well-Being Scale to examine the association of spiritual well-being with suicidal ideation/behavior, posttraumatic stress disorder (PTSD), and depression and alcohol use disorders in a randomized sample of Ohio Army National Guard soldiers. The participants were 418 soldiers, mostly white and male, with nearly three-quarters indicating that they had been deployed at least once during their careers. Higher spirituality, especially in the existential well-being subscale, was associated with significantly less lifetime PTSD, depression, and alcohol use disorders and with less suicidal ideation over the past year. Future research in this area may benefit from a longitudinal design that can assess spirituality and mental health behaviors in addition to diagnoses at different time points, to begin to explore spirituality in a larger context.

Does manual T-wave window adjustment affect microvolt T-wave alternans results in patients with structural heart disease?

INTRODUCTION: Microvolt T-wave alternans (MTWA) analysis can identify patients at low risk of sudden cardiac death who might not benefit from an implantable cardioverter-defibrillator (ICD). Current spectral methodology for performing MTWA analysis may "miss" part of the T-wave in patients with QT prolongation. The value of T-wave window adjustment in patients with structural heart disease has not been studied. METHODS: We assembled MTWA data from 5 prior prospective studies including 170 patients with reduced left ventricular ejection fraction, adjusted the T-wave window to include the entire T-wave, and reanalyzed MTWA. RESULTS: Of 170 patients, 43% required T-wave window adjustment. Only 3 of 170 patients (1.8%) had a clinically significant change in MTWA results. CONCLUSIONS: In 98.2% of patients, T-wave window adjustment did not improve the accuracy of MTWA analysis. Spectral MTWA as currently implemented remains effective for identifying patients with structural heart disease unlikely to benefit from ICD therapy.

New insights on acute expansion and longitudinal elongation of bioresorbable vascular scaffolds in vivo and at bench test: a note of caution on reliance to compliance charts and nominal length.

OBJECTIVES: We performed systematic optical coherence tomography (OCT) analyses after bioresorbable vascular scaffolds (BVS) implantation in a "real world" setting aiming at evaluating scaffold expansion and longitudinal integrity. BACKGROUND: a comprehensive elucidation of BVS acute performance in the "real-world" setting is lacking. METHODS: acute BVS expansion compared with compliance chart information and longitudinal integrity were assessed in 29 patients (32 lesions) by OCT. In addition, bench experiments with four scaffolds were performed with different combinations of deployment pressures and tube stiffness. RESULTS: scaffold underexpansion, using compliance chart information as reference, was observed in 97% of OCT cross-sections in vivo; however, only 8.3% of the cross-section analyzed revealed BVS area <5 mm(2) . Calcified plaques were more common in the lowest (9.7%) compared with the mid (8.8%) and highest (6.3%) tertiles of scaffold expansion (P = 0.003 and P = 0.001 for lowest vs. mid, and lowest vs. highest, respectively). Seventeen (54.8%) scaffolds were elongated during implantation, but no signs of scaffold fracture were revealed. Elongation and impaired expansion were reproduced in the bench testing when the scaffold was deployed with high pressure in a hard tube. CONCLUSIONS: compliance chart information should not be used to predict final BVS dimensions in the clinical setting. While BVS expansion could be potentially impaired by calcified plaques, they may elongate during deployment. Bench experiments confirmed the elongation phenomenon when BVS were deployed with high pressure in hard tubes.

Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine: results from a 6-week randomized, placebo-controlled trial.

In adults with schizophrenia, early response/non-response (ER/ENR) to antipsychotics at 2 weeks robustly predicts ultimate response/non-response (UR/UNR). However, less data about the predictive value of ER/ENR exist in adolescents with schizophrenia. Post hoc analysis of a 6-week trial in adolescents aged 13-17 with schizophrenia were randomized 2:1 to olanzapine or placebo. ER was defined as ≥20 % reduction in Brief Psychiatric Rating Scale-children (BPRS-C) total score at week 2 (ER2) or 3 (ER3); UR was defined with increasing stringency as total BPRS-C score reduction ≥20, ≥30, ≥40 or ≥50 %; remission was defined cross-sectionally using Andreasen et al. (2005) criteria. By week 2 (n = 69) and 3 (n = 66), olanzapine-treated youth achieved 73.3 and 85.5 % of their overall BPRS-C score reduction at 6 weeks last observation carried forward. ER and ENR patients did not differ significantly regarding baseline demographic, illness and treatment variables. ER 2 (frequency = 68.1 %) and ER 3 (frequency = 65.2 %) significantly predicted UR and remission (p = 0.0044-p < 0.0001), with ER3 having more predictive power. A ≥ 20 % BPRS-C reduction threshold for ER had best predictive validity (area under the curve = 0.88-0.92). At 6 weeks, patients with ER had significantly greater improvements in BPRS-C, Clinical Global Impressions Improvement and Severity scores, greater cross-sectional remission and less all-cause discontinuation (p = 0.047-p < 0.0001). Adverse event profiles were similar in the ER and ENR groups. Adolescents with schizophrenia experienced the majority of symptomatic improvement early during olanzapine treatment. ER predicted UR and remission, with ER3 having best predictive power. A ≥ 20 % improvement threshold for defining ER was confirmed as a robust outcome indicator.

Differences in intracellular protein levels in monocytes and CD4+ lymphocytes between bipolar depressed patients and healthy controls: A pilot study with tyramine-based signal-amplified flow cytometry.

BACKGROUND: Molecular biomarkers for bipolar disorder (BD) that distinguish it from other manifestations of depressive symptoms remain unknown. The aim of this study was to determine if a very sensitive tyramine-based signal-amplification technology for flow cytometry (CellPrint™) could facilitate the identification of cell-specific analyte expression profiles of peripheral blood cells for bipolar depression (BPD) versus healthy controls (HCs). METHODS: The diagnosis of psychiatric disorders was ascertained with Mini International Neuropsychiatric Interview for DSM-5. Expression levels for eighteen protein analytes previously shown to be related to bipolar disorder were assessed with CellPrint™ in CD4+ T cells and monocytes of bipolar patients and HCs. Implementation of protein-protein interaction (PPI) network and pathway analysis was subsequently used to identify new analytes and pathways for subsequent interrogations. RESULTS: Fourteen drug-naïve or -free patients with bipolar I or II depression and 17 healthy controls (HCs) were enrolled. The most distinguishable changes in analyte expression based on t-tests included GSK3ß, HMGB1, IRS2, phospho-GSK3αß, phospho-RELA, and TSPO in CD4+ T cells and calmodulin, GSK3ß, IRS2, and phospho-HS1 in monocytes. Subsequent PPI and pathway analysis indicated that prolactin, leptin, BDNF, and interleukin-3 signal pathways were significantly different between bipolar patients and HCs. LIMITATION: The sample size of the study was small and 2 patients were on medications. CONCLUSION: In this pilot study, CellPrint™ was able to detect differences in cell-specific protein levels between BPD patients and HCs. A subsequent study including samples from patients with BPD, major depressive disorder, and HCs is warranted.