Evaluation of two doses (20 mL and 15 mL) of 0.25% bupivacaine in pericapsular nerve group block for patient positioning for sub-arachnoid block during hip fracture surgery: A single-centre, randomised comparative trial.

Background and Aims: Peri-capsular nerve group (PENG) block is a novel ultrasound (US)-guided technique to achieve regional analgesia in hip fractures. We compared the effectiveness of two doses of 0.25% bupivacaine (20 mL and 15 mL) in the US-guided PENG block for positioning patients for sub-arachnoid block (SAB) during hip fracture surgery. Methods: The randomised trial included 60 patients aged 40-90 years undergoing hip fracture surgery under SAB. PENG block was given by a US-guided approach with the patient in a supine position 20 minutes before SAB, and a total of 20 mL and 15 mL of bupivacaine (0.25%) were given in groups A and B, respectively. The primary outcome was to measure and compare the ease of positioning (EOP) of patients for the conduct of SAB. The secondary outcome was the pain assessment at rest and 15° leg raise position at baseline and 10 and 20 minutes post block using the verbal analogue scale (VAS). Continuous variables were compared using the t-test, and categorical variables were analysed using Pearson's Chi-square test or Fisher's exact test. Results: The mean (standard deviation) grade of EOP for SAB was significantly better in group A (2.47 (0.73) (95% confidence interval [CI]: 2.19-2.69)) than in group B (1.86 (0.62) (95% CI: 1.65-2.1)) (P = 0.001). The decrease in VAS scores was significantly higher in group A compared to group B at resting and 15° leg raise position at all-time points (P < 0.05). Conclusion: A dose of 20 mL of 0.25% bupivacaine shows better outcomes than 15 mL regarding the patient's positioning during the SAB.

Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Novel Nebulized Milrinone Formulation for the Treatment of Acute Heart Failure Requiring Inotropic Therapy: A Phase 1 Study.

BACKGROUND: Nonintravenous inotropic-delivery options are needed for patients with inotropic-dependent heart failure (HF) to reduce the costs, infections and thrombotic risks associated with chronic central venous catheters and home infusion services. METHODS: We developed a novel, concentrated formulation of nebulized milrinone for inhalation and evaluated the feasibility, safety and pharmacokinetic profile in a prospective, single-arm, phase I clinical trial. We enrolled 10 patients with stage D HF requiring inotropic therapy during a hospital admission for acute HF. Milrinone 60 mg/4 mL was inhaled via nebulization 3 times daily for 48 hours. The coprimary outcomes were adverse events and pharmacokinetic profiles of inhaled milrinone. Acute changes in hemodynamic parameters were secondary outcomes. RESULTS: A concentrated nebulized milrinone formulation was well tolerated, without hypotensive events, arrhythmias or inhalation-related adverse events requiring discontinuation. Nebulized milrinone produced serum concentrations in the goal therapeutic range with a median plasma milrinone trough concentration of 39 (17-66) ng/mL and a median peak concentration of 207 (134-293) ng/mL. There were no serious adverse events. From baseline to 24 hours, mean pulmonary artery saturation increased (60% ± 7%-65 ± 5%; P = 0.001), and mean cardiac index increased (2.0 ± 0.5 mL/min/1.73m2-2.5 ± 0.1 mL/min/1.73m2; P = 0.001) with nebulized milrinone. CONCLUSIONS: In a proof-of-concept study, a concentrated, nebulized milrinone formulation for inhalation was safe and produced therapeutic serum milrinone concentrations. Nebulized milrinone was associated with improved hemodynamic parameters of cardiac output in a population with advanced HF. These promising results require further investigation in a longer-term trial in patients with inotrope-dependent advanced HF.

Differences in Leukocyte Transcriptomes of Morbidly Obese Patients With High Output Heart Failure: A Pilot Study.

Background and Objectives: Heart failure is characterized by alterations of gene expression that provide insight into the underlying pathophysiologic mechanisms. However, obesity-related high output heart failure (HOHF) is a specific phenotype of heart failure that has not been studied using gene expression. Our aim in this study was to examine the variances in leukocyte transcriptomes of morbidly obese patients with HOHF. Methods: In this cross-sectional study, we applied stranded total RNA-sequencing to six patients with morbid obesity and HOHF and 6 patients with morbid obesity and non-HOHF. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and networks in these patients. Results: We found in patients with HOHF that there were 116 differentially expressed genes with upregulation of 114 genes and downregulation of 2 genes. The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. We identified GATA binding protein 1 as an upstream regulator and nuclear factor kappa-light-chain-enhancer of activated B cells associated network. Conclusions: We are the first to report the differential gene expression in patients with obesity-related HOHF and reveal the various pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Recruitment Strategies of a Decentralized Randomized Placebo Controlled Clinical Trial: The Canagliflozin Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF) Trial.

BACKGROUND: There has been growing Interest in patient-centered clinical trials using mobile technologies to reduce the need for in-person visits. The CHIEF-HF (Canagliflozin Impact on Health Status, Quality of Life and Functional Status in Heart Failure) trial was designed as a double-blind, randomized, fully decentralized clinical trial (DCT) that identified, consented, treated, and followed participants without any in-person visits. Patient-reported questionnaires were the primary outcome, which were collected by a mobile application. To inform future DCTs, we sought to describe the strategies used in successful trial recruitment. METHODS: This article describes the operational structure and novel strategies employed in a completely DCT by summarizing the recruitment, enrollment, engagement, retention, and follow-up processes used in the execution of the trial at 18 centers. RESULTS: A total of 18 sites contacted 130,832 potential participants, of which 2572 (2.0%) opened a hyperlink to the study website, completed a brief survey, and agreed to be contacted for potential inclusion. Of these, 1333 were eligible, and 658 consented; there were 182 screen failures, due primarily to baseline Kansas City Cardiomyopathy Questionnaire scores' not meeting inclusion criteria, resulting in 476 participants' being enrolled (18.5%). There was significant site-level variation in the number of patients invited (median = 2976; range 73-46,920) and in those agreeing to be contacted (median = 2.4%; range 0.05%-16.4%). At the site with the highest enrollment, patients contacted by electronic medical record portal messaging were more likely to opt into the study successfully than those contacted by e-mail alone (7.8% vs 4.4%). CONCLUSIONS: CHIEF-HF used a novel design and operational structure to test the efficacy of a therapeutic treatment, but marked variability across sites and strategies for recruiting participants was observed. This approach may be advantageous for clinical research across a broader range of therapeutic areas, but further optimization of recruitment efforts is warranted. REGISTRATION: NCT04252287 https://clinicaltrials.gov/ct2/show/NCT04252287.

Impact of Biopsy Proven Liver Fibrosis on Patients Undergoing Evaluation and Treatment for Advanced Heart Failure Surgical Therapies.

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p = 0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p = 0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p = 0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings.

Left Atrial to Coronary Sinus Shunting for Treatment of Symptomatic Heart Failure.

BACKGROUND: Heart failure (HF) is associated with both mortality and a significant decline in health status. Interatrial shunting is increasingly being investigated as a novel therapeutic option. OBJECTIVES: The ALT FLOW Early Feasibility Study was designed to evaluate the safety of the Edwards left atrial to coronary sinus APTURE Transcatheter Shunt System in patients with symptomatic HF. METHODS: A total of 18 centers enrolled patients with symptomatic HF with a pulmonary capillary wedge pressure >15 mm Hg at rest or 25 mm Hg during exercise. RESULTS: Between May 2018 and September 2022, 87 patients underwent attempted APTURE shunt implantation. Mean age was 71 years, and 53% were male. At baseline, mean left ventricular ejection fraction was 59% with 90% of the patients being in NYHA functional class III. Device success was achieved in 78 patients (90%), with no device occlusions or associated adverse events identified after implantation. The primary safety outcome occurred in only 2 patients (2.3%) at 30 days. At 6 months, health status improved: 67% of participants achieved NYHA functional class I to II status, with a 23-point improvement (P < 0.0001; 95% CI: 17-29 points) in the Kansas City Cardiomyopathy Questionnaire overall summary score. Also at 6 months, 20-W exercise pulmonary capillary wedge pressure was 7 mm Hg lower (P < 0.0001; 95% CI: -11 to -4 mm Hg) without change in right atrial pressure or other right heart function indices. CONCLUSIONS: In this single-arm experience, the APTURE Transcatheter Shunt System in patients with symptomatic HF was observed to be safe and resulted in reduction in pulmonary capillary wedge pressure and clinically meaningful improvements in HF symptoms and quality of life indices.

The impact of adjunctive aripiprazole on QT interval: A 12-week open label study in patients on olanzapine, clozapine or risperidone.

OBJECTIVE: To evaluate the effect of adjunct aripiprazole on QT of patients clinically stabilized on atypical antipsychotics. METHODS: The dataset was from an open-label 12-week prospective trial that evaluated adjunctive use of 5 mg/day of aripiprazole on metabolic profile in patients with schizophrenia, or schizoaffective disorder stabilized on olanzapine, clozapine, or risperidone. Bazett-corrected QT (QTc) was manually calculated from ECGs measured at baseline (before aripiprazole) and week 12, by two doctors blind to the diagnosis and atypical antipsychotic. The change in QTc (∆QTc: baseline QTc-week 12 QTc) and the number of participants in normal, borderline, prolonged, and pathological groups after 12 weeks were analyzed. RESULTS: Fifty-five participants, mean age of 39.3 (SD 8.2) years, were analyzed. The ∆QTc after 12 weeks was 5.9 ms (p = 0.143) for the whole sample; 16.4 ms (p = 0.762), 3.7 ms (p = 0.480) and 0.5 ms (p = 0.449), for the clozapine, risperidone and olanzapine group, respectively. There was no significant statistical difference comparing the change in QTc overall, and between atypical antipsychotic groups, when evaluating from baseline to endpoint. However, stratifying the sample based on sex-dependent QTc cut-offs showed a 45% decrease in abnormal QTc readings (p = 0.049) after aripiprazole initiation; 20 subjects had abnormal QTc at baseline, while only 11 subjects had abnormal QTc at 12 weeks. 25.5% of participants showed a reduction in at least one QTc severity group, while 65.5% had no change and 9.0% worsened in QTc group, after 12 weeks of adjunct aripiprazole. CONCLUSION: Low-dose adjunctive aripiprazole did not prolong QTc in patients stabilized on either olanzapine, risperidone, or clozapine. More controlled studies evaluating the QTc effect of adjunctive aripiprazole should be done to confirm and support these findings.

Prevalence and impact of peer victimisation among youth seeking treatment at a tertiary psychiatric institution in Singapore: a cross-sectional study.

BACKGROUND: Peer victimization is common among adolescents and leads to negative consequences. However, few studies have examined the extent of peer-victimization and its correlates among adolescent patients in a psychiatric setting. The current study aimed to examine the prevalence and correlates of peer victimisation among youth with mental illness and to examine its association with depressive symptoms and health-related quality of life (HRQOL). METHODS: A sample of 239 youths aged 15-24 years were recruited from the outpatient clinics of a tertiary psychiatric hospital in Singapore using convenience sampling. All participants were administered the Multidimensional Peer Victimisation Scale (MPVS), Short Form 12 (SF-12) questionnaire and the Patient Health Questionnaire-8 (PHQ-8). The effect of MPVS  total and subscores on depression scores, quality of life subscores and quality of life total scores were examined using multiple linear regression analyses. RESULTS: The majority of the patients reported that they had experienced at least one form of peer victimisation (95.8%, n = 229) during their school years. Higher levels of 'verbal victimisation', 'attacks on property' and higher total MPVS scores were significantly associated with lower social functioning; additionally, higher levels of 'verbal victimisation' were significantly associated with lower mental component summary scores in the quality of life assessment. Higher scores on all four subscales as well as higher total scores on the MPVS were significantly associated with more severe depressive symptoms. CONCLUSIONS: Given the high prevalence of peer victimisation in our sample and its associations with more severe depressive symptoms and lower quality of life, it is vital to implement interventions that prevent peer victimisation in educational and other social settings and to provide youth with strategies to more effectively manage instances of peer victimisation.

Comparative evaluation of three techniques for paramedian subarachnoid block: Point-of-care preprocedural ultrasound assisted, real-time ultrasound guided and landmark based.

Background and Aims: Preprocedural ultrasound (US) assisted and real-time US-guided subarachnoid block (SAB) are useful adjuncts for successful SAB. This study compared the feasibility and efficacy of real-time US-guided SAB with preprocedural US-assisted and landmark-based SAB using paramedian approach. Methods: The study enroled 150 American Society of Anesthesiologists I and II patients, aged 20-65 years, scheduled for lower limb orthopaedic surgery under SAB. In group L (n = 50), the patients underwent landmark-guided SAB utilising paramedian approach. In group P (n = 50), preprocedural US-assisted SAB was instituted and in group M (n = 50) real-time US-guided SAB was administered. The number of needle attempts for a successful SAB was the primary outcome. The secondary outcomes included successful SAB in first attempt, time taken to perform SAB and patients' satisfaction. Results: The number of attempts for SAB were (mean ± standard deviation = 1.05 ± 0.35, 1.00 ± 0.28, 1.03 ± 0.26) in groups L, P and M, respectively (P = 0.436). The SAB was successful in the first attempt in 82%, 82% and 80% in groups L, P and M, respectively (P = 0.207). The time taken for the successful SAB was more in group M as compared to groups L and P (groups L and M, P = 0.045 and groups P and M, P = 0.004). The patients' satisfaction score was comparable. Conclusion: Real-time US guidance for spinal anaesthesia resulted in needle attempts comparable to landmark and preprocedural US-assisted SAB in patients with a normal spine. The time required for the completion of the block was more in real-time US-guided SAB.

Comparative evaluation of airway dynamics in patients undergoing laparoscopic cholecystectomy under general anaesthesia with controlled ventilation using ProSeal laryngeal mask airway, I-Gel™ and Baska mask.

Background and Aims: TheProSeal™ laryngeal mask airway (PLMA) and I-Gel™ are second-generation supraglottic airway devices (SADs). The Baska mask is a SAD having a non-inflatable cuff with a tendency to increase the perilaryngeal seal with an increase in airway pressures. This study compared the efficacy of I-Gel™, PLMA and Baska mask with respect to airway dynamics in patients scheduled for laparoscopic surgeries under general anaesthesia (GA). Methods: Ninety patients, of American Society of Anesthesiologists physical status I and II, aged 20-65 years scheduled for laparoscopic cholecystectomy under GA were enroled. The patients were randomised into three groups: Group P (n = 30): airway secured using PLMA, Group I (n = 30): airway secured using I-Gel™ and Group B (n = 30): airway secured using Baska mask. The primary outcome was the change in dynamic compliance, and the secondary outcomes included insertion time, changes in peak inspiratory pressure (PIP) and oropharyngeal leak pressure (OLP) at different time intervals. Results: After insertion of the SADs, the dynamic compliance was highest in group B and least in the group I (p = 0.01). The maximum decrease in dynamic compliance was observed in group I. The insertion time for SAD placement was more in group P. The group B had least PIP as compared to groups P, I at insertion. After carboperitonium, groups P and B had comparable PIP, and group I had highest PIP (p = 0.001). OLP was highest in group B, whereas group I had least OLP. Conclusion: The airway dynamics are better maintained with Baska mask as compared to the PLMA and I-Gel™.

Effect of aripiprazole as an adjunct to atypical antipsychotics on weight and metabolic profile: a 12-week open-label trial.

BACKGROUND: Atypical antipsychotics are widely prescribed, yet have been associated with weight gain and metabolic syndrome. AIM: To study the effect of adjunct low-dose aripiprazole on weight and metabolic parameters of subjects on atypical antipsychotics (olanzapine, clozapine or risperidone). METHODS: The study was carried out as an open-label trial with a fixed dose of 5 mg aripiprazole added to the patient's current antipsychotic for 12 weeks. The primary outcome measure was mean change in weight, while secondary outcome measures included change in waist circumference; fasting blood glucose; HbA1c; triglycerides; total, HDL and LDL cholesterol levels; functioning; and neurocognition. RESULTS: For the overall study (n = 55), there was no significant effect of adjunct aripiprazole on the weight of the subjects. However, the clozapine group achieved significant weight loss (p = 0.002) and also had significant improvements in total cholesterol (p < 0.001), HDL (p = 0.016), LDL (p = 0.044) and triglyceride levels (p = 0.038). The olanzapine group had significant improvement in triglycerides (p = 0.001), and other metabolic parameters for this group showed improvement trends, but did not reach statistical significance. The risperidone group did not show any significant improvement in weight or metabolic parameters. CONCLUSIONS: The study adds support to the adjunctive use of aripiprazole to clozapine for weight loss and improvement in metabolic profile, and for reduction in cardiometabolic risk for patients on olanzapine. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02949752.

Right Heart Catheterization in Cardiogenic Shock Is Associated With Improved Outcomes: Insights From the Nationwide Readmissions Database.

Background The usefulness of right heart catherization (RHC) has long been debated, and thus, we aimed to study the real-world impact of the use of RHC in cardiogenic shock. Methods and Results In the Nationwide Readmissions Database using International Classification of Diseases, Tenth Revision (ICD-10), we identified 236 156 patient hospitalizations with cardiogenic shock between 2016 and 2017. We sought to evaluate the impact of RHC during index hospitalization on management strategies, complications, and outcomes as well as on 30-day readmission rate. A total 25 840 patients (9.6%) received RHC on index admission. The RHC group had significantly more comorbidities compared with the non-RHC group. During the index admission, the RHC group had lower death (25.8% versus 39.5%, P<0.001) and stroke rates (3.1% versus 3.4%, P<0.001). Thirty-day readmission rates (18.7% versus 19.7%, P=0.04) and death on readmission (7.9% versus 9.3%, P=0.03) were also lower in the RHC group. After adjustment, RHC was associated with lower index admission mortality (odds ratio, 0.69; 95% CI, 0.66-0.72), lower stroke rate (odds ratio, 0.81; 95% CI, 0.72-0.90), lower 30-day readmission (odds ratio, 0.83; 95% CI, 0.78-0.88), and higher left ventricular assist device implantations/orthotopic heart transplants (odds ratio, 6.05; 95% CI, 4.43-8.28) during rehospitalization. Results were not meaningfully different after excluding patients with cardiac arrest. Conclusions RHC use in cardiogenic shock is associated with improved outcomes and increased use of downstream advanced heart failure therapies. Further blinded randomized studies are required to confirm our findings.

Obstruction of the inferior vena cava following bicaval orthotopic heart transplantation: a case series.

BACKGROUND: Inferior vena cava (IVC) obstruction is a rare complication of orthotopic heart transplantation (OHT) and is unique to bicaval surgical technique. The clinical significance, diagnosis, complications, and management of post-operative IVC anastomotic obstruction have not been adequately described. CASE SUMMARY: Two patients with end-stage heart failure presented for bicaval OHT. Post-operative course was complicated with shock refractory to fluid resuscitation and inotropic/vasopressor support. Obstruction at the IVC-right atrial (RA) anastomosis was diagnosed on transoesophageal echocardiography (TOE), prompting emergent reoperation. In both cases, a large donor Eustachian valve was found to be restricting flow across the IVC-RA anastomosis. Resection of the valve resulted in relief of obstruction across the anastomosis and subsequent improvement in haemodynamics and clinical outcome. DISCUSSION: Presumably rare, we present two cases of IVC obstruction post-bicaval OHT. Inferior vena cava obstruction is an under-recognized cause of refractory hypotension and shock in the post-operative setting. Prompt recognition using TOE is crucial for immediate surgical correction and prevention of multi-organ failure. Obstruction can be caused by a thickened Eustachian valve caught in the suture line at the IVC anastomosis, which would require surgical resection.

Individual-fMRI-approaches reveal cerebellum and visual communities to be functionally connected in obsessive compulsive disorder.

There is significant interest in understanding the pathophysiology of Obsessive-Compulsive Disorder (OCD) using resting-state fMRI (rsfMRI). Previous studies acknowledge abnormalities within and beyond the fronto-striato-limbic circuit in OCD that require further clarifications. However, limited information could be inferred from the conventional way of investigating the functional connectivity differences between OCD and healthy controls. Here, we identified altered brain organization in patients with OCD by applying individual-based approaches to maximize the identification of underlying network-based features specific to the OCD group. rsfMRI of 20 patients with OCD and 22 controls were preprocessed, and individual-fMRI-subspace was derived for each subject within each group. We evaluated group differences in functional connectivity using individual-fMRI-subspace and established its advantage over conventional-fMRI methodology. We applied prediction-based approaches to highlight the group differences by evaluating the differences in functional connections that predicted the clinical scores (namely, the Obsessive-Compulsive Inventory-Revised (OCI-R) and Hamilton Anxiety Rating Scale). Then, we explored the brain network organization of both groups by estimating the subject-specific communities within each group. Lastly, we evaluated associations between the inter-individual variation of nodes in the communities to clinical measures using linear regression. Functional connectivity analysis using individual-fMRI-subspace detected 83 connections that were different between OCD and control groups, compared to none found using conventional-fMRI methodology. Connectome-based prediction analysis did not show significant overlap between the two groups in the functional connections that predicted the clinical scores. This suggests that the functional architecture in patients with OCD may be different compared to controls. Seven communities were found in both groups. Interestingly, within the OCD group but not controls, we observed functional connectivity between cerebellar and visual regions, and lack of connectivity between striato-limbic and frontal areas. Inter-individual variations in the community-size of these two communities were also associated with the OCI-R score (p < .005). Due to our small sample size, we further validated our results by (i) accounting for head motion, (ii) applying global signal regression (GSR) in data processing, and (iii) using an alternate atlas for parcellation. While the main results were consistently observed with accounting for head motion and using another atlas, the key findings were not reproduced with GSR application. The study demonstrated the existence of disconnectedness in fronto-striato-limbic community and connectedness between cerebellar and visual areas in OCD patients, which was also related to the clinical symptomatology of OCD.

Understanding Obesity-Related High Output Heart Failure and Its Implications.

Morbid obesity remains most common cause of high output failure. The prevalence of the obesity is growing when two-thirds of American adults already are overweight or obese. Obesity is the risk factor for heart disease and eventually leads to heart failure. High output heart failure is common in obese patients and is characterized by high cardiac output, decreased systemic vascular resistance, and increased oxygen consumption. It often occurs in patients with chronic severe anemia, hyperthyroidism, pregnancy, arterial-venous fistulas, and liver disease. However, the pathogenesis of obesity-related high output heart failure is not fully understood. The clinical management of obesity-related high output heart failure follows conventional heart failure regimens due to lack of specific clinical recommendations. This article reviews the possible pathophysiological mechanisms and causes that contribute to obesity-related high output heart failure. This review also focuses on the implications for clinical practice and future research involved with omics technologies to explore possible molecular pathways associated with obesity-related high output heart failure.

Negative affect moderates the link between body image dissatisfaction and disordered eating among psychiatric outpatients in a multi-ethnic Asian setting.

INTRODUCTION: Few studies have investigated the factors that affect the relationship between body image dissatisfaction and disordered eating locally. Our study aimed to investigate the moderating effects of depression and anxiety levels on the body dissatisfaction-disordered eating link in Singapore. METHODS: A total of 329 participants completed a set of questionnaires that included various scales pertaining to eating behaviours, body image, psychological distress and quality of life. RESULTS: Participants were diagnosed with schizophrenia (47.4%), depression (46.8%) and substance use disorders (5.8%). Moderation analyses revealed that depression (F [9, 251] = 18.50, p < 0.001, R2 change = 0.021) and anxiety levels (F [9, 268] = 19.54, p < 0.001, R2 change = 0.014) were significant moderators of the relationship between body dissatisfaction and disordered eating scores. Subsequent multivariate linear logistic regression analyses showed that high disordered eating scores were significantly associated with lower physical (F [8, 273] = 9.59, R2 = 0.22, p < 0.001, ß = -0.27, p < 0.001), psychological (F [8, 273] = 10.51, R2 = 0.49, p < 0.001, ß = -0.27, p < 0.001), social (F [8, 256] = 6.78, R2 = 0.18, p < 0.001, ß = -0.18, p = 0.004) and environment (F [8, 273] = 5.29, R2 = 0.13, p < 0.001, ß = -0.19, p = 0.001) quality of life scores after controlling for sociodemographic covariates. CONCLUSION: Greater effort should be dedicated to the screening of disordered eating behaviours in psychiatric outpatients presenting with greater psychological distress.

PROVIDE-HF primary results: Patient-Reported Outcomes inVestigation following Initiation of Drug therapy with Entresto (sacubitril/valsartan) in heart failure.

BACKGROUND: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) versus enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice. METHODS: PROVIDE-HF was a prospective study within a national research network (Patient-Centered Outcomes Research Network) of HFrEF outpatients recently initiated on sacubitril/valsartan versus controls with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change. The primary end point was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12 weeks. Other end points included responder analyses: ≥5-point and ≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting. RESULTS: Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and N-terminal pro-brain natriuretic peptide 1083 pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference +4.76; P = .027) and were more likely to have a ≥5-point and ≥20-point response (all P < .05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI -0.89 to 9.99; P = .101) and likelihood of ≥5-point increase (odds ratio 1.55; 95% CI: 0.84-2.86; P = .16); ≥20-point increase remained statistically significant (odds ratio 3.79; 95% CI 1.47-9.73; P = .006). CONCLUSIONS: In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change, the between-group difference in the primary end point, mean KCCQ change at 12 weeks was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-point improvement in KCCQ at 12 weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice.

Potential use of ubiquinol and d-ribose in patients with heart failure with preserved ejection fraction.

•Manuscript Highlights.•HFpEF is associated with reduced ATP production in the myocardium.•Ubiquinol and d-ribose both contribute to the generation of myocardial ATP.•Both ubiquinol and d-ribose are being studied as supplemental treatments for patients with HFpEF.