Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.

Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.

An Effective Hybrid Deep Learning Model for Single-Channel EEG-Based Subject-Independent Drowsiness Recognition.

Nowadays, road accidents pose a severe risk in cases of sleep disorders. We proposed a novel hybrid deep-learning model for detecting drowsiness to address this issue. The proposed model combines the strengths of discrete wavelet long short-term memory (DWLSTM) and convolutional neural networks (CNN) models to classify single-channel electroencephalogram (EEG) signals. Baseline models such as support vector machine (SVM), linear discriminant analysis (LDA), back propagation neural networks (BPNN), CNN, and CNN merged with LSTM (CNN+LSTM) did not fully utilize the time sequence information. Our proposed model incorporates a majority voting between LSTM layers integrated with discrete wavelet transform (DWT) and the CNN model fed with spectrograms as images. The features extracted from sub-bands generated by DWT can provide more informative & discriminating than using the raw EEG signal. Similarly, spectrogram images fed to CNN learn the specific patterns and features with different levels of drowsiness. Furthermore, the proposed model outperformed state-of-the-art deep learning techniques and conventional baseline methods, achieving an average accuracy of 74.62%, 77.76% (using rounding, F1-score maximization approach respectively for generating labels) on 11 subjects for leave-one-out subject method. It achieved high accuracy while maintaining relatively shorter training and testing times, making it more desirable for quicker drowsiness detection. The performance metrics (accuracy, precision, recall, F1-score) are evaluated after 100 randomized tests along with a 95% confidence interval for classification. Additionally, we validated the mean accuracies from five types of wavelet families, including daubechis, symlet, bi-orthogonal, coiflets, and haar, merged with LSTM layers.

Safety of catheter ablation in patients with recently implanted cardiac implantable electronic device: A 5-year experience.

INTRODUCTION: Catheter ablation (CA) can interfere with cardiac implantable electronic device (CIED) function. The safety of CA in the 1st year after CIED implantation/lead revision is uncertain. METHODS: This single center, retrospective cohort included patients who underwent CA between 2012 and 2017 and had a CIED implant/lead revision within the preceding year. We assessed the frequency of device/lead malfunctions in this population. RESULTS: We identified 1810 CAs in patients between 2012 and 2017, with 170 CAs in 163 patients within a year of a CIED implant/lead revision. Mean age 68 ± 12 years (68% men). Time between the CIED procedure and CA was 158 ± 99 days. The CA procedures included AF ablation (n = 57, 34%), AV node ablation (n = 40, 24%), SVT ablation (n = 37, 22%), and PVC/VT ablations (n = 36, 21%). The cumulative frequency of lead dislodgement, significant CIED dysfunction, and/or CIED-related infection following CA was (n = 1/170, 0.6%). There was a single atrial lead dislodgement (0.6%). There were no instances of power-on-reset or CIED-related infection. Following CA, there was no significant difference in RA or RV lead sensing (p = 0.52 and 0.84 respectively) or thresholds (p = 0.94 and 0.17 respectively). The RA impedance slightly decreased post-CA from 474 ± 80 Ohms to 460 ± 73 Ohms (p = 0.002), as did the RV impedance (from 515 ± 111 Ohms to 497 ± 98 Ohms, p < 0.0001). CONCLUSIONS: CA can be performed within 1 year following CIED implantation/lead revision with a low risk of CIED/lead malfunction or lead dislodgement. The ideal time to perform CA after a CIED remains uncertain.

Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. METHODS: We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus <90%. RESULTS: We included 75 patients (age 74 ± 11 years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and <90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90% versus <90% (15.7 ± 9.3% vs. 7.5 ± 9.6%, p = .003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p = .005 and .02, respectively). CONCLUSION: A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.

Lipid peroxidation and stress-induced signalling molecules in systemic resistance mediated by azelaic acid/AZELAIC ACID INDUCED1: signal initiation and propagation.

Systemic acquired resistance protects plants against a broad spectrum of secondary infections by pathogens. A crucial compound involved in the systemic spread of the threat information after primary pathogen infection is the C9 oxylipin azelaic acid (AZA), a breakdown product of unsaturated C18 fatty acids. AZA is generated during lipid peroxidation in the plastids and accumulates in response to various abiotic and biotic stresses. AZA stimulates the expression of AZELAIC ACID INDUCED1 (AZI1), and a pool of AZI1 accumulates in the plastid envelope in association with AZA. AZA and AZI1 utilize the symplastic pathway to travel through the plasmodesmata to neighbouring cells to induce systemic stress resistance responses in distal tissues. Here, we describe the synthesis, travel and function of AZA and AZI1 and discuss open questions of signal initiation and propagation.

COVID-19 associated multisystemic mucormycosis from India: a multicentric retrospective study on clinical profile, predisposing factors, cumulative mortality and factors affecting outcome.

PURPOSE: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). METHODS: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. RESULTS: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. CONCLUSION: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.

Multicenter assessment of the outcomes of subcutaneous ICD implantation in patients with prior or future sternotomy.

BACKGROUND: The subcutaneous ICD (S-ICD) is a viable alternative to transvenous ICD and avoids intravascular complications in patients without a pacing indication. The outcomes of S-ICD implantation are uncertain in patients with prior sternotomy. OBJECTIVE: We aim to compare the implant techniques and outcomes with S-ICD implantation in patients with and without prior sternotomy. METHODS: Multicenter retrospective cohort study including adult patients with an S-ICD implanted between January 2014 and June 2020. Outcomes were compared between patients with and without prior sternotomy. RESULTS: Among the 212 patients (49 ± 15 years old, 43% women, BMI 30 ± 8 kg/m2 , 68% primary prevention, 30% ischemic cardiomyopathy, LVEF median 30% IQR 25%-45%) who underwent S-ICD implantation, 47 (22%) had a prior sternotomy. There was no difference in the sensing vector (57% vs. 53% primary, p = 0.55), laterality of the S-ICD lead to the sternum (94% vs. 96% leftward, p = 0.54), or the defibrillation threshold (65 ± 1.4 J vs. 65 ± 0.8 J, p = 0.76) with versus without prior sternotomy. The frequency of 30-day complications was similar with and without prior sternotomy (n = 3/47 vs. n = 15/165, 6% vs. 9%, p = 0.56). Over a median follow-up of 28 months (IQR 10-49 months), the frequency of inappropriate shocks was similar between those with and without prior sternotomy (n = 3/47 and n = 16/165, 6% vs. 10%, p = 0.58). CONCLUSION: Implantation of an S-ICD in patients with prior sternotomy is safe with a similar risk of 30-day complications and inappropriate ICD shocks as patients without prior sternotomy.

Efficacy of Repetitive Transcranial Magnetic Stimulation on Comorbid Anxiety and Depression Symptoms in Obsessive-Compulsive Disorder: A Meta-Analysis of Randomized Sham-Controlled Trials.

OBJECTIVE: To systematically evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in reducing comorbid anxiety and depressive symptoms in patients with obsessive-compulsive disorder (OCD). METHODS: Three electronic databases were searched for randomized, sham-controlled clinical trials evaluating rTMS for the treatment of OCD. Hedge's g was calculated as the effect size for anxiety/depression symptom severity (primary outcome) and OCD severity (secondary outcome). Subgroup analyses and meta-regression analyses were carried out to evaluate the most promising target and whether a reduction in OCD severity moderates the change in anxiety or depression scores. RESULTS: Twenty studies (n = 688) were included in the meta-analysis. rTMS had small-medium effect size on OCD (Hedge's g = 0.43; 95% confidence interval [CI]: [0.20, 0.65]; P < 0.001), anxiety (Hedge's g = 0.3; 95% CI: [0.11, 0.48]; P = 0.001) and depression (Hedge's g = 0.24; 95% CI: [0.07, 0.40]; P = 0.003) symptoms. Subgroup analysis showed that protocols targeting dorsolateral prefrontal cortex (DLPFC) were effective for 3 outcome measures. The change in anxiety, but not depression severity, was moderated by a change in OCD symptom scores. However, the findings are uncertain as a majority of the studies had some concerns or a high risk of bias. CONCLUSIONS: Active rTMS protocol targeting DLPFC is effective in reducing the comorbid anxiety/depression symptoms along with OCD severity. The antidepressant effect is not moderated by the anti-obsessive effect of rTMS.

Quantification and comparison of salivary neutrophils in periodontal health and disease.

Background: Neutrophils continuously migrate into the oral cavity from various sources like gingival crevicular fluid and saliva both in health and in inflammation. The migration of the neutrophils into the various tissues and into the oral cavity occurs when the host microbial interplay tips the balance favoring the initiation of the inflammatory and immune reactions which depending on the amount of the microbial load results in the development of acute and chronic infections in the susceptible host. Aim: The present study was designed to quantify and compare the oral salivary neutrophil levels in patients with gingivitis and chronic and aggressive periodontitis as well as in healthy controls, before and after scaling and root planing (SRP) and to compare the difference within the selected study groups. Materials and Methods: Forty subjects were classified into four groups, that is, healthy controls, gingivitis, and chronic and aggressive periodontitis. Oral rinse samples were collected using Hank's balanced salt solution from each patient before and after phase I periodontal therapy. Cells in the rinse samples were stained with Acridine orange, and neutrophil counts were carried out using a fluorescence microscope and a hemocytometer. Results: Baseline oral salivary neutrophil levels were maximum in the chronic periodontitis group followed by the aggressive group and then the gingivitis group. Oral salivary neutrophil levels also positively correlated to probing pocket depth, plaque index, calculus index, and gingival index in all four study groups. Maximum reduction in the oral salivary neutrophil levels after phase I periodontal therapy was seen in the gingivitis group. Conclusion: From our study, we conclude that the oral salivary neutrophil levels decreased significantly after SRP. Estimation of changes in the oral salivary neutrophil levels has the potential to aid in monitoring treatment outcomes. Thus, it suggests that it could be used as a simple, noninvasive laboratory technique to monitor the periodontal status and disease progression.

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Electromagnetic interference from left ventricular assist devices detected in patients with implantable cardioverter-defibrillators.

INTRODUCTION: Electromagnetic interference (EMI) from left ventricular assist devices (LVADs) can cause implantable cardioverter-defibrillator (ICD) oversensing. We sought to assess the frequency of inappropriate shocks/oversensing due to LVAD-related EMI and prospectively compare integrated (IB) versus dedicated bipolar (DB) sensing in patients with LVADs. METHODS: Single-center study in LVAD patients with Medtronic or Abbott ICDs between September 2017 and March 2020. We excluded patients that were pacemaker dependent. Measurements were obtained of IB and DB sensing and noise to calculate a signal-to-noise ratio (SNR). Device checks were reviewed to assess appropriate and inappropriate sensing events. RESULTS: Forty patients (age 52 ± 14 years, 75% men, 38% ischemic cardiomyopathy) were included with the median time between LVAD implantation and enrollment of 6.7 months (2.3, 11.4 months). LVAD subtypes included: HeartWare (n = 22, 55%), Heartmate II (n = 10, 25%), and Heartmate III (n = 8, 20%). Over a follow-up duration of 21.6 ± 12.9 months after LVAD implantation, 5% of patients (n = 2) had oversensing of EMI from the LVAD (both with HeartWare LVADs and Abbott ICDs) at 4 days and 10.8 months after LVAD implantation. Both patients underwent adjustment of ventricular sensing with resolution of oversensing and no further events over 5 and 15 months of further follow-up. The SNR was similar between IB and DB sensing (50 [29-67] and 57 [41-69], p = 0.89). CONCLUSION: ICD oversensing of EMI from LVADs is infrequent and can be managed with reprogramming the sensitivity. There was no significant difference in the R-wave SNR with IB versus DB ICD leads.

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

UltraSound Axillary Vein Access (USAA): Learning curve and randomized comparison to traditional venous access for cardiac device implantation.

BACKGROUND: Many techniques exist for venous access (VA) during cardiac implantable electronic device (CIED) implantation. OBJECTIVE: We sought to evaluate the learning curve with ultrasound (US) guided axillary vein access (USAA). METHODS: Single-center prospective randomized controlled trial of patients undergoing CIED implantation. Patients were randomized in a 2:1 fashion to USAA versus conventional VA techniques. The primary outcomes were the success rates, VA times and 30-day complication rates. RESULTS: The study included 100 patients (age 68 ± 14 years, BMI 27 ± 4 kg/m2 ). USAA was successful in 66/70 implants (94%). Initial attempts at conventional VA included 47% axillary (n = 14), 30% (n = 9) cephalic, and 23% (n = 7) subclavian. The median access time was longer for USAA than conventional access (8.3 IQR 4.2-15.3 min vs. 5.2 IQR 3.4-8.6 min, p = .009). Among the five inexperienced USAA implanters, there was a significant improvement in median access time from first to last tertile of USAA implants (17.0 IQR 7.0-21.0 min to 8.6 IQR 4.5-10.8 min, p = .038). The experienced USAA implanter had similar access times with USAA compared with conventional access (4.0 IQR 3.3-4.7 min vs. 5.2 IQR 3.4-8.6 min, p = .15). Venograms were less common with USAA than conventional access (2% vs. 33%, p < .0001). The 30-day complication rate was similar with USAA (n = 4/70, 6%) versus conventional (n = 3/30, 10%, p = .44). CONCLUSION: Although the success rate with USAA was high, there was a significant learning curve. Once experienced with the USAA technique, there is the potential for reduced complications without adding to the procedure duration.

Impact of ultra-conservative ICD programming in patients with LVADs: Avoiding potentially unnecessary tachy-therapies.

BACKGROUND: Patients with left ventricular assist devices (LVAD) often tolerate ventricular arrhythmias (VA). We aim to assess the frequency and outcomes of ICD therapies averted by ultraconservative ICD programming (UCP) in LVAD patients. METHODS: This single center, retrospective cohort study included patients with LVADs and ICDs implanted from 2015 to 2019 that had UCP. The aim for UCP was to maximally delay VA treatments and maximize anti-tachycardia pacing (ATP) prior to ICD shocks. VA events were reviewed after UCP and evaluated under prior conservative programming to assess for potentially averted events (that would have resulted in either ATP or defibrillation with prior programming). RESULTS: Fifty patients were included in the study with follow-up of median 16 ± 10.2 months after UCP. The median time from LVAD implantation to reprogramming was 7 days (IQR 5-9 days). Fourteen patients (28%) had potentially averted VA events that would have been treated with their prior ICD programming (82 total events, median two events per patient, IQR 1-10 events). Treated VA events occurred in 15 patients (30%). Eleven of the 14 patients with potentially averted VAs had treated events as well. Only one patient reported definitive symptoms of self-limited "dizziness" during a potentially averted event that did not result in hospitalization. No patients died of complications from or needed emergent care/hospitalization due a potentially averted VA. CONCLUSIONS: UCP in LVAD patients likely prevented unnecessary VA treatments in many patients with minimal reported symptoms during these potentially averted events. Prospective studies are necessary to confirm these findings.

Diagnosis and Severity Evaluation of Ulnar Neuropathy at the Elbow by Ultrasonography: A Case-Control Study.

Background: Traditional diagnostic techniques such as clinical examination and electrodiagnosis are less sensitive in diagnosing ulnar neuropathy at the elbow (UNE). Ultrasonography (USG) is increasingly being used to diagnose UNE. However, clinical applicability is limited by the lack of uniformity in the previous studies. Therefore, we aimed to study in the Indian patients the diagnostic utility of the ulnar nerve cross-sectional area (CSA) and a novel parameter-entrapment index (EI) in UNE measured by USG and to find if both these parameters correlate with the electrodiagnostic severity. Methods: This retrospective casecontrol study included 28 patients (36 nerves) of UNE and 12 (24 nerves) age- and gender-matched healthy controls. Electrodiagnostic severity was graded using the Padua classification. USG was performed in both groups, and CSA was measured at the medial epicondyle (ME) and 5 cm proximally and distally. EI was calculated by multiplying the ratio of CSA above ME over CSA at ME by 100. Best cutoffs were derived by the receiver operating characteristic curve analysis. Results: UNE group had significantly higher CSA at all three locations and lower EI than the control group. CSA at ME ≥9.7 mm2 and EI ≤61.5 has sensitivity and specificity of 88.9%/87.5% and 72.2%/79.2%, respectively. There was no significant difference in CSA and EI between nonsevere and severe UNE groups. Conclusion: CSA at ME and EI have good sensitivity and specificity in diagnosing UNE. However, they cannot differentiate nonsevere from severe UNE.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Co-administration of zinc phthalocyanine and quercetin via hybrid nanoparticles for augmented photodynamic therapy.

The photodynamic anticancer activity of a photosensitizer can be further increased by co-administration of a flavonoid. However, this requires that both molecules must be effectively accumulated at the tumor site. Hence, in order to enhance the activity of zinc phthalocyanine (ZnPc, photosensitizer), it was co-encapsulated with quercetin (QC, flavonoid) in lipid polymer hybrid nanoparticles (LPNs) developed using biodegradable & biocompatible materials and prepared using a single-step nanoprecipitation technique. High stability and cellular uptake, sustained release, inherent fluorescence, of ZnPC were observed after encapsulation in the LPNs, which also showed a higher cytotoxic effect in breast carcinoma cells (MCF-7) compared to photodynamic therapy (PDT) alone. In vivo studies in tumor-bearing Sprague Dawley rats demonstrated that the LPNs were able to deliver ZnPc and QC to the tumor site with minimal systemic toxicity and increased antitumor effect. Overall, the photodynamic effect of ZnPc was synergized by QC. This strategy could be highly beneficial for cancer management in the future while nullifying the side effects of chemotherapy.