ABSTRACT
Sub-estrus is a condition when buffaloes do not display behavioural estrus signs, despite being in estrus and causes a delay in conception and increases the service period. The present study describes the effect of synthetic prostaglandin (PGF2α) alone and in combination with trace minerals on the follicular and corpus luteum (CL) dynamics, serum estradiol (E2) and progesterone (P4) concentration correlating estrus response and pregnancy outcome in sub-estrus buffaloes during the breeding season. A total of 50 sub-estrus buffaloes, identified through ultrasonography (USG) examination, were randomly allocated into three groups, viz. T1 (Synthetic PGF2α, Inj. Cloprostenol 500 µg, i.m, n = 17), T2 (Synthetic PGF2α + Trace mineral supplementation, Inj. Stimvet 1 mL/100 kg body weight, i.m., n = 17) and control (untreated; n = 16). Following treatment, 100% of sub-estrus buffaloes were induced estrus in the T1 and T2 groups, while only 18.75% were induced in the control. The CL diameter and serum P4 concentration were significantly lower at post-treatment, whereas the pre-ovulatory follicle (POF) size and serum E2 concentration were significantly higher in the T1 and T2 groups as compared to the control (p < .05). The buffaloes of the T2 group had a greater proportion of moderate intensities estrus than those of T1. Moreover, the proportion of buffaloes conceived in the T1 and T2 were 41.2% and 52.95%, respectively. The larger POF diameter and higher serum E2 concentration were associated with intense intensity estrus and higher conception rate (66.7%) in sub-estrus buffaloes. Similarly, CL regression rate, POF size and serum E2 concentration were relatively higher in the buffaloes conceived as compared to those not conceived. It is concluded that synthetic PGF2α in combination with trace minerals induces moderate to intense intensities estrus in a greater proportion of sub-estrus buffaloes and increases the conception rate during the breeding season. Moreover, behavioural estrus attributes correlating follicle and luteal morphometry, serum E2 and P4 concentration could be used to optimise the breeding time for augmenting the conception rate in sub-estrus buffaloes.
Subject(s)
Buffaloes , Corpus Luteum , Dinoprost , Estradiol , Estrus Synchronization , Estrus , Ovarian Follicle , Progesterone , Animals , Buffaloes/physiology , Female , Pregnancy , Dinoprost/pharmacology , Dinoprost/administration & dosage , Progesterone/blood , Progesterone/pharmacology , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Estradiol/blood , Estradiol/pharmacology , Estradiol/administration & dosage , Estrus/drug effects , Estrus/physiology , Corpus Luteum/drug effects , Corpus Luteum/physiology , Trace Elements/pharmacology , Trace Elements/administration & dosage , Cloprostenol/pharmacology , Cloprostenol/administration & dosageABSTRACT
A 9-year-old boy presented to the emergency department after noticing a painless mass on the right testicle during self-examination in the shower. On physical examination, both testes were mobile and painless, with the right testis twice as big as the left and exhibiting palpable resistance. Sonographic examination revealed a uniformly demarcated mass with a ventral protrusion on the right testis. Tumor markers and blood tests were normal. The testis was exposed inguinally and the tumor was enucleated, which revealed a dermoid cyst. The testicle could thus be preserved. Final histology confirmed complete excision of the benign dermoid cyst (mature teratoma). As testicular tumors in prepubertal boys are rare and usually benign, an organ-preserving procedure with perioperative biopsy should be aimed for. Due to the rarity of studies on recurrence after organ-preserving testicular surgery, we recommended regular ultrasound examinations during the first year after surgery, followed by annual examinations for a period of 5 years.
ABSTRACT
The design, development, and successful implementation of pop-up Langmuir probes installed in the water-cooled divertor of W7-X are described. The probes are controlled by drive coils (actuators) installed behind the divertor plates. These drive coils make use of the magnetic field in W7-X to move the probe tips into and out of the plasma. The drive coils were installed in the vacuum vessel after extensively testing the durability of the coils and analyzing the criteria for safe operation. The probe design is carefully tailored for each of the 36 probe tips in order to be suitable for the different magnetic field configurations used in W7-X and ensure that the probes do not present leading edges to the magnetic flux tubes. An electronic bridge circuit is used for measurement to compensate for the effects of signal propagation time on the long cable lengths used. The diagnostic is integrated with the segment control of W7-X for automated operation and control of the diagnostic. The evaluation of the results from the plasma operation is presented after accounting for appropriate sheath expansion for negative bias voltage on the probes.
ABSTRACT
INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.
Subject(s)
Rifampin , Thrombocytopenia , Humans , Rifampin/adverse effects , Antitubercular Agents/adverse effects , Pyrazinamide/therapeutic use , Isoniazid/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapyABSTRACT
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
Subject(s)
Heart Failure , Myocardial Infarction , Rats , Mice , Humans , Animals , Swine , Myocardial Infarction/pathology , Myocardial Infarction/therapy , Heart Failure/metabolism , Myocytes, Cardiac/metabolism , Ventricular Function, Left , Macrophages/metabolismABSTRACT
Metal, carbon and conducting polymer nanoparticles are blended with organic phase change materials (PCMs) to enhance the thermal conductivity, heat storage ability, thermal stability and optical property. However, the existing nanoparticle are expensive and need to be handle with high caution during operation as well during disposal owing to its toxicity. Subsequently handling of solid waste and the disposal of organic PCM after longevity usage are of utmost concern and are less exposed. Henceforth, the current research presents a new dimension of exploration by green synthesized nanoparticles from a thorny shrub of an invasive weed named Prosopis Juliflora (PJ) which is a agro based solid waste. Subsequently, the research is indented to decide the concentration of green synthesized nanoparticle for effective heat transfer rate of organic PCM (Tm = 35-40 °C & Hm = 145 J/g). Furthermore, an in-depth understanding on the kinetic and thermodynamic profile of degradation mechanism involved in disposal of PCM after usage via Coats and Redfern technique is exhibited. Engaging a two-step method, we fuse the green synthesized nanomaterial with PCM to obtain nanocomposite PCM. On experimental evaluation, thermal conductivity of the developed nanocomposite (PCM + PJ) increases by 63.8% (0.282 W/mâ K to 0.462 W/mâ K) with 0.8 wt% green synthesized nanomaterial owing to the uniform distribution of nanoparticle within PCM matrix thereby contributing to bridging thermal networks. Subsequently, PCM and PCM + PJ nanocomposites are tested using thermogravimetric analyzer at different heating rates (05 °C/min; 10 °C/min; 15 °C/min & 20 °C/min) to analyze the decomposition kinetic reaction. The kinetic and thermodynamic profile of degradation mechanism involved in disposal of PCM and its nanocomposite of PCM + PJ provides insight on thermal parameters to be considered on large scale operation and to understand the complex nature of the chemical reactions. Adopting thirteen different chemical mechanism model under Coats and Redfern method we determine the reaction mechanism; kinetic parameter like activation energy (Ea) & pre-exponential factor (A) and thermodynamic parameter like change in enthalpy (ΔH), change in Gibbs free energy (ΔG) and change in entropy (ΔS). Dispersion of PJ nanomaterial with PCM reduces Ea from 370.82 kJ/mol-1 to 342.54 kJ/mol-1 (7.7% reduction), as the developed nanomaterial is enriched in carbon element and exhibits a catalytic effect for breakdown reaction. Corresponding, value of ΔG for PCM and PCM + PJ sample within heating rates of 05-20 °C/min varies between 168.95 and 41.611 kJ/mol-1. The current research will unbolt new works with focus on exploring the pyrolysis behaviour of phase change materials and its nanocomposite used for energy storage applications. This work also provides insights on the disposal of PCM which is an organic solid waste. The thermo-kinetic profile will help to investigate and predict the optimum heating rate and temperature range for conversion of micro-scale pyrolysis to commercial scale process.
Subject(s)
Nanocomposites , Prosopis , Solid Waste , Thermogravimetry , Thermodynamics , CarbonABSTRACT
Cellulose nanofibers (CNFs) were employed in the aqueous electrodeposition of nickel and cadmium for battery metal recycling. The electrowinning of mixed Ni-Cd metal ion recycling solutions demonstrated that cadmium with a purity of over 99% could be selectively extracted while leaving the nickel in the solution. Two types of CNFs were evaluated: negatively charged CNFs (a-CNF) obtained through acid hydrolysis (-75 µeq. g-1) and positively charged CNFs (q-CNF) functionalized with quaternary ammonium groups (+85 µeq. g-1). The inclusion of CNFs in the Ni-Cd electrolytes induced growth of cm-sized dendrites in conditions where dendrites were otherwise not observed, or increased the degree of dendritic growth when it was already present to a lesser extent. The augmented dendritic growth correlated with an increase in deposition yields of up to 30%. Additionally, it facilitated the formation of easily detachable dendritic structures, enabling more efficient processing on a large scale and enhancing the recovery of the toxic cadmium metal. Regardless of the charged nature of the CNFs, both negatively and positively charged CNFs led to a significant formation of protruding cadmium dendrites. When deposited separately, dendritic growth and increased deposition yields remained consistent for the cadmium metal. However, dendrites were not observed during the deposition of nickel; instead, uniformly deposited layers were formed, albeit at lower yields (20%), when positively charged CNFs were present. This paper explores the potential of utilizing cellulose and its derivatives as the world's largest biomass resource to enhance battery metal recycling processes.
ABSTRACT
BACKGROUND: Streptococcus pneumoniae is leading bacterial cause of community acquired pneumonia and according to World Health Organization, responsible for 14 % death in children. There is effective vaccine available against Streptococcus pneumoniae. Hence the primary objective was to isolate Streptococcus pneumoniae from nasopharyngeal swabs in children aged 2-59 months with and without community acquired pneumonia and to assess their serotypes. METHODS: This case-control study was conducted in tertiary teaching institutes in northern India. Hospitalized children, aged 2-59 months, with World Health Organization-defined community acquired pneumonia were included as cases. Age matched healthy controls were recruited from immunization clinic. All enrolments were done after written informed parental consent. Nasopharyngeal swabs were taken from both cases and controls, and were cultured on 5 % sheep blood agar with gentamycin plate for growth of Streptococcus pneumoniae and incubated in a jar at 370 for 18-24 hrs. Quellung reaction test was used for serotyping. RESULTS: From March 2017 to December 2022, 2693 children (1910 cases and 783 controls), were recruited. The median age of cases was 7 months and controls 10 months. Almost all the cases had received antibiotics prior to hospitalization. Streptococcus pneumoniae positivity in nasopharyngeal swab was 8.1 % in cases, of which 56.8 % were vaccine serotypes and 23.6 % in controls, of which 37.8 % were vaccine serotypes. Adjusted odds ratio of isolating vaccine serotypes among cases as compared to controls was 1.77 (95 % CI, 1.09-2.88). CONCLUSION: Streptococcus pneumoniae isolation from nasopharyngeal was found to be in lower proportion in cases as compared to control, though colonization with vaccine serotypes was higher in cases as compared to control. Therefore, pneumococcal vaccine coverage must be increased to prevent community acquired pneumonia.
Subject(s)
Community-Acquired Infections , Pneumococcal Infections , Pneumonia , Humans , Child , Infant , Streptococcus pneumoniae , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/microbiology , Serogroup , Case-Control Studies , Carrier State/microbiology , Pneumococcal Vaccines , Nasopharynx/microbiology , India/epidemiologyABSTRACT
Background Self-administration of investigational intranasal L-type calcium channel blocker etripamil during paroxysmal supraventricular tachycardia (PSVT) appeared safe and well-tolerated in the phase 3 NODE-301 (Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia) trial of adults with sustained atrioventricular nodal-dependent PSVT. The NODE-302 open-label extension further characterized etripamil safety and efficacy. Methods and Results Eligible patients were monitored via self-applied cardiac monitoring system for 5 hours after etripamil self-administration. The primary end point was time-to-conversion of positively adjudicated PSVT to sinus rhythm after etripamil treatment. Probability of conversion to sinus rhythm was reported via Kaplan-Meier plot. Adverse events were based on self-reported symptoms and clinical evaluations. Among 169 patients enrolled, 105 self-administered etripamil ≥1 time for perceived PSVT (median [range], 232 [8-584] days' follow-up). Probability of conversion within 30 minutes of etripamil was 60.2% (median time to conversion, 15.5 minutes) among 188 PSVT episodes (92 patients) positively adjudicated as atrioventricular nodal dependent by independent ECG analysis. Among 40 patients who self-treated 2 episodes, 75% had a significantly consistent response by 30 minutes; 9 did not convert on either episode, and 21 converted on both episodes (χ2=8.09; P=0.0045). Forty-five of 105 patients (42.9%) had ≥1 treatment-emergent adverse event, generally transient and mild-to-moderate, including nasal congestion (14.3%), nasal discomfort (14.3%), or rhinorrhea (12.4%). No serious cardiac safety events were observed within 24 hours of etripamil. Conclusions In this extension study, investigational etripamil nasal spray was well tolerated for self-treating recurrent episodes of PSVT without medical supervision. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635996.
Subject(s)
Tachycardia, Paroxysmal , Tachycardia, Supraventricular , Tachycardia, Ventricular , Adult , Humans , Atrioventricular Node , Nasal Sprays , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/drug therapy , Clinical Trials, Phase III as TopicSubject(s)
Rectal Fistula , Humans , Rectal Fistula/surgery , Rectum/surgery , Perineum/surgery , Anal Canal/surgeryABSTRACT
Polymer networks and biological tissues are often swollen by a solvent such that their properties emerge from a coupling between swelling and elastic stress. This poroelastic coupling becomes particularly intricate in wetting, adhesion, and creasing, for which sharp folds appear that can even lead to phase separation. Here, we resolve the singular nature of poroelastic surface folds and determine the solvent distribution in the vicinity of the fold tip. Surprisingly, two opposite scenarios emerge depending on the angle of the fold. In obtuse folds such as creases, it is found that the solvent is completely expelled near the crease tip, according to a nontrivial spatial distribution. For wetting ridges with acute fold angles, the solvent migration is reversed as compared to creasing, and the degree of swelling is maximal at the fold tip. We discuss how our poroelastic fold analysis offers an explanation for phase separation, fracture, and contact angle hysteresis.
Subject(s)
Solvents , WettabilityABSTRACT
Our primary goal here is to demonstrate that innovative analytics of aneurismal velocities, named velocity-informatics, enhances intracranial aneurysm (IA) rupture status prediction. 3D computer models were generated using imaging data from 112 subjects harboring anterior IAs (4-25 mm; 44 ruptured and 68 unruptured). Computational fluid dynamics simulations and geometrical analyses were performed. Then, computed 3D velocity vector fields within the IA dome were processed for velocity-informatics. Four machine learning methods (support vector machine, random forest, generalized linear model, and GLM with Lasso or elastic net regularization) were employed to assess the merits of the proposed velocity-informatics. All 4 ML methods consistently showed that, with velocity-informatics metrics, the area under the curve and prediction accuracy both improved by approximately 0.03. Overall, with velocity-informatics, the support vector machine's prediction was most promising: an AUC of 0.86 and total accuracy of 77%, with 60% and 88% of ruptured and unruptured IAs being correctly identified, respectively.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Computer Simulation , Informatics , HemodynamicsABSTRACT
Carbon nanotubes (CNTs), are safe, biocompatible, bioactive, and biodegradable materials, and have sparked a lot of attention due to their unique characteristics in a variety of applications, including medical and dye industries, paper manufacturing and water purification. CNTs also have a strong film-forming potential, permitting them to be widely employed in constructing sensors and biosensors. This review concentrates on the application of CNT-based nanocomposites in the production of electrochemical sensors and biosensors. It emphasizes the synthesis and optimization of CNT-based sensors for a range of applications and outlines the benefits of using CNTs for biomolecule immobilization. In addition, the use of molecularly imprinted polymer (MIP)-CNTs in the production of electrochemical sensors is also discussed. The challenges faced by the current CNTs-based sensors, along with some the future perspectives and their future opportunities, are also briefly explained in this paper.
RESEARCH HIGHLIGHTSReview article on advanced Carbon-Nanotube (CNT)-based sensors and biosensors.The advantages of using CNTs for biomolecule immobilization and in electrochemical sensors and biosensors are discussed.The use of molecularly imprinted polymer-CNT nanocomposites in the production of electrochemical sensors is also discussed.Several characteristics, including sensor manufacturing, linear ranges, detection limits, and repeatability, are described in depth.Challenges and prospects using CNTs modified sensors have been proposed.
ABSTRACT
BACKGROUND: We aimed to determine whether the addition of yoga to a regular exercise training regimen improves cardiometabolic risk profile. METHODS: Sixty individuals with diagnosed hypertension (≥ 140/90 mm Hg for 3 measurements on different days) were recruited in an exercise training program. In addition to aerobic exercise training, participants were randomised into either a yoga or a stretching control group. Participants, over the 3-month intervention regimen, performed 15 minutes of either yoga or stretching in addition to 30 minutes of aerobic exercise training 5 times weekly. Blood pressure, anthropometry, high-sensitivity C-reactive protein (hs-CRP), glucose, and lipid levels as well as the Framingham and Reynolds Risk Scores were measured. RESULTS: At baseline, there was no difference in age, sex, smoking status, body mass index, blood pressure, heart rate, lipid and glucose levels, and Framingham Risk Score between groups. After the 3-month intervention period, the decrement in systolic and diastolic blood pressures (before vs after stretching: 126 ± 11/76 ± 7 vs 122 ± 11/73 ± 8 mm Hg; before vs after yoga: 130 ± 13/77 ± 10 vs 119 ± 11/69 ± 8 mm Hg) and heart rate was greater (P < 0.001) in the yoga group, with similar decreases in lipid, glucose, and hs-CRP levels and Framingham Risk Score in both groups. Reynolds Risk Score decrement was higher in the yoga vs the control group (absolute reduction -1.2 ± 1.2 vs -0.6 ± 0.8; relative reduction 13.2 ± 11.8% vs 9.3 ± 6.5%; P < 0.05). CONCLUSION: In patients with hypertension, the practice of yoga incorporated in a 3-month exercise training program was associated with greater improvement in resting blood pressure and heart rate and Reynolds Risk Score compared with stretching.
Subject(s)
Cardiovascular Diseases , Hypertension , Yoga , Humans , Cardiovascular Diseases/prevention & control , C-Reactive Protein , Risk Factors , Hypertension/therapy , Exercise/physiology , Heart Disease Risk Factors , Lipids , GlucoseABSTRACT
Although applying machine learning (ML) algorithms to rupture status assessment of intracranial aneurysms (IA) has yielded promising results, the opaqueness of some ML methods has limited their clinical translation. We presented the first explainability comparison of six commonly used ML algorithms: multivariate logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), multi-layer perceptron neural network (MLPNN), and Bayesian additive regression trees (BART). A total of 112 IAs with known rupture status were selected for this study. The ML-based classification used two anatomical features, nine hemodynamic parameters, and thirteen morphologic variables. We utilized permutation feature importance, local interpretable model-agnostic explanations (LIME), and SHapley Additive exPlanations (SHAP) algorithms to explain and analyze 6 Ml algorithms. All models performed comparably: LR area under the curve (AUC) was 0.71; SVM AUC was 0.76; RF AUC was 0.73; XGBoost AUC was 0.78; MLPNN AUC was 0.73; BART AUC was 0.73. Our interpretability analysis demonstrated consistent results across all the methods; i.e., the utility of the top 12 features was broadly consistent. Furthermore, contributions of 9 important features (aneurysm area, aneurysm location, aneurysm type, wall shear stress maximum during systole, ostium area, the size ratio between aneurysm width, (parent) vessel diameter, one standard deviation among time-averaged low shear area, and one standard deviation of temporally averaged low shear area less than 0.4 Pa) were nearly the same. This research suggested that ML classifiers can provide explainable predictions consistent with general domain knowledge concerning IA rupture. With the improved understanding of ML algorithms, clinicians' trust in ML algorithms will be enhanced, accelerating their clinical translation.
Subject(s)
Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnosis , Bayes Theorem , Neural Networks, Computer , Algorithms , Machine LearningABSTRACT
Streptococcus pneumoniae (SP) infections cause morbidity and mortality among children worldwide. Hence India introduced 13-valent pneumococcal conjugate vaccine (PCV-13) in 2017 in a phased manner. The primary objective of this study was to assess the proportion of healthy children having nasopharyngeal colonization (NP) with SP. Secondary objective was to determine prevalent serotype of SP among the PCV13 vaccinated and non-vaccinated children. This cross-sectional study was conducted in 4 hospitals of Lucknow District, Northern India. Three hundred healthy children (2-59 months) were recruited between July and August 2019 from vaccination-clinics of hospitals. NP specimen was cultured using 5% sheep blood agar plate containing gentamicin. Pneumococcal isolates were identified by optochin sensitivity and bile-solubility tests. Serotyping was done using Quellung Method. Of the 300 healthy children, 56.7% (170/300) were males and 59.3% (181/300) had received at least one dose of PCV13 vaccine. The NP carriage rate of SP among healthy children was 37.7% (113/300). Vaccine serotypes were found in 33.3% (22/66) in PCV vaccinated children and 48.9% (23/47) in non-vaccinated children (p 0.09). Common vaccine serotypes that isolated were: 18C, 19A, 19F, 23F, 3, 4, 6A, 6B, 9 V. Thus more than one-third of healthy children had NP colonization with SP. Adjusting for age, there was a trend for significant reduction in vaccine serotypes in the NP with one doses versus two or more doses (ptrend = 0.04).
Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Male , Animals , Sheep , Female , Serogroup , Cross-Sectional Studies , Carrier State , Pneumococcal Infections/prevention & control , IndiaABSTRACT
BACKGROUND: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT. METHODS: NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration. RESULTS: NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events. CONCLUSIONS: Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03464019.