Abstract: Disclosed herein are methods of improving cognitive function in a patient as measured by, for example, improvement in score on a validated scale that measures cognitive function, such as the Behavior Rating Inventory of Executive Function (BRIEF), by administering the test to a patient and obtaining a pre-treatment test score, treating the patient with fenfluramine or its pharmaceutically acceptable salt, and after treatment, re-administering the test of cognitive function to the patient and obtaining a post-treatment score, to allow observation of an improvement in the test score. In some embodiments, the patient is also being treated for the symptoms of epilepsy.

Abstract: A method of treating symptoms of a subtype of epilepsy, e.g., Dravet syndrome, in a patient diagnosed with a subtype of epilepsy, by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient. Also provided are compositions and kits finding use in practicing embodiments of the methods.

Abstract: A method of treating symptoms of Lennox-Gastaut syndrome in a patient diagnosed with Lennox-Gastaut syndrome, by administering an effective dose of fenfluramine to that patient over a period of time sufficient to reduce or completely eliminate seizures in the patient. The fenfluramine may be administering in an oral liquid formulation on a daily basis of 0.7 mg/kg/day, over a period of weeks until seizures are reduced by 25% or more, 50% or more, 75% or more.

Abstract: The present disclosure provides methods of treating and/or preventing symptoms of epilepsy or epileptic encephalopathy where fenfluramine or a pharmaceutically acceptable salt thereof is or has been administered to a patient or population of patients. The present disclosure encompasses a recognition of contraindication of fenfluramine and certain serotonin receptor agonists, particularly a CNS penetrant serotonin receptor antagonist. The present disclosure provides methods where said patients being administered fenfluramine have been warned against co-administration of certain serotonin receptor antagonists, are not co-administered a serotonin receptor antagonist, and/or in which co-administration of a serotonin-receptor antagonist is discontinued.

Abstract: Disclosed herein are methods of improving cognitive function in a patient as measured by, for example, improvement in score on a validated scale that measures cognitive function, such as the Behavior Rating Inventory of Executive Function (BRIEF), by administering the test to a patient and obtaining a pre-treatment test score, treating the patient with fenfluramine or its pharmaceutically acceptable salt, and after treatment, re-administering the test of cognitive function to the patient and obtaining a post-treatment score, to allow observation of an improvement in the test score. In some embodiments, the patient is also being treated for the symptoms of epilepsy.

Abstract: Provided herein is a method of treating a selected patient population, wherein the patient population is selected based on a determination that the patients have previously been non-responsive when treated with cannabidiol. In some embodiments, the method comprises selecting the patient based on a previously failed treatment with cannabidiol, based on lack of efficacy or tolerability. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. The method comprises identifying a population of patients diagnosed with Dravet syndrome who were found previously to have been non-responsive when treated with cannabidiol.

Abstract: A method of treating symptoms of a subtype of epilepsy, e.g., Dravet syndrome, in a patient diagnosed with a subtype of epilepsy, by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient. Also provided are compositions and kits finding use in practicing embodiments of the methods.

Abstract: A method of treating symptoms of a subtype of epilepsy, e.g., Dravet syndrome, in a patient diagnosed with a subtype of epilepsy, by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient. Also provided are compositions and kits finding use in practicing embodiments of the methods.

Abstract: Provided herein is a method of treating a selected patient population, wherein the patient population is selected based on a determination that the patients have previously been non-responsive when treated with cannabidiol. In some embodiments, the method comprises selecting the patient based on a previously failed treatment with cannabidiol, based on lack of efficacy or tolerability. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. The method comprises identifying a population of patients diagnosed with Dravet syndrome who were found previously to have been non-responsive when treated with cannabidiol.

Abstract: A method of treating symptoms of a subtype of epilepsy, e.g., Dravet syndrome, in a patient diagnosed with a subtype of epilepsy, by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient. Also provided are compositions and kits finding use in practicing embodiments of the methods.

Abstract: Provided herein is a method of treating a selected patient population, wherein the patient population is selected based on a determination that the patients have previously been non-responsive when treated with stiripentol. In some embodiments, the method comprises selecting the patient based on a previously failed treatment with stiripentol, based on lack of efficacy or tolerability. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. The method comprises identifying a population of patients diagnosed with Dravet syndrome who were found previously to have been non-responsive when treated with stiripentol.

Abstract: Disclosed herein are methods of improving cognitive function in a patient as measured by, for example, improvement in score on a validated scale that measures cognitive function, such as the Behavior Rating Inventory of Executive Function (BRIEF), by administering the test to a patient and obtaining a pre-treatment test score, treating the patient with fenfluramine or its pharmaceutically acceptable salt, and after treatment, re-administering the test of cognitive function to the patient and obtaining a post-treatment score, to allow observation of an improvement in the test score. In some embodiments, the patient is also being treated for the symptoms of epilepsy.

Abstract: A method of reducing dosing of a concomitant medication in a human patient diagnosed with Dravet syndrome, by administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of days while reducing the dose of one or more concomitant anti-seizure or anti-epileptic drugs (AEDs) from baseline and thereby decreasing the amount of medication given to the patient while reducing adverse side effects. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided.

Abstract: A cutting tool includes a pocket with a top wall, a bottom wall, a side wall and a rear wall. The cutting tool has an insert cartridge and a wedge clamp. The threaded member exerts a force vector in a radial direction when threaded into the wedge clamp to place the cutting tool in a locked condition, and the wedge clamp exerts a force vector into the body of the cutting tool radially inward of an adjacent pocket, thereby reducing deflection of the adjacent pocket when the cutting tool is placed in the locked condition.

Abstract: A wedge clamp includes a top wall, a bottom wall, a front wall, a rear wall opposite the front wall, and a fluid port traversing from the front wall to the rear wall. The fluid port has a front opening and a rear opening to allow cooling fluid to pass therethrough. In one embodiment, the front opening is a rounded isosceles trapezoid in shape with a pair of parallel substantially planar side walls of different length and a pair of arcuate side walls connecting the pair of planar side walls. The rear opening has a greater surface area proximate the rear wall and a smaller surface area proximate the front opening, resulting in a funnel-shaped opening to cause an increase in velocity of the cooling fluid passing through the fluid port.

Abstract: A wedge clamp includes a top wall, a bottom wall, a front wall, a rear wall opposite the front wall, and a fluid port traversing from the front wall to the rear wall. The fluid port has a front opening and a rear opening to allow cooling fluid to pass therethrough. In one embodiment, the front opening is a rounded isosceles trapezoid in shape with a pair of parallel substantially planar side walls of different length and a pair of arcuate side walls connecting the pair of planar side walls. The rear opening has a greater surface area proximate the rear wall and a smaller surface area proximate the front opening, resulting in a funnel-shaped opening to cause an increase in velocity of the cooling fluid passing through the fluid port.

Abstract: A cutting tool includes a pocket with a top wall, a bottom wall, a side wall and a rear wall. The cutting tool has an insert cartridge and a wedge clamp. The threaded member exerts a force vector in a radial direction when threaded into the wedge clamp to place the cutting tool in a locked condition, and the wedge clamp exerts a force vector into the body of the cutting tool radially inward of an adjacent pocket, thereby reducing deflection of the adjacent pocket when the cutting tool is placed in the locked condition.

Abstract: A cutting tool includes a pocket with a top wall, a bottom wall, a side wall and a rear wall. The cutting tool has a wedge clamping system that includes an insert cartridge and a clamp wedge. The insert cartridge includes a recess that interacts with a protrusion on the clamp wedge in such a way that the clamp wedge exerts a force vector in an axial direction when the clamp wedge is threaded into the pocket, thereby reducing deflection of an adjacent pocket of the cutting tool when the cutting tool is placed in a locked condition.

Abstract: A cutting tool includes a pocket with a top wall, a bottom wall, a first side wall for engaging an insert cartridge, a second side wall, a first rear wall, and a second rear wall. The top wall and the bottom wall are formed at a negative angle with respect to each other to provide a closed pocket design that resists centrifugal forces when the insert cartridge and the clamp wedge are in a locked condition during a cutting operation.

Abstract: A cutting tool includes a body having a forward end and a rearward end. The forward end includes an insert-receiving pocket with a threaded hole having a center axis. The cutting tool further includes a cutting insert with a countersunk bore with a center axis. The cutting tool includes an error proofing feature for preventing the cutting insert to be properly mounted in an insert-receiving pocket when an offset distance between the center axis of the threaded hole of the insert-receiving pocket and the center axis of the countersunk bore of the cutting insert is greater than a predetermined percentage of the outer diameter of the threaded screw.