Patent Publication Number: US-2022219882-A1

Title: System and method for reliably dispensing pre-packaged pharmaceuticals

Description:
RELATED APPLICATIONS 
     The present application is a continuation of and claims priority to U.S. patent application Ser. No. 15/710,503, filed Sep. 20, 2017, which claims priority from and the benefit of U.S. Provisional Patent Application No. 62/398,652, filed Sep. 23, 2016, the disclosure of each of which is hereby incorporated herein in its entirety. 
    
    
     FIELD 
     The present invention relates generally to devices for dispensing items, and more specifically, to systems and methods for assisting patients in taking prescription medication, in accordance with a desired regimen prescribed by a physician. 
     BACKGROUND 
     Even with the present day advances in medicines and healthcare, people, especially senior citizens and disabled persons, face a number of challenges in taking care of their health at home. Typically there is little assistance for the ‘home patient’ in managing multiple prescriptions and inventories of medicines. According to some estimates, the average senior person is prescribed up to thirteen different oral medications that must be taken correctly at different times each day. These medications are typically delivered in bulk supply and must be sorted, managed, and then taken correctly by the individual, leading to numerous errors and omissions, including failing to take the medications at the prescribed time, taking the medications at the wrong time and/or in the incorrect amount, misusing the medications, fatally combining the medications with other medications, under-using the medications, or over-using the medications, collectively referred to “non-compliance.” 
     The costs associated with such non-compliance are higher than the costs associated with a number of major illnesses. Studies have shown that 10% of admissions to regular hospitals in the United States are due to non-compliance, at a cost of $15 billion a year, and 30% of hospital admissions for people over the age of 65 are directly caused by non-compliance. Non-compliance causes 125,000 deaths per year—twice as many as are caused by auto accidents. Twenty-three percent to forty percent of nursing home admissions are due to noncompliance and inability to take medications at home unsupervised. According to estimates, nearly half of all prescriptions are taken incorrectly, contributing to prolonged or additional illness. People who miss doses need 3 times as many doctor visits as others and face an average of $2,000 more in medical costs per year. 
     The fact that the aging population continues to grow, combined with the steady increase in the average number of medications prescribed per person, indicates that these issues will continue to compound along with the associated costs. 
     In order to ensure that medications are taken at the proper time, a variety of devices, such as the ones disclosed in U.S. Pat. Nos. 4,361,408 and 7,944,342, have been devised to generate audible and/or visible prompting or alarm signals that remind a patient or his caretaker to administer the correct dosages at the correct time. Various dispensing devices have also been developed to help patients adhere to their medication protocols or regimens. Examples of such devices are provided in U.S. Pat. Nos. 8,060,246 and 8,196,774. 
     There may be a need for a simple yet efficient system that not only reminds a patient to take medication according to their prescribed schedule, but also provides the required medicines to the patient in a simple, convenient and reliable manner. 
     SUMMARY 
     As a first aspect, embodiments of the invention are directed to a cartridge for a pharmaceutical dispensing system, comprising: a frame with opposed sidewalls and having a floor and a base, the floor positioned above the base and including a routing hole; and a plurality of individually sealed pouches of pharmaceuticals to be dispensed, the pouches formed as an elongate strip, the strip of pouches being wound into a roll over an axle member that extends between the sidewalls of the frame. A free end of the strip extends through the routing hole in the floor and between the floor and the base. A flapper baffle extends from the floor to separate the roll from the free end of the strip. 
     As a second aspect, embodiments of the invention are directed to a pharmaceutical dispensing system comprising: a housing with an opening, the housing having an internal compartment and a delivery outlet; a drive unit mounted in the housing; and a cartridge as described above. 
     As a third aspect, embodiments of the invention are directed to a method of loading a pharmaceutical dispensing system, comprising the steps of: 
     (a) providing a cartridge as described above; 
     (b) providing a pharmaceutical dispensing system comprising:
         a housing with an opening, the housing having an internal compartment and a delivery outlet; and   a drive unit mounted in the housing; and       

     (c) inserting the cartridge into the housing through the opening in the housing and into the compartment of the housing such that the free end of the strip is positioned adjacent the drive unit so that operation of the drive unit conveys the free end of the strip toward the delivery outlet. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other features and advantages of the present invention will be appreciated, as they become better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein: 
         FIG. 1  is a schematic diagram that illustrates an overall arrangement that is utilized by the present system for dispensing medicines; 
         FIG. 2  is a top view of an exemplary pouch of medication, attached to a strip of pouches in a roll, to be dispensed by a dispensing system according to embodiments of the invention; 
         FIG. 3A  is a front perspective view of an exemplary cartridge: 
         FIG. 3B  is a rear perspective view of the cartridge of  FIG. 3A ; 
         FIG. 4  is a perspective view of a dispensing unit according to embodiments of the invention; 
         FIG. 5A  is a front perspective view of the cover of a cartridge for use with the dispensing unit of  FIG. 4 ; 
         FIG. 5B  is a rear perspective view of the cover of the cartridge of  FIG. 5A ; 
         FIG. 6  is a perspective view of a cartridge frame loaded with a strip of medication pouches for use with the cartridge of  FIG. 3A ; 
         FIG. 7  is a front perspective view of a cartridge frame of  FIG. 6  without the cylinder; 
         FIG. 8  is a perspective view of two modular halves of the cylinder portion of the cartridge of  FIG. 3A ; 
         FIG. 9  is a perspective view of the halves of  FIG. 8  in an assembled condition; 
         FIG. 10  is a front perspective view of the cartridge frame and cylinder of the cartridge of  FIG. 3A ; 
         FIG. 11A  is a rear perspective view of the cartridge frame of  FIG. 7 ; 
         FIG. 11B  is a top view of the cartridge frame of  FIG. 11A  showing the floor of the cartridge: 
         FIG. 12A  is a section view of the cartridge frame of  FIG. 10 ; 
         FIG. 12B  is a section view of the cartridge frame of  FIG. 10  with a medication strip loaded on the cylinder and following its path through the frame; 
         FIG. 13  is a top view of the base of the cartridge of  FIG. 3A ; 
         FIG. 14  is a bottom view of the base of the cartridge of  FIG. 3A ; 
         FIG. 15  is perspective view of the flattened form of the cartridge frame of  FIG. 3A ; 
         FIG. 16  is a perspective view of the opposite side of the flattened form of the cartridge frame of  FIG. 15 ; 
         FIG. 17A  is a top perspective view of the dispensing unit of  FIG. 4  with the top door removed to show the compartment into which the cartridge fits; 
         FIG. 17B  is a top perspective view of the dispensing unit of  FIG. 17A , showing the other side of the compartment; 
         FIG. 17C  is a top view of the dispensing unit of  FIG. 17A  showing the bottom of the compartment; 
         FIG. 18  is a perspective section view of the dispenser of  FIG. 17A  with a cartridge loaded in it; 
         FIG. 19A  is a side section view of the dispenser of  FIG. 17A  with a cartridge loaded in it, showing the dispensing path of the medication strip; 
         FIG. 19B  is a side section view of the dispenser of  FIG. 17A  with a cartridge loaded in it, showing the exception path of a medication pouch; 
         FIG. 20  is a flow chart of the operational flow of the dispensing unit of  FIG. 4 : 
         FIG. 21  is a chart of the mechanical flow of the dispensing unit of  FIG. 4 ; 
         FIG. 22  is a chart of the manual dispense flow of the dispensing unit of  FIG. 4 ; 
         FIG. 23  is a flow chart of the validation of cartridge data during the cartridge load process of the dispensing unit of  FIG. 4 ; 
         FIGS. 24A, 24B and 25  are a flow chart of the validation of pouch data during the pouch dispensing process of the dispensing unit of  FIG. 4 ; 
         FIG. 26  is a top view of an exemplary pouch of medication to be dispensed by a dispensing system according to embodiments of the invention; 
         FIG. 27A  is a perspective view of a cartridge according to alternative embodiments of the invention; 
         FIG. 27B  is a perspective view of one half of the cartridge of  FIG. 27A  with the free-spinning hub shown therein; 
         FIG. 27C  is an enlarged reverse partial perspective view of the cartridge of  FIG. 27A  installed in a dispenser, with a spring for maintaining the pouches in position; 
         FIG. 27D  is an enlarged partial perspective view of the cartridge of  FIG. 27A  in a dispenser with a spring release mechanism for releasing the spring shown in  FIG. 27C ; 
         FIG. 28  is a perspective view of a portion of the dispenser of  FIG. 27C  with a cartridge of  FIG. 27A  loaded therein, showing an embodiment for placement of cameras to read the barcodes on the cartridge and pouches; 
         FIG. 29A  is a perspective view of the door locking mechanism of the dispenser of  FIG. 32  shown in the unlocked position; 
         FIG. 29B  is a perspective view of the door locking mechanism of  FIG. 29A  shown in the locked position; 
         FIG. 29C  is a perspective view of the cam of the door locking mechanism of  FIG. 29A  shown in the locked position; 
         FIG. 29D  is a perspective view of the cam of the door locking mechanism of  FIG. 29A  shown in the unlocked position; 
         FIG. 29E  is a perspective view of the door sensor of the door locking mechanism of  FIG. 29A : 
         FIG. 30A  is a partial perspective view of the inside of the dispenser door, loaded with a cartridge and the door closed, showing a spring-loaded bracket located on the inside of the door; 
         FIG. 30B  is a partial perspective view of the spring loaded bracket of  FIG. 30A  without a cartridge; 
         FIG. 31  is a perspective view of a cartridge according to additional embodiments of the invention: 
         FIG. 32  is a perspective view of a dispenser according to additional embodiments of the invention; 
         FIG. 33  is a perspective view of a cartridge cover of the cartridge of  FIG. 31 ; 
         FIG. 34  is a perspective view of a cartridge frame of the cartridge of  FIG. 31  with a pouch strip mounted therein; 
         FIG. 35  is a perspective view of the cartridge frame of  FIG. 34  without the hub/axle and pouch strip; 
         FIG. 36  is a perspective view of the free-spinning hub/axle of the cartridge frame of  FIG. 34 ; 
         FIG. 37  is a perspective view of the cartridge frame of  FIG. 34  without the pouch strip: 
         FIG. 38  is a top view of the cartridge frame of  FIG. 34 ; 
         FIG. 39  is a section view of the cartridge frame of  FIG. 34 , including the pouch strip and hub; 
         FIG. 40  is a bottom section view of the cartridge frame of  FIG. 34 ; and 
         FIG. 41  is a section view of the dispenser of  FIG. 32 , without a cartridge loaded therein. 
         FIG. 42A  is a partial perspective view of the cartridge frame with a flapper baffle included therein according to alternative embodiments of the invention. 
         FIG. 42B  is a partial side view of the cartridge frame and flapper baffle of  FIG. 42A . 
         FIG. 42C  is a partial perspective view of the cartridge frame with a flapper baffle included therein according to further embodiments of the invention. 
         FIG. 42D  is a partial side view of the cartridge frame and flapper baffle included therein according to still further embodiments of the invention. 
     
    
    
     DETAILED DESCRIPTION 
     The present specification discloses a method and system that assists people at home in taking medication according their prescribed regimen. In one embodiment, the present system reminds a patient to take their medication at the scheduled time, and also provides all the required medicines to be taken at that time in one or more convenient pouches. The system may be useful for patients taking medication on a daily schedule, patients participating in a clinical study, or anyone needing to take medications, supplements, etc. on a regular, consistent basis. 
     In one embodiment, the present system allows a user to simply drop a cartridge into a receptacle and have the medicine pouches with the appropriate medication dosages dispensed at the requisite times, without the need for any programming, installation, aligning, fitting or other work. In one embodiment, the cartridge contains pouches of medicines spooled around a cartridge cylinder, which is used to dispense pouches as and when required. The cartridge is typically mailed or otherwise delivered to or received by the person on a regular basis. 
     The present invention will now be described more fully hereinafter, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In the drawings, like numbers refer to like elements throughout. Thicknesses and dimensions of some components may be exaggerated for clarity. 
     Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. 
     The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. As used herein the expression “and/or” includes any and all combinations of one or more of the associated listed items. 
     In addition, spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature&#39;s relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. 
     Well-known functions or constructions may not be described in detail for brevity and/or clarity. 
     As described above, the invention relates generally to a system and process for dispensing pharmaceuticals. A high level process incorporating the invention is described generally with reference to  FIG. 1 . The process begins with a medicine supplier  102 , such as a pharmacy, that receives and processes prescriptions for a patient in any suitable manner. In one embodiment, the prescriptions are sent to the medicine supplier  102  through a network, computer system, a cloud or any other communication mechanism  104 , or they may originate through a paper prescription provided to the medicine supplier by the patient, as received from their physician or via a phone call or fax from a physician. Such prescriptions also may be refills of previously filled prescriptions for the patient. The medicine supplier packages the medications in pouches, according to the time that the medication is to be taken by the patient. Exemplary systems for the packaging of medications in pouches are described in U.S. Pat. Nos. 5,671,592 and 6,202,385, and are herein incorporated by reference in their entirety. Medications that are to be taken at the same time are packaged in the same pouch and each pouch is assigned a time of administration, in accordance with the prescription(s). It should be noted that more than one pouch may be required to package all the medications for a given administration time. For the sake of simplicity, a single pouch will be referred to herein, but should be understood to include one or more pouches, as necessary to accommodate a patient&#39;s medication regimen. U.S. Pat. No. 8,311,853 describes an exemplary system that can be used to assign administration times for groups of medications and align the refills for the prescriptions to facilitate the refill process for all medications packaged in the pouches for a single patient and is herein incorporated by reference in its entirety. In one embodiment, a series of pouches are connected together to form a strip, such that a pouch may be removed from the strip, one at a time, through a cutting, tearing, or other removal mechanism. Pouches are ordered in the strip in chronological order, based on the date and time of administration. In one embodiment, a strip of medication pouches is loaded in a cartridge  200  (as shown in  FIG. 6 ), and sent to the user&#39;s home  108 . In one embodiment, the cartridge  200  is sent periodically to the patient, and the periodicity is based on the patient&#39;s preference—such as every week, every ten days, or once per month. The cartridge  200  contains medicines sufficient to last the predetermined period of time. 
     At the patient&#39;s home, the cartridge of packaged prescription medication is loaded by the patient into a dispensing unit  110 . In one embodiment, the cartridge  200  is designed to automatically self-align with the dispensing unit  110 , without the need for any installation work on the user&#39;s part. Therefore, the user may simply drop the cartridge  200  into the housing of dispensing unit  110  and apply sufficient pressure (either manually or via a mechanism in the dispenser) to cause the cartridge to seat in place (some embodiments employ a snapping action). Once the cartridge  200  seats in place, it is automatically aligned with the dispensing mechanisms and capable of dispensing medicines without further work, adjustment, or installation by the user as described in more detail below. 
       FIG. 2  illustrates exemplary pouches of medication, with each pouch containing the medicines to be taken by the patient at a particular time of administration, in accordance with their prescription(s). Individual pouches of medicine  112  are connected together to form a medication strip  114 , which is loaded into a cartridge  200 . In one embodiment, the number of pouches  112  in the strip  114  depends on the number of days for which the patient has ordered the medicines. Thus, for example, a patient may order prescription medicines for one week; then the number of pouches  112  in the strip  114  corresponds to the number of times the patient has to take medicines each day times seven days. In one embodiment the patient may have a schedule established with the medicine supplier to automatically receive a new strip of pouches on a regular basis (i.e., every two weeks, once per month, etc.) 
     Thus, one or more single or multi-medicine pouches  112  are prepared for each medication administration time for a predetermined period of time, and connected in the correct sequence to form a strip  114 . The medication administration time may be time based or event based. For example, the administration time may be “9.00 a.m.” or “Breakfast”.  FIG. 26  illustrates another exemplary pouch in which the administration time is indicated as “7:00 AM, Monday, Aug 01”. Individual pouches may be separated along the strip  114  by a transverse perforation or seam  116  that allows for easy separation of the pouches from the strip one at a time. Individual medicine pouches may be labeled with information  118 , such as the name of the patient, date of packaging or manufacturing, expiry date(s) of the medications, date and time of administration, instructions for taking the medication (i.e., take with food), warnings (i.e., do not operate heavy machinery when taking this medication, do not drink alcohol when taking this medication), and pouch contents, including the name, dosage, and number of pills of each medication; such information may be modified as necessary to comply with state and/or federal regulations. The medicine pouches  112  may each include a bar code  120  for identifying the individual pouch  112 . The bar code  120  may also contain some or all of the information  118 . In some embodiments, the bar code  120  may contain a unique pouch ID. The bar code  120  also may include an encoded index which determines its order within the strip  114  and may be used to determine the dispense time for that pouch  112 . Each bar code  120  also may contain information about the prior pouch  112  and/or the subsequent pouch  112 . This information can be used in processes for error recovery when the data collected from a bar code  120  is incomplete or determined to be invalid, as discussed below. Pouches  112  may include duplicate bar codes  120  located in separate areas of the pouch  112  (for example, in either corner). Identification of pouches  112  may additionally or alternatively be accomplished by RFID tag, colors, symbols, etc. Pouches  112  may include one or more registration symbols  122  that may be used to facilitate pouch  112  detection, particularly when using computer vision applications. Registration symbols  122  may be of any appropriate shape or size suitable for detection such as, for example, T-shaped, a vertical line, horizontal line, bar, dot, etc. and may be located in any appropriate area of the pouch  112 . In one embodiment, the pouches  112  are made from any suitable material that meets federal requirements for medication packaging and is of any size suitable to properly accommodate medications and the dispensing unit  110 . 
     It may be noted that the medicine supplier  102  that packages the medication into the pouches  112 /strip  114  may be a pharmacy themselves, or may be a third party with which the pharmacy has contracted for packaging/distributing the medications. 
     After the medications are packaged into pouches  112  corresponding to the appropriate doses for each time of administration for a single patient, the strip  114  of pouches for that patient is loaded into a dispensing cartridge  200 . Each cartridge  200  is loaded with medicine pouches  112  sufficient to last a predetermined time frame specified by the patient, as explained above. The cartridge  200  with loaded medicines may be mailed, or otherwise delivered, to the patient on a regular basis. The cartridge  200  then can be loaded into a dispensing unit  110  for the patient and the individual pouches  112  can be dispensed at the appropriate times of administration. When the medication pouches  112  have all been dispensed, the used cartridge  200  may be disposed of, recycled, or may be returned to the medicine supplier  102 , or other designated facility, for reuse. 
       FIGS. 3A and 3B  illustrate an exemplary cartridge  200  which comprises a cartridge cover  202  and a cartridge frame  204 . Cartridge  200  also comprises a cylinder  206  about which the medication strip  114  is wound (see, e.g.,  FIG. 6 ). Any discussion herein that references the loading of a cartridge  200  into a dispensing unit  110 , includes the medication strip  114  loaded in the cartridge  200 . 
       FIG. 4  illustrates an exemplary dispensing unit  110 . As can be seen in  FIG. 4 , dispensing unit  110  comprises a housing  300  with a front  302 , back  304 , sides  306 ,  308 , top  310  and bottom  312 . Top  310  includes a door  314  which is openable to expose an opening  316  in the housing  300 ; the opening  316  provides access to the compartment  322  for receiving a cartridge  200  as described above. In the given example, an opening  316  is defined on the top  310  of the dispenser housing  300  such that the cartridge  200  may be dropped into the compartment  322  of the dispensing unit  110 . It may be appreciated however, that an opening may also be defined in any portion of the dispensing unit  110 , as long as it serves the purpose of conveniently inserting a cartridge  200  in the compartment  322 . The door  314  may include a lock  315  to restrict access to the components of the dispensing unit  110  and, in particular, to the contents of the cartridge  200 . The lock may be of a standard type requiring a key or combination, and/or may require radio frequency or biometric identification or other suitable security feature to unlock and provide access to the opening  316  and the contents of the dispensing unit  110 . This locking feature may be desirable for both security and child-safety considerations. Further, screen functions also may be locked and require a user-defined PIN, biometrics or other security mechanism to unlock. The patient may choose whether or not to enable the various locking functions of the dispensing unit. 
     The dispensing unit  110  comprises a delivery slot  318  to dispense a medication pouch  112  at the requisite time of administration. In one embodiment, delivery slot  318  may be covered by a door. In one embodiment, the dispensing unit  110  further comprises a display screen  320  suitable for communicating with the patient and providing buttons and menus for the patient to interact with the dispensing unit  110  and make selections. Information communicated to the patient may include dosage information, notification that a pouch is ready to be dispensed, alerts for missed medication, refill requirement, errors, etc. as needed. In one embodiment, the dispensing unit  110  further includes a local or remote audible, visual, and/or tactile alarm or other device for notifying the patient that a medication pouch  112  is ready to be dispensed, has been missed or that a message is on the display screen. In one embodiment, the screen  320  may be used to allow the patient to enter information, answer questions, confirm his/her identity, etc. In one embodiment, the screen  320  of the dispensing unit  110  may be used as a digital photo frame when communications on the display are not required. 
     In one embodiment, dispensing unit  110  also is equipped with a radio receiver, which allows a user to tune into radio stations when a medicine pouch  112  is not being dispensed. 
     In one embodiment, dispensing unit  110  is equipped for networking with a secured wireless network such as a home Wi-fi or cellular broadband service. In one embodiment, dispensing unit  110  is additionally or alternately equipped with a secured Ethernet connection as well as an RJ-45 jack (i.e., a telephone jack) as means of communication. A network connection enables the dispensing unit  110  to communicate with the cloud  104 , as necessary, to receive information such as updates, electronic medication administration records (eMARs), schedules, and alerts provided to the cloud  104  by the patient&#39;s medicine supplier  102 , physician, clinical study coordinator, etc. The dispensing unit  110  also may provide information to the cloud  104  such as adherence data, verification information, answers to questions, etc. The dispensing unit  110  may further use this communication path to send out requests for replenishment or help, or to communicate discrepancies in data (i.e., downloaded eMAR does not match patient identification) or a change in medications or schedules. In one embodiment, all data is sent and received via the cloud  104 . 
     In one embodiment, dispensing unit  110  comprises a suitable controller or microprocessor to control the operation of various components of the dispensing unit  110  and to communicate with the medicine supplier  102 , caregiver, or other appropriate individual or organization (i.e., study teams, insurance providers, etc.). Dispensing unit  110  further comprises an internal memory, such as RAM, for storing the controller&#39;s instructions and an internal or external memory for downloading and uploading required data to the cloud  104 . 
     In one embodiment, the dispenser unit  110  has a graphical user interface (GUI), which is displayed on the screen  320  and helps a user to navigate through and select various options from the functions of the dispensing unit  110 . 
     The structure and features of the cartridge components will now be described. Referring to  FIGS. 3A, 3B, 5A and 5B , cartridge cover  202  comprises a top  220 , sides  222 ,  224 , front  226 , and back  228 . The top  220  may include a handle  230  to facilitate handling and loading of the cartridge  200  into the compartment  322  of the dispensing unit  110 . In the embodiment illustrated herein, on each side  222 ,  224  of cover  202  are holes  232 , slots  234  and recesses  236  to accommodate features of the cartridge frame  204  and will be discussed in detail later with regard to frame  204 . Side  224  also includes recess  238  which accommodates a feature of the cartridge frame  204  and also will be discussed further with regard to frame  204 . Other embodiments may employ different alignment/guide/retention features. 
       FIG. 6  illustrates an exemplary cartridge  200  with the cover  202  removed. The frame  204  is loaded with a strip  114  of medication pouches that have been rolled around the cylinder  206 . In one embodiment, the cartridge frame  204  is sized and configured to fit into a dispenser unit  110  located in the patient&#39;s home. 
     The structure of the cartridge frame  204  will now be described with reference to  FIG. 7 .  FIG. 7  is a perspective view of the cartridge frame  204 . In one embodiment, the cartridge frame  204  comprises sidewalls  208 ,  210 , a floor  216 , and a base  218  with a bottom surface  227 , top surface  229 , front section  217  and a back section  219 , base side walls  221 ,  223  and base rear wall  225 . In one embodiment, the frame may be made of injection moldable plastic, such polypropylene, ABS or polyethylene, for example, metal, such as steel or aluminum, for example, or a composite material, such as fiberglass or a heavy-duty cardboard, for example. 
     In one embodiment, the cartridge sidewalls  208 ,  210  are substantially pentagonal in shape, with the rectangular portion  209  of the pentagon forming the lower portion of each sidewall, below the triangular portion  211 . As can be seen in  FIG. 7 , the rectangular portion  209  of each sidewall  208 ,  210  includes a variety of features which will be described now. Sidewall  208  includes a wedge  244 , which is a hollow, outward protrusion from the sidewall  208 . Wedge  244  is located substantially in the center of the rectangular portion of sidewall  208 . Two latches  242  are present on each sidewall  208 ,  210  of the frame  204 . Latches  242  are each a substantially square-shaped member that is separated from the sidewall on three sides, such that it protrudes slightly out of the plane of the sidewall while connected to the sidewall at the bottom of the latches  242  by an angled portion  250  ( FIG. 10 ) of the sidewall, forming an upward-facing, flat, hook-like portion of the sidewall. Latches  242  are located near the lower edge of the rectangular portion  209  of each sidewall  208 ,  210 . Within the face of the latch  242  is a protrusion  248  that faces back toward the sidewall  208 ,  210 , creating a bump in the latch  242 . Additionally, sidewalls  208 ,  210  each include two tabs  240 . Tabs  240  are wedge-shaped, outward protrusions of the sidewall  208 ,  210 , each located at the end of a strip of the sidewall  208 ,  210  that is disconnected laterally along its length; this allows for freedom of movement of the tabs  240  into and out of the plane of the sidewall  208 ,  210 . Tabs  240  are located approximately in an equatorial plane of the rectangular portion  209  of the sidewall  208 ,  210  and are spaced equidistantly from a horizontal line in the center of the rectangular portion  209  of the sidewall  208 ,  210 . On sidewall  208 , tabs  240  are located far enough apart as to flank wedge  244 . One of skill in the art will recognize that latches  242 , tabs  240 , and wedge  244  could be located elsewhere on the sidewalls  208 ,  210 , provided that other features of the system with which each feature interacts are likewise relocated. 
     Referring back to  FIGS. 5A and 5B , the cartridge cover  202  includes holes  232 , slots  234  and recesses  236  and  238 , which are designed to accommodate the previously discussed features of the sidewalls  208 ,  210 . As can be seen in  FIGS. 3A and 3B , and with reference to  FIGS. 5A and 5B , when the cartridge cover  202  is placed over the cartridge frame  204 , side  224  of cover  202  is aligned with sidewall  208  of cartridge frame  204  so that recess  238  can receive wedge  244 ; this allows wedge  244  to be accessible for alignment of the cartridge  200  when inserted in the dispensing unit  110 , as will be discussed later. When the cover  202  and cartridge frame  204  are aligned, tabs  240  fit into holes  232  and extend outward from the cartridge  200 . Slots  234  and recesses  236  accommodate latches  242 : recesses  236  receive the angled portion  250  of the sidewall  208 ,  210  that makes up the lower portion of each latch  242 , and the protrusion  248  of each latch  242  is received by its respective slot  234 . The fit of the cover  202  of the frame  204  is tight enough such that the protrusions  248  “snap” into place in the slots  234  which allows the cover  202  of the cartridge  200  to fit removably but securely in place on the frame  204 . 
     Again referring to  FIG. 7 , each of the triangular portions  211  of sidewalls  208 ,  210  includes a hole  212 ,  214 , respectively, into which a central cylinder  206  is inserted to serve as an axle (see  FIG. 8 ). The cylinder  206  may be made of injection-moldable plastic, such polypropylene or polyethylene, for example, metal, such as steel or aluminum, for example, or composite material, such as fiberglass or a heavy-duty cardboard, for example.  FIG. 8  and  FIG. 9  show that, in one embodiment, the cylinder  206  may be created by assembling two identical halves  252 . Located substantially in the center at each end of each cylinder half  252  is a longitudinal tab  260 . Each longitudinal tab  260  is separated from the adjacent portion of the cylinder  206  along the length of the longitudinal tab  260  and has an upturned lip  262  at its end. Extending perpendicularly to the cylinder  206  near each end and circumferentially in all regions except for the longitudinal tabs  260  is a radial ridge  254 . On one longitudinal edge of the cylinder half  252 , each ridge  254  extends from the cylinder  206  and ends in a small hook tab  256 . On the other longitudinal edge of the cylinder half  252 , aligned with the radial ridge  254  and opposite each hook tab  256 , is a small receiver tab  258 . 
     When the two halves  252  are assembled to make the complete cylinder  206  ( FIG. 9 ), each hook tab  256  snaps onto its respective receiver tab  258  on the other half  252  to secure the halves  252  together. When the cylinder  206  is assembled, the halves are separated slightly along their length between the radial ridges  254 , creating a longitudinal slot  264  along the cylinder  206 . The halves  252  may be assembled around the edge of the first pouch  112  of a medication strip  114 ; the plates  266  secure the edge of the first pouch  112 , which then extends through the slot  264 , thus anchoring the strip  114  and facilitating the process of winding the strip  114  on the cylinder  206 . In this instance, the “first” pouch  112 , is the first pouch to be wound around the cylinder  206 , as opposed to the first pouch  112  to be dispensed, which would be at the opposite end of the strip  114  and will be referenced later. The first pouch  112  to be wound around the cylinder  206  may be the last pouch  112  to be dispensed from the strip  114  or may be an empty pouch  112  or one of a series of empty pouches  112 . Alternatively, a strip of paper or plastic or other suitable material may be attached to the end of the strip  114  and used for attachment of the strip  114  to the cylinder  206 . The paper/plastic strip or empty pouch or pouches  112  may include notifications to the patient that the cartridge  200  is empty, refill information, pharmacy contact information, the next scheduled time for medication administration, and/or other information helpful to the patient. The medication strip  114  may then be wound around the cylinder  206  prior to insertion of the cylinder  206  into the frame holes  212 ,  214 . U.S. Patent Publication No. 2013/0264376 describes an exemplary system that can be used to wind a strip of medication pouches into a roll and is hereby incorporated by reference in its entirety. 
     Loading of the strip  114  of pouches onto the cylinder  206  may be performed as the strip of pouches is produced and its contents verified for accuracy. When inserting the cylinder  206  into the holes  212 ,  214  of the cartridge frame  204 , the cylinder tabs  260  can be displaced inwardly to facilitate the insertion process. One end of the cylinder  206  is inserted through each hole  212 ,  214  on the inner side of the cartridge frame  204 , thereby connecting the two sidewalls  208 ,  210  via the cylinder  206  ( FIG. 10 ). As the cylinder end is inserted into the holes  212 ,  214 , the radial ridge  254  limits the distance that the cylinder  206  can pass through the holes  212 ,  214 . Once inserted to the furthest extent allowable by the radial ridges  254 , the lips  262  of the tabs  260  latch on the outer side of the respective sidewall  208 ,  210 , thereby preventing, in concert with the radial ridges  254 , lateral movement of the cylinder  206  within the cartridge frame  204 . When inserted into the frame  204 , the cylinder  206  acts as an independently rotating hub within the cartridge such that the medication strip  114  can be unwound as necessary during dispensing of the medication pouches  112  from the dispensing unit  110 . 
     Turning now to  FIGS. 11A and 11B , viewing the cartridge frame  204  from the rear, further features of the cartridge frame  204  will now be described. The floor  216  of the frame  204  contains a routing hole  270  located in the rear-most quarter of the floor  216 . The hole  270  is substantially rectangular with its longer side (width) extending across most of the width of the floor  216 . The width of the hole  270  is at least wide enough to accommodate the width of the medication strip  114 . Along the forward-most edge of the hole  270  is a series of loops  268 . In one embodiment, there are four loops  268 . The outer diameter of the loops  268  may range from 0 mm to 40 mm. In one embodiment the outer diameter of the loops is in the range of 20 mm-30 mm. In one embodiment, the outer diameter of the loops is approximately 20 mm. One of skill in the art will recognize that the number and size of the loops may be varied while still maintaining functionality. A second, substantially rectangular hole  272  is located in the front  217  quadrant of the floor  216  closest to sidewall  208 , with its longer edge parallel with the sidewall  208 . As can be seen clearly in the cross-section view of the cartridge frame  204  shown in  FIG. 12A , extending forward from the rear edge of the hole  272 , adjacent the longer edge of hole  272  parallel with sidewall  208 , is an arm  274  that serves as a brake member. Where the arm  274  attaches to the floor  216 , the arm  274  slopes downward toward the cartridge base  218  and includes a hollow rib  275  on the top surface of arm  274  to provide more stiffness and stability to arm  274 . The free end of arm  274  is arched and is positioned over a notch  284  on the upper surface  229  of base  218  (see  FIG. 13 ). Turning back to  FIGS. 11A and 11B , extending from sidewall  208  is arm  276  with hollow rib  277  on the top edge of arm  276  to stabilize arm  276 . Arm  276  is positioned above the center of arm  274  and extends downwardly toward and near arm  274 . The length and angle of arm  276  are such that arm  274  resides at a height approximately 12 mm or less above the upper surface  229  of base  218  when the cartridge  200  is inserted in the dispensing unit  110 .  FIG. 12B  shows the location of a medication strip  114  when loaded on the cartridge frame  204 . The medication strip  114  is loaded on the cylinder  206  so that its free end exits the roll in the direction of the rear of the cartridge frame  204  (defined by the rear section  219  of the cartridge base  218 ). The free end of the strip  114  is then fed through the hole  270  in the floor  216 . The loops  268  provide a rounded surface past which the strip  114  can more easily move. The strip  114  is now in the space between the base  218  and the floor  216 . The strip then passes under arm  274 , moving toward the front of the cartridge (defined by the front section  217  of the cartridge base  218 ). The strip  114  remains between the base  218  and floor  216  such that it passes between notch  284  and the arch  279  of arm  274 . This positioning of the strip between the notch  284  and arch  279  of arm  274  allows the strip to be held securely in place, particularly during transport. As the strip  114  follows this path it passes over hole  280 . 
     Turning now to  FIGS. 13 and 14 , features of the base  218  of cartridge frame  204  are illustrated. In  FIG. 13 , the notch  284 , discussed above, on the upper surface  229  of the base  218  is illustrated. This notch  284  is positioned directly below the arch  279  in the free end of arm  274 . A rectangular recess  281  in the front quadrant of base  218  adjacent sidewall  208  forms hole  280  and is positioned below hole  272  in the floor  216 . Notch  284  is adjacent the forward edge of hole  280 . A laterally adjacent recess in base wall  221  creates window  283  (see  FIGS. 10 and 15 ). Viewing the base  218  from below in  FIG. 14 , feet  278  are positioned in each corner on the bottom surface  227  of base  218 . The bottom surface  227  of base  218  may also include identifying information  282  for the cartridge  200 . In one embodiment, identifying information may be provided in the form of an RFID tag. One of skill in the art will recognize that the identifying information may be provided in other suitable formats (such as bar code, for example), or in other locations on the cartridge. Identifying information that may be included in the RFID tag may include, but not be limited to, cartridge identification number, patient name, patient identification number, patient address, physician name, pharmacist name, pharmacy name, pharmacy address, prescription number(s), refill information, medical record number, cartridge fill date, cartridge expiration date, time zone information, and/or other information specific to the patient, the medication regimen, including medication administration times. In some embodiments, the identifying information may include administration times for some or all pouches  112  in the medication strip  114 . 
     Provision of the cylinder  206  as two halves  252  can be advantageous with respect to helping to secure the medication strip  114  with the cylinder  206  for loading, as discussed elsewhere. Providing two halves  252  also may be desirable for ease of packing and shipping as the two halves  252  may be stackable and thus take up less room than the fill cylinder  206 . Cartridge frame  204  also may be provided to the medicine supplier in a flat, stackable form as shown in  FIGS. 15 and 16 . In order to accommodate this, some features of the cartridge frame  204  are made hollow, such as the ribs  275  and  277 , tabs  240 , and wedge  244 , as well as latches  285  and stops  289 , described below. Loops  268  also facilitate stacking of the flat frame; forming this region as a solid tube or cylinder would not as easily accommodate stacking. This structure provides for ease of packing and shipping of the cartridge frame  204 ; this form can then be folded into the final arrangement ( FIG. 7 ) in conjunction with loading the cartridge frame  204  with the cylinder  206  containing the medication strip  114 . Referring to  FIG. 15 , viewing the flat cartridge  204  from the perspective of the top of the floor  216 , each side  208 ,  210  would be folded up at 90 degree angles to the floor  216  (out of the plane of the page) and secured in place with wedge-shaped latches  285  which interlock with slots  287  in sidewall  208 ,  210 . Similarly, base  218  folds 180 degrees underneath (into the plane of the page for  FIG. 15 ) floor  216  by bending 90 degrees at each edge of base rear wall  225 . Wedge-shaped stops  289  prevent base rear wall  225  from folding further than 90 degrees on either edge. Base  218  is secured in place by interaction of latches  286  at the bottom edges of sidewalls  208 ,  210  (see  FIG. 16 ) with receiver slots  288  in each of the base side walls  221 ,  223 . 
       FIGS. 17A and 17B  illustrate a dispensing unit  110  with the door  314  removed to reveal the opening  316  and the compartment  322  into which the cartridge  200  is inserted for dispensing of medication pouches  112  from the cartridge  200 . Compartment  322  includes channel  326  ( FIG. 17A ) to accommodate wedge  244  of the cartridge frame  204 . The singular location of channel  326  ensures that the cartridge can be loaded in one direction only and will be properly aligned within the compartment  322 , with the front of the cartridge (front  217  of the cartridge base  218 ) facing toward the front  302  of the dispensing unit  110 . Feet or pegs  278  on the bottom of cartridge frame  204  are another alignment feature; feet  278  help to properly seat the cartridge  200  in compartment  322 . As can be seen in  FIG. 17C , a channel  332  or receiving hole runs across the width of the front of the floor of the compartment  322 . The two feet  278  located in the front  217  of the base  218  of the cartridge  204  are seated into the channel  332 . Thus, the alignment features, feet  278  and wedge  244 , ensure that the cartridge  200  is positioned correctly within the compartment  322  so that the medication pouches can be properly dispensed, as will be discussed further below. As can be seen in both  FIGS. 17A and 17B , compartment  322  also includes slots  324  on both sides of the compartment  322 . Tabs  240  on the frame  204 , which protrude through holes  232  of the cover  202 , are received in slots  324  and removably snap into place to secure the cartridge  200  in position for dispensing. Two channels  328  on each side of compartment  322  also are provided to accommodate the protrusion of latches  242  of the cartridge  200 . As discussed above, in other embodiments the cartridge and compartment may include other features that retain the cartridge in place. 
     Additionally, the dispensing unit  110  contains a roller  330  or other drive unit that extends into the compartment  322 . When a cartridge  200  is properly loaded into the compartment  322 , roller  330  is positioned in line with hole  280 , along its lateral edge adjacent sidewall  208 , directly opposed to arm  274  (in other embodiments, a hard stop may be employed instead—see  FIG. 27C  at  1220 ).  FIG. 18  shows a cross-section of the dispensing unit  110  with a cartridge  200  loaded in compartment  322 . Roller  330  extends through hole  280 , contacting the strip  114  along its side seam and pressing it against arm  274  such that, when it is time to dispense a pouch  112 , roller  330  is able to move strip  114  forward through frictional interaction with the pouch  112  against arm  274 . Arm  276  provides resistance to the pressure of roller  330  against arm  274  by limiting the ability of arm  274  to move away from the roller  330 . 
       FIGS. 19A and 19B  illustrate further detail of the dispensing unit  110  relative to movement of the medication strip  114  and pouches  112 ; some components, not relevant to this discussion, have been removed for clarity. As can be seen in  FIG. 19A , the forward (dispensing) path F of the medication strip  114  continues past a cutting mechanism  334  (i.e., scissors, blade, etc.) and sensor  340 . The sensor  340  detects a perforation or seam  116  between pouches so that cutting mechanism  334  can cut and separate the forward-most pouch  112  at the appropriate time, as will be detailed later. Sensor  340  may be a redundant sensor (more than one sensor closely spaced) to ensure detection of the seam  116  and cutting of the pouches  112  in the correct location. As the medication strip  114  moves forward, it moves along ramp  350  and is engaged by roller  336  which helps to pull the strip  114  forward. Roller  336 , as well as roller  330 , may be made of a type of foam, such as urethane, for example, or other sufficiently soft material so that the medications within the pouches  112  are not crushed or otherwise damaged as the pouches are moved by the rollers  330 ,  336  in the dispensing process. When positioned on the edge of hole  280  and only contacting the pouch  112  side seam, roller  330  may be made of a harder material such as rubber or plastic, since it does not come in contact with the medication. When a pouch  112  is paused in the forward path F such that the following perforation or seam  116  is placed in position to be cut by the cutting mechanism  334 , sensor  342  may view the bar code  120  on the medication pouch  112  to confirm that the correct pouch  112  is in position to be dispensed. Once pouch  112  is confirmed and the perforation or seam  116  has been cut, the released pouch  112  is moved forward by roller  336  onto staging platform  337 . Sensor  344  is positioned to detect if a pouch is present on the platform  337 . When dispensing of the pouch  112  is requested by the patient, roller  336  can move the pouch  112  through the slot  318  to be retrieved by the patient. One of skill in the art will recognize that sensors,  340 ,  342 , and  344  may be LED, camera or any other type of sensor appropriate for detecting the events and for the environment. The dispensing unit  110  may also include door lock sensor  348  and cartridge identifier  282  sensor  346  (i.e., RFID reader, bar coder reader, camera, etc., as appropriate for identifier  282  on cartridge  204 ). 
       FIG. 19B  illustrates the path R of the pouch  112  under certain circumstances, such as when the wrong pouch  112  is in position for dispensing or the patient does not retrieve the pouch  112  during the allowed administration window. Under these circumstances, roller  336  may operate in reverse and move pouch  112  along path R. Due to the upwardly sloping geometry of ramp  350 , when the pouch  112  is moved rearwardly by the reverse movement of roller  336 , the pouch  112  slides under the ramp  350  and falls into exception tray  338 . Tray  338  may include a locking mechanism (not shown) for security and child-safety purposes, but may be opened by appropriate individuals to access medication pouches  112  contained therein. Some embodiments may lack an exception tray altogether. 
       FIG. 20  is a flowchart illustrating the operation of the dispensing unit to automatically dispense a medicine pouch at a requisite and predetermined time. Referring to  FIG. 20 , firstly in step  401  a cartridge frame is loaded with a strip of medicine pouches covered with the cartridge cover and delivered to the patient/customer. The customer opens the door of the dispensing unit in step  402 , drops the cartridge into the dispensing unit and closes the door in step  403 . The controller in the dispensing unit senses the cartridge by means of a suitable sensor and initiates a startup sequence. The startup sequence, in one embodiment, comprises validation of the patient, medicine strip and the cartridge, as shown in step  404 . Through appropriate sensors in the dispensing unit, information about the cartridge and medications contained therein is read from the identifier on the cartridge (i.e., bar code, RFID, etc.). The dispensing unit itself may be patient agnostic; that is, the dispensing unit may not be assigned to a particular patient or waiting for a certain cartridge. The specifics of the medication regimen for that patient may be determined when the cartridge is inserted into the dispensing unit. When the information of the identifier on the cartridge is read, the controller of the dispensing unit may require validation of the patient&#39;s identity in step  404  to confirm that the correct medications have been received for the correct patient. The controller may employ a user-specific PIN, RFID identification, biometric or other appropriate identifying data for patient validation. The controller may communicate information about the patient and cartridge to the cloud and patient-specific information retained by the cloud may then be downloaded to the dispensing unit. The electronic medication administration record (eMAR) for that patient, which includes medication administration times (hour of administration, or HOA), is created by the pharmacist and maintained in the cloud for access by the dispensing unit. When the eMAR is downloaded in step  405 , the controller of the dispensing unit contains the schedule for dispensing the mediation pouches to the patient. Access to the cloud also provides a means of data recovery if the data collected from the identifier is determined to be incomplete or invalid. 
     When the dispensing unit is inactive (in terms of dispensing medication) other features may be used such as the radio or digital photo frame features of the dispensing unit, as in step  406 . Other options include webcams, Bluetooth devices, and the like. 
     When the time for administration of the first medication pouch arrives, the dispensing unit issues an alert to the patient in step  407 . Alerts may consist of any appropriate means of notifying the patient of availability of the medication and may include, but not be limited to, audible alerts such as bells, buzzers, chimes, etc.; tactile alerts such as vibration; visual alerts such as flashing lights which may be on the unit, on a device carried by the patient, including cell phone, smart phone, MP3 player or other mobile device, or may be through control of the room lighting; text alerts; email alerts, phone calls or the like. The eMAR may include information defining a time period within which each medication dose may be administered (the HOA window). During the HOA window, the patient is able to dispense the appropriate medication pouch; once the HOA window expires (the time period for administration of that medication dose has been exceeded) the patient will no longer be able to dispense the pouch through the usual path. With the opening of the HOA window, the medication pouch is made accessible within the dispensing unit in step  408 . When the patient is ready to dispense the medication pouch and if the time is still within the HOA window, the patient selects the dispense button on the dispensing unit screen in step  409 . In step  410 , the medication pouch is dispensed to the patient and adherence data is transmitted to the cloud in real time, reporting that the patient&#39;s medication was taken. In one embodiment, the dispensing unit may display achievements or provide a game (i.e., health-related game, game related to adherence progress, etc.) to the patient in step  411 . In one embodiment, in step  412  the dispensing unit may display promotional or informational messages, such as information about the drug or a message for the patient, which has been configured in the cloud by the pharmacy, physician, clinical study coordinators, etc. In one embodiment, a series of questions for the patient may be configured in and delivered from the cloud, with the patient&#39;s answers being delivered back to the cloud in step  413 . This may be particularly useful for clinical studies or questions from the patient&#39;s physician relative to side effects of the medications and/or the patient&#39;s general health. Steps  411 ,  412 , and  413  are not all required and are not mutually exclusive; any or all of these steps may be utilized with the dispensing unit. 
     Alternatively, if the patient does not dispense the medication pouch when the HOA window opens, the dispensing unit may provide additional alerts of escalating frequency and urgency to remind the patient that the pouch is ready to dispense, as in step  419 . Escalating alerts may include, but not be limited to, louder audible alerts, changes in the sound or pattern of audible alerts, increased strength and length of tactile alerts, brighter or faster flashing lights, increased frequency of texts, emails, phone calls, etc. If the patient does not select the dispense button before the HOA window expires, information may be sent to the cloud in step  415  indicating that the patient has missed the medication administration event and an alert may be sent to an appropriate individual such as a caregiver, pharmacist, physician, family member, etc. In step  416 , if an exception tray is included, the missed pouch is moved to the exception tray to remove it from the dispensing path. The pouches in the exception tray can still be accessed. In one embodiment, access to the exception tray may be limited to a caregiver in cases where it is not advisable to allow the patient access to the medications. A sensor in the dispensing unit may monitor contents of the exception tray and notify the patient or other individual when the tray is full. If the tray becomes full, the dispensing unit may stop dispensing until the tray has been emptied or at least enough pouches have been removed so that it is no longer full. 
     At decision point  417 , sensors of conventional construction determine if the end of the medication strip has been reached. If sensors determine that the end of the medication strip has not been reached, then a new HOA window will open at the appropriate time and the process will move back to step  407 . If the end of the medication strip is sensed, the dispensing unit will not open an HOA window and flow will move to step  418  where a message is delivered to the patient that the end of the strip has been reached and prompting the patient to remove the empty cartridge and load a new one. The system may also ask the patient if they would like to order another refill cartridge to have on hand and may submit refill requests automatically through the cloud to the medicine supplier. In one embodiment, the status of all the events generated at the dispensing unit, such as alarms, refill requests, and dispensing activity indicators may be uploaded to the cloud. 
       FIG. 21  illustrates an exemplary mechanical flow of the dispensing unit during the operation of the unit. At step  501 , the HOA window opens and the patient is alerted to dispense a medication pouch, as in step  407  of  FIG. 20 . At decision point  502 , the unit determines if the user has selected the button to dispense the medication pouch. If the user selects the dispense button during the HOA window, at step  503  a sensor confirms the identification of the first pouch in the strip by reading the bar code, RFID tag, etc. If the data collected at this step is determined to be invalid or incomplete, the system may access the cloud to retrieve the relevant information (see  FIG. 23 , dashed lines). Alternatively, the system may attempt error recovery using approaches discussed below. At step  504  the pouch is then advanced past a sensor that identifies the location across which to cut the pouch strip in order to separate the first pouch from the remainder of the strip. A perforation may be provided within the seam between the pouches and the cut may occur at or near the perforation, but at least within the seam. The strip is cut at step  505  and the pouch is advanced to a platform within the dispensing unit at step  506  and moved forward through the dispensing slot to be dispensed to the patient at step  507 . The system then waits for the next HOA window at step  519 . 
     In one embodiment, one or more cameras are used for the sensors and a computer vison subsystem may use one or more pouch features (including but not limited to the registration symbols, barcode regions, pouch seams, physical material characteristics) in the pouch detection and evaluation process. This process can identify various aspects of the pouch and enable system functionality, including but not limited to seam detection discussed above, reading of bar code information, and counting and indexing of pouches as they are removed from the cartridge. 
     If the patient does not select the dispense button during the HOA window at step  502 , if an exception tray is present, the process moves to decision point  508  and the sensor monitoring the status of the exception tray (also called the exception bin) determines if the tray is full. If the sensor determines that the bin is not full, at step  509  a sensor confirms the identification of the first pouch in the strip by reading the bar code, RFID tag, etc. At step  510 , the pouch is advanced past a sensor that identifies the location across which to cut the pouch strip in order to separate the first pouch from the remainder of the strip. The strip is cut at step  511  and the pouch is then advanced to a platform within the dispensing unit at step  512 . At this point, the pouch is rerouted at step  513  to move it to the exception tray. A missed dispense alert may be shown on the display screen of the dispensing unit at step  514  and an alert may be sent to an appropriate individual such as a caregiver, physician, family member, etc. The system then waits for the next HOA window at step  519 . 
     At decision point  508 , if the sensor determines that the exception tray is full, the pouch remains attached to the medication strip at step  515 . An alert is provided at step  516  notifying the user that the tray must be emptied and dispensing is halted until further action is taken to empty the tray. The alert may take any form, as described above for other alerts of the system, as appropriate to notify the user, and may be made distinguishable from other types of alerts of the system. At step  517 , the bin is emptied and at step  518  the system progresses to the exception routine (steps  509  through  514 ). After completion of the exception routine, the system resumes normal operation and waits for the next HOA window at step  519 . Alternatively, a “full” determination at step  508  may trigger a visual alert that a medication was missed. 
       FIGS. 23-25  illustrate steps in the cartridge loading and pouch dispensing processes of the dispensing unit. With the exception of steps specific to online mode operation (which are shown with dashed arrows in  FIG. 23 ), the steps described here can be used in an offline mode, which may be used when there is not access to the cloud to obtain the necessary information for dispensing. Referring to  FIG. 23 , at step  601 , the cartridge is loaded in the dispensing unit and at step  602  the unit may scan and collect data from the cartridge barcode (or RFID tag, as appropriate). The data collected may include, but may not be limited to, schedule information pertaining to administration times for the pouches in the strip; patient name; patient ID; cartridge ID; prescription numbers; the date the cartridge was filled with the medication strip; time zone information; any other information required and/or desirable to identify the patient, the medications in the cartridge, and the dispensing schedule, and any information required and/or desirable to properly dispense medication from the cartridge to the patient at the appropriate time without requiring access to the cloud. At step  603 , the system may evaluate if all cartridge data is valid. If the barcode or RFID information is damaged or otherwise unreadable making the data invalid, the system may attempt error recovery at step  604 . It is well known in the art that 2D Data Matrix barcodes incorporate duplicated data encoded in and distributed throughout the barcode image. This duplication of data provides the potential for data to be reconstructed from one part of the barcode if the data in another part of the barcode is damaged. The system may make a determination at step  605  as to whether the data has been recovered—depending upon the level of damage done to the code, the data may or may not be recoverable. If the data cannot be recovered, the cartridge load process fails (step  606 ); in this case the unit may display a message to the user indicating that the medication cannot be dispensed. The unit also may provide additional guidance such as: a recommendation to the user to contact their pharmacist or another individual who can address the issue; a notification that the medication can be dispensed manually until the dispensing issues are addressed; notification of the time to manually dispense a pouch; the appropriate pouch identification number for each administration time for manual dispensing, instructions on how to manually dispense the pouches; contact information for the pharmacist or other individual to contact; an option for the patient to request a call-back from the pharmacy; etc. The unit also may still provide alerts to the user at the appropriate medication administration times. 
     Turning briefly to the online mode (dashed lines in  FIG. 23 ), if the data is not recovered at step  605  and the system is online, the system may access the cloud at step  607  to recover the necessary information. At step  608 , the system again evaluates whether the data has been recovered. If the data has not been recovered from the cloud, the cartridge load process fails (step  606 ) and the unit may provide messages, guidance, alerts, etc., as described above. If the data has been recovered, the system may move to the steps identified in  FIGS. 24A and 24B , as described below. 
     If the cartridge data is determined to be valid at step  603 , or if the system determines at step  605  or step  608  that the data has been recovered, the system may move to the steps identified in  FIGS. 24A and 24B . At step  701  ( FIG. 24A ), the system may scan and read the data from the barcode (or RFID or other identifier, as applicable) on the first pouch in the strip. At step  702 , the system may evaluate if all pouch data is valid. If the information obtained from the scan is damaged or otherwise unreadable, the system may attempt error recovery at step  703  ( FIG. 24B ). The system may attempt to utilize the built-in error correction of the barcode, as discussed above with respect to the cartridge identifier/barcode. Alternatively or in addition, the system may read a second, duplicate bar code located in another area of the pouch to determine if the data contained there is valid. At step  704 , the system may evaluate if the pouch data has been recovered as a result of the local error recovery process. If all data has not been recovered, the system may attempt data recovery using data obtained from the next pouch, at step  705 . If the data can be more easily read from the neighboring pouch, the information can be extrapolated to the first pouch—the system can determine the number of the first pouch as well as the administration time (using information obtained about the schedule from the cartridge barcode). The system may again determine at step  706  if the data for the first pouch has been recovered. If the data has not been recovered, the system may check the pouch index at step  707  and, by identifying the pouch number, may retrieve schedule information from the cartridge data. By keeping an accurate count of the pouches, the system always knows the sequence of the pouches in the administration schedule. The system may again determine at step  708  if the data has been recovered. If the data cannot be recovered, the pouch read process fails at step  709 . The unit may display a message to the user indicating that the medication cannot be dispensed. The unit also may provide additional guidance such as: a recommendation to the user to contact their pharmacist or another individual who can address the issue; contact information for the pharmacist or other individual to contact; an option for the patient to request a call-back from the pharmacy; etc. 
     If the pouch barcode scan is successful at step  702 , or if the data can be successfully recovered at any of steps  704 ,  706 , or  708 , the system may proceed to step  710  where it evaluates if the data acquired from the pouch matches the data acquired from the cartridge. Some of the information provided in the pouch barcode (such as, for example, patient identification, cartridge identification, prescription numbers, etc.) can be redundant to the information provided in the cartridge barcode, allowing for this validation step. This verification process ensures that the correct cartridge was used to load the correct strip of medications and does not allow the dispensing to proceed based only on the cartridge information. If the matching is successful at step  710 , the system may proceed to step  711  where it makes a determination as to whether the cartridge is empty. If the cartridge is determined to be empty, the load process fails at step  712  and the system may provide one or more messages to the user such as, for example: notification that a new cartridge must be loaded; instructions on how to load a cartridge; identification of the next cartridge to be loaded; instruction to contact the pharmacy to order a new cartridge; contact information for the pharmacy; an option for the patient to request a call-back from the pharmacy; etc. If the cartridge is not empty, the system may proceed to step  713  and make a determination as to whether the cartridge has expired. If the cartridge has expired, the load process fails at step  714 . The user may be notified of the failure and instructed to load a new cartridge or contact the pharmacy to obtain a new cartridge. The system also may provide additional information to the user such as, for example: instructions on how to load a cartridge; identification of the next cartridge to be loaded; contact information for the pharmacy; an option for the patient to request a call-back from the pharmacy; etc. Referring back to step  710 , if the pouch data and cartridge data do not match, the load process fails at step  715 . The system may display a message to the user such as, for example: instruction to contact the pharmacy; contact information for the pharmacy; an option for the patient to request a call-back from the pharmacy. 
     If the system determines that the cartridge is not expired at step  713 , the process moves to  FIG. 25 . At step  801 , the system may display the patient name for the loaded cartridge and request verification from the user. When the user verifies that he/she is the correct patient for that cartridge, the system may determine at step  802  if the loaded cartridge has been previously loaded in that unit. Some circumstances, for example, regarding when a cartridge may have previously been used in the unit may include: 1) a patient uses multiple units to dispense their medication; for example, the patient might use one unit at home and another unit at a family member&#39;s house, thereby moving the cartridge back and forth between units when they travel; 2) one unit may serve several patients in the same household; in this case there may be situations where patient #1 removes their cartridge and patient #2 inserts theirs, and vice versa; 3) some patients may remove their cartridge from the unit in order to manually dispense one or more pouches from the cartridge to take with them if they will be away from the unit for the day or for an extended period of time. Under circumstances where a cartridge is reinserted in a unit in which it has previously been used, the system knows which pouches have been dispensed and which pouch to expect next. If the system determines at step  802 , that the cartridge has been previously used in that unit, the system may proceed to step  803  to retrieve information regarding the last medication pouch that was dispensed from that cartridge. Once the system retrieves this information, or if it determines at step  802  that it is a new cartridge, the system may evaluate if the first pouch in the strip is the pouch that it expects, at step  804 ; this expectation may be based on the retrieved data regarding the last pouch dispensed, if the cartridge is a previously used cartridge, or it may be the expected first pouch in a strip, if it is a new cartridge. In either situation, the system may use the data acquired from the cartridge barcode and pouch barcode to make this determination. If the system determines that the first pouch is not the expected pouch, it may then assess, at step  805 , whether the first available pouch appears later in the dispensing schedule for that cartridge. If the pouch does not appear later in the schedule, the load process fails at step  806 . The system may display a message to the user such as, for example: instruction to contact the pharmacy; contact information for the pharmacy; an option for the patient to request a call-back from the pharmacy. If the system determines, at step  805 , that the first pouch is to be dispensed later in the schedule, the system may notify the user, at step  807 , that some pouches have been removed from the cartridge. If the first pouch is the expected pouch (step  804 ) or appears later on the dispensing schedule (step  807 ), the system may then move to step  808 , retrieving the schedule and dispensing data. This information may be used to display to the user the scheduled administration time for the first pouch in the strip (step  809 ), which will then be dispensed at the scheduled time (step  810 ). 
     One of skill in the art will recognize that not all of the steps enumerated above need necessarily occur in the order in which they are described here. As nonlimiting examples, the system may first collect data from the first pouch and then from the cartridge, or it may collect the data from each source simultaneously; the system may make a determination on whether the cartridge is new or has been previously loaded in the unit prior to determining whether the cartridge is empty or expired. One of skill in the art will also recognize that many of the same steps may be performed in the cartridge loading and dispensing process regardless of whether the information is obtained from the cloud or offline but that the collection of data from the barcodes, in particular, provides the local information to enable offline dispensing. Additionally, one of skill in the art will recognize that, while these steps are discussed with respect to the “first” pouch, this process occurs for each pouch in the strip as it becomes the first pouch in the roll (i.e., next pouch to be dispensed), not only for the first pouch in a new cartridge. In one embodiment, the dispensing unit of the present specification also provides a user with an option of “Manual dispense”. When this option is selected, medicine pouches can be dispensed outside the designated HOA; this may be desirable if the patient is traveling or has other reason to be away from the dispensing unit during one or more HOA events.  FIG. 22  is a flowchart illustrating an exemplary process flow to carry out the manual dispense option. Referring to  FIG. 22 , steps  651  to  656  are identical to steps  401  to  406  of  FIG. 20 . At step  657  the patient selects a manual dispense option provided in a menu on the display screen of the dispensing unit. When choosing the manual dispense option, the patient is able to select the time period for which he wishes to manually dispense medication pouches. In one embodiment, the user may select a time period—such as 1 day or 2 days—for which they want the medication. The user may instead select a number of pouches, such as 2 or 3. The user may select as few or as many pouches as needed within a certain range; a limit may be set on the total number of pouches to be dispensed manually without consultation with the patient&#39;s physician, pharmacist, etc. The GUI of the dispensing unit prompts the user for a confirmation of the manual dispense and time period or number of pouches selected, as shown in step  658 . On receiving a confirmation from the patient, the dispensing unit dispenses a cut or uncut strip (as desired) consisting of the appropriate pouches for the selected timeframe and an update about the manual dispense is then submitted to the cloud, as shown in step  659 . At step  660 , normal dispensing flow continues, accounting the for the appropriate HOA events covered by the manual dispensing activity. 
     Referring now to  FIGS. 31-41 , another dispenser unit, designated broadly at  1110 , is illustrated therein (and shown in full in  FIG. 32 ). Many of the components of the dispenser unit  1110  and the cartridge  1200  residing therein are the same as or similar to those of the dispenser unit  110  in operation and function. Some of the differences in the dispenser units  110 ,  1110  and the cartridges  200 ,  1200  are discussed below. 
     Referring first to  FIG. 33 , a cartridge cover  1202  of the cartridge  1200  is illustrated therein. The cover  1202  includes is generally rectangular, and includes a dispensing window  1202   a  in its lower front edge. A handle  1230  projects from the center of the top  1220  of the cover  1202 . The cover  1202  also includes a hole  1202   b  in the floor  1202   c . In some embodiments, the cover  1202  is formed of cardboard, and is typically constructed by folding a single flat blank of cardboard into a rectangular box. As can be seen in  FIG. 31 , the cover  1202  overlies a cartridge frame  1204  (discussed in more detail below); the combination of the cover  1202  and the cartridge frame  1204  comprise the cartridge  1200  that is loaded into the dispenser  1110 . 
     Referring now to  FIGS. 34-40 , the cartridge frame  1204  includes rectangular side walls  1208 ,  1210  rising from a floor  1216 . Two support braces  1209  extend from side wall  1208  and interlock with corresponding support braces  1211  that extend from side wall  1210 . Each side wall also includes corresponding tabs  1212 ,  1214  on which a free spinning hub  1206  (see  FIGS. 36  and  37 ) is rotatably mounted. The tabs  1212 ,  1214  are deflectable to enable the hub  1206  to be easily installed and removed. As shown in  FIG. 39 , a rolled strip  1114  is mounted on the hub  1206 . 
     As can be seen in  FIG. 39 , the floor  1216  has an open-celled configuration, with an upper surface  1216   a  and a lower surface  1216   b  separated by ribs  1216   c . The upper surface  1216   a  is sloped at its rear end. An idle roller  1216   d  is located below the rear end of the floor  1216  and provides a movable arcuate surface to facilitate advancement of the strip  1114 . A base  1218  (also curved at its rear end) is positioned below the lower surface  1216   b  and forms a gap  1218   a  through which the strip  1114  can travel. 
     Referring to  FIGS. 42A through 42D , the floor  1216  may include a flapper baffle  1216   e ,  1216   f  located at the rear above the idle roller  1216   d . The flapper baffle  1216   e ,  1216   f ,  1216   i  is a flexible divider that extends from the floor  1216  into the space between the rolled strip  1114  and the portion of the strip  1114  that is separated from the roll as it enters the hole in the floor  1216 . Because the roll naturally resists staying tightly wound, as the roll is spun during advancement of the strip  1114  to dispense a pouch, the outer layer of the roll tends to follow the portion of the strip that is leaving the roll to exit through the floor  1216 ; this often causes the roll to jam as the outer layer gets stuck with the moving strip  1114 . The location and design of the flapper baffle  1216   e ,  1216   f  forces the roll to stay on the inside of the flapper baffle, thus preventing having the outer layer of the roll “hang up” in the exiting strip  1114 , which is on the outside of the flapper baffle  1216   e ,  1216   f .  FIGS. 42A and 42B  illustrate a looped flapper baffle  1216   e , which can pivot at both attachment locations to allow flexibility during travel of the pouch strip  1114 . The flapper baffle  1216   e  may be made from Mylar® or a similar polyester film or plastic sheet material.  FIG. 42C  illustrates an alternative flapper baffle  1216   f  comprising a thin, flat, extended bendable member which may have a living hinge  1216   g  or similar feature at its connection to the floor  1216  to allow flexibility during travel of the pouch strip.  FIG. 42D  illustrates another alternative flapper baffle  1216   i  that is convex relative to the travel path of the strip  1114  (in contrast, the flapper baffle  1216   f  is concave). The flapper baffles  1216   f ,  1216   i  may be made of polypropylene or a similar material. In some embodiments the flapper baffles  1216   f ,  1216   i  may be spring loaded in the forward direction so that it catches the roll and only the strip  1114  can get behind it. In some embodiments there is a fixed spacer  1216   h  located at the top of the flapper baffle  1216   i  so that the strip  1114  and roll are required to be separated by a set distance (determined by the size of the spacer  1216   h ). In other embodiments, such as that shown at  1216   f , the flapper baffle has a sharp free edge to assist in separating the strip  1114  from the roll. The flapper baffles  1216   e ,  1216   f ,  1216   i  are of a width so as not to interfere with pills in the pouch (the flapper baffles  1216   e ,  1216   f ,  1216   i  are located to one edge of the strip  1114  and overlap a small portion of the width of the pouch). 
     A window  1218   b  is present in the base  1218  (see also  FIG. 40 ) and receives a drive roller  1330  mounted to the dispenser that drives the pouch strip through the gap  1218   a  and out of the dispensing window  1202   a  in the cover  1202 . It can also be seen that an elongate, rigid stop member  1220  depends from the lower surface  1216   b  of the floor  1216  to provide purchase against the drive roller  1330 ; in some embodiments, the lower surface of the stop member  1220  is treated to have low friction. 
     A spring  1221  extends transversely across the gap  1218   a  and can replace the arm  274  discussed above (see  FIG. 27C ). A spring release mechanism  1223  ( FIG. 27D ) can deflect the spring  1221  upwardly when the cartridge  1200  is inserted in the dispenser  1110  to enable the strip  1114  to more freely if desired. 
     A guide  1222  also projects from the lower surface  1216   b  near the dispensing window  1202   a . Guide posts  1224  extend downwardly from the base  1218 ; these seat in holes in the cutter/exit assembly of the dispenser  1110  to align the cartridge  1200  and the dispenser  1110 . A notch  1229  is present between the stop member  1220  and guide  1222  ( FIG. 39 ). 
     As can be seen in  FIG. 28  and envisioned from  FIG. 41 , the cartridge  1200  fits within a cavity in the dispenser  1110  located above the drive roller  1330 . The guideposts  1224  are received in receptacles in the dispenser  1110 . The drive roller  1330  protrudes through the window  1218   b  (see  FIG. 27C ) and engages the stop member  1220  to form a nip through which the strip  1114  travels. The upper surface of the cartridge  1200  is held in place by a spring-loaded bracket  1231  that is pivotally attached to the door  1314  of the dispenser  1100  at a pivot  1233  and biased away from the door  1314  by a spring  1234  (see  FIGS. 30A and 30B ). A depending edge  1236  contacts the top surface of the cartridge  1200  and helps to maintain the cartridge  1200  in position by providing downward pressure on the cartridge  1200 . 
     Referring now to  FIGS. 29A-29E , a door locking mechanism  1240  is illustrated. The door locking mechanism  1240  includes a slide bar  1242  and a cam  1244 . The slide bar  1242  has two slots  1246 ,  1248  in its main portion; the forward slot  1246  is tripartite, with its middle segment sloping downwardly and rearwardly. Posts  1245 ,  1247  mounted on the side wall of the dispenser  1110  are received in the slots  1246 ,  1248 , respectively. The slide bar  1242  also includes a vertical slot  1250  at its rear end. A tab  1252  extends upwardly from the main portion of the slide bar  1242 ; a rim that follows the periphery of the tab  1252  forms a pocket  1254  that is open to the rear. A tab  1256  is mounted on the underside of the door  1314 . 
     The cam  1244  (best seen in  FIGS. 29C and 29D ) is pivotally mounted onto the shaft  1258  of a motor mounted to the side wall of the dispenser  1110 . A post  1260  is mounted on one end of the body  1262  of the cam  1244 . The post  1260  is received in the vertical slot  1250  of the slide bar  1242 . 
     As can be seen in  FIGS. 29A and 29D , in the unlocked position, the cam  1244  is oriented so that the post  1260  is forward of the shaft  1258 . In this position, the slide bar  1242  is forced forwardly, such that the posts  1245 ,  1247  are in the rear ends of the slots  1244 ,  1246 . When a sensor  1261  mounted to the wall of the dispenser ( FIG. 29E ) detects that the door  1314  is closed, the system activates the motor to rotate the shaft  1258  (clockwise from the vantage point of  FIG. 29D ), which draws the slide bar  1242  rearwardly (guided by the posts  1245 ,  1247  in the slots  1244 ,  1246 ). As it moves rearwardly, the slide bar  1242  tilts so that its rear end rises and its front end descends. The rearwardly and angular movement of the slide bar  1242  positions the pocket  1254  to capture the tab  1256  on the door  1314 , thereby locking the door  1314  in place (see  FIGS. 29B and 29C ). Sensors  1265  and  1267  are positioned to verify the position of the cam  1244  (see  FIGS. 29C and 29D ). 
     Referring now to  FIGS. 28 and 41 , the dispenser  1110  also includes two cameras  1400 ,  1402  mounted therein. The camera  1400  is mounted facing downwardly to take a “vertical” image of the pouch barcodes. The camera  1400  can also determine the position of the pouch strip for cutting of a pouch from the strip  1114  with the cutting assembly (thus, the camera  1400  can replace the sensor  340  discussed above). The camera  1402  is mounted to face downwardly and rearwardly in order to read both the pouch barcodes and the cartridge barcodes; the cartridge barcodes are affixed to the cover of the cartridge and are visible through a window  1406  in the compartment/cavity of the dispenser. 
     It should also be noted that  FIGS. 27A and 27B  illustrate a slightly different configuration of a cartridge frame  1204 ′. The cartridge frame  1204 ′ includes only one brace  1209 ′,  1211 ′ rather than two of each. 
     The present invention has been described herein with reference to flowchart and/or block diagram illustrations of methods, systems, and devices in accordance with exemplary embodiments of the invention. It will be understood that each block of the flowchart and/or block diagram illustrations, and combinations of blocks in the flowchart and/or block diagram illustrations, may be implemented by computer program instructions and/or hardware operations. These computer program instructions may be provided to a processor of a general purpose computer, a special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions specified in the flowchart and/or block diagram block or blocks. 
     These computer program instructions may also be stored in a computer usable or computer-readable memory that may direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer usable or computer-readable memory produce an article of manufacture including instructions that implement the function specified in the flowchart and/or block diagram block or blocks. 
     The computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer implemented process such that the instructions that execute on the computer or other programmable apparatus provide steps for implementing the functions specified in the flowchart and/or block diagram block or blocks. 
     It will be further appreciated that the functionality of any or all of the program modules may also be implemented using discrete hardware components, one or more application specific integrated circuits (ASICs), or a programmed digital signal processor or microcontroller. The program code may execute entirely on a single processor and/or across multiple processors, as a stand-alone software package or as part of another software package. The program code may execute entirely on an electronic device or only partly on the electronic device and partly on another device. In the latter scenario, the other device may be connected to the electronic device through a wired and/or wireless local area network (LAN) and/or wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider). 
     The above examples are merely illustrative of the many applications of the system of present invention. Although only a few embodiments of the present invention have been described herein, it should be understood that the present invention might be embodied in many other specific forms without departing from the spirit or scope of the invention. Therefore, the present examples and embodiments are to be considered as illustrative and not restrictive, and the invention may be modified within the scope of the appended claims.