Abstract:
The disclosed invention pertains to methods for diagnosing clinical conditions that are common in hemodialysis patients and that may be related to abnormal carnitine metabolism resulting from hemodialysis. Further, the present invention pertains to methods for monitoring and improving the administration of therapeutic intravenous levocarnitine to such patients. Clinical algorithms have been developed for the clinical symptoms seen in end-stage renal disease (ESRD) patients that may be related to carnitine deficiency. Monitoring tools to assist healthcare professionals in implementing the clinical algorithms are also provided.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]    The present application claims priority from U.S. Provisional Patent Application Serial No. 60/352,505, METHODS FOR THE DIAGNOSIS OF HEMODIALYSIS PATIENTS AND UTILIZATION OF SUCH METHODS TO IMPROVE THE ADMINISTRATION OF INTRAVENOUS LEVOCARNITINE TREATMENTS TO HEMODIALYSIS PATIENTS, filed Jan. 31, 2002, which is hereby incorporated by reference. Furthermore, the present application is related in subject matter to U.S. Pat. No. 6,335,369, TREATING CHRONIC UREMIC PATIENTS UNDERGOING PERIODICAL DIALYSIS, issued Jan. 1, 2002, the specification of which is hereby incorporated by reference in its entirety. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates to methods for diagnosing and treating various conditions prevalent in hemodialysis patients with end stage renal disease. In particular, the present invention pertains to methods for diagnosing clinical conditions that are common in hemodialysis patients and that may be related to abnormal carnitine metabolism resulting from hemodialysis; thus, the present invention provides methods for monitoring and improving the administration of therapeutic intravenous levocarnitine to such patients.  
         BACKGROUND OF THE INVENTION  
         [0003]    Studies indicate that more than 70% of the carnitine present in the plasma of a hemodialysis patient can be removed during a dialysis session. Carnitine is a naturally occurring substance in the human body required for energy metabolism at the cellular level because it transports fatty acid-derivatives into the inner aspect of the mitochondrionia to produce energy and removes various acyl moeities from the mitochondria and cells. Dialytic loss of carnitine by patients undergoing hemodialysis is thought to be attributable to the compound&#39;s relatively small molecular weight, high water solubility, and poor protein binding. Carnitine levels are further diminished in end stage renal disease patients by reduced renal synthesis and reduced intake of meat and dairy foods.  
           [0004]    Primary and secondary carnitine deficiency syndromes are well-described entities whose clinical sequelae could result in serious illness or death. Carnitine deficiency syndromes are characterized by such diverse symptoms as cardiomyopathy, muscle weakness, lipid storage myopathy, hepatic dysfunction, encephalopathy, failure to thrive, and recurrent infections.  
           [0005]    As described in U.S. Pat. No. 6,335,369, the administration of levocarnitine may be beneficially used to treat carnitine deficiency in patients with end stage renal disease (“ESRD”) who are undergoing regular hemodialysis. Chronic uremic patients undergoing periodical hemodialysis are treated with carnitine or one of its salts to prevent or treat carnitine deficiency in patients with end stage renal disease. An effective dose of levocarnitine (the recommended starting intravenous dosage is typically 10-20 mg of drug per kg of patient dry body weight) is administered intravenously via a venous return line after each dialysis session. Initiation of such levocarnitine injection therapy may be prompted by pre-dialysis plasma free carnitine concentrations that are below normal (normal concentrations being approximately 40-50 micromoles/liter (μmol/L)). Such intravenous administration of levocarnitine to end stage renal disease patients on hemodialysis results in increased plasma carnitine concentrations and thereby makes it possible to correct for the loss of plasma carnitine which otherwise takes place during hemodialysis therapy. Importantly, immediately after giving intravenous carnitine to a patient at the end of a dialysis session, carnitine levels in the patient&#39;s plasma rise to high levels and then return to a pre-dialysis baseline levels after approximately 10-24 hours (presumably because the carnitine has entered the tissues). In this manner, it is possible to avoid tissue carnitine depletion, which is a long-term consequence of repeated losses of carnitine from plasma that the patient undergoes during successive dialytic sessions over a prolonged period of time.  
           [0006]    Prior studies have listed specific subsets of patients in whom intravenously administered carnitine had been associated with improvement in clinical parameters. These subsets of patients have included those with cardiomyopathy, skeletal muscle weakness/myopathy, anemia of uremia unresponsive to or requiring large doses of erythropoietin (EPO), lack of energy (which has a negative effect upon quality of life), severe and persistent muscle cramps, and/or intradialytic hypotensive episodes. Despite these studies, the use of levocarnitine in dialysis patients is sometimes limited.  
           [0007]    Cardiomyopathy, muscle weakness, and fatigue are often due to factors other than carnitine deficiency. The ability to methodically analyze these common conditions is critical to the appropriate application of this therapy. Non-critical use of carnitine is both medically incorrect and economically wasteful. Thus, there remains a need in the art for methods to differentiate other etiologies for clinical conditions that have been associated with dialysis related carnitine deficiency and for which intravenous levocarnitine therapy is being considered in the treatment of dialysis patients.  
         SUMMARY OF THE INVENTION  
         [0008]    In light of the above-described and other deficiencies, the present invention as disclosed herein is intended to help health care professionals in the diagnosis of ESRD patients undergoing dialysis with diagnosing clinical conditions and symptoms that are common in hemodialysis patients and to help document the medical necessity of selected treatments. Cliniãal algorithms have been developed for the clinical symptoms seen in ESRD patients that may be related to carnitine deficiency. These symptoms include secondary cardiomyopathy, dialysis related hypotension, cardiac arrhythmia, muscle wasting or weakness, muscle cramping, protein catabolism, lack of energy, and delayed or diminished response to erythropoietin (“EPO”). Monitoring tools to assist health care professionals in implementing the clinical algorithms are also provided.  
           [0009]    ESRD patients with the above conditions, as well as those with poor erythropoietin response, who have demonstrated an inadequate response to appropriate therapy are prescribed a course of intravenous levocarnitine In a recommended range of drug dose and duration of therapy. Once patients have been on this therapy in recommended dose and duration a clinical outcome monitoring tool is used to evaluate a response.  
           [0010]    Embodiments of the present invention provide methods for monitoring and improving the administration of therapeutic levocarnitine to ESRD patients by providing clinical algorithms and accompanying tools that are adapted to assist health care professionals in assessing patient status from such symptoms and identifying appropriate therapeutic actions to take. These methods can also be incorporated as a computer-based software application that records the data for individual patents and systematically guides the health care practitioner through the required steps. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0011]    [0011]FIG. 1 is a schematic diagram depicting the basic patient symptoms and associated diagnostic modules of the present invention.  
         [0012]    [0012]FIG. 2 is a schematic diagram depicting the steps for a cardiomyopathy diagnostic module.  
         [0013]    [0013]FIG. 2 b  is a schematic diagram depicting alternate steps for a cardiomyopathy diagnostic module according to one embodiment of the invention.  
         [0014]    [0014]FIG. 3 is an example of a charting tool for implementing a cardiomyopathy clinical algorithm according to the embodiments of the present invention.  
         [0015]    [0015]FIG. 4 is a schematic diagram depicting the steps for a cardiac arrhythmias diagnostic module.  
         [0016]    [0016]FIG. 5 is an example of a charting tool for implementing a cardiac arrhythmias clinical algorithm according to the embodiments of the present invention.  
         [0017]    [0017]FIG. 6 is a schematic diagram depicting the steps for a muscle weakness diagnostic module.  
         [0018]    [0018]FIG. 7 is an example of a charting tool for implementing a muscle weakness clinical algorithm according to the embodiments of the present invention.  
         [0019]    [0019]FIG. 8 is a schematic diagram depicting the steps for a muscle myopathy diagnostic module.  
         [0020]    [0020]FIG. 9 is an example of a charting tool for implementing a muscle myopathy clinical algorithm according to the embodiments of the present invention.  
         [0021]    [0021]FIG. 10 is a schematic diagram depicting the steps for a malaise/fatigue diagnostic module.  
         [0022]    [0022]FIG. 11 is an example of a charting tool for implementing a malaise/fatigue clinical algorithm according to the embodiments of the present invention.  
         [0023]    [0023]FIG. 12 is a schematic diagram depicting the steps for a delayed or diminished erythropoietin (“EPO”) response diagnostic module.  
         [0024]    [0024]FIG. 13 is an example of a charting tool for implementing a delayed or diminished EPO response clinical algorithm according to the embodiments of the present invention.  
         [0025]    [0025]FIG. 14 is part one of a schematic diagram depicting the steps for a dialysis related hypotension diagnostic module.  
         [0026]    [0026]FIG. 15 is part two of the schematic diagram depicting the steps for a dialysis related hypotension diagnostic module.  
         [0027]    [0027]FIG. 16 is an example of a charting tool for implementing a dialysis related hypotension clinical algorithm according to the embodiments of the present invention.  
         [0028]    [0028]FIG. 17 is an example of a clinical outcome monitoring tool to track a patient&#39;s response to levocarnitine therapy according to the embodiments of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0029]    As shown in FIGS.  1 - 16 , embodiments of the present invention are methods that help health care professionals to associate common symptoms identified in end stage renal disease (“ESRD”) patients with one or more appropriate diagnosing algorithms and their associated tools for monitoring and improving the potential administration of therapeutic levocarnitine to such patients.  
         [0030]    As shown in FIG. 1, symptoms can be associated with one of six diagnosing algorithm and tool sets, namely, the pairs for cardiomyopathy (FIGS.  2 - 3 ), cardiac arrhythmia (FIGS.  4 - 5 ), muscle myopathy (FIGS.  6 - 9 ), malaise/fatigue (FIGS.  10 - 11 ), delayed/diminished response to EPO (FIGS.  12 - 13 ), and dialysis related hypotension (FIGS.  14 - 16 ). In use, a health care professional applies the appropriate diagnosing algorithm (for example, the cardiomyopathy algorithm of FIG. 2) depending upon the symptom(s) (e.g., secondary cardiomyopathy) presented by the ESRD patient to determine the patient&#39;s status and potential suitability for levocarnitine administration. Additionally, the health care professional concurrently with the application of the diagnosing algorithm uses the appropriate monitoring and treatment tool (in the case of the above example, the cardiomyopathy tool illustrated by FIG. 3) to record the patient&#39;s response to the diagnostics (and, potentially, treatments) performed according to the related diagnosing algorithm (i.e., FIG. 2 for cardiomyopathy). FIGS.  2 - 16  describe the application of the diagnosing algorithms and tools according to the invention in detail.  
         [0031]    [0031]FIG. 2 depicts the appropriate diagnosing algorithm for cardiomyopathy  200  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of secondary cardiomyopathy as shown in FIG. 1. According to the algorithm in FIG. 2, a patient with these symptoms is evaluated by clinical exam  210  and considered for a series of treatments  220  known to those skilled in the art that include controlling fluid volume during dialysis, controlling blood pressure, treating arrhythmia, adjusting hematocrit (HCT)/hemoglobin (HGB), and reducing after-load. If these treatments provide adequate improvement upon evaluation  230 , then they are continued  235 , and the patient will continue to be monitored in subsequent clinical exams  210 . If the treatments  220  do no provide adequate improvement upon evaluation  240 , then the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  241 , determine if the pre-dialysis carnitine level is below normal  242 , and, if so, initiate levocarnitine injection therapy  243 . The steps of algorithm  200  are charted in FIG. 3, such that a health care professional can effectively monitor the diagnostic process.  
         [0032]    In one embodiment of the appropriate diagnosing algorithm for cardiomyopathy  200 , step  220  is made of additional steps. One step is considering the possibility of global Hypokinesis  221 , and if present, implementing appropriate treatments such as strict volume control, angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) treatments, beta blocker treatment, arrhythmia treatment, maximum HCT, (not to be excessive), afterload reduction, or strict blood pressure control. Another step is determining if there may be a diastolic dysfunction  224 , and if so, treating appropriately  225 . An additional step is determining if regional abnormalities are present with/without suggestive symptoms through a cardiac catheterization or non-invasive screen  223 . If a remedial lesion  227  is found, then surgery or angioplasty  228  is required. If no remedial lesion is found  226 , then the patient is re-evaluated by clinical exam  229 .  
         [0033]    [0033]FIG. 4 depicts the appropriate diagnosing algorithm  400  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of cardiac arrhythmia as shown in FIG. 1. According to the algorithm in FIG. 4, a patient with these symptoms is evaluated by clinical exam  410 , and the health care professional determines whether the symptoms are related to an underlying medical condition  420  or are related to effects from dialysis  430 . If the arrhythmia symptoms are related to an underlying medical condition, then appropriate treatment  425  relating to the underlying condition must first be provided, and the patient will continue to be monitored in subsequent clinical exams  410 . If the arrhythmia symptoms are determined to be related to dialysis treatment  430 , a series of adjustments to the dialysis process  440  known to those skilled in the art are considered that include optimizing the volume status, adjusting the dialysate if possible, prolonging dialysis to moderate fluid shifts, and administering oxygen during dialysis. If these changes to the dialysis process control the arrhythmia symptoms upon evaluation  450 , then they are continued  455 , and the patient will continue to be monitored in subsequent clinical exams  410 . If changes to the dialysis process do not control the arrhythmia symptoms  450 , then the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  461 , determine if the pre-dialysis carnitine level is below normal  462 , and, if so, initiate levocarnitine injection therapy  463 . The steps of algorithm  400  are charted in FIG. 5, such that a health care professional can effectively monitor the diagnostic process.  
         [0034]    [0034]FIG. 6 depicts the appropriate diagnosing algorithm  600  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of muscle weakness as shown in FIG. 1. Different clinical algorithms are available for symptoms of muscle weakness, as compared to symptoms of general fatigue. According to the algorithm in FIG. 6, a health care professional examines the muscle groups of a patient with these symptoms  610  to determine if the patient exhibits demonstrable muscle weakness. If no demonstrable muscle weakness is identified  620 , then the patient is evaluated for malaise/fatigue  625  in accordance with the steps of FIG. 10. If demonstrable muscle weakness is identified  630 , then the health care professional must rule out the possible effects of an arthritic or injured joint  640  or a sensory abnormality  645  as the cause of the apparent muscle weakness before proceeding to further evaluation. If there are no sensory abnormalities or joint weakness, then the stretch reflexes of the patient are evaluated  650 . If the evaluation shows decreased proximal stretch reflexes or predominant proximal weakness, then the patient is evaluated for muscle myopathy  670  in accordance with the steps of FIG. 8. The steps of algorithm  600  are charted in FIG. 7, such that a health care professional can effectively monitor the diagnostic process.  
         [0035]    [0035]FIG. 8 depicts the appropriate diagnosing algorithm  800  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of muscle weakness/wasting or muscle cramping as shown in FIG. 1. According to the algorithm in FIG. 8, a patient with these symptoms is evaluated by clinical exam  810 , to determine the cause or origin of the muscle cramping of the demonstrated muscle weakness beyond the evaluation of FIG. 6. The health care professional must rule out the possible symptoms of muscle myopathy unrelated to dialysis before proceeding to further evaluation of possible carnitine deficiency.  
         [0036]    Reviewing the steps in FIG. 8, possible acquired infection, inflammation, or malignancy  820  must be considered and, if present, treated using skills known in the art. Also, thyroid disorders  830  must be considered and, if present, treated accordingly. Furthermore, Cushing&#39;s disease  840  must be considered and, if present, treated with appropriate drug therapy or surgery as determined by the health care professional. Additionally, alcohol or drug use  850  may be the cause of the muscle myopathy symptoms, and, if so, the use of the offending agent must be eliminated. Uncontrolled hyperparathyroidism  860  is yet another possibly cause that must be considered, and if present, treated appropriately with suppressive therapy or surgery. Also, osteomalacia  870  must be considered and, if present, treated with appropriate treatment such as vitamin D therapy. Moreover, aluminum toxicity  880  must be considered as a possible cause of muscle myopathy, and, if present, treated with appropriate means such as chelation therapy. Finally, if none of the previous etiologies are present, a carnitine deficiency  890  is a likely cause of muscle myopathy symptoms. As shown in FIG. 8, the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  891 , determine if the pre-dialysis carnitine level is below normal  892 , and, if so, initiate levocarnitine injection therapy  893 . The steps of algorithm  800  are charted in FIG. 9, such that a health care professional can effectively monitor the diagnostic process.  
         [0037]    [0037]FIG. 10 depicts the appropriate diagnosing algorithm  1000  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of protein catabolism or lack of energy as shown in FIG. 1. According to the algorithm in FIG. 10, a patient with these symptoms is evaluated by clinical exam  1010  to rule out a non-renal illness or condition as the cause or origin of the symptoms before evaluating factors specific to dialysis  1020 . The health care professional must consider inadequate dialysis  1030  and incompletely compensated anemia  1040  as possible causes of a patients symptoms of malaise or fatigue. If both inadequate dialysis  1030  and incompletely compensated anemia  1040  are excluded as possible causes  1060 , then the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  1061 , determine if the pre-dialysis carnitine level is below normal  1062 , and, if so, initiate levocarnitine injection therapy  1063 .  
         [0038]    Still referring to FIG. 10, if inadequate dialysis  1030  is a possible cause of the malaise or fatigue symptoms, the dialysis must be adjusted  1050 . If the adjusted dialysis  1050  relives the symptoms of malaise or fatigue  1051 , then the successful measures should be continued  1052  and the patient re-evaluated as necessary  1080 . If the adjusted dialysis  1050  does not relieve the symptoms of malaise or fatigue  1055 , then the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  1061 , determine if the pre-dialysis carnitine level is below normal  1062 , and, if so, initiate levocarnitine injection therapy  1063 . If incompletely compensated anemia  1040  is a possible cause of the malaise or fatigue symptoms, the EPO dose must be adjusted  1070 . If the adjusted EPO dose  1070  produces an adequate response (e.g., relives the symptoms of malaise or fatigue)  1071 , then the successful measures should be continued  1072  and the patient reevaluated as necessary  1080 . If the adjusted EPO dose  1070  produces an inadequate response (e.g., does not relive the symptoms of malaise or fatigue)  1073 , then the patient is evaluated for delayed/diminished response to EPO  1074  in accordance with the steps of FIG. 12. The steps of algorithm  1000  are charted in FIG. 11, such that a health care professional can effectively monitor the diagnostic process.  
         [0039]    [0039]FIG. 12 depicts the appropriate diagnosing algorithm  1200  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of delayed or diminished response to EPO as shown in FIG. 1. According to the algorithm in FIG. 12, a patient is evaluated by clinical exam  1210  to rule out symptoms of delayed or diminished response to EPO that are unrelated to reduced carnatine levels before proceeding to further evaluation of possible carnitine deficiency.  
         [0040]    Reviewing the steps in FIG. 12, iron deficiency  1220  must be considered and, if present, treated accordingly with, for example, supplemental iron. Also, possible acquired infection, inflammation, or malignancy  1230  must be considered and, if present, treated using skills known in the art. Furthermore, occult blood loss  1240  must be considered and, if present, the source of bleeding identified and treated with appropriate measures. Additionally, an underlying hematologic disease  1250 , such as thalassemia, refractory anemia, or other myelodysplastic disorders, may be the cause of the delayed or diminished response to EPO symptoms, and, if so, these diseases must be treated accordingly. Hemolysis  1260  is yet another possibly cause that must be considered, and if present, treated appropriately. Also, osteitis fibrosa cystica  1270  must be considered and, if present, treated with standard medical treatment. Moreover, aluminum intoxication  1280  must be considered as a possible cause of delayed or diminished response to EPO, and, if present, treated with appropriate means such as chelation therapy. Likewise, vitamin deficiencies  1285 , such as a lack of folic acid or vitamin B12, must be considered and, if present, treated accordingly with, for example, supplemental vitamins. Finally, if none of the previous indications are present, a carnitine deficiency  1290  is a likely cause of the delayed or diminished response to EPO symptoms. As shown in FIG. 12, the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  1291 , determine if the pre-dialysis carnitine level is below normal  1292 , and, if so, initiate levocarnitine injection therapy  1293 . The steps of algorithm  1200  are charted in FIG. 13, such that a health care professional can effectively monitor the diagnostic process.  
         [0041]    [0041]FIG. 14 a  depicts the appropriate diagnosing algorithm  1400  to determine a patient&#39;s status and potential suitability for levocarnitine administration given the symptoms of dialysis related hypotension as shown in FIG. 1. According to the algorithm in FIG. 14 a , a patient with these symptoms is evaluated by clinical exam  1410  for hypotension (e.g., sustained pre- or post-dialysis blood pressure less than 110 systolic or a decline in systolic blood pressure greater than 20 mm Hg which is either (a) associated with symptoms referable to hypotension, (b) requires intervention, or (c) compromises the intended dialysis prescription). From the examination  1410 , the health care professional determines whether the symptoms of hypotension are an acute episode  1420  or a chronic sustained condition  1450 . If the symptoms indicate an acute episode  1420 , then the health care professional initiates immediate corrective measures  1430 , such as repositioning said the patient into a Trendelenberg position, using IV fluid, decreasing or zeroing ultrafiltration rate (UFR) for the dialysis, considering use of oxygen, or considering the causes as in chronic sustained step  1450 . If the acute episode is not indicative of repetitive intradialytic hypotension, then intermittent acute treatment is continued  1445 . If the acute episode  1420  is indicative of repetitive intradialytic hypotension, then the health care professional must apply initial measures  1490  known to those skilled in the art as appropriate to the patient&#39;s situation, such as using a machine with ultrafiltration control, counseling patient to limit salt, aiming for intradialytic weight gain greater than 1 kg/d, re-evaluating dry weight and avoiding ultrafiltration below that value, using bicarbonate containing dialysate, and reviewing anemia treatment to see if improvements are necessary.  
         [0042]    Continuing with FIG. 14 a , if the symptoms are a chronic sustained condition  1440 , then the health care professional conducts a series of diagnostics  1450 , including electrocardiograms, evaluating for pericarditis, testing for congestive heart failure (CHF), considering possible valve problems, checking for ischemia, testing for infections, considering hematologic disorders, and evaluating for sepsis. If the diagnostics  1450  indicate persistent hypotension despite treatment of the underlying condition, then the health care professional must apply initial measures  1490  known to those skilled in the art as appropriate to the patient&#39;s situation. If the diagnostics  1450  indicate hypotension is related to the underlying condition, then the treatment of the underlying condition is continued  1475 , as necessary.  
         [0043]    Referring to FIG. 14 b , if the initial measures of step  1490  show inadequate improvement  1500 , the health care professional must apply additional measures  1510  according to his skill in the art and patient tolerance, such as withholding pre hemodialysis blood pressure medications, lowering dialysate temperature, omitting specific foods or glucose containing solutions, adjusting dialysate calcium, conducting high sodium or sodium gradient dialysis, using a blood volume monitor, adding additional treatment(s) per week, and conducting sequential treatments. If these measures provide adequate improvement  1560  for the patient&#39;s conditions, then the successful measures should be continued  1570  and the patient reevaluated as necessary  1580 . If the additional measures of step  1510  show inadequate improvement  1520 , then health care professional must consider pharmacological therapy measures  1530 , such as Midodrine, Caffeine, Florinef, and Pseudoephridrine. If these pharmacological therapy measures provide adequate improvement  1560  for the patient&#39;s conditions, then the successful measures should be continued  1570  and the patient re-evaluated as necessary  1580 . If the measures of step  1530  show inadequate improvement  1540 , then the health care professional will evaluate the patient&#39;s pre-dialysis plasma carnitine concentration  1541 , determine if the pre-dialysis carnitine level is below normal  1542 , and, if so, initiate levocarnitine injection therapy  1543 . If the levocarnitine injection therapy  1543  provides adequate improvement  1560  for the patient&#39;s conditions, then the successful measures should be continued  1570  and the patient re-evaluated as necessary  1580 . If the measures of step  1543  show inadequate improvement  1545 , then the health care professional will reevaluate the underlying pathology, consider Parkinsons Disease, and evaluate transplant urgency. The steps of algorithm  1400  are charted in FIG. 15, such that a health care professional can effectively monitor the diagnostic process.  
         [0044]    ESRD patients with the above conditions, as well as those with erythropoietin resistance, who are unresponsive to standard therapy are prescribed levocarnitine, generally 20 mg/kg/dialysis session. Once patients are on the therapy, the clinical outcome monitoring tool, as shown in FIG. 16, is used to evaluate a patient&#39;s response. The monitoring tool provides a map of key indicators from laboratory test results, patient intake of medication and supplements, and patient assessments. These key indicators are measured preferably before initiating levocarnitine injection therapy, after one month, after three months and after six months from the start of therapy.  
         [0045]    As will be readily understood by one of ordinary skill in the art, the present invention can preferably be automated with software as is known in the art such that a computing device can be adapted to interact with health care professionals via a software interface and assist such professionals in appropriately utilizing and applying the algorithms and tools disclosed herein. In this manner, the health care professional can be automatically prompted to consider appropriate follow-up questions or considerations, or prompted to take appropriate diagnostic actions based upon the application of the algorithms and tools herein disclosed to the feedback data provided by the user. Once the health care professional has provided sufficient feedback data to the software automating the present invention, he or she can then be provided with a well-defined clinical picture that helps him or her identify a recommended course of action with respect to therapeutic carnitine administration.  
         [0046]    Various modifications of the embodiments herein disclosed will be readily apparent to one skilled in the art after reading the above. For example, algorithms and tools automated by software according to alternative embodiments of the present invention may be adapted to store patient data and thereby automatically create patient logs and charts based upon the feedback data entered by the users of tools. Any and all such modifications are intended to be covered by the application as claimed.