Does Femoral Component Cementation Affect Costs or Clinical Outcomes After Hip Arthroplasty in Medicare Patients?

BACKGROUND: Bundled payment initiatives were introduced to reduce costs and improve quality of care. Cemented vs cementless femoral fixation is a modifiable variable that may influence the cost and quality of care. New bundled payment data from the Centers for Medicare and Medicaid Services allowed us to study the influence of femoral fixation strategy on (1) 90-day costs; (2) readmission rates; (3) reoperation rates; (4) length of stay (LOS); and (5) discharge disposition for Medicare patients undergoing total hip arthroplasty. METHODS: We retrospectively studied 1671 primary total hip arthroplasty Medicare cases, comparing 359 patients who received cemented femoral fixation to 1312 patients who received cementless fixation. Centers for Medicare and Medicaid Services cost data as well as clinical data were reviewed. Demographic differences were present between the 2 cohorts. Statistical analyses were performed, including multiple regression models to adjust for baseline differences. RESULTS: Controlling for cohort differences, cemented patients were significantly more likely to be discharged home compared to cementless patients. Cemented patients also demonstrated trends toward lower costs, lower readmission rates, and shorter LOS compared to cementless patients. All reoperations within the early postoperative period occurred in patients managed with cementless femoral fixation. CONCLUSION: Among Medicare patients, cemented femoral fixation outperformed cementless fixation with respect to discharge disposition and also trended toward superiority with regards to LOS, readmission, cost of care, and reoperation. Cemented femoral fixation remains relevant and useful despite the rising popularity of cementless fixation.

Direct treatment cost outcomes among patients with medial meniscus deficiency: results from a 24-month surveillance study.

Objective: Meniscus deficiency is highly prevalent in the United States and represents a substantial societal cost burden. The objective of this case series was to evaluate and compare direct costs associated with treatment for acute or degenerative medial meniscus deficiency.Methods: Case series patients (n = 50) received either non-surgical therapy or an operative partial meniscectomy based on clinical assessment by the principal study investigator which included physical examination and MRI. Cumulative 24-month direct treatment costs were compared between non-surgical and operative cohorts. Direct treatment costs were calculated using billing record reimbursements for all medical services administered by the treating institution, and imputed for medical services prescribed by the treating physician but provided external to the treating institution.Results: At study initiation, 33 patients (67%) were treated with non-surgical care, and 17 patients (33%) received a partial medial meniscectomy. By 24 months, average direct treatment costs were highest for patients who received a partial medial meniscectomy at study initiation ($4488 ± $1265) compared to patients who received non-surgical care at study initiation ($4092 ± $7466), although differences in average direct treatment costs were not statistically significant across treatment cohorts (p = .830). Average direct treatment costs were highest for the subgroup of patients who initiated non-surgical therapy but received a subsequent total knee arthroplasty during the study period (n = 2; $32,197 ± $169).Conclusion: Findings from this case series suggests that patients with acute or degenerative meniscus deficiency incur substantial direct treatment costs related to their knee pathology, particularly for patients receiving total knee arthroplasty.

Monitoring Surgical Incision Sites in Orthopedic Patients Using an Online Physician-Patient Messaging Platform.

BACKGROUND: Prompt identification and treatment of wound complications is essential after joint arthroplasty, but emergency department and office visits for urgent evaluation of normal incisions are a source of unnecessary cost. The purpose of this study is to evaluate the use of an online image messaging platform for remote monitoring of surgical incision sites. METHODS: We conducted a retrospective review of 1434 hip and knee arthroplasty patients who registered for an online platform in the perioperative period. We reviewed images sent by patients to evaluate potential wound abnormalities. Medical records were reviewed to determine whether assessments based on wound photographs corresponded with subsequent in-person findings and ultimate disposition. RESULTS: Four hundred thirty patients (42%) sent at least one text or image message to their provider. Elimination of redundant images resulted in 104 image encounters, with 76 discrete encounters in 41 patients related to the surgical wound. Most showed normal wound appearance; patients were reassured and urgent visits were avoided. At scheduled in-person follow-up, none of these patients demonstrated unrecognized wound complications. Seventeen image encounters in 7 patients showed possible wound abnormalities. These prompted in-person follow-up on average less than 1 day later for 4 issues deemed urgent (2 patients received surgical treatment) and 5 days later for issues deemed nonurgent. Photos were also used to monitor abnormal wounds over time and to send information unrelated to wounds. CONCLUSION: Utilization of an online physician-patient messaging platform can prevent unnecessary visits for normal appearing wounds, while facilitating rapid in-person treatment of wound complications.

Surgical and Medical Costs for Fibromyalgia Patients Undergoing Total Knee Arthroplasty.

The potential added costs of managing fibromyalgia patients after total knee arthroplasty (TKA) have not been assessed. Therefore, the purpose of this study was to perform a cost analysis of fibromyalgia versus nonfibromyalgia patients who underwent TKA. Specifically, we evaluated the following episodes of care: (1) readmission rates, (2) total costs, (3) total reimbursements, and (4) net losses for surgical and medical complications. Patients who underwent TKAs between 2005 and 2014 from the Medicare Standard Analytical Files of the PearlDiver supercomputer were propensity score matched by patients with and without fibromyalgia in a 1:1 ratio based on age, sex, and the Charlson Comorbidity Index, yielding a total of 305,510 patients distributed equally between the cohorts for analysis. Odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated. Mean costs, total costs, and total reimbursements were assessed as along with total net losses, which were defined as total costs minus total reimbursements. Fibromyalgia patients had similar 90-day readmission rates compared with nonfibromyalgia patients (OR: 1.03; 95% CI: 1.00-1.06; p = 0.06) but incurred lower readmission costs (US$2,318,384,295 vs. US$2,534,482,404; p < 0.001). Although fibromyalgia patients had higher total reimbursements for medical complications ($27,758,057 vs. US$18,780,610; p < 0.001), the increased management costs (US$106,049,870 vs. US$66,080,469; p < 0.001) led to greater net losses (US$78,291,813 vs. US$47,299,859; p < 0.001). Similarly, although fibromyalgia patients had higher total reimbursements for surgical complications (US$94,192,334 vs. US$73,969,026; p < 0.001), the increased surgical costs (US$382,122,613 vs. US$306,359,910; p < 0.001) led to greater net losses (US$287,930,279 vs. US$232,390,884; p < 0.001). This study highlights some of the potential financial discrepancies of managing patients with fibromyalgia. Our findings suggest medical and surgical complication costs to be greater than reimbursement, resulting in overall net financial losses. These findings need to be considered in the light of health care reform and cost structuring.

A nationwide comparative analysis of medical complications in fibromyalgia patients following total knee arthroplasty.

BACKGROUND: Fibromyalgia is a disease primarily characterized by chronic widespread pain and associated symptoms of fatigue, mild cognitive impairment, and sleep disturbance. The condition affects 1% to 6% of the general population in the United States and is more commonly diagnosed in women (2:1 ratio). There is evidence to suggest that fibromyalgia patients may be more at risk of postoperative complications. The rate of total knee arthroplasties (TKAs) performed worldwide is escalating and thus it is expected that the proportion of fibromyalgia patients under orthopaedic care will increase accordingly. However, the literature on TKA outcomes in this subpopulation is limited. We assessed whether fibromyalgia patients have a higher likelihood of developing medical complications compared to a matched cohort of non-fibromyalgia patients following TKA. Specifically, we assessed the likelihood of developing (I) any medical complication and (II) specific medical complications. METHODS: Using the Medicare Standard Analytical Files of the PearlDiver supercomputer, patients who underwent a TKA between 2005 and 2014 were queried. Propensity score matching was used to match patients with and without fibromyalgia in a 1:1 ratio based on age, sex, and the Charlson Comorbidity Index (CCI). A total cohort of 305,510 patients (female =242,198; male =59,810; and unknown =3,502) with (n=152,755) and without fibromyalgia (n=152,755) was identified. Statistical analyses involved the calculation of odds ratios, 95% confidence intervals (95% CI), and P values (<0.05) were utilized to evaluate the occurrence of any and specific medical complications. RESULTS: Compared to a matched cohort of non-fibromyalgia patients, fibromyalgia patients had increased odds of developing any medical complication following TKA [odds ratio (OR): 1.95, 95% CI: 1.86-2.04, P<0.001]. Furthermore, compared to a matched cohort, these patients had significantly greater odds of developing urinary tract infections (OR: 2.08, 95% CI: 1.89-2.29, P<0.001), acute post-hemorrhagic anemia (OR: 1.56, 95% CI: 1.41-1.73, P<0.001), thoracic or lumbosacral neuritis or radiculitis (OR: 5.85, 95% CI: 4.82-7.10, P<0.001), shortness of breath (OR: 3.02, 95% CI: 2.60-3.51, P<0.001), other diseases of lung not elsewhere classified (OR: 2.32, 95% CI: 1.77-3.03, P<0.001), other respiratory abnormalities (OR: 3.49, 95% CI: 2.87-4.24, P<0.001), transfusion of packed cells (OR: 1.69, 95% CI: 1.36-2.10, P<0.001), pneumonia (OR: 2.17, 95% CI: 1.71-2.76, P<0.001), acute kidney failure (OR: 1.27, 95% CI: 1.02-1.57, P<0.05), and neuralgia neuritis and radiculitis (OR: 5.29, 95% CI: 3.53-7.92, P<0.001). CONCLUSIONS: As the number of fibromyalgia patients under orthopaedic care is expected to rise, it is imperative that the TKA outcomes of these patients are tracked in order to provide optimal patient care. This study identified fibromyalgia as a risk factor for a number of medical complications following TKA. Orthopaedic surgeons must be aware of the potential for poor TKA outcomes among these patients and should provide them with appropriate medical care and pre-operative guidance.

Survivorship and Radiographic Analysis of Highly Porous Acetabular Cups Designed for Improved Osseointegration Potential.

INTRODUCTION: A variety of highly porous materials have been used to obtain biological acetabular fixation after total hip arthroplasty (THA). Due to their improved surface-coated properties, new highly porous titanium metal implants have shown potential to promote prosthesis osseointegration. Therefore, the purpose of this multicenter study was to evaluate: 1) overall acetabular cup survivorship; 2) postoperative complications; and 3) radiographic signs of loosening and radiolucencies in patients who received a new highly porous titanium metal cup. MATERIALS AND METHODS: A total of 81 patients who underwent primary THA and received a new porous acetabular cup between May 16, 2013 and January 27, 2016 at three academic centers were included for analysis. There were 40 women (49%) and 41 men (51%) who had a mean age of 65 years (range, 38 to 95 years) and a mean body mass index (BMI) of 28 kg/m2 (range, 16 to 43 kg/m2). The minimum follow up time was two years and seven months (range, 2 to 4 years). The cup was engineered with fully interconnected porosity designed for potential long-term biologic fixation. Medical records were reviewed to assess for any revision surgeries and postoperative complications, and the most recent radiographs were reviewed for signs of loosening or radiolucencies. RESULTS: Overall, acetabular component survivorship, free of fixation failure or aseptic loosening, was 100%. Two patients underwent revision due to dislocations; however, revisions were performed because no constrained or dual mobility liners were available for the shell at the time. Both patients had successful outcomes and were doing well at final follow up with no further episodes of dislocation. There was one open reduction internal fixation for a periprosthetic femoral fracture, and three polyethylene revisions were performed for instability. In all of these cases, the acetabular cup was retained. On radiographic evaluation of antero-posterior pelvis radiographs, there was one patient who had radiolucencies of <1mm in Zone 1 and Zone 2 at 15 months after surgery, and another patient demonstrated radiolucencies of <1mm in Zone 2 and 3 at one-year follow up. At a minimum of two-year follow up, both patients had non-progressive and stable findings. CONCLUSION: The results of this study demonstrated excellent survivorship, and there were no radiographic failures of this acetabular cup in primary total hip arthroplasty patients. Although two patients were found to have minimal (<1mm) radiolucencies, these were not progressive. Longer follow-up studies are needed to further assess the survivorship and outcomes of this new acetabular cup; however, based on the results of this study, these are expected to be favorable.

Genetic addiction risk score (GARS) ™, a predictor of vulnerability to opioid dependence.

The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS). Innovative strategies to combat epidemic opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, are proposed. Sensitivity to pain may reside in the mesolimbic projection system, where genetic polymorphisms associate with a predisposition to pain vulnerability or tolerance. They provide unique therapeutic targets that could assist in the treatment of pain, and identify risk for subsequent addiction. Pharmacogenomic testing of candidate genes like CB1, mu receptors, and PENK might result in pharmacogenomic, personalized solutions, and improved clinical outcomes. Genetically identifying risk for all RDS behaviors, especially in compromised populations, may be a frontline tool to assist municipalities to provide better resource allocation.

Pro-Dopamine Regulator - (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome (RDS).

We are faced with a worldwide opiate/opioid epidemic that is devastating. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day in America due to narcotic overdose. The Food and Drug Administration (FDA) has approved Medication-Assisted Treatments (MATs) for opiate/opioids as well as alcohol and nicotine. The mechanism of action of most MATS favors either blocking of dopaminergic function or a form of Opiate Substitution Therapy (OST). These treatment options are adequate for short-term treatment of the symptoms of addiction and harm reduction but fail long-term to deal with the cause or lead to recovery. There is a need to continue to seek better treatment options. This mini-review is the history of the development of one such treatment; a glutaminergic-dopaminergic optimization complex called KB220. Growing evidence indicates that brain reward circuitry controls drug addiction, in conjunction with "anti-reward systems" as the "anti-reward systems" can be affected by both glutaminergic and dopaminergic transmission. KB220 may likely alter the function of these regions and provide for the possible eventual balancing the brain reward system and the induction of "dopamine homeostasis." Many of these concepts have been reported elsewhere and have become an integral part of the addiction science literature. However, the concise review may encourage readership to reconsider these facts and stimulate further research focused on the impact that the induction of "dopamine homeostasis" may have on recovery and relapse prevention.

Neurogenetics of acute and chronic opiate/opioid abstinence: treating symptoms and the cause.

This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets. Alterations in functional brain connectivity based on neurobiological mechanisms in heroin dependence and abstinence are also reviewed. A new clinical model an alternative to merely blocking acute withdrawal symptoms as identified in the DSM -5 is proposed. Genetic diagnosis at the onset of detoxification, to determine risk stratification, and identify polymorphic gene targets for pharmaceutical and nutraceutical interventions, followed by the simultaneous initiation of Medication Assisted Therapy (MAT), to enable psychological extinction, and steady pro-dopaminergic therapy with the goal of developing "dopamine homeostasis" is recommended. The objective of these interventions is to prevent future relapse by treating all "Reward Deficiency Syndrome" (RDS) behaviors and eventually make an addiction-free life possible.

Hypothesizing That Neuropharmacological and Neuroimaging Studies of Glutaminergic-Dopaminergic Optimization Complex (KB220Z) Are Associated With "Dopamine Homeostasis" in Reward Deficiency Syndrome (RDS).

BACKGROUND: There is need for better treatments of addictive behaviors, both substance and non-substance related, termed Reward Deficiency Syndrome (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal. OBJECTIVES: It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation. METHODS: We are thus proposing a paradigm shift in addiction treatment, with the long-term goal of achieving "Dopamine Homeostasis." While this may be a laudable goal, it is very difficult to achieve. Nevertheless, this commentary briefly reviews past history of developing and subsequently, utilizing a glutaminergic-dopaminergic optimization complex [Kb220Z] shown to be beneficial in at least 20 human clinical trials and in a number of published and unpublished studies. RESULTS: It is our opinion that, while additional required studies could confirm these findings to date, the cited studies are indicative of achieving enhanced resting state functional connectivity, connectivity volume, and possibly, neuroplasticity. Conclusions/Importance: We are proposing a Reward Deficiency Solution System (RDSS) that includes: Genetic Addiction Risk Score (GARS); Comprehensive Analysis of Reported Drugs (CARD); and a glutaminergic-dopaminergic optimization complex (Kb220Z). Continued investigation of this novel strategy may lead to a better-targeted approach in the long-term, causing dopamine regulation by balancing the glutaminergic-dopaminergic pathways. This may potentially change the landscape of treating all addictions leading us to the promised land.

Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape.

BACKGROUND: In 1990, Blum and associates provided the first confirmed genetic link between the DRD2 polymorphisms and alcoholism. This finding was based on an earlier conceptual framework, which served as a blueprint for their seminal genetic association discovery they termed "Brain Reward Cascade." These findings were followed by a new way of understanding all addictive behaviors (substance and non-substance) termed "Reward Deficiency Syndrome" (RDS). RDS incorporates a complex multifaceted array of inheritable behaviors that are polygenic. OBJECTIVE: In this review article, we attempt to clarify these terms and provide a working model to accurately diagnose and treat these unwanted behaviors. METHOD: We are hereby proposing the development of a translational model we term "Reward Deficiency Solution System™" that incorporates neurogenetic testing and meso-limbic manipulation of a "hypodopaminergic" trait/state, which provides dopamine agonistic therapy (DAT) as well as reduced "dopamine resistance," while embracing "dopamine homeostasis." RESULT: The result is better recovery and relapse prevention, despite DNA antecedents, which could impact the recovery process and relapse. Understanding the commonality of mental illness will transform erroneous labeling based on symptomatology, into a genetic and anatomical etiology. WC: 184.

Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs.

The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli's effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies.

Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic.

Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of "dopamine resistance" by inducing "dopamine homeostasis." While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion Certainly, it is our position that there is an overlap between food- and drug-seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted.

Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity.

Willuhn et al., observed that habitual cocaine use was correlated with reductions in D2/D3 receptors linked to decreased cue activation in occipital cortex and cerebellum. Dopamine agonist therapy maintains dopamine function and is a relapse prevention tactic focused on psychoactive drug and behavioral addictions. Medication Assisted Treatment (MAT) with emphasis on glutaminergic medications fails in the long-term treatment of Reward Deficiency Syndrome Behaviors (RDS). While the careful use of "dopamine antagonist-therapy" short-term is supported, the research-based concept of "dopamine agonist therapy" in long-term is proposed. Neurogenetics and epigenetics are important in understanding treatment response and clinical outcomes. The neuro-mechanisms involving "dopamine homeostasis" are key to understanding recovery from drug and non-drug addictive behaviors. For example, patients who carry the DRD2 A1 allele (30-40 less D2 receptors) should consider Neuronutriant-Amino-Acid therapy (KB220 variants) a prevention modality. DRD2 A1 allele carriers show amplified striatal function of L-amino acid decarboxylase, prior to dopamine biosynthesis. Another example is the effect of Acute Tyrosine Phenylalanine Depletion (ATPD) on decision-making and reward found carriers with amino-acid deficiency (ATPD). They experienced attenuated reward and reduced decision-making ability as quantified by Iowa Gambling Task (IGT). Future research should be directed at asking the question; Would "dopamine agonist therapy" using KB220 variants reduce methylation and increase acetyl groups to enhance DRD2 expression especially in DRD2 A1 allele carriers and lead to increased dopamine function and a reduction of drug and non-drug seeking behaviors?

Should the United States Government Repeal Restrictions on Buprenorphine/Naloxone Treatment?

Attention must be focused on needed changes to the current United States law that restricts physicians who prescribe buprenorphine for the detoxification or treatment of Opioid Use Disorder, to accepting no more than 100 patients. The current system does not provide comprehensive treatment as defined by the American Society of Addiction Medicine (ASAM) criteria. In addition, it suffers from both fragmentation and stigma and will require a significant change to comply with ASAM's call for integrated delivery of comprehensive addiction treatment. This commentary calls for the development and implementation of "best practice," by recommending caution in lifting the 100 patient limit until substantial achievement of this goal occurs. The authors call for an increase to 200 in the patient limit to be restricted to those physicians who are Board Certified in Addiction Medicine by the American Board of Addiction Medicine (ABAM) or in Addiction Psychiatry by the American Board of Psychiatry and Neurology (ABPN), or other responsible medical organizations. Any additional restriction lifting should follow a systemic evolution that rewards and documents competency. Such a system would involve the integration of treatment, treatment systems, and recovery with prescription medication. In addition, it should monitor emotional blunting, treatment progress and initiation of genetic addiction risk testing.

THE BENEFITS OF CUSTOMIZED DNA DIRECTED NUTRITION TO BALANCE THE BRAIN REWARD CIRCUITRY AND REDUCE ADDICTIVE BEHAVIORS.

DNA Customization of nutraceutical products is here. In the truest sense, "Gene Guided Precision Nutrition™" and KB220 variants (a complex mixture of amino-acids, trace metals, and herbals) are the pioneers and standard-bearers for a state of the art DNA customization. Findings by both, Kenneth Blum, Ph.D. and Ernest Noble, Ph.D. concerning the role of genes in shaping cravings and pleasure- seeking, opened the doors to comprehension of how genetics control our actions and effect our mental and physical health. Moreover, technology that is related to KB220 variants in order to reduce or eradicate excessive cravings by influencing gene expression is a cornerstone in the pioneering of the practical applications of nutrigenomics. Continuing discoveries have been an important catalyst for the evolution, expansion, and scientific recognition of the significance of nutrigenomics and its remarkable contributions to human health. Neuro-Nutrigenomics is now a very important field of scientific investigation that offers great promise to improving the human condition. In the forefront is the development of the Genetic Addiction Risk Score (GARS™), which unlike 23andMe, has predictive value for the severity of drug and alcohol abuse as well as other non-substance related addictive behaviors. While customization of neuronutrients has not yet been commercialized, there is emerging evidence that in the future, the concept will be developed and could have a significant impact in addiction medicine.

Hypothesizing that a Pro-Dopaminergic Regulator (KB220z™ Liquid Variant) can Induce "Dopamine Homeostasis" and Provide Adjunctive Detoxification Benefits in Opiate/Opioid Dependence.

In order to explore the initiation of detoxification of addictive patients to opiates/opioids (along with some other anti-withdrawal agents), we developed a protocol to be utilized in treatment centers particularly with heavily dependent opiate/opioid subjects. Out of 17 subjects, only three received Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a dose of KB220Z of 2 oz twice daily before meals along with clonidine and benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The dose of KB220Z was maintained for 6 days in five individuals. In a second scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period. The higher dose was employed in another 12 patients. It is noteworthy that only 3 people have relapsed utilizing these two protocols during the first two weeks of the study, allowing for the remaining 82% to be maintained on KB220Z. The patients have been maintained without any additional Bup/nx for a minimum of 120 days and in one subject, 214 days. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates utilizing data from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates. While this does not constitute an acceptable controlled experiment, it does provide some preliminary evidence that agrees with an earlier study. Moreover, because of the utilization of standard detoxifying agents in this detoxification protocol, we cannot make any inference to KB220Z's effects. However, out of 17 subjects, only three required Bup/nx suggesting an interesting finding. If further confirmed in larger studies, the utilization for opiate/opioid detoxification may provide a novel way to eliminate the need for addictive opioids during withdrawal and detoxification. This paradigm shift may translate to a reduction in utilizing powerful and addictive opioids like buprenorphine and methadone (especially in these patients at high genetic risk for addiction) as not only detoxifying agents, but also maintenance drugs. While extensive research is required, this pilot paves the way for future investigations that could assist in the reduction of addictive opiate/opioid use and mortalities amongst both the young and old in America.

KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

BACKGROUND: Recent reports by our laboratory have indicated that lucid dreams may be linked to psychiatric conditions, including Attention Deficit Hyperactivity Disorder (ADHD) and other Reward Deficiency Syndrome-related diagnoses. In the latter case, it has been our observation that such lucid dreams can be unpleasant and frequently terrifying. CASE PRESENTATIONS: We present four cases of a dramatic and persistent alleviation of terrifying, lucid dreams in patients diagnosed with ADHD/PTSD and/or opiate/opioid addiction. The amelioration of such dreams could well be permanent, since the patients had stopped taking the nutraceutical for between 10 to 12 months, without their recollection or recurrence. In the first case, the patient is a 47-year-old, married male who required continued Buprenorphine/ Naloxone (Suboxone) treatment. The second case involved a 32-year-old female with the sole diagnosis of ADHD. The third case involves a 38-year-old male who carried the diagnoses of Substance Use Dependence and ADHD. The fourth case involved a 50-year-old female with the diagnoses of Alcohol Abuse, ADHD and Posttraumatic Stress Disorder. RESULTS: In order to attempt to understand the possibility of neuroplasticity, we evaluated the effect of KB220Z in non-opioid-addicted rats utilizing functional Magnetic Resonance Imaging methodology. While we cannot make a definitive claim because rat brain functional connectivity may not be exactly the same as humans, it does provide some interesting clues. We did find following seeding of the dorsal hippocampus, enhanced connectivity volume across several Regions of Interest (ROI), with the exception of the pre- frontal cortex. Interestingly, the latter region is only infrequently activated in lucid human dreaming, when the dreamer reports that he/she had the thought that they were dreaming during the lucid dream. CONCLUSIONS: The four patients initially reported a gradual but, then, complete amelioration of their long-term, terrifying, lucid dreams, while taking KB220Z. The persistent amelioration of these dreams continued for up to 12 months, after a self-initiated, cessation of use of KB220Z. These particular cases raise the scientific possibility that KB200Z increases both dopamine stability as well as functional connectivity between networks of brain reward circuitry in both rodents and humans. The increase in connectivity volume in rodents suggest the induction of neuroplasticity changes, which may be analogous to those involved in human lucid dreaming as well as Rapid Eye Movement sleep. The possibility that the complex induces long-term, neuroplasticity changes must await more intensive investigations, involving large-population, double-blinded studies.

Hypothesizing that, A Pro-Dopamine Regulator (KB220Z) Should Optimize, but Not Hyper-Activate the Activity of Trace Amine-Associated Receptor 1 (TAAR-1) and Induce Anti-Craving of Psychostimulants in the Long-Term.

Unlike other drugs of abuse such as alcohol, nicotine, opiates/opioids, the FDA has not approved any agent to treat psychostimulant dependence. Certainly, it is widely acceptable that dopaminergic signaling is a key factor in both the initiation and continued motivation to abuse this class of stimulant substances. It is also well accepted that psychostimulants such as cocaine affect not only the release of neuronal dopamine at the nucleus accumbens (NAc), but also has powerful inhibitory actions on the dopamine transporter system. Understandably, certain individuals are at high risk and very vulnerable to abuse this class of substances. Trace-amine-associated receptor 1 (TAAR1) is a G -protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to beta-phenylethylamine, p-tyramine, octopamine, and tryptamine. This gene is thought to be intronless. TAAR1 agonists reduce the neurochemical effects of cocaine and amphetamines as well as attenuate addiction and abuse associated with these two psychostimulants. The mechanism involves blocking the firing rate of dopamine in the limbic system thereby decreasing a hyperdopaminergic trait/state, whereby the opposite is true for TAAR1 antagonists. Based on many studies, it is accepted that in Reward Deficiency Syndrome (RDS), there is weakened tonic and improved phasic dopamine discharge leading to a hypodopaminergic/glutamatergic trait. The dopamine pro-complex mixture KB220, following many clinical trials including neuroimaging studies, has been shown to enhance resting state functional connectivity in humans (abstinent heroin addicts), naïve rodent models, and regulates extensive theta action in the cingulate gyrus of abstinent psychostimulant abusers. In this article, we are hypothesizing that KB220 may induce its action on resting state functional connectivity, for example, by actually balancing (optimizing) the effects of TAAR1 on the glutamatergic system allowing for optimization of this system. This will lead to a normalized and homeostatic release of NAc dopamine. This proposed optimization, and not enhanced activation of TAAR1, should lead to well-being of the individual. Hyper-activation instead of optimizing the TAAR1 system unfortunately will lead to a prolonged hypodopaminergic state and as such, will cause enhanced craving for not only psychoactive substances, but also other drug-related and even non-drug related RDS behaviors. This hypothesis will require extensive research, which seems warranted based on the global epidemic of drug and behavioral addictions.

Neurobiology of KB220Z-Glutaminergic-Dopaminergic Optimization Complex [GDOC] as a Liquid Nano: Clinical Activation of Brain in a Highly Functional Clinician Improving Focus, Motivation and Overall Sensory Input Following Chronic Intake.

BACKGROUND: With neurogenetic and epigenetic tools utilized in research and neuroimaging, we are unraveling the mysteries of brain function, especially as it relates to Reward Deficiency (RDS). We encourage the development of pharmaceuticals or nutraceuticals that promote a reduction in dopamine resistance and balance brain neurochemistry, leading to dopamine homeostasis. We disclose self-assessment of a highly functional professional under work-related stress following KB220Z use, a liquid (aqua) nano glutaminergic-dopaminergic optimization complex (GDOC). CASE PRESENTATION: Subject took GDOC for one month. Subject self-administered GDOC using one-half-ounce twice a day. During first three days, unique brain activation occurred; resembling white noise after 30 minutes and sensation was strong for 45 minutes and then dissipated. He described effect as if his eyesight improved slightly and pointed out that his sense of smell and sleep greatly improved. Subject experienced a calming effect similar to meditation that could be linked to dopamine release. He also reported control of going over the edge after a hard day's work, which was coupled with a slight increase in energy, increased motivation to work, increased focus and multi-tasking, with clearer purpose of task at hand. Subject felt less inhibited in a social setting and suggested Syndrome that GDOC increased his Behavior Activating System (reward), while having a decrease in the Behavior Inhibition System (caution). CONCLUSION: These results and other related studies reveal an improved mood, work-related focus, and sleep. These effects as a subjective feeling of brain activation maybe due to direct or indirect dopaminergic interaction. While this case is encouraging, we must await more research in a larger randomized placebo-controlled study to map the role of GDOC, especially in a nano-sized product, to determine the possible effects on circuit inhibitory control and memory banks and the induction of dopamine homeostasis independent of either hypo- or hyper-dopaminergic traits/states.