scholarly journals Retrospective Analysis of Healthcare Resource Use, Treatment Patterns, and Treatment-related Events in Patients with Huntington’s Disease–associated Chorea Initiated on Tetrabenazine

10.36469/9779 ◽  
2018 ◽  
Vol 6 (1) ◽  
pp. 15-24
Author(s):  
Victor W. Sung ◽  
Sanjay K. Gandhi ◽  
Victor Abler ◽  
Brian Davis ◽  
Debra E. Irwin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Median Time ◽  
Index Date ◽  
Neurodegenerative Disorder ◽  
Psychiatric Disturbance ◽  
Treatment Persistence ◽  
Before And After ◽  
Median Daily Dose

Background: Huntington’s disease (HD) is a multifaceted neurodegenerative disorder characterized by involuntary movements, specifically chorea, as well as behavioral and psychiatric disturbance, and cognitive dysfunction. Tetrabenazine was the first approved treatment for chorea, although tolerability concerns exist. Objectives: To characterize demographic and clinical characteristics of HD patients with chorea based on tetrabenazine use and examine treatment persistence with tetrabenazine in a real-world setting. Methods: Patients with a claim for HD-associated chorea (ICD-9-CM code 333.4) between 1/1/08 and 9/30/15 were selected from the MarketScan® Commercial and Medicare Supplemental databases. The first diagnosis date during the study period was considered the index date, with ≥6 months of continuous medical and prescription coverage before and after the index date. Treatment persistence was defined as the number of days from initiation to discontinuation or end of follow-up period. Discontinuation was defined as a gap in therapy of ≥60 days. Results: 1644 patients met selection criteria (mean age ± standard deviation: 54.5 ± 15.5), of which 151 (9.2%) were treated with tetrabenazine during the study period. The average (median) daily dose of tetrabenazine during the treatment period was 45.5 (42.3) mg/day. A total of 41.8% (59/141) of HD patients who initiated tetrabenazine experienced a ≥60-day gap in tetrabenazine therapy, with a median time to discontinuation of 293.5 days. During the 6-month post-index period after HD diagnosis, HD patients incurred higher all-cause healthcare costs ($20 204) vs the 6-month pre-index period ($6057), driven by higher hospitalization and pharmacy costs. Conclusions:A small percentage of HD patients with chorea were treated with tetrabenazine and discontinuation rates were high among those receiving treatment, with a median time to discontinuation of 9 months.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2020 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n=81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.

scholarly journals Purinergic Signaling in the Pathophysiology and Treatment of Huntington’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Melissa Talita Wiprich ◽  
Carla Denise Bonan
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Purinergic Signaling ◽  
Neuronal Loss ◽  
Movement Control ◽  
Motor Dysfunction ◽  
Purine Nucleotides ◽  
Psychiatric Disturbance

Huntington’s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder inherited in an autosomal dominant manner. This condition is characterized by motor dysfunction (chorea in the early stage, followed by bradykinesia, dystonia, and motor incoordination in the late stage), psychiatric disturbance, and cognitive decline. The neuropathological hallmark of HD is the pronounced neuronal loss in the striatum (caudate nucleus and putamen). The striatum is related to the movement control, flexibility, motivation, and learning and the purinergic signaling has an important role in the control of these events. Purinergic signaling involves the actions of purine nucleotides and nucleosides through the activation of P2 and P1 receptors, respectively. Extracellular nucleotide and nucleoside-metabolizing enzymes control the levels of these messengers, modulating the purinergic signaling. The striatum has a high expression of adenosine A2A receptors, which are involved in the neurodegeneration observed in HD. The P2X7 and P2Y2 receptors may also play a role in the pathophysiology of HD. Interestingly, nucleotide and nucleoside levels may be altered in HD animal models and humans with HD. This review presents several studies describing the relationship between purinergic signaling and HD, as well as the use of purinoceptors as pharmacological targets and biomarkers for this neurodegenerative disorder.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2019 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records & UHDRS TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at and duration of illness at the time of death, were 53 years and 7 years respectively, which is much shorter than in Europe and USA. The patients who could be contacted (n=81) were assessed for symptomatic morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The vast majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and many other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality & other psychiatric symptoms, suboptimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable for interventions.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2019 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records & UHDRS TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early agewhich is much shorter than in Europe and USA. The patients who could be contacted (n=81) were assessed for morbid symptoms and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The vast majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and many other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality & other psychiatric symptoms, suboptimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable for interventions.

scholarly journals The Novel Alpha-2 Adrenoceptor Inhibitor Beditin Reduces Cytotoxicity and Huntingtin Aggregates in Cell Models of Huntington’s Disease

2021 ◽  
Vol 14 (3) ◽  
pp. 257
Author(s):  
Elisabeth Singer ◽  
Lilit Hunanyan ◽  
Magda M. Melkonyan ◽  
Jonasz J. Weber ◽  
Lusine Danielyan ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Resonance Energy Transfer ◽  
Neuronal Cell ◽  
Resonance Energy ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Cell Models

Huntington’s disease (HD) is a monogenetic neurodegenerative disorder characterized by the accumulation of polyglutamine-expanded huntingtin (mHTT). There is currently no cure, and therefore disease-slowing remedies are sought to alleviate symptoms of the multifaceted disorder. Encouraging findings in Alzheimer’s and Parkinson’s disease on alpha-2 adrenoceptor (α2-AR) inhibition have shown neuroprotective and aggregation-reducing effects in cell and animal models. Here, we analyzed the effect of beditin, a novel α2- adrenoceptor (AR) antagonist, on cell viability and mHTT protein levels in cell models of HD using Western blot, time-resolved Foerster resonance energy transfer (TR-FRET), lactate dehydrogenase (LDH) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) cytotoxicity assays. Beditin decreases cytotoxicity, as measured by TUNEL staining and LDH release, in a neuronal progenitor cell model (STHdh cells) of HD and decreases the aggregation propensity of HTT exon 1 fragments in an overexpression model using human embryonic kidney (HEK) 293T cells. α2-AR is a promising therapeutic target for further characterization in HD models. Our data allow us to suggest beditin as a valuable candidate for the pharmaceutical manipulation of α2-AR, as it is capable of modulating neuronal cell survival and the level of mHTT.

scholarly journals RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Miguel A. Andrade-Navarro ◽  
Katja Mühlenberg ◽  
Eike J. Spruth ◽  
Nancy Mah ◽  
Adrián González-López ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Gene Expression Signature ◽  
Interferon Response ◽  
Peripheral Blood Cells

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.

scholarly journals Huntington's Disease: An Immune Perspective

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Annapurna Nayak ◽  
Rafia Ansar ◽  
Sunil K. Verma ◽  
Domenico Marco Bonifati ◽  
Uday Kishore
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Typical Feature ◽  
Trinucleotide Repeats ◽  
Mutant Huntingtin Protein ◽  
Unexplored Area ◽  
Cag Trinucleotide Repeats ◽  
The Brain ◽  
Abnormal Expansion

Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.

Three-year follow-up after presymptomatic testing for Huntington's disease in tested individuals and partners.

1997 ◽  
Vol 16 (1) ◽  
pp. 20-35 ◽  
Author(s):  
Aad Tibben ◽  
Reinier Timman ◽  
Erna C. Bannink ◽  
Hugo J. Duivenvoorden
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Presymptomatic Testing

scholarly journals Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models

2021 ◽  
Vol 14 (10) ◽  
pp. 1044
Author(s):  
Letizia Pruccoli ◽  
Carlo Breda ◽  
Gabriella Teti ◽  
Mirella Falconi ◽  
Flaviano Giorgini ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Death ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Positive Impact ◽  
Neuroprotective Effects ◽  
Drosophila Model ◽  
Exon 1 ◽  
Transgenic Drosophila

Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic Drosophila melanogaster model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic Drosophila model. Although ESC did not modify the lifespan of the transgenic Drosophila, it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD.

scholarly journals Comparison of Real-world Outcomes Between Patients Treated with Tapentadol ER or Oxycodone CR

10.36469/9905 ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 221-232
Author(s):  
Mike Durkin ◽  
Jacqueline Pesa ◽  
Jessica Lopatto ◽  
Rachel Halpern ◽  
Damon Van Voorhis ◽  
...  
Keyword(s):  
Emergency Department ◽  
Emergency Department Visit ◽  
Healthcare Costs ◽  
Index Date ◽  
Opioid Therapy ◽  
Care Utilization ◽  
Research Database ◽  
Before And After ◽  
Pain Patients

Background: The objective of this study was to compare health care utilization and costs between matched cohorts of chronic pain patients treated with the opioids tapentadol extended release (ER) or oxycodone controlled release (CR). Methods: This retrospective study used claims data from the Optum Research Database. Commercial and Medicare Advantage adult patients with ≥1 prescription fill for oxycodone CR or tapentadol ER between September 1, 2011 and September 30, 2012 were eligible. The date of the first observed oxycodone CR or tapentadol ER claim was the index date. Patients had continuous health plan enrollment for 6 months before and after the index date, ≥ 90 days supply of opioid therapy, and no index drug claims in the preindex period. Patients were propensity score matched in a 1:2 ratio (tapentadol ER : oxycodone CR). Results: The attributes of the matched cohorts (1,120 tapentadol ER and 2,240 oxycodone CR patients) appeared similar. In the 6 month post-index period, lower proportions of the tapentadol ER cohort than the oxycodone CR cohort had ≥1 inpatient stay (14.6% versus 20.5%; p&lt;0.001) and ≥1 emergency department visit (33.4% versus 37.5%; p=0.021). The tapentadol ER compared with the oxycodone CR cohort had higher mean pharmacy costs ($4,263 versus $3,694; p &lt;0.001), lower mean inpatient costs ($3,625 versus $6,309; p&lt;0.001), and lower mean total healthcare costs ($16,510 versus $19,330; p=0.004). Conclusions: During follow-up, total mean healthcare costs were lower among tapentadol ER patients than oxycodone CR patients, and tapentadol ER patients were less likely to have an inpatient admission or emergency department visit.

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