Healthcare resource utilization and cost among individuals with late-onset versus adult-onset Huntington's disease: a claims­based retrospective cohort study.

AIMS: Quantify healthcare resource utilization (HRU) and costs for individuals with late-onset Huntington's disease (LoHD) and compare these with adult-onset HD (AoHD) and non-HD controls. METHODS: This retrospective cohort study used US healthcare claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases. Individuals newly diagnosed with HD between 1/1/2009 and 12/31/2017 were selected (index date was first HD claim). Individuals ≥60 years of age at the index date were categorized as having LoHD while individuals 21-59 years of age were categorized as having AoHD. Non­HD controls were exact matched 2:1 to LoHD and AoHD cohorts. Individuals were required to have continuous enrollment for ≥12 months pre- and post-index. Twelve-month all-cause HRU and healthcare costs were assessed for each cohort. RESULTS: In total, 763 individuals with LoHD and 1,073 individuals with AoHD were matched with 3,762 non-HD controls. Unadjusted all-cause HRU in the 12 months post-index was higher for individuals with LoHD and AoHD compared with non-HD controls across most service categories. Adjusted all-cause HRU for the LoHD cohort was significantly higher compared with non-HD controls across all service categories. In the 12 months post-index, mean total costs for the LoHD cohort ($29,055) were significantly higher than for non-HD controls (≥60 years old: $17,286; 21-59 years old: $12,688; p <.001) and similar to total costs in the AoHD cohort ($31,701; p =.47). LIMITATIONS: It was not possible to control for differences in HD stage but regression models were adjusted for baseline HRU. Evaluations of costs did not include indirect costs, which are known to be significant components of the wider HD burden. CONCLUSIONS: This study provides the first analysis of HRU and costs in LoHD, demonstrating that individuals with LoHD experience a significantly higher healthcare burden compared with non-HD controls and a similarly high burden compared with individuals with AoHD.

Huntington's disease (HD) usually develops between the ages of 30­50 but can develop earlier/later. This study looked at healthcare use in people who developed HD at age 60 or later in the United States. Researchers found that people who develop HD at age 60 or later have similar health needs to people with adult-onset HD. Furthermore, they have much greater health needs than people of a similar age who do not have HD.

Clustering and prediction of disease progression trajectories in Huntington's disease: An analysis of Enroll-HD data using a machine learning approach.

Introduction: Huntington's disease (HD) is a rare neurodegenerative disease characterized by cognitive, behavioral and motor symptoms that progressively worsen with time. Cognitive and behavioral signs of HD are generally present in the years prior to a diagnosis; however, manifest HD is typically assessed by genetic confirmation and/or the presence of unequivocal motor symptoms. Nevertheless, there is a large variation in symptom severity and rate of progression among individuals with HD. Methods: In this retrospective study, longitudinal natural history of disease progression was modeled in individuals with manifest HD from the global, observational Enroll-HD study (NCT01574053). Unsupervised machine learning (k-means; km3d) was used to jointly model clinical and functional disease measures simultaneously over time, based on one-dimensional clustering concordance such that individuals with manifest HD (N = 4,961) were grouped into three clusters: rapid (Cluster A; 25.3%), moderate (Cluster B; 45.5%) and slow (Cluster C; 29.2%) progressors. Features that were considered predictive of disease trajectory were then identified using a supervised machine learning method (XGBoost). Results: The cytosine adenine guanine-age product score (a product of age and polyglutamine repeat length) at enrollment was the top predicting feature for cluster assignment, followed by years since symptom onset, medical history of apathy, body mass index at enrollment and age at enrollment. Conclusions: These results are useful for understanding factors that affect the global rate of decline in HD. Further work is needed to develop prognostic models of HD progression as these could help clinicians with individualized clinical care planning and disease management.

Qualitative Evaluation of the Personal KinetiGraphTM Movement Recording System in a Parkinson's Clinic.

BACKGROUND: Wearable sensors provide accurate, continuous objective measurements, quantifying the variable motor states of patients with Parkinson's disease (PD) in real time. OBJECTIVES: To evaluate the impact of using continuous objective measurement using the Personal KinetiGraph™ (PKG®) Movement Recording System in the routine clinical care of patients with PD (PwP). METHODS: Physicians employed the use of the PKG in patients for whom they were seeking objective measurement. Patients wore a PKG data logger for ≥6 days during routine daily living activities. During the survey period of December 2015 through July 2016, physician surveys were completed by four Movement Disorder Specialists for whom measurements from the PKG were available during a subsequent routine clinic visit. RESULTS: Of 112 completed physician surveys, 46 (41%) indicated the PKG provided relevant additional information sufficient to consider adjusting their therapeutic management plan; 66 (59%) indicated the PKG provided no further information to support a therapeutic decision differing from that made during a routine clinical evaluation. Upon further review of these 46 surveys, 36 surveys (78%) revealed the information provided by the PKG ultimately resulted in adjusting the patient's medical management. CONCLUSIONS: The PKG provided novel additional information beyond that captured during a routine clinic visit sufficient to change the medical management of PwP. Physicians adjusted treatment nearly a third of the time based on data provided by real-time, remote monitoring outside the clinic setting. The use of the PKG may provide for better informed therapeutic decisions, improving the quality of life for PwP.

Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson's disease.

BACKGROUND: Gastrointestinal symptoms, such as dysphagia, postprandial bloating, and defecatory straining are common in Parkinson's Disease (PD) and they impact quality of life. Endoscopic botulinum neurotoxin (BoNT) injection has been used in the treatment of dysphagia, gastroparesis and chronic anismus. AIMS: To examine the feasibility, safety and efficacy of endoscopically delivered BoNT injection to distal esophagus, pylorus or anal canal aiming at relieving regional gastrointestinal symptoms in patients with PD. METHODS: This is a retrospective open cohort pilot study to assess the clinical response to endoscopic BoNT injection on selected PD patients with symptoms and identifiable abnormalities on high-resolution manometry and wireless motility capsule, to generate early uncontrolled data on feasibility, tolerability, safety and efficacy. Baseline symptoms and response to therapy were assessed by questionnaires. RESULTS: Fourteen PD patients (10 M:4 F), mean age 73 (range: 62-93) were treated. Three patients had esophageal Botox for ineffective esophageal motility (IEM) (n = 1), esophago-gastric junction outlet obstruction (EGJOO) & IEM (n = 1), and diffuse esophageal spasm (DES) (n = 1). Nine patients were treated with pyloric BoNT injection for gastroparesis with mean gastric transit time of 21.2 h; range 5.2-44.2 h. Two patients received anal Botox for defecatory dyssynergia ((Type I) (n = 1) and overlap (slow-transit and dyssynergic) constipation (n = 1). Endoscopic BoNT injection (100-200 units) was well tolerated and there were no significant adverse events. CONCLUSIONS: Endoscopic BoNT injection to esophagus, pylorus or anal canal is safe, well-tolerated and leads to symptomatic improvement that lasts up to several months. The procedure can be repeated as needed and combined with other therapies.

A practical review of gastrointestinal manifestations in Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease with prominent motor and non-motor symptoms. Gastrointestinal (GI) dysfunction is among the most common and bothersome of non-motor symptoms that physicians will encounter while caring for their patients. Patients are subject to a wide variety of GI symptoms involving organs from the oropharynx to the anorectum. Our awareness and understanding of GI involvement in PD continues to evolve. In this review, we use a gastroenterologist's perspective to provide practical considerations for the diagnosis and symptom-based management of GI dysfunction seen in PD. Our aim is to assist neurologists and specialists as they encounter these symptoms while caring for the many neurologic manifestations of PD.

Utility of the wireless motility capsule and lactulose breath testing in the evaluation of patients with Parkinson's disease who present with functional gastrointestinal symptoms.

BACKGROUND: The aetiology and origin of gastrointestinal symptoms in Parkinson's disease (PD) remains poorly understood. Gastroparesis, small bowel transit delay and bacterial overgrowth may, individually or collectively, play a role. AIMS: In patients with PD and functional gastrointestinal symptoms, we aimed to determine the utility of the wireless motility capsule and lactulose breath tests in further defining their symptoms' aetiology. METHODS: In this retrospective cohort study, consecutive patients with PD and functional gastrointestinal symptoms underwent clinical assessment, as well as wireless motility capsule and lactulose breath testing using standard protocols. RESULTS: We studied 65 patients with PD and various gastrointestinal symptoms. 35% exhibited gastroparesis by the wireless motility capsule study, 20% small bowel transit delay, while 8% had combined transit abnormalities, suggestive of overlapping gastric and small bowel dysmotility. Small bowel bacterial overgrowth was seen in 34% of cases. Symptoms of abdominal pain, regurgitation, bloating, nausea, vomiting, belching and weight loss could not distinguish between patients with or without gastroparesis, although bloating was significantly more prominent (p<0.001) overall and specifically more so in patients with slow small bowel transit (p<0.01). There was no relationship between delayed small bowel transit time and bacterial overgrowth (p=0.5); PD scores and duration were not correlated with either the transit findings or small bowel bacterial overgrowth. CONCLUSIONS: Functional gastrointestinal symptoms in patients with PD may reflect gastroparesis, small bowel transit delay or both, suggesting motor and/or autonomic dysfunction, and may be associated with small bowel bacterial overgrowth. The wireless motility capsule and lactulose breath testing are non-invasive and useful in the assessment of these patients.

Utility of high-resolution anorectal manometry and wireless motility capsule in the evaluation of patients with Parkinson's disease and chronic constipation.

BACKGROUND: The aetiology of constipation in Parkinson's disease remains poorly understood. Defaecatory dyssynergia, anal sphincter spasticity and slow transit constipation may, individually or collectively, play a role. AIMS: In this retrospective cohort analysis of patients with Parkinson's disease and chronic constipation, we determined the utility of high-resolution anorectal manometry, balloon expulsion and wireless motility capsule testing in defining the underlying aetiology for constipation. METHODS: In this retrospective cohort study, consecutive patients with Parkinson's disease and chronic constipation underwent clinical assessment, manometry with balloon expulsion and wireless motility capsule testing using standard protocols. RESULTS: We studied 66 patients fulfilling Rome IV criteria for functional constipation. Most patients (89%) had abnormal manometry, exhibiting various types of defaecatory dyssynergia (mostly types II and IV), abnormal balloon expulsion, diminished rectal sensation and, in some, lacking rectoanal inhibitory reflex. 62% exhibited colonic transit delay by wireless motility capsule study, while 57% had combined manometric and transit abnormalities, suggesting of overlap constipation. Symptoms of infrequent defaecation, straining and incomplete evacuation were not discriminatory. There was a relationship between constipation scores and colonic transit times (p=0.01); Parkinson's disease scores and duration were not correlated with either the manometric or transit findings. Faecal incontinence was seen in 26% of the patients. CONCLUSIONS: Chronic constipation in patients with Parkinson's disease may reflect pelvic floor dyssynergia, slow transit constipation or both, and may be associated with faecal incontinence, suggesting both motor and autonomic dysfunction. Anorectal manometry and wireless motility capsule testing are useful in the assessment of these patients.