Addressing the Value of Multidisciplinary Clinical Care in Huntington’s Disease: A Snapshot of a New Huntington’s Disease Center

Abstract

Background:

Clinical care for Huntington’s disease (HD) is often provided in experienced centers that provide multidisciplinary care. However, the value of these centers and their uptake by HD families remain unknown.

Objective:

To describe the services provided by a new HD center, including estimates of capture of the population served.

Methods:

Retrospective review of a HD Center launched in 2015, including quantitative and qualitative data on clinic visits, demographic and clinical data.

Results:

We observed a rapid and ongoing growth on the annual number of clinic encounters, with high demand for in-clinic multidisciplinary care. Using census data and estimates of HD prevalence, we determined that we served about 20% of local patients with HD. Most HD patients received pharmacological treatment for psychiatric symptoms, and over half were treated for chorea. About 25% of new HD diagnoses were on patients without family history of HD. Finally, the demand for predictive testing in at risk individuals significantly increased following the press release reporting the successful completion of the Ionis-HTTRx (RG 6042) trial.

Conclusions:

This report indicates a high demand for multidisciplinary care by HD families, supporting its value, providing a snapshot of the organization and function of a single center. Furthermore, it demonstrates how dissemination of news related to research advances influence clinical behavior. Reporting similar information from other HD centers to would provide us with a more global view of the status of HD care across multiple geographical areas.

Keywords

Multidisciplinary Huntington’s disease outcomes health services

INTRODUCTION

Huntington’s disease (HD) is a rare inherited neurodegenerative disease that preferentially affects psychiatric health, motor function and cognition, with additional manifestations being increasingly recognized [1, 2]. As a result, patients require care that spans across multiple healthcare domains, from genetic counseling to treatment of chorea or psychiatric symptoms or non-pharmacological approaches to motor dysfunction, among others [3, 4]. The combination of low prevalence with the presence of clinical manifestations and social needs that require multiple skills from the healthcare provider makes it challenging for patients to identify appropriate sources of care [4]. As it occurs with other rare and complex diseases, a way to overcome these limitations is through the organization of clinical centers that provide multidisciplinary care [5, 6]. Often, disease-centered organizations confer special recognition to clinical centers that meet specific quantitative and qualitative criteria as a way to assist patients in finding centers for appropriate clinical care. In the US, the most common recognition for HD clinical centers is designation as Huntington’s Disease Society of America Center of Excellence (HDSA CoE) (https://hdsa.org/about-hdsa/centers-of-excellence/). Although HD Clinics without this designation can obviously provide the same optimal level of care, HDSA CoE designation ensures that a given clinic evaluates and treats at least a threshold amount of HD patients per year, providing a minimal level of multidisciplinary care. The organization of centers of excellence in healthcare institutions, concentrating high level of expertise focused on a given disease and delivered in a multidisciplinary fashion, is thought to be advantageous for patients, their families and the health care team [6]. The value of experienced skilled teams that provide care to a minimal amount of patients has been evaluated for surgical interventions, such as those treating cerebrovascular malformations [7]. For non-surgical neurological approaches, however, data is scarce. A first step to determine the value of such centers is to describe and evaluate the experience of individual centers as, for instance, it has been reported for a specialized center for lysosomal storage disorders [5]. The value of such centers in the setting of HD remains to be proven.

In this work, we report the experience of a new HD Center since its inception, estimating the uptake of this center on the population served, describing the care provided and measuring changes in patient behavior in response to release of research-related information.

METHODS

We performed a retrospective review of all patients seen at the HD Center of the University of Pennsylvania since 2014. We collected demographic, clinical and genetic information. For patients evaluated in 2018, we collected additional information, including providers seen in each clinic visit, if they came accompanied to the clinic visit and whether they were receiving pharmacological treatment for chorea, psychiatric or behavioral manifestations or sleep disorder. Based on the prominent motor, cognitive and psychiatric manifestations of the disease, our multidisciplinary team was designed to include neurologist, psychiatrist, neuropsychologist, and physical, occupational and speech therapists. Due to its genetic etiology and common demand for counseling and predictive testing, we included a genetic counselor. A social worker is a widely recognized key member of HD care teams due to the frequent deleterious impact of the disease on employment and income, and support required by caregivers along the course of the disease, including residential changes. Finally, to facilitate coordination of clinic appointments, communication of the team with HD families and other external health care providers, a full time HD nurse clinic coordinator was included.

To estimate the number of patients with HD, or at risk, in our main referral area we used quantitative population information from the 2010 US census (https://www.census.gov/programs-surveys/decennial-census/decade.2010.html) for Philadelphia county (where our HD Center is located), all counties with physical borders with Philadelphia county (referred to as first ring) and all counties physically bordering with those in the 1st ring (referred to as second ring). Residential location for each patient was determined by the zip code documented in their last visit. This study was approved by the Institutional Review Committee at the University of Pennsylvania.

RESULTS

The Department of Neurology at the University of Pennsylvania Health System assembled a team to provide multidisciplinary care to HD patients and families in 2015. There were no specific marketing efforts from the institution to publicize this clinic, but the HDSA local chapter and other regional HD foundations and advocacy groups were informed. This clinic gained HDSA Center of Excellence designation in January 2016, gaining additional visibility through the HDSA Center of Excellence program and outreach. Up to November of 2016, the clinic took place every other week. Since that month, the clinic has been occurring weekly. As shown in Fig. 1A, this translated into an increasing number of HD clinical encounters in the department demonstrating an uptake of the multidisciplinary care provided by the population served. In that period, the total number of unique patients seen in the HD clinic was 266. Figure 1B shows the CAG repeat length and age at motor onset for patients in whom that information is available, while Fig. 1C shows CAG repeat length and age at the last visit in pre-manifest individuals seen. We estimated the percentage of the HD population from our main referral area seen at our center (Table 1) using data from the 2010 US Census for Philadelphia County and its suburbs, and the reported frequency of HD and subjects at 25% and 50% risk reported for North America [8].

Fig.1

Characteristics of visits and patients seen in a new HD Center. A) Number and type of clinic visits scheduled by year. B) CAG repeat and age at reported motor onset for manifest HD patients in whom this information as available. C) CAG repeat and age at most recent clinic visit in pre-manifest CAG expansion carriers.

Table 1

Estimates of percentage of patients with manifest HD that were seen in our center from Philadelphia county (where the center is located), immediate suburbs (1st ring of surrounding counties) and more distant suburbs (2nd ring) based on the population in those areas and estimated prevalence of HD in North America

		Philadelphia	1st ring	2nd ring	Total***
	Population*	1,526,006	2,186,047	4,852,804	8,564,857
Predicted**	HD	209	299	665	1,173
Predicted**	25–50% Risk	1,245	1,784	3,960	6,989
Clinic	All Subjects	59	99	75	233
Clinic	HD Subjects	34	56	38	128
	% HD capture	16	19	6	11

*Pennsylvania Census, 2010. **Fisher and Hayden. Mov Dis (2014) [8]. ***33 patients seen in the center were from outside this area.

Next, we evaluated in more detail the clinical care provided at the Penn HDSA CoE during the year 2018. We focused on this year because we had collected more standardized data. A total of 320 appointments were made, 77 for new patients and 243 for follow ups. A total of 284 of those appointments were completed with a clinic encounter (89% completion rate, 92% for new patient encounters and 88% for follow ups). A total of 145 patients (81 women and 64 men) were seen through those encounters, 88 with manifest HD and 57 in other groups (at risk or premanifest). The mean CAG repeat length for manifest patients was 44.4, with an average age at motor onset of 47.3 years and average age at diagnosis of 49.9 years (i.e., almost 2 year diagnostic delay). Most patients (n:110) were seen once or twice within a year span, while a smaller number required multiple clinic visits (22 patients with 3 annual visits, 10 with 4 visits and 3 patients with 5 or more visits in 2018). The distribution of the 57 patients seen in this clinic without manifest HD includes 28 premanifest mutation carriers, 12 subjects at risk who underwent predictive testing and did not carry an expanded allele, 8 at risk subjects in whom predictive testing was requested but was not completed, 7 at risk subjects who decided not to proceed with predictive testing and two phenocopies with negative testing.

In this clinic, all patients are evaluated by the neurologist and dedicated HD nurse in all visits. In-clinic evaluation by other members of the multidisciplinary team is offered based on patient need in the first appointment. Encounters with each multidisciplinary team member in follow up appointments were variable and determined based on the recommendation of the providers in previous visits and the intake information collected by the HD nurse coordinator in a phone call preceding the visit. As shown in Table 2, there is a large need for multidisciplinary care in HD. Most patients came to the clinic with at least one companion, which facilitates care delivery and follow up care. It should be noted that encounters outside clinic time were not captured and, therefore, not included in Table 2 (i.e., phone contacts with HD nurse or social worker, outpatient dietician encounters, physical therapy outside clinic or in-home therapy or nursing care, among others). Although not formally quantified, we estimate an average of 25–30 daily contacts outside clinic by the HD nurse coordination, about 80% of them via phone calls and the rest via the electronic medical record communication system. Of those, a large majority are with patients or caregivers, while about 10–15% are related to pharmacy inquires, prior authorization of services, referring providers or other administrative tasks.

We evaluated how many of our manifest patients seen in 2018 were receiving pharmacological treatment for chorea in their last visit, being risperidone the agent most commonly used (Table 3). We also recorded how many of those patients were receiving treatment in their last visit for psychiatric manifestations or sleep disorders, although with no data about the specific agents used (Table 3).

Table 2

Distribution of services provided in-clinic per encounter in 2018 for patients with manifest HD and other patients. PT, physical therapist; OT, occupational therapist; SLP, speech and language pathologist; GC, genetic counselor; SW, social worker; Npsy, neuropsychologist. Companion indicates number of visits in which the patient was accompanied to the clinic visit

	Encounters	Neurologist	Nurse	Psychiatrist	PT/OT/SLP	GC	SW	Npsy	Companion
HD	187	187	187	127	98	40	63	19	178
Other	97	97	97	52	9	69	14	3	71
Total	284	284	284	179	107	109	77	22	249

Table 3

Frequency of pharmacological treatment for chorea or for psychiatric manifestations in patients with manifest HD. TBZ, tetrabenazine; Risp, risperidone

	Manifest HD
	N	%
Risperidone	23	26
TBZ	15	17
DeuTBZ	2	2
Other	5	6
TBZ+Risp	5	6
Total	50	57
Psychiatric	66	75
Sleep	25	28

Next, we asked what proportion of new HD diagnoses occur in patients with no known family history as this influences genetic counseling, education and has an acute impact in the expanded family. In 42 of 178 of new HD diagnoses (24%), this disease was reportedly new to the family. Presumed reasons for lack of previous diagnosis in the family include 13 patients with undiagnosis or misdiagnosis of family members who retrospectively likely had HD, 7 were adopted, 8 had no contact with their family, 1 case of non-paternity, 1 with parental early death and 12 patients with ultimately “negative” family history. Finally, we evaluated whether dissemination of information about research advances can impact patient behavior and clinical care. Because we witnessed significant excitement in the HD population after a press release on December 2017 announced successful completion of the Ionis-HTTRx (RG 6042) trial, we asked if this could motivate subjects at risk to consider predictive testing. We quantified the type of clinic visits 6 months preceding and 6 months following this announcement, finding a significant increase in the number individuals requesting evaluation for predictive testing (Table 4).

Table 4

Type of clinic visits in the 6 months preceding (before) or following (after) the press announcing the successful completion of the Ionis-HTTRx (RG 6042) trial in December 2017

	Visits	Before	After
	Follow up	102	105
New	Predictive	6	21
	Other	16	16
	Total	124	142

DISCUSSION

In this report, we first describe the growth of a new HD center over a 4 period year after being launched in a large metropolitan area, estimating the uptake of the services offered by the population served. Next, we provide more detailed quantitative and qualitative data on the population served during a period of a year, illustrating the services provided in-clinic, with quantitative data on pharmacological treatment of some manifestations of the disease. Third, we determine the percentage of new HD diagnoses that involve families new to the disease. Finally, we quantify how perception of research advances by subjects at risk influences behavior towards clinical care. Ultimately, we believe this information will help those involved in delivering clinical care for HD, assist institutions plan new HD centers and provide quantitative data in an attempt to demonstrate the value of multidisciplinary centers. The information provided here is evidently influenced by the local characteristics of this single center, which likely differ from other HD clinics. However, collecting similar data from other HD centers, at different geographical locations and within different health systems will be very valuable to demonstrate and improve the value of these clinical centers through resource optimization.

Rapid growth of HD population served supports the need for multidisciplinary HD centers

In the year prior to the establishment of the HD Center at the University of Pennsylvania (2014), there were only 10 encounters for the diagnosis of HD in the Department of Neurology (Fig. 1). Once the center was organized the demand for services increased significantly, requiring doubling the number of clinical days in less than 2 years. Although no specific marketing efforts were pursued by the institution, this is an uncontrolled study and other factors in addition to the HDSA, such as distribution of information by local HD foundations and groups, likely contributed to the robust growth. Although an indirect estimate based on the population in the Philadelphia metropolitan area and estimates on disease prevalence, almost 20% of predicted manifest HD patients living in Philadelphia and its closest suburbs were evaluated at this center. There are multiple potential reasons why the predicted remaining 80% did not seek care in the only HD center providing this type of multidisciplinary care ion the region. Some HD patients might be misdiagnosed or not seeking clinical care. Moreover, despite designation as a HDSA CoE in 2016 with widespread distribution of information about our clinic in the HDSA website, many HD families lack access or are not aware of the existence of the center. Finally, HD patients are likely seeking and receiving clinical care in competing health systems in this area, academic and private. The inverse relationship between distance to the center and “market penetration” indicates that transportation is a possible obstacle for HD families to access HD Centers. The implementation of satellite clinic locations, even for a more limited version of the multidisciplinary team, could be a way to partly overcome this barrier.

Through this work, we attempt to provide quantitative data on how a new HD Center has on attracting HD families for care, genetic counseling and predictive testing. It would be interesting to collect similar quantitative data from other HDSA CoEs or multidisciplinary HD Clinics to estimate how many HD families seek clinical care, and to evaluate the distribution of that care between expert-based centers versus other clinical environments (such as general neurology clinics). The identification of differences based on geography (rural versus urban areas), availability of academic tertiary centers and other factors that could influence patient behavior will help better planning of resources to deliver the best possible care to the largest number of families. In our case, the rapid growth indicates a high demand for services even in populated urban areas with proper health systems, and an appetite for HD families to establish care at such centers.

HD families benefit from multidisciplinary care

The need for multidisciplinary care in HD, based on the characteristic of the disease, has been stressed [3, 4]. Previous reports indicate the benefits of this approach [9 –15]. Our data adds additional support to this view. In addition to seeing an HD neurologist and dedicated HD nurse, over 60% of clinical encounters also included seeing a psychiatrist, near 40% of encounters included evaluations by physical, occupational and speech therapists and about a quarter of encounters included an in-clinic visit with a social worker. A smaller percentage had a neuropsychological evaluation in the same clinical visit, as this requires an extended visit and is often performed outside the HD Clinic. The relatively low percentage of patients who meet with the social worker in clinic is misleading for two reasons. First, the dedicated HD clinic nurse likely performs many duties that overlap with those of the social worker. In addition, many encounters occur outside clinic hours over the phone, and those are not reflected here. Overall, this data supports the need and demand for multidisciplinary care, likely being a key driver of the rapid uptake of the program by the HD population. However, to demonstrate the value of multidisciplinary versus traditional care, future controlled studies should include multiple multidisciplinary and traditional care clinics and employ formal patient- and caregiver-based outcome measures.

High incidence of HD in previously “unaffected” families

The diagnosis of HD in families previously unaware of this disorder is relatively high, consistent with previous reports [16]. About a quarter of new HD diagnoses were delivered in this situation. When HD is previously known to a family, those undergoing diagnostic evaluations are more likely to be educated on the genetic and clinical features of HD, ongoing research, resources available and treatment options. An HD diagnosis entering a family for the first time, however, has significant implications that demand special education and counseling, not only for the patient but also for many family members that suddenly find themselves at risk. Due to the relatively high frequency of this clinical scenario, the implications of the diagnosis and not infrequent misconceptions about the disease among many physicians, we believe that patients undergoing testing for HD as an index case for a family should always be referred to an experienced center with knowledgeable health care providers.

The influence of research news on behavior

It is a widespread view in the HD field that the availability of disease-modifying therapies would rapidly increase the uptake of predictive testing in subjects at risk. The release in a non-peer reviewed form of the successful completion of the phase 1b/2a Ionis-HTTRx (RG 6042) trial caused significant excitement among HD families. Our data suggests that this press release might have encouraged subjects at risk to move forward with predictive testing. In addition to supporting the hypothesis stated above, this has additional implications for genetic counselors and other members of the HD healthcare team. First, clinical care teams should prepare for an increased demand for these services after encouraging results of clinical trials are released. Second, it is important that those counseling these patients before predictive testing are aware of the trial and knowledgeable about what information is available. This will help set appropriate expectations before the testing process, indicating this is primarily a clinical test and not a baseline evaluation for inclusion in a trial. Finally, those releasing news about ongoing or completed clinical trials should consider how their message potentially influences behavior of HD families towards clinical care. This is a very exciting time in HD translational research and, as scientific advances are closer to clinical application, the gap between research and clinical activities is closing with growing cross-influence between both activities.

Conclusions

In summary, the data presented here provides a snapshot of a new HD clinical center, quantifying its potential “market penetration” on the population served and demonstrating the demand for multidisciplinary care. Moreover, we provide important information on the frequency of HD diagnosis in unaware families and the growing relationship between translational research and the decision to enter clinical care. We hope that this information would be beneficial for other healthcare teams planning to provide clinical services for HD families in a multidisciplinary approach. Moreover, as all HD multidisciplinary care centers likely have differences in their organization, we encourage other centers to describe their unique experiences. This would help better quantify the uptake of HD multidisciplinary care in different geographical areas and healthcare systems, and promote cross-fertilization of ideas among centers to improve delivery of care.

CONFLICTS OF INTEREST

Pedro Gonzalez-Alegre has been a consultant for Spark Therapeutics, Sage Therapeutics and Acorda Therapeutics. Tanya Bardakjian declares that she has no conflict of interest. Jennifer Klapper declares that she has no conflict of interest. Adrianna Carey declares that she has no conflict of interest. Julia Wood declares that she has no conflict of interest. Meredith Pauly declares that she has no conflict of interest. Kelly Gasper declares that she has no conflict of interest. Kathy Lawler declares that she has no conflict of interest. Baochan Tran declares that she has no conflict of interest. Yuliis Bell declares that she has no conflict of interest. Alex Zwil declares that he has no conflict of interest.

Footnotes

ACKNOWLEDGMENTS

Clinical care in our HD Center is supported by the Huntington’s Disease Society of America, Hoppy’s Hope To End Huntington’s Disease, Philly Cure HD, Harrison Memorial Fund, and the Neurogenetics Translational Center of Excellence, Department of Neurology, Perelman School of Medicine, the University of Pennsylvania.

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