Abstract
Background
Juvenile Huntington's disease (JHD) is a childhood‐onset neurodegenerative disorder. Although it is caused by the same pathologic expansion of CGA repeats as adult‐onset Huntington's disease, JHD has distinct clinical features. Most clinical research in HD focuses in the adult‐onset disease; therefore, little is known about acute care outcomes for patients with JHD.
Methods
The Kids' Inpatient Database (KID) was used to examine hospitalizations of children with JHD and to determine the diagnoses and procedures associated with inpatient care for JHD. Regression models were built to examine acute care outcomes, including death, length of stay, and disposition at discharge in patients with JHD compared with patients in the general KID data.
Results
The proportion of JHD cases among hospitalized children was 1.23 per 100,000 KID inpatient stays. Seizures/convulsions (58.5%) and psychiatric conditions (26.1%) were the most common primary or secondary diagnoses among JHD patient hospitalizations. The most common procedure was percutaneous endoscopic gastrostomy tube placement (8.6%). Compared with hospitalizations of the general population, hospitalizations of patients with JHD had a lower odds of discharge to home (adjusted odds ratio [AOR], 0.23; 95% confidence interval [CI], 0.14–0.37) and an increased likelihood of death (AOR, 8.03; 95% CI, 2.98–21.60) or discharge to a short‐term care facility (AOR, 4.44; 95% CI, 2.59–7.61). A diagnosis of JHD was associated with increased length of stay (7.04 vs. 3.75 days; P < 0.01).
Conclusions
Children with JHD have unique acute care patterns. Future studies are needed to determine the extent to which coordinated care may impact inpatient and disposition needs.
Keywords: Epidemiology, Huntington's disease, juvenile Huntington's disease, pediatric neurology
Huntington's disease (HD) is fatal, autosomal‐dominant neurodegenerative disorder caused by an unstable trinucleotide (CAG) repeat expansion the huntingtin gene (HTT).1 Although HD classically presents in adulthood, symptoms can manifest in childhood, typically in children with longer CAG repeat length, and those affected before 20 years of age are considered to have the juvenile form of this disease. Juvenile HD (JHD) represents about 5% of the total HD population.2 It typically presents in a phenotypically different fashion compared with adults and is characterized by cognitive and behavioral changes, parkinsonism, oropharyngeal dysfunction, and seizures.3, 4, 5, 6 Chorea occurs later in the disease course, and end‐stage disease involves loss of mobility and increasing seizures.
Improving quality survivorship for individuals with HD requires not only symptomatic therapy but also an understanding of health service needs. Health care utilization has been studied less JHD than in adult HD. One study used the Nationwide Inpatient Sample database to examine 3612 inpatient hospitalizations of adults diagnosed with HD from 1996 to 2002. In that report, more than 60% of admissions were emergent, most often for pneumonia, psychiatric disturbances, malnutrition, and percutaneous gastrostomy tube placement. Importantly, the study reported that over one‐half of hospitalized patients with HD were newly discharged to long‐term care facilities, and nearly all who were admitted from a long‐term care facility returned to one. These data suggest that hospitalized adults with HD often present with symptoms of late‐stage HD7 and that hospitalization serves as a potentially avoidable conduit to nursing home placement or hospice care.
In contrast, very little is known about health care outcomes in children with HD. Although previous data suggest that the time from diagnosis to death is 20 years in patients with JHD, children with HD likely have greater acute care needs compared with the general population. Knowing the reasons for hospitalization, whether they are related to unique disease symptoms, end‐stage disability, or unmet outpatient needs, can inform efforts to improve care for patients with JHD. To address this knowledge gap, we used the Kids' Inpatient Database (KID), a national database of hospital discharge data in the United States, to examine the acute care of children and adolescents with JHD.
Materials and Methods
Data Source
The KID database, which is among the databases developed for the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality,8 was used for this study. The KID is an all‐payer database that contains patient, clinical, geographic, socioeconomic, payer, and cost data from approximately 3 million hospitalizations of individuals ages 21 years and younger each year. States that participate in the Healthcare Cost and Utilization Project provide hospital characteristic and patient discharge data from all community hospitals (nonfederal, general, short‐term, and specialty) in that state. Data are collected every 3 years and include sampling weights that allow researchers to generate estimates for the entire US population. We performed a serial cross‐sectional analysis of KID hospitalizations in 2003, 2006, and 2009.
Study Population
Hospitalizations of all children (ages 5–11 years), adolescents (ages 12–17 years), and young adults (ages 18–20 years) were extracted. JHD was identified according to its unique International Classification of Diseases, 9th Revision (ICD‐9) code (333.4). We constructed a control group consisting of all KID hospitalizations without a diagnosis of JHD. For convenience, hereinafter, we refer to all individuals in the KID dataset as “children.”
Outcomes and Covariates
Our primary outcomes were the reason for admission, the length of stay (LOS), and disposition. We identified the primary reason for admission using the principal diagnosis/procedure code in the KID dataset. The remaining diagnosis codes were queried to examine comorbid conditions. We extracted data on documented inpatient procedures, such as seizure monitoring, intubation, or surgery, using standard procedure billing codes, and LOS (in days) also was extracted. Hospitalization outcome was categorized as: 1) home (routine), 2) home with home health care, 3) transfer to short‐term facility, or 4) inpatient death. We extracted patient, hospital, and geographic data associated with each admission to examine covariates or stratification variables in secondary analyses. Patient characteristics included race, age, sex, patient zip code income (categorized in quartiles), and primary payer (private insurance, Medicare, Medicaid, uninsured, and health maintenance organization). Hospital characteristics included teaching status (teaching, nonteaching), and location (urban, rural).
Secondary Analyses
Although comparing acute care outcomes between patients with JHD and the general pediatric inpatient population was the primary focus of our study, additional perspective may be gained from considering whether JHD patterns also differ from those observed for other rare neurodegenerative diseases. Therefore, we performed secondary analysis comparing acute care outcomes between children JHD and hospitalizations of children diagnosed with either neurodegenerative ataxia (Friedreich's ataxia, primary cerebellar degeneration, and spinocerebellar disease, identified by ICD‐9 codes 334.0, 334.8, 334.3, 334.2, 334.4, 334.1, and 334.9) or muscular dystrophy (Duchenne muscular dystrophy and congenital hereditary dystrophy, identified by ICD 9 codes 359.1 and 359.0).
Statistical Analyses
We applied sampling weights to account for the design of the KID to produce national estimates of hospitalizations for JHD in the United States from 2003 to 2009 and to estimate the prevalence of JHD. Descriptive analyses compared the weighted proportions of patient and hospital characteristics and LOS between hospitalizations of children with and without a JHD diagnosis. We used χ2 analysis and the Student t test to assess the statistical significance of categorical and normally distributed continuous variables.
Next, we built logistic regression models to determine the relative odds of emergency department admission, inpatient death, discharge home with home health care, transfer to a short‐term facility, and routine discharge in the JHD population compared with controls while adjusting for age, sex, race, primary insurance payer, zip code income quartile, and hospital teaching status. Through model fitting, we determined that the best count model to use for the analysis of LOS was a negative binomial count regression, based on descriptive analyses that found over‐dispersion (non‐normal distribution) of the dependent variable (LOS) across the predictor variable (JHD). The negative binomial count regression model was run without sampling weights using JHD status as the predictor variable and the same covariates described above. We used this model to generate adjusted incidence rate ratios (IRRs)—the ratio of the predicted average LOS, adjusting for confounders—for children who had JHD compared with controls. Thus, an IRR greater than 1 indicates that patients with JHD, on average, had longer a LOS than those without JHD. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).
Results
Patient Characteristics
In our inpatient sample, the proportion of JHD cases was 1.23 per 100,000 discharges from 2003 through 2009 among inpatients ages 5 to 20 years. This estimate took into account the sample weights of the KID. We identified a weighted total of 271 hospitalizations in children ages 5 to 20 years with a JHD diagnosis. The demographic characteristics of children with JHD differed from those of the general inpatient population, as shown in Table 1. Hospitalizations of children with JHD had slightly higher proportions of males (56.5% vs. 35.1%; P < 0.001) and blacks (23.4% vs. 19.0%) than the control group. The majority of children with HD were in older age categories. Most children in KID states received care at urban hospitals; however, larger proportions of patients with JHD were discharged from teaching hospitals (76.0%) versus the control group (56.4%). Medicaid insurance was the most common payer for both hospitalized children with JHD (52.1%) and the control group (47.6%).
Table 1.
Characteristics of hospitalizations of juvenile Huntington's disease (Kids' Inpatient Database, 2003–2009)
| Patient and Hospital Characteristic | No. of Patients (%) | |
|---|---|---|
| Juveniles with HD | Controls | |
| Race | ||
| White | 113 (54.3) | 2,574,762 (51.2) |
| Black | 49 (23.4) | 956,612 (19.0) |
| Hispanic | 38 (18.1) | 1,127,986 (22.5) |
| Asian | 0 (0.0) | 91,192 (1.8) |
| Native American | 0 (0.0) | 39,266 (0.8) |
| Other | a | 233,907 (4.7) |
| Sex | ||
| Male | 153 (56.5) | 2,271,820 (35.1) |
| Female | 118 (43.5) | 4,196,196 (64.9) |
| Age, y | ||
| 5–10 | 59 (21.5) | 1,242,764 (19.0) |
| 11–14 | 75 (27.4) | 989,695 (15.1) |
| 15–18 | 93 (34.2) | 2,218,615 (33.9) |
| ≥19 | 46 (16.9) | 2,090,335 (32.0) |
| Insurance type | ||
| Medicare | a | 30,000 (0.5) |
| Medicaid | 142 (52.1) | 3,106,779 (47.6) |
| Private | 103 (38.0) | 2,698,161 (41.3) |
| Self‐pay | a | 371,893 (5.7) |
| No charge | a | 27,946 (0.4) |
| Other | 18 (6.6) | 293,285 (4.5) |
| Zip income quartile | ||
| 0 to 25th percentile | 89 (32.6) | 2,089,909 (32.7) |
| 26th to 50th percentile: Median | 76 (27.8) | 1,687,032 (26.4) |
| 51st to 75th percentile | 58 (21.4) | 1,451,196 (22.7) |
| 76th to 100th percentile | 50 (18.2) | 1,155,259 (18.1) |
| Admission source | ||
| Emergency department | 101 (55.9) | 1,903,974 (39.4) |
| Another hospital | 13 (7.3) | 169,387 (3.5) |
| Other health facility | a | 51,607 (1.1) |
| Court/law | a | 13,101 (0.3) |
| Routine | 65.1 (36.0) | 2,691,797 (55.7) |
| Missing | 92 | 1,638,150 |
| Admission type | ||
| Emergency | 144 (60.6) | 2,403,991 (42.0) |
| Urgent | 50 (21.0) | 1,652,520 (28.9) |
| Elective | 42 (17.8) | 1,621,331 (28.3) |
| Other | a | 49,964 (0.9) |
| Discharge status | ||
| Routine | 191 (70.2) | 6,060,050 (92.7) |
| Transfer to short‐term hospital | a | 87,092 (1.3) |
| Transfer, other | 19 (7.1) | 134,260 (2.1) |
| Home health care | 42 (15.4) | 194,196 (3.0) |
| Against medical advice | a | 41,989 (0.6) |
| Died | a | 18,958 (0.3) |
| Discharged alive, destination unknown | 0 (0.0) | 1,663 (0.0) |
| Hospital teaching status | ||
| Nonteaching | 63 (24.0) | 2,748,644 (43.6) |
| Teaching | 198 (76.0) | 3,559,872 (56.4) |
| Hospital location | ||
| Rural | 16 (6.1) | 791,805 (12.6) |
| Urban | 245 (93.9) | 5,516,711 (87.4) |
HD, Huntington's disease.
Only categories with percentages or numbers greater than 10 can be displayed according to the Kids' Inpatient Database use agreement.
Hospitalization Characteristics
JHD admissions were often unplanned, with 55.9% originating from emergency departments. Unlike studies of adults with HD.7 we identified no pediatric admissions from long‐term care facilities. Transfers from other hospitals were uncommon (7.3%), likely because academic medical centers provided the majority of initial inpatient care.
Billing codes for epilepsy, seizures, and convulsions were identified in 58.5% (n = 159) of JHD admissions, followed by psychiatric diagnoses (26.1%; n = 70), and respiratory infection/aspiration (15.9%; n = 43), as shown in Table 2. Seizures or epilepsy accounted for 16.4% of primary admitting diagnoses. The most common procedure was percutaneous endoscopic gastrostomy, which was performed during 13.1% (n = 36) of admissions; and 11.9% (n = 32) of JHD hospitalizations involved endotracheal intubation.
Table 2.
Inpatient medical conditions and procedures for children with Huntington's disease (Kids' Inpatient Database, 2003–2009)
| Condition category: No. of patients (%)a | ICD‐9/CPT code | Billing code description |
|---|---|---|
| Diseases of the nervous system and sense organs | ||
| 271 (100.00) | 333.4 | Hereditary and degenerative nervous system conditions |
| 28 (10.23) | 345.3 | Grand mal status epileptic |
| 82 (30.11) | 780.39 | Convulsions |
| 49 (18.18) | 345.90 | Epilepsy unspecified without intractable epilepsy |
| 15 (5.68) | 343.9 | Paralysis |
| Diseases of the respiratory system | ||
| 23 (8.52) | 486 | Respiratory infections |
| 20 (7.39) | 507.0 | Aspiration pneumonitis; food/vomitus |
| 18 (6.82) | 493.90 | Asthma |
| Endocrine; nutritional; and metabolic diseases and immunity disorders | ||
| 37 (13.64) | 276.0, 276.51 | Fluid and electrolyte disorders |
| 34 (12.50) | 783.3, 783.40 | Other nutritional; endocrine; and metabolic disorders |
| Mental illness | ||
| 20 (7.39) | 311 | Mood disorders |
| 18 (6.82) | 319 | Developmental disorders |
| 17 (6.25) | 312.30 | Impulse‐control disorders not elsewhere classified |
| 15 (5.68) | 314.01 | Attention deficit, conduct, and disruptive behavior disorders |
| Diseases of the digestive system | ||
| 86 (31.82) | 564.00, V441 | Other gastrointestinal disorders |
| 23 (8.52) | 530.81 | Upper gastrointestinal disorders |
| Operations on the cardiovascular system | ||
| 36 (13.10) | 389.3 | Venous catheterization |
| Operations on the digestive system | ||
| 36 (13.10) | 431.1 | Gastrostomy; temporary and permanent |
| Other diagnostic and therapeutic procedures | ||
| 36 (13.10) | 966 | Enteral and parenteral nutrition |
| 32 (11.90) | 960.4 | Endotracheal intubation |
ICD‐9/CPT, International Classification of Diseases, 9th Revision/Common Procedural Terminology.
Only categories with percentages of numbers greater than 10 can be displayed according to the Kids' Inpatient Database data use agreement.
Hospitalization Outcomes in JHD
Hospitalizations of children with JHD lasted on average 7.04 days (standard error, 0.92 days), which was almost twice as long as hospitalizations in controls, who had an average LOS of 3.75 ± 0.05 days (Wilcoxon test on LOS by JHD status; P < 0.0001). Using a count regression model that also accounted for patient, hospital, and insurance characteristics, hospitalizations of children with JHD had a greater incidence of prolonged LOS compared with the control population (IRR, 1.73; 95% confidence interval [CI], 1.50–2.00); that is, children with JHD had a mean adjusted LOS that was 1.75 times greater than that of the control population.
Logistic regression models compared the odds of death, home health care, transfer to a short‐term facility, and routine discharge for admissions of children who had JHD with the odds in controls, adjusting for sociodemographic and hospital characteristics. As shown in Table 3, Children with JHD were 8 times more likely than controls to die during their hospitalization (adjusted odds ratio [AOR], 8.03; 95% CI, 2.98–21.60). A discharge status indicating home health care was 4.4 times more likely among inpatients with JHD (AOR, 4.44; 95% CI, 2.59–7.61) than among controls, a discharge status indicating transfer to a short‐term facility was 2.9 times more likely among inpatients with JHD (AOR, 2.93; 95% CI, 1.22–7.07) than among controls; and patients with JHD were 77% less likely to be routinely discharged than controls (AOR, 0.23; 95% CI, 0.14–0.37).
Table 3.
Outcomes of hospitalizations in children who had Huntington's disease compared with general pediatric inpatients (Kids' Inpatient Database, 2003–2009)
| Outcome | Juvenile HD (vs. general pediatric inpatients): AOR (95% CI)a | P value |
|---|---|---|
| Inpatient death | 8.03 (2.98–21.60) | <0.0001 |
| Home health care | 4.44 (2.59–7.61) | <0.0001 |
| Transfer to short‐term hospital | 2.93 (1.22–7.07) | <0.0001 |
| Emergency admission | 1.21 (0.74–2.00) | 0.4478 |
| Routine discharge | 0.23 (0.14–0.37) | <0.0001 |
HD, Huntington's Disease; AOR, adjusted odds ratio; CI, confidence interval.
Odds ratios were adjusted for payer type, race, sex, zip income quartile, age, and hospital teaching status.
Hospitalization Outcomes in JHD Versus Neurodegenerative Ataxias and Muscular Dystrophies
We identified 2439 hospitalizations of children with neurodegenerative ataxias and 7315 hospitalizations of children with muscular dystrophies. The demographic characteristics of children with neurodegenerative ataxias were very similar to those of children with JHD, as shown in Table 4, with the exception of age distribution. Over 40% children with neurodegenerative ataxias were between ages 5 and 10 years, compared to 21.5% of children with JHD. Characteristics of children with muscular dystrophies were less similar to those of children with JHD. Lower percentages of hospitalizations of children with muscular dystrophy were African American (8.8% vs. 23.4% hospitalizations of children with JHD), and higher percentages were male (78.7% vs. 56.5% hospitalizations of children with JHD). Compared with JHD admissions, neurodegenerative ataxia and muscular dystrophy hospitalizations were more frequently planned/not emergent and less often involved a child from one of the poorest neighborhoods. (Table 4).
Table 4.
Characteristics of hospitalizations of children with neurodegenerative ataxias and muscular dystrophies (Kids' Inpatient Database, 2003–2009)
| Patient and hospital characteristic | No. of patients (%) | |||
|---|---|---|---|---|
| Neurodegenerative ataxias, n = 2439 | Muscular dystrophies, n = 7315 | Juvenile HD, n = 271 | Controls | |
| Race | ||||
| White | 1,074 (54.8) | 3,575 (61.5) | 113 (54.3) | 2,574,762 (51.2) |
| Black | 351 (17.9) | 510 (8.8) | 49 (23.4) | 956,612 (19.0) |
| Hispanic | 365 (18.6) | 1,285 (22.1) | 38 (18.1) | 1,127,986 (22.5) |
| Asian | 62 (3.2) | 170 (2.9) | 0 (0.0) | 91,192 (1.8) |
| Native American | 14 (0.7) | 37 (0.6) | 0 (0.0) | 39,266 (0.8) |
| Other | 94 (4.8) | 240 (4.1) | a | 233,907 (4.7) |
| Sex | ||||
| Male | 1,401 (57.8) | 5,739 (78.7) | 153 (56.5) | 2,271,820 (35.1) |
| Female | 1,022 (42.2) | 1,554 (21.3) | 118 (43.5) | 4,196,196 (64.9) |
| Age, y | ||||
| 5–10 | 981 (40.2) | 1,522 (20.8) | 59 (21.5) | 1,242,764 (19.0) |
| 11–14 | 592 (24.3) | 1,932 (26.4) | 75 (27.4) | 989,695 (15.1) |
| 15–18 | 586 (24.0) | 2,494 (34.1) | 93 (34.2) | 2,218,615 (33.9) |
| ≥19 | 279 (11.5) | 1,366 (18.7) | 46 (16.9) | 2,090,335 (32.0) |
| Insurance type | ||||
| Medicare | 27 (1.1) | 40 (0.5) | a | 30,000 (0.5) |
| Medicaid | 1,163 (47.7) | 3,733 (51.1) | 142 (52.1) | 3,106,779 (47.6) |
| Private | 1,041 (42.7) | 3,002 (41.1) | 103 (38.0) | 2,698,161 (41.3) |
| Self‐pay | 35 (1.4) | 138 (1.9) | a | 371,893 (5.7) |
| No charge | 13 (0.5) | 11 (0.2) | a | 27,946 (0.4) |
| Other | 161 (6.6) | 386 (5.3) | 18 (6.6) | 293,285 (4.5) |
| Zip code income quartile | ||||
| 0 to 25th percentile | 619 (25.9) | 1,837 (25.7) | 89 (32.6) | 2,089,909 (32.7) |
| 26th to 50th percentile | 637 (26.7) | 1,932 (27.0) | 76 (27.8) | 1,687,032 (26.4) |
| 51st to 75th percentile | 581 (24.4) | 1,808 (25.3) | 58 (21.4) | 1,451,196 (22.7) |
| 76th to 100th percentile | 548 (23.0) | 1,575 (22.0) | 50 (18.2) | 1,155,259 (18.1) |
| Admission source | ||||
| Emergency department | 781 (42.6) | 2,422 (44.0) | 101 (55.9) | 1,903,974 (39.4) |
| Another hospital | 125 (6.8) | 432 (7.9) | 13 (7.3) | 169,387 (3.5) |
| Other health facility | 32 (1.7) | 77 (1.4) | a | 51,607 (1.1) |
| Court/law | 0 (0.0) | a | a | 13,101 (0.3) |
| Routine | 897 (48.9) | 2,568 (46.7) | 65.1 (36.0) | 2,691,797 (55.7) |
| Missing | 604 | 1,814 | 92 | 1,638,150 |
| Admission type | ||||
| Emergency | 1,001 (46.9) | 3,055 (48.8) | 144 (60.6) | 2,403,991 (42.0) |
| Urgent | 467 (21.9) | 1,543 (24.6) | 50 (21.0) | 1,652,520 (28.9) |
| Elective | 648 (30.4) | 1,623 (25.9) | 42 (17.8) | 1,621,331 (28.3) |
| Other | 16 (0.8) | 40.7 (0.7) | a | 49,964 (0.9) |
| Discharge status | ||||
| Routine | 1,905 (78.2) | 5,398 (73.8) | 191 (70.2) | 6,060,050 (92.7) |
| Transfer to short‐term hospital | 82 (3.4) | 303 (4.1) | a | 87,092 (1.3) |
| Transfer, other | 166 (6.8) | 371 (5.1) | 19 (7.1) | 134,260 (2.1) |
| Home health care | 252 (10.4) | 979 (13.4) | 42 (15.4) | 194,196 (3.0) |
| Against medical advice | 0 (0.0) | 17 (0.2) | a | 41,989 (0.6) |
| Died | 30 (1.2) | 244 (3.3) | a | 18,958 (0.3) |
| Discharged alive, destination unknown | 0 (0.0) | a | 0 (0.0) | 1,663 (0.0) |
| Hospital teaching status | ||||
| Nonteaching | 396 (17.3) | 1,647 (24.2) | 63 (24.0) | 2,748,644 (43.6) |
| Teaching | 1,902 (82.7) | 5,168 (75.8) | 198 (76.0) | 3,559,872 (56.4) |
| Hospital location | ||||
| Rural | 110 (4.8) | 508 (7.4) | 16 (6.1) | 791,805 (12.6) |
| Urban | 2,188 (95.2) | 6,307 (92.6) | 245 (93.9) | 5,516,711 (87.4) |
HD, Huntington's disease.
Only categories with percentages or numbers greater than 10 can be displayed according to the Kids' Inpatient Database data use agreement.
Table 5 displays the results of logistic regression models that compare the odds of death, home health care use, transfer to other facilities, and routine discharge of children with JHD with hospitalizations of children with neurodegenerative ataxias and muscular dystrophies. Overall, there was a tendency toward lower odds of inpatient death, home health care, and transfer to short‐term facilities in children with neurodegenerative ataxias or muscular dystrophies; however, these differences were not statistically significant.
Table 5.
Outcomes of hospitalizations of children with Huntington's disease compared with pediatric hospitalizations of children with other neurodegenerative disorders (Kids' Inpatient Database, 2003–2009)
| Outcome | Juvenile HD vs. neurodegenerative spinocerebellar ataxias: AOR (95% CI) | P value | JHD vs. neuromuscular disorders: AOR (95% CI) | P value |
|---|---|---|---|---|
| Inpatient death | 2.46 (0.80–7.56) | 0.1150 | 1.03 (0.38–2.82) | 0.9502 |
| Home health care | 1.24 (0.63–2.41) | 0.5360 | 1.12 (0.63–1.98) | 0.6983 |
| Transfer to short‐term hospital | 0.88 (0.39–2.00) | 0.7616 | 1.42 (0.58–3.48) | 0.4403 |
| Emergency admission | 0.86 (0.51–1.45) | 0.5759 | 1.09 (0.65–1.84) | 0.7337 |
| Routine discharge | 0.80 (0.48–1.31) | 0.3694 | 0.84 (0.53–1.34) | 0.4625 |
HD, Huntington's disease; AOR, adjusted odds ratio; CI, confidence interval; JHD, juvenile Huntington's disease.
Discussion
JHD is a hereditary neurodegenerative disorder caused by the same mutation in the HTT gene as in adult‐onset HD, although JHD usually includes longer CAG repeat expansions. JHD is characterized by progressive motor, psychiatric, cognitive, and behavioral symptoms. Previous studies of patients with JHD have focused on outpatient care. To the best of our knowledge, this is the first JHD study focused on inpatient care, morbidity, and mortality.
Our study estimate of 1.23 cases per 100,000 hospitalizations is greater than the population estimates of 0.6 cases per 100,000 children, although the exact prevalence of JHD is unknown. Previous epidemiologic studies reported rates of 4 to 10 cases per 100,000 Caucasians and lower proportions in Asian, African American, and Latino populations9, 10; however, lower rates in minorities are often (and probably inaccurately) attributed to ascertainment bias.2, 11, 12 Interestingly, race was almost evenly distributed in our inpatient JHD sample—23.4% of children hospitalized with JHD were black, and 18.1% were Hispanic. These numbers are greater than what were previously described in the literature and what may have previously been considered a predominantly Caucasian disease.2, 9, 10 More studies are needed to determine the extent to which there are racial/ethnic differences among children with HD.
We observed that inpatients with JHD most often received public insurance (Medicaid), which insures individuals living below the poverty line, the blind, and/or disabled.13 HD itself is a chronic disabling disease, which potentially makes most, if not all, individuals with HD eligible for Medicaid coverage. However, we did not find a statistically significant difference in the socioeconomic status of children with HD, as represented by zip code income quartile. This is a unique finding, because many chronic neurologic disorders are associated with a downward socioeconomic drift. Socioeconomic downward drifts have been well documented in neurologic diseases like epilepsy, migraines, and multiple sclerosis.14, 15, 16, 17, 18 These conditions are associated with marked disability, leading to numerous hospitalizations, lack of work productivity, loss of work days, and even unemployment, eventually leading to a fall to a lower socioeconomic quartile than at the time of diagnosis. Our data may suggest that caring for a child with JHD impacts the family's socioeconomic status or possibly reflect the finding that patients with JHD likely have other older family members with HD.
Numerous studies have described seizures as a clinical manifestation of JHD.2, 5, 6, 19 Our findings are consistent with this literature. Epilepsy, seizures, and convulsion‐related diagnoses comprised almost 20% of all of admitting diagnoses and were listed as comorbidities in greater than 50% of JHD hospitalizations. This is in contrast with data from hospitalized adults with HD, in which pneumonia was the primary admitting diagnosis.7 Other primary manifestations of JHD, such as intellectual disability, stiffness, or gait disturbances,2, 5, 6, 19 were not reported as common admitting diagnoses in our study. This discrepancy likely reflects a greater need for acute care associated with seizures, but it also may reflect coding preferences. Psychiatric disorders or events (such as suicide attempt or ideation) were not the most predominant admitting diagnoses in our study but were important comorbid diagnoses. At first, this may seem to be in contrast with a recent retrospective review of the clinical presentation of 29 patients with JHD in which severe psychiatric and cognitive disturbances were identified in 65.5% (19 of 29 patients).4 However, our study focused on the hospitalization of children with known JHD, rather than prediagnosis symptomatology, suggesting that psychiatric symptoms may respond to outpatient treatment better than seizures.
Our study also provides important data on JHD‐related morbidity and mortality. JHD hospital admissions were associated with an 8‐fold increased likelihood of death. Compared with the general pediatric inpatient population, patients with JHD were also over 4 times more likely to receive home health care and were almost 3 times more likely to be transferred to a short‐term care facility after a hospitalization. Compared with other progressive, inherited pediatric neurologic conditions (neurodegenerative ataxias and muscular dystrophies), we observed a trend toward greater morbidity and mortality among children hospitalized with JHD. Our finding of a substantial risk of inpatient death in patients with JHD has not been reported previously and demands further investigation. Inpatient death in a patient with a known fatal neurodegenerative condition can reflect: (1) failure to rescue from an acute (but expected), nonterminal clinical event, such as seizure; (2) adverse reaction to treatments or preventable hospital complications related to unfamiliarity with the condition; or (3) failure to recognize hospice and palliative care rather than hospitalization.
We present novel, informative data on the acute care of patients with JHD. Nevertheless, there are several potential limitations with our study. All nonrandomized and retrospective studies are vulnerable to outcome or exposure variable misclassification, selection bias, and case mix bias. Furthermore, the use of ICD‐9 codes in administrative data may not accurately identify patients with specific medical conditions, although genetic conditions may be less vulnerable to misdiagnosis.
Our finding of a greater proportion of children in urban hospitals highlights a potential selection bias rather than an urban predominance of JHD. Hospitals in urban settings might be able to provide more specialized care in neurologic conditions, which could lead to patients in rural areas seeking care in urban hospitals. Alternatively, urban hospitals might be able to provide more accurate diagnosis of neurologic disease. These discrepancies in rural neurologic care and selection bias have been reported previously in other more common neurologic conditions, such as dementia and epilepsy.20, 21, 22, 23, 24
It is possible that a significant proportion of patients with JHD are never hospitalized before adulthood; therefore, we cannot assume that our data reflect the overall true prevalence of JHD among all children in the United States. Despite these potential limitations, this study provides novel and hypothesis‐generating information on the clinical presentation of JHD in the acute setting and related outcomes.
Author Roles
1. Research Project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing the First Draft, B. Review and Critique.
A.M.: 3A, 3B
A.T.N.V.: 3A, 3B
D.T.: 2B, 2C, 3A
P.G.A.: 3A, 3B
A.W.: 1A, 1B, 1C, 2A, 3A, 3B
Disclosures
Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflict of Interest: The authors report no conflicts of interest relevant to this work.
Financial Disclosures for the previous 12 months: Pedro Gonzalez‐Alegre has received licensing fees from Spark Therapeutics and consulting fees from TEVA Pharmaceuticals for participation in their Huntington's Disease Advisory Board. Allison Willis receives research support from the National Institutes of Health (grant K23NS081087), the Patient Centered Outcomes Research Institute (PCORI), and the University of Pennsylvania. Adys Mendizabal, Anh‐Thu Ngo Vu, and Dylan Thibault report no sources of funding and no conflicts of interest.
Relevant disclosures and conflicts of interest are listed at the end of this article.
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