Ethnic Disparities in AL Amyloidosis Outcomes Among Hospitalized Patients in the United States


 INTRODUCTION
 Health disparities in immunoglobulin light chain (AL) amyloidosis have not been well described. We aimed to assess if health disparities between non-Hispanic (NH)-Whites, NH-Blacks and Hispanics exist and to describe differences between different ethnic/racial groups.
 METHODS
 We conducted a retrospective cross-sectional analysis of in-patient AL amyloidosis hospitalizations from 2016 to 2018 using the Nationwide Inpatient Sample (NIS), a database which provides nationally representative information on hospitalizations in the U.S. The studied period was chosen to capture data from the ICD-10-CM codes to avoid misclassification of AL amyloidosis which was grouped with other cases of ATTR amyloidosis in the ICD-9-CM coding system. All hospitalizations in adults (age ≥18 years) were included. The exposure for the study was the occurrence of AL amyloidosis in the discharge records. Outcomes were [1] in-hospital death [2] chemotherapy use; [3] intensive care unit (ICU) utilization; [4] palliative care consultation. The analysis for this study was performed using R program version 3.5.1; a 5% type I error rate for all hypothesis tests (two-sided) was assumed.
 RESULTS
 Admissions related to AL amyloidosis constituted 0.03% of all hospitalizations in the study period (25,470 of 90,869,381). The prevalence of AL amyloidosis related hospitalizations was higher in NH-Blacks when compared with NH-Whites (42.8 vs.28.1 per 100,000 hospitalizations). AL amyloidosis related in-hospital mortality rate was higher in NH-Whites and Hispanics when compared to NH-Blacks (6.6%% and 6.2% vs. 4.9%). In-hospital mortality with AL amyloidosis was higher in older patients, males and those who self-paid for their treatment. Utilization of ICU care was more common in NH-Blacks when compared to NH-Whites (6% vs. 4.8%). Hispanics had the lowest inpatient chemotherapy use (1.7% vs. 2.9%). Multivariable adjusted association between race/ethnicity and various outcomes showed a trend towards lower in-hospital mortality in NH-Blacks when compared to NH-Whites (OR: 0.76, 95% CI: 0.55-1.05, p=0.09) and lower utilization of palliative care services in NH-Blacks when compared with NH-Whites (OR: 0.61, 95% CI: 0.42-0.88, p=0.01). Despite very low numbers of transplant related admissions, such admissions occurred only in NH-Whites.
 CONCLUSIONS
 Our findings highlight disparities in AL amyloidosis care for NH-Blacks and Hispanics. NH-Blacks tend to have lower in-hospital mortality with higher utilization of ICU care, nevertheless, they receive the lowest palliative care services. Despite the higher utilization of ICU care, data suggest possible superior outcomes of AL amyloidosis in NH-Blacks when compared to NH-Whites.
 
 
 No relevant conflicts of interest to declare.


provides nationally representative information on hospitalizations [5]. The HCUP transitioned from International Classification of Diseases (ICD)-9-CM to ICD-10-CM Clinical Modification (CM) coding format on October 1, 2015. Only ICD-10-CM codes were utilized in this study to avoid inclusion of Transthyretin amyloidosis: ATTR amyloidosis, which was not separated out from AL amyloidosis in the ICD-9-CM coding system. We included all hospitalizations in adults (age ≥ 18 years) during the study period from 2016 to 2018. The exposure for the study was the occurrence of AL amyloidosis in the discharge records of adults, where up to 30 diagnosis codes are captured for each in-hospital stay. Outcomes were [1] in-hospital death [2] chemotherapy use; [3] intensive care unit (ICU) utilization; [4] palliative care consultation.
Socio-demographic characteristics included in the analysis were patient age (categorized into 18-34, 35-49, 50-64, 65 + years), race/ethnicity (sub-classified as non-Hispanic (NH) White, NH-Black, Hispanic, other), gender (female or male), zip code-based median household income (lowest, 2nd, 3rd and highest quartile), primary insurance (Medicare, Medicaid, private insurance, self-pay, other). Other health status indicators documented during the hospitalization and included in the analysis were Elixhauser Comorbidity Index (0, 1-4, 5 +) [6] and severity of illness (mild, moderate, severe, extreme); patients' length of stay and mean cost of hospitalization. The latter was calculated by multiplying the charge associated with each hospitalization to the costto-charge ratio, which is made available by the HCUP [5].
Joinpoint regression to assess temporal trends in the national incidence of in-hospital death among all Al amyloidosis hospitalizations was done. We conducted adjusted survey logistic regression to generate adjusted odds ratios to measure the likelihood of in-hospital death among AL amyloidosis-related hospitalizations. The analysis for this The frequency of AL amyloidosis-related hospitalizations as compared to all hospitalizations was higher in older individuals, males, and NH-Blacks (Table 1). Admissions related to AL amyloidosis accounted for 0.03% of all hospitalizations in the study period (25,470 of 90,869,381). The prevalence of AL amyloidosis-related hospitalizations was higher in NH-Blacks when compared with NH-Whites (42.8 versus 28.1 per 100,000 hospitalizations). AL amyloidosisrelated in-hospital mortality rate was higher in NH-Whites and Hispanics when compared to NH-Blacks (6.6%% and 6.2% versus 4.9%, p < 0.01). In-hospital mortality with AL amyloidosis was higher in older patients, males, and those who self-paid for their treatment. Utilization of ICU care was more frequent in NH-Blacks when compared to NH-Whites (6% versus 4.8%). Hispanics had the lowest inpatient chemotherapy use (1.7% versus 2.9%). No difference was found between mean cost of hospitalization (overall: 19,451 USD/admission) and mean length of stay (overall: 7.4 days/ admission).
A multivariable analysis adjusted for patient's gender, age, income quartile, primary payor and comorbidities showed a trend towards lower in-hospital mortality and higher ICU utilization in NH-Blacks when compared to NH-Whites (OR 0.76, 95% CI 0.55-1.05, p = 0.09 and OR 1.29, 95% CI 0.96-1.72, p = 0.09, respectively) and lower utilization of palliative care services in NH-Blacks when compared with NH-Whites (OR 0.61, 95% CI 0.42-0.88, p = 0.01) ( Table 2). A very low number of transplant-related admissions (n = 10) was reported, with such admissions occurring only in NH-Whites. No blood product transfusion-related hospitalizations were reported in the study period.
The management of AL amyloidosis is changing with better therapies currently used in the frontline setting, which comprises autologous stem cell transplantation It has been suggested that NH-Black Americans have a higher prevalence of a difference between involved and uninvolved free light chains > 180 mg/L (39% versus 22-33%, p = 0.044) which indicates a more aggressive phenotype [4].
In our analysis, we showed important disparities in AL amyloidosis care for NH-Blacks and Hispanics in the largest nationwide inpatient sample.
We observed a trend towards lower in-hospital mortality despite a trend for higher utilization of ICU care in NH-Blacks when compared to NH-Whites. This may suggest better outcomes in NH-Blacks which can be explored further with a future follow up analysis of longer duration.
There is a paucity of data that address symptoms management and palliative care in AL amyloidosis, though many physical and psychological challenges are associated with its diagnosis and treatment [10]. We found a 39% lower inhospital utilization of palliative care in NH-Blacks when compared to NH-Whites. This difference may result in lack of subsequent symptom control, under-utilization of available palliative therapies and worse quality of life [11].
Our analysis has some important limitations. NIS dataset provides hospitalization level information with no patient level data. There is lack of some significant variables such as stage of AL amyloidosis, organ involvement, and laboratory data. Moreover, it did not include information on outpatient or acute care hospitals, and thus palliative care utilization as an outpatient cannot be ascertained from our analysis.
In conclusion, NH-Blacks tend to have lower in-hospital mortality with higher utilization of ICU care, but, they receive the lowest number of palliative care services. Despite the higher utilization of ICU care, the data suggest possible superior outcomes of AL amyloidosis in NH-Blacks when compared to NH-Whites.