Gender Disparities in Hospitalization Outcomes and Healthcare Utilization Among Patients with Systemic Lupus Erythematosus in the United States

Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various clinical manifestations. Despite efforts to improve outcomes, mortality rates remain high, and certain disparities, including gender, may influence prognosis and mortality rates in SLE. This study aims to examine the gender disparities in outcomes of SLE hospitalizations in the US. Methods We conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) database between 2016 and 2020. The NIS database is the largest publicly available all-payer database for inpatient care in the United States, representing approximately 20% of all hospitalizations nationwide. We selected every other year during the study period and included hospitalizations of adult patients (≥18 years old) with a primary or secondary diagnosis of SLE using International Classification of Diseases, Tenth Revision (ICD-10) codes. The control population consisted of all adult hospitalizations. Multivariate logistic regression was used to estimate the strength of the association between gender and primary and secondary outcomes. The regression models were adjusted for various factors, including age, race, median household income based on patients' zip codes, Charlson comorbidity index score, insurance status, hospital location, region, bed size, and teaching status. To ensure comparability across the years, revised trend weights were applied as the healthcare cost and use project website recommends. Stata version 17 (StataCorp LLC, TX, USA) was used for the statistical analyses, and a two-sided P-value of less than 0.05 was considered statistically significant. Results Among the 42,875 SLE hospitalizations analyzed, women accounted for a significantly higher proportion (86.4%) compared to men (13.6%). The age distribution varied, with the majority of female admissions falling within the 30- to 60-year age range, while most male admissions fell within the 15- to 30-year age category. Racial composition showed a slightly higher percentage of White Americans in the male cohort compared to the female cohort. Notably, more Black females were admitted for SLE compared to Black males. Male SLE patients had a higher burden of comorbidities and were more likely to have Medicare and private insurance, while a higher percentage of women were uninsured. The mortality rate during the index hospitalization was slightly higher for men (1.3%) compared to women (1.1%), but after adjusting for various factors, there was no statistically significant gender disparity in the likelihood of mortality (adjusted odds ratio (aOR): 1.027; 95% confidence interval (CI): 0.570-1.852; P=0.929). Men had longer hospital stays and incurred higher average hospital costs compared to women (mean length of stay (LOS): seven days vs. six days; $79,751 ± $5,954 vs. $70,405 ± $1,618 respectively). Female SLE hospitalizations were associated with a higher likelihood of delirium, psychosis, and seizures while showing lower odds of hematological and renal diseases compared to men. Conclusion While women constitute the majority of SLE hospitalizations, men with SLE tend to have a higher burden of comorbidities and are more likely to have Medicare and private insurance. Additionally, men had longer hospital stays and incurred higher average hospital costs. However, there was no significant gender disparity in the likelihood of mortality after accounting for various factors.


Methods
We conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) database between 2016 and 2020. The NIS database is the largest publicly available all-payer database for inpatient care in the United States, representing approximately 20% of all hospitalizations nationwide. We selected every other year during the study period and included hospitalizations of adult patients (≥18 years old) with a primary or secondary diagnosis of SLE using International Classification of Diseases, Tenth Revision (ICD-10) codes. The control population consisted of all adult hospitalizations. Multivariate logistic regression was used to estimate the strength of the association between gender and primary and secondary outcomes. The regression models were adjusted for various factors, including age, race, median household income based on patients' zip codes, Charlson comorbidity index score, insurance status, hospital location, region, bed size, and teaching status. To ensure comparability across the years, revised trend weights were applied as the healthcare cost and use project website recommends. Stata version 17 (StataCorp LLC, TX, USA) was used for the statistical analyses, and a two-sided P-value of less than 0.05 was considered statistically significant.

Results
Among the 42,875 SLE hospitalizations analyzed, women accounted for a significantly higher proportion (86.4%) compared to men (13.6%). The age distribution varied, with the majority of female admissions falling within the 30-to 60-year age range, while most male admissions fell within the 15-to 30-year age category. Racial composition showed a slightly higher percentage of White Americans in the male cohort compared to the female cohort. Notably, more Black females were admitted for SLE compared to Black males. Male SLE patients had a higher burden of comorbidities and were more likely to have Medicare and private insurance, while a higher percentage of women were uninsured. The mortality rate during the index hospitalization was slightly higher for men (1.3%) compared to women (1.1%), but after adjusting for various factors, there was no statistically significant gender disparity in the likelihood of mortality (adjusted odds ratio (aOR): 1.027; 95% confidence interval (CI): 0.570-1.852; P=0.929). Men had longer hospital stays and incurred higher average hospital costs compared to women (mean length of stay (LOS): seven days vs. six days; $79,751 ± $5,954 vs. $70,405 ± $1,618 respectively). Female SLE hospitalizations were associated with a higher likelihood of delirium, psychosis, and seizures while showing lower odds of hematological and renal diseases compared to men.

Conclusion
While women constitute the majority of SLE hospitalizations, men with SLE tend to have a higher burden of comorbidities and are more likely to have Medicare and private insurance. Additionally, men had longer hospital stays and incurred higher average hospital costs. However, there was no significant gender disparity in the likelihood of mortality after accounting for various factors.

Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation that can affect multiple organ systems [1,2]. This complex condition is reported to predominantly affect women, with a significantly higher prevalence compared to men [3,4]. While the gender bias in SLE is well-established, the extent to which gender influences hospitalizations and inpatient outcomes, particularly mortality, among patients with SLE remains an area of vital research and inquiry. Understanding these disparities is important for ensuring equitable healthcare provision and improving outcomes within this patient population.
The index study presents the findings of an extensive nationwide population-based study aimed at examining the profound impact of gender disparities on hospitalizations and inpatient outcomes for patients with SLE in the United States, with a particular focus on mortality and other critical outcome measures. By harnessing a vast and diverse dataset, the study aims to assess the contribution of gender to differential outcomes within the context of SLE.
Beyond well-documented epidemiological differences, including disease prevalence and age of onset, gender is believed to exert a significant influence on disease management, treatment response, and longterm prognosis in SLE [5]. Existing research has hinted at the likelihood of more severe disease manifestations, higher disease activity, and increased disease-related damage among females with SLE compared to males [6][7][8]. However, limited attention has been given to the role of gender disparities in hospitalization rates and subsequent outcomes within the SLE population, particularly concerning mortality and other crucial measures.
In this study, we examined a large, representative cohort of patients diagnosed with SLE, spanning diverse geographic regions. We aim to unravel the specific dimensions of gender disparities in hospitalizations and inpatient outcomes within this population, with a particular emphasis on mortality as a critical outcome measure. Our investigation encompasses an assessment of outcomes such as hospitalization rates, length of stay, complications, and mortality, all stratified by gender.
The findings from this study have potential implications for clinical practice, healthcare policies, and public health interventions. By identifying and quantifying the impact of gender on hospitalizations and inpatient outcomes, particularly mortality, we can devise targeted strategies to optimize care delivery, allocate resources effectively, and enhance patient outcomes for both male and female individuals living with SLE.

The Nationwide Inpatient Sample Database (NIS)
We conducted a retrospective cohort study utilizing data from the Nationwide Inpatient Sample (NIS) database spanning the years 2016 to 2020. The NIS database stands as the largest all-payer inpatient dataset, providing discharge data that approximate national figures in the United States [9,10]. The NIS database is a robust and widely utilized resource in healthcare research, providing valuable insights into inpatient hospitalizations across the United States. It encompasses a representative sample of discharges from community hospitals, including academic medical centers, teaching hospitals, and non-teaching facilities. With its extensive coverage spanning diverse geographic regions, the NIS offers a comprehensive snapshot of the nation's inpatient healthcare landscape. Its wealth of data encompasses a wide range of clinical, demographic, and utilization variables, allowing researchers to explore various aspects of healthcare delivery, disease patterns, and outcomes. The meticulous design employed in constructing the NIS ensures data accuracy, reliability, and generalizability, empowering researchers to derive meaningful and evidencebased conclusions to inform healthcare policies, improve patient care, and advance medical knowledge.

Inclusion criteria and study variables
This study included all hospital admissions of individuals aged 15 years and older (reproductive age group) whose primary discharge diagnosis was SLE. The primary diagnosis, all confounders, and complications of SLE were defined using the International Classification of Diseases Tenth Revision Clinical Modification and Procedure Coding System (ICD-10-CM/PCS). The total cohort was dichotomized based on gender into male and female categories, while age categories were defined as 15-30, 31-60, and >60 years. Hospitalizations with missing data or incomplete records were excluded from the study.

Ethical considerations
Institutional Review Board approval was not required because the database used for this study is deidentified, publicly available, and does not include protected healthcare information.

Outcome measures
The primary outcome of interest was inpatient mortality, while secondary outcomes included the mean length of hospitalization, the mean total hospital charges, and the likelihood of experiencing SLE complications between males and females. Mortality is recorded within a dichotomous variable (DIED) in the NIS. The mortality variable is recorded as one (died during the index admission) or 0 (did not die during the index admission). The length of stay and hospital charges variables are recorded as numerical variables, allowing for quantitative analysis such as calculating averages, performing statistical tests, and examining trends or patterns in hospital charges.

Statistical analysis
Data analysis was performed using Stata version 17 software (StataCorp LLC, Texas, USA). Sample weighting was applied during analyses to ensure compliance with the Healthcare Cost and Utilization Project regulations concerning the use of the NIS database for generating national estimates. Baseline patient and hospital-level characteristics and comorbidities between the male and female groups were compared using chi-square tests. An initial univariate screen including all variables listed in Table 1 was performed to identify factors related to the outcomes of interest.  The association between outcomes and gender was subsequently assessed using multivariate regression analyses, including relevant variables with a p-value less than 0.1 on the univariate screen. The likelihood of mortality was calculated as an adjusted odds ratio, while the secondary outcomes were calculated as an adjusted mean difference. The threshold for statistical significance was set at a p-value of less than 0.05 for all analyses.

Primary outcome: mortality
During the index hospitalization, the mortality rate among men admitted for SLE was 1.3%, slightly higher than the rate of 1.1% observed in the female population. However, after accounting for various patient and hospital-level factors, a comprehensive multivariate analysis revealed no statistically significant gender disparity in the likelihood of mortality (adjusted odds ratio (

Discussion
The findings of the index study reveal distinct sociodemographic characteristics between male and female SLE patients. While the mean age of both groups was comparable, there were notable differences in the age distribution. Females comprised the majority of SLE admissions within the age range of 30 to 60 years, whereas males had a higher proportion of admissions in the 15 to 30 age category. Moreover, a significant percentage of male SLE admissions were among individuals aged over 60, compared to the female cohort. These age-related differences have important clinical implications. Younger male SLE patients may require increased attention and targeted interventions to address disease manifestations and complications specific to this age group [11,12]. Additionally, the higher proportion of older males with SLE highlights the need for comprehensive management strategies that consider age-related comorbidities and treatment interactions [13].
Racial disparities were also observed, with White Americans accounting for a slightly higher proportion of male SLE admissions compared to females. Conversely, a greater number of Black females were admitted for SLE compared to Black males. These racial and gender disparities in SLE hospitalizations warrant further investigation into the underlying factors contributing to these disparities. Tailored approaches that consider the unique needs and challenges faced by different racial and gender groups can help improve SLE outcomes and reduce disparities [14,15]. The burden of comorbidities and insurance coverage showed some gender differences, with males carrying a higher burden of comorbidities and a greater percentage having Medicare and private insurance. Females, on the other hand, had a higher percentage of uninsured individuals. These findings emphasize the importance of comprehensive care coordination and access to healthcare services for all SLE patients, regardless of gender [16]. Addressing the disparities in comorbidities and insurance coverage can enhance overall disease management and improve outcomes [17,18].
The primary outcome of interest in this study was inpatient mortality among SLE admissions. The analysis revealed a slightly higher mortality rate among males compared to females during the index hospitalization. However, after adjusting for various patient and hospital-level factors, no statistically significant gender disparity in the likelihood of mortality was observed. These findings suggest that while there may be initial differences in mortality rates between male and female SLE patients, other factors, such as disease severity, comorbidities, and access to care, may contribute more significantly to mortality risks [19][20][21]. This underscores the need for comprehensive assessment and management of these factors to improve survival outcomes for all SLE patients.
The secondary outcomes of this study focused on the length of hospital stay, hospital charges, and the likelihood of SLE-related complications. Male SLE patients had longer hospital stays compared to females, accompanied by higher average hospital costs. Although the differences were not statistically significant, these findings suggest the need for closer monitoring and management of male SLE patients during hospitalization to ensure timely and efficient care. Additionally, healthcare providers should be mindful of potential financial burdens on patients and explore strategies to mitigate costs without compromising the quality of care.
In terms of complications related to SLE, females exhibited a higher probability of experiencing delirium, psychosis, and seizures compared to males. On the other hand, females had lower chances of developing hematological and renal diseases. These findings contrast with previous studies that have documented higher seizure rates in men [22]. The observed gender differences in complications suggest a potential shift in the prevailing trends and underscore the significance of tailored approaches to managing and monitoring these specific complications. Healthcare providers should remain vigilant in detecting and addressing these complications, particularly in female SLE patients, to enhance outcomes and improve their overall quality of life.
The findings of this study have several clinical implications. Firstly, understanding the sociodemographic characteristics of SLE patients, such as gender, age, and racial disparities, can inform healthcare providers in tailoring their approaches to address the specific needs and challenges faced by different patient populations. Comprehensive care plans that consider age-related comorbidities, disease manifestations, and treatment interactions can improve patient outcomes and quality of life. Secondly, the absence of a significant gender disparity in mortality rates after adjusting for confounding factors suggests that other factors play a more substantial role in determining mortality risks in SLE. Identifying and addressing these factors, including disease severity, comorbidities, and access to care, is crucial for reducing mortality rates in both male and female SLE patients. Lastly, the gender differences in SLE-related complications highlight the importance of tailored management approaches. Healthcare providers should be vigilant in recognizing and managing complications such as delirium, psychosis, and seizures, as well as hematological and renal diseases, especially among female SLE patients. Early detection and targeted interventions can help minimize the impact of these complications and improve overall patient outcomes.
The study has some limitations related to the use of administrative databases. These limitations include non-randomization and inadequate records of disease severity, which could potentially impact the assessment of mortality. Additionally, owing to the nature of the NIS, the identification of comorbidities in this study was conducted without utilizing admission indicators to differentiate between pre-existing comorbid conditions and complications that arise during hospitalization, potentially resulting in a significant overlap between comorbidity and complications.

Conclusions
In conclusion, this study demonstrates that gender disparities exist in sociodemographic characteristics, insurance status, inpatient complications, and resource utilization among patients admitted with SLE. The findings highlight the need for tailored approaches that consider the sociodemographic characteristics, burden of comorbidities, and insurance coverage of SLE patients. Addressing these disparities and implementing targeted interventions can lead to improved outcomes, reduced complications, and enhanced quality of care for all SLE patients, irrespective of their gender. Further research is needed to explore the underlying mechanisms contributing to gender disparities in SLE outcomes and to develop evidence-based strategies for mitigating these disparities and optimizing patient care.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.