Jennifer Bello Kottenstette, MD, MS; Nathaniel Dell, PhD, LCSW; Aaron Laxton, LCSW; Mary Conte, BS
Background: Reproductive-aged women with opioid use disorder (OUD) are at risk of pregnancy exposed to opioids. Despite the known benefits of Medication for Addiction Treatment (MAT), many individuals do not receive treatment. The prevalence of MAT among reproductive-aged women seeking treatment in publicly funded treatment centers is unknown.
Methods: We used administrative records data from the Treatment Episode Data Set-Admissions (TEDS-A) to identify characteristics and planned receipt of MAT for 12-49-year-old women with OUD who entered treatment from 2015-2019 (N = 153,830). We used descriptive statistics and logistic regression to identify characteristics associated with receipt of MAT. Fifty-one percent of the sample was 25-34 years old and 79% identified as non-Hispanic White.
Results: At admission, 32.47% of the sample were enrolled in MAT. Of those receiving MAT, 8.06% were pregnant compared to 3.67% not receiving MAT. Approximately half of pregnant women (51.38%, n = 3,953) received MAT and pregnancy was associated with MAT in adjusted models (OR = 2.43, 95% CI [2.30, 2.56]). Compared to non-Hispanic whites, all other racial/ethnic groups had higher odds of MAT: non-Hispanic Black (OR=1.15, 95% CI [1.10, 1.20]) and Hispanic (OR=1.26, 95% CI [1.21, 1.32]). MAT was less likely in residential (OR=0.17, 95% CI [0.16, 0.18]) or detoxification (OR=0.12, 95% CI [0.12, 0.13]) compared to ambulatory settings.
Conclusions: While the majority of reproductive-aged women with OUD seeking treatment in publicly funded treatment centers do not receive MAT, pregnancy increased the likelihood of MAT. Disparities in MAT by race and service setting need further exploration.
Haider Al-Hakeem, Zidong Zhang, Elisabeth C. DeMarco, Leslie Hinyard, PhD, MSW
Background: Parkinson’s disease (PD), a neurodegenerative disorder primarily observed in older age groups, is a condition that manifests a wide range of symptoms and can be comorbid with other chronic diseases. This study examines the reasons for emergency department (ED) visits in a cohort of patients with PD to identify comorbidity profiles that increase the risk for requiring emergency medical care.
Methods: We conducted a four-class Latent Class Analysis (LCA) to classify PD patients with ED visits based on pre-existing comorbid conditions in the 6 months prior to their first ED visit following PD diagnosis. We conducted multiple logistic regression models with the outcome of reason-for-visit to determine the associations with comorbidity-profile class, adjusting for patient demographics and socio-economic characteristics.
Results: The most common reasons for ED admission were injuries, diseases of the circulatory system, and general signs and symptoms, including abdominal pain, malaise, and fatigue. Compared to those in the “Poorest Health” classification of the LCA, both classes with “Moderate Physical & Mental Health” had greater odds for a circulatory system admission and reduced odds of admission for digestive system disease and injury or poisoning. Those classified as “Moderate Physical & Mental Health with Diabetes” were less likely to be admitted for a nervous system disease compared to those in “Poorest Health.”
Conclusions: Clarifying the complex medical needs of patients with PD is the first step to further individualize care, which may reduce emergency department visits in this population, improve quality of life, and lessen the footprint on the healthcare system.
Matthew Amick, MS; Jeffrey Scherrer, PhD
Background: Non-specific effects of tetanus, diphtheria, and pertussis (Tdap) and other routine adult vaccinations may reduce the risk of incident Alzheimer’s and related dementias (ADRD). However, reduction of risk by sex has not been investigated despite documented gender differences in vaccine uptake and immune response.
Methods: Data was obtained from Veterans Health Affairs (VHA) medical records. Patients were at least 65 years of age, free of dementia for 2 years prior to index date, and either did or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2019. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing-risk survival regression models in males and females before and after e-balance weighting calculated hazard ratios and 95% confidence intervals for the relationship of Tdap vaccination and incident dementia.
Results: On average, men (n=118,086) were 75.7 (±7.5) and women (n=4,860) were 73.2 (±8.5) years of age. Women had higher healthcare utilization, greater vaccine uptake, and a larger percentage of general and sex-specific preventive care screens. After controlling for confounders and healthy patient bias, the association between Tdap vaccination and incident ADRD did not significantly differ by gender. Tdap vaccination was associated with a 52% risk reduction for women and 37% risk reduction for men.
Conclusions: Consistent with the literature, these findings strengthen the link between vaccination and decreased risk of ADRD beyond any sex-specific discrepancies in health behaviors or immunological differences.
Jennifer Brinkmeier, MD; Noor Al-Hammadi, MPH; Elisabeth C. DeMarco; Leslie J. Hinyard, PhD, MSW
Background: Elective surgical procedures considered appropriate for same day surgery (SDS) are performed in a variety of settings with diverse resources which may lead to variations in care received. Furthermore, SDS is variably defined in the literature, complicating efforts to assess variations in care received and patterns of healthcare utilization. This study examines patient characteristics and outcomes for select procedures appropriate for SDS by length of stay to validate use of this information to identify variations in care.
Methods: Eligible procedure codes for surgeries considered appropriate for SDS were selected from the literature. Cohort included patients 18 years or older from the Optum® de-identified Electronic Health Record (EHR) dataset between January 1, 2008, and December 31, 2018 undergoing SDS. Patients grouped by length of stay (groups: <24h, 24-<48h, 48+h). Patient characteristics (sociodemographic information, comorbidities) and postoperative complications and readmission rates within 30 days were analyzed to examine for variability across groups.
Results: Of the 48,646 procedures in the study, 55.19% resulted in discharge within 24 hours. Analysis of patient characteristics by procedure and length of stay group is forthcoming. Across length of stay groups and procedure type, there was variation in the proportion of patients experiencing postoperative complications and readmission rates within 30 days.
Conclusions: Grouping patients by length of stay can reveal variations in patient characteristics and care received across a range of procedures considered appropriate for SDS. Further work is needed to identify contributing factors to this care variation as the first step to optimizing patient centered surgical care.
Nina K. Cheranda; Suhong Luo, MS; Kristen M. Sanfilippo, MD, MSPH; Martin W. Schoen, MD, MPH
Background: In metastatic castrate resistant prostate cancer (mCRPC), there is a lack of studies that explore the interaction of race on treatment outcomes. Black men have greater incidence, lower five-year survival, and higher mortality due to prostate cancer when compared to white men. However, variations in risk factors, healthcare access, and other covariate prognostic factors have helped explain why more aggressive and advanced prostate cancer are found in black men.
Methods: Patients initially treated with abiraterone or enzalutamide for mCRPC from May 2011 to June 2017 were identified within the Veterans Health Administration (VHA). Kaplan-Meier and Cox proportional hazards modeling was used to assess the association between overall survival and covariates, including treatment, age, Charlson Comorbidity Index, body-mass index, baseline PSA, prior docetaxel, hemoglobin, creatinine clearance, bilirubin, and albumin at start of treatment.
Results: Of 11,027 patients, 2550 (23.1%) were identified as black. Black patients with mCRPC were younger (72.6 vs. 75.8 years, p<0.001), had higher median PSA (60.3 vs. 37.0, p<0.001) and a higher Charlson comorbidity index (4.5 vs. 3.9, p<0.001). Black men lived a median of 2.0 months longer than non-black men (22.0 vs. 20.0, p<0.001), and in multivariable models, black race was associated with longer survival (adjusted Hazard Ratio 0.76, 95% CI 0.72-0.80). Black patients lived longer with enzalutamide compared to abiraterone (24.5 vs. 21.3 months, p<0.001).
Conclusions: In the VHA, which provides more equitable access to care, black men have longer survival, are younger, and have higher PSA when starting treatment than non-black patients
Sarah C. Gebauer, MD, MSPH; Timothy Chrusciel, MPH; Joanne Salas, MPH; Jeffrey Scherrer, PhD
Background: Osteoarthritis (OA) is a common cause of chronic pain and disability world-wide with its most efficacious treatment being walking. Neighborhood environment is associated with physical activity (PA) in older adults and may be connected to OA severity. This study explored whether high vs low neighborhood Socioeconomic Status (nSES) was associated with increasing knee OA severity via a novel osteoarthritis severity index (OASI) in older adults.
Methods: Data were extracted from the SSM-SLU AHEAD Institute Virtual Data Warehouse (2008-2021). This retrospective cohort analysis used Poisson regression modeling on number of different types of treatments received following knee OA diagnosis before and after adjusting for demographics and comorbidities. Eligible patients were 45-80 years old with knee OA (ICD-9/10 codes) with no history of knee arthroplasty (n=3,772). nSES was measured via a validated index using American Community Survey 5-year estimates linked to patient ZIP code. OASI measured knee OA severity and was the sum of the number of different types of diagnostic tests/treatments received identified via CPT codes and medication prescriptions (X-ray, advanced imagine, joint injection, NSAIDs, opioids and physical therapy).
Results: The sample was about 70% female and mean age was 62.1 years. X-ray (57.1%), injection (52.3%), NSAID (63.9%) and opioid (61.8%) were the most prevalent treatments. Fully adjusted analysis revealed that nSES was unassociated with OASI (RR=0.97[95%CI0.93-1.01]).
Conclusions: This study found no association between nSES and OASI. Future studies will investigate other neighborhood factors, such as built environment & violent crime rates.
Kaushik Gokul, BS; Zidong Zhang, MPH; Divya Subramaniam, PhD, MPH; Seri Park
Background: Minimal research examining the impact of palliative care on the outcomes of pancreatic cancer patients in the U.S. exists. The purpose of this study was to determine the incidence of palliative care consultations (PCC) among pancreatic cancer patients. Aggressive interventions at the end of life and demographic variables were also explored.
Methods: A retrospective study utilizing de-identified Electronic Health Record was conducted by identifying deceased patients with a diagnosis of pancreatic cancer. Clinical history was examined at end of life (0-6 months) for the presence of PCC. Aggressive interventions were defined as chemotherapy, ICU admissions, or E.D. visits in the last six months of life. Demographic variables such as race, gender, ethnicity, education, and others were extracted. The utilization of services was compared between the PCC and the non-PCC groups using Whitney U-test and Chi-squared test.
Results: A total of 2,883 patients were diagnosed with pancreatic cancer but only 858 received PCC. The average age of death was greater at 70.5 years within the PCC group when compared to 68.9 without PCC. This difference was statistically significant. Of the patients who received PCC, 22.4% had chemotherapy while 10.6% had chemotherapy in the group that did not receive PCC. The other aggressive interventions showed similar trends with statistically significant differences.
Conclusions: Our study found that less than 30% of pancreatic cancer patients received PCC. Findings highlight the need to increase PCC among these patients following diagnosis. Additionally, targeted educational interventions must be developed to increase palliative care utilization among pancreatic cancer patients.
Srinivas Govindan; Nina K. Cheranda; Suhong Luo, MS; Martin W. Schoen, MD, MPH
Background: In metastatic castrate resistant prostate cancer (mCRPC), there is a lack of studies to assess responses to Enzalutamide and Abiraterone based on HbA1c while accounting for important covariates such as obesity.
Methods: Patients treated with abiraterone or enzalutamide for mCRPC from September 10, 2014 to June 2, 2017 were identified within the Veterans Health Administration. The patients were classified into 4 groups separated by most recent HbA1c values collected prior to the start of treatment (<5.6%, 5.6% - 6.4%, 6.5% - 7.1%, >=7.2%). Cox proportional hazards modeling was used to assess the association between overall survival and covariates, including age, body-mass index, baseline PSA, and HbA1c.
Results: 3421 patients treated with abiraterone or enzalutamide had HbA1c data available. There were 658 patients with HbA1c <5.6%, 1430 with 5.6-6.4%, 667 with 6.5%-7.1%, and 666 with HbA1c >=7.2. The cox model showed no significance in median survival between enzalutamide vs abiraterone in patients with HbA1c <5.6% group (adjusted hazard ratio (aHR) 1.15 (95% CI, 0.960-1.370)). However, there was significantly greater survival in patients who received enzalutamide compared to abiraterone in all other groups as follows: 5.6%-6.4% aHR 0.86 (0.759-0.965), 6.5%-7.1% aHR 0.74(0.623-0.879) and >=7.2% aHR 0.80 (0.669-0.948).
Conclusions: In patients with HbA1c ≥ 5.6%, enzalutamide was associated with significantly greater survival than in patients who received abiraterone, even when including baseline BMI and other important covariates. Further studies of interactions between patient factors and treatment are warranted to guide treatment selection in the clinic.
Alexandria Jenkins, BS; Divya Subramaniam, PhD, MPH; Zidong Zhang, MPH; Leslie Hinyard, PhD, MSW
Background: Breast cancer is one of the most diagnosed cancers in women; it is estimated that there will be 280,000 new cancers and over 40,000 women will die from breast cancer in the United States in 2022. Metastatic breast cancer (MBC) has a greater symptom toward the end of life (EOL) than earlier stages of disease. Palliative care has been demonstrated to improve quality of life and decrease symptom burden in advanced cancers but has been underutilized. The current study estimates the inpatient palliative care consultations (PCC) in women and compares health service utilization at the EOL before and after PCC.
Methods: A retrospective study of women with a diagnosis of MBC between 2010-2018 was performed using de identified electronic medical record data from a national healthcare informatics provider and insurer.
Results: Overall, 37.4% of the study population received at least one PCC during their last recorded hospital admission while 62.6% had none. Those that did have PCC had higher rates of comorbidities than those that did not. There were more ICU and chemotherapy encounters after a patient's referral compared to before any PCC. The proportion of patients with at least one ED visit during the study period went from 50.7% prior to PCC, to 45.9% following at least one PCC.
Conclusions: There is still limited utilization of palliative care interventions for patients with advanced MBC at the EOL. Our study infers sicker patients tend to have higher rates of PCC. Earlier PCC interventions are needed for patients with MBC to increase its efficacy.
Jordan Perkins, MD; Joe Rodriguez, MD; Maho Kurashima, MD; Christian Saliba, MD; Christopher Blewett, MD; Shin Miyata, MD
Background: Pyloromyotomies for infantile hypertrophic pyloric stenosis in academic centers are generally performed by pediatric surgeons (PS), while in non-specialized centers these are performed by general surgeons (GS). This study aims to correct the paucity of data comparing the safety between PS and GS in performing a pyloromyotomy.
Methods: Data from 2012-2020 was obtained from the ACS-National Surgical Quality Improvement Program Pediatric database. All patients who underwent pyloromyotomy by GS or PS were included. Patients who underwent other concurrent procedures were excluded. Patient characteristics and postoperative outcomes were queried and compared between the two groups. Bivariate analysis and logistic regression analysis were performed with a P-value < 0.05 being considered statistically significant.
Results: A total of 18,453 pyloromyotomies were identified. 4% (n=731) of cases were performed by GS and 96% (n=17,722) by PS. The analysis indicated that several patient characteristics (weight, race, ASA class, comorbidities) and intra- and post-operative characteristics (operative length and hospital length of stay) were significantly different between the groups. After adjusting for known risk factors, the post-operative complications, re-admission rate, mortality and rate of re-operation were statistically similar between GS and PS. However, logistical regression showed a significantly higher number of GS performed the surgery laparoscopically when compared to PS (Adjusted OR 1.24, 95% Confidence Interval 1.04 - 1.49).
Conclusions: Our study demonstrated no difference in post-operative outcome or safety between GS and PS in performing pyloromyotomies. We suggest that GS who feel comfortable performing pyloromyotomies should keep this in their scope of practice.
Forest Riekhof, BS; Suhong Luo, MS; Kristen Marie Sanfilippo, MD, MPHS; Martin Schoen, MD, MPH
Background: Abiraterone (AA) and Enzalutamide (ENZ) are hormone therapies used in the treatment of metastatic castrate resistant prostate cancer (mCRPC). Due to a lack of large comparative studies, they are used interchangeably, but have different adverse profiles.
Methods: The Veterans Health Administration database was used to identify patients with mCRPC treated with AA or ENZ between 5/13/2011 and 12/31/2019. Hospitalization ICD codes were used to determine cause. Hospitalizations from one year prior were used to make baseline incidence rates. Incidence rate difference (IRD) was calculated using chi-square test and difference in IRD using poisson regression for specific adverse events of interest.
Results: 19,775 patients were treated with AA (68.4%) or ENZ (31.6%). ENZ cohort had higher baseline comorbidities. Of the 11,494 hospitalizations, 72.2% occurred in AA cohort and 27.7% occurred in ENZ cohort. AA hospitalizations for CHF, ischemic stroke, ischemic heart disease, A fib, and infections increased. ENZ hospitalizations for CHF, ischemic stroke, ischemic heart disease, and sepsis increased. Total hospitalization rate increased 22% in AA vs 3% in ENZ. A fib, AKI, seizure, infections, and hepatitis occurred more in AA. CHF occurred more in ENZ. Ischemic heart disease, stroke, and QT prolongation showed no difference. AA had a larger increase from baseline for CHF, A fib, AKI, infections, and total hospitalizations.
Conclusions: This study provides safety profile data for two frequently used hormone therapies in prostate cancer. Hospitalizations for infection, cardiovascular disease, and renal complications were common, and increased in patients initially treated with abiraterone compared to enzalutamide.
Joanne Salas, MPH; Jeffrey F. Scherrer, PhD; Sara Gebauer, MD, MSPH
Background: Posttraumatic stress disorder (PTSD) is associated with poor health behaviors. PTSD symptom improvement has been shown to increase healthy behaviors like medication adherence and use of substance abuse treatment programs. This study sought to determine whether patients with vs. without clinically meaningful PTSD symptom improvement were more likely to stop smoking.
Methods: This study used Veterans’ Health Administration EHR data (2008-2015). Eligible patients were aged 18-70 years with PTSD and a PTSD symptom checklist (PCL) score ≥50, ≥1 PCL from ≥8-52 weeks following first PCL≥50 (‘exposure year’), and persistent smokers in the exposure year (n=449). Index date is the end of the exposure year. Change from first to last PCL score in exposure year was classified as clinically meaningful vs. less than clinically meaningful improvement (≥20 vs. <20-point decrease). The outcome was time to smoking cessation in the 2-years after index. Entropy balancing controlled for confounding in Cox proportional hazard models.
Results: Overall, patients were 39.4 (±12.9) years old, 19.8% had a clinically meaningful PCL score decrease, and 32.7% quit smoking. After entropy weighting, PCL decrease ≥ 20 vs. < 20 was associated with a 57% increased likelihood of smoking cessation (HR=1.57; 95%CI=1.04-2.36). Among patients who quit, about half remained non-smokers in the 12-months after initial quit date.
Conclusions: Clinically meaningful PTSD symptom improvement was associated with smoking cessation. Not all patients with PTSD have access to PTSD treatment modalities that integrate smoking cessation therapy; however, PTSD treatment alone may improve patient self-efficacy and enable smoking cessation.
Sumana Shashidhar; Dhiren Patel, MD; Jennifer Brinkmeier, MD; Noor Al-Hammadi
Background: Aerodigestive care is one model of multi-disciplinary care, which is proven to be a valuable tool for both providers and patients. These care models are associated with improved outcomes, reduced anesthesia exposure, reduction in hospital admissions, and fewer days of missed work or school. This is the first study to explore national trends in combined endoscopy utilization to identify gaps in care.
Methods: Data from the Healthcare Cost and Utilization Project (HCUP) Kid’s Inpatient Sample was used from 2003, 2006, 2009, 2012, and 2016. Diagnoses and procedures were identified using ICD-9 and ICD-10 codes, for patients with hospital length of stay less than 1 day. Demographic data was identified for these cohorts and survey-weighted means and proportions were computed in addition to Rao Scott Chi-Square tests. National estimates of charges were computed with discharge weights, developed using the American Hospital Association (AHA) universe.
Results: White, high-income patients, and those at urban teaching hospitals received the greatest proportion of combined endoscopic procedures. The charges associated with combined endoscopies are not notably greater than for gastrointestinal (GI) or airway only endoscopies. However, combined procedures comprise a smaller share of national aggregate cost.
Conclusions: National utilization trends highlight racial and socioeconomic disparities as well as differences in access based on hospital characteristics. Without clear insurance payor trends, most efforts to offer combined procedures comes from clinician decision-making rather than system-based efforts. By understanding these trends and where gaps exist, improved systems can be developed to benefit all patients.
Justin K. Zhang, BS; Georgio Alexopoulos, MD, MS; Philippe Mercier, MD, PhD
Background: Glioblastoma multiforme (GBM) are the most common primary CNS tumors. Existing literature regarding the effect of demographics on patient survival remains inconclusive.
Methods: Adult patients with intracranial GBMs from the Surveillance Epidemiology and End Results (SEER)-9 population database spanning 1975–2018 were included. A time series analysis with autoregressive moving averages was performed to forecast the annual GBM incidence in the US population up to 2060. After testing for the proportional hazards assumption, a survival analysis based on parametric models was performed to characterize GBM-specific time to death.
Results: We identified 32,746 patients with GBM. Our time series analysis demonstrated that by the year 2060, over 1,800 cases will be reported annually in the SEER, with the year 2005 serving as the cutoff associated with an increased survival probability. Accelerated Failure Time (AFT) lognormal regression was the best model to describe the survival pattern, identifying age >30 years old as a poor prognostic and patients >70 years old as having the worst survival. Annual income >USD 75,000 and supratentorial tumors had good prognostics, while surgical intervention provided the strongest survival benefit.
Conclusions: Our results demonstrate that annual GBM incidence rates will continue to increase by almost 50% in the upcoming 30 years. AFT lognormal distribution best describes the SEER GBM-specific survival pattern and should be utilized for survival analyses in population-based studies. In our analysis, surgical intervention provides the strongest survival benefit, while age >70 years old is the worst prognostic. Gender, race, and county were not meaningful prognostics.
Justin K. Zhang, BS; Georgio Alexopoulos, MD, MS; Philippe Mercier, MD, PhD
Background: The primary site and histology of systemic malignancy are known predictors of progression to brain metastases (BM). We investigated the combinational interactions of ICD-O primary topography and morphology types on the survival of BM after controlling for relevant clinical and demographic covariates.
Methods: Adult patients with BM at diagnosis of an invasive malignancy were identified from the National Cancer Database (NCDB) spanning 2010-2018. A survival analysis of the topography and histology-specific time-to-death was performed. Multivariate Cox regression revealed violations of the proportional hazard assumption for multiple covariates. Therefore, parametric models using a log-logistic distribution were built to describe the population survival pattern.
Results: Of 14,279,749 cancer patients screened, 180,150 were included. The primary topography “prostate” and morphology “choriocarcinoma” provided the strongest survival benefit among ICD-O types, with BM from the prostate demonstrating a 14-month median overall increase in survival probability. Favorable prognostics were BM from the breast, bone/joints, and testis. Favorable morphologies included carcinoid tumor, mature B-cell lymphoma, and papillary adenocarcinoma. Poor prognostics were BM from gastrointestinal organs (liver, biliary tree, pancreas, and gallbladder) and gynecologic malignancies. Morphologies of spindle cell carcinoma, hemangiosarcoma, undifferentiated carcinoma, Ewing sarcoma, pseudosarcomatous carcinoma, renal cell carcinoma/sarcomatoid, signet ring cell carcinoma, spindle cell sarcoma, and squamous cell carcinoma/spindle cell were associated with poor survival.
Conclusions: We report the largest cohort providing an unbiased estimate of the effect of adjusted ICD-O topography and morphology on survival following BM. These results may help guide clinicians in management strategies for patients with BM secondary to systemic malignancy.
Dixie Meyer, PhD; Tim Chrusciel, MPH; Joanne Salas, MPH; Jeffrey Scherrer, PhD
Background: Psychiatric conditions are linked to white blood cell counts (WBC) demonstrating routine blood work could potentially be used as a diagnostic measure for mental health concerns.
Methods: After excluding patients with inflammatory conditions and cancer, we used a random sample of nationally distributed adult medical EHR data (N=652,199) from 2014-2018 to examine WBC (if >1, highest count used) and depression, anxiety, and SUDs after controlling for demographics and health conditions.
Results: After controlling for confounders, regression analysis (p <.001) demonstrated depression and SUDs were associated with higher WBC. A second regression analysis (p <.001), controlling for confounders, showed cumulating mental health diagnoses (1-3) were also linked to higher WBC.
Conclusion: Despite significance, depression may only be nominally related to WBC. SUDs and the cumulation of mental health diagnoses may worsen inflammation. While WBC are not sensitive enough to diagnosis depression or anxiety, WBC in the higher normal range could signal to practitioners a psychiatric evaluation may be warranted. This study demonstrates the utility of medical record data for studies of inflammation in mental illness.