Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population.

BACKGROUND: Multimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized. OBJECTIVES: To examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer. METHODS: We conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors. RESULTS: Of the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001. CONCLUSIONS: Multimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life.

Significant mortality, morbidity and resource utilization associated with advanced heart failure in congenital heart disease in children and young adults.

BACKGROUND: Children with congenital heart disease (CHD) are at risk for advanced heart failure (AHF). We sought to define the mortality and resource utilization in CHD-related AHF in children and young adults. METHODS: All hospitalizations in the Pediatric Health Information System database involving patients ≤21 years old with a CHD diagnosis and heart failure requiring at least 7 days of continuous inotropic support between 2004 and 2015 were included. Hospitalizations including CHD surgery were excluded. RESULTS: Of 465,482 CHD hospitalizations, AHF was present in 2,712 (0.6%) [58% infant, 55% male, 30% single ventricle]. AHF therapies frequently used included extracorporeal membrane oxygenation (ECMO) (15%) and cardiac transplant (16%). Ventricular assist device (VAD) support was rare (3%), although VAD use significantly increased from 2004 to 2015 (P < .0010). Hospital mortality in CHD with AHF was 26%, with higher mortality associated with single ventricle heart disease (OR 1.64, 95% CI 1.23-2.19; P = .0009), infancy (OR 1.71, 95% CI 1.17-2.5; P = .0057), non-white race (OR 1.28, 95% CI 1.04-1.59; p=0.0234), and chronic complex comorbidities (OR 1.76, 95% CI 1.34-2.30; P < .0001). Over the 11-year study period, despite the significant increase in CHD-related AHF hospitalizations (P < .0001), hospital mortality improved (P = .0011). Median hospital costs were $252,000, a 6-fold increase above those without AHF, and was primarily driven by hospital length of stay (P < .0001). CONCLUSION: AHF in children with CHD in uncommon but increasing and is associated with significant morbidity, mortality and resource utilization. Approximately 1 in 5 children do not survive to hospital discharge. Many risk factors for mortality may not be modifiable, and further study is needed to identify modifiable risk factors and improve care for this complex population.

Simple prediction scores predict good and devastating outcomes after stroke more accurately than physicians.

Introduction: physicians are often asked to prognosticate soon after a patient presents with stroke. This study aimed to compare two outcome prediction scores (Five Simple Variables [FSV] score and the PLAN [Preadmission comorbidities, Level of consciousness, Age, and focal Neurologic deficit]) with informal prediction by physicians. Methods: demographic and clinical variables were prospectively collected from consecutive patients hospitalised with acute ischaemic or haemorrhagic stroke (2012-13). In-person or telephone follow-up at 6 months established vital and functional status (modified Rankin score [mRS]). Area under the receiver operating curves (AUC) was used to establish prediction score performance. Results: five hundred and seventy-five patients were included; 46% female, median age 76 years, 88% ischaemic stroke. Six months after stroke, 47% of patients had a good outcome (alive and independent, mRS 0-2) and 26% a devastating outcome (dead or severely dependent, mRS 5-6). The FSV and PLAN scores were superior to physician prediction (AUCs of 0.823-0.863 versus 0.773-0.805, P < 0.0001) for good and devastating outcomes. The FSV score was superior to the PLAN score for predicting good outcomes and vice versa for devastating outcomes (P < 0.001). Outcome prediction was more accurate for those with later presentations (>24 hours from onset). Conclusion: the FSV and PLAN scores are validated in this population for outcome prediction after both ischaemic and haemorrhagic stroke. The FSV score is the least complex of all developed scores and can assist outcome prediction by physicians.

Epidemiology of Polypharmacy and Potential Drug-Drug Interactions Among Pediatric Patients in ICUs of U.S. Children's Hospitals.

OBJECTIVES: Polypharmacy is common in hospitalized children in the United States and has been identified as a major risk factor for exposure to potential drug-drug interactions. Little is known about the characteristics and prevalence of exposure of pediatric patients to polypharmacy and potential drug-drug interactions in PICUs. DESIGN: Retrospective cohort study using the Pediatric Health Information System database. SETTING: Forty-two freestanding children's hospitals throughout the United States. PATIENTS: A total of 54,549 patients less than 18 years old cared for in PICUs in 2011. Patients in neonatal ICUs were not included. MEASUREMENTS AND MAIN RESULTS: PICU patients were on average exposed to 10 distinct drugs each hospital day and to 20 drugs cumulatively during their hospitalization. Seventy-five percent of patients were exposed to greater than or equal to one potential drug-drug interaction regardless of severity level, 6% to greater than or equal to one contraindicated potential drug-drug interaction, 69% to greater than or equal to one major potential drug-drug interaction, 57% to greater than or equal to one moderate potential drug-drug interaction, 19% to greater than or equal to one minor potential drug-drug interaction. Potential drug-drug interaction exposures were significantly associated with specific diagnoses (p < 0.001), presence of complex chronic conditions (p < 0.001), increasing number of total distinct drugs used (p < 0.001), increasing length of stay in PICU (p < 0.001), and white race (p < 0.001). CONCLUSIONS: Many PICU patients are exposed to substantial polypharmacy and potential drug-drug interactions. Future research should identify the risk of adverse drug events following specific potential drug-drug interaction exposures, especially the risk of adverse drug events due to multiple potential drug-drug interaction exposures, and determine the probability and magnitude of the actual harm (if any) for each specific potential drug-drug interaction, especially for multiple potential drug-drug interaction exposures.

Pediatric exposure to opioid and sedation medications during terminal hospitalizations in the United States, 2007-2011.

OBJECTIVE: To describe the use of opioids and sedatives to pediatric patients dying in the hospital in the 2 weeks preceding death. STUDY DESIGN: We conducted a retrospective study on opioid and sedation medication exposure among children who die in hospitals in the US by using large administrative data sources. We described patterns of exposure to these medications for deceased inpatients (<21 years of age) between 2007 and 2011 (n = 37,459) and factors associated with the exposure. Multivariable logistic regression models were used to estimate the ORs. RESULTS: Overall, 74% patients were exposed to opioids or sedatives in the 14 days before death. Among patients with 6 or more hospital days before death, the daily exposure rate ranged from 73% (the sixth day before death) to 89% (the day of death). The most commonly used medications were fentanyl (52%), midazolam (44%), and morphine (40%). Older age (ORs 1.6-3.7), black race (ORs 0.8), longer hospital stay (ORs 6.6-9.3), receiving medical interventions (including mechanical ventilation, surgery, and stay in the intensive care unit, ORs 1.7-2.6), having comorbidities (ORs 1.7-2.4), and being hospitalized in children's hospitals (ORs 4.0-4.5) were associated with exposure of opioid and sedation medication on adjusted analysis. CONCLUSION: Although most pediatric patients terminally hospitalized are exposed to opioid and sedation medication, some patients do not receive such medications before death. Given that patient and hospital characteristics were associated with opioid/sedative exposure, these findings suggest areas of potential quality improvement and further research.

Gastric Acid Suppressant Prophylaxis in Pediatric Intensive Care: Current Practice as Reflected in a Large Administrative Database.

OBJECTIVES: Stress-related gastrointestinal bleeding may occur in PICU patients. Raising gastric pH with acid suppressant medications is the accepted treatment. We describe the use of histamine 2 receptor blockers and proton pump inhibitors and associated factors among a national sample of PICU patients. DESIGN: Retrospective cohort analysis using Pediatric Health Information System clinically detailed administrative database. SETTING: Forty-two children's hospitals throughout the United States. PATIENTS: All hospitalizations for all patients 20 years old or younger, admitted directly to a PICU, from January 1, 2007, through December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was treatment with a histamine 2 receptor blocker, proton pump inhibitor, or both on the first day of PICU admission. Demographics, principal and additional diagnoses, and procedure codes were assessed. For each hospitalization, principal diagnosis, coagulation disorder, head trauma, spinal trauma, severe burns, sepsis, gastrointestinal hemorrhage, mechanical ventilation, blood product transfusion, and 10 complex chronic conditions were identified. The frequency of principal diagnoses was determined to identify the most prevalent PICU diseases. Acid suppressant use was categorized as high or low. Three hundred and thirty-six thousand ten inpatient hospitalizations were sampled. Histamine 2 receptor blocker or proton pump inhibitor was used in 60.0%, with histamine 2 receptor blocker alone in 70.4%, proton pump inhibitor alone in 17.8%, and both agents in 11.8%. Use increased over the sample years 2007 through 2011. Gastrointestinal bleeding occurred in 1.32% of hospitalizations with transfusion needed in 0.1%. Among most prevalent diagnoses, histamine 2 receptor blocker and proton pump inhibitor use ranged from 33% to 87%. Sepsis, coagulopathy, and mechanical ventilation identified higher use. Use of histamine 2 receptor blocker or proton pump inhibitor among hospitals varied considerably ranging from 28% to 87%. CONCLUSIONS: Histamine 2 receptor blocker and proton pump inhibitor are prescribed in most PICU patients, but significant variation exists across health conditions and hospitals. Institutional preferences likely influence variation. Gastrointestinal hemorrhage is infrequent in the current era. Study data limitations prevent examination of associations between medication use and patient outcomes.

Predictors of antiemetic alteration in pediatric acute myeloid leukemia.

BACKGROUND: Better knowledge of patient and cancer treatment factors associated with nausea/vomiting (NV) in pediatric oncology patients could enhance prophylaxis. We aimed to describe such factors in children receiving treatment for acute myeloid leukemia (AML). METHODS: Retrospective longitudinal cohort study of 1,668 hospitalized children undergoing treatment for AML from the Pediatric Health Information System database (39 hospitals, 1999-2010). Antiemetic alteration, which included switch (a change in prescribed 5-HT3 receptor antagonists) and rescue (receipt of an adjunct antiemetic), were first validated and then used as surrogates of problematic NV. Logistic and negative binomial regression modeling were used to test whether patient characteristics were associated with problematic NV. RESULTS: Increasing age is associated with greater odds of experiencing antiemetic switch and higher relative rate of antiemetic rescue. Within a treatment cycle, each consecutive inpatient chemotherapy day decreased the likelihood of requiring antiemetic alteration. Each consecutive inpatient-day post-chemotherapy was associated with decreased need for switch, but increased need for rescue. Subsequent cycles of AML therapy were associated with lower odds of antiemetic switch on both chemotherapy and non-chemotherapy days, a lower rate of antiemetic rescue on chemotherapy days, and an increased rate of rescue on non-chemotherapy days. CONCLUSION: In pediatric patients with AML, increasing age is strongly associated with greater antiemetic alteration. Antiemetic alteration occurs early in treatment overall, and early within each admission. While additional cycles of therapy are associated with less alteration overall, there is persistent rescue in the days after chemotherapy, suggesting additional etiologies of NV in pediatric cancer patients.

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation.

BACKGROUND: The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. RESULTS: The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. CONCLUSIONS: The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

Multimorbidity in Atherosclerotic Cardiovascular Disease and Its Associations With Adverse Cardiovascular Events and Healthcare Costs: A Real-World Evidence Study.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality and disability in the United States and worldwide. Objective: To assess the multimorbidity burden and its associations with adverse cardiovascular events (ACE) and healthcare costs among patients with ASCVD. Methods: This is a retrospective observational cohort study using Aetna claims database. Patients with ASCVD were identified during the study period (1/1/2018-10/31/2021). The earliest ASCVD diagnosis date was identified as the index date. Qualified patients were ≥18 years of age and had ≥12 months of health plan enrollment before and after the index date. Comorbid conditions were assessed using all data available within 12 months prior to and including the index date. Association rule mining was applied to identify comorbid condition combinations. ACEs and healthcare costs were assessed using all data within 12 months after the index date. Multivariable generalized linear models were performed to examine the associations between multimorbidity and ACEs and healthcare costs. Results: Of 223 923 patients with ASCVD (mean [SD] age, 73.6 [10.7] years; 42.2% female), 98.5% had ≥2, and 80.2% had ≥5 comorbid conditions. The most common comorbid condition dyad was hypertension-hyperlipidemia (78.7%). The most common triad was hypertension-hyperlipidemia-pain disorders (61.1%). The most common quartet was hypertension-hyperlipidemia-pain disorders-diabetes (30.2%). The most common quintet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity (16%). The most common sextet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity-osteoarthritis (7.6%). The mean [SD] number of comorbid conditions was 7.1 [3.2]. The multimorbidity burden tended to increase in older age groups and was comparatively higher in females and in those with higher social vulnerability. The increased number of comorbid conditions was significantly associated with increased ACEs and increased healthcare costs. Discussion: Extremely prevalent multimorbidity should be considered in the context of clinical decision-making to optimize secondary prevention of ASCVD. Conclusions: Multimorbidity was extremely prevalent among patients with ASCVD. Multimorbidity patterns varied considerably across ASCVD patients and by age, gender, and social vulnerability status. Multimorbidity was strongly associated with ACEs and healthcare costs.

Pragmatic estimates of the proportion of pediatric inpatients exposed to specific medications in the USA.

PURPOSE: To provide pragmatic national estimates of the proportion of hospitalized pediatric patients exposed to specific drugs in the USA. METHODS: We used Premier Perspective Database and the Pediatric Health Information System data including specific drug exposures of 1.15 million inpatients <18 years old in 411 general and 52 children's hospitals throughout the USA in 2006, extrapolating this information into the probability-based Kids' Inpatient Database, which has demographic and clinical characteristics but no drug exposure data. We used a multivariable stratified resampling (MSR) technique to estimate the proportion of drug exposure for the 700 most commonly used drugs and performed additional stability and sensitivity analyses for 19 drugs. RESULTS: The estimated proportion of pediatric inpatients exposed to specific drugs in 2006 ranged from high levels such as that of acetaminophen (17.36; 95%CI: 17.32, 17.41) to rare exposures such as bosentan (0.0018; 95%CI: 0.0013, 0.0023). Additional analyses for 19 drugs revealed that the MSR estimates were close to estimates generated by multivariable multiple imputation, with a maximum absolute difference of 0.03 for acetaminophen (17.36 vs. 17.33) and famotidine (1.90 vs. 1.93), and that even with 50% of the hospitals removed at random, the proportion estimates did not vary by more than 2.5-fold at the upper 97.5 percentile. CONCLUSIONS: These pragmatic national estimates of the proportion of pediatric inpatient drug exposures, generated using an MSR technique, provide a context for interpretation of drug-related adverse event reports and prioritization of pediatric pharmacology research.

Patterns of medication exposures in hospitalized pediatric patients with acute renal failure requiring intermittent or continuous hemodialysis.

OBJECTIVES: Care for the pediatric patient with acute renal failure who requires hemodialysis (including continuous renal replacement therapy) is made more complex, as this intervention may significantly affect drug clearance, potentially altering, to a degree that is largely unknown, the effectiveness and safety of the multiple medications used to manage this complex patient population. This study aims to describe patterns of drug utilization among a large cohort of pediatric patients requiring hemodialysis and to document the easily accessible existing data available for dosing guidance of frequently prescribed medications. STUDY DESIGN: Retrospective cohort using the Pediatric Health Information System database. SETTING: Forty freestanding children's hospitals throughout the United States. PATIENTS: Two thousand seven hundred thirty-eight pediatric patients with acute renal failure treated with hemodialysis from 2007 to 2011. INTERVENTION: A retrospective review of all patients requiring hemodialysis from 2007 to 2011 was conduction using the Pediatric Health Information System Database. MAIN RESULTS: Over 6% of pediatric patients with acute renal failure treated with hemodialysis were exposed to hemodialysis for over 2 weeks. Cumulative exposure to distinct drugs increased substantially with more prolonged courses of hemodialysis. Of the 50 most frequently prescribed medications in the cohort with acute renal failure treated with hemodialysis, 10% have readily available and easily accessible information to guide dosing adjustments with the use of hemodialysis. Furthermore, only 18% of these medications have clear recommendations for dosing in pediatric patients of all age groups with renal failure. CONCLUSIONS: Pediatric patients with acute renal failure managed with hemodialysis are exposed to a broad variety of medications, with a high prevalence of polypharmacy. There is a trend for longer courses of hemodialysis in these patients, which leads to an increase in cumulative drug exposure, complexity of drug interactions, and potential toxicity. For the vast majority of medications that are being used to treat this complex patient population, pediatric dosing guidance is not easily accessible. These findings underscore the need for targeted pharmacologic studies of medications used in the pediatric population managed with hemodialysis.

Comparative Effectiveness of Transcutaneous Afferent Patterned Stimulation Therapy for Essential Tremor: A Randomized Pragmatic Clinical Trial.

Background: Transcutaneous afferent patterned stimulation (TAPS) is a wrist-worn, non-invasive therapy delivering calibrated stimulation to the median and radial nerves. Previous randomized controlled studies have demonstrated the efficacy and safety of TAPS therapy in some patients with essential tremor (ET), but evidence supporting therapeutic benefits of TAPS versus standard of care (SOC) is lacking. This randomized prospective study evaluated the clinical benefit of adding TAPS treatment to SOC versus SOC alone. Methods: This randomized pragmatic trial recruited patients from a large health plan's Commercially Insured and Medicare Advantage population. All 310 patients received a TAPS device and were randomized 1:1 to either one month adding TAPS therapy to usual care (TX arm) or usual care with tremor assessment only (SOC arm). The pre-specified endpoints were changes in tremor power measured by motion sensors on the device (primary) and improvement in Bain & Findley Activities of Daily Living (BF-ADL) upper limb scores (secondary) between TX and SOC in all patients who completed the one-month study. Results: 276 patients completed the one-month study (N = 133 TX, N = 143 SOC). The study met the primary and secondary endpoints, with significantly reduced tremor power in TX compared with SOC (0.017 (0.003) versus 0.08 (0.014) (m/s2)2; geometric mean (SE); p < 0.0001) and greater improvement in the BF-ADL score in TX than SOC (1.6 (0.43) vs 0.2 (0.37) points; mean (SE); p < 0.05). No serious device-related adverse events were reported. Discussion: This trial demonstrates that adding TAPS treatment to SOC significantly improves tremor power and BF-ADLs in patients with ET compared to SOC alone over one month of home use. Highlights: This study found that adding TAPS treatment to SOC significantly improves tremor power and BF-ADL scores in patients with ET compared to SOC alone over one month of home use. This real-world evidence study suggests that non-invasive TAPS therapy is a safe and valuable treatment option for patients with ET.

Anxiety, Depression, and Stress Reaction/Adjustment Disorders and Their Associations with Healthcare Resource Utilization and Costs Among Newly Diagnosed Patients With Breast Cancer.

Background: Breast cancer is the most common cancer among women in the United States. Newly diagnosed patients with breast cancer often experience anxiety, depression, and stress. However, the impact of psychological distress on healthcare resource utilization (HCRU) and costs has not been adequately assessed. Objectives: To evaluate the incidence and prevalence of anxiety, depression, and stress reaction/adjustment disorder among patients newly diagnosed with breast cancer, to examine HCRU and costs, and to assess the association of these psychiatric disorders with costs. Methods: This retrospective observational cohort study was conducted using a large US administrative claims database with an index date of newly diagnosed breast cancer. Demographics and comorbidities (including anxiety, depression, and stress reaction/adjustment disorder) were assessed using data collected 12 months before and after the index date. HCRU and costs were assessed using data collected 12 months after the index date. Generalized linear regressions were performed to examine the association between healthcare costs and anxiety, depression, and stress reaction/adjustment disorder. Results: Of 6392 patients with newly diagnosed breast cancer, 38.2% were diagnosed with psychiatric disorders including anxiety (27.7%), depression (21.9%), or stress reaction/adjustment disorder (6%). The incidence of these psychiatric disorders was 15% and the prevalence was 23.2%. Patients with anxiety, depression, or stress reaction/adjustment disorder had higher rates of several types of HCRU (P < .0001) and higher total all-cause costs compared with patients without these psychiatric disorders (P < .0001). Patients with incident anxiety, depression, or stress reaction/adjustment disorder incurred higher all-cause costs in the first year following breast cancer diagnosis than those with prevalent anxiety, depression, or stress reaction/adjustment disorder (P < .0003), or those without these psychiatric disorders (P < .0001). Discussion: Of patients with anxiety, depression, or stress reaction/adjustment disorder, those with incident psychiatric disorders had higher healthcare costs, suggesting that new-onset psychological distress may contribute to higher costs incurred by the payer. Timely treatment of psychiatric disorders in this population may improve clinical outcomes and reduce HCRU and costs. Conclusions: Anxiety, depression, and stress reaction/adjustment disorder were common among patients newly diagnosed with breast cancer and were associated with increased healthcare costs in the first year following breast cancer diagnosis.

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

OBJECTIVE: To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). METHODS: We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. RESULTS: The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CONCLUSIONS: CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

Developing predictive models of excellent and devastating outcome after stroke.

BACKGROUND: models to predict functional status post-stroke have utility in balancing groups in randomised trials, for outcome comparison between stroke centres and may assist in outcome prediction. This study aimed to develop models of both excellent [modified Rankin score (mRS) 0-1] and devastating outcomes (mRS of 5-6). METHODS: patients admitted with ischaemic or haemorrhagic stroke in 2001-02 to the Halifax Infirmary, Canada, were enrolled. Sixteen clinical variables from the first neurological assessment and six radiological variables from the acute CT scan were used to the model outcome at 6 months. RESULTS: five hundred and thirty-eight stroke patients were enrolled. Thirty per cent had an excellent outcome and 30% had a devastating outcome. Three models of the excellent outcome were developed [area under the receiver operator curve (AUC) 0.866-882] including the variables age, pre-stroke functional status, stroke severity, ability to lift both arms, walk independently, normal verbal Glasgow Coma Scale and leukoaraiosis. Predictive models of the devastating outcome (AUC of 0.859-0.874) included additional variables living alone pre-stroke and total anterior circulation stroke. The simplest models of both outcomes were externally validated (AUC of 0.856-0.885). CONCLUSION: this study demonstrates new externally validated predictive models of both excellent and devastating outcomes. Leukoaraiosis was the only independent radiological predictor of both outcomes. Living alone pre-stroke predicted devastating outcome post-stroke.

Patterns of Comorbidity and Multimorbidity Among Patients With Multiple Sclerosis in a Large US Commercially Insured and Medicare Advantage Population.

Background: Comorbidities are common in patients with multiple sclerosis (MS), thus increasing the complexity of disease management and economic burden and worsening their prognosis and quality of life. Real-world evidence comparing comorbidities and multimorbidity patterns of commercially insured vs Medicare enrollees with MS is lacking. Objective: To evaluate the patterns of comorbidity and multimorbidity among patients with MS in a US commercially insured and Medicare Advantage population. Methods: This retrospective observational cohort study was conducted using Aetna health claims data from January 1, 2015, to October 31, 2019. Eligibility criteria were (1) at least 3 MS-related inpatient/outpatient (ICD-10-CM: G35), or disease-modifying therapy claims within 1 year (date of first claim = index date); (2) Aetna commercial health plan or Medicare Advantage medical and pharmacy benefits at least 12 months pre-/post-index; and (3) age 18 and older. Commercially insured patients, Medicare Advantage patients younger than 65 years of age, and Medicare Advantage patients 65 years and older were compared. Results: Among 5000 patients (mean [SD] age, 52.6 [12.9]; 75.2% female), 53% had commercial insurance and 47% had Medicare Advantage (59.2% disabled age <65). Medicare Advantage patients were older (age <65: 53.3 [7.9]; age ≥65: 70.8 [5.2]) vs commercial (age, 45.7 [10.2]), had greater comorbidity burden (Charlson Comorbidity Index; age <65: 1.17 [1.64], age ≥65: 1.65 [1.95]) vs commercial (0.53 [1.02]) (all P < .0001). Symptoms specific to MS (ie, malaise, fatigue, depression, spasms, fibromyalgia, convulsions) were more common among patients younger than 65 (all P < .0001). Age-related and other comorbidities (ie, hypertension, hyperlipidemia, dyspepsia, osteoarthritis, osteoporosis, glaucoma, diabetes, cerebrovascular, cancer) were more common among patients 65 years and older Medicare Advantage (all P < .0001). Multiple comorbidities were highly prevalent (median, 4 comorbidities), particularly among Medicare Advantage patients younger than 65 (median, 6) and Medicare Advantage patients 65 and older (median, 7). Conclusions: Comorbidities and multimorbidity patterns differed between patients with MS with commercial insurance and patients with Medicare Advantage. Multimorbidity was highly prevalent among patients with MS and should be considered in the context of clinical decision making to ensure comprehensive MS management and improve outcomes.

Multiple Comorbidities, Psychiatric Disorders, Healthcare Resource Utilization and Costs Among Adults with Essential Tremor: A Retrospective Observational Study in a Large US Commercially Insured and Medicare Advantage Population.

Background: Essential tremor (ET), the most common movement disorder, often impairs patients' ability to perform activities of daily living, mental health, and quality of life. Objectives: To assess comorbidities, psychiatric disorders, healthcare resource utilization (HCRU), and costs among patients with ET compared with patients without ET. Methods: This retrospective observational study was conducted using a large US administrative claims database. Patients with ET were identified during the study period (1/1/2017-12/31/2019). The earliest claim date with ET diagnosis was identified as the index date. An index date was assigned randomly for each non-ET patient. Patients had to be at least 22 years old and be enrolled in the health plan for at least 6 months before and at least 12 months after the index date. Patients with and those without ET were matched 1:1 on age, gender, payer type, and first 3 digits of their ZIP code. Comorbidities were assessed using data within 6 months prior to the index date. Psychiatric disorders, HCRU, and costs were examined using data within 12 months after the index date. Results: The mean (SD) age of ET patients (n = 5286) was 70.8 (11.8) years, 49.1% were female, and 82.9% were Medicare Advantage members. In the 12 months following the index date, 26.0% of patients had no insurance claims for ET-related pharmacotherapy or invasive therapies. Patients with ET had a higher number of comorbidities than non-ET patients (5.3 [3.2] vs 4.0 [3.3]); a higher prevalence of psychiatric disorders (depression: 25.6% vs 15.3%; adjusted odds ratio (AOR) [95% CI], 1.56 [1.41-1.73]; anxiety: 27.7% vs 15.5%, AOR: 1.78 [1.61-1.96]); and higher total healthcare costs: $17 560 [$39 972] vs $13 237 [$27 098], adjusted cost ratio [95% CI]: 1.11 [1.06-1.16]; all P<.0001. Discussion: Highly prevalent multiple comorbidities and psychiatric disorders should be considered in the context of clinical decision-making to optimize ET management. Conclusions: This study represents the largest observational study to report ET disease and economic burdens in a real-world setting. The data demonstrate increased comorbidity, mental health, and healthcare cost burdens among ET patients compared with matched non-ET patients. These findings underscore the need for innovative care for this complex population.

Multiple comorbid conditions and healthcare resource utilization among adult patients with hyperkalemia: A retrospective observational cohort study using association rule mining.

Objectives: To estimate the prevalence of specific comorbid conditions (CCs) and multiple comorbid conditions (MCCs) among adult patients with hyperkalemia and examine the associations between MCCs and healthcare resource utilization (HRU) and costs. Methods: This retrospective observational cohort study was conducted using a large administrative claims database. We identified patients with hyperkalemia (ICD-10-CM: E87.5; or serum potassium >5.0 mEq/L; or NDC codes for either patiromer or sodium polystyrene sulfonate) during the study period (1/1/2016-6/30/2019). The earliest service/claim date with evidence of hyperkalemia was identified as index date. Qualified patients had ≥12 months of enrolment before and after index date, ≥18 years of age. Comorbid conditions were assessed using all data within 12 months prior to the index date. Healthcare resource utilization and costs were estimated using all data within 12 months after the index date. Association rule mining was applied to identify MCCs. Generalized linear models were used to examine the associations between MCCs and HRU and costs. Results: Of 22,154 patients with hyperkalemia, 94% had ≥3 CCs. The most common individual CCs were chronic kidney disease (CKD, 85%), hypertension (HTN, 83%), hyperlipidemia (HLD, 81%), and diabetes mellitus (DM, 47%). The most common dyad combination of CCs was CKD+HTN (71%). The most common triad combination was CKD+HTN+HLD (62%). The most common quartet combination was CKD+HTN+HLD+DM (36%). The increased number of CCs were significantly associated with increased ED visits, length of hospital stays, and total healthcare costs (all p-value < 0.0001). Conclusions: MCCs are very prevalent among patients with hyperkalemia and are strongly associated with HRU and costs.

Incidence of life-threatening events in children with Wolff-Parkinson-White syndrome: Analysis of a large claims database.

BACKGROUND: Previous estimates of life-threatening event (LTE) risk in Wolff-Parkinson-White (WPW) syndrome are limited by selection bias inherent to tertiary care referral-based cohorts. OBJECTIVE: This analysis sought to measure LTE incidence in children with WPW syndrome in a large contemporary representative population. METHODS: A retrospective cohort study was conducted using claims data from the IBM MarketScan Research Databases, evaluating subjects with WPW syndrome (age 1-18 years) from any encounter between January 1, 2013, and December 31, 2018. Subjects with congenital heart disease and cardiomyopathy were excluded. The primary outcome was diagnosis of ventricular fibrillation (VF); a composite outcome, LTE, was defined as occurrence of VF and/or cardiac arrest. VF and LTE rates were compared to matched representative controls without WPW syndrome (3:1 ratio). RESULTS: The prevalence of WPW syndrome was 0.03% (8733/26,684,581) over a median follow-up of 1.6 years (interquartile range 0.7-2.9 years). Excluding congenital heart disease/cardiomyopathy, 6946 subjects were analyzed. An LTE occurred in 49 subjects (0.7%), including VF in 20 (0.3%). The incidence of VF was 0.8 events per 1000 person-years, and the incidence of LTE was 1.9 events per 1000 person-years. There were no occurrences of VF in controls; the rate of LTE was 70 times higher in subjects with WPW syndrome (0.7%; 95% confidence interval 0.5%-0.9%) than in controls (0.01%; 95% confidence interval 0%-0.02%). CONCLUSION: The use of a large claims data set allowed for an evaluation of VF and LTE risk in an unselected pediatric population with WPW syndrome. The observed range of 0.8-1.9 events per 1000 person-years is consistent with prior reports from selected populations. A comparison of event rates to matched controls confirms and quantifies the significant elevation in VF and LTE risk in pediatric WPW syndrome.

A Predictive Model for Progression of Chronic Kidney Disease to Kidney Failure Using a Large Administrative Claims Database.

BACKGROUND: To create an appropriate chronic kidney disease (CKD) management program, we developed a predictive model to identify patients in a large administrative claims database with CKD stages 3 or 4 who were at high risk for progression to kidney failure. METHODS: The predictive model was developed and validated utilizing a subset of patients with CKD stages 3 or 4 derived from a large Aetna claims database. The study spanned 36 months, comprised of a 12-month (2015) baseline period and a 24-month (2016-2017) prediction period. All patients were ≥18 years of age and continuously enrolled for 36 months. Multivariate logistic regression was used to develop models. Prediction model performance measures included area under the receiver operating characteristic curve (AUROC), calibration, and gain and lift charts. RESULTS: Of the 74,114 patients identified as having CKD stages 3 or 4 during the baseline period, 2476 (3.3%) had incident kidney failure during the prediction period. The predictive model included the effect of numerous variables, including age, gender, CKD stage, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, peripheral vascular disease, anemia, hyperkalemia (HK), prospective episode risk group score, and poor adherence to renin-angiotensin-aldosterone system inhibitors. The strongest predictors of progression to kidney failure were CKD stage (4 vs 3), HTN, DM, and HK. The ROC and calibration analyses in the validation sample demonstrated good predictive accuracy (AUROC=0.844) and calibration. The top two prediction deciles identified 70.8% of patients who progressed to kidney failure during the prediction period. CONCLUSION: This novel predictive model had good accuracy for identifying, from a large national database, patients with CKD who were at high risk of progressing to kidney failure within 2 years. Early identification using this model could potentially lead to improved health outcomes and reduced healthcare expenditures in this at-risk population.