Impact of Caring for Individuals With Heart Failure in the United States: A Systematic Literature Review.

BACKGROUND: Given the functional impairments and complex care routines associated with heart failure (HF), patients often rely on the support of informal caregivers. Although the importance of caregivers' roles is widely recognized, the intensity and time required for care duties may negatively impact caregiver health and well-being, potentially precipitating their own need for care. OBJECTIVE: The aim of this study was to synthesize estimates of economic, clinical, burden, and health-related quality-of-life impact among caregivers of those with HF in the United States. METHODS: A systematic review was conducted to identify studies reporting estimates of caregiver impact. Abstract and full-text review as well as data extraction were performed according to established guidelines. Patient and caregiver characteristics were summarized, as well as estimates of impact of caring for those with HF. RESULTS: From 3680 abstracts, 44 studies reporting caregiver burden estimates were included. Mean caregiver age ranged from 41.4 to 71.4 years; caregivers were primarily female (range, 49%-100%) and the patient's spouse/partner (21%-100%). Time spent caregiving (6 studies) ranged from 2 to 52 h/wk, and depression was identified in up to 40% of caregivers (9 studies). Numerous instruments were used to measure burden, which consistently documented the high impact of caregiving. CONCLUSIONS: This review demonstrates the multifaceted impact of caregiving for patients with HF. Despite limited data, notable findings included the considerable burden to caregivers, variability in time spent caregiving, and frequent experience of depression among caregivers, possibly leading to increased healthcare resource use. Future research is needed to better characterize the caregiving impact in HF, including evaluating the drivers of burden.

Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 1999-2020.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date. Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time. Design, Setting, and Participants: To establish prevalence of CRM conditions, nationally representative, serial cross-sectional data included in the January 2015 through March 2020 National Health and Nutrition Examination Survey (NHANES) were evaluated in this cohort study. To assess temporal trends in CRM overlap, NHANES data between 1999-2002 and 2015-2020 were compared. Data on 11 607 nonpregnant US adults (≥20 years) were included. Data analysis occurred between November 10, 2020, and November 23, 2022. Main Outcomes and Measures: Proportion of participants with CRM conditions, overall and stratified by age, defined as cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes (T2D), or all 3. Results: From 2015 through March 2020, of 11 607 US adults included in the analysis (mean [SE] age, 48.5 [0.4] years; 51.0% women), 26.3% had at least 1 CRM condition, 8.0% had at least 2 CRM conditions, and 1.5% had 3 CRM conditions. Overall, CKD plus T2D was the most common CRM dyad (3.2%), followed by CVD plus T2D (1.7%) and CVD plus CKD (1.6%). Participants with higher CRM comorbidity burden were more likely to be older and male. Among participants aged 65 years or older, 33.6% had 1 CRM condition, 17.1% had 2 CRM conditions, and 5.0% had 3 CRM conditions. Within this subset, CKD plus T2D (7.3%) was most common, followed by CVD plus CKD (6.0%) and CVD plus T2D (3.8%). The CRM comorbidity burden was disproportionately high among participants reporting non-Hispanic Black race or ethnicity, unemployment, low socioeconomic status, and no high school degree. Among participants with 3 CRM conditions, nearly one-third (30.5%) did not report statin use, and only 4.8% and 3.0% used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, respectively. Between 1999 and 2020, the proportion of US adults with multiple CRM conditions increased significantly (from 5.3% to 8.0%; P < .001 for trend), as did the proportion having all 3 CRM conditions (0.7% to 1.5%; P < .001 for trend). Conclusions and Relevance: This cohort study found that CRM multimorbidity is increasingly common and undertreated among US adults, highlighting the importance of collaborative and comprehensive management strategies.

Persistent Steroid Exposure Before Coronavirus Disease 2019 Diagnosis and Risk of Hospitalization in Patients With Chronic Obstructive Pulmonary Disease.

Background: It is unclear whether persistent inhaled steroid exposure in chronic obstructive pulmonary disease (COPD) patients before coronavirus disease 2019 (COVID-19) is associated with hospitalization risk. Objective: Our objective was to examine the association between persistent steroid exposure and COVID-19-related hospitalization risk in COPD patients. Study Design and Methods: This retrospective cohort study used electronic health records from the Kaiser Permanente Northern California health care system (February 2, 2020, to September 30, 2020) for patients aged ≥40 years with COPD and a positive polymerase chain reaction test result for COVID-19. Primary exposure was persistent oral and/or inhaled steroid exposure defined as ≥6 months of prescriptions filled in the year before the COVID-19 diagnosis. Multivariable logistic regression was performed for the primary outcome of COVID-19-related hospitalization or death/hospice referral. Steroid exposure in the month before a COVID-19 diagnosis was a covariate. Results: Of >4.3 million adults, 697 had COVID-19 and COPD, of whom 270 (38.7%) had COVID-19-related hospitalizations. Overall, 538 (77.2%) were neither exposed to steroids in the month before COVID-19 diagnosis nor persistently exposed; 53 (7.6%) were exposed in the month before but not persistently; 23 (3.3%) were exposed persistently but not in the month before; and 83 (11.9%) were exposed both persistently and in the month before. Adjusting for all confounders including steroid use in the month before, the odds ratio for hospitalization was 0.77 (95% confidence interval 0.41-1.46) for patients persistently exposed to steroids before a COVID-19 diagnosis. Interpretation: No association was observed between persistent steroid exposure and the risk of COVID-19-related hospitalization in COPD patients.

Low Peak Inspiratory Flow Rates are Common Among COPD Inpatients and are Associated with Increased Healthcare Resource Utilization: A Retrospective Cohort Study.

Background: Patients with chronic obstructive pulmonary disease (COPD) can have low peak inspiratory flow (PIF), especially after hospitalization for acute exacerbation of COPD (AECOPD). Purpose: To characterize patients hospitalized for AECOPD, and to assess the prevalence of low PIF, changes in PIF after hospitalization, and the association of low PIF with healthcare resource utilization (HRU) outcomes. Patients and Methods: A retrospective cohort study was conducted using electronic health record data of hospitalized COPD patients in the Wake Forest Baptist Health system (01/01/2017 through 06/30/2020). Patients with a first eligible AECOPD hospitalization (index hospitalization) who were discharged before 05/31/2020 were included. PIF was measured using the In-Check DIAL™ at both medium-low resistance (R-2) and high resistance (R-5) during the index hospitalization. For R-2 and R-5, PIF was divided into low PIF (< 60 L/min; < 30 L/min) and high PIF (≥ 60 L/min; ≥ 30 L/min) groups. The primary outcome was the prevalence of low PIF. The stability of PIF after hospitalization was described. Adjusted regression models evaluated associations between low PIF and subsequent 30-day readmissions, 90-day readmissions, and HRU outcomes, including hospitalizations, emergency department visits, inpatient days, and intensive care unit (ICU) days. Results: In total, 743 patients with PIF measured at R-2 and R-5 during a AECOPD hospitalization were included. The prevalence of low PIF was 56.9% at R-2 and 14.7% at R-5. PIF values were relatively stable after hospitalization. Adjusted analyses showed significant increases in HRU (all-cause hospitalizations [31%], COPD hospitalizations [33%], COPD inpatient days [46%], and COPD ICU days [24%]) during the follow-up period among patients with low PIF (< 60 L/min) at R-2. The 30- and 90-day readmission risks were similar between patients with low PIF and high PIF. Conclusion: Low PIF is common among patients hospitalized for AECOPD, relatively stable after hospital discharge, and associated with increased HRU.

Assessing Preferences for Rare Disease Treatment: Qualitative Development of the Paroxysmal Nocturnal Hemoglobinuria Patient Preference Questionnaire (PNH-PPQ©).

PURPOSE: To develop a patient preference questionnaire (PPQ) assessing eculizumab and ravulizumab treatment for paroxysmal nocturnal hemoglobinuria (PNH). PATIENTS AND METHODS: The development of the PNH-PPQ© was consistent with Food and Drug Administration guidelines for patient-reported outcome measure development, and included 1) a targeted literature review; 2) PNH expert clinician input on treatment preferences; 3) review of existing qualitative data on the PNH treatment and disease experience; 4) concept elicitation interviews with 8 PNH patients who received eculizumab and/or ravulizumab; 5) translatability review; and 6) cognitive debriefing with 5 patients. Interview participants were recruited through a United Kingdom PNH patient advocacy group and a Canadian clinical site involved in clinical trial ALXN1210-PNH-302. RESULTS: Six themes were identified as most relevant to the PNH treatment experience from the concept elicitation interviews: disease symptoms (n=8/8); treatment frequency (n=7/8); quality of life impact of treatment/disease (n=7/8); treatment burden (n=7/8); treatment efficacy (n=5/8); and treatment side effects (n=5/8). An initial list of 88 preference questions was reduced to 11 highly relevant and non-redundant questions reflecting the 6 themes. Cognitive interview participants unanimously agreed that the PNH-PPQ instructions were clear; response options were understandable, easy to use, and provided enough choices; and the questions captured the factors that inform treatment preferences. DISCUSSION: When new drugs have similar efficacy to existing medications, documenting patient preferences is important for confirming patient benefit from the new medication. Understanding what matters most to patients is essential for delivering patient-centered care and may play a particularly significant role in treatment decision making. The availability of such a tool may be especially important as new orphan drugs are developed and patients with rare diseases have more than one treatment option to consider. CONCLUSION: The PNH-PPQ provides a patient-centered approach for evaluating preferences for the treatment of PNH. The PNH-PPQ has subsequently assessed patient preference in the clinical trial sub-study ALXN1210-PNH-302s.

Economic Impact of Early-in-Hospital Diagnosis and Initiation of Eculizumab in Atypical Haemolytic Uraemic Syndrome.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare, potentially life-threatening condition caused by dysregulation of the complement pathway. Eculizumab is currently the only approved treatment for this disorder. OBJECTIVE: Our objective was to investigate the impact of early administration of eculizumab on inpatient resource use and hospitalisation costs in 222 patients with aHUS. METHODS: We conducted a retrospective analysis of the Premier Perspective® Hospital Database, including patients with a diagnosis of aHUS and evidence of eculizumab use for aHUS. Early initiation was defined as having received eculizumab within 7 days of admission, with late initiation defined as starting eculizumab on day 8 or later. This date represents the average time required to obtain a specific diagnostic test to discriminate aHUS from a similar haemolytic syndrome that requires a different treatment. Outcome measures were time from first eculizumab initiation to discharge, discharge status or death, days spent in the intensive care unit (ICU), readmission indicators, dialysis indicators, and total hospital costs. Time from first eculizumab initiation to discharge was analysed using a generalised linear model with a log link and an assumed underlying negative binomial distribution. Logistic regression models were used to test the statistical significance of early versus late initiation as a predictor of the occurrence of readmissions, dialysis, and death. Total hospital costs were analysed using a generalised linear model with a log link and an assumed underlying gamma distribution. RESULTS: Before modelling, total length of stay and ICU duration were significantly longer for late initiators than for early initiators, and significantly more late initiators were readmitted within 90 days. Late initiation was associated with significantly higher hospital costs than early initiation. After multivariable analysis, late initiators were 3.2 times more likely to require dialysis. However, there was no significant association between early initiation and time to discharge, readmission, or death for any definition or early initiation after multivariable analysis. Estimated total hospital costs (year 2017 values) were $US103,557 in late initiators and $US85,776 in early initiators (p = 0.0024). CONCLUSION: Initiation of eculizumab within 7 days of hospitalisation is associated with lower dialysis rates, less time in ICU, less plasmapheresis, and lower hospitalisation costs compared with late initiation.

Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review.

BACKGROUND: Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by bone mineralization defects and systemic complications. Understanding of the clinical course and burden of HPP is limited by its rarity. This systematic literature review and synthesis of case report data aimed to determine the frequency and timing of clinical HPP manifestations and events. METHODS: Case reports and series of patients with HPP who had been followed longitudinally for ≥1 year were identified. Demographics and clinical data of interest, identified through consultation with clinical experts in HPP, were extracted. Occurrences of clinical manifestations/events of interest were categorized, classified by age at first reported occurrence of HPP manifestations and visualized over time. Clinical manifestations/events considered to contribute to the clinical burden of HPP were identified. Kaplan-Meier curves were used to estimate the median (range) age at first occurrence of the most frequently reported manifestations/events. RESULTS: From the 283 studies that met the inclusion criteria, 265 patients with HPP with ≥1 year of longitudinal follow-up were identified (median [interquartile range] age 4 [0-34] years; 45% male). The types of clinical manifestations/events of interest experienced by individuals with ≥1 such manifestation/event (n = 261) often differed between older and younger patients. Most (94%) of the 265 patients experienced ≥1 manifestation/event deemed to contribute to the clinical burden of HPP; premature tooth loss (53.5%), fractures (35.8%), pain (33.6%), and gross motor/ambulation difficulties (30.9%) were most frequently reported. The median (range) age at first reported occurrence of respiratory symptoms, cranial abnormalities, and premature tooth loss ranged from 0.3 to 10 years, whereas the median age at first reported occurrence of fractures, pain, gross motor/ambulation difficulties, and surgery ranged from 33 to 70 years. CONCLUSIONS: HPP is associated with a high clinical burden of disease, regardless of age at first reported occurrence of HPP manifestations. Over an individual's lifetime, the types of manifestations/events experienced can change and multiple HPP-related clinical manifestations/events can accumulate. These observations may reflect evolution and progression of the disease.

Methods of sample size calculation in descriptive retrospective burden of illness studies.

BACKGROUND: Observational burden of illness studies are used in pharmacoepidemiology to address a variety of objectives, including contextualizing the current treatment setting, identifying important treatment gaps, and providing estimates to parameterize economic models. Methodologies such as retrospective chart review may be utilized in settings for which existing datasets are not available or do not include sufficient clinical detail. While specifying the number of charts to be extracted and/or determining whether the number that can feasibly extracted will be clinically meaningful is an important study design consideration, there is a lack of rigorous methods available for sample size calculation in this setting. The objective of this study was to develop recommended sample size calculations for use in such studies. METHODS: Calculations for identifying the optimal feasible sample size calculations were derived, for studies characterizing treatment patterns and medical costs, based on the ability to comprehensively observe treatments and maximize precision of resulting 95% confidence intervals. For cost outcomes, if the standard deviation is not known, the coefficient of variation cv can be used as an alternative. A case study of a chart review of advanced melanoma (MELODY) was used to characterize plausible values for cv in a real-world example. RESULTS: Across sample sizes, any treatment given with greater than 1% frequency has a high likelihood of being observed. For a sample of size 200, and a treatment given to 5% of the population, the precision of a 95% confidence interval (CI) is expected to be ±0.03. For cost outcomes, for the median cv value observed in the MELODY study (0.72), a sample size of approximately 200 would be required to generate a 95% CI precise to within ±10% of the mean. CONCLUSION: This study presents a formal guidance on sample size calculations for retrospective burden of illness studies. The approach presented here is methodologically rigorous and designed for practical application in real-world retrospective chart review studies.

The epidemiologic burden of hepatitis C virus infection in Latin America .

Chronic infection with hepatitis C virus (HCV) is a major and growing public health concern worldwide, including in Latin America. With more efficacious therapies becoming available, decision-makers will require accurate estimates of disease prevalence to assess the potential impact of new treatments. However, few estimates of the epidemiologic burden, either overall or by country, are available for Latin America; and the potential impact of currently-available treatments on the epidemiologic burden of HCV in Latin America has not been assessed. To address this, we systematically reviewed twenty-five articles presenting population-based estimates of HCV prevalence from general population or blood donor samples, and supplemen- ted those with publically-available data, to estimate the total number of persons infected with HCV in Latin America at 7.8 million (2010). Of these, over 4.6 million would be expected to have genotype 1 chronic HCV, based on published data on the risk of progression to chronic disease and the HCV genotype distribution of Latin America. Finally, we calculated that between 1.6 and 2.3 million persons with genotype 1 chronic HCV would potentially benefit from current treatments, based on published estimates of genotype-specific treatment responsiveness. In conclusion, these estimates demonstrate the substantial present epidemiologic burden of HCV, and quantify the impending societal and clinical burden from untreated HCV in Latin America.

Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer.

OBJECTIVES: Examine the association between clinical, demographic, and socioeconomic factors and the receipt of systemic chemotherapy for bladder cancer. Examine factors influencing the use of combination chemotherapy plus cystectomy and use of specific chemotherapy drugs over time for bladder cancer. MATERIALS AND METHODS: Data from the SEER-Medicare database were analyzed for patients diagnosed with urothelial carcinoma of the bladder between 1992 and 2002. Cox proportional hazards regression analyses were used to assess differences in use of systemic chemotherapy based on demographic and clinical factors, site of care, and year of diagnosis. We assessed the proportion of patients who received chemotherapy in the adjuvant and neoadjuvant settings as well as use of chemotherapy in the monotherapy setting. We estimated the proportion of claims made for several commonly used chemotherapy agents in the outpatient setting by year. RESULTS: During follow-up, 13%, 28%, 37%, and 57% of patients with stages 1 through 4, respectively, received systemic chemotherapy for bladder cancer. Chemotherapy use in the neoadjuvant or adjuvant settings within 6 months of diagnosis was not commonly found. Neoadjuvant chemotherapy was delivered to 1.4% of stage 2 patients and 11% of stage 4 patients. In 2003, the most frequent claims for intravenous chemotherapy were for gemcitabine, carboplatin, and placlitaxel. CONCLUSIONS: Chemotherapy was not generally used as recommended for persons with invasive bladder cancer in this patient population. Studies to clarify potential underutilization and variation in patterns of administration are warranted.

Treatment patterns in patients with advanced breast cancer who were exposed to an anthracycline, a taxane, and capecitabine: a descriptive report.

OBJECTIVE: The aim of this work was to analyze chemotherapy treatment patterns in patients with advanced breast cancer who had been previously exposed to an anthracycline, a taxane, and capecitabine. METHODS: This retrospective cohort study used medical and pharmacy administrative claims with health-plan enrollment data and medical-record review from a large, US-based health insurer database, the HealthCore Integrated Research Database. Women were included if they were aged > or =18 years at the initial breast cancer diagnosis between January 1999 and July 2005 and had received all 3 drug classes of interest, as well as an initial diagnosis of American Joint Committee on Cancer stage I to III breast cancer with metastatic recurrence or an initial diagnosis of stage IV disease. Information about demographics, clinical and pathologic characteristics, survival, and treatments were obtained from computerized data and medical record review. Descriptive analyses were conducted to characterize the treatment patterns. RESULTS: One hundred forty-four women with advanced breast cancer were identified. Patients ranged in age from 28 to 76 years, with a mean (SD) age of 48.2 (9.1) years, and with 54 patients (37.5%) aged 40 to 49 years and 48 patients (33.3%) aged 50 to 59 years at the time of initial diagnosis. Ninety-three patients (64.6%) were white, 15 (10.4%) were black, 7 (4.9%) were Hispanic, and 4 (2.8%) were Asian. Overall, 89 patients (61.8%) received > or =1 additional chemotherapy regimen after exposure to all 3 chemotherapy agents of interest; 55 (38.2%) received > or =2 additional regimens. A variety of chemotherapeutic regimens were prescribed; 14 monotherapy regimens and 37 combination therapy regimens were used. The most common regimens (both as single agents and combination therapy) included gemcitabine, vinorelbine, or retreatment with a taxane. Of the 89 patients who received > or =1 retreatment, 7 (7.9%) were retreated with anthracycline, 12 (13.5%) with a taxane, and 9 (10.1%) with capecitabine. For first and second treatment after exposure to all 3 agents of interest, the most common single-agent regimens were gemcitabine (first: 17 patients [19.1%]; second: 9 patients [16.4%]) and vinorelbine (first: 14 patients [15.7%]; second: 9 patients [16.4%]). The most common combination therapies for first retreatment were carboplatin based (6 patients [6.7%]). CONCLUSIONS: Of these patients with advanced breast cancer, 61.8% received > or =1 additional chemotherapy regimen after previous treatment with an anthracycline, a taxane, and capecitabine. The variety of agents prescribed suggests a lack of standard of care. Rigorous clinical effectiveness studies of common regimens in heavily pretreated and chemotherapy-resistant populations with breast cancer are warranted.