The Role of Blood Testing in Prevention, Diagnosis, and Management of Chronic Diseases: A Review.

Blood tests are vital to prevention, diagnosis, and management of chronic diseases. Despite this, it can be challenging to construct a comprehensive view of the clinical importance of blood testing because relevant literature is typically fragmented across different disease areas and patient populations. This lack of collated evidence can also make it difficult for primary care providers to adhere to best practices for blood testing across different diseases and guidelines. Thus, this review article synthesizes the recommendations for, and importance of, blood testing across several common chronic conditions encountered in primary care and internal medicine, including cardiovascular diseases, diabetes mellitus, chronic kidney disease, vitamin D deficiency, iron deficiency, and rheumatoid arthritis. Future research is needed to continue improving chronic disease management through clearer dissemination and awareness of clinical guidelines among providers, and better access to blood testing for patients (e.g., via pre-visit laboratory testing).

A medical chart audit to assess endocrinologist perceptions of the burden of endogenous Cushing's syndrome.

PURPOSE: This study was undertaken to assess the unmet needs within the endogenous Cushing's syndrome (CS) care paradigm from the endocrinologist's perspective, including data abstracted from patient charts. The study evaluated endocrinologists' perceptions on burden of illness and treatment rationale along with the long-term clinical burden of CS, tolerability of CS treatments, and healthcare resource utilization for CS. METHODS: Retrospective medical chart data from treated patients with a confirmed diagnosis of CS was abstracted using a cross-sectional survey to collect data from qualified endocrinologists. The survey included a case report form to capture patient medical chart data and a web-enabled questionnaire to capture practitioner-level data pertaining to endocrinologists' perceptions of disease burden, CS treatments, and treatment attributes. RESULTS: Sixty-nine endocrinologists abstracted data from 273 unique medical charts of patients with CS. Mean patient age was 46.5 ± 13.4 years, with a 60:40 (female:male) gender split. The mean duration of endogenous CS amongst patients was 4.1 years. Chart data indicated that patients experienced a high burden of comorbidities and symptoms, including fatigue, weight gain, and muscle weakness despite multi-modal treatment. When evaluating treatments for CS, endocrinologists rated improvement in health-related quality of life (HRQoL) as the most important treatment attribute (mean score = 7.8; on a scale of 1 = Not at all important to 9 = Extremely important). Surgical intervention was the modality endocrinologists were most satisfied with, but they agreed that there was a significant unmet treatment need for patients with CS. CONCLUSION: Endocrinologists recognized that patients with CS suffered from a debilitating condition with a high symptomatic and HRQoL burden and reported that improvement in HRQoL was the key treatment attribute influencing their treatment choices. This study highlights unmet needs for patients with CS. Patients with CS have a high rate of morbidity and comorbidity, even after treatment.

Holistic burden of illness in patients with endogenous Cushing's syndrome: A systematic literature review.

OBJECTIVE: The objective of this systematic literature review (SLR) was to summarize the latest studies evaluating the burden of illness in endogenous Cushing's syndrome (CS), including the impact of CS on overall and domain-specific health-related quality of life (HRQoL) and the economic burden of CS to provide a holistic understanding of disease and treatment burden. METHODS: An SLR was conducted in PubMed, MEDLINE and Embase using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to identify peer-reviewed manuscripts and conference abstracts published in English from 2015 to December 4, 2020. RESULTS: Forty-five publications were eligible for inclusion; data were extracted from 37 primary studies while 8 SLRs were included for reference only. Thirty-one studies reported HRQoL using validated patient reported outcome (PRO) measures in pre- or post-surgery, radiotherapy and pharmacotherapy patients. Overall, this SLR found that patients with CS have worse outcomes relative to healthy populations across specific dimensions, such as depression, despite an improvement in HRQoL post-treatment. These findings reveal that CS symptoms are not fully resolved by the existing care paradigm. Few studies report on the economic burden of CS and currently available data indicate a high direct healthcare system cost burden. CONCLUSIONS: Patients with CS experience a significant, complex and multifactorial HRQoL burden. Symptom-specific burden studies are sparse in the literature and the understanding of long-term CS symptomatic burden and economic burden is limited. This review intends to provide an updated reference for clinicians, payers and other stakeholders on the burden of CS as reported in published literature and to encourage further research in this area.

Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn's perianal fistulas.

BACKGROUND: Patients with Crohn's disease (CD) are at risk of developing complications such as perianal fistulas. Patients with Crohn's perianal fistulas (CPF) are affected by fecal incontinence (FI), bleeding, pain, swelling, and purulent perianal discharge, and generally face a higher treatment burden than patients with CD without CPF. AIM: To gain insights into the burden of illness/quality of life in patients with CPF and their treatment preferences and satisfaction. METHODS: This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries (April-August 2021). Patients were recruited into three cohorts: Cohort 1 included patients without perianal fistulas; cohort 2 included patients with perianal fistulas without fistula-related surgery; and cohort 3 included patients with perianal fistulas and fistula-related surgery. Validated patient-reported outcome measures were used to assess quality of life. Drivers of treatment preferences were measured using a discrete choice experiment (DCE). RESULTS: In total, 929 patients were recruited (cohort 1, n = 620; cohort 2, n = 174; cohort 3, n = 135). Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CPF (cohorts 2 and 3) than for those with CD without CPF (cohort 1): Mean score 3.8 and 3.7 vs 4.1, respectively, (P < 0.001). Similarly, mean Revised FI and FI Quality of Life scores were worse for patients with CPF than for those with CD without CPF. Quality of Life with Anal Fistula scores were similar in patients with CPF with or without CPF-related surgery (cohorts 2 and 3): Mean score 41 and 42, respectively. In the DCE, postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice: Mean relative importance 35.7 and 24.7, respectively. CONCLUSION: The burden of illness in CD is significantly higher for patients with CPF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.

Evaluating the burden of endogenous Cushing's syndrome using a web-based questionnaire and validated patient-reported outcome measures.

INTRODUCTION: Endogenous Cushing's syndrome (CS) is a rare endocrine condition caused by chronic oversecretion of cortisol, resulting in a diverse constellation of symptoms. This study examined the ongoing burden of illness (BOI), from the first appearance of symptoms through treatment, which is currently not well evaluated. METHODS: A quantitative, cross-sectional, web-enabled survey including 5 validated patient reported outcomes (PRO) measures was conducted in patients with CS who had been diagnosed ≥ 6 months prior and who had received ≥ 1 treatment for their endogenous CS at the time of the survey. RESULTS: Fifty-five patients participated in this study; 85% were women. The mean age was 43.4 ± 12.3 years (± standard deviation, SD). On average, respondents reported a 10-year gap between the first occurrence of symptoms and diagnosis; 80% underwent surgical treatment for CS. Respondents experienced symptoms on 16 days in a typical month, and their health-related quality of life was moderately impacted based on the CushingQoL score. Weight gain, muscle fatigue, and weakness were the most common symptoms and 69% percent of patients reported moderate or severe fatigue using the Brief Fatigue Inventory. Following treatment, the occurrence of most symptoms declined over time, although anxiety and pain did not significantly decrease. Overall, 38% of participants reported an annual average of 25 missed workdays due to CS symptoms. CONCLUSIONS: These results demonstrate a BOI in CS despite ongoing treatment and illustrate the need for interventions to address persistent symptoms, particularly weight gain, pain, and anxiety.

Clinical and economic impact of primary hyperoxaluria: a retrospective claims analysis.

BACKGROUND: Primary hyperoxaluria (PH) is a family of rare, life-threatening genetic liver disorders characterized by elevated production and excretion of oxalate. To date, the clinical and economic burden associated with PH has not been well characterized due to the rarity of the disease and previous challenges with diagnostic coding that prevented proper identification of patients with PH in claims data. OBJECTIVE: To characterize the clinical and economic costs, as well as health care resource utilization (HCRU), associated with PH relative to a matched cohort of patients without PH. METHODS: Data from the IQVIA PharMetrics Plus Database were used to conduct a retrospective matched-cohort study to compare differences in clinical characteristics, HCRU, and pharmacy and medical costs in patients with PH compared with a matched cohort of patients without PH from January 2014 to December 2019. RESULTS: Overall, 324 patients were included in the PH cohort and 1,620 patients were in the non-PH cohort. The mean age of PH patients was 48.1 years, and approximately 58% of the sample were male. Significantly more patients in the PH cohort than the non-PH cohort were diagnosed with stage 2 chronic kidney disease (CKD; 3.1% vs 0.4%, respectively; P < 0.001), stage 3 CKD (4.6% vs 0.5%; P < 0.001), stage 4 CKD (2.5% vs 0.1%; P < 0.001), and stage 5 CKD or end-stage renal disease (ESRD; 2.2% vs 0.1%; P < 0.001). PH patients had a significantly higher mean Charlson Comorbidity Index composite score than patients in the non-PH cohort (0.79 vs 0.37; P < 0.001). HCRU was significantly higher in patients with PH. The PH cohort had a significantly higher proportion of patients with at least 1 visit to clinicians specializing in nephrology (19% vs 0.4%, respectively; P < 0.001), cardiology (22% vs 12%; P < 0.001), ophthalmology (16% vs 7%; P < 0.001), general surgery (9% vs 6%; P = 0.011), and urology (65% vs 6%; P < 0.001) compared with patients without PH. Mean total annual health care costs in the PH cohort were 65% higher than in the non-PH cohort ($22,549 vs $7,852, respectively; P < 0.001). Similar results were found for total prescription drug costs ($4,125 vs $2,464; P = 0.012). CONCLUSIONS: Despite the rarity of PH, patients with this disease incur substantial clinical and economic burden and may cause financial strain on the health care system. Additional research is warranted to understand the economic and clinical burden of PH stratified by the 3 subtypes of the disease. DISCLOSURES: Funding for this research was provided by Dicerna Pharmaceuticals. Mucha and Hoppe are employed by Dicerna Pharmaceuticals. Silber Miyasoto, Skaar, and Wang are employed by Trinity Life Sciences, which was contracted by Dicerna Pharmaceuticals to conduct the study analysis. Langman is consultant to Dicerna Pharmaceuticals. This study was presented as a poster at the AMCP Nexus 2020 (virtual), October 19-23, 2020, and American Society of Nephrology 2020 (virtual), October 19-25, 2020.

Economic burden of congenital athymia in the United States for patients receiving supportive care during the first 3 years of life.

AIMS: Congenital athymia is an ultra-rare pediatric condition characterized by the lack of thymus in utero and the naïve T cells critical for infection defense and immune regulation. Patients with congenital athymia receive supportive care to minimize and treat infections, autoimmune phenomena, and autologous graft-versus-host disease (aGVHD) manifestations, but historically, die within the first 3 years of life with supportive care only. We estimated the healthcare resource utilization and economic burden of supportive care over patients' first 3 years of life in the United States. METHODS: A medical chart audit by the treating physician was used to collect patient data from birth to age 3 on clinical manifestations associated with congenital athymia (clinical manifestations due to underlying syndromic conditions excluded). Using costs and charges from publicly available sources, the total economic burden of direct medical costs and charges for the first 3 years of life (considered "lifetime" for patients receiving supportive care) and differences in economic burden between patients with higher and lower inpatient hospitalization durations were estimated. RESULTS: All patients (n = 10) experienced frequent infections and aGVHD manifestations; 40% experienced ≥1 episode of sepsis, and 20% had recurrent sepsis episodes annually. The estimated mean 3-year economic burden per patient was US$5,534,121 (2020 US dollars). The annual mean inpatient hospitalization duration was 150.6 days. Inpatient room charges accounted for 79% of the economic burden, reflecting the high costs of specialized care settings required to prevent infection, including isolation. Patients with high inpatient utilization (n = 5; annual mean inpatient hospitalization duration, 289.6 days) had an estimated 3-year economic burden of US$9,926,229. LIMITATIONS: The total economic burden may not be adequately represented due to underestimation of some direct costs or overestimation of others. CONCLUSIONS: Current treatment of patients with congenital athymia (supportive care) presents a high economic burden to the healthcare system.

Defining the Clinical, Emotional, Social, and Financial Burden of Congenital Athymia.

INTRODUCTION: Characterize the burden of illness in pediatric patients with congen̄ital athymia who were receiving supportive care. METHODS: This cross-sectional study of adult caregivers of patients with congenital athymia used both a quantitative survey and qualitative interviews. Caregivers of patients currently receiving supportive care responded to questions about the past 12 months and completed the parent proxy version of the Pediatric Quality of Life Inventory Generic instrument (PedsQL) for patients aged 2-4 years. For caregivers of patients who had received supportive care in the past, questions were asked about the period when they were receiving supportive care only. RESULTS: The sample included caregivers of 18 patients, 5 who were currently receiving supportive care and 13 who received investigational cultured human thymus tissue implantation before study enrollment and had received supportive care in the past. The impact of congenital athymia was substantial. Reports included the need to live in isolation (100% of respondents); caregiver emotional burden such as fear of death, infection, and worries about the future (100%); financial hardship (78%); and the inability to meet family/friends (72%). Patients had frequent and prolonged hospitalizations (78%) and had high utilization of procedures, medications, and home medical supplies. Caregiver-reported PedsQL scores for patients currently receiving supportive care (n = 4) indicated low health-related quality of life. CONCLUSIONS: Caregivers of patients with congenital athymia reported high clinical, emotional, social, and financial burden on patients and their families.

Congenital Athymia: Genetic Etiologies, Clinical Manifestations, Diagnosis, and Treatment.

Congenital athymia is an ultra-rare disease characterized by the absence of a functioning thymus. It is associated with several genetic and syndromic disorders including FOXN1 deficiency, 22q11.2 deletion, CHARGE Syndrome (Coloboma, Heart defects, Atresia of the nasal choanae, Retardation of growth and development, Genitourinary anomalies, and Ear anomalies), and Complete DiGeorge Syndrome. Congenital athymia can result from defects in genes that impact thymic organ development such as FOXN1 and PAX1 or from genes that are involved in development of the entire midline region, such as TBX1 within the 22q11.2 region, CHD7, and FOXI3. Patients with congenital athymia have profound immunodeficiency, increased susceptibility to infections, and frequently, autologous graft-versus-host disease (GVHD). Athymic patients often present with absent T cells but normal numbers of B cells and Natural Killer cells (T-B+NK+), similar to a phenotype of severe combined immunodeficiency (SCID); these patients may require additional steps to confirm the diagnosis if no known genetic cause of athymia is identified. However, distinguishing athymia from SCID is crucial, as treatments differ for these conditions. Cultured thymus tissue is being investigated as a treatment for congenital athymia. Here, we review what is known about the epidemiology, underlying etiologies, clinical manifestations, and treatments for congenital athymia.