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1.
    
Background: Lung cancer is one of the most prevalent cancers in the US. This study was designed to evaluate the actual drug wastage and cost to the healthcare system using patient-level retrospective observational electronic medical record (EMR) data from a cohort of lung cancer patients in the US.

Methods: Data from the Flatiron Health advanced non-small cell lung cancer (NSCLC) cohort was used for this study. Drug administered amount (in mg) was used to determine an optimal set of available vial sizes to minimize waste. Drug wastage was defined as the difference between the drug amount in the optimal set of vials and the administered amount. Wholesale acquisition costs were used to value the cost of drugs, with and without vial sharing assumptions. The amount and cost of waste were quantified over the 2-year study period (January 2015–December 2016).

Results: There were 8,467 eligible patients included in this study, providing data from 103,826 unique drug administrations across multiple lines of therapy. Overall wastage was 4.37% of the total medication used to care for patients. While costs per administration were low, the total cost of wastage for the study population represented $16,630,112 across the 2-year study period. Assuming that vial sharing occurred at the site level slightly reduced waste to 3.74% (reducing costs to $15,953,212 over 2 years).

Conclusions: Drug wastage is an important concern and has implications on healthcare costs in NSCLC. Evaluation of these real-world data suggest that pharmacists and physicians are able to reduce drug wastage by optimizing vial combinations and sharing vials among patients. Even small amounts of reduction in wastage could be useful in reducing healthcare costs in the US; however, caution is needed with drug rounding efforts to ensure patients do not receive a sub-optimal dose of medication.  相似文献   

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Abstract

Purpose: This study aimed to evaluate the healthcare resource utilization (HCRU) and costs for patients with severe aplastic anemia (SAA) using US claims data.

Methods: This retrospective, observational database study analyzed claims data from the Truven MarketScan databases. SAA patients aged ≥2?years identified between 2014 and 2017 who were continuously enrolled for 6?months before their first SAA treatment or blood transfusion, with a ≥6-month follow-up, were included. Baseline demographics and comorbidities were evaluated. Monthly all-cause and SAA-related HCRU and direct costs in the follow-up period were analyzed and differences were presented for all patients and across age groups.

Results: With an average follow-up period of 21.5?months, 939 patients were included in the study. Monthly all-cause and SAA-related HCRU [mean (SD)] were 1.65 days (2.61 days) and 0.18 days (0.70 days) for length of stay, 0.18 (0.23) and 0.01 (0.04) for hospital admissions, 0.25 (0.30) and 0.02 (0.07) for ER visits, 2.24 (1.40) and 0.46 (0.99) for office visits, and 2.90 (2.64) and 0.55 (1.31) for outpatient visits, respectively. On average, SAA patients received 0.15 (0.57) blood transfusions per month. Mean monthly all-cause direct costs were $28,280 USD ($36,127) [US dollars, mean (SD)]. Direct costs related to admissions were $11,433 USD (SD $25,040), followed by $624 USD ($1,703) for ER visits, $528 USD ($694) for office visits, $7,615 USD ($13,273) for outpatient visits, and $5,998 USD ($11,461) for pharmacy expenses. Monthly SAA-related direct costs averaged $7,884 USD (SD $16,254); of these costs, $1,608 USD ($7,774) were from admissions, $47 USD ($257) from ER visits, $127 USD ($374) from office visits, $1,462 USD ($4,994) from outpatient visits, and $4,451 USD ($10,552) from pharmacy expenses.

Conclusion: SAA is associated with high economic burden, with costs comparable to blood malignancies, implying that US health plans should consider appropriately managing SAA while constraining the total healthcare costs when making formulary decisions.  相似文献   

3.
    
Aims: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically.

Materials and methods: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010–2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept.

Results: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p?p?p?p?=?.021), and numerically lower all-cause costs ($4,444 vs $4,741, p?=?0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p?=?.031), and numerically higher ED visits (IRR = 1.32, p?=?.093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p?Limitations and conclusions: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.  相似文献   

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Abstract

Background: Thrombocytopenia (TCP), a common complication of chronic liver disease (CLD), can cause uncontrolled bleeding during procedures. As such, CLD patients with TCP and platelet counts <50,000/μL often receive prophylactic platelet transfusions before invasive procedures. However, platelet transfusions are associated with clinical complications, which may result in increased healthcare utilization and costs.

Objective: This retrospective database analysis describes the clinical and economic burden in CLD patients with TCP, CLD patients without TCP, and CLD patients with TCP who receive platelet transfusions.

Methods: Adult CLD patients with or without TCP were identified in the IBM MarketScan Commercial Claims and Medicare Supplemental data from 1 January 2012 to 31 December 2015. CLD patients with or without TCP were propensity-score matched (1:1) for the analysis of annual healthcare utilization and costs. Platelet transfusions among CLD patients with TCP were identified using procedure codes.

Results: Of the 601,626 patients with CLD, 8,292 (1.4%) patients with TCP were matched to patients without TCP. Among CLD patients with TCP, 981 (11.8%) patients received ≥1 platelet transfusions and met inclusion/exclusion criteria. Compared to patients without TCP, CLD patients with TCP had more complications, including higher prevalence of neutropenia (11.4% vs 2.9%) and bleeding events (21.4% vs 10.9%), greater resource utilization including greater average hospital admissions (1.2 vs 0.7, p?<?.01), greater average ER visits (2.1 vs 1.3, p?<?.01), higher average outpatient office visits (20.1 vs 18.4, p?<?.01), and higher average healthcare costs including total costs (p?<?.01), inpatient costs (p?<?.01), ER visit costs (p?<?.01), and outpatient office visit costs (p?<?.01). The mean annual total costs in CLD and TCP patients with platelet transfusions were $206,396.

Conclusions: CLD patients with TCP, and particularly those who received platelet transfusions, experienced significantly greater clinical and economic burden compared to CLD patients without TCP. Safer and more cost-effective treatments to increase platelets are necessary.  相似文献   

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Abstract

Aim: Acute myeloid leukemia (AML) is associated with high disease burden. This analysis estimated HRU and costs among newly diagnosed AML patients in a US commercially insured population.

Materials and methods: This was a retrospective observational study using the IMS Health PharMetrics Plus and Hospital Charge Detail Master databases. Patients included adults who were newly diagnosed with AML between January 2007 and June 2016 (“study period”). Patients with <12 months of continuous enrollment prior to the index date were excluded, as were those whose first diagnosis was AML in remission/relapse, those diagnosed with acute promyelocytic leukemia, those on Medicare supplemental insurance, or those with a diagnosis of AML in remission/relapse without evidence of treatment during the study period. Patients were stratified by receipt of AML treatment (chemotherapy/hematopoietic cell transplantation [HCT]), and their follow-up was partitioned into initial, remission, and relapsed health states. Mean HRU and costs were tallied by treatment and, for treated patients, by health state and time since entry into health state (≤6 vs >6 months).

Results: A total of 9,455 patients met study criteria, including 6,415 (68%) treated and 3,040 (32%) untreated patients, with mean follow-up of 18.3 and 16.4 months, respectively. Mean age was 55 years in treated patients and 60 years in untreated patients. Mean total costs per patient were $386,077 in treated patients and $79,382 in untreated patients. For treated patients, 60% of total costs ($231,867 per patient) were incurred during the initial health state, representing time without remission/relapse. Mean monthly total healthcare costs were $21,055 and $4,854 among treated and untreated patients, respectively.

Limitations and conclusions: HRU and costs of managing AML patients are substantial. In treated patients, the majority of costs were incurred during the initial treatment period, without claims indicating remission/relapse.  相似文献   

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Aim: To estimate direct and indirect costs in patients with a diagnosis of cluster headache in the US.

Methods: Adult patients (18–64 years of age) enrolled in the Marketscan Commercial and Medicare Databases with ≥2 non-diagnostic outpatient (≥30 days apart between the two outpatient claims) or ≥1 inpatient diagnoses of cluster headache (ICD-9-CM code 339.00, 339.01, or 339.02) between January 1, 2009 and June 30, 2014, were included in the analyses. Patients had ≥6 months of continuous enrollment with medical and pharmacy coverage before and after the index date (first cluster headache diagnosis). Three outcomes were evaluated: (1) healthcare resource utilization, (2) direct healthcare costs, and (3) indirect costs associated with work days lost due to absenteeism and short-term disability. Direct costs included costs of all-cause and cluster headache-related outpatient, inpatient hospitalization, surgery, and pharmacy claims. Indirect costs were based on an average daily wage, which was estimated from the 2014?US Bureau of Labor Statistics and inflated to 2015 dollars.

Results: There were 9,328 patients with cluster headache claims included in the analysis. Cluster headache-related total direct costs (mean [standard deviation]) were $3,132 [$13,396] per patient per year (PPPY), accounting for 17.8% of the all-cause total direct cost. Cluster headache-related inpatient hospitalizations ($1,604) and pharmacy ($809) together ($2,413) contributed over 75% of the cluster headache-related direct healthcare cost. There were three sub-groups of patients with claims associated with indirect costs that included absenteeism, short-term disability, and absenteeism?+?short-term disability. Indirect costs PPPY were $4,928 [$4,860] for absenteeism, $803 [$2,621] for short-term disability, and $3,374 [$3,198] for absenteeism?+?disability.

Conclusion: Patients with cluster headache have high healthcare costs that are associated with inpatient admissions and pharmacy fulfillments, and high indirect costs associated with absenteeism and short-term disability.  相似文献   

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Objective: Opioid use disorder (OUD) can be managed with medication assisted therapy (MAT) (methadone [MET], buprenorphine [BUP], or extended-release naltrexone [XR-NTX]) or counseling alone (non-pharmacological therapy [NPT]). The objective of this study was to evaluate healthcare resource utilization and costs associated with XR-NTX compared with alternative treatments for opioid dependence.

Methods: Adults with a diagnosis of opioid dependence who initiated treatment with XR-NTX, BUP, MET, or NPT between January 1, 2011 and December 31, 2014 were identified in the Truven Health MarketScan Commercial administrative claims database. Healthcare resource utilization, costs (inpatient [IP], emergency department [ED], outpatient [OP], and pharmacy) and adherence were evaluated for each cohort during 12-month baseline and follow-up periods.

Results: A total of 29,235 patients were included in the analysis; 1,041, 20,566, 745, and 6,883 received XR-NTX, BUP, MET, and NPT, respectively. Patients in the XR-NTX cohort were significantly younger and had more comorbidities compared with the other cohorts. Patients in the XR-NTX group had the largest percentage decrease in IP and ED utilization and costs from baseline to follow-up. OP and pharmacy costs increased significantly from baseline to follow-up for all cohorts. Overall, there was no significant change in total healthcare costs for the XR-NTX group, whereas the costs increased significantly for other groups (BUP?=?+43%, MET?=?+47.7%, NPT?=?+38.8%).

Conclusions: Healthcare resource utilization and costs increased from baseline to follow-up in BUP, MET, and NPT patients, whereas patients receiving XR-NTX experienced no such increase. This analysis suggests there may be economic value in the use of XR-NTX for OUD.  相似文献   

10.
Introduction and objectives: This study has two objectives: (1) to examine healthcare resource utilization in heart failure (HF) patients; and (2) to examine the treatment costs associated with HF in China.

Methods: The data used in this study was from the 2014 national insurance database sponsored by the China Health Insurance Research Association (CHIRA), that covers national urban employees and residents. ICD-10 codes and keywords indicating heart failure diagnoses were used to identify patients with heart failure. Drug utilization, hospital visits, re-admission, and treatment costs in different service categories were examined.

Results: A total of 7,847 patients were included in this analysis, of which 1,157 patients had a 1-year complete follow-up period. In total, 48.16% of patients received the combination treatment of angiotensin-converting-enzyme inhibitor (ACEI)/angiotensin II receptor blockers (ARB) and beta-blockers (BB); and 22.87% of patients received the combination treatment of ACEI/ARB, beta-blockers and Mineralocorticoid receptor antagonists (MRAs). The annual treatment cost per patient with HF diagnosis was RMB 28,974, of which 66% was for inpatient care. The cost on HF medications accounted for 8.2% of annual cost. Treatment cost was much higher in provincial-level municipalities than that of prefecture-level and other cities.

Discussion and conclusion: Hospitalization is a major driver of HF treatment cost. Compared to the requirements in international treatment guidelines, HF standard of care medication treatment was under-utilized among HF patients in China. The high re-admission rate among Chinese patients indicates that the management of HF needs to be improved. The percentage of GDP spent on treating HF patients was much lower than that in the developed countries.  相似文献   


11.
    
Aims: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs.

Methods: Adults with MM diagnosis between January 1, 2010–December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index?=?first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016?US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar’s tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs.

Results: Each cohort included 848 patients (mean age?=?61 – 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p?<?.0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p?<?.0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE.

Limitations: SRE misclassification and residual confounding are possible.

Conclusions: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.  相似文献   

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Aim: To assess the cost-effectiveness in Canada of atezolizumab compared with docetaxel or nivolumab for the treatment of advanced NSCLC after first-line platinum-doublet chemotherapy.

Materials and methods: A three-state partitioned-survival model was developed. Clinical inputs were obtained from the phase III OAK trial comparing atezolizumab with docetaxel in patients with advanced NSCLC who progressed after first-line platinum-doublet chemotherapy. Overall survival (OS) and progression-free survival (PFS) were extrapolated beyond the trial period using parametric models. A cure model assuming a 1% cure fraction was fitted to the OS data for atezolizumab. Outcomes for nivolumab were informed by a network meta-analysis (NMA) vs atezolizumab. Resource use and costs were informed by clinical expert opinion and published Canadian sources. Utility values were obtained from the OAK trial. The perspective of the analysis was that of the Canadian publicly-funded healthcare system. The base case time horizon was 10?years, and the discount rate was 1.5% annually for both costs and effects. Scenario analyses were performed to test the robustness of the results and all analyses were performed probabilistically.

Results: Atezolizumab demonstrated a quality-adjusted life-year (QALY) gain of 0.60 compared with docetaxel at an incremental cost of $85,073, resulting in an incremental cost-effectiveness ratio (ICER) of $142,074/QALY. Atezolizumab dominated nivolumab (regardless of dosing regimen), based on modest differences in both QALYs and costs. Docetaxel was most likely to be cost effective at willingness-to-pay (WTP) thresholds below $125,000/QALY gained, while atezolizumab was most likely to be cost effective beyond this WTP threshold. In most scenario analyses, the results remained robust to changes in parameters. A reduced time horizon and alternative approaches to the NMA had the greatest impact on cost-effectiveness results.

Conclusion: Atezolizumab represents a cost-effective therapeutic option in Canada for the treatment of patients with advanced NSCLC who progress after first-line platinum doublet chemotherapy.  相似文献   

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Abstract

Objective: Patients with cancer are at high risk for developing primary but also recurrent venous thromboembolism (VTE). This study examined healthcare utilization (HRU) and costs related to VTE recurrence among cancer patients.

Methods: Medical and pharmacy claims from the Humana Database were used to compare HRU (outpatient visits, emergency room visits, hospitalizations, and hospitalization days) and healthcare costs among cancer patients with a single VTE event (between 01/2013 and 06/2015) and those with recurrent VTE during the follow-up period (from initiation of anticoagulant therapy until end of eligibility or data availability). All-cause and VTE-related HRU and costs were evaluated using Poisson regression, and healthcare costs were compared using mean differences reported as per-patient-per-year (PPPY).

Results: Of 2,428 newly diagnosed cancer patients who developed VTE, 413 (17.1%) experienced recurrent VTE during the follow-up period (mean = 9 months). Patients with recurrent VTE had higher all-cause and VTE-related HRU and costs compared to those without recurrence. Patients with recurrent VTE also had over 3.19-times more VTE-related hospitalizations (RR [95% CI]?=?3.19 [2.93–3.47]), and 3.88-times more VTE-related hospitalization days (RR [95% CI]?=?3.88 [3.74–4.02]) than patients without a VTE recurrence. Total VTE-related healthcare costs were $39,641 PPPY among patients with recurrent VTE, $29,142 higher compared to those without recurrence ($10,499 PPPY). This difference was mainly driven by hospitalization costs.

Conclusion: Recurrent VTE among cancer patients is associated with significant HRU and healthcare costs, notably hospitalizations. Strategies to reduce VTE recurrence in patients with cancer can contribute to reducing healthcare cost.  相似文献   

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Aims: To assess incremental charges of patients experiencing venous thromboembolisms (VTE) across various types of elective inpatient surgical procedures with administration of general anesthesia in the US.

Methods: The authors performed a retrospective study utilizing data from a nationwide hospital operational records database from July 2014 through June 2015 to compare a group of inpatients experiencing a VTE event post-operatively to a propensity score matched group of inpatients who did not experience a VTE. Patients included in the analysis had a hospital admission for an elective inpatient surgical procedure with the use of general anesthesia. Procedures of the heart, brain, lungs, and obstetrical procedures were excluded, as these procedures often require a scheduled ICU stay post-operatively. Outcomes examined included VTE events during hospitalization, length of stay, unscheduled ICU transfers, number of days spent in the ICU if transferred, 3- and 30-day re-admissions, and total hospital charges incurred.

Results: The study included 17,727 patients undergoing elective inpatient surgical procedures. Of these, 36 patients who experienced a VTE event were matched to 108 patients who did not. VTE events occurred in 0.2% of the study population, with most events occurring for patients undergoing total knee replacement. VTE patients had a mean total hospital charge of $60,814 vs $48,325 for non-VTE patients, resulting in a mean incremental charge of $11,979 (p?<?.05). Compared to non-VTE patients, VTE patients had longer length of stay (5.9 days vs 3.7 days, p?<?.001), experienced a higher rate of 3-day re-admissions (3 vs 0 patients) and 30-day re-admissions (7 vs 2 patients).

Conclusions: Patients undergoing elective inpatient surgical procedures with general anesthesia who had a VTE event during their primary hospitalization had a significantly longer length of stay and significantly higher total hospital charges than comparable patients without a VTE event.  相似文献   

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Aims: To describe healthcare resource utilization (HCRU) and costs among biologic-treated psoriasis patients in the US, overall and by disease severity.

Materials and methods: IQVIA PharMetrics Plus administrative claims data were linked with Modernizing Medicine Data Services Electronic Health Record data and used to select adult psoriasis patients between April 1, 2010 and December 31, 2014. Eligible patients were classified by disease severity (mild, moderate, severe) using a hierarchy of available clinical measures. One-year outcomes included all-cause and psoriasis-related outpatient, emergency department, inpatient, and pharmacy HCRU and costs.

Results: This study identified 2,130 biologic-treated psoriasis patients: 282 (13%) had mild, 116 (5%) moderate, and 49 (2%) severe disease; 1,683 (79%) could not be classified. The mean age was 47.6 years; 45.4% were female. Relative to mild psoriasis patients, patients with moderate or severe disease had more median all-cause outpatient encounters (28.0 [mild] vs 32.0 [moderate], 36.0 [severe]), more median psoriasis-related outpatient encounters (6.0 [mild] vs 7.5 [moderate], 8.0 [severe]), and a higher proportion of overall claims for medications that were psoriasis-related (28% [mild] vs 37% [moderate], 34% [severe]). Relative to mild psoriasis patients, patients with moderate or severe disease had higher median all-cause total costs ($37.7k [mild] vs $42.3k [moderate], $49.3k [severe]), higher median psoriasis-related total costs ($32.7k [mild] vs $34.9k [moderate], $40.5k [severe]), higher median all-cause pharmacy costs ($33.9k [mild] vs $36.5k [moderate], $36.4k [severe]), and higher median psoriasis-related pharmacy costs ($32.2k [mild] vs $33.9k [moderate], $35.6k [severe]).

Limitations: The assessment of psoriasis disease severity may not have necessarily coincided with the timing of biologic use. The definition of disease severity prevented the assessment of temporality, and may have introduced selection bias.

Conclusions: Biologic-treated patients with moderate or severe psoriasis cost the healthcare system more than patients with mild psoriasis, primarily driven by higher pharmacy costs and more outpatient encounters.  相似文献   

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Abstract

Aims: To assess the real-world clinical burden and healthcare resource utilization (HRU) among patients with chronic hypoparathyroidism, overall and by adequately controlled (AC) vs not adequately controlled (NAC) disease, informed by guideline-recommended clinical management targets, including biochemistry and symptoms.

Materials and methods: In this retrospective online chart review, endocrinologists in the US, Canada, the UK, France, Germany, Italy, and Spain were randomly selected to review the medical charts of adult patients with chronic hypoparathyroidism receiving calcium and activated vitamin D. Patients’ demographics, disease characteristics, symptoms, comorbidities, and hypoparathyroidism-related HRU during the 1 year before the review date were assessed. Clinical burden and HRU were compared between patients with NAC and AC hypoparathyroidism.

Results: Of 614 patients with hypoparathyroidism (AC, N?=?442; NAC, N?=?172), the mean age was 43.6?years, and the majority were female (61.6%), Caucasian (78.8%), and had post-surgical hypoparathyroidism (74.4%). Mean duration of hypoparathyroidism was 46.0?months. Hypoparathyroidism-related symptoms and comorbidities were reported in 59.4% and 46.7% of patients, respectively; 90.7% of patients had ≥1 hypoparathyroidism-related HRU event. More patients with NAC (57.6%) vs AC (42.5%) hypoparathyroidism experienced ≥1 comorbidity including calcium/phosphate imbalances, and brain, cardiovascular, metabolic, and renal disorders (all p?<?0.01). More patients with NAC vs AC hypoparathyroidism incurred ≥1 hypoparathyroidism-related hospitalization (27.9% vs 16.3%) and emergency room visits (47.7% vs 38.5%), and patients with NAC vs AC hypoparathyroidism had a higher number of outpatient visits (3.6 vs 2.6; all p?<?0.05), in the 1-year observation period.

Limitations and conclusions: Limitations of this online chart review include possible under-estimation of disease burden, limited sample size, and the inability to rule out selection bias. Findings indicate that patients with chronic hypoparathyroidism experience substantial symptomatic and comorbid burdens resulting in frequent HRU, suggesting an unmet need, particularly in NAC disease.  相似文献   

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