Healthcare Resource Utilization and Cost Burden of BCG-Treated Non-Muscle Invasive Bladder Cancer Patients in Germany: A Retrospective Claims Analysis.

Background: Intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) is typically managed with transurethral resection of the bladder tumour (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy; however, NMIBC patients can become refractory or unresponsive to BCG treatment, and/or progress to muscle-invasive bladder cancer (MIBC). Healthcare resource utilization (HCRU) and costs in these patient populations are high. Methods: A retrospective longitudinal cohort design of adult (≥18 years) patients with bladder cancer and BCG treatment (01/01/2012-31/12/2017) was conducted using data from a representative subset of the German statutory health insurance database. During the follow-up period after last BCG, patients were categorized into subgroups of No further NMIBC treatment, Continuous treatment for NMIBC, or MIBC evidence; HCRU and costs were tabulated for each subgroup and for the entire cohort. Results: A total of 1049 patients met the study inclusion criteria (mean age, 70.9 years; 84.8% male). Across the different subgroups, patients showing MIBC evidence had more than two times higher hospitalization rates compared to the other subgroups. Overall, the entire BCG-treated cohort's total direct medical cost including hospitalizations, outpatient care and drugs was €33.9 million and €9250 per patient-year. Cost for patients with MIBC evidence was much higher, at €17,983 per patient-year, than patients with No further NMIBC treatment (€6617) and patients with Continuous treatment for NMIBC (€7786). Across the subgroups, hospitalization was the largest driver of cost and contributed the most to cost for those with MIBC evidence. Conclusion: The overall cost burden of this BCG-treated cohort of 1049 patients is high (€38 million whereof 4.1 million are indirect costs) over a mean follow-up of 3.9 years; economic burden is especially substantial for patients who fail BCG treatment and those who progress.

Direct Oral Anticoagulant (DOAC) Dosing in Patients with Non-valvular Atrial Fibrillation (NVAF) in the United Kingdom: A Retrospective Cohort Study Using CPRD Gold Database.

INTRODUCTION: Per-label dosing of direct oral anticoagulants (DOACs) is important for the prevention of stroke and systemic embolism among patients with non-valvular atrial fibrillation (NVAF), especially those with poor renal function, advanced age, low body weight or concomitant P-glycoprotein inhibitors. The study described DOAC use and dosing patterns in patients with NVAF in the UK. METHODS: Using Clinical Practice Research Datalink (CPRD Gold), patients' profiles were described at DOAC initiation (1 January 2016-31 March 2021) and followed for a mean [standard deviation (SD)] 2 (1) years. Patients were categorised as under-dosing: received a lower dose with no indication for a reduced dose; over-dosing: received a standard dose with an indication for a reduced dose; per-label dosing, according to Summary Product Characteristics (SmPC). RESULTS: Forty thousand seven hundred forty-four adult patients with NVAF were identified (mean age: 75.3 (11.2) years; males: 55.4%); 22,827 (56.0%) initiated treatment with apixaban, 930 (2.3%) dabigatran, 5633 (13.8%) edoxaban and 11,354 (27.9%) rivaroxaban. Baseline Charlson comorbidity index ≥ 4 was 65.1%; CHA2DS2-VASc score ≥ 4 was 22.5%; HAS-BLED score ≥ 3 was 18.3%; ~ 2% had prior major bleed and 4.4% a stroke ≤ 2 years before DOAC initiation. Overall, 18.0% of patients received incorrect dosing (~ one in five). Under-dosing was highest for dabigatran (156, 16.8%) and over-dosing was highest for rivaroxaban (1084, 9.6%). Per-label dosing was highest for edoxaban (4773, 84.7%), followed by apixaban (18,756, 82.2%), rivaroxaban (9161, 80.7%) and dabigatran (732, 78.7%). Treatment persistence (no switching or discontinuation) was 79% among edoxaban users, followed by 75% for apixaban, 69% for rivaroxaban and 62% for dabigatran. About 15% of dabigatran users, 10% of rivaroxaban users, 5% of apixaban users and 4% of edoxaban users switched treatment to another DOAC during follow-up. CONCLUSION: Although most patients received per-label dosing, ~ one in five patients was incorrectly dosed with DOAC, which may lead to serious clinical consequences and increased healthcare burden.

Incidence of adult primary immune thrombocytopenia in England-An update.

BACKGROUND: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause. Recent estimates of its incidence and trend over time were acquired for England. METHOD: The primary ITP population (using ICD 10 code D693 and excluding secondary ITP cases; positive predictive value: 82.6%) was sourced from NHS Digital inpatient and outpatient. Incidence rate (IR) for England and by age groups, sex, and regions were calculated and trends were assessed using average annual percent change (AAPC). RESULTS: A total of 25 805 patients (mean age 59 years; females 57.8%) diagnosed between 2003 and 2014 was identified. IRs increased from 4.2/100 000 to 6.4/100 000 over this period (AAPC:4.3%). For all sex-specific age groups, the IRs significantly increased over time, except 18-29 years males. The greatest increase was among females aged 30-39 (AAPC:8.7%). In contrast, among ≥70 years, ITP was more common in males (highest IR among ≥80 years males: 23.9/100 000). England's average annual IR was 6.1/100 000 for 2010-14. An estimated 2.5/100 000 (based on UKITP Registry data) was estimated to require 1st line treatment whereas 2.4/100 000 would have 1st and 2nd line treatments within 6 months from diagnosis. IRs for London and East Midlands were the highest (6.5/100 000). CONCLUSIONS: This study found a rising incidence of primary ITP, with sharp increases among young women and elderly men. These findings put in context the impact of ITP on patients' lives and the healthcare services in England, especially with 17%-50% who may develop chronic ITP and require long-term care.

Fractures in untreated patients with osteoporosis in Germany: an InGef healthcare insurance database analysis.

Osteoporosis is a skeletal disease that may result in low-trauma fracture if untreated. Among men and women ≥ 70 years untreated for osteoporosis, 30% (43,514) sustained at least one post-index fracture. Care for patients with osteoporosis diagnosis directly contributed to a cost burden of €786 million. INTRODUCTION: Osteoporosis is a skeletal disease that manifests as bone mineral density loss and low-trauma fractures. This database analysis describes the characteristics of untreated osteoporosis patients, and their rate of fractures, health resource utilization, and cost burden. METHODS: From the InGef database (2011-2016), eligible patients (≥ 70 years) untreated for osteoporosis were identified via a recorded diagnosis of osteoporosis (ICD-10 codes M80/M81) or an initial fragility fracture (index point). All patients were followed up for fractures post index. Direct costs included inpatient, outpatient, pharmacy, and ancillary care costs. RESULTS: A total of 144,752 patients (mean age 79 years; 73% female, median follow-up of 3.2 years) met the eligibility criteria; 23% had a history of fractures. Forty-eight percent of patients had cardiac diseases, 32% diabetes, and 27% cerebrovascular disease. Thirty percent (43,514) of patients had at least one post-index fracture; two or more post-index fractures were experienced in 7% (10,262) of patients. Median time from index date to first fracture was 145.5 days. Bisphosphonates were the most prescribed osteoporosis treatment following a first fracture post-index (n = 4102, 9.2%). There was a total of 107,055 patients (74.0%) who had at least one all-cause hospital stay. The total number of fracture-related admissions was 63,595 and that of outpatient visits was 323,460. A total of 34,764 (24%) patients died during follow-up. Costs for fracture-related care for patients directly contributed to a cost burden of €786 million. CONCLUSIONS: Osteoporosis patients and patients who sustain a fragility fracture remain undertreated for osteoporosis, increasing their risk of future fractures. Diagnosing and treating this group of patients should remain a priority to alleviate the clinical and economic burden of osteoporosis-related fractures.

Primary immune thrombocytopenia (ITP) treated with romiplostim in routine clinical practice: retrospective study from the United Kingdom ITP Registry.

BACKGROUND: Romiplostim is a thrombopoietin-mimetic peptibody for adult refractory chronic immune thrombocytopenia (ITP). We aimed to describe ITP patients receiving romiplostim, platelet counts and romiplostim usage in UK clinical practice. METHODS: This was a retrospective cohort study of patients in the UKITP Registry who received romiplostim between October 2009 and January 2015, including data up to 6 months before romiplostim initiation through follow-up. RESULTS: Of 1440 patients in the UKITP Registry, 118 adults with primary ITP were eligible. Before romiplostim, 22% had splenectomy, 12% received platelet transfusion, 97% received ≥ 1 different ITP medication and 77% received ≥ 3. Most patients (73%) initiated romiplostim ≥ 1 year after ITP diagnosis (chronic phase). The mean duration of romiplostim treatment was 5.7 (SE 0.9) months, and the median was 1.4 months (IQR: 0.2, 6.5). Mean platelet count before romiplostim was 38 × 109 /L, rising to 103 × 109 /L within 1 month, and remaining 50-150 × 109 /L through up to 3 years of follow-up. After romiplostim, 4% of patients had splenectomy, 6% received platelet transfusion, and 57% received just one ITP medication other than romiplostim. CONCLUSION: The study provides valuable insights into the real-world use of romiplostim in primary ITP in routine practice and highlighted the timing of romiplostim initiation at different ITP disease phases.

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis.

Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies.

Variation of lipoprotein associated phospholipase A2 across demographic characteristics and cardiovascular risk factors: a systematic review of the literature.

BACKGROUND: Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III clinical trials of vascular disease prevention. We assessed in a variety of different population settings variation of Lp-PLA(2) mass and activity across gender, ethnicity, diabetes, kidney disease and metabolic syndrome. We also assessed correlations with measures of circulating lipids, systemic inflammation and adiposity. METHODS: Systematic review of studies measuring Lp-PLA(2) and at least one of the relevant characteristics in >50 participants. RESULTS: We identified a total of 77 studies involving 102,499 participants meeting the inclusion criteria. Lp-PLA(2) mass and activity were consistently approximately 10% higher in males than females and 15% higher in Caucasians than African Americans or Hispanics. There were no clear associations of Lp-PLA(2) mass or activity with type II diabetes, markers of systemic inflammation (C-reactive protein, fibrinogen) or with body mass index. Correlations of Lp-PLA(2) mass or activity with low density lipoprotein cholesterol and apolipoprotein B were moderate and positive, whilst correlations with high density lipoprotein cholesterol were negative and moderate to weak. There was no clear differences in associations with any of the above characteristics in groups defined based upon prevalent cardiovascular disease or its risk factors. CONCLUSIONS: Despite considerable variability in absolute levels of Lp-PLA(2) across studies, the variability of Lp-PLA(2) across gender, ethnicity, and levels of circulating lipids and markers of systemic inflammation are more consistent and appear not to vary importantly across categories defined by CVD or its risk factors.

Head and neck cancer in South East England between 1995-1999 and 2000-2004: An estimation of incidence and distribution by site, stage and histological type.

Population-based data on head and neck cancer (HNC) stage and histological type are poorly described for England; these data are essential for clinical management and research. The aim of this study was to describe the distribution and incidence of all HNC and selected anatomical sites by sex, age, stage and histological type using a population-based cancer registry in South East England, and determine if the incidence changed between 1995-1999 and 2000-2004. We identified all HNC cancer cases registered by the Thames Cancer Registry for 1995-1999 and 2000-2004. Frequency distributions and age-standardised incidence rates were calculated by sex, age, stage and histological type and trends in incidence between the two time periods were described using incidence rate ratios and 95% confidence intervals. A total of 8700 HNC cases were reported in 2000-2004, representing an age-standardised incidence rate of 8.59 per 100000, which did not change significantly from 1995-1999. The three commonest HNC sites were intra-oral cavity, larynx and tonsil. Males were two to six times as likely as females to be diagnosed with HNC and there was a trend toward younger age at diagnosis over time. Significant increases in the incidence rate of intra-oral cavity cancer for both sexes and tonsillar cancer among males were observed. Conversely, laryngeal cancer incidence decreased over time. Staging data was only available for about 40% of HNC cases. Seventy six percent of HNC cases were squamous cell carcinomas. Trends in incidence varied between HNC sites, highlighting the importance of presenting data for individual HNC sites. The high proportion of unstaged cancers may result from incomplete recording in medical records; thus, the reporting of staging data should be made a priority.