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Applied Longitudinal Data Analysis Modeling Change And Event Occurrence

a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS2 index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS2 score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. Conclusion The 2 existing classification schemes and especially a new stroke risk index, CHADS2, can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation☆

Atrial fibrillation (AF) is a major public health burden worldwide, and its prevalence is set to increase owing to widespread population ageing, especially in rapidly developing countries such as Brazil, China, India, and Indonesia. Despite the availability of epidemiological data on the prevalence of AF in North America and Western Europe, corresponding data are limited in Africa, Asia, and South America. Moreover, other observations suggest that the prevalence of AF might be underestimated-not only in low-income and middle-income countries, but also in their high-income counterparts. Future studies are required to provide precise estimations of the global AF burden, identify important risk factors in various regions worldwide, and take into consideration regional and ethnic variations in AF. Furthermore, in response to the increasing prevalence of AF, additional resources will need to be allocated globally for prevention and treatment of AF and its associated complications. In this Review, we discuss the available data on the global prevalence, risk factors, management, financial costs, and clinical burden of AF, and highlight the current worldwide inadequacy of its treatment.

Global epidemiology of atrial fibrillation

TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/- )ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin-like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients.

/pdf/the-type-iv-mucolipidosis-associated-protein-trpml1-is-an-2bdpm8loz1.pdf

The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel

Objective To determine the economic impact of medication non-adherence across multiple disease groups. Design Systematic review. Evidence review A comprehensive literature search was conducted in PubMed and Scopus in September 2017. Studies quantifying the cost of medication non-adherence in relation to economic impact were included. Relevant information was extracted and quality assessed using the Drummond checklist. Results Seventy-nine individual studies assessing the cost of medication non-adherence across 14 disease groups were included. Wide-scoping cost variations were reported, with lower levels of adherence generally associated with higher total costs. The annual adjusted disease-specific economic cost of non-adherence per person ranged from $949 to $44 190 (in 2015 US$). Costs attributed to ‘all causes’ non-adherence ranged from $5271 to $52 341. Medication possession ratio was the metric most used to calculate patient adherence, with varying cut-off points defining non-adherence. The main indicators used to measure the cost of non-adherence were total cost or total healthcare cost (83% of studies), pharmacy costs (70%), inpatient costs (46%), outpatient costs (50%), emergency department visit costs (27%), medical costs (29%) and hospitalisation costs (18%). Drummond quality assessment yielded 10 studies of high quality with all studies performing partial economic evaluations to varying extents. Conclusion Medication non-adherence places a significant cost burden on healthcare systems. Current research assessing the economic impact of medication non-adherence is limited and of varying quality, failing to provide adaptable data to influence health policy. The correlation between increased non-adherence and higher disease prevalence should be used to inform policymakers to help circumvent avoidable costs to the healthcare system. Differences in methods make the comparison among studies challenging and an accurate estimation of true magnitude of the cost impossible. Standardisation of the metric measures used to estimate medication non-adherence and development of a streamlined approach to quantify costs is required. PROSPERO registration number CRD42015027338.

https://bmjopen.bmj.com/content/bmjopen/8/1/e016982.full.pdf

Economic impact of medication non-adherence by disease groups: a systematic review

Background
Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management.

/pdf/review-of-the-cost-of-venous-thromboembolism-483dxxai14.pdf

Review of the cost of venous thromboembolism.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial clinical and economic burden on the U.S. health care system. Despite national guidelines that recommend oral anticoagulation for stroke prevention, the literature consistently reports its underuse in AF patients with moderate to high stroke risk.  OBJECTIVE: To assess the economic burden of underuse and nonadherence of warfarin therapy among patients with nonvalvular AF in a commercially insured population. METHODS: Claims data between January 2003 and December 2007 from the Thomson Reuters MarketScan Research Database were used. Patients diagnosed with nonvalvular AF who were continuously enrolled for at least 12 months prior to and 2 months following their diagnosis, who had a CHADS2 score ≥2, and were not at high risk of bleeding (ATRIA score less than  5, HEMORR2HAGE score less than  4, and HAS-BLED score less than  3) at baseline were included. Patients were followed for up to 18 months after the AF diagnosis date to assess the level of warfa...

https://www.jmcp.org/doi/pdf/10.18553/jmcp.2013.19.4.302

The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective.

BACKGROUND: Bleeding is a major complication of warfarin therapy. Assessing the cost of warfarin-associated bleeding may more fully describe the costs associated with warfarin use. OBJECTIVE: To assess health care costs related to warfarin-associated bleeding in patients with newly diagnosed atrial fibrillation (AF). METHODS: Medical and pharmacy claims were analyzed for patients with AF (ICD-9-CM code 427.31) in the Medstat MarketScan database from January 2003 to December 2007. Eligible patients had no warfarin pharmacy claim or AF diagnosis in the 4 months prior to AF index date, a warfarin pharmacy claim within 30 days of AF diagnosis, and 12 months follow-up data after the index warfarin claim. Subjects were categorized based on the first type of bleeding event observed during follow-up, and only bleeding events occurring within 30 days following a warfarin claim were considered. Intracranial hemorrhage (ICH) and gastrointestinal (GI) events were assessed based on primary or secondary ICD-9-CM codes, and major GI bleeding was defined as a GI bleed associated with hospitalization. Annual total all-cause allowed charges in patients with and without bleeding events after the index warfarin claim were compared using generalized linear model (GLM) regression with gamma distribution and log link, controlling for demographics, insurance status, and comorbidities. Costs for claims with a primary or secondary diagnosis of bleeding were calculated separately. RESULTS: Of the 47,437 patients who were analyzed, 194 (0.4%) had an ICH, 919 (1.9%) had a major GI bleed, and 1,804 (3.8%) had a minor GI bleed within 30 days after a warfarin claim during follow-up. Compared with patients who had no bleeding events after a warfarin claim (n = 44,520, 93.9%) during the study period, patients with at least 1 bleeding event were older and had more comorbidities (P < 0.01). Patients with at least 1 ICH or major GI bleed had more all-cause hospitalizations (P < 0.05) and hospital days (P < 0.01) than patients without bleeding events. Patients with at least 1 ICH, major GI bleed, or minor GI bleed had more all-cause emergency room visits (P < 0.01) than patients without bleeding events. Mean (SD) unadjusted all-cause health care costs in the 12 months after the warfarin index claim were $41,903 ($56,654), $40,586 ($65,164), and $24,347 ($56,488) for patients with at least 1 ICH, major GI bleed, and minor GI bleed, respectively, compared with $24,129 ($36,425) for patients with no bleeding events. Claims with a primary or secondary diagnosis of bleeding accounted for 49.6%, 30.2%, and 2.6% of annual cost in patients with ICH, major GI bleeding, and minor GI bleeding, respectively. On average, 50.9%, 33.5%, and 10.8% of annual all-cause costs occurred within 30 days after the first ICH, major GI bleeding event, and minor GI bleeding event, respectively. GLM regression showed that annual all-cause costs were 64.4% and 49.0% higher (P < 0.001) for patients with ICH and major GI bleeding, respectively, than for patients with no bleeding events. CONCLUSION: ICH and major GI bleeding associated with warfarin therapy are rare but costly.

https://www.jmcp.org/doi/pdf/10.18553/jmcp.2011.17.9.672

All-Cause and Bleeding-Related Health Care Costs in Warfarin-Treated Patients with Atrial Fibrillation

Background Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA).

Methods and Results A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23 807 AF patients and 136 649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20 933 for IS, $59 054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P <0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs.

Conclusion Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

/pdf/impact-of-atrial-fibrillation-on-stroke-related-healthcare-sg177r82lj.pdf

Impact of Atrial Fibrillation on Stroke-Related Healthcare Costs

Background:The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient char...

https://journals.sagepub.com/doi/pdf/10.1177/2050312115613350

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2

Winghan Jacqueline Kwong

Papers

Review of the cost of venous thromboembolism.

The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective.

All-Cause and Bleeding-Related Health Care Costs in Warfarin-Treated Patients with Atrial Fibrillation

Impact of Atrial Fibrillation on Stroke-Related Healthcare Costs

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2