ABSTRACT
BACKGROUND: The prespecified on-treatment analysis of ASCEND-ND (NCT02876835) raised concerns about a higher relative risk of cancer-related adverse events (AEs) with daprodustat vs darbepoetin in patients with anaemia of CKD. This concern was not observed in dialysis patients in ASCEND-D (NCT02879305). METHODS: ASCEND-ND randomized 3872 patients to daprodustat or darbepoetin. ASCEND-D randomized 2964 patients to daprodustat or conventional erythropoiesis-stimulating agents (ESAs). In both studies ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). The prespecified on-treatment approach examined relative risks for cancer AEs up to the last dose date + 1 day. In these analyses, owing to different dosing intervals between arms, Cox models were used to estimate the daprodustat effect by various follow-up periods (censoring at last dose date, last dose date + dosing intervals, or end of study). RESULTS: In ASCEND-ND, the safety of daprodustat vs darbepoetin on cancer-related AEs depended on the duration of follow-up after last dose date: hazard ratio (HR) 1.04 [95% confidence interval (CI) 0.77, 1.40] at end of study [HR 1.12 (95% CI 0.81, 1.56) for last dose date + dosing interval; HR 1.50 (95% CI 1.04, 2.15) for last dose date + 1 day]. In ASCEND-D, no excess risk of cancer-related AEs was observed with any model examined. CONCLUSIONS: Prespecified on-treatment analyses for cancer-related AEs appeared to result in biased risk estimates in ASCEND-ND by preferentially under-counting events from patients assigned to darbepoetin. Analyses accounting for longer darbepoetin dosing intervals, or extending follow-up, resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D, where ESA comparator dosing intervals are closer to daprodustat. TRIAL REGISTRATION: The ASCEND-ND trial is registered with ClinicalTrials.gov (NCT02876835); the ASCEND-D trial is registered with ClinicalTrials.gov (NCT02879305).
Subject(s)
Erythropoietin , Hematinics , Neoplasms , Renal Insufficiency, Chronic , Humans , Hematinics/adverse effects , Erythropoietin/adverse effects , Erythropoiesis , Renal Dialysis , Darbepoetin alfa/adverse effects , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/chemically induced , Renal Insufficiency, Chronic/drug therapy , HemoglobinsABSTRACT
Aim: This retrospective chart review was designed to evaluate physician adherence to the prescribing information for fondaparinux regarding adjunctive anticoagulant use during percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome (ACS). Methods and results: Medical record abstractors at each site obtained information regarding the use of fondaparinux and adjunctive anticoagulants during PCI. Physician adherence to fondaparinux prescribing information regarding the administration of an adjunctive anticoagulant during PCI was estimated using generalized estimating equations. This retrospective study, conducted in 2008-2010, included a total of 1056 patient records from 27 sites across 6 countries (Canada, France, Germany, Greece, Poland, and Sweden). Over 98% of patients had been treated with fondaparinux at the recommended 2.5 mg dose. Use of adjunctive anticoagulant during PCI was 97.5%, giving an adjusted adherence rate of 98.8% (95% confidence interval: 0.97-0.99), with 86.3% of patients receiving unfractionated heparin. Although the sub-group of patients with ST-elevation myocardial infarction who underwent primary PCI was too small to make a definitive conclusion, 70.4% of the 159 patients did not receive fondaparinux immediately prior to (<24 h) or during primary PCI, suggesting that their treating physicians may have been adherent to the prescribing information. Conclusion: Physician adherence to the prescribing information for adjunctive anticoagulation during PCI in patients with an ACS receiving fondaparinux was high. The results were consistent in each of the six countries and across patient sub-groups.
Subject(s)
Acute Coronary Syndrome/therapy , Anticoagulants/therapeutic use , Factor Xa Inhibitors/therapeutic use , Fondaparinux/therapeutic use , Percutaneous Coronary Intervention , Practice Patterns, Physicians'/standards , ST Elevation Myocardial Infarction/therapy , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Adult , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Canada , Europe , Factor Xa Inhibitors/adverse effects , Female , Fondaparinux/adverse effects , Guideline Adherence/standards , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Practice Guidelines as Topic/standards , Product Surveillance, Postmarketing , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , Treatment OutcomeABSTRACT
This article explains the components of disability as related to rheumatoid arthritis (RA) using an expansion of Nagi's Model of Disability (Jette, 2006) and the World Health Organization's (WHO) International Classification of Functioning, Disability, and Health (ICF). In addition, suggestions for ways in which nurses can offer patients choices in physical functional therapy and psychosocial aspects of coping with the chronicity of RA are discussed. Understanding how RA relates to the holistic management of the patient will allow nurses to modify and suggest additional measures to enhance the outcomes of patient-centered care. Many degrees of disability exist that affect the physical and psychosocial domains of RA. Nurses should identify the primary issues influencing disability and assemble supporting resources or a multidisciplinary team to manage a person's disabilities. As nurses develop and maintain relationships with patients, they are able to follow through with the care plan continuum and recognize when modifications are needed.
