Abir O. Kanaan

Adverse Drug Events After Hospital Discharge in Older Adults: Types, Severity, and Involvement of Beers Criteria Medications

To characterize adverse drug events (ADEs) occurring within the high‐risk 45‐day period after hospitalization in older adults.

A Polypill for all? Critical Review of the Polypill Literature for Primary Prevention of Cardiovascular Disease and Stroke

Objective: To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke. Data Sources: A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified. Bibliographies of pertinent review articles and studies were scanned for additional references. A similar search was conducted to identify literature related to the use of polypill components for primary prevention of CVD and stroke. Study Selection and Data Extraction: Studies that evaluated the hypothetical benefits of a polypill and controlled trials that assessed a formulation of the polypill related to prevention of CVD and stroke were included. Studies were assessed for efficacy, safety, drug interactions, and clinical pharmacokinetics. Data Synthesis: An initial study to predict benefit estimated that a hypothetical polypill would reduce diastolic blood pressure by 11 mm Hg and low-density lipoprotein cholesterol (LDL-C) by 70 mg/dL, thus reducing the relative risks of CVD and stroke by 68% and 80%, respectively. One clinical trial in patients at low risk for CVD and stroke found that diastolic Wood pressure was reduced by 1.6 mm Hg and LDL-C was reduced by 17.7 mg/dL, correlating with 44% and 21% reduction in the relative risks of CVD and stroke, respectively. Studies in higher risk patients reported reductions in systolic blood pressure of up to 28.8 mm Hg and in LDL-C of up to 54 mg/dL, correlating with 62% and 60% relative reduction in risks of CVD and stroke, respectively. Conclusions: Polypill study results have been more modest than originally theorized. However, results show promise in patients at higher risk for CVD and stroke.

Mixed treatment comparison meta-analysis of aspirin, warfarin, and new anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation.

BACKGROUND Warfarin and aspirin are used to prevent stroke in patients with atrial fibrillation (AF). There are inherent challenges with both treatments, including variable and inconsistent benefit and increased bleeding risks. The availability of new anticoagulants offers some alternatives. OBJECTIVE A mixed treatment comparison meta-analysis to evaluate direct and indirect treatment data including aspirin, warfarin apixaban, dabigatran, edoxaban, and rivaroxaban for the prevention of primary or secondary stroke in patients with AF. METHODS A comprehensive, systematic literature search was conducted to identify randomized trials comparing aspirin, warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban in patients with AF requiring treatment for stroke prevention. Open-label and blinded designs were included if they evaluated any stroke or any bleeding event. Data on stroke and bleeding events were abstracted, verified, evaluated, scored, and entered into Aggregate Data Drug Information System version 1.16 to generate a mixed treatment comparison meta-analysis. Direct and indirect comparisons were evaluated, and we looked for inconsistency in closed loop structures. Data are reported as rate ratios with 95% credible intervals. In addition, we reviewed variance statistics and explored variance with node-splitting models. RESULTS Our literature search yielded 30 articles, 21 of which were included. All treatments except aspirin reduced the risk of any stroke compared with placebo. Warfarin (0.43 [0.33-0.57]), apixaban (0.37 [0.27-0.54]), dabigatran (0.34 [0.21-0.57]), rivaroxaban (0.36 [0.22-0.60]), and aspirin with clopidogrel (0.73 [0.53-0.99]) were more protective than aspirin alone. Warfarin and the new anticoagulants were similar in the reduction of stroke, vascular death, and mortality. There was no difference in major bleeding between any treatment group. There were more nonmajor bleeding events when comparing warfarin and apixaban (1.83 [1.05-4.03]); no other differences between warfarin and the other new anticoagulants were found. CONCLUSIONS This mixed treatment comparison meta-analysis found similarity between warfarin and the new anticoagulants with the exception of one comparison, in which warfarin was associated with more non-major bleeding than apixaban. Thus, the new anticoagulants are therapeutically comparable when warfarin is inappropriate.

Evaluation of Antiplatelet Agents for Secondary Prevention of Stroke Using Mixed Treatment Comparison Meta-analysis

BACKGROUND The current guidelines recommend various antiplatelet agents used alone or in combination for secondary prevention of noncardioembolic stroke. OBJECTIVE The purpose of this study was to conduct a mixed treatment comparison meta-analysis to determine which antiplatelet or combination of antiplatelet agents is most efficacious and tolerable in patients with prior stroke. METHODS A comprehensive literature search was conducted in MEDLINE (1945 through March 2012), EMBASE (1974 through March 2012), and the Cochrane Controlled Trials Registry (1975 through April 2012) to identify randomized trials evaluating the role of various antiplatelet agents and combinations for the secondary prevention of stroke. Key articles were cross-referenced for additional studies. Data were screened and evaluated to generate direct and indirect comparisons for recurrent stroke and overall hemorrhagic events. Data were reported as rate ratios (RRs) and 95% CIs. RESULTS A total of 24 articles were included in the analysis. Eleven antiplatelet regimens were compared in >88,000 patients. The combination of acetylsalicylic acid (ASA) plus dipyridamole (DP) was more protective against recurrent stroke than ASA alone (RR = 0.78; 95% CI, 0.64-0.93), and no differences were found in all other direct and indirect comparisons with active treatment. ASA plus DP was associated with more overall hemorrhagic events than DP (RR = 1.83; 95% CI, 1.17-2.81), cilostazol (RR = 2.12; 95% CI, 1.21-3.48), and triflusal (RR = 1.67; 95% CI, 1.05-2.78) but fewer events than the combination of ASA plus clopidogrel (RR = 0.38; 95% CI, 0.25-0.56). The combination of ASA plus clopidogrel was associated with an excess of overall hemorrhagic events compared with clopidogrel (RR = 2.81; 95% CI, 1.96-4.10), cilostazol (RR = 5.56; 95% CI, 3.03-9.66), DP (RR = 4.78; 95% CI, 2.80-8.21), sarpogrelate (RR = 3.59; 95% CI, 1.96-6.45), terutroban (RR = 2.13; 95% CI, 1.21-3.61), ticlopidine (RR = 2.80; 95% CI, 1.69-5.00), and triflusal (RR = 4.36; 95% CI, 2.62-7.81). CONCLUSION We found that ASA plus DP was more protective than ASA alone for preventing recurrent stroke; however, no difference was found between most direct and indirect comparisons of antiplatelet agents and combinations. More overall hemorrhagic events seemed to occur with the combination of ASA and clopidogrel than with other treatments. Selection of antiplatelet therapy for the secondary prevention of stroke must be individualized according to patient comorbidities, including risk of stroke recurrence and bleeding.

An electronic health record-based intervention to increase follow-up office visits and decrease rehospitalization in older adults

To assess the effect of an electronic health record–based transitional care intervention involving automated alerts to primary care providers and staff when older adults were discharged from the hospital.

Evaluating the Role of Compression Stockings in Preventing Post thrombotic Syndrome: A Review of the Literature

Background. Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT). Up to 50% of patients with DVT will develop the disease within two years following the diagnosis of acute DVT. Various risk factors for developing PTS have been identified and different modalities have been used to prevent its development. Compression stockings have been studied for the prevention of PTS in patients diagnosed with proximal DVT. Methods. MEDLINE and EMBASE databases were searched to identify relevant original articles. Results. Several trials including two metaanalyses have examined the role of compression stockings for the prevention of PTS. Although most trials showed significant reduction in the development of PTS with the use of compression stockings, limitations in study design prevent the generalizability of the data. Two studies supported an individualized tailored duration especially in patients at low risk for developing the syndrome. A randomized double-blind placebo-controlled trial involving 800 patients is currently ongoing and may confirm the results of older studies. Conclusions. Clinical trials support the use of compression stockings in patients diagnosed with proximal DVT for the prevention of PTS.

Heparin-induced thrombocytopenia in the pediatric population: a review of current literature

Heparin-induced thrombocytopenia is a rare and serious reaction to unfractionated heparin and low-molecular-weight heparins in children. Quick recognition, discontinuation of heparin, and subsequent treatment with an alternative anticoagulant are essential steps to prevent serious complications such as thrombus and limb amputation. The purpose of this review is to describe the clinical features of heparin-induced thrombocytopenia in children and to summarize the data available for its management. This paper summarizes data and relates the use of direct thrombin inhibitors with clinical outcomes. A literature search was conducted with Ovid, using the key terms argatroban, bivalirudin, hirulog, danaparoid, lepirudin, direct thrombin inhibitor, heparin-induced thrombocytopenia, thrombosis, warfarin, and fondaparinux. Articles were excluded if they were classified as editorials, review articles, or conference abstracts or if they involved patients 18 years of age or older or described disease states not related to thrombosis. Nineteen articles containing 33 case reports were identified and evaluated for this review. Of the 33 cases, 14, 10, 4, and 2 cases described the use of lepirudin, danaparoid, argatroban, and bivalirudin, respectively. Two cases did not report the type of anticoagulant used, and 1 case used aspirin. The most commonly reported complication was bleeding.

Dissemination of Evidence-Based Antipsychotic Prescribing Guidelines to Nursing Homes: A Cluster Randomized Trial.

To evaluate the effectiveness of efforts to translate and disseminate evidence‐based guidelines about atypical antipsychotic use to nursing homes (NHs).

Antipsychotic use in nursing homes varies by psychiatric consultant

Background:The relationship between psychiatric consultation and antipsychotic prescribing in nursing homes (NH) is unknown. Objective:To identify the association between psychiatric consultant groups and NH-level antipsychotic prescribing after adjustment for resident case-mix and facility characteristics. Research Design and Subjects:Nested cross-sectional study of 60 NHs in a cluster randomized trial. We linked facility leadership surveys to October 2009–September 2010 Minimum Data Set, Nursing Home Compare, the US Census, and pharmacy dispensing data. Measures:The main exposure is the psychiatric consultant group and the main outcome is NH-level prevalence of atypical antipsychotic use. We calculated annual means and interquartile ranges of NH-level antipsychotic use for each consultant group and arrayed consultant groups from lowest to highest prevalence. Generalized linear models were used to predict antipsychotic prescribing adjusting for resident case-mix and facility characteristics. Observed versus predicted antipsychotic prescribing levels were compared for each consultant group. Results:Seven psychiatric consultant groups served a range of 3–27 study facilities. Overall mean facility-level antipsychotic prescribing was 19.2%. Mean prevalence of antipsychotic prescribing ranged from 12.2% (SD, 5.8) in the lowest consultant group to 26.4% (SD, 3.6) in the highest group. All facilities served by the highest-ranked consultant group had observed antipsychotic levels exceeding the overall study mean with half exceeding predictions for on-label indications, whereas most facilities served by the lowest-ranked consultant group had observed levels below the overall study and predicted means. Conclusions:Preliminary evidence suggests that psychiatric consultant groups affect NH antipsychotic prescribing independent of resident case-mix and facility characteristics.

Multisite parent-centered risk assessment to reduce pediatric oral chemotherapy errors.

PURPOSE Observational studies describe high rates of errors in home oral chemotherapy use in children. In hospitals, proactive risk assessment methods help front-line health care workers develop error prevention strategies. Our objective was to engage parents of children with cancer in a multisite study using proactive risk assessment methods to identify how errors occur at home and propose risk reduction strategies. METHODS We recruited parents from three outpatient pediatric oncology clinics in the northeast and southeast United States to participate in failure mode and effects analyses (FMEA). An FMEA is a systematic team-based proactive risk assessment approach in understanding ways a process can fail and develop prevention strategies. Steps included diagram the process, brainstorm and prioritize failure modes (places where things go wrong), and propose risk reduction strategies. We focused on home oral chemotherapy administration after a change in dose because prior studies identified this area as high risk. RESULTS Parent teams consisted of four parents at two of the sites and 10 at the third. Parents developed a 13-step process map, with two to 19 failure modes per step. The highest priority failure modes included miscommunication when receiving instructions from the clinician (caused by conflicting instructions or parent lapses) and unsafe chemotherapy handling at home. Recommended risk assessment strategies included novel uses of technology to improve parent access to information, clinicians, and other parents while at home. CONCLUSION Parents of pediatric oncology patients readily participated in a proactive risk assessment method, identifying processes that pose a risk for medication errors involving home oral chemotherapy.