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Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF).We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively.Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA₂DS₂-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA₂DS₂-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1).Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Aim There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear. Methods Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight. Results Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03). Conclusion Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.

Drug discovery for disease‐modifying therapies for Alzheimer's disease and related dementias (ADRD) based on the traditional paradigm of experimental animal models has been disappointing. We describe the rationale and design of the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study, an innovative multidisciplinary alternative to traditional drug discovery. First, we use a systems biology perspective in the "hypothesis generation" phase to identify metabolic abnormalities that may either precede or interact with the accumulation of ADRD neuropathology, accelerating the expression of clinical symptoms of the disease. Second, in the "hypothesis refinement" phase we propose use of large patient cohorts to test whether drugs approved for other indications that also target metabolic drivers of ADRD pathogenesis might alter the trajectory of the disease. We emphasize key challenges in population‐based pharmacoepidemiologic studies aimed at quantifying the association between medication use and ADRD onset and outline robust causal inference principles to safeguard against common pitfalls. Candidate ADRD treatments emerging from this approach will hold promise as plausible disease‐modifying therapies for evaluation in randomized controlled trials.

Purpose In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc analyses of clinical trials suggested an increased risk of heart failure with the use of these products. As such, we assessed disproportionate reporting of major adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015. Methods We assessed the empirical Bayes geometric mean (EBGM) and its lower bound (EB05) of the relative reporting ratio for MACE among DPP-4i reports in the full FAERS database and in a subset of reports limited to cardiovascular and diabetic drugs. We then compared the EB05 in these 2 analyses and calculated the percent positive agreement for signals of disproportional reporting (SDRs) involving MACE. Results Of 180.3 million adverse event reports, 13.4 million were for diabetic and cardiovascular drugs. In the cardiovascular subset, there was an SDR for heart failure with linagliptin (EB05 = 2782.47) and saxagliptin (EB05 = 2.40), myocardial infarction with alogliptin (EB05 = 290.11), and cerebral infarction with sitagliptin (EB05 = 2.80). Of the 14 MACE, 8 had a percent positive agreement ≥50% for an SDR in both analyses. Overall, the cardiovascular subset elicited 11 more SDRs for DPP-4i than the full dataset. Conclusions Postmarketing surveillance of DPP-4i through FAERS suggest increased reporting of MACE, supporting the current FDA warning of heart failure risk. This suggests the need for additional longitudinal, observational research into the association of DPP-4i and other MACE.

Objective To examine the use of antimuscarinics for treating urinary incontinence (UI) in older adults with varying levels of cognition. Design Cross-sectional. Setting National Alzheimer's Coordinating Center from 2005 through 2015. Participants Community-dwelling men and women aged 65 and older (N = 24,106). Measurements Clinicians and staff evaluated each participant's dementia status during annual in-person assessments. Participants or their informants reported all medications taken in the 2 weeks before each study visit. Results Overall, 5.2% (95% confidence interval (CI) = 4.9–5.5%) of the cohort took a bladder antimuscarinic. Participants with impaired cognition were more likely to be taking an antimuscarinic than those with normal cognition. Rates of bladder antimuscarinic use were 4.0% (95% CI = 3.6–4.4%) for participants with normal cognition, 5.6% (95% CI = 4.9–6.3%) for those with mild cognitive impairment, and 6.0% (95% CI = 5.5–6.4%) for those with dementia (p < .001). Of 624 participants with dementia who took antimuscarinics, 16% (95% CI = 13–19%) were simultaneously taking other medicines with anticholinergic properties. Conclusion Use of bladder antimuscarinics was more common in older adults with impaired cognition than in those with normal cognition. This use is despite guidelines advising clinicians to avoid prescribing antimuscarinics in individuals with dementia because of their vulnerability to anticholinergic-induced adverse cognitive and functional effects. A substantial proportion of cognitively impaired individuals who took antimuscarinics were simultaneously taking other anticholinergic medications. These findings suggest a need to improve the treatment of UI in individuals with impaired cognition.

Objectives To quantify prescription analgesic use of elderly nursing home (NH) residents with persistent noncancer pain and to identify individual and facility traits associated with no treatment. Design Cross-sectional study. Setting Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. Participants Individuals aged 65 and older with persistent noncancer pain were identified from a cross-section of all long-stay U.S. NH residents with an MDS assessment and Medicare Part D enrollment in 2008, excluding those who were terminally ill, those with Alzheimer's disease, and those with the most-severe cognitive impairment. Measurements Residents with moderate to severe daily pain on consecutive assessments at least 90 days apart constituted the cohort with persistent pain. Part D dispensing for an opioid or nonsteroidal anti-inflammatory drug (NSAID) within 30 days of persistent pain onset was identified. Information on resident and facility characteristics was obtained from MDS and OSCAR records. Associations between resident and facility attributes and pain treatment were estimated using multilevel mixed-effects logistic regression analyses. Results Of the study sample of 18,526 residents with persistent pain, 3,094 (16.7%) did not receive prescription analgesics, 12,815 (69.2%) received a prescription opioid, 485 (2.6%) received a prescription NSAID, and 2,132 (11.5%) received a prescription opioid and NSAID. After adjusting for potentially confounding covariates, residents who were older (≥95, odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.70–2.49), more cognitively impaired (moderately severe cognitive impairment, OR = 2.12, 95% CI = 1.71–2.62), or black (OR = 1.20, 95% CI = 1.03–1.39) or Asian (OR = 1.97, 95% CI = 1.22–3.20) were less likely to receive a prescription analgesic. Conclusion Through 2008, pain remained undertreated in NHs, especially in certain subpopulations, including cognitively impaired and older residents. Changes in pain management practice and policies may be necessary to target these vulnerable residents.

Previous reviews of childhood obesity prevention have focused largely on schools and findings have been inconsistent. Funded by the US Agency for Healthcare Research and Quality (AHRQ) and the National Institutes of Health, we systematically evaluated the effectiveness of childhood obesity prevention programmes conducted in high-income countries and implemented in various settings. We searched MEDLINE®, Embase, PsycINFO, CINAHL®, ClinicalTrials.gov and the Cochrane Library from inception through 22 April 2013 for relevant studies, including randomized controlled trials, quasi-experimental studies and natural experiments, targeting diet, physical activity or both, and conducted in children aged 2–18 in high-income countries. Two reviewers independently abstracted the data. The strength of evidence (SOE) supporting interventions was graded for each study setting (e.g. home, school). Meta-analyses were performed on studies judged sufficiently similar and appropriate to pool using random effect models. This paper reported our findings on various adiposity-related outcomes. We identified 147 articles (139 intervention studies) of which 115 studies were primarily school based, although other settings could have been involved. Most were conducted in the United States and within the past decade. SOE was high for physical activity-only interventions delivered in schools with home involvement or combined diet–physical activity interventions delivered in schools with both home and community components. SOE was moderate for school-based interventions targeting either diet or physical activity, combined interventions delivered in schools with home or community components or combined interventions delivered in the community with a school component. SOE was low for combined interventions in childcare or home settings. Evidence was insufficient for other interventions. In conclusion, at least moderately strong evidence supports the effectiveness of school-based interventions for preventing childhood obesity. More research is needed to evaluate programmes in other settings or of other design types, especially environmental, policy and consumer health informatics-oriented interventions.

Purpose The purpose of this study was to evaluate the impact of switching from branded to generic statins on medication compliance. Methods In this historic cohort study, we identified patients taking branded statins between January 2003 and December 2012 from Sutter Health's electronic health records in Northern California. Patients with ≥2 consecutive pharmacy claims for generic statins after initiating branded statins were classified as switchers. Switchers and non-switchers were matched 1:1 on the propensity for switching. Medication possession ratio (MPR) was calculated as the sum of days supply of therapy divided by treatment duration. We assessed between-group differences in compliance (MPR ≥ 0.80) by logistic regression. Results Among 16,364 patients meeting eligibility criteria, 8470 were retained in the matched cohort. No significant differences in compliance with statin therapy were observed for non-switchers versus switchers, overall, or versus patients switched from a branded to generic statin of the same agent (generic substitutions). Patients switched from a branded to generic statin of a different agent (therapeutic substitutions) more frequently received less potent statin dosing relative to those with generic substitutions (42.2% vs.

Purpose Antihyperglycemic medication intensification practices among patients with incident diabetes are incompletely understood. We characterized the first intensification the year after oral antihyperglycemic medication initiation among incident diabetes patients. Methods This retrospective cohort study across 11 US health systems included adults identified with incident diabetes between 2005 and 2009 who started oral antihyperglycemic monotherapy or combination therapy within 6 months after diabetes identification. We determined intensification, defined as increased index medication dosage, addition of another oral medication, or switch to/addition of insulin 31–365 days after initial antihyperglycemic dispensing. Cox regression was used to assess intensification for patient, temporal, and system covariates, adjusting for glycosylated hemoglobin (HbA1c) as a time-dependent variable. Results Among 41 233 patients, 33.5% and 45.3% had treatment intensified within 6 and 12 months, respectively. This first intensification was most often with increased index medication dosage (78%), least often with insulin (

Purpose To propose methods for the quantitative assessment of the applicability of evidence from a trial to a target sample using individual data. Methods Demonstration was with a trial of drug therapy to prevent mortality and an accompanying registry of people with heart failure. Principal components analysis with biplots did not identify measurement discrepancies. Multiple imputation with chained equations addressed missing predictor values. A proportional hazards model with interaction term, including graphical interpretation and a multivariate interaction test, identified heterogeneity of treatment effect. An interval of homogeneity of treatment effect was the interval of the baseline risk of outcome in which no two treatment effects were statistically significantly different. Absolute risk reduction for individuals was estimated for both benefit and harm outcomes and presented in a bivariate treatment effects scatterplot. Results Overall, the trial evidence applied to most of the registry according to overlapping distributions of estimated benefit and harm. However, 52% of trial and 33% of registry participants were estimated to have net benefit, and 14% of trial and 36% of registry participants were estimated to have strong net harmful treatment effect, that is, the individual estimate of harm was more than twice the estimate of benefit. Conclusions The proposed methods provide quantitative assessment of the applicability of trial evidence to a target sample. They combine the strengths of different study designs, namely, unbiased effects estimation from trials and representation in observational studies, while addressing the practical challenges of combining information, namely, measurement discrepancies and missing data. Copyright © 2012 John Wiley & Sons, Ltd.

BACKGROUND: Plasma exchange, the standard treatment for thrombotic thrombocytopenic purpura (TTP), has significantly decreased disease mortality. However, TTP recurs in 20% to 50% of patients who survive the initial episode. We aimed to describe the clinical spectrum of TTP, to determine the valid endpoint for plasma exchange cessation, and to explore the risk factors for disease relapse. STUDY DESIGN AND METHODS: Using the ICD-9 diagnosis code, we identified patients treated for TTP at the Johns Hopkins Hospital between 1992 and 2008. Complete demographic, clinical, laboratory, treatment, and outcome data were collected from the medical records. RESULTS: A total of 72 patients were treated for 134 episodes of TTP at the Johns Hopkins Hospital during the study period. With standardized combined immunosuppression and plasma exchange treatment, the all-cause mortality rate was 4%. Lactate dehydrogenase (LDH) normalization lagged behind platelet (PLT) recovery by an average of 9 days and did not predict response. Relapse occurred in 36% of patients during a median follow-up of 30 months with most (76%) occurring in the first 24 months. African American ethnicity was associated with increased risk of relapse (odds ratio = 4.8, p = 0.03). CONCLUSIONS: Excellent outcomes in patients with TTP are achievable with multimodality therapy. LDH normalization lags behind PLT recovery and might not be an informative endpoint for plasma exchange cessation. Prospective studies are warranted to confirm the influence of race on relapse and identify additional risk factors for adverse outcomes that could be targeted to improve therapeutic outcomes for patients with TTP.

Purpose: The aim of this study was to evaluate the evidence on the optimal duration of vitamin K antagonist (VKA) therapy for venous thromboembolism (VTE). Methods: Randomized controlled trials of VKA for VTE were identified by a computerized database search. Summary event rates for relevant outcomes were calculated using a random effects model with 95% confidence intervals (95% CI). Results: Ten studies met inclusion criteria. The incidence of recurrent VTE (3 months, 7.9 VTE per 100 patient-years [95% CI, 5.2 to 10] versus 4–12 months, 4.9 VTE per 100 patient-years [95% CI, 3.6 to 6.2] versus continuous therapy, 0.7 VTE per 100 patient-years [95% CI, 0.3 to 1.1]) and total adverse events (3 months, 11.2 events per 100 patient-years [95%CI, 7.1 to 15.4] versus 4–12 months, 7.4 events per 100 patient-years [95%CI, 6.2 to 8.5] versus continuous therapy 3.1 events per 100 patient-years [95%CI, 2.2 to 4.0] declined as VKA therapy duration increased. Continuous reduced intensity therapy (INR 1.5–2) was associated with more recurrent VTE (2.3 VTE per 100 patient-years [95%CI, 1.5 to 3.0]). Continuous VKA therapy (INR 2–3) was beneficial for patients with a second VTE and antiphospholipid antibodies. The incidence of recurrent VTE was similar with 6 or 12 weeks of therapy for isolated calf DVT. Conclusion: Randomized controlled trials indicate that continuous VKA therapy (INR 2–3) for VTE is associated with better clinical outcomes than shorter durations. Patients with a second VTE or antiphospholipid antibodies also benefit from continuous anticoagulation. Patients with calf DVT should be treated for at least 6 weeks. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.

BACKGROUND: The literature was systematically reviewed to determine whether a prolonged prothrombin time or elevated international normalized ratio predicts bleeding during invasive diagnostic procedures. STUDY DESIGN AND METHODS: MEDLINE and CENTRAL were searched through August 2004, with no language restriction, and reference lists were reviewed. For inclusion, articles must have reported on bleeding in more than five patients with abnormal test results undergoing diagnostic procedures. RESULTS: One trial and 24 observational studies were included. In 2 studies of bronchoscopy, the bleeding rates were similar among those with normal and abnormal tests, with wide confidence intervals (CIs) around the risk differences. During central vein cannulation (3 studies), bleeding rates among those with abnormal tests was unlikely to exceed 2.3 percent. The largest of 3 studies of arteriography found equivalent bleeding rates in patients with and without abnormal tests (risk difference, 0%; 95% CI, −3% to 2%). In the 3 studies of liver biopsy with plugging, bleeding rates were 0, 4, and 5 percent with the upper bounds of the CI as high as 17 percent. In the largest study of transjugular biopsy, the bleeding rate was 1.5 percent (95% CI, 0.3%-4%) in patients with abnormal tests. The highest bleeding rate in the 3 studies of percutaneous liver biopsy was 5.3 percent (95% CI, 1%-13%), similar to the rate in patients with normal test results. CONCLUSION: There is insufficient evidence to conclude that abnormal test results predict bleeding. Randomized controlled trials should be performed to provide stronger evidence for clinical decision making regarding preprocedure transfusion.

BACKGROUND: Acute normovolemic hemodilution (ANH) involves withdrawal of whole blood with concurrent infusion of fluids to maintain normovolemia. The aim of this study was to quantify the efficacy and safety of preoperative ANH with a systematic review and meta-analysis. STUDY DESIGN AND METHODS: Randomized controlled trials were identified through MEDLINE (1966-2002) and the Cochrane Controlled Trials Database and with hand searching of journals. All trials of preoperative ANH reporting on allogeneic transfusion, bleeding, or adverse outcomes were included. Paired reviewers independently abstracted data. Outcomes were pooled using random-effects models. RESULTS: A total of 42 trials compared hemodilution to usual care or to another blood conservation method. The risk of allogeneic transfusion was similar among patients receiving ANH and those receiving usual care (relative risk [RR], 0.96; 95% CI, 0.90-1.01), or another blood conservation method (RR, 1.11; 95% CI, 0.96-1.28). Hemodiluted patients, however, were transfused from 1 to 2 fewer units of allogeneic blood. They had less total bleeding than patients receiving usual care (91 mL; 95% CI, 25-158 mL), although more intraoperative bleeding. Only one-third of studies reported on adverse events. CONCLUSIONS: The literature supports only modest benefits from preoperative ANH. The safety of the procedure is unproven. Widespread adoption of ANH cannot be encouraged.

BACKGROUND: Acute chest syndrome (ACS) is a complication of sickle cell disease that can cause significant morbidity. Transfusion therapy has been shown to significantly increase oxygenation in patients with ACS and RBC exchange is considered the standard of care in patients at high risk of respiratory failure. CASE REPORT: A patient with ACS and several high-risk features, including thrombocytopenia, profound anemia, bilateral pulmonary infiltrates, staphylococcal sepsis, and pulmonary embolism is presented. The patient refused transfusion on religious grounds and received 12 units of human polymerized Hb solution (poly SFH-P injection, PolyHeme, Northfield Laboratories) over the course of 13 days. The patient's respiratory status improved and she was discharged home without receiving RBC transfusions. CONCLUSION: This is the first reported case that describes the use of PolyHeme in a patient with sickle cell disease, ACS, and sepsis. This therapy is thought to have been lifesaving for this patient.

BACKGROUND : Preoperative donation of blood lowers the risk of allogeneic RBC transfusion. The use of autologous blood is not well quantified. This study aimed at identifying the frequency and determinants of use of autologous transfusion in the United States. STUDY DESIGN AND METHODS: This national cross-sectional study, using the Nationwide Inpatient Sample, included all patients admitted to 900 hospitals in 19 states in 1996. Logistic regression with weighting yielded nationally representative results for the independent effects of clinical and nonclinical patient characteristics on autologous blood use. RESULTS: Autologous transfusion was used in 19 of 1000 hospitalizations. The procedures using autologous blood most frequently were knee arthroplasty, hip replacement, prostatectomy, spinal fusion, and hysterectomy. Blacks and Hispanics were less likely to receive autologous transfusion than were whites (OR, 0. 64; 95% CI, 0.45-0.83); patients with Medicaid were less likely than the privately insured to receive autologous transfusions (OR, 0.29; 95% CI, 0.20-0.43), with racial differences greatest among the privately insured. Women received autologous blood for cardiovascular surgeries much less often than men (OR, 0.32; 95% CI, 0.20-0.49). CONCLUSION: Ethnic minorities, women, and patients with Medicaid appear to receive fewer autologous blood transfusions than the rest of the population. Although this could reflect either better or worse quality of care, nonclinical determinants of transfusion practice warrant attention and further investigation.

BACKGROUND: Administrative data are used often for research, but without validation of their accuracy. The validity of the billing for blood transfusion was assessed in one tertiary-care hospital. MATERIALS AND METHODS: Patient discharge data were retrieved from a database containing demographics, diagnoses, and charges. There was random selection of 358 patients who were billed for RBC transfusion and 358 who were not, within a 2-month period. The blood bank's transfusion records were reviewed. Sensitivity was defined as the proportion of transfused patients who were billed, and specificity as the proportion of nontransfused patients who were not billed. Patient characteristics were compared by using Wilcoxon's rank sum test and the chi-square test. RESULTS: Sixty-one transfused patients were not billed for the transfusion. No patient was billed without transfusion. Thus, the sensitivity and specificity were 83 percent (95% CI, 79-87%) and 100 percent, respectively. Nine patients who were not issued RBCs were appropriately not billed for RBCs, although the billing record suggests they had a procedure involving transfusion. These patients were called true-negative. The patients not billed were older (58 years vs. 55 years; p = 0.046) and less likely to have commercial insurance (5% vs. 15%; p = 0.035) than billed patients. CONCLUSIONS: The billing for RBC transfusion in one large institution is reassuringly valid. The specificity is excellent, and the sensitivity is higher than that seen in other studies of coding validity.

Objective Diagnosis of the crystal-induced arthritides is primarily based on microscopic identification of crystals in synovial fluid. Therefore, we aimed to estimate the operating characteristics of this test and demonstrate its clinical use. Methods Medline was searched for relevant studies. Sensitivity and specificity of identification of crystals were calculated, as were measures of interobserver agreement. Likelihood ratios were calculated and curves constructed using the solutions to the Bayesian equations. Results Four studies were identified. The rates of interobserver agreement were low; the false-negative rates in identifying calcium pyrophosphate crystals were particularly high. Only one study allowed calculation of the test operating characteristics, and this was a study that used synthetic crystals and therefore may not be directly useful in a clinical setting. Conclusion There is a paucity of data about the accuracy of crystal identification. As it is clearly not a perfectly sensitive and specific test, the most prudent diagnostic strategy, as with essentially all diagnostic tests, is to establish a posterior probability of disease from a prior probability, based on the clinical features of the patient. Determining the operating characteristics of this test in conventional and reference laboratories should be a research priority for high quality clinical research on crystal arthropathies.

Reports of the incidence of ITP are few and their methodology is variable. Accurate estimates of the incidence of immune thrombocytopenic purpura (ITP) are important to understand the medical and public health impact of the disease. To critically review all published reports on the incidence of ITP in children and adults, all articles identified on the Medline database (searched January 1, 1966-August 7, 2009) that reported data on the incidence of ITP were retrieved. Articles which directly estimated the incidence of ITP were selected for review. Eight articles reported the incidence of acute ITP in children. After review, four were determined to have the strongest estimates, based on the method of patient identification and study design. The lowest incidence estimate in these four studies was 2.2 per 10(5) children/year (95% confidence interval 1.9, 2.4) and the highest incidence estimate was 5.3 per 10(5) children/year (95% confidence interval 4.3, 6.4). Three studies reported the incidence of ITP in adults. The estimate from the article with the strongest methodology reported an incidence estimate of 3.3 per 10(5) adults/year. The current strongest estimate of the incidence of acute ITP in children is between 1.9 and 6.4 per 10(5) children/year; for adults the current strongest estimate of the incidence of ITP is 3.3 per 10(5) adults/year. An important limitation of these studies is that they are primarily from Europe and may not be generalizable to all regions.

Reason for withdrawal from publication Date: May 20th 2006 (Issue 3 2006) This review is out of date and had been withdrawn. This topic is now the subject of a published systematic review "Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks." By M Aguilar, R Hart. To view the published versions of this article, please click the 'Other versions' tab.